Screening Assessment

Acetone
Chemical Abstracts Service Registry Number
67-64-1

Environment Canada
Health Canada
September 2014

(PDF Format - 880 KB)

Table of Contents

List of Tables

Synopsis

Pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Ministers of the Environment and of Health have conducted a screening assessment of acetone (Chemical Abstracts Service Registry Number 67-64-1). Acetone was identified as a priority for assessment on the basis of greatest potential for human exposure.

Acetone has both natural and anthropogenic sources. It is produced by thermal combustion, such as from forest fires; it is an oxidation product of natural humic substances; and it is excreted as a metabolic by-product from many organisms, including mammals, plants and microorganisms. Important anthropogenic sources of acetone in air include chemical manufacturing, solvent use, petroleum production, automobile emissions, tobacco smoke, wood burning, pulping, refuse, plastics combustion and off-gassing from landfill sites. Anthropogenic sources of acetone emissions to the aquatic environment include wastewater discharges from industries and leaching from industrial and municipal landfills.

Acetone is used as a formulating solvent for a variety of paints, inks, resins, varnishes, lacquers, surface coatings, paint removers and automotive care products. The largest applications of acetone globally are solvent uses and for the production of methyl methacrylate and bisphenol A. In 2010, total global production of acetone was estimated to be 5.5 million tonnes.

In Canada, acetone is employed for a variety of uses, including use as an industrial and laboratory solvent, as a cleaner and degreaser, and in paints, dyes, adhesives and coatings. Acetone may be used in Canada in food, food packaging, pharmaceuticals, natural health products, veterinary drugs, cosmetics and pest control products.

Based on the results of a survey conducted under section 71 of CEPA 1999 for the year 2000, approximately 1000 tonnes of acetone was manufactured in Canada as a by-product of industrial processes, and 15 000 tonnes of acetone was imported into Canada, at a concentration higher than 1%. However, a facility that accounted for 98% of Canadian acetone production in the year 2000 stopped manufacturing it in 2002.

Acetone was included in the National Pollutant Release Inventory (NPRI) until 1998. In 1998, facilities across Canada reported on-site environmental releases totalling approximately 3570 tonnes, mostly to air. Since 2009, facilities located in the province of Ontario must again report acetone releases to the NPRI. In 2009, total releases of acetone in Ontario were 1039 tonnes (mainly to air), compared with 1379 tonnes in 1998.

Acetone has been measured in ambient and indoor air, and drinking water in Canada, and in the United States and elsewhere in surface water, groundwater, food, and soil. Acetone has been identified in numerous products and building materials, as well as in cigarettes and tobacco smoke. Acetone is produced endogenously in the body and has been detected in the blood of individuals living in the United States.

Acetone has an estimated tropospheric half-life of 22 to 23 days and is predicted to be subject to long-range atmospheric transport ( greater than  5000 km); therefore, it is persistent in air. It will biodegrade in soil and water and is therefore not persistent in these media.

Acetone is not expected to bioaccumulate in organisms, based on empirical as well as modelled data. Based on empirical data, acetone at low concentrations is not hazardous to aquatic organisms, terrestrial plants or mammals.

Acetone is predicted to stay mainly in the environmental compartment to which it is released. This is especially true when acetone is released to water ( greater than  99% is predicted to remain in water).

For the ecological portion of this screening assessment, the predicted environmental concentrations in air and surface water did not exceed concentrations associated with effects, even when using very conservative scenarios.

Based on the information presented in this screening assessment, there is low risk of harm to organisms or the broader integrity of the environment from this substance. It is concluded that acetone does not meet the criteria under paragraphs 64(a) or (b) of CEPA 1999 as it is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity or that constitute or may constitute a danger to the environment on which life depends.

Consideration of the available information indicates that acetone is not likely to be genotoxic or carcinogenic. Critical health effects associated with repeated exposure to acetone are considered to be hematological changes and kidney effects. The general population of Canada has daily exposure to acetone from environmental media, food and acetone-containing products that are used frequently. The margins of exposure between critical effect levels and the upper-bounding total daily intake estimates are considered to be adequate to address uncertainties in the health effects and exposure databases.

No critical health effects were identified for characterization of risk from acute exposures that are expected to occur from occasional, intermittent use of certain products containing acetone. Effects at exposure levels associated with such uses were considered mild, transient and reversible in nature; therefore, they were not considered adverse.

Based on the information available, it is concluded that acetone does not meet the criteria under paragraph 64(c) of CEPA 1999 as is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.

Overall Conclusion

Based on available information for environmental and human health considerations, it is concluded that acetone does not meet any of the criteria set out in section 64 of CEPA 1999.

1. Introduction

This screening assessment report was conducted pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999). This section of the Act requires that the Ministers of the Environment and of Health conduct screening assessments of substances that have met the categorization criteria set out in the Act to determine whether these substances present or may present a risk to the environment or to human health.

A screening assessment was undertaken on acetone (Chemical Abstracts Service Registry Number 67-64-1), a substance on the Domestic Substances List (DSL). Acetone was identified during the categorization of substances on the DSL as a priority for assessment as it met the criteria for greatest potential for human exposure. Acetone met the categorization criteria for persistence, but it did not meet the criteria for bioaccumulation potential or inherent toxicity to aquatic organisms.

Screening assessments focus on information critical to determining whether a substance meets the criteria as set out in section 64 of CEPA 1999. Screening assessments examine scientific information and develop conclusions by incorporating a weight of evidence approach and precaution.Footnote[1]

This screening assessment includes consideration of information on chemical properties and uses of acetone, exposure to acetone and hazards associated with exposure to acetone. Data relevant to the screening assessment of this substance were identified in original literature, review and assessment documents, stakeholder research reports and reports written under contract for Health Canada, as well as from recent literature searches, up to September 2011 for ecological sections of the document and December 2011 for human health sections of the document. In addition, an industry survey was conducted in 2001 through a Canada Gazette Notice issued under the authority of section 71 of CEPA 1999 (Canada 2001); this survey collected data on the Canadian manufacture and import of acetone in the year 2000 (Environment Canada 2004). Key studies were critically evaluated; modelling results were used to reach conclusions.

The approach taken in the ecological screening assessment is to examine various supporting information and develop conclusions based on a weight of evidence approach as required under section 76.1 of CEPA 1999. The screening assessment does not present an exhaustive review of all available data. Instead, it presents the critical studies and lines of evidence supporting the conclusions.

Evaluation of risk to human health involves consideration of data relevant to estimation of exposure of the general population (non-occupational) as well as information on health hazards. Decisions for human health are based on the nature of the critical effect and/or margins between conservative effect levels and estimates of exposure, taking into account confidence in the completeness of the identified databases on both exposure and effects, within a screening context. The screening assessment does not represent an exhaustive or critical review of all available data. Rather, it presents a summary of the critical information upon which the conclusion is based.

This screening assessment was prepared by staff in the Existing Substances programs at Health Canada and Environment Canada, and the content was reviewed by senior staff for adequacy of data coverage and defensibility of the evaluation. The ecological and health assessments have undergone external written peer review and/or consultation  Comments on the technical portions relevant to human health assessment were received from scientific experts selected and directed by Gradient Consulting. Additionally, the draft of this screening assessment was subject to a 60-day public comment period. Although external comments were taken into consideration, the final content and outcome of the screening assessment remain the responsibility of Health Canada and Environment Canada.

The critical information and considerations upon which the screening assessment is based are summarized in the following sections.

Top of Page

2. Substance Identity

For the purposes of this document, this substance will be referred to as acetone, a common name for the substance. Information relevant to the identity of the substance is presented in Table 2-1.

Table 2-1: Substance identity for acetone
CAS RN67-64-1
DSL namesAcetone, 2-propanone
NCI names

Acetone (DSL, EINECS, PICCS, REACH)

Dimethyl ketone (PICCS)

2-Propanone (AICS, ASIA-PAC, DSL, ECL, ENCS, NZIoC, PICCS, SWISS, TSCA)

Other namesDimethylformaldehyde, β-ketopropane, methyl ketone, NSC 135802, propanone, pyroacetic ether, Taimax, UN 1090, UN 1090 (DOT)
Chemical group (DSL stream)Discrete organics
Major chemical class or useCarbonyls
Major chemical subclassKetones
Chemical formulaC3H6O
Chemical structure Chemical structure CAS RN 67-64-1
SMILESO=C(C)C
Molecular mass58.08 g/mol

Abbreviations:

AICS, Australian Inventory of Chemical Substances;

ASIA-PAC, Asia-Pacific Substances Lists;

CAS RN, Chemical Abstracts Service Registry Number;

DOT, Department of Transportation (US);

DSL, Domestic Substances List;

ECL, Korean Existing Chemicals List;

EINECS, European Inventory of Existing Commercial Chemical Substances;

ENCS, Japanese Existing and New Chemical Substances;

NCI, National Chemical Inventories;

NZIoC, New Zealand Inventory of Chemicals;

PICCS, Philippine Inventory of Chemicals and Chemical Substances;

REACH, Registration, Evaluation, Authorisation and Restriction of Chemical Substances;

SMILES, Simplified Molecular Input Line Entry Specification;

SWISS, Swiss Giftliste 1 and Inventory of Notified New Substances;

TSCA, Toxic Substances Control Act Chemical Substance Inventory

Source: NCI (2006)

Top of Page

3. Physical and Chemical Properties

Acetone is a clear, colourless liquid with a strong “fruity” odour that is highly flammable and is miscible with water and organic solvents, such as ether, methanol, ethanol and esters (WHO 1998). Reagent-grade acetone can contain up to 0.5% water as well as small amounts of other polar solvents (OECD 1999). Selected physical and chemical properties of acetone are presented in Table 3-1.

Table 3-1: Physical and chemical properties of acetone
PropertyTypeValueTemperature (°C)Reference
Melting point (°C)Experimental−94--Windholz 1989
Boiling point (°C)Experimental56.2--Weast and Lide 1989
Density (g/mL)Experimental0.789920Weast and Lide 1989
Vapour pressure (kPa)Experimental24.720Howard 2011
Vapour pressure (kPa)Experimental30.825Riddick et al. 1986
Henry’s Law constant (Pa·m3/mol)Experimental

4.32

(4.26  × 10−5 atm·m3/g·mol)Footnote Table 3-1[a]

25.2Rathbun and Tai 1987
Henry’s Law constant (Pa·m3/mol)Experimental3.5525Benkelberg et al. 1995
Log Kow (dimensionless)Experimental−0.24--Collander 1951
Log Koc (dimensionless)Experimental0.99--KOCWIN 2010
Water solubility (mg/L)ExperimentalMiscible with water20Windholz 1989
Water solubility (mg/L)ExperimentalInfinite--Riddick et al. 1986
Water solubility (mg/L)Modelled2.7 × 10525WATERNT (2010)
pKa (dimensionless)Experimental20--Serjeant and Dempsey 1979

Abbreviations:

Koc, organic carbon–water partition coefficient;

Kow, octanol–water partition coefficient;

pKa, acid dissociation constant

Footnote Table 3-1 a

There is a typographical error in the original reference; the value is given as 4.26 × 105atm·m3/g·mol in Rathbun and Tai (1987).

Return to footnote Table 3-1 a referrer

The very high acid dissociation constant (pKa value) of 20 indicates that acetone will be present in an un-ionized form in the natural environment.

Top of Page

4. Sources

Atmospheric emissions of acetone occur from both natural and anthropogenic sources. Natural sources of emission include forest fires and volcanic eruptions. Acetone is also produced endogenously as a metabolic by-product in humans and other animals, microorganisms and plants and is expired as a component of expired air from mammals (Graedel et al. 1986). It is formed in the atmosphere from the photochemical oxidation of propane and possibly propylene oxide and epichlorohydrin (ATSDR 1994). Acetone is released as a biodegradation product of sewage, solid wastes and alcohols and as an oxidation product of natural humic substances (WHO 1998). Important anthropogenic sources of acetone in air include chemical manufacturing, solvent use, petroleum production, automobile emissions, tobacco smoke, wood burning, pulping, refuse, plastics combustion and off-gassing from landfill sites (WHO 1998). Acetone is manufactured mainly by cumene peroxidation, as a co-product with phenol (SRI 2011).

Anthropogenic sources of acetone emissions to the aquatic environment include wastewater discharges from industries and leaching from industrial and municipal landfills (WHO 1998). Acetone is released into surface water as a component of wastewater from a variety of manufacturing processes and industries, including paper, plastics, pharmaceuticals, specialty cleaning and polishing products, paint and allied products, gum and wood chemicals, industrial organic chemicals, gypsum products, paperboard products and energy-related industries, such as coal gasification and oil shale processing (ATSDR 1994; WHO 1998). The principal sources of acetone emissions to subsurface soil are releases from municipal and industrial discharges in landfills (US EPA 1988). Acetone can also leach from landfills into groundwater (ATSDR 1994).

A survey conducted pursuant to section 71 of CEPA 1999 indicated that in Canada, during the year 2000, approximately 1000 tonnes of acetone was manufactured at a concentration higher than 1% by weight and about 15 000 tonnes was imported at a concentration higher than 1% by weight (Environment Canada 2004). In addition, 16 companies reported either importing or manufacturing acetone at a concentration lower than 1% and in a quantity meeting the reporting threshold of 10 000 kg (Environment Canada 2004). Companies manufacturing acetone in Canada indicated that it was formed as a by-product of their operations (Environment Canada 2004). One of these facilities, which accounted for 977 tonnes (or 98%) of Canadian acetone production in the year 2000, shut down the process that was producing acetone in 2002. The two other companies that reported manufacturing acetone were pulp and paper plants (Environment Canada 2004).

Top of Page

5. Uses

Acetone is the simplest aliphatic ketone and the most commercially important. Total global production in 2010 was estimated to be 5.5 million tonnes (SRI 2011). Total global acetone consumption in 2010 was estimated to have increased by 5% from 2009, and it is expected to increase on average by 4.0% per year from 2010 to 2015, slowing to 2.4% per year from 2015 to 2020 (SRI 2011). Based on 2008 estimates, the largest volume applications of acetone globally are solvent uses (1.82 million tonnes), methyl methacrylate production (1.44 million tonnes) and bisphenol A production (1.23 million tonnes) (Sifniades et al. 2011). These three categories consumed approximately 80% of global acetone consumption in 2010; other applications for acetone include acetone cyanohydrin and isopropyl alcohol production (SRI 2011).

Worldwide, major end uses of acetone can be divided into three separate categories. These include uses as chemical feedstock, a formulating solvent for commercial products and an industrial process solvent (OECD 1999). Several chemicals, such as methyl isobutyl ketone, methyl isobutyl carbinol, isophorone and diacetone alcohol, are also prepared directly from nascent acetone (OECD 1999). Acetone is used as a formulating solvent for a variety of paints, inks, resins, varnishes, lacquers, surface coatings, paint removers and automotive care products. As an industrial process solvent, acetone is used to manufacture cellulose acetate yarn, polyurethane foam, vitamin C and smokeless gun powder (OECD 1999). Acetone is also used in small volume applications for the creation of functional compounds such as antioxidants, herbicides, larger ketones, condensates with formaldehyde or diphenylamine, and vitamin intermediates (Howard 2011).

Uses of acetone in Canada are consistent with international use patterns. In Canada, acetone is employed for a variety of uses, including as an industrial solvent, cleaner, in paints, adhesives and coatings (e.g., automotive finishing coatings) and in laboratories (Environment Canada 2004). Many of these uses were reported to be “dispersive uses where the substance is released into the environment,” including use as a solvent, industrial cleaner, and spray-on adhesive.

Acetone is excluded from the volatile organic compound (VOC) definition under Schedule 1 of CEPA 1999. As such, acetone may be used in formulations of products regulated under the Volatile Organic Compound (VOC) Concentration Limits for Architectural Coatings Regulations (2009) (Canada 2009a) and the Volatile Organic Compound (VOC) Concentration Limits for Automotive Refinishing Products Regulations (2009) (Canada 2009b).  Environment Canada is also looking at opportunities for the further reduction of VOC emissions from products. As a result, it is possible that acetone usage in Canada may increase should companies substitute acetone for VOCs in their products.

Acetone is used in food preparation as an extraction solvent for fats and oils and as a flavouring agent (FAO/WHO 1998). It is permitted for use as a food additive in Canada under the Food and Drug Regulations, as a carrier or extraction solvent (e.g., spice extracts, meat and egg marking inks), at maximum levels of use specified by the List of Permitted Carrier or Extraction Solvents (Health Canada 2012a). These uses must meet all of the conditions specified in that list as incorporated by reference into the Marketing Authorization for Food Additives That May Be Used as Carrier or Extraction Solvents(Health Canada 2012a). Acetone may be used as a solvent for many applications related to food packaging and may be found as a residual impurity in some food packaging matterials such as polyethylene and polypropylene resins as a result of manufacturing process  (2013 email from Food Directorate, Health Canada, to Risk Management Bureau, Health Canada; unreferenced).

Acetone is listed in the Natural Health Products Ingredients Database (NHPID) with a medical ingredient role, as it meets the criteria under Schedule 1, item 2 (an isolate), of the Natural Health Products Regulations (Canada 2006; NHPID 2011). It is also listed in the NHPID with a non-medicinal ingredient role as a denaturant, flavour enhancer and solvent in natural health products (NHPID 2011). Acetone is listed in the Licensed Natural Health Products Database (LNHPD) as a medicinal and non-medicinal ingredient in currently licensed natural health products (LNHPD 2011). Acetone is not listed in the Drug Product Database as an active ingredient in pharmaceuticals (human/veterinary) (DPD 2011); however, it forms part of the name (as “acetone-precipitated”) of certain allergenic extracts administered to humans that are regulated under Schedule D (biological products) of the Food and Drug Regulations(Canada 1986). Acetone is listed as a Class 3 residual solvent (i.e., solvent that should be limited by Good Manufacturing Practices) in the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline Q3C (R4) (ICH 2009), which is adopted by the Therapeutic Products Directorate (Health Canada 1999) and the Natural Health Products Directorate (Health Canada 2007); and the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products Guideline GL18 (VICH 2000), which is adopted by the Veterinary Drugs Directorate (Health Canada 2003). Acetone is used primarily as an extraction solvent and may be present as a residual in pharmaceutical products, natural health products and veterinary drugs with a specified limit of less than 50 mg/day or 0.5% in any product, in accordance with the respective ICH/VICH guideline.

Acetone is used as a denaturant, fragrance and solvent in cosmetics (Personal Care Products Council 2011). In Canada, acetone is a constituent of cosmetics  such as manicure preparation products, hair grooming products, skin cleansers and skin moisturizers (2011 email from Risk Management Bureau, Consumer Product Safety Directorate,Health Canada, to Risk Management Bureau, Safe Environments Directorate, Health Canada;  unreferenced).

In Canada, acetone is a formulant in pest control products regulated under the Pest Control Products Act at concentrations ranging from just over 0% to 41.2% (2011 email from Risk Management Bureau, Health Canada, to Existing Substances Risk Assessment Bureau, Health Canada; unreferenced). Product types include rodenticides, insecticides, insect repellents, fungicides, wood preservatives, antifouling paints, dog, bear and deer repellents, seed treatments, material preservatives and slimicides.

Top of Page

6. Releases to the Environment

6.1 Global Releases

Natural sources, such as vegetative releases and forest fires, are estimated to account for nearly half (47%) of the estimated annual emissions of acetone (OECD 1999), most of which are to air. According to a study by Jacob et al. (2002), up to 77% of annual acetone emissions are attributable to natural sources, such as terrestrial vegetation, the oceans and biomass burning.

Singh et al. (1995) estimated that 50–66% of global tropospheric acetone  results from the tropospheric photooxidation of mostly anthropogenic propane and other alkanes and alkenes, while Jacob et al. (2002) estimated that the atmospheric oxidation of anthropogenic isoalkanes, including propane, isobutane and isopentane, contributes 22% of the total acetone in the atmosphere on a global scale. Goldstein and Schade (2000) estimated, based on acetone to acetylene ratios, that 99% of the anthropogenic acetone (13.9% of total acetone) found in the air of a forested rural area (Sierra Nevada Mountains, California) is from secondary formation during the photochemical aging of polluted air as it is transported downwind from urban areas. The most likely source of this secondarily formed acetone is suggested to be the oxidation of reactive alkenes, such as isobutene and isopentene.

It is estimated that only 1% of the estimated 40 million tonnes of acetone that are released annually to the environment worldwide is released from primary (direct) anthropogenic emissions (Jacob et al. 2002), such as from chemical manufacturers and end users. Goldstein and Schade (2000) further concluded that only 1% of anthropogenic acetone (0.14% of total acetone) found in the air of a rural environment is from primary emissions.

6.2 Canadian Releases

Acetone is released from facilities that manufacture the substance or use it as a solvent or as an intermediate in the production of other chemicals. Acetone was included in the Canada-wide National Pollutant Release Inventory (NPRI) until 1998, and facilities manufacturing, importing or otherwise using more than 10 tonnes of the substance per year reported their releases. In 1997, facilities from across Canada reported to the NPRI on-site environmental releases of acetone totalling 4425 tonnes. Releases to air accounted for 3778.4 tonnes (85.4%), releases to underground injection, 560 tonnes (12.7%), releases to surface water, 85.2 tonnes (1.9%), and releases to land, 1.1 tonnes ( less than  0.1%). On-site releases in 1998 totalled 3567 tonnes, with 95% going to air, 3.1% to underground injection and 1.6% to water. In addition, 1807.5 tonnes were transferred off-site for disposal, and 1777 tonnes were transferred off-site for recycling (Environment Canada 2011a). The releases to surface water were mainly from two chemical manufacturing facilities (52.4 tonnes), with small releases from six pulp and paper facilities (3.2 tonnes total). There were no reported on-site releases to soil, although some companies reported transfers for disposal to landfill of up to 122 tonnes of acetone per facility (Environment Canada 2011a). In the United States, the amount of acetone released into soil from landfill leachate accounted for approximately 0.1% of the total environmental release of acetone, based on data from the 1990 US Toxics Release Inventory (ATSDR 1994).

Acetone was delisted from the US Toxics Release Inventory in 1993 (US EPA 2012). Following a request by Canadian industry to Environment Canada, an independent review (Ritter 1999) was carried out to evaluate whether acetone should be delisted from the NPRI for the 1999 reporting year. The conclusion reached was that ambient levels of acetone in the atmosphere, even at sites adjacent to the largest releases, were below the levels of concern for exposure of humans and that acetone was not likely to adversely impact aquatic or terrestrial wildlife based on median lethal concentrations (LC50 values) generally greater than 2000 parts per million (ppm) (Ritter 1999). Based on the results of this review, acetone was delisted from the NPRI in 1999. Acetone releases are again being reported to the NPRI since 2009 for facilities located in the province of Ontario only, to fulfil VOC reporting requirements under Ontario Reg. 127/01 under the Ontario Toxics Reduction Act, 2009 (Ontario 2009).

NPRI release data for Ontario from 1998 and 2009 were compared. In 1998 in Ontario, total releases of acetone were 1379 tonnes, which represented 38.7% of the Canadian total. In 2009, total releases were 1039 tonnes, which is 24.7% lower than 1998 levels, despite acetone being excluded from federal VOC regulations. The lower acetone releases by facilities in Ontario may be attributed to a decline in manufacturing activity in this province.

In 2009, almost all releases in Ontario were to air, the largest release to air being 52 tonnes from a plastic products manufacturer. No facilities reported releases to soil, and only one facility reported releases to water (28 tonnes by a chemical products manufacturer). The total amount disposed of in 2009 was 36 tonnes, and none was sent for off-site recycling, which is a large drop from 1998, when 800 tonnes were disposed of and 1201 tonnes were sent for off-site recycling.

A survey conducted pursuant to section 71 of CEPA 1999 indicated that Canadian companies reported environmental releases totalling approximately 2100 tonnes of acetone during the year 2000. Only companies manufacturing or importing more than 10 tonnes in 2000 were required to report to this survey. Releases were reported from companies representing various industry sectors, including chemical and pulp and paper. The media of release were not specified.

Top of Page

7. Environmental Fate

The environmental partitioning of acetone in the environment was modelled using Level III (steady-state, non-equilibrium) of the Equilibrium Criterion (EQC) model for Type 1 chemicals (Mackay et al. 1996; EQC 2003). Inputs to the model included half-lives in air, water, soil and sediment and emission rates to each environmental compartment.

In all release scenarios in Table 7-1, acetone tends to partition mainly ( greater than  73-97%) to the compartment to which it is released. This is especially true when acetone is released to air or water.

Table 7-1: Level III fugacity modelling for acetone, percent partitioning into each medium for three release scenarios (EQC 2003)Footnote Table 7-1[a]
Substance released to:Air (%)Water (%)Soil (%)Sediment (%)
100% to Air95.52.22.28less than 0.01
100% to Water1.9897.90.0470.036
100% to Soil6.221.172.7less than 0.01
Footnote Table 7-1 a

Input parameters: aqueous solubility, 2.7 × 105 mg/L (WATERNT 2010); vapour pressure, 30.8  kPa; log Kow, −0.24; melting point, −94 ºC. Half-lives are based on data from Tables 4a and 4b below (water, 168 hours; sediments, 672 hours; air, 552 hours; soil, 168 hours, fish, negligible; aerosol, 168 hours.  The half-life in sediment was extrapolated from that in water using the ratio 1:4 for water:sediment half-lives (Boethling et al. 1995).

Return to footnote Table 7-1 a referrer

Based on its very low organic carbon–water partition coefficient (log Koc value) of 0.99, acetone will be very mobile in soil. Acetone showed no adsorption to montmorillonite, kaolinite clay or stream sediment (Rathbun et al. 1982; Wolfe et al. 1986). Volatilization of acetone from both moist and dry soil surfaces is expected, given acetone’s moderate Henry’s Law constant of 4.32 Pa·m3/mol and its very high vapour pressure of 24.7 kPa.

Volatilization from water surfaces is expected based on the Henry’s Law constant. Using this Henry’s Law constant and an estimation method, estimated volatilization half-lives for a model river and model lake are 38 and 333 hours, respectively (HSDB 1983). Experimentally determined volatilization half-lives in a shallow stream were measured in the range of 8–18 hours (Rathbun et al. 1988, 1991, 1993). Biodegradation of this compound is expected, but volatilization has been shown to be the primary mechanism for the removal of acetone from water (Rathbun et al. 1988, 1991, 1993).

The Transport and Persistence Level III Model (TaPL3) (TaPL3 2003) was used to assess the long-range transport potential of acetone when it is released into air or water. The model calculates the characteristic distance that a substance will travel in a mobile medium until the concentration decreases to 37% (1/e) of its initial value as a consequence of intermedia partitioning and degradation reactions. Advective losses are not included (Beyer et al. 2000; TaPL3 2003). With a modelled characteristic travel distance (CTD) greater than 8000 km, acetone is predicted to be subject to long-range atmospheric transport to remote regions, such as the Arctic.

The Persistent Organic Pollutants (POPs) Screening Model from the Organisation for Economic Co-operation and Development (OECD) can also be used to help identify chemicals with high persistence and long-range transport potential (Scheringer et al. 2006). The OECD model is a global model that compartmentalizes Earth into air, water and soil. This model is “transport oriented” rather than “target oriented,” as it simply identifies the CTD without indicating specifically where a substance may be transported (Fenner et al. 2005). Klasmeier et al. (2006) suggested that a threshold of 5098 km, based on the model’s CTD estimate for the polychlorinated biphenyl PCB-180, can be used to identify substances with high long-range transport potential. PCB-180 is empirically known to be found in remote regions. The CTD calculated for acetone using the OECD model is 5394 km, indicating that acetone has potential for long-range atmospheric transport. The OECD POPs Screening Model also calculates the transfer efficiency (TE), which is the percentage of emission flux to air that is deposited to the surface (water and soil) in a remote region (TE % = D/E × 100, where E is the emission flux to air and D is the deposition flux to surface media in a target region). The TE for acetone was calculated to be 13.1%, which is well above the boundary of 2.25% (PCB-28) established based on the model’s reference substances empirically known to be deposited from air to soil or water. The high TE means that acetone will likely be deposited to some degree to Earth’s surface in remote regions.

Acetone has been measured in Arctic air at an average concentration of 385 ppt  (vol) (approximately 0.3 mg acetone/m3 air) (Grannas et al. 2002). The dominant sources of acetone at Alert, in the Canadian High Arctic, were modelled to be oxidation of isoalkanes (mainly anthropogenic) and plant decay (Jacob et al. 2002).

Top of Page

8. Environmental Persistence and Bioaccumulation Potential

8.1 Environmental Persistence

Acetone has an estimated tropospheric half-life of 22–23 days (see Table 8-1) and is therefore considered to be persistent in air. Acetone is removed from the atmosphere through reaction with hydroxyl (OH) radicals and photolysis. At low altitudes ( less than  5 km), the reaction of acetone with OH radicals determines its loss rate. At higher altitudes, the loss via the OH radical reaction decreases due to the lower concentration of OH radicals and the decrease in temperature, and the photolysis reaction controls the loss rate (Gierczak et al. 1998).

Table 8-1: Environmental half-lives and processes for the removal of acetone in air
Media/removal processHalf-life (unless otherwise noted)Reference
Reaction with OH radicals and photolysis23 days (in lower troposphere at 40°N)Gierczak et al. 1998
Reaction with OH radicals and photolysis22 days (mean in troposphere at 40°N)Meyrahn et al. 1986
Reaction with OH radicals at 25°C134 days (0.37 year)Footnote Table 8-1 [a] (total tropospheric lifetime)Vasvári et al. 2001
Reaction with OH radicals and photolysis254 days (0.70 year) (total lifetime in upper troposphere at 50°N)Arnold et al. 2004
Footnote Table 8-1 a

Based on OH concentration of 5 × 105 molecules/cm3 in the troposphere, a standard value for the northern hemisphere (ECJRC 2003).

Return to footnote Table 8-1 a referrer

Acetone will biodegrade and volatilize in water bodies and soil within a time frame of days to weeks and therefore is not considered to be persistent in water or soil (see Table 8-2). The estimated log Koc value of 0.99 (see Table 2) suggests that adsorption of acetone to sediments and suspended solids is not significant, and this has been shown experimentally (Rathbun et al. 1982).

Many aerobic biological screening studies have examined the biodegradability of acetone and have found it to be readily biodegradable (WHO 1998). Studies with several different strains of anaerobic bacteria from municipal wastewater treatment plants have shown that acetone is completely degraded to carbon dioxide following acetoacetate formation through an initial carboxylation reaction (Platen and Schink 1989). Acetone was 84% and 78% degraded in 20-day and 28-day (OECD Test Guideline 301D) closed bottle biological oxygen demand tests, respectively (Waggy et al. 1994). Acetone was 89% biodegraded after 25 days, as measured by percent theoretical methane recovery, when incubated with a sediment/groundwater mixture from an anoxic aquifer contaminated with municipal landfill leachate (Suflita and Mormile 1993).

Grove and Stein (2005) studied the removal of acetone from post-primary treatment municipal wastewater in microcosm constructed wetlands. The 90% removal of acetone required 5–10 days in summer (daytime/nighttime temperatures of 24°C and 16°C, respectively) and 10–14 days in winter (daytime/nighttime temperatures of 13°C and 7°C, respectively).

DeWalle and Chian (1981) studied the migration of organics, including acetone, from a landfill site in Delaware, USA, through the surrounding soil and into an aquifer. The concentration of acetone in the landfill leachate was 43 700 µg/L. DeWalle and Chian (1981) calculated attenuation factors for the organics through 500 m of soil by dividing the leachate concentration by the concentration measured in a recovery well located 500 m away. The attenuation factor for acetone was 48 560, meaning that the concentration of acetone found in the recovery well was approximately 0.9 µg/L.

Table 8-2: Environmental half-lives and processes for the removal of acetone in water and soil
Media/removal processHalf-life (unless otherwise noted)Reference
Aqueous biodegradation, laboratory (disappearance of acetone measured)

2.1–21 h, mean = 4.3 h, after lag period of 5–19 h, non-acclimatized bacteria

4.8–38 h, mean = 12 h, after lag period of 1–2 h, acclimatized bacteria

Rathbun et al. 1982
Aqueous biodegradation in natural stream waterComplete disappearance of acetone in 7 days after lag period of 4–5 daysRathbun et al. 1991
Volatilization, river2–10 daysHoward et al. 1990
Volatilization, river18–19 hThomas 1982
Volatilization, lake16–186 daysHoward et al. 1990
Volatilization, pond9 daysWHO 1998
Aqueous photolysis40 daysBetterton 1991
Biodegradation in groundwater2–14 daysFootnote Table 8-2[a]Howard et al. 1991
Removal from post-primary treatment municipal wastewater in microcosm constructed wetlands

90% removal of acetone in 5–10 days in summer (daytime/nighttime temperature of 24/16°C)

and 10–14 days in winter (daytime/nighttime temperature of 13/7°C)

Grove and Stein 2005
Soil biodegradation1–7 days[a]Howard et al. 1991
Footnote Table 8-2 a

Scientific judgment based on unacclimatized aqueous aerobic biodegradation half-life.

Return to footnote Table 8-2 a referrer

8.2 Bioaccumulation Potential

Acetone has a very low log Kow value of −0.24 (Table 2).  Only one bioconcentration study was found for acetone: Rustung et al. (1931) measured a BCF of 0.69 in haddock. The BCF for acetone was estimated to be 3.2 L/kg by the BCFBAF (2008) program, and its middle trophic level BAF was estimated to be 0.96 L/kg (BCFBAF 2008).  Based on the above information, acetone is not expected to bioconcentrate, biomagnify or bioaccumulate.

Top of Page

9. Potential to Cause Ecological Harm

9.1 Ecological Exposure Assessment

This section discusses the environmental exposure data for acetone, and the choice of the predicted environmental concentrations (PECs) to be used in the risk quotient (RQ) calculations (see Characterization of Ecological Risk section).  Natural background concentrations of acetone are quite low,  based on very low or non-detect levels of acetone measured in many instances in air and water samples from locations not in proximity to point sources (Appendix Tables A1 and A2). Therefore, natural background concentrations were not taken into account in the selection of the PECs.

9.1.1 Air

Acetone has been measured extensively in outdoor air in Canada and the United States. Acetone is commonly included in studies analysing VOCs in air. Concentrations of acetone in air are presented in Table A1 of Appendix A.

Acetone is measured and reported as part of Environment Canada’s National Air Pollution Surveillance (NAPS) program (Environment Canada 2011b) (see Table A1, Appendix A). Four- and 24-hour concentrations from 22 monitoring stations nationwide are collected in agricultural, rural, wilderness (e.g., Kejimkujik National Park), urban and industrial locations. Acetone concentrations at all locations, from 2000 to 2009, ranged from 0.003 to 80.2 μg/m3.  The maximum acetone concentration was measured at a rural station in Egbert, Ontario, where the median and 95th percentile concentrations were 5.7 μg/m3 and 18.2 μg/m3, respectively, in 4-hour samples (Environment Canada 2011b).

Acetone was also measured in outdoor air outside of homes in Windsor and Ottawa, Ontario, Regina, Saskatchewan, and Halifax, Nova Scotia, in four recent Canadian studies (Zhu et al. 2005; Health Canada 2010a, b, 2011; see Table A1, Appendix A). Outdoor air concentrations in these Canadian studies ranged from 0.015 to 544.1 μg/m3, with median concentrations ranging from 0.2 to 12.9 μg/m3 and 95th percentile concentrations from 6.0 to 245.9 μg/m3, respectively (Zhu et al. 2005; Health Canada 2010a, b, 2011). The highest outdoor air concentrations were measured in Windsor (Health Canada 2010a).

Acetone has been measured in air near an industrial site in the United States. Twenty-four-hour average concentrations measured at the fence-line of the Eastman Chemical Co. in Tennessee ranged from 50 to 500 µg/m3 (OECD 1999). Acetone has also been measured in municipal landfill gases in the United States; average concentrations were 6838 and 32 500 parts per billion (ppb) by volume (Zimmerman and Goodkind 1981; Lang 1989). This is equivalent to about 16.2  and 77.2 mg/m3 in the landfill gases at standard temperature and pressure (STP)Footnote[2].

The highest 95th percentile outdoor air concentration of acetone measured in Canada (245.9 μg/m3 measured in Windsor, Ontario; Health Canada 2010a) was used as a predicted environmental concentration (PEC) in the risk quotient (RQ) calculations for terrestrial plants and mammals (see Table 9-1 below).

9.1.2 Water

No Canadian measurements of acetone in surface water or groundwater or in effluent from point sources were identified. Table A2 in Appendix A contains data on concentrations of acetone in surface water, groundwater and drinking water samples as well as in industrial and landfill effluents in the United States.

Based on concentrations found in seawater, lakes and streams (see A2 of Appendix A), it appears that ambient background levels of acetone in natural waters vary from below the limit of detection (LOD) to 68 µg/L.

From 2002 to 2005, the National Water-Quality Assessment (NAWQA) Program of the US Geological Survey (USGS) measured acetone in over 600 groundwater, surface water and finished water samples in 24 selected community water systems in the United States (USGS 2007). The majority of the samples had non-detectable levels of acetone ( less than  6 or 7 µg/L). Acetone was quantified in two groundwater samples at a maximum concentration of 68 µg/L. Acetone levels ranged from 0.2 to 0.7 µg/L in six residential well waters adjacent to a landfill in Wilmington, Delaware (DeWalle and Chian 1981).

According to the Screening Information Data Set (SIDS) for acetone (OECD 1999), levels of acetone in natural water and industrial monitoring wells rarely exceed 1 mg/L, and levels found in surface water and groundwater samples are highly dependent on the type of water sample, such as industrial, commercial, residential, sea, surface, ground or well.

No data on the concentrations of acetone in natural waters in Canada have been identified. Therefore, environmental concentrations have been estimated for a worst-case aquatic industrial release scenario based on NPRI data (Environment Canada 2011a). The largest amount of acetone reported released or transferred for disposal to water in the years 1997–1998 and 2009–2010 at a single site was input into the equation below (Q). This was a transfer of 39 tonnes for disposal to a municipal sewage treatment plant in 1998 by a manufacturer in the Toronto area.  These time periods were used because 1997–1998 were the last 2 years in which there was Canada-wide reporting of acetone to the NPRI, and 2009–2010 were the years when data were available for acetone reporting from Ontario to comply with Ontario VOC regulations (see Releases to the Environment section).

The equation used to estimate the aquatic concentration resulting from an industrial release is as follows:

Aquatic concentration (mg/L) = [1000 × Q × L × (1-R)] ÷ (N × F × D)

where:

Q: 
total substance quantity used annually at an industrial site (39 000 kg/year)
L: 
loss to wastewater (fraction), equal to 1
R: 
wastewater system removal rate (fraction), equal to 0
N: 
number of annual release days (250 days/year)
F: 
wastewater system effluent flow (3456 m3/day)
D: 
receiving water dilution factor (dimensionless), equal to 1

The above scenario uses highly conservative assumptions, such as no removal in a wastewater treatment system before discharge, a relatively small effluent flow volume, equal to wastewater treatment plant effluent flow at the 10th percentile (3456 m3/day) of the wastewater treatment plant effluent discharge rates across Canada, and no dilution in the receiving water. Based on these assumptions, this scenario yields a PEC value of 45.1 mg/L. This PEC value represents the level of exposure in the receiving water near the point of discharge. This PEC is used in the RQ calculation for pelagic organisms and for water ingestion by terrestrial mammals (see Table 9-1 below).

In comparison, the highest concentration of acetone found in industrial wastewater from the United States is 37.7 mg/L (OECD 1999).

9.1.3 Soil

No measured concentrations of acetone in soil in Canada were identified. In the United States, acetone has been detected in 43% of the soil samples from designated waste disposal sites that were tested for acetone (ATSDR 1994). The mean concentration of acetone in soil from Summit National Site, a Superfund cleanup site in Ohio, was 9484 µg/kg dry weight (US EPA 1988). The maximum value found in soil from another Superfund site in Puerto Rico was 9500 µg/kg (ATSDR 1994) (the mean concentration was not reported).

The concentration of acetone measured in septic tank effluent from a community septic tank serving 97 homes in Tacoma, Washington, USA was 70.3 mg/L (DeWalle et al. 1985). Septic tank effluent is released to the soil surrounding the septic tank, where it is then subject to dispersion, biodegradation and volatilization. There are some small communities in Canada that use communal septic tanks as their sewage disposal method. From federal inventory information for First Nations communities (Environment Canada 2006), there are 14 First Nations communities with communal septic systems serving populations between 100 and 360 people. Ontario Ministry of the Environment data (OMOE 2003) also indicate three communities in Ontario using communal septic systems serving populations of 165–1240 people; however, it is known that the largest of these communities recently built a sewage lagoon.

Given that virtually no releases of acetone to soil were reported to the NPRI in the years 1997–1998 and 2009, except for 1.1 tonnes in 1997, which represented 0.1% of total releases that year (see Releases to the Environment section), a PEC for soil was not developed.

9.2 Ecological Effects Assessment

A large data set of toxicity values is available for microorganisms, aquatic plants, vertebrates, invertebrates and soil organisms. Summaries of acute and chronic toxicity data for algae, aquatic invertebrates, microorganisms, fish, terrestrial plants, insects, birds and mammals are available in OECD (1999), WHO (1998) and, for aquatic organisms, Hutchinson et al. (2006).

The ability of acetone to inhibit cell multiplication has been examined in a wide variety of microorganisms (5 studies involving 11 species) (OECD 1999). No-observed-effect concentrations (NOECs) were greater than 1700 mg/L for exposures lasting from 6 hours to 4 days.

Studies with aquatic plants, including algae and diatoms, are summarized in OECD (1999), WHO (1998) and Hutchinson et al. (2006). More recently, Han et al. (2008) studied the effects of acetone on spore release by the green alga Ulva pertusa, and Tsai and Chen (2007) and Cho et al. (2009) studied the acute (48-hour) toxicity of acetone to the green microalga Pseudokirchneriella subcapitata. In total, 11 studies involving 20 species of aquatic plants were identified. Toxicity thresholds or median effective concentrations (EC50 values) were all higher than 2400 mg/L, except for one lowest-observed-effect concentration (LOEC) of 530 mg/L, obtained with the blue-green alga Microcystis aeruginosa in an 8-day study (Bringmann and Kühn 1978).

A large data set of acute toxicity values is available for aquatic organisms (WHO 1998; Hutchinson et al. 2006), including 11 studies involving 10 species of aquatic invertebrates, 8 studies involving 6 fish species and 2 amphibian studies. Acute LC50s ranged from greater than  100 to 64 300 mg/L (WHO 1998), with one 10 mg/L result, which was obtained with Daphnia magna (Dowden and Bennett 1965). This result is an outlier, as the other four LC50s for D. magnawere over 9000 mg/L.

The following early-life stage studies were identified: Marquis et al. (2006) found no significant effects on common frog (Rana temporaria) embryos and larvae at acetone concentrations of 0.001–0.1 mL/L (0.79–79 mg/L) during 96/48-hour exposures. Hallare et al. (2006) found no effects of acetone on the survival of zebrafish (Danio rerio) embryos after a 96-hour exposure, even at the highest concentration tested (2.0% volume per volume [v/v]), but found a LOEC of 1.5% v/v (approximately 11 766 mg/L) for developmental effects.

Two chronic toxicity studies were identified with fish, and one was identified with amphibians (Hutchinson et al. 2006). The two fish studies found no significant effects at concentrations of 10 μL/L (about 7.9 mg/L) in a 52 day study with lake trout (Salvelinus namaycush) (Mac and Seelye 1981) and at 2000 μL/L (about 1580 mg/L) in a 60 day study with zebrafish (Danio rerio) (Weber et al. 2003).  Pollard and Adams (1988) found an acceleration of metamorphosis in the southern cricket frog (Acris gryllus) at acetone concentrations of 10 and 50 mg/L, as evidenced by acceleration in forelimb development as well as significant decreases in tail length for both treatments and in total body length for the 50 mg/L treatment compared with the control over the 15-day test period. Metamorphosis was completed in 15 days in the acetone treatment groups compared with 25 days for the control group. In the two acetone treatments, the tail length decreased by 25% and 44% over 15 days, respectively, while in the control group, the tail length increased by 20%. Only two concentrations of acetone were tested in this study, and there was no replication. This study was considered to be of low quality and so was not considered for use in the selection of a critical toxicity value (CTV).

Five chronic or early life-stage exposure studies involving three species were found for aquatic invertebrates (Hutchinson et al. 2006). The two studies of acceptable quality that found adverse effects are described as follows: Bluzat et al. (1979) studied the toxicity of acetone at concentrations of 0.1% [] to 0.6% by volume (equivalent to 790 to 4740 mg/L at 20°C) to the freshwater snail Lymnea stagnalis over a 10-month period. Acetone did not cause any mortality, even at the highest treatment level. However, there were sublethal adverse effects: 1) all concentrations of acetone (0.1–0.6%) caused a significant decrease in shell mineralization, as measured by a decrease in its weight/size factor ratio, but this effect was not concentration dependent; 2) the overall fecundity was decreased, starting with a weak effect at 0.2% (1578 mg/L) and proportional to concentration; and 3) a teratogenic effect (double or multiple embryos) was observed in all treatment groups, but the effect was most pronounced at the lower concentrations: at 0.1–0.2%, the rate was 10–12 times higher than in the control group, whereas at 0.4% and 0.6%, the rate was only double that of the control group. The lowest effect value of 0.2% (1578 mg/L) (reduction of fecundity) was used as the CTV for pelagic organisms (see Table 9-1 below).  This study was deemed to be of satisfactory quality (Environment Canada 2013).

LeBlanc and Surprenant (1983) studied the survival of Daphnia magna over 28 days. The NOEC from this study was 1400 mg/L, and the LOEC was 2800 mg/L. Given the large spread between the NOEC and LOEC, the geometric mean of these two concentrations (1980 mg/L) was calculated, which is often called the maximum acceptable toxicant concentration (MATC).

For soil-dwelling organisms, four acetone toxicity studies were identified--one with plants and three with invertebrates. Gorsuch et al. (1990) tested the effects of acetone exposure on the germination and growth of radish (Raphanus sativus), lettuce (Lactuca sativa) and perennial ryegrass (Lolium perenne). Acetone solution (0.1–100 mg/L) was used to soak paper towels in a cellophane wrapper (growth pouch), which also contained the plant seeds. No effects were observed on the germination, shoot or root growth of any of the plant species at the highest concentration tested (100 mg/L) after exposure for 7 days.

An acute test was conducted with the soil ciliate Colpoda inflata (Ciliophora, Protozoa), which inhabits the soil pore water. The EC50 was greater than  3000 mg/L (Berthold and Jakl 2002). A 48-hour contact toxicity test was conducted with the earthworm Eisenia foetida (Roberts and Dorough 1984), where the exposure was through contact with moist filter paper to which the test substance had been added. The LC50 for acetone was in the range 100–1000 µg/cm2 (exact value not given). Using the ECOSAR (2008) program, a 14-day earthworm (Lumbricus terrestris) LC50 value of 172 mg/L was predicted. Anderson et al. (2004) performed acute (4-hour) toxicity tests with the soil nematode Caenorhabditis elegans, with the endpoint being behavioural--the rate of movement compared with control replicates. The EC50 (the concentration needed to reduce average worm movement to 50% of control movement) with acetone was 0.65 mM (37.8 mg/L). This value is the lowest soil toxicity value; however, this study received a low reliability score during the evaluation of its quality, mainly due to incomplete reporting of the test methodology (Environment Canada 2013). Therefore, the ECOSAR (2008) modelled 14-day LC50 value of 172 mg/L is considered more reliable for evaluating toxicity to soil organisms. A CTV was not derived for soil, however, as this exposure route is considered unlikely.

Only one avian study was identified, summarized as follows: The 5-day LC50s of acetone for Japanese quail (Coturnix coturnix japonica) and ring-necked pheasant (Phasianus colchicus) following dietary exposures were greater than 40 000 mg/kg (Hill et al. 1975).

No toxicity data for mammalian wildlife were identified; therefore, toxicity data for laboratory mice and rats were used as a surrogate. Mammalian toxicity data are summarized in the Health Effects Assessment section of this report. The CTVs for mammalian exposures through inhalation and drinking water are reported in Table 9-1.

Studies containing the most sensitive values for endpoints of concern (i.e., aquatic organisms, terrestrial plants, wildlife ingestion, wildlife inhalation) were critically reviewed for integrity. The most sensitive values from the studies deemed to be of acceptable quality were selected as CTVs and are listed in Table 9-1 below. Effects on benthic organisms were not considered, as acetone does not partition appreciably to sediment (see Environmental Fate section). The studies used to derive the CTVs for mammalian exposure through air (Mast et al. 1988) and water (Dietz et al. 1991) were evaluated by Health Canada and determined to be the most sensitive acceptable studies for these endpoints (see Health Effects Assessment section).

For terrestrial plant exposure through air, only one study was identified (Schubert et al. 1995), involving exposure of hydrated pollen to acetone vapours to determine whether the germination rate would be affected. The test method is summarized as follows:  An amount of 0.5 mg pollen of Nicotiana tabacum was placed into 3.5 cm petri dishes and held in a water saturated atmosphere for one hour, followed by application of germination medium.  Then the petri dishes were put into small, tightly-sealed glass troughs (325 cm3 each), into which acetone was injected by syringe, where it evaporated at once.  The pollen was exposed to different concentrations (no concentration data provided) of the test compounds in the dark at 22°C for 2 hours, following which the percentage of germinated pollen was counted by microscopy, and compared to the germination in a control treatment.  The effective dose causing a 25% decrease in germination relative to the control treatment (ED25) was calculated as 12 200 mg/m3 for acetone.  The Schubert et al. (1995) study had some deficiencies, particularly the lack of full data reporting from the experiments with acetone (Environment Canada 2013).  However, this lack of full reporting was not considered to have affected the results of the study, and therefore, it was still deemed acceptable to use it to derive the CTV, given the lack of other studies of plant exposure to acetone in air. 

9.3 Characterization of Ecological Risk

The approach taken in this ecological screening assessment is to examine various supporting information and develop conclusions based on a weight of evidence approach as required under section 76.1 of CEPA 1999. Particular consideration has been given to sources, releases, occurrence in the environment, risk quotient (RQ) analyses, persistence, bioaccumulation and toxicity.

Acetone has natural and anthropogenic sources throughout Canada. It is manufactured in Canada only as a by-product, but is imported and used by a variety of industrial sectors. Releases of acetone to the environment as reported by Canadian industry are primarily to air, with smaller amounts to water and landfill, and virtually none to soil. Acetone tends to stay mainly in the compartment to which it is released. It is persistent in air, but not in water or soil. Acetone is not bioaccumulative and has low toxicity to aquatic organisms and terrestrial plants and mammals.

RQs were developed for key exposure scenarios in media of concern--namely, air and water. Endpoint organisms were selected based on analysis of exposure pathways. For each endpoint organism, a conservative (worst-case) predicted exposure concentration (PEC) and a predicted no-effect concentration (PNEC) have been determined. The PNEC was arrived at by selecting the lowest CTV for the organism of interest and dividing it by an application factor (AF) appropriate to account for the following sources of uncertainty: interspecies and intraspecies variations in sensitivity, extrapolation of results from laboratory to field and the use of short-term studies to model long-term exposure. AFs of 10 were used for long-term (chronic) toxicity values, and AFs of 100 were used for acute values. An RQ (= PEC/PNEC) was calculated for each of the endpoint organisms. A summary of values used for the RQs is presented in Table 9-1.  Derivation of PEC values for air and water is described in the Ecological Exposure Assessment section.

RQs for air and water indicate that acetone concentrations likely do not exceed concentrations associated with effects, even using very conservative scenarios and assumptions.  Therefore, there is low risk of harm to aquatic or terrestrial organisms from this substance.

Table 9-1: Summary of values used to calculate risk quotients for acetone
Exposure mediumOrganismCTVAFPNECPECRQ
Urban airTerrestrial plants (Nicotiana tabacum)12 200 mg/m3100122 mg/m30.246 mg/m30.002
Urban airTerrestrial wildlife: inhalation (rat)26 100 mg/m3100261 mg/m30.246 mg/m30.001
Water, near industrial dischargePelagic organisms (freshwater snail)1578 mg/L10158 mg/L45.1 mg/L0.29
Water, near industrial dischargeTerrestrial wildlife: ingestion from water (mink)Footnote Table 9-1 [a]9272 mg/kg-bw per dayFootnote Table 9-1[b]10927 mg/kg-bw per day4.96 mg/kg-bw per dayFootnote Table 9-1[c]0.005
Footnote Table 9-1 a

CTV for male rat was converted to CTV for mink because mink is a species native to Canada.

Return to footnote Table 9-1 a referrer

Footnote Table 9-1 b

bw = body weight.  To derive the CTVmink, the CTVrat (1700 mg/kg-bw per day) was multiplied by an interspecies scaling factor for a typical adult female mink (Mustela vison), using the equation: CTVmink = (CTVrat × BWmink)/ DWImink, where BWmink is body weight (0.6 kg) and DWImink is daily water intake (0.11 kg/kg-bw per day) (US EPA 1993). This equation assumes that all exposure to the substance is via water and that the substance is completely bioavailable for uptake by the organism.

Return to footnote Table 9-1 b referrer

Footnote Table 9-1 c

This value represents the daily dose for a mink and was obtained by multiplying the aquatic PEC of 45.1 mg/L by the daily water ingestion rate of an adult female mink, 0.11 kg/kg bw per day (US EPA 1993).

Return to footnote Table 9-1 c referrer

Based on the information presentedin this screening assessment, it is concluded that acetone does not meet the criteria under paragraph 64(a) or (b) of CEPA 1999, as it is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity or that constitute or may constitute a danger to the environment on which life depends.

9.4 Uncertainties in Evaluation of Ecological Risk

Uncertainty was associated with the exposure characterization of acetone. 

Non-industrial, anthropogenic sources of acetone in the Canadian environment (e.g., from automobiles and other combustion sources), as well as releases from natural sources and natural background concentrations, have not been quantified in Canada. Nevertheless, there were ample Canadian ambient air data from which to select a PEC in air to represent a very conservative or worst-case exposure scenario. The exposure value used for air was the maximum concentration measured in Canada during the period 2000–2009, and no risk was identified for terrestrial plants or mammals.

No measured concentrations of acetone were identified for surface water or groundwater, effluents from industrial sources or soils in Canada. The exposure value used for water was therefore modelled based on a worst-case exposure scenario using the largest amount of acetone reported to be released or transferred to water at a single site during the years 1997, 1998 and 2009, with no treatment prior to discharge or dilution in the receiving water body. No risk was predicted for aquatic organisms or mammals exposed to acetone in water.

Regarding the effects characterization, only one toxicity study involving exposure of terrestrial plants to acetone vapours was found, and this study contained deficiencies, mainly in the reporting of the data; however, it was nevertheless used to derive a CTV, due to the absence of better studies or information. The RQ for exposure of terrestrial plants to atmospheric acetone was several orders of magnitude below 1. A study of the effects of acetone in soil on the germination and growth of terrestrial plants also showed that acetone caused no effects (see Ecological Effects Assessment section).

Top of Page

10. Potential to Cause Harm to Human Health

10.1 Exposure Assessment

10.1.1 Environmental Media and Food

Data pertaining to concentrations of acetone in ambient air, indoor air, personal air, drinking water, food, soil and humans were identified for Canada and elsewhere. Although numerous studies were identified, only those considered most relevant for assessing exposure of the general population of Canada are summarized and presented in Appendix A (Tables A1 to A4).

Upper-bounding estimates of total daily intake of acetone from air, water, food and beverages, and soil for the general population of Canada are summarized in Appendix B. Total daily intake of acetone ranged from 133 μg/kg-bw per day for breastfed infants to 650 μg/kg-bw per day for children aged 0.5–4 years. Acetone in food, which is primarily naturally occurring, and acetone in air, which is primarily from anthropogenic indoor sources, including household and cosmetic products, were estimated to be the highest contributors to total daily intake of acetone. Acetone is produced endogenously in the body during natural biological processes. The following exposure characterization focuses on external (non-endogenous) sources of acetone from environmental media, food and products.

10.1.1.1 Ambient Air, Indoor Air and Personal Air

Acetone has been measured extensively in ambient (outdoor) and indoor air in Canada and the United States. Acetone is commonly included in studies analyzing VOCs in air. Concentrations of acetone in air are presented in Table A1 of Appendix A.

Acetone is measured and reported as part of Environment Canada’s NAPS program. Four- and 24-hour acetone concentration data from 22 monitoring stations nationwide are collected in agricultural, rural, urban and industrial locations. In 3688 24-hour samples collected from 2000 to 2009, acetone concentrations ranged from 0.007 to 35.2 μg/m3, with a median concentration of 2.9 µg/m­­3 and a 95th percentile concentration of 6.6 µg/m­­3. Over the same time period, in 5754 4-hour samples, acetone concentrations ranged from 0.003 to 80.2 μg/m3, with a median concentration of 2.9 µg/m­­3 and a 95th  percentile concentration of 12.4 µg/m­­3. The maximum acetone concentration was measured at an agricultural station in Egbert, Ontario, where median and 95th percentile concentrations were 5.7 μg/m3 and 18.2 μg/m3, respectively (Environment Canada 2011b).

Acetone was also measured in ambient and indoor air in four recent Canadian studies. Measurements took place in Windsor, Ontario, Regina, Saskatchewan, Halifax, Nova Scotia, and Ottawa, Ontario, as part of the Windsor Ontario Exposure Assessment Study (Health Canada 2010a), the Regina Indoor Air Quality Study (Health Canada 2010b), the Halifax Indoor Air Quality Study (Health Canada 2011) and the Ottawa Residential Home Study (Zhu et al. 2005). In the Windsor study, 45–48 non-smoking participant homes were monitored between January 2005 and August 2006, with samples collected over 24-hour periods for 5 consecutive days. In the Regina study, 146 homes, of which 34 homes had at least one smoking participant, were monitored in 2007 with 24-hour and 5-day samples. In the Halifax study, 50 homes were recruited in both the winter and the summer of 2009, and acetone concentrations indoors and outdoors for seven consecutive 24-hour periods were collected. In these three studies, active air samplers were deployed concurrently inside and outside the home. The Ottawa study is an earlier study sponsored by Health Canada in which acetone was measured in 75 homes between November 2002 and March 2003. Each home was sampled once, and indoor and outdoor active samplers were deployed, with 10 L of air collected over 100 minutes (Zhu et al. 2005).

Ambient air concentrations in these Canadian studies ranged from 0.015 to 544.1 μg/m3, with median and 95th  percentile concentrations ranging from 0.2 to 12.9 μg/m3 and from 6.0 to 245.9 μg/m3, respectively (Zhu et al. 2005; Health Canada 2010a, b, 2011). The maximum ambient air concentration was measured in Windsor (Health Canada 2010a). Indoor air concentrations were generally higher than ambient air concentrations and ranged from 0.01 to 3755.5 μg/m3, with median and 95th percentile concentrations ranging from 21.8 to 173.8 μg/m3 and from 101.8 to 647.2 μg/m3, respectively (Zhu et al. 2005; Health Canada 2010a, b, 2011). Both the lowest and highest indoor air concentrations were measured in Windsor (Health Canada 2010a). Indoor and ambient (outdoor) air concentrations have also been measured in several American studies (Heavner et al. 1996; Girman et al. 1999; NYSDOH 2005; Weisel et al. 2005, 2008). In the United States, reported acetone concentrations in homes ranged from less than  0.25 μg/m3 (NYSDOH 2005) to 664.99 μg/m3 (Heavner et al. 1996).

Two general trends were observed from these studies: indoor air concentrations of acetone are higher than ambient air concentrations, and concentrations of acetone are higher in the summer than in the winter. In the Windsor study, the indoor/outdoor ratio for acetone was greater than 10, indicating predominately indoor sources for acetone (Stocco et al. 2008).

The presence of acetone in indoor air may be attributed to various anthropogenic sources, including evaporative loss and releases from products and as a by-product from incomplete combustion (gas stove, gas fireplace, smoking). Natural sources may include plants and exhaled air. Solomon et al. (2008) examined diurnal patterns in indoor VOC concentrations in Germany in 2005. That study showed elevated levels of acetone indoors at most times during the day; the authors concluded that this likely was not caused by typical anthropogenic sources, such as off-gassing from the building, but rather was related to the occupants’ expired air, a local kitchen and indoor plants (Solomon et al. 2008).

Acetone is a component of cigarettes and tobacco smoke, which are sources of acetone exposure from indoor air. Health Canada requires tobacco companies to report information about 26 chemical constituents found in tobacco and 41 chemical emissions found in tobacco smoke; acetone is on this list (2011 email from Risk Management Bureau, Health Canada, to Existing Substances Risk Assessment Bureau, Health Canada; unreferenced). Median indoor acetone concentrations in smoking and non-smoking households in the Regina Indoor Air Quality Study were similar; however, smoking households had higher maximum concentrations in the winter and lower maximum concentrations in the summer (Health Canada 2010b). Lower acetone concentrations in smoking households during the summer months could be due to increased ventilation in these homes. In a study conducted in New Jersey, concentrations of acetone in indoor air were highest in smoking environments, particularly in workplaces, where concentrations up to 21 083 μg/m3were measured (Heavner et al. 1996).

Typically, air concentration data from fixed ambient air monitoring stations and fixed indoor air samplers are used to characterize population air exposures. However, for acetone, several studies, including one Canadian study conducted in Windsor, Ontario, measured concentrations of acetone in personal air in addition to indoor air over a 24-hour period (Weisel et al. 2005; Health Canada 2010a; Geiss et al. 2011). Selected participants in the Windsor study wore backpacks equipped with sampling apparatus over 24-hour periods for 5 consecutive days to measure personal exposure to acetone in air. Participants were asked to wear the sampling equipment during the normal course of a day; however, individuals with expected occupational exposure to acetone were not eligible. The highest concentration reported among Windsor participants wearing personal backpackswas 1871.9 μg/m3, while the corresponding median and 95th percentile values were 116.1 and 475.9 μg/m3, respectively (Health Canada 2010a). Personal air data, as opposed to fixed ambient and indoor air data, are considered to be more representative of acetone intake through inhalation, as the sampling apparatus samples the air surrounding the individual, similar to what is present in the breathing zone. This value is expected to provide a conservative estimate of daily intake to acetone from air, as acetone concentrations in indoor and outdoor air in Windsor were higher than in Regina, Halifax and Ottawa, and personal air samples were collected in the summer, when acetone air concentrations are generally higher than in the winter. Note that the 95th  percentile concentrations of acetone in personal air, indoor air and outdoor air measured in the summer of 2005 in Windsor were 475.9, 647.2 and 19.8 µg/m3, respectively. Therefore, the 95th  percentile value for the concentration of acetone from personal air sampling from the study conducted in Windsor (475.9 µg/m3) was used to calculate total daily intake of acetone from air.

In analyzing data collected in Windsor (Health Canada 2010a), Stocco et al. (2008) found that indoor air acetone concentrations were higher than personal concentrations in the summer, but not in the winter. The annual personal/indoor air acetone concentration ratio was 1.01. A mixed effects model indicated that approximately 46% of the variability in personal acetone levels could be accounted for using indoor concentrations, season and air exchange rates. In the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study conducted in three US cities, the study authors concluded that indoor air concentration accounted for less than 20% of the variance of personal exposure variability for acetone (Weisel et al. 2005; Liu et al. 2007). In addition, personal exposure was significantly higher than residential indoor concentrations. The personal exposure was largely attributed to yard and gardening activities and nail polish hardener/remover use (Liu et al. 2007). In a study conducted in 11 cities across Europe (AIRMEX), median personal air concentrations of acetone were similar to concentrations in private homes, slightly higher than concentrations in public buildings (offices, schools) and much higher than concentrations in outdoor air (2011 email Geiss to Existing Substances Risk Assessment Bureau, unreferenced; Geiss et al. 2011), implicating indoor air as a major contributor to personal air concentrations.

It is recognized that the use of products containing acetone in indoor environments could result in higher peak acetone exposures over a short period; intake estimates resulting from these uses are discussed in the Products section.

10.1.1.2 Drinking Water

Acetone is not routinely measured as part of provincial or municipal drinking water surveillance programs in Canada. Acetone was measured in tap water collected from 71 homes in Ottawa, Ontario, in 2002 and 2003; concentrations ranged from less than 2 to 131 μg/L, with a 95th  percentile concentration of 48 μg/L and a mean concentration of 11.0 μg/L (2003 personal communication from J. Zhu Health Canada Chemistry Research Division to Existing Substances Risk Assessment Bureau, unreferenced). Acetone was not detected during sampling of 30 potable water treatment facilities across Canada in 1979, but this was likely due to the very high quantification limit (~1000 μg/L) (Otson et al. 1982). In the United States, acetone was detected in drinking water from 10 cities as part of the 1975 National Organics Reconnaissance Survey; however, it was quantified at only one site in Seattle, Washington, at a concentration of 1 μg/L (US EPA 1975). In Texas, a maximum acetone concentration of 10.7 μg/L was reported in water samples taken from eight residences as part of the Lower Rio Grande Valley Environmental Monitoring Study (US EPA 1994). Acetone levels ranged from 0.2 to 0.7 µg/L in six residential wells adjacent to a landfill in Wilmington, Delaware (DeWalle and Chian 1981).

Acetone was measured in over 600 groundwater, surface water and finished water samples from 2002 to 2005 in 24 selected community water systems in the United States (USGS 2007). The majority of the samples had non-detectable levels of acetone ( less than  6 or 7 µg/L); however, acetone was quantified in seven finished water samples at a maximum concentration of 11.73 µg/L (Carter et al. 2007; USGS 2007). Finished water was defined as water that had passed through all the processes in a water treatment plant and was ready to be delivered to consumers.

A number of Canadian and US studies measured acetone in drinking water; concentrations are presented in Table A2 of Appendix A. The 95th percentile value for the concentration of acetone in 71 samples of tap water from homes in Ottawa, Ontario (48 µg/L), was used to calculate total daily intake of acetone from drinking water.

10.1.1.3 Food and Beverages

Acetone occurs naturally in a wide variety of foods, including fruits, vegetables and dairy products. It has been detected in baked potatoes (Coleman et al. 1981), nectarines (Takeoka et al. 1988), kiwi fruit (Bartley and Schwede 1989), roasted filbert nuts (Kinlin et al. 1972), chicken (Grey and Shrimpton 1967; Shahidi et al. 1986), cured pork (Hinrichsen and Anderson 1994), mutton and beef (Shahidi et al. 1986) and blue cheese (Day and Anderson 1965). Based on the compilation by the Division for Nutrition and Food Research TNO, acetone was also detected in papaya, raspberries, blackberries, ginger, parsley, cocoa, endives, asparagus, sherry and orange juice (van Straten and Maarse 1983; Maarse and Visscher 1989). Acetone has been detected, but not quantified, in human milk of nursing mothers (Pellizzari et al. 1982; Giroux et al. 1992).

Concentrations of acetone quantified in food are presented in Table A3 of Appendix A. Acetone was measured at concentrations up to 3000 µg/kg in strawberries (van Straten and Maarse 1983), the mean value was 2000 µg/kg in black currants from Sweden (Andersson and von Sydow 1966) and the mean concentration (dry weight) was 600 µg/kg in apples (Feys et al. 1980; Maarse and Visscher 1989) and at trace levels in mangos from Sri Lanka (MacLeod and Pieris 1984). The highest concentration of acetone identified in vegetables was 16 000 µg/kg in tomatoes (van Straten and Maarse 1983), with lower levels found in canned and frozen sweet corn (Bills and Keenan 1968), beans (common, lima and mung beans, soybeans), split peas and lentils (Lovegren et al. 1979), potato chips (Mookherjee et al. 1965) and carrots (Heatherbell et al. 1971; Maarse and Visscher 1989). Acetone was measured at concentrations ranging from 20 to 1700 µg/kg in beer (Rosculet and Rickard 1968; van Straten and Maarse 1983) and from 6 to 200 µg/L in apple cider from Britain (Williams et al. 1980). Acetone was quantified in bread at concentrations up to 10 100 µg/kg (Maarse and Visscher 1989). Although many of the concentrations of acetone in food commodities were measured over 30 years ago, these data are considered relevant today, as it is not anticipated that naturally occurring concentrations of acetone in unprocessed food will have changed significantly over this period.

Acetone is produced endogenously in dairy cattle. Milk from healthy cows typically contains up to 11.6 mg/L (approximately 11 600 µg/L, using a density of 1.03 kg/L for milk) of acetone (ACC 2003). A US Environmental Protection Agency (EPA) study investigated the presence of VOCs in commercially available whole, 1% and 2% milk samples from Las Vegas, Nevada. In all milk samples (whole, 2%, 1%), the average acetone concentration ranged from 0.029 to 0.031 mg/L (from 29 to 30 µg/kg), and the maximum concentration ranged from 0.037 to 0.043 mg/L (from 36 to 42 µg/kg) (Hiatt and Pia 2004). However, high acetone levels have been reported in cow’s milk from cattle under ketotic stress, which occurs in approximately 4–5% of cows due to glucose shortages caused by milk production or metabolic demands associated with later stages of gestation (ACC 2003). In a study involving 10 375 registered Holsteins in southern Ontario dairy herds, the mean and maximum concentrations of acetone in raw milk were 1.32 mg/L (1280 µg/kg raw milk) and 278 mg/L (269 900 µg/kg raw milk), respectively, although only 7% of the samples analyzed contained detectable levels of acetone (detection limit not specified) (Wood et al. 2004). In a study of the diurnal variations of milk production in hyperketonemic Swedish dairy cows, milk acetone levels ranging from 18.6 to 225.6 mg/L (18 000 to 219 000 µg/kg raw milk) were also reported (Andersson and Lundstrom 1984). In other studies involving dairy products, the average concentrations of acetone in cheddar cheese and fresh sweet cream butter samples from the United States were reported to be approximately 8500 µg/kg and 130 µg/kg, respectively (Day et al. 1960; Siek and Lindsay 1970).

Acetone is on the Flavour and Extract Manufacturers Association (FEMA) Generally Recognised as Safe (GRAS) list in the United States when present in beverages, baked foods, desserts and preserves at concentrations ranging from 5 to 8 mg/L (Oser and Ford 1973). In Canada, acetone is a permitted food additive where it may be used as a carrier or extraction solvent in spice extracts leaving a maximum residue of 30 ppm and in meat/egg marking inks at levels consistent with Good Manufacturing Practices, according to the List of Permitted Carrier or Extraction Solvents as incorporated by reference into the Marketing Authorization for Food Additives That May Be Used as Carrier or Extraction Solvents (Health Canada 2012a). Additionally, acetone may be used as a solvent for many applications related to food packaging components, and the presence of acetone in food packaging applications is the result of impurities deriving from normal manufacturing and processing practices. In the United States, acetone is permitted at concentrations up to 30 ppb as an extraction residue in spice oleoresins, as an extraction solvent for obtaining paprika oleoresin and turmeric oleoresin, as a diluent in colour additive mixtures for food, as a pH adjusting agent in preparations of the colour additive annatto extract and as an indirect additive in food contact packaging, according to the Everything Added to Food in the United States (EAFUS) database (US FDA 2011). The use of acetone in foods in Canada is consistent with international uses of acetone (FAO/WHO 1998; US FDA 2011). According to Fenaroli’s Handbook of Flavor Ingredients, acetone is reported to be used in the following food categories (usual use level; maximum use level): alcoholic beverages (0.37 ppm; 0.37 ppm), baked goods (3.00 ppm; 9.00 ppm), fats and oils (14.00 ppm; 20.00 ppm), frozen dairy (3.00 ppm; 5.00 ppm), gelatins and puddings (0.60 ppm; 0.60 ppm), jams and jellies (0.27 ppm; 0.27 ppm), milk products (1.60 ppm; 1.60 ppm), non-alcoholic beverages (0.57 ppm; 0.57 ppm), snack foods (5.00 ppm; 10.00 ppm), soft candy (0.88 ppm; 5.40 ppm) and sweet sauce (1.30 ppm; 1.30 ppm) (Burdock 2010).

Screening-level (or upper-bounding) dietary intake estimates for acetone were generated using maximum levels reported in the literature and are outlined in Appendix B. Dietary intake was lowest in the 60+ years age group, with an intake estimate of 126 µg/kg-bw per day, and highest in infants aged 0–6 months (not formula fed), at 396 µg/kg-bw per day. Vegetables and cereal products were the primary contributors to dietary intake estimates. However, it is noted that the reported concentrations of acetone in foods were obtained mainly from non-Canadian databases, which may not necessarily represent primary sources of these foods for the Canadian population. Furthermore, use of maximum concentrations may overestimate potential dietary intake to acetone, particularly since concentrations vary widely among published data sets and maximum values were extended to all foods within a food group.

10.1.1.4 Soil and Dust

Only limited data were identified on concentrations of acetone in soil (Table A4 in Appendix A). The mean concentration of acetone in soil from the Summit National Site, a waste disposal site located in Ohio, and the maximum concentration of acetone in soils from the Vega Alta Public Supply well sites in Puerto Rico were 9484 and 9500 ng/g, respectively (US EPA 1988; ATSDR 1994). Acetone was also identified in 43% of the soil samples taken from designated waste disposal sites in the United States (ATSDR 1994). No data were found quantifying acetone concentrations in dust.

10.1.2 Products

Data pertaining to concentrations of acetone in various products in Canada, the United States and Europe were identified and are summarized below.

A survey conducted pursuant to section 71 of CEPA 1999 indicated that a wide range of products contain acetone, including automobile refinishing paints, paints and coatings, automotive care and maintenance products (e.g., air intake cleaners, brake cleaners, carburetor cleaners), and spray-grade contact adhesives with levels of acetone ranging from less than  1% to 100% (Environment Canada 2004). The list of products and concentration ranges identified in the above survey were generally consistent with identified uses in the United States. The US Household Products Database lists over 500 products containing acetone, including various paints, glazes and varnishes, paint products (thinners and cleaners), cleaners, arts and craft supplies, sealants, wood fillers and hardeners, pesticide products, adhesives and lubricants. The concentration of acetone in these products ranges from 1% to 100% for all forms (aerosol, gel, liquid and paste) (HPD 1993– ). A summary of the types of products and the concentrations of acetone in these products is provided in Table 10-1.

10-1: Summary of products identified by the US Household Products Database (HPD 1993– )
Type of productNumber of productsConcentration range (%)
Paint / glaze / varnish (aerosol)37615–60
Paint / glaze / varnish (liquid)15less than 35–58
Paint thinner (liquid)315–95
Glue / adhesive (aerosol)105–65.5
Glue / adhesive (liquid / paste)370–75
Cleaner (aerosol)201–100
Cleaner (liquid, gel, cream)251–100
Sealant (aerosol)9less than 5–30
Wood hardener (liquid)172
Wood filler (paste)45–35
Pet deodorizer (aerosol)160–80
Lubricant (aerosol)310–40
Pesticidal spray (aerosol)510–21.5

The US EPA’s Source Ranking Database also provided a list of approximately 1300 products that contain acetone, including paint (aerosol and liquid), paint remover, cleaners, stains, varnishes, sealants, furniture and lubricants (SRD 2004). The percentage of acetone contained in these products ranged from less than  0.1% to 100%. In studies carried out by the Danish Environmental Protection Agency, acetone was detected in animal care products (Nylén et al. 2004), adult toys (Nilsson et al. 2006), balloons (Nilsson 2007), candles (Eggert et al. 2002), Christmas sprays (Laursen and Trap 2002), creams for treatment of sports injuries (Hansen et al. 2006), electronic products (Malmgren-Hansen et al. 2003), hairstyle products (Poulsen et al. 2002), hobby adhesives (Nilsson and Staal Jensen 2003), joint sealants (Nilsson et al. 2004), perfume in toys and children’s articles (Glensvig and Ports 2006), printed material (Hansen and Eggert 2003), products made of exotic wood (Witterseh 2004), products used in live role play (weapons, masks, etc.) (Vogt-Nielsen and Hagedorn-Rasmussen 2007), proofing sprays (Feilberg et al. 2008), shoe care products (Engelund and Sørensen 2005), spray paint (Nielsen et al. 2003), stain removers (Engelund et al. 2003), tents and tunnels for children (Hansen et al. 2004) and textile colorants (Egmose and Pors 2005). Acetone has also been detected in air fresheners (Steinemann et al. 2011) and flooring materials (European Commission 1997).

Acetone has been reported as an ingredient in approximately 300 cosmetic  product formulations notified to Health Canada; a summary of the concentration ranges for the various types of products is presented in Table 10-2. Health Canada has been notified that acetone may be present at concentrations up to 30% by weight in hairspray, eyelash adhesives and eyelash removers and up to 100% by weight in artificial nail and nail polish removers (2011, emails from the Consumer Product Safety Directorate, Health Canada, to the Existing Substances Risk Assessment Bureau, Health Canada; unreferenced). It has also been reported in face mask products, in which acetone may be present at a concentration range of 30–100% by weight (2011, emails from the Consumer Product Safety Directorate, Health Canada, to the Existing Substances Risk Assessment Bureau, Health Canada; unreferenced).

Table 10-2: Summary of cosmetic products notified  under the Cosmetic Regulations to Health Canada
Type of productConcentration range (%)
Nail polish remover (liquid / gel)greater than 10–100
Artificial nail remover (liquid / gel)greater than 10–100
Nail polishgreater than 0.1–100
Polish thinner (liquid)greater than 10–100
Manicure product other (liquid / gel)greater than 3–100
Eyelash adhesive (liquid / gel)greater than 10–30
Eyelash remover (liquid / gel)greater than 10–30
Eyelash products other (liquid / gel)greater than 10–100
Hairspray (aerosol)greater than 1–30
Hairspray (pump)greater than 3–30
Tanning spray (pump)greater than 1–10
Anti-wrinkle preparation (lotion)greater than 0.3–1
Moisturizer (lotion)greater than 0.1–0.3
Cleanser (lotion)greater than 0.3–10
Mask (liquid)greater than 30–100

Air concentrations and inhalation intake estimates from the use of household and cosmetic products were generated and are presented in Appendix C. The information provided in the US Household Products Database was considered recent and representative of the Canadian market; concentrations listed in Table 10-2 were used in the estimate of general population intake from the use of household products. Based on the products identified, intake estimates were generated for three scenarios considered to represent highest exposures: inhalation exposure from spray painting, inhalation exposure from sealing a concrete floor in a basement, and dermal and inhalation exposure from use of acetone cleaner as a degreasing agent. In addition, intake estimates were generated for the use of five product categories identified in Table 10-2, including artificial/gel nail removers, hairsprays, face masks, moisturizers and cleansers. Although nail polish and nail polish removers are the most common cosmetic products containing acetone, quantitative intake estimates were not generated, as exposure to acetone is anticipated to be greater from the removal of artificial/gel nails. Intake estimates generated for the nail removal scenario are considered protective of nail polish and polish remover uses. Intake estimates were generated using the American Industrial Hygiene Association (AIHA) Exposure Assessment Strategies Committee Industrial Hygiene Modelversion 0.198 (IHMod) and the AIHA Industrial SkinPerm Model version 1.03 (SkinPerm model) (AIHA 2009a, 2010). IHMod was considered to be a relevant and suitable model for acetone, as it is suitable for substances with low boiling points, it is able to model evaporation from a standing pool and it is able to model a dermal flux for acetone, all of which were required for the infinite dose exposure scenarios. A dermal absorption rate of 100% was assumed for finite dose exposure scenarios. Dermal absorption of acetone has also been shown to occur rapidly in humans. In a Japanese study, when volunteers were exposed to an unspecified dose of acetone via skin for 2 hours/day for 4 days, immediate absorption with peak levels at the end of each application was reported (Fukabori et al. 1979). Acetone is often used as a vehicle for dermal studies of other chemicals, but no studies have quantitatively measured the uptake of acetone via the dermal route.

The spray paint intake estimate was derived based on an individual spraying an entire can of paint, containing 60% acetone, over a 15-minute period in a well-ventilated garage and remaining in the area an additional 5 minutes after the application period was complete. The concrete sealant scenario modelled an individual painting a 37.5 m2 basement room for 1 hour; typical ventilation rates were utilized, recognizing that ventilation would be limited in a basement, but that the individual would likely make efforts to maximize air exchange. The ventilation rate was assumed to be 2.5 times lower than in the spray paint scenario, and the release of acetone from the product was assumed to be linear over the drying time of the product. For the cleaner/degreaser intake estimate, dermal and inhalation exposures were expected to occur while cleaning objects with acetone (e.g., auto parts). The scenario modelled an individual pouring acetone onto a rag and using this to clean an object. As acetone is highly volatile, it was assumed that acetone would be added to the rag throughout the process to maintain a constant “wetness.” For dermal exposure, it was assumed that one half the surface area of the individual’s hand was in contact with acetone for the duration of the activity and that acetone was absorbed at the maximal rate for this time frame; the mean event concentration was estimated assuming a linear rate of evaporation of acetone from the cloth during the process and that all acetone had evaporated by the end of the activity. Mean and peak air concentrations of acetone during the event were estimated using the well-mixed room model with constant emission rate algorithm in IHMod.

The artificial nail removal scenario modelled an individual soaking her fingertips in a tray filled with acetone; the individual was exposed to acetone both dermally and via inhalation due to evaporation of acetone from the tray. IHMod was used to estimate a rate of evaporation of acetone from the tray. Air concentrations were estimated using a one-box model (well-mixed room) (AIHA 2009b). The dermal intake estimate for this scenario (soaking fingertips in pure solvent) was based on the maximum flux of dermal absorption for acetone estimated by the SkinPerm model (AIHA 2010). The hairspray, face mask, skin cleanser and moisturizer scenarios were set in a bathroom, and the individual was assumed to remain in the bathroom for a total of 25 minutes. For hairspray, acetone released from an aerosol can was considered to be in the vapour form and available for inhalation intake. In the case of skin cleanser, it was assumed that, after application, the majority (99%) was either rinsed or washed off; the acetone in the fraction remaining on the skin (1%) was100% dermally absorbed. As lotions remain on the skin, the upper-bounding estimate of exposure from use of moisturizer assumes that all of the acetone in the applied product is 100% dermally absorbed. As all of the acetone was assumed to be dermally absorbed in the skin cleanser and moisturizer scenarios, an inhalation exposure estimate was unnecessary.

Peak acetone air concentrations following the use of spray paint, concrete sealant and 100% acetone as a cleaner/degreaser were estimated at 4415, 3830 and 1500 mg/m3, respectively, while 4-hour time-weighted average (TWA) concentrations were estimated at 232, 526 and 32 mg/m3, respectively. Acetone concentrations in air following the use of artificial/gel nail removers, hairsprays and face masks were also generated. Peak air concentrations ranged from 117 to 209 mg/m3, while 4-hour TWA concentrations (per event) ranged from 8 to 15 mg/m3. Total exposure estimates following the use of cosmetic products ranged from 0.03 to 0.95 mg/kg body weight (kg-bw) per event; the highest exposure was following the use of artificial/gel nail removers. These exposure estimates are considered to represent the upper bounds of potential acute exposure from occasional, intermittent use of products containing acetone. These estimates are considered conservative, as they were derived using products with the highest identified acetone concentrations.

Frequent use of household and cosmetic products containing acetone contributes to acetone concentrations measured in personal air samples, which were used to derive the total daily intake estimates, as presented in Appendix B. Therefore, the total daily acetone intake estimates reflect the contribution from frequent use of household and cosmetic products containing acetone.

10.1.3 Biomonitoring Data

Acetone is produced naturally in the body when fats and lipids are metabolized; this occurs primarily in the liver. Acetone is then transported to all tissues and organs of the body, where it can be used as a source of energy. The majority of acetone is eliminated from the body through expired air, either unchanged or following metabolism, with lesser amounts excreted in urine (ATSDR 1994). Acetone has been measured extensively in a variety of biological media, including blood, exhaled air and urine. As previously stated, the focus of this exposure characterization is the non-endogenous (environmental media, food and products) component of total exposure, described above.

Reference ranges of acetone concentrations in whole blood for the general US population were established based on the analysis of 1062 blood samples from non-occupationally exposed adults as part of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994; median, 5th and 95th percentile concentrations of acetone in blood are 1800 ppb (~1.8 mg/L), 640 ppb (~0.6 mg/L) and greater than 6000 ppb ( greater than 6.0 mg/L), respectively (Ashley et al. 1994). Wu (2006) presented reference intervals for acetone concentrations in blood, which include less than 20 mg/L for a healthy individual, less than 100 mg/L following occupational exposure and 100–700 mg/L for an individual with diabetic ketoacidosis; greater than  200 mg/L is considered a toxic concentration. Morgott (2001) presented average concentrations of acetone in normal healthy adults ranging from 0.41 to 4.35 mg/L in plasma samples, from 0.84 to 1.8 mg/L (minimum–maximum: 0.0–17.4 mg/L) in whole blood samples, from 0.76 to 3.02 mg/L (minimum–maximum:  0.13–9.35 mg/L) in urine samples and from 0.71 to 1.52 µg/L (minimum–maximum: 0.02–8.25 µg/L) in expired air samples. Peden (1964) reported average serum levels in infants and children ranging from 12 mg/L in newborns to 9 mg/L in teenagers; concentrations up to 140 mg/L were found in 2- to 5-day-old healthy infants. In studies of occupational exposure to acetone, inhaled acetone concentrations are strongly related to concentrations in expired air and blood (Morgott 2001).

It has been estimated that normal healthy adults produce acetone at levels ranging from 20 to 72 mg/kg-bw per day, with a typical rate of 40.9 mg/kg-bw per day (i.e., 2.9 g/day) (Reichard et al. 1979; Morgott 2001). Endogenous acetone production has normal diurnal variations. Dieting, vigorous physical exercise, high fat consumption, lactation and other physiological states can appreciably increase the body burden of acetone through the process of ketogenesis (ATSDR 1994). For example, infants, pregnant women and exercising humans can have ketone body levels that are 2–20 times higher than normal because of their higher energy requirements (Morgott 2001). Increased acetone production is also associated with certain disease states (i.e., starvation, alcoholism, diabetes mellitus, hypoglycemia), and blood acetone levels in normal healthy adults, fasting adults, moderate diabetics and severe diabetics have been reported to be 11, 44, 90 and 189 mg/L, with corresponding production rates of 41, 105, 81 and 637 mg/kg-bw per day, respectively (Morgott 2001). Because acetone levels in the body are influenced by so many factors, endogenous levels can be expected to vary widely between individuals.

It should be noted that exposure to other chemicals that are metabolized to acetone, such as isopropyl alcohol, or to any chemical that can cause oxidative stress through lipid peroxidation can also lead to elevated blood, expired air or urinary levels of acetone (Morgott 2001).

10.1.4 Confidence in Exposure Database

Overall confidence in the exposure database for determining estimates of acetone intake from environmental media and food is considered moderate. Representative, high-quality Canadian data were available for acetone concentrations in ambient air, indoor air, personal air and drinking water, resulting in high confidence in the upper-bounding intake estimates from these media. Very few data were available quantifying acetone concentrations in soil and dust; however, due to the volatility of acetone, significant concentrations are not anticipated in these media, and soil and dust are considered to be minor contributors to total acetone intake. Although acetone has been detected in breast milk, there are no data quantifying concentrations in breast milk; thus, the contribution from breast milk was not captured in the dietary intake assessment for infants, which is an uncertainty. There are very limited data quantifying concentrations of acetone in different food commodities. The use of maximum concentrations may overestimate potential dietary exposure to acetone, particularly since concentrations vary widely among published data sets and maximum values were extended to all foods within a food group.

Overall confidence in the exposure database for products is low to moderate. The following uncertainties limit the ability to quantify the level of conservatism associated with the estimate of exposure from consumer use of products. Due to the wide range of products that contain acetone at concentrations up to 100%, individual exposures are expected to vary greatly, and not all products and uses may have been identified--for example, the exact use pattern associated with acetone as a household cleaner. In the absence of data on the rate of emission of acetone from concrete sealant, it was assumed to be linear over the drying time of the product; the actual emission rate is unknown and may be higher. While acetone is known to be readily absorbed via the dermal route, the actual flux is unknown; therefore, models were used to estimate dermal absorption for products and scenarios where acetone was the primary formulant. Estimates of exposure from products are considered to be in the upper bounds, because exposure estimates were calculated using the product with the highest identified acetone concentration, and the frequency of use was based on those who perform the activity.

Determining total systemic concentrations of acetone is complicated by its endogenous production; as such, intake estimates were presented separately from endogenous production levels. Intake of acetone from environmental media, food and products is a minor contributor to total acetone levels in the body.

10.2 Health Effects Assessment

Acetone has not been classified by any agency or regulatory body on the basis of its toxicological properties, including genotoxicity and carcinogenicity. WHO (1998) concluded that acetone is not genotoxic, and the US EPA (2003) described acetone as negative in almost all of the available genotoxicity assays, but did not provide an overall weight of evidence evaluation. Numerous authoritative reviews have been published on acetone. These include assessments by the International Programme on Chemical Safety (WHO 1998), OECD (OECD 1999) and US EPA (US EPA 2003), an earlier assessment and an update by the Agency for Toxic Substances and Disease Registry (ATSDR 1994, 2011), an International Uniform Chemical Information Database (IUCLID) dossier (European Commission ©2000a), a major toxicology review (Morgott 2001), documentation on the Acute Exposure Guidance Limit (AEGL) (NRC 2005) and a submission as part of the US EPA’s Voluntary Children’s Chemical Evaluation Program (ACC 2003). Relevant studies on acetone toxicity and toxicokinetics in animals and humans as well as information on mode of action were identified from these reviews. In addition, information on acetone was obtained from reviews by IUCLID (European Commission ©2000b), the International Agency for Research on Cancer (IARC 1999), WHO (1990) and a Screening Information Data Set (SIDS) dossier (OECD 2002).

The following sections present a summary of the available information on the health effects of acetone in animals and humans. Further details for each study are provided in Appendices D and E.

10.2.1 Toxicokinetics

Acetone is miscible in water and has a high vapour pressure and a high blood/air partition coefficient (KB/A). The low Kow indicates that acetone selectively partitions into an aqueous phase rather than a lipid phase; however, acetone is also slightly lipophilic, allowing for some diffusion into tissues. Overall, the physicochemical parameters and related biological factors allow for rapid absorption of acetone via the respiratory and gastrointestinal tracts and also for wide distribution within the body, particularly to the organs with high water content. The toxicokinetics of acetone is similar in humans and rodents.

Rapid absorption via the oral route was demonstrated in human studies in which 65–93% of administered acetone was metabolized and residual material was excreted from the body over a period of 2 hours (Haggard et al. 1944). Case studies of accidental poisonings through ingestion of liquid cement or nail polish or by accidental administration of acetone through a gastric tube also provide evidence of extensive and rapid acetone absorption via the oral route (Ramu et al. 1978; Gamis and Wasserman 1988; Sakata et al. 1989; Herman et al. 1997).

Rodent studies demonstrated that acetone is rapidly absorbed through the inhalation route, with the peak blood concentration occurring rapidly after the onset of inhalation exposure and steady state being reached 2 hours, 6 hours and 3–4 days after exposure to 150 ppm, 500 ppm and 2210 ppm acetone, respectively (Haggard et al. 1944; Geller et al. 1979b; Wigaeus et al. 1982). The increase in time to reach steady state with increasing dose suggests dose-dependent kinetics. Studies conducted on volunteers showed that approximately 40–50% of inhaled acetone is absorbed by the body (DiVincenzo et al. 1973; Wigaeus et al. 1981). The low lipid solubility of acetone is believed to cause resistance when absorbing acetone from the air in the nasal tissue to the bloodstream, resulting in a lower uptake than expected.

Similar to the oral and inhalation routes, dermal absorption of acetone has also been shown to occur rapidly in humans.

Acetone is widely distributed throughout the body in animals, particularly into organs with high water content, due to its high water solubility. Although no data on acetone distribution in humans were located, it is expected that it would also be widely distributed in humans.

Animal studies indicate that acetone can be found in blood, lung, kidney, liver, brain, pancreas, spleen, thymus, heart, testis, vas deferens, muscle and subcutaneous and intraperitoneal white adipose tissue (Wigaeus et al. 1982). A 24-hour exposure to 500 ppm (1200 mg/m3) of 14C-labelled acetone caused little or no tissue accumulation, except in brown adipose tissue and liver. ATSDR (1994) suggested that the accumulation of radioactivity in the liver and brown adipose tissue could be the result of high metabolic turnover in these tissues. The conversion of 14C-labelled acetone to glucose, acetyl coenzyme A and other Krebs cycle components can lead to the incorporation of acetone-derived 14C into a variety of cellular macromolecules and components. The concentration of acetone is higher in blood than in other tissues (Bruckner and Peterson 1981a; Wigaeus et al. 1982; Scholl and Iba 1997), reflecting its high water content.

Acetone has been reported in breast milk of some lactating women, although it is not known whether the acetone was from exogenous exposure or was formed endogenously (Pellizzari et al. 1982). Acetone can cross the placenta, based on the observation of acetone in maternal and cord blood (Dowty et al. 1976).

The main route of acetone excretion in humans is via the respiratory tract, regardless of the route of exposure. A small fraction of acetone is eliminated through urine. After inhalation, respiratory excretion is complete within 20 hours, while peak urinary excretion occurs from 1 to 3.5 hours after exposure (Matsushita et al. 1969b; Wigaeus et al. 1981). In exhaled air, acetone is excreted both as unmetabolized acetone and as carbon dioxide following metabolism. The rate and pattern of acetone excretion (respiratory and urinary) following human inhalation exposure are affected by exposure concentration, duration, level of physical activity and possibly the sex of the individual.

In a study of subjects exposed to acetone at 700 or 1300 mg/m3 with or without exercise, about 20% of the absorbed acetone was exhaled as unmetabolized parent compound. Urinary excretion represented around 1% of the absorbed acetone (Wigaeus et al. 1981). While the alveolar concentration remained constant at around 30–40% of the inhaled acetone concentration, the respiratory excretion increased with higher exposure levels and with exercise, suggesting saturation of acetone metabolism. More specifically, the respiratory and urinary excretion were 16%, 20% and 27% for the low-dose low-exercise, high-dose moderate-exercise and high-dose increasing-exercise groups, respectively. Half-times for acetone in alveolar air, arterial blood and venous blood averaged 4.3, 3.9 and 6.1 hours, respectively. Urinary concentrations, in contrast, were shown to increase only when workers were exposed to acetone concentrations higher than 15 ppm (36 mg/m3) (Kawai et al. 1992). Wang et al. (1994) found blood and urinary concentrations at the end of a shift of 23 mg/L and 22 mg/L, respectively, in workers with a mean occupational exposure to acetone of 141.8 ppm (336.8 mg/m3). Grampella et al. (1987) reported average urinary acetone levels of 93 mg/L and 62 mg/L in workers exposed to TWA concentrations of 948–1048 ppm (2.25 × 103–2489 mg/m3) and 549–653 ppm (1.30 × 103–1.55 × 103mg/m3), respectively.

While total body clearance in rats is independent of dose, the half-time for elimination from blood increased from 2.4 hours to 4.9 hours to 7.2 hours when exposure was 196.1 mg/kg-bw, 784.4 mg/kg-bw and 1961 mg/kg-bw, respectively (Plaa et al. 1982).

10.2.2 Acute Effects

The acute toxicity of acetone is low in laboratory animals following inhalation, oral or dermal exposure. In these animal studies, regardless of the route, death is generally preceded by signs of central nervous system (CNS) depression, including weakness, incoordination and unconsciousness. The lowest inhalation LC50 values for acetone were 71 000 mg/m3for a 4-hour exposure in rats and 44 000 mg/m3 for a 4-hour exposure in mice (Safronov et al. 1993). Via the oral route, the lowest median lethal dose (LD50) in rats was identified at 1700 mg/kg-bw in newborns (Kimura et al. 1971), while in adults, the lowest value was 5800 mg/kg-bw (Freeman and Hayes 1985). The only oral acute lethality study identified in mice showed an LD50 of 5200 mg/kg-bw (Tanii et al. 1986). However, those animals also received an intraperitoneal injection of olive oil. In rabbits, an oral LD50 of 5300 mg/kg-bw was identified (Krasavage et al. 1982). No deaths were observed after dermal application of 15 800 mg/kg-bw to rabbits or 7400 mg/kg-bw to guinea pigs (Smyth et al. 1962; Roudabush et al. 1965).

The potential for acetone to cause irritation has been evaluated in animals following inhalation and dermal exposure. Based on an RD50 (concentration estimated to result in a 50% decrease in respiratory rate) of 77 516 ppm (184 136 mg/m3) in male Swiss Webster mice (four per group) exposed by inhalation for 10 minutes, Kane et al. (1980) considered acetone to be a very weak sensory irritant. A similarly high RD50 of 23 480 ppm (55 776 mg/m3), indicating weak sensory irritation, was observed in male Swiss OF1 mice exposed for 15 minutes to unspecified concentrations (De Ceaurriz et al. 1984). Schaper and Brost (1991) did not observe any changes in respiratory parameters measured in a body plethysmograph (a chamber set to measure changes in pressure with each breath), lung weights or lung pathology in male Swiss Webster mice exposed for 30 minutes to 6000 ppm (1.425 × 104 mg/m3) of acetone vapour.

Several sensory irritation studies following inhalation exposure are also available in humans. Although Matsushita et al. (1969a) reported very slight irritation at concentrations as low as 240 mg/m3 in subjects exposed to two 3-hour sessions in 1 day, effects were very mild and inconsistent. For the purpose of this report, 1190 mg/m3 was considered the most appropriate LOEC because the irritation was more clearly defined and was observed more consistently among the subjects. Throat irritation at an incidence greater than in controls was reported in subjects exposed to 2370 mg/m3 for 3 or 7.5 hours (Stewart et al. 1975). Other studies reported no subjective effects at 551 mg/m3 for 2 hours (Ernstgård et al. 1999) and “awareness” but no subjective symptoms following exposure to up to 240 or 1190 mg/m3 for 2 or 4 hours (DiVincenzo et al. 1973). Based on an exposure of 3–5 minutes, an early study concluded that 475 mg/m3 was the highest exposure that would be tolerable for an 8-hour exposure, while 713 mg/m3 was considered slightly irritating (Nelson et al. 1943). Throat irritation was reported in subjects exposed to 2375 mg/m3 for 4 or 8 hours (Seeber et al. 1992); lower concentrations were not tested in this study. Based on consistency of the observed effects and level of discomfort experienced by the subjects, it appears that the most appropriate lowest-effect level for sensory irritation (irritation to the nose, eyes, throat and trachea) is 1190 mg/m3 (Matsushita et al. 1969a). Thresholds for the onset of sensory irritation measured among these studies likely reflect a combined effect of odour detection and sensory irritation. Two studies designed to distinguish between odour detection and sensory irritation are presented below. It should be noted that in many of the studies reporting irritation, an increase in the sensory irritation threshold was noted with either increased exposure time or repeated exposures, indicating that adaptation may be occurring.

Well-controlled studies that measured sensory irritation alone (Cometto-Muñiz and Cain 1993; Wysocki et al. 1997) identified sensory irritant thresholds much higher than in the other studies. However, the set of studies identifying the lower threshold are relevant, since they reflect actual response perception under relevant exposure conditions. The interplay between odour and irritancy is important, since perceived sensory irritation in subjective tests has been shown to be affected by the perceived odour of acetone (Dalton et al. 1997). Wysocki et al. (1997) concluded that acetone is a weak sensory irritant and that sensory adaptation is an important factor affecting its overall irritancy. Acetone olfactory detection thresholds were 855 ppm (2031 mg/m3) in acetone-exposed workers, compared with 41 ppm (97 mg/m3) in unexposed workers. The sensory irritation threshold (as measured by identifying the concentration at which a subject can distinguish the nostril to which the test chemical has been presented) was 36 669 ppm (87 106 mg/m3) in acetone-exposed workers and 15 758 ppm (37 433 mg/m3) in unexposed workers. Cometto-Muñiz and Cain (1993) more specifically measured the acetone thresholds for odour and nasal pungency (physical sensation of irritation, such as burning, stinging and tingling) in four subjects lacking a sense of smell (anosmics) and four age- and sex-matched controls. Acetone was pushed into a nostril using a squeezing bottle in both anosmic and normosmic subjects. The detection threshold in anosmics represented pungency, while detection by normosmics represented the odour threshold. Acetone’s odour threshold was approximately 10 000 ppm (23 755 mg/m3), and the nasal pungency threshold was 100 000 ppm (237 500 mg/m3).

In humans, blood parameters were also assessed following acute exposure. DiVincenzo et al. (1973) found no effect on measures of liver and kidney function or on hematological values (hemoglobin, hematocrit and differential count) following exposure to acetone at 240 or 1190 mg/m3 for 2 or 4 hours. A temporary decrease in phagocytic activity of neutrophils and a slight increase in eosinophil and leukocyte counts in peripheral blood were reported in subjects exposed to 1190 or 2400 mg/m3 for two 3-hour sessions in 1 day and were attributed to an inflammatory reaction resulting from irritation (Matsushita et al. 1969a).

Several acute studies in laboratory animals and humans investigated neurological effects using various tests and endpoints. Those studies are presented in the Effects on the Nervous System section.

Taken together, along with the toxicokinetics information, the database on acute effects does not identify critical effects following acute exposure. The majority of acute effects were noted to be mild, transient and reversible in nature and often attributed to odour detection or mild sensory irritation. This is consistent with the AEGLs for hazardous substances published by the US EPA and the US National Research Council, which identified AEGL-2 levels of 11 000 mg/m3 and 3400 mg/m3 for 30-minute and 4-hour exposures, respectively (NRC 2005). At concentrations below AEGL-2 levels, “the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.”

10.2.3 Short-term Effects

A 14-day oral drinking water study conducted in rats and mice by the US National Toxicology Program (NTP 1991) (also referenced as Dietz et al. 1991) is considered the most meaningful short-term acetone study, because it was conducted in two rodent species, exposed animals through a route relevant to human exposure and assessed numerous systemic endpoints. The TWA equivalent doses were 0, 714, 1616, 2559, 4312 and 6942 mg/kg-bw per day for male rats and 0, 751, 1485, 2328, 4350 and 8560 mg/kg-bw per day for female rats. In mice, the acetone intakes were 0, 965, 1579, 3896, 6348 and 10 314 mg/kg-bw per day for males and 0, 1569, 3023, 5481, 8804 and 12 725 mg/kg-bw per day for females. Decreased terminal body weight compared with controls was observed only in the rats and was the critical effect, with a lowest-observed-adverse-effect level (LOAEL) of 4312 mg/kg-bw per day. Changes in relative organ weights were also reported in rats, but were not considered adverse in the absence of supporting data on histopathology or absolute organ weight. Bone marrow hypoplasia was also reported in all of the male rats treated with 6942 mg/kg-bw per day, consistent with the hematological effects seen in the subchronic study. In the mouse study, the LOAEL was 3896 mg/kg-bw per day, considering increased liver weight accompanied by liver hypertrophy to be adverse; less severe changes in increased liver weight in the absence of hypertrophy were considered a lowest-observed-effect level (LOEL).

Repeated short-term exposure studies in humans are available only for the inhalation route. Matsushita et al. (1969b) conducted a follow-up to the single day study described in the above section on acute toxicity. In the follow-up study, subjects were exposed to 250 ppm (590 mg/m3) (resting or exercising) or 500 ppm (1190 mg/m3) for 6 hours/day (with a 45-minute break) for 6 days. Subjective scores indicated mucous membrane irritation, but exercising (and the resulting increased minute volume) did not increase the degree of irritation. The degree of reported irritation decreased with exposure time, reflecting adaptation. Neurobehavioural tests (reaction time to a visual stimulus) were also conducted. Although an increased reaction time was reported at the low concentration on the first 2 exposure days, the difference from controls (non-pooled absolute values) was not statistically significant. There was a change of 5% in simple reaction time at 590 mg/m3 and 10% at 1190 mg/m3 (as reported in Dick et al. 1989). As in the single day study, a statistically significant increase in white blood cell counts and decrease in phagocytic activity of neutrophils were also observed at 1190 mg/m3.

Stewart et al. (1975) conducted an extensive evaluation of the effects of short-term inhalation exposure to acetone in healthy male and female adult humans. Groups of four males were exposed on successive weeks (one control exposure followed by 4 days of exposure) to 0, 200, 1000 or 1250 ppm (0, 475, 2370 and 2970 mg/m3). One group was exposed for 3 hours/day and another for 7.5 hours/day. Additional groups of females were exposed successively to 0 and 1000 ppm (0 and 2370 mg/m3) for 1 hour/day (two subjects) or 3 or 7.5 hours/day (four subjects per group). The subjects underwent extensive pre-exposure testing and testing during exposure. A number of measurements were conducted on selected days of each exposure week, including spontaneous electroencephalogram recordings and visual evoked response (control and days 2 and 4), pulmonary function testing (day 4), cognitive tests (control and days 2 and 4) and complete blood count (including differential white count) and clinical chemistry (once per week, day not specified). The only effect in these tests was a significant change in amplitude of the visual evoked response test in the male subjects exposed to acetone at 2970 mg/m3 for 7.5 hours/day, on both the 2nd and 4th  days of exposure.

Other short-term studies are presented in the section on Effects on the Nervous System.

10.2.4 Subchronic Effects

Bruckner and Peterson (1981b) exposed male rats to acetone at 0 or 45 100 mg/m3 in an inhalation chamber 3 hours/day, 5 days/week, for 8 weeks. Body weight gain was slightly, but not significantly, decreased throughout the experiment. Absolute brain weight was decreased after 4 and 8 weeks and returned to within control values after a 2-week recovery. Absolute kidney weight was consistently lower during the exposure period, but the decrease was not statistically significant. No effects on other organ weights, blood chemistry or histopathology of major organs were observed. Hematology was not evaluated. Christoph et al. (2003) conducted a schedule-controlled operant behaviour study with male rats exposed to 0, 2400, 4800 or 9500 mg/m3 6 hours/day, 5 days/week, for 13 weeks. Exposure to concentrations up to 9500 mg/m3 in this study did not lead to adverse effects on learning. Buron et al. (2009) examined the effects of acetone on the olfactory function (behaviour and histopathology) of mice. Female mice were exposed to fresh air or to acetone placed on cotton in the inhalation chamber 5 hours/day, 5 days/week, for 4 weeks. The acetone concentration in the chamber reached approximately 19 000 mg/m3 after 1.5 hours and remained steady. Changes in several sensitive olfactory markers (number of cells, thickness of epithelium and number of proliferating cell nuclear antigen–positive cells) as well as changes in olfactory sensitivity were observed in exposed mice.

Subchronic toxicity via the oral route has been examined in a series of drinking water studies and an oral gavage study. The drinking water study conducted on rats and mice by the US NTP (NTP 1991) was identified as one of the critical studies in risk characterization. In the rat study, male and female rats were exposed to acetone in drinking water for 13 weeks at equivalent doses of 0, 200, 400, 900, 1700 and 3400 mg/kg-bw per day for males and 0, 300, 600, 1200, 1600 and 3100 mg/kg-bw per day for females (NTP 1991). In females, kidney and liver weights were significantly increased at the middle and high dose levels. In males, only the liver weight increase was statistically significant at the middle dose level, while in the high dose group, the increases were significant for kidney, liver and testis weights. Examination of the kidney tissue revealed increased incidence and severity of nephropathy in male rats, which were considered adverse at the two highest doses.

Several treatment-related changes in hematological parameters that were most prominent in males were observed. The changes were in the order of 10% or less, except for the decrease in reticulocytes, which varied between 68% and 80% (152–179 × 103/µL) of the control values, depending on dose. Although some hematological changes occurred beginning at the lowest dose tested in males, doses of 1700 mg/kg-bw per day and above generated a consistent pattern of statistically significant biologically related changes. While effects on splenic red pulp were observed, no changes were noted from the bone marrow examination. Thus, for hematological effects, the LOEL is 200 mg/kg-bw per day, based on a statistically significant increase in mean corpuscular hemoglobin and mean cell volume in males, with effects that were more consistent at 1700 mg/kg-bw per day.

Overall, the study LOAEL is 1700 mg/kg-bw per day, based on biologically significant hematological changes in male rats and the onset of adverse effects on the kidney (increased kidney weight in females and mild nephropathy in males) at the same dose. Some statistically significant effects were observed at lower doses, but these effects are not considered adverse; as the lowest level at which they were observed represents a LOEL, it cannot serve as the critical effect level for the study.

For the mouse portion of the study, male and female mice were exposed to acetone in drinking water for 13 weeks; doses were 0, 380, 611, 1353, 2258 and 4858 mg/kg-bw per day in males and 0, 892, 2007, 4156, 5945 and 11 298 mg/kg-bw per day in females. Changes in several organ weights were reported for females, but not for males. Histopathological findings were limited to minimal hepatocellular hypertrophy in high-dose females. Statistically significant changes in hematological parameters were also observed, but those changes were small and did not parallel changes observed in rats. Overall, the only significant biological effect observed in mice in this study was the change in liver weight accompanied by a consistent pattern of histopathology; thus, a LOAEL of 11 298 mg/kg-bw per day is identified based on this effect.

Woolhiser et al. (2003) exposed male CD-1 mice (eight per group) to acetone in drinking water at concentrations of 0, 600, 3000 or 6000 mg/L for 28 days (actual TWA doses reported by the authors were 0, 121, 621 and 1144 mg/kg-bw per day, respectively). There were no effects on survival and no clinical signs of toxicity attributable to acetone treatment, and terminal body weight was not affected by acetone treatment. There were no treatment-related effects on hematological parameters (total and differential white blood cell counts, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and platelets). The immunotoxicity portion of the study is summarized in the corresponding section below.

Subchronic effects reported for rats and mice in several other drinking water studies are considered unreliable due to their study limitations (Sollman 1921; Spencer et al. 1978; Ladefoged et al. 1989).

American Biogenics Corporation (1986) administered acetone via gavage to male and female rats at a dose of 0, 100, 500 or 2500 mg/kg-bw per day for 90 days. Increased body weights were observed in females in the middle and high dose groups. The increase was not considered toxicologically meaningful based on the absence of a clear dose–response relationship and the absence of an effect on body weight in males. Changes in organ weights were reported for the kidneys, liver, brain and heart. With the exception of the kidneys, these changes were not accompanied by histopathological findings. Accentuation of renal proximal tubule degeneration and intracytoplasmic hyaline droplet accumulation was observed in males at the middle and high doses. In females, effects were limited to the accentuation of renal proximal tubular degeneration in the high-dose group only. The study authors reported a treatment-related increase in the severity and distribution of these kidney effects, which are also associated with aging rats, particularly in male rats through α2u-globulin nephropathy. However, since some of these effects were observed in treated female rats, there is likely another cause for the kidney effects than that mediated by α2u-globulin. Thus, the observed kidney effects are considered relevant. Of the three serum measures related to hepatotoxicity examined, only alanine aminotransferase (ALT) was increased in high-dose males. Effects on serum cholesterol were noted at interim sacrifice only. Changes in several other clinical chemistry parameters were observed, but their toxicological relevance is unclear. Treatment-related changes in hematological parameters (significantly increased red blood cell count) were also observed and were limited to male rats exposed to the highest dose level. However, no effects were noted on the tissues of the spleen and bone marrow.

Overall, effects of acetone treatment were observed on the kidneys, liver and hematology. The study identified a LOAEL of 2500 mg/kg-bw per day, based on increased kidney weight supported by histopathological findings. Toxicologically significant kidney effects were observed in both sexes at this dose. Liver weight increases were also observed at 500 mg/kg-bw per day, but evidence for an adverse effect became apparent only at the highest dose (2500 mg/kg-bw per day), as indicated by clinical chemistry findings (increased ALT). Statistically significant hematological findings were limited to the highest dose, and generally the magnitude of the changes was small and of unknown clinical significance. This study was not chosen as the basis for risk characterization because the gradual administration from drinking water studies is considered to be a more relevant route of administration from the human exposure perspective.

Two studies were identified in which laboratory animals were exposed to acetone via dermal application. One study observed cataracts in two of eight guinea pigs exposed to 0.5 mL acetone twice daily, 5 days/week, for 8 weeks (Rengstorff et al. 1972). In contrast, three other experiments exposing rabbits or guinea pigs to 0.5 or 1 mL of acetone on the skin 2–5 times per week for up to 6 months did not show evidence of cataracts (Rengstorff et al. 1976; Taylor et al. 1993).

10.2.5 Cancer and Chronic Effects

No studies assessing chronic toxicity or carcinogenicity are available via the oral or inhalation route for acetone. Via the dermal route, the database consists mainly of carcinogenicity studies of various durations in which acetone was used as a vehicle control (Park and Koprowska 1968; Barr-Nea and Wolman 1977; van Duuren et al. 1978; Zakova et al. 1985; Ward et al. 1986; Iversen et al. 1988; DePass et al. 1989; Holden et al. 1998). These studies involve various strains of mice to which acetone was applied dermally for durations ranging from 1 month to a lifetime. Applications were administered from once a day to once a week, and the doses (when specified) varied between 290 and 5300 mg/kg-bw per day. However, many limitations were identified in some of these studies, including the absence of a control group, the lack of a dose–response relationship, the less than chronic duration, the small number of animals and the use of relatively low daily doses. In summary, of the eight studies, six did not observe any signs of tumour, even when, in one study, a chemical initiator was applied to the skin prior to acetone exposure. The remaining two studies are presented below.

In the study by DePass et al. (1989), 2 mice out of 40 were diagnosed with subcutaneous mesenchymal neoplasms after being exposed to approximately 290 mg/kg-bw per day for a lifetime. No skin tumours were observed. The only other effects reported were skin effects at the site of application. No systemic endpoints were evaluated. Ward et al. (1986) conducted a skin painting study in a particularly sensitive strain of mice bred for skin initiation and promotion protocols. In one group of 30 mice, 0.2 mL of formalin solution (37–40% formaldehyde solution in acetone) was applied once to the back at 8 weeks of age. Four weeks later, 0.2 mL (5300 mg/kg-bwFootnote[3]) acetone was applied once weekly for 88 weeks (average daily dose of 750 mg/kg-bw per day). In another group of 30 mice, 0.2 mL of acetone was applied twice weekly (average daily dose of 1520 mg/kg-bw per day) to their backs from 8 weeks of age for 92 weeks. There was no control group in this study. In both groups, neoplastic and non-neoplastic lesions occurred with similar incidence, and survival was similar. The most common neoplastic lesions reported were histiocytic sarcoma, lung tumours and mammary gland tumours. The study authors stated that the incidence of the observed tumours was similar to that in the CD-1 mouse, the parent strain, but did not provide any quantitative supporting evidence. Taking into consideration the sensitivity of the strain, the absence of a control group and the similarity of tumour incidence with historical controls, the relevance of the results cannot be determined.

As mentioned, no chronic studies are available for acetone. Thus, the only data available on chronic effects of acetone come from the carcinogenicity studies noted above. Aside from local dermal effects caused by the application of acetone, two studies reported systemic effects (Barr-Nea and Wolman 1972; Ward et al. 1986). However, the significance of the observations cannot be determined due to limitations in both studies.

Several epidemiological studies of acetone-exposed workers are available, but they are generally limited by confounding exposures that were not accounted for in the statistical analysis, relatively small sample sizes and self-reporting of effects. However, the epidemiological studies qualitatively support the findings of the animal studies and acute human studies--namely, that there is no evidence of increased mortality due to acetone exposure and that acetone is a sensory irritant (Ott et al. 1983a, b, c). While there are some positive findings in neurological tests and subjective reports of CNS symptoms, these findings are limited by study design limitations (Raleigh and McGee 1972; Satoh et al. 1996; Mitran et al. 1997). No clinical chemistry findings indicative of kidney or liver effects were reported at occupational exposure levels, and there were no hematological effects, although the endpoints for which results were most consistent in animal studies (mean corpuscular hemoglobin and mean corpuscular volume) were not evaluated (Grampella et al. 1987; Soden 1993). Summaries of the key epidemiological studies are presented in a later section.

Although acetone has not been adequately tested for carcinogenicity via all routes of exposure, the available information indicates that it is not carcinogenic. This is supported by the use of acetone as a solvent in many types of studies, including carcinogenicity studies, to test other substances. This is further supported by the absence of genotoxicity, as described in the following section.

10.2.6 Genotoxicity

In the only study with positive results, Zimmermann et al. (1985) reported that a concentration of approximately 8% acetone caused aneuploidy in Saccharomyces cerevisiae, but did not induce point mutations or mitotic recombinations. All other in vitro and in vivo assays in an extensive battery of tests had negative results. Acetone was negative for gene mutation in the bacterium Salmonella typhimurium(McCann et al. 1975; De Flora et al. 1984; Ishidate et al. 1984; Zeiger et al. 1992), in two species of yeast (Abbondandolo et al. 1980; Yadav et al. 1982) and in mammalian cells (mouse lymphoma and lung fibroblast cells) at several different loci (Lankas 1979; Amacher et al. 1980; Cheng et al. 1981; Friedrich and Nass 1983; McGregor et al. 1988). Acetone was also negative for chromosomal aberrations in Chinese hamster ovary cells and human lymphocytes (Norppa et al.1981; Tates and Kriek 1981; Ishidate et al. 1984; Loveday et al. 1990) and was negative for the development of micronuclei (a measure of clastogenicity) both in vitro in human lymphocytes (Zarani et al. 1999) and in vivo in hamsters and mice (Basler 1986; NTP 1991). A variety of measures of deoxyribonucleic acid (DNA) damage were also negative, including prophage induction assays (DeMarini et al. 1991; Rossman et al. 1991), which measure induction of the “SOS” response in bacteria, the SOS chromotest (Nakamura et al. 1987), sister chromatid exchange assays in mammalian cells (e.g., Tates and Kriek 1981; von der Hude et al. 1987; Loveday et al. 1990) and unscheduled DNA synthesis in human skin cells (Lake et al. 1978). A number of studies evaluated cellular transformation, a more integrative assay that evaluates the occurrence of multiple changes in a cell, rather than only genotoxicity. Acetone was also negative in the cell transformation studies (Freeman et al. 1973; Mishra et al. 1978; Pienta 1980; Lillehaug and Djurhuus 1982). The complete list of genotoxicity studies identified for acetone is presented in Appendix D. No in vivo studies in humans were identified.

Acetone is commonly used as a vehicle for water-insoluble chemicals in in vitro genotoxicity testing (Anderson and MacGregor 1980), consistent with the general conclusion that acetone itself is not genotoxic.

10.2.7 Reproductive Effects

There were no effects on male fertility and no testicular damage in rats administered acetone at 800 mg/kg-bw per day in drinking water for 6 weeks (Larsen et al. 1991), no effects on male fertility, reproductive organ weights or testes histopathology in rats treated with acetone at 1400 mg/kg-bw per day in drinking water for 4 weeks or 700 mg/kg-bw per day in drinking water for 9 weeks (Dalgaard et al. 2000), no effects on the weight or histopathology of reproductive organs in male and female rats treated by gavage with up to 2500 mg/kg-bw per day (American Biogenics Corporation 1986) and no effects on reproductive structure or histopathology in female rats exposed to up to 3100 mg/kg-bw per day in drinking water for 90 days (NTP 1991).

Effects on reproductive organs and sperm parameters were observed in male rats in a 13-week drinking water study as well as in its accompanying 14-day dose range–finding study (NTP 1991). In the 14-day study, the only effect observed was an increase in relative testis weight at 4312 mg/kg-bw per day. In the 13-week study, statistically significant effects were reported in the high-dose group (3400 mg/kg-bw per day). Those effects include increased relative testis weight, decreased caudal epididymal and right epididymal weight, increased percentage of abnormal sperm and decreased sperm motility. The increase in relative testis weight is considered to be secondary to a decrease in body weight (Feron et al. 1973). All of the other effects are consistent with adverse effects on spermatogenesis. Accordingly, a LOAEL of 3400 mg/kg-bw per day was identified for the effects on reproductive organs and sperm parameters in male rats.

In humans, the database on reproductive toxicity is limited. One clinical study reported premature menstruation, but the significance of the finding is unknown, due mainly to small sample size and the possibility of other factors, such as diabetic status, influencing the results (Stewart et al. 1975). One study found inconsistent effects on sperm parameters in plastics production workers (Jelnes 1988). The co-exposure to styrene, small sample size and use of fertility clinic patients with potential fertility problems as controls are major weaknesses of this study. However, the results are in line with the effects observed on sperm parameters in male rats in the NTP (1991) study. Other studies provided no clear evidence for spontaneous abortions or miscarriages in solvent-exposed workers (Axelsson et al. 1984; Taskinen et al. 1994).

10.2.8 Developmental Effects

Developmental toxicity of acetone has been studied in Sprague-Dawley (CD) rats and Swiss (CD-1) mice via inhalation exposure (Mast et al. 1988Footnote[4]). Pregnant rats (32 per dose group) were exposed to acetone vapours at a concentration of 0, 440, 2200 or 11 000 ppm (0, 1045, 5200 or 26 100 mg/m3, respectively) for 6 hours/day, 7 days/week, during gestation days 6–19. Pregnant mice (32 per dose group) were exposed to acetone vapour at a concentration of 0, 440, 2200 or 6600 ppm (0, 1045, 5200 or 15 670 mg/m3) for 6 hours/day, 7 days/week, during gestation days 6–17. Each treatment group also included 10 virgin females as controls.

In the rat developmental toxicity portion of the study, at the highest concentration of 26 100 mg/m3, there were statistically significant decreases (compared with controls) in maternal gestation day 20 body weights (7.5% decrease), extragestational weight gainsFootnote[5] (34% decrease), uterine weights (19% decrease) and fetal weights (male, female and combined). The fetal weights were approximately 13% lower than the contemporary control values provided, and the decreases were considered treatment related. Non-mated controls also exhibited a decrease in body weight (5.9% decrease), but this was not statistically significant. The percentage of litters with resorptions (77% vs. 50%) and percentage of litters with at least one malformation (11.5% vs. 3.8%) were greater in the high-exposure group, compared with control values. In addition, four malformations were observed in one control litter compared with nine malformations in four high-dose litters. The incidences of fetal malformations, variations and reduced ossifications were not statistically significantly different from control values in any exposure group. However, in the 26 100 mg/m3 group, these changes were considered biologically significant, because the litter values (number and percent of litters/fetuses with malformations) were three times higher than the contemporary control values (1 vs. 3 and 3.8% vs. 11.5%, respectively), and the observed malformations were of a different spectrum than those seen in the control group. 

The lowest-observed-adverse-effect concentration (LOAEC) for maternal toxicity in rats was 26 100 mg/m3, based on significant decreases in body weight gain, extragestational weight gains and uterine weight. The LOAEC for developmental effects in rats was 26 100 mg/m3, based on a significant decrease in fetal weight, an increase in fetal malformations and increased resorptions. Based on the results of this study, NTP (1988) has concluded that acetone had not caused a teratogenic effect in rats.

In the mouse developmental toxicity portion of the study, the high concentration was initially designed to be 11 000 ppm (26 100 mg/m3). However, severe narcosis was observed in this group on the 1st day of exposure (gestation day 6), and consequently the concentration for this group was reduced to 6600 ppm (15 670 mg/m3) for the remainder of the study. Thus, the final exposure levels in the mouse study were 0, 1045, 5200 and 15 670 mg/m3. There were no clinical signs or deaths at exposures up to the highest level of 15 670 mg/m3. Incidences of fetal variations when all types were combined were not significantly different from control values; however, the incidence of litters with reduced sternebrae ossification was significantly increased in the 15 670 mg/m3 group.

The single day of higher exposure in the high-concentration group was not considered to affect the study results, because any adverse developmental outcome at this early stage of gestation would likely have manifested itself as early resorptions. Absolute liver weight and liver to body weight ratio were increased in the dams at 15 670 mg/m3 (by 21% and 22%, respectively). No other liver endpoints were examined. Increased liver weight alone is generally considered adaptive. However, in light of the magnitude of the change and based on the supporting effects observed in mice in a 14-day study from NTP (1991) in which liver hypertrophy was also observed, the effects on the liver were considered relevant. Developmental effects were limited to the high-concentration group and included an increased percentage of late resorptions, decreased fetal weight and increased incidence of reduced sternebrae ossification. Thus, a LOAEC of 15 670 mg/m3 has been identified for both maternal and developmental toxicity, based on increased relative liver weight in pregnant mice (maternal toxicity) and decreased fetal weight and an increased percentage incidence of late resorptions and retarded ossification development (developmental toxicity).

10.2.9 Immunological Effects

In a study on immunological effects, CD-1 male mice were exposed to acetone at 0, 121, 621 or 1144 mg/kg-bw per day via drinking water for 28 days (Woolhiser et al. 2003). The sheep red blood cell antibody-forming cell (AFC) assay was performed to measure the T cell–dependent, anti-sheep red blood cell immunoglobulin M response, and hematology and thymus weights were evaluated. Body weights, white blood cell numbers, red blood cell counts and hemoglobin and hematocrit levels showed no treatment-related effects. Eosinophil percentages were variable, but also showed no dose-related trends. Spleen and thymus weights were not statistically different from controls, and there were no effects on spleen cellularity or AFC response as a result of acetone administration. The AFC responses were not statistically different from those of controls. The no-observed-adverse-effect level (NOAEL) in this study was determined to be 1144 mg/kg-bw per day, the highest dose tested.

No effects on B cells, T cells or ratio of CD4+ to CD8+ T cells were observed when mice were topically treated with 0, 50, 100, 200 or 300 µL of acetone either once or twice weekly for 2 or 4 weeks (average daily applied dose ranging from 187 to 380 mg/kg-bw per day, with a total dose range from 1125 to 2250 mg/kg-bw). The sheep red blood cell assay indicated statistically significant depression in humoral immunity at 300 µL, while results at other doses appeared schedule dependent. Thus, interpretation of some of the immunosuppressive effects was limited by the internally inconsistent results (Singh et al. 1996).

Immunological endpoints examined in systemic toxicity studies were limited to histopathological examination of the spleen and thymus and leukocyte counts (American Biogenics Corporation 1986; NTP 1991). Increases in leukocyte counts were observed in male and female rats in the drinking water study, but not in the mouse drinking water study or in the rat gavage study.

In humans, a temporary decrease in phagocytic activity of neutrophils and a slight increase in eosinophil and leukocyte counts in peripheral blood were reported in subjects exposed to 1190 or 2400 mg/m3 for two 3-hour sessions in 1 day and were attributed to an inflammatory reaction resulting from irritation (Matsushita et al. 1969a).

10.2.10 Effects on the Nervous System

Several acute studies have also investigated neurobehavioural effects using various endpoints. The lowest LOAEC in the acute animal database is 6129 mg/m3 for 4 hours based on decreases in mobility time in the behavioural despair swimming test in rats (De Ceaurriz et al. 1984). A no- observed-adverse-effect concentration (NOAEC) of 4827 mg/m3 was also identified based on the absence of neurobehavioural effects.

In neurotoxicity studies, rats that were repeatedly exposed to high vapour concentrations of acetone showed mild, reversible neurobehavioural changes. When Goldberg et al. (1964) exposed female rats to acetone at 0, 7120, 14 240, 28 480 or 37 975 mg/m3 for 4 hours/day for 2 weeks, a concentration-dependent increase in inhibition of avoidance behaviour was observed starting at 14 240 mg/m3. Animals in the two highest dose levels showed ataxia several minutes after a single exposure, but tolerance developed rapidly. Similarly, in more recent performance studies in which rats were exposed to acetone at concentrations up to 9500 mg/m3for 13 weeks, the rats did not show any permanent effects (Christoph et al. 2003).

In an acute study, Bruckner and Peterson (1981a) exposed mice to 29 900, 45 100, 60 100 or 120 200 mg/m3) for up to 3 hours and conducted five tests of unconditioned performance and reflexes. Concentration-dependent increases in depth of CNS depression and rate of depression were reported. While the exposure to 120 200 mg/m3 was lethal within 2 hours, exposure to 29 900 mg/m3 led to impaired performance and reflexes. Animals showed normal behaviour approximately 9–21 hours after termination of exposure. Glowa and Dews (1987) observed that a 7130 mg/m3 concentration caused a 10% decrease in response to food presentation in a fixed interval operant behavioural test after exposing mice to six nominal concentrations of acetone ranging from 100 to 56 000 ppm (240–133 000 mg/m3) for 1 day. The rate of response to food presentation returned to normal 30 minutes after the end of a serial exposure. Overall, studies are consistent with the presumption that CNS effects are more dependent on the total dose than on the exposure concentration (Mashbitz et al. 1936; Haggard et al. 1944).

Effects were seen in a match-to-sample operant behavioural test in four baboons exposed to 1200 mg/m3 continuously for 7 days, but the study is useful primarily for hazard characterization, since only one concentration was tested, results were highly variable for each animal and the sample size was small (Geller et al. 1979a).

In an oral neurobehavioural study, Ladefoged et al. (1989) compared the effects of exposure to ethanol, acetone and 2,5-hexanedione alone or in combination for 6 weeks. From the 3rd week on, rats were monitored for nerve conduction velocity and rotarod performance. No effects on nerve conduction velocity or on balance time with the rotarod test were observed in male Wistar rats administered 0.5% acetone in the drinking water.

Two early studies focused on evaluation of the concentration–time relationship of various CNS effects. In the first study, Mashbitz et al. (1936) exposed white mice to acetone at 40 000, 60 000, 80 000, 100 000, 120 000, 133 000 or 200 000 mg/m3 under static exposure conditions for varying durations up to 4 hours. The time to narcosis was reported as 158, 92, 59, 38, 33, 38 and 34 minutes, respectively. At the four highest concentrations, the first effects observed were drowsiness followed by a period of excitement. Other effects that followed included impaired coordination, deep narcosis and frequent rhythmical clonic movement of the hind legs and abdominal muscles. In the second study, Haggard et al. (1944) exposed rats to acetone at 5000, 10 000, 25 000, 50 000, 100 000, 200 000 or 300 000 mg/m3 for durations ranging up to 8 hours. “Intoxication” (defined as the first visible evidence of slight incoordination) was dose related and seen at concentrations of 25 000 mg/m3 and above at durations of 100–250, 40–80, 15–35, 10–15 and 5–7 minutes of exposure, respectively. Exposure to concentrations up to 10 000 mg/m3 for durations up to 8 hours did not result in any intoxication. Loss of righting reflex (50 000 mg/m3 and above) and loss of corneal reflex (100 000 mg/m3 and above) were observed subsequently. The authors determined that slight incoordination was seen at blood concentrations of approximately 1000–2000 mg/L, loss of righting reflex at about 3000 mg/L, loss of corneal reflex at 5000 mg/L and respiratory failure at 9100–9300 mg/L.

Two studies conducted sensitive objective testing of CNS effects following acute inhalation exposures in humans. Dick et al. (1989) reported small but statistically significant changes in two neurobehavioural tests (auditory tone discrimination and anger-hostility scale) in subjects exposed to the only acetone concentration tested, 600 mg/m3, for 4 hours. The authors suggested that the observed changes may have been an artifact of the large number of statistical tests, but the finding of differences at multiple time points, with the magnitude of the difference from control paralleling the blood acetone level, suggests that this study identified a sensitive effect level. The current report considers that the CNS effect level identified in the Dick et al. (1989) study is inconsistent with the rest of the hazard database, noting that occupational epidemiological studies indicate that workers are often exposed daily to concentrations ranging between 1000 and 2000 mg/m3 without observing adverse and more permanent systemic effects, aside from the transient sensory irritation-related effects (Oglesby et al. 1949; Raleigh and McGee 1972; Ott et al. 1983a, b, c; Grampella et al. 1987; Soden 1993). Stewart et al. (1975) reported transient dizziness and tiredness, along with one report of vertigo, in subjects exposed to acetone concentrations up to 2970 mg/m3 for up to 7.5 hours. These effects did not appear to be concentration or duration related, and there were no effects on the two objective neurobehavioural tests. However, the suggestion that exposure to 2970 mg/m3 for up to 7.5 hours causes sensitive neurological effects is supported by the report in the Stewart et al. (1975) study that there was a significant change in amplitude of the visual evoked response test in male subjects exposed under these conditions for 2 or 4 days; the visual evoked response was not measured on the 1st exposure day. It should be noted that the dose groups from this study are particularly small, 2–4 per group, which considerably limits the interpretation of the data, despite the extensive tests conducted.

The neurotoxicity database for acetone indicates that mild, transient, reversible CNS effects may be noted in individuals acutely exposed to acetone. Dizziness and other symptoms were more common following the initial exposure, while adaptation (reduction in prevalence and severity of effects) was noted in workers exposed to higher concentrations for longer periods of time. The available information indicates that neurological effects are not a critical effect for risk characterization following either single or periodic, intermittent acute exposures to acetone.

10.2.11 Epidemiological Studies

Satoh et al. (1996) conducted a cross-sectional study on 110 Japanese male shift workers who were employed for an average of 18.9 years in an acetate fibre plant and 67 male unexposed shift workers employed for an average of 22.2 years. The age of the exposed workers ranged from 18.7 to 56.8 years (mean 37.6 years), and the length of exposure ranged from 0.5 to 34.5 years (mean 14.9 years). The age of the unexposed workers ranged from 20.7 to 57.5 years (mean 41.9 years). The mean TWA acetone concentration in the breathing zone over the course of a workday was 361 ppm (858 mg/m3), but individual exposures varied widely, from 5 to 1212 ppm (12 to 2888 mg/m3). Blood concentrations of acetone ranged from 4 to 220 mg/L (mean 66 mg/L). The authors reported exposure-related increases in eye irritation, tearing and acetone odour at the end of the workshift and in heavy, vague or faint feeling in the head, nausea, loss of weight and slow healing of an external wound within the previous 6 months. No differences between the exposed and unexposed groups were reported for the Manifest Anxiety Scale or the Self-rating Depression Scale scores, R-R interval variation on electrocardiogram, hematological parameters (hemoglobin, packed cell volume, total and differential white blood cell count) or biochemical parameters (alkaline phosphatase, aspartate aminotransferase [AST], ALT, gamma-glutamyltransferase).

Mitran et al. (1997) examined the neurotoxic effects of acetone in 71 occupationally exposed workers at a coin and medal factory. The mean length of exposure of the workers was 14 years. The acetone concentration over an 8-hour shift ranged from 988 to 2114 mg/m3. Compared with 86 matched controls, acetone-exposed workers exhibited an increased prevalence of mood disorders, irritability, memory difficulties, sleep disturbances, headache, numbness in hands and feet and upper respiratory tract irritation and significant differences in motor nerve conduction velocity in median, ulna and peroneal nerves. The authors concluded that chronic acetone exposure impaired human performance and elicited neurotoxic effects in these workers, but that the motor nerve conduction results should not be overinterpreted and that the use of standardized psychological and neurobehavioural tests was needed. It is unclear why this study reported neurological effects at such low concentrations, when urinary acetone concentrations (53–101 mg/L) were within a factor of 2 of normal. However, Graham (2000) raised a number of issues about the methods of the Mitran et al. (1997) study, particularly noting that nerve conduction velocity is very sensitive to the temperature at which testing is conducted, and the observed differences could be explained if the controls were tested at warmer ambient temperatures. Other issues noted by Graham (2000) included insufficient information about the number of diabetics in the test and control groups and the surprising consistency in the average age and exposure duration in three different factories, raising questions about how the subjects were selected. In reply, Mitran (2000) noted that the subjects were selected from a much larger pool, but did not specifically address the temperature or diabetes issues.

Ott et al. (1983a, b, c) examined employees of a cellulose fibre plant in which acetone was used as the only solvent. The TWA air concentration of acetone reported by the authors was about 1000 ppm (2400 mg/m3). There was no significant excess risk of mortality from any cause or of cardiovascular disease or total malignant neoplasms in workers in this study.

Grampella et al. (1987) examined systemic effects including organ damage in 60 volunteers employed for at least 5 years at an acetate fibre manufacturing plant. Based on their level of exposure, workers were divided equally into high and low acetone exposure groups. The TWA acetone concentrations ranged from 948 to 1048 ppm (2300 to 2500 mg/m3) and from 549 to 653 ppm (1300 to 1600 mg/m3) in the high- and low-exposure groups, respectively. The reported average urinary acetone levels were 93 mg/L and 62 mg/L for the high- and low-exposure groups, respectively. Another group of 60 subjects that had never been exposed to acetone was included in this evaluation. Several hematological and biochemical parameters were analyzed. After adjusting for confounding factors, such as smoking, alcohol consumption, age and past medical histories (liver and kidney damage), the authors found no statistically significant differences in hematological parameters or biochemical markers of liver and kidney effects.

Oglesby et al. (1949) examined the effect of acetone vapours on sensory irritation and systemic toxicity (hematology and urinalysis, endpoints evaluated not further specified) in the workplace in 800 acetone-exposed employees. Acetone concentrations at the workplace ranged from 1425 to 5100 mg/m3. The mean length of exposure was not reported. The secondary source reported a NOEC for human sensory irritation of 3560 mg/m3, but acetone exposure did not elicit systemic toxicity or adverse health effects.

Soden (1993) evaluated the effects of acetone on hematology and blood chemistry in 150 occupationally exposed workers at a triacetate fibre plant. The workers were exposed to an average 8-hour TWA concentration of 900 ppm (2140 mg/m3) for an unspecified duration. Compared with 260 non-exposed controls, there were no significant differences in ALT, AST, total bilirubin or hematocrit in the exposed group. The response rates for symptoms such as loss of memory, headache or dizziness were also not different between exposed subjects and controls.

Raleigh and McGee (1972) monitored nine filter press operators involved in removing and replacing filter cloths saturated with cellulose acetate dissolved in acetone. These workers had short-term (about 2–3 hours) exposures to much higher acetone concentrations than those normally present in the work area. The average acetone concentrations of 2300 ppm (5500 mg/m3) and 300 ppm (710 mg/m3) were measured in the breathing zone of workers pulling filters and those dressing presses, respectively, for the 1st and 2nd years of the study, compared with 110 ppm (260 mg/m3) measured in the general air. Exposure caused transient and intermittent eye, throat and nasal irritation as well as headaches and light-headedness in some individuals when exposure exceeded 1000 ppm (2400 mg/m3). There were no other CNS effects attributable to acetone exposure in this study, as assessed by finger-to-nose test and joint position sense test.

10.2.12 Uncertainties in the Hazard Database

The confidence in the available data set is considered to be high. The effects of acetone following acute and daily exposure are well characterized in animal studies for a range of endpoints and species. The animal data are supported by an extensive database of effects in humans following acute exposure. The long-term effects of acetone exposure have been evaluated in several epidemiological studies; however, most studies had design limitations. Epidemiological studies indicate that effects of repeated exposure are comparable to those observed in shorter-duration studies in humans; therefore, shorter-term studies are relevant to risk characterization for daily exposure of the general population.

The acute human data are adequate for evaluation of a concentration–response relationship. Data from humans and experimental animals support the conclusion that the most sensitive toxicological endpoints for acute exposure are sensory irritation and CNS effects. Chemical-specific data on the concentration–duration–response relationship for extrapolating across exposure durations are limited to animal studies. Also, while animals are known to metabolize acetone through the same pathways as humans, the rates appear to differ, adding some uncertainty to the time-to-effect data from animal studies.

While the mode of action for the critical effects for daily exposure (hematological and renal effects) is not well understood, the pattern of effects is fairly consistent for the identification of the critical effect level. The renal effects in male rats may be due only partially to α2u-globulin nephropathyFootnote[6]. Since this α2u-globulin phenomenon cannot fully explain the observed effects, the observed renal effects were assumed to be relevant to humans.

Although acetone has not been adequately tested for carcinogenicity via all routes of exposure, the available information indicates that it is not carcinogenic. Acetone is often used as a solvent in chronic dermal toxicity studies, and it is not genotoxic. Chronic toxicity data are available only via the inhalation route; however, the metabolic pathway is the same regardless of route of exposure.

10.3 Characterization of Risk to Human Health

Upper-bounding estimates of daily intake of acetone for the general population were derived based on concentrations of acetone in air, water, food and beverages and soil. Total daily intake is estimated to range from 133 µg/kg-bw per day for breastfed infants aged 0–6 months to 650 µg/kg-bw per day for children aged 0.5–4 years (Appendix B). Estimates of exposure from exogenous sources are a small fraction of levels of acetone present in the body due to endogenous production.

Two shorter-term animal studies have been identified as critical studies to characterize the risk to human health from daily exposure. These studies are considered relevant, as the human health effects database indicates that the effects observed in clinical studies of shorter duration are comparable in nature and severity to effects observed in epidemiological studies in which occupationally exposed individuals are typically exposed for several years. The first study is a 13-week drinking water study in rats (NTP 1991). The overall LOAEL was 1700 mg/kg-bw per day, based on biologically significant hematological changes and adverse kidney effects (increased kidney weight with mild nephropathy) in male rats. The second study is an inhalation developmental toxicity study in rats by Mast et al. (1988). The LOAEC was 11 000 ppm (26 100 mg/m3, 2300 mg/kg-bw per day), based on decreased fetal body weight and increases in malformations. These developmental effects occurred at maternally toxic doses in rats and occurred at higher levels than the hematological changes and adverse kidney effects observed in the NTP (1991) study. Accordingly, margins of exposure based on the LOAEL (1700 mg/kg-bw per day) reported in the NTP (1991) drinking water study are considered protective of potential developmental effects. These two studies were selected based on the endpoints examined, the quality of the methodology and the identification of the most appropriate lowest LOAEL values.

The margins of exposure between the upper-bounding total daily intake estimate from air, water, food and beverages and soil and critical effect levels from a 13-week drinking water study in rats at 1700 mg/kg-bw per day ranged from 2600 for children aged 0.5–4 years (650 µg/kg-bw per day) to 13 000 for infants aged 0–6 months (133 µg/kg-bw per day). The margin of exposure between the LOAEC of 26 100 mg/m3and upper-bounding concentrations of acetone in air from personal air sampling data of 475.9 µg/m3 is 55 000. These margins of exposure are considered adequate to address uncertainties in the exposure and health effects databases.

Peak and 4-hour TWA air concentrations of acetone were derived for use of certain household and cosmetic products containing acetone. Peak air concentrations ranged from 117 to 4415 mg/m3; 4-hour TWA air concentrations were an order of magnitude lower and ranged from 8 to 526 mg/m3. The effects observed (sensory irritation and mild CNS depression) following acute exposure to acetone within this range of concentrations are mild, transient and reversible once the subject is removed from the exposure source. While the odour threshold (sensory irritation) may be in the range of estimated exposures, which generally starts to be felt at concentrations of approximately 1000 mg/m3 in humans, irritancy of mucous membranes occurs at concentrations that are orders of magnitude higher than the estimated peak exposures.

In the human health effects literature, CNS effects were generally limited to symptoms such as dizziness and headache. Sensitive measures such as auditory tone discrimination and self-reported anger/hostility were noted by Dick et al. (1989) at a dose as low as 600 mg/m3 over a 4-hour exposure period. Such effects may be considered adaptable, since several studies of occupationally exposed individuals noted an absence of effects in longer-duration studies in individuals exposed to higher concentrations of acetone. Additionally, CNS effects are more dependent on the total dose than on the exposure concentration; hence, shorter exposure requires a much higher concentration of acetone to exert effects. For a 10-minute exposure, a concentration of 200 000 mg/m3 was required to induce CNS effects in rats (Haggard et al. 1944).

Overall, no critical health effects were identified for the purpose of the acute risk characterization. This is consistent with outcomes of assessments from other agencies. OECD (1999) determined that the acute toxicity of acetone is low, and the US EPA (2003) considered acute effects reported in human studies (occupational and volunteer) to be mild and transient (occurring on initial exposure and then dissipating over time).

Based on the information available, it is concluded that acetone does not meet the criteria under paragraph 64(c) of CEPA 1999 as it is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.

10.4 Uncertainties in Evaluation of Risk to Human Health

No chronic studies in animals have been conducted with acetone; however, epidemiological studies indicate that effects of repeated exposure are similar to effects observed in shorter clinical studies in humans.

Although the available information indicates that acetone is not carcinogenic, the absence of a standard carcinogenicity study by the predominant route of exposure is an uncertainty.

Overall confidence in the acetone total daily intake estimates from environmental media, food, cosmetic products and household products is moderate. Data on acetone concentrations in Canadian environmental media were available for personal air samples and water; however, there were no Canadian data for levels of acetone in food and no data for levels of acetone in breast milk. The use of maximum concentrations may overestimate potential dietary exposure to acetone, particularly since concentrations vary widely among published data sets and maximum values were extended to all foods within a food group. Acetone is used in a wide range of products at concentrations up to 100%; therefore, individual exposures are expected to vary greatly. Additionally, in the absence of data, assumptions were made on the rate and quantity of acetone released from products, and the level of conservatism in these assumptions is not known. However, exposure to acetone from environmental media, food and products is estimated to represent less than 2% of the acetone produced endogenously in the human body and falls within the range of human variability of endogenous acetone production.

Top of Page

11. Conclusion

Based on the information presented in this screening assessment, there is low risk of harm to organisms or the broader integrity of the environment from this substance. It is therefore concluded that acetone does not meet the criteria under paragraph 64(a) or 64(b) of CEPA 1999, as it is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity or that constitute or may constitute a danger to the environment on which life depends. It is also concluded that acetone does not meet the criteria under paragraph 64(c) of CEPA 1999, as it is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.

Based on available information for environmental and human health considerations, it is concluded that acetone does not meet any of the criteria set out in section 64 of CEPA 1999.

Top of Page

References

Abbondandolo A, Bonatti S, Corsi C, Corti G, Fiorio R, Leporini C, Mazzaccaro A, Nieri R, Barale R, Loprieno N. 1980. The use of organic solvents in mutagenicity testing. Mutat Res 79:141–150. [cited in WHO 1998].

[ACC] American Chemistry Council Acetone Panel. 2003. Acetone (CAS No. 67-64-1). VCCEP [Voluntary Children’s Chemical Evaluation Program] submission. Peer consultation document submitted to US Environmental Protection Agency [Internet]. September 10, 2003. [cited 2011 Nov]. Available from: www.tera.org/peer/VCCEP/ACETONE/acevccep.pdf

[AIHA] American Industrial Hygiene Association. 2009a. Exposure Assessment Strategies Committee Industrial Hygiene Model version 0.198. Fairfax (VA): AIHA.

[AIHA] American Industrial Hygiene Association. 2009b. Mathematical models for estimating occupational exposure. 2nd ed. Fairfax (VA): AIHA.

[AIHA] American Industrial Hygiene Association. 2009c. Exposure Assessment Strategies Committee Industrial SkinPerm Model version 1.03. Fairfax (VA): AIHA.

[AIHA] American Industrial Hygiene Association. 2010. Exposure Assessment Strategies Committee SkinPerm Model version 1.03.  Fairfax (VA): AIHA.

Albertini S. 1991. Reevaluation of the 9 compounds reported conclusive positive in yeast Saccharomyces cerevisiaeaneuploidy test systems by the Gene-Tox program using strain D61.M of Saccharomyces cerevisiae. Mutat Res 260:165–180. [cited in Morgott 2001].

Amacher DE, Paillet SC, Turner GN, Verne V, Salsburg DS. 1980. Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells: 2. Test validation and interpretation. Mutat Res 72:447–474. [cited in WHO 1998].

American Biogenics Corporation. 1986. Ninety-day gavage study in albino rats using acetone. Study 410-2313. Washington (DC): US Environmental Protection Agency, Office of Solid Waste. 950 p.

Anderson D, MacGregor DB. 1980. The effect of solvents upon the yield of revertants in the Salmonella/activation mutagenicity assay. Carcinogenesis 1:363–366. [cited in WHO 1998].

Anderson GL, Cole RD, Williams PL. 2004. Assessing behavioral toxicity with Caenorhabditis elegans. Environ Toxicol Chem 23(5):1235–1240.

Andersson J, von Sydow E. 1966. The aroma of black currants. Acta Chem Scand 20:522–528.

Andersson L, Lundstrom K. 1984. Milk and blood ketone bodies, blood isopropanol and plasma glucose in dairy cows; methodological studies and diurnal variations. Zentralbl Vet Med A 31:340–349.

Arnold SR., Chipperfield MP, Blitz MA, Heard DE, Pilling MJ.  2004.  Photodissociation of acetone: atmospheric implications of temperature-dependent quantum yields.  Geophys. Res. Let., 31 (L07110).

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten JV. 1994. Blood concentrations of volatile organic compounds in a nonoccupationally exposed US population and in groups with suspected exposure. Clin Chem 40(7):1401–1404.

[ATSDR] Agency for Toxic Substances and Disease Registry. 1988. Health assessment for Vega Alta public supply wells site: Vega Alta, Puerto Rico, Region 2. CERCLIS No. PRS187147. Atlanta (GA): US Department of Health and Human Services, Public Health Service. [cited in ATSDR 1994].

[ATSDR] Agency for Toxic Substances and Disease Registry. 1994. Toxicological profile for acetone. Atlanta (GA): US Department of Health and Human Services, Public Health Service.

[ATSDR] Agency for Toxic Substances and Disease Registry. 2011. Addendum to the toxicological profile for acetone. Atlanta (GA): US Department of Health and Human Services, Public Health Service.

Axelsson G, Luetz C, Rylander R. 1984. Exposure to solvents and outcome of pregnancy in university laboratory employees. Br J Ind Med 41:305–312.

Barale R, Rusciano D, Stretti G, Zucconi D, Monaco M, Mosesso P, Principe P. 1983. The induction of forward gene mutation and gene conversion in yeasts by treatment with cyclophosphamide in vitro and in vivo. Mutat Res 111:295–312. [cited in Morgott 2001].

Barr-Nea L, Wolman M. 1972. The effects of cutaneous applications of beach-polluting oil on mice. Isr J Med Sci 8:1745–1749. [cited in Barr-Nea and Wolman 1977].

Barr-Nea L, Wolman M. 1977. Tumors and amyloidosis in mice painted with crude oil found on bathing beaches. Bull Environ Contam Toxicol 18:385–391.

Bartley JP, Schwede AM. 1989. Production of volatile compounds in ripening kiwi fruit (Actinidia chinensis). J Agric Food Chem 37:1023–1025.

Basler A. 1986. Aneuploidy-inducing chemicals in yeast evaluated by the micronucleus test. Mutat Res 174(1):11–13. [cited in WHO 1998].

[BCFBAF] Bioaccumulation Program for Windows [Estimation Model]. 2008. Version 4.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Benkelberg HJ, Hamm S, Warneck P. 1995. Henry’s Law coefficients for aqueous solutions of acetone, acetaldehyde and acetonitrile, equilibrium constants for the addition compounds of acetone and acetaldehyde with bisulfite. J Atmos Chem 20:17–34. [cited in EPI Suite 2008].

Berthold A, Jakl T. 2002. Soil ciliate bioassay for the pore water habitat: a missing link between microflora and earthworm testing in soil toxicity assessment. J Soils Sediments 2(4):179–193.

Betterton EA. 1991. The partitioning of ketones between the gas and aqueous phases. Atmos.Environ. 25A, 1473-1477. [as cited in OECD 1999]

Beyer A, Mackay D, Matthies M, Wania R, Webster E. 2000. Assessing long-range transport potential of persistent organic pollutants. Environ Sci Technol 34:699–703.

Bills DD, Keenan TW. 1968. Dimethyl sulfide and its precursor in sweet corn. J Agric Food Chem 16(4):643–645.

Bluzat R, Jonot O, Lespinasse G, Seugé J. 1979. Chronic toxicity of acetone in the fresh water snail Lymnea stagnalis. Toxicology 14:179–190.

Bremmer HJ, van Engelen JGM. 2007. Paint products fact sheet: to assess the risks for the consumer. Updated version for ConsExpo 4 [Internet]. Bilthoven (NL): RIVM [National Institute for Public Health and the Environment]. RIVM report 320104008/2007. Available from: www.rivm.nl/bibliotheek/rapporten/320104008.pdf

Bremmer HJ, Prud’homme de Lodder LCH, van Engelen JGM. 2006. Cosmetics facts sheet: to assess the risks for the consumer: updated version for ConsExpo4. Bilthoven (NL): RIVM [National Institute for Public Health and the Environment]. RIVM report 320104001/2006. Available from: www.rivm.nl/bibliotheek/rapporten/320104001.pdf

Bringmann G, Kühn R. 1978. Testing of substances for their toxicity threshold: model organisms Microcystis(Diplocystis) aeruginosa and Scenedesmus quadricauda. Mitt Int Verein Limnol21:275–284. [cited in OECD 1999].

Brosseau J, Heitz M. 1994. Trace gas compounds from municipal landfill sanitary sites. Atmos Environ 28(2):285–293. 

Brown KW, Donnelly KC. 1988. An estimation of the risk associated with the organic constituents of hazardous and municipal waste landfill leachates. Hazard Waste Hazard Mater 5:1–30.

Bruckner JV, Peterson RG. 1981a. Evaluation of toluene and acetone inhalant abuse. I. Pharmacology and pharmacodynamics. Toxicol Appl Pharmacol 61:27–38.

Bruckner JV, Peterson RJ. 1981b. Evaluation of toluene and acetone inhalant abuse: II. Model development and toxicology. Toxicol Appl Pharmacol 61(3):302–312.

Burdock GA. 2010. Fenaroli’s handbook of flavor ingredients. 6th ed. Orlando (FL): Burdock Group.

Burmaster DE. 1982. The new pollution--groundwater contamination. Environment 24:6–13, 33–36 [cited in WHO 1998].

Buron G, Hacquemand R, Pourié G, Brand G. 2009. Inhalation exposure to acetone induces selective damage on olfactory neuroepithelium in mice. Neurotoxicology 30:114–120.

Canada. 1986. Food and Drugs Act, 1985. R.S., c., F-27, s.1. Available from: http://laws-lois.justice.gc.ca/eng/acts/F-27/

Canada. 1999. Canadian Environmental Protection Act, 1999. S.C., 1999, c. 33. Canada Gazette Part III, vol. 22, no. 3. Available from: www.gazette.gc.ca/archives/p3/1999/g3-02203.pdf

Canada, Dept. of the Environment. 2001. Canadian Environmental Protection Act, 1999: Notice with respect to certain substances on the Domestic Substances List (DSL). Canada Gazette, Part I, vol. 135, no. 46, p. 4194–4210. Available from: www.gazette.gc.ca/archives/p1/2001/2001-11-17/pdf/g1-13546.pdf

Canada. 2006. Food and Drugs Act: Natural Health Products Regulations, P.C. 2003-847, 5 June 2003, SOR/2003-196. Available from: http://laws.justice.gc.ca/eng/regulations/SOR-2003-196/index.html

Canada. 2008. Canadian Environmental Protection Act, 1999: Volatile Organic Compound (VOC) Concentration Limits for Certain Products Regulations. Canada Gazette, Part I, April 26, 2008. Available from: http://www.gazette.gc.ca/rp-pr/p1/2008/2008-04-26/html/reg3-eng.html

Canada. 2009a. Canadian Environmental Protection Act, 1999: Volatile Organic Compound (VOC) Concentration Limits for Architectural Coatings Regulations, P.C. 2009-1535, 9 September 2009, SOR/2009-264. Available from: www.gazette.gc.ca/rp-pr/p2/2009/2009-09-30/html/sor-dors264-eng.html

Canada. 2009b. Canadian Environmental Protection Act, 1999: Volatile Organic Compound (VOC) Concentration Limits for Automotive Refinishing Products Regulations, P.C. 2009-1036, 18 June 2009, SOR/2009-197. Available from: http://canadagazette.gc.ca/rp-pr/p2/2009/2009-07-08/html/sor-dors197-eng.html

Carpenter CP, Smyth HF Jr. 1946. Chemical burns of the rabbit cornea. Am J Ophthalmol 29:1363–1372.

Carter JM, Delzer GC, Kingsbury JA, Hopple JA. 2007. Concentration data for anthropogenic organic compounds in ground water, surface water, and finished water of selected community water systems in the United States, 2002–05: US Geological Survey Data Series 268. [Internet]. Reston (VA): US Geological Survey. [cited 2011 Dec 12]. Available from: http://pubs.usgs.gov/ds/2007/268/

Chen TH, Kavanagh TJ, Chang CC, Trosko JE. 1984. Inhibition of metabolic cooperation in Chinese hamster cells by various organic solvents and simple compounds. Cell Biol Toxicol 1:155–171. [cited in Morgott 2001].

Cheng SJ, Sala M, Li MH, Courtois I, Chouroulinkov I. 1981. Promoting effect of Roussin’s red identified in pickled vegetables from Linxian China. Carcinogenesis 2:313–319. [cited in Morgott 2001].

Cho C-W, Pham TPT, Kim S, Kim Y-R, Jeon Y-C, Yun Y-S. 2009. Toxicity assessment of common organic solvents using a biosensor based on algal photosynthetic activity measurement. J Appl Phycol 21(6):683–689.

Christoph GR, Malley LA, Stadler JC. 2003. Subchronic inhalation exposure to acetone vapor and scheduled controlled operant performance in male rats. Inhal Toxicol 15(8):781–798.

Coleman EC, Ho CT, Chang SS. 1981. Isolation and identification of volatile compounds from baked potatoes. J Agric Food Chem 29(1):42–48.

Collander R. 1951. The partition of organic compounds between higher alcohols and water. Acta Chem Scand 5:774–780.

Cometto-Muñiz JE, Cain WS. 1993. Efficacy of volatile organic compounds in evoking nasal pungency and odour. Arch Environ Health 48(5):309–314.

[ConsExpo] Consumer Exposure Model [Internet]. 2006. Version 4.1. Bilthoven (NL): Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment). Available from: www.rivm.nl/en/healthanddisease/productsafety/ConsExpo.jsp#tcm:13-42840

Corwin JF. 1969. Volatile oxygen-containing organic compounds in sea water: determination. Bull Mar Sci 19:504–509.

Dalgaard M, Ostergaard G, Lam HR, Hansen EV, Ladefoged O. 2000. Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats. Pharmacol Toxicol 86:92–100.

Dalton P, Wysocki CJ, Brody MJ, Lawley HJ. 1997. The influence of cognitive bias on the perceived odor, irritation and health symptoms from chemical exposure. Int Arch Occup Environ Health 69:407–417.

Day EA, Anderson DF. 1965. Gas chromatographic and mass spectral identification of natural components of the aroma fraction of blue cheese. J Agric Food Chem 13:2–4.

Day EA, Bassette R, Keeney M. 1960. Identification of volatile carbonyl compounds from cheddar cheese. J Dairy Sci 43:463–474.

De Ceaurriz J, Micillino JC, Marignac B, Bonnet P, Muller J, Guenier JP. 1984. Quantitative evaluation of sensory irritating and neurobehavioral properties of aliphatic ketones in mice. Food Chem Toxicol 22:545–549.

Deco-Crete Supply. 2010a. Material Safety Data Sheet: Clearguard 25 [Internet]. Orrville (OH): Deco-Crete Supply. [cited 2012 Jan]. Available from: www.deco-cretesupply.com/sites/default/files/ClearGaurdmsds.pdf

Deco-Crete Supply. 2010b. Technical Data Sheet: Clearguard 25. Orrville (OH): Deco-Crete Supply. [cited 2012 Jan]. Available from: www.deco-cretesupply.com/sites/default/files/ClearGuard25TechSheet.pdf

De Flora S, Zanacchi P, Camoirano A, Bennicelli C, Badolati GS. 1984. Genotoxic activity and potency of 135 compounds in the Ames reversion test and in a bacterial DNA-repair test. Mutat Res 133:161–198. [cited in Morgott 2001].

DeMarini DM, Lawrence BK, Brooks HG, Houk VS. 1991. Compatibility of organic solvents with the Microscreen prophage-induction assay: solvent–mutagen interactions. Mutat Res 263:107–113. [cited in Morgott 2001].

DePass LR, Ballantyne B, Fowler EH, Weil CS. 1989. Dermal oncogenicity studies on two methoxysilanes and two ethoxysilanes in male C3H mice. Fundam Appl Pharmacol 12:579–583.

Descotes J. 1988. Identification of contact allergens: the mouse ear sensitization assay. J Toxicol Cutan Ocular Toxicol 7(4):2263–2272.

DeWalle FB, Chian ESK. 1981. Detection of trace organics in well water near a solid waste landfill. J Am Water Works Assoc 73:205–211.

DeWalle FB, Kalman DA, Norman D, Sung J, Plews G. 1985. Determination of toxic chemicals in effluent from household septic tanks. Cincinnati (OH): US Environmental Protection Agency. Report No.: EPA 600/S2-85-050.

Dick RB, Setzer JV, Taylor BJ, Shukla R. 1989. Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone. Br J Ind Med 46(2):111–121.

Dietz DD, Leininger JR, Rauckman EJ, Thompson MB, Chapin RE, Morrissey EJ, Levine BS. 1991. Toxicity studies of acetone administered in the drinking water of rodents. Fundam Appl Toxicol 17:347–360.

DiVincenzo GD, Yanno FJ, Astill BD. 1973. Exposure of man and dog to low concentrations of acetone vapor. Am Ind Hyg Assoc J 34:329–336. [cited in ATSDR 1994].

Dowden BF, Bennett HJ. 1965. Toxicity of selected chemicals to certain animals. J Water Pollut Control Fed 37(9):1308–1316.

Dowty BJ, Laseter JL, Storer J. 1976. The transplacental migration and accumulation in blood of volatile organic constituents. Pediatr Res 10:696–701. [cited in ATSDR 1994].

[DPD] Drug Product Database [database on the Internet]. 2011. Ottawa (ON): Health Canada. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php.

[ECJRC] European Commission, Joint Research Centre. 2003. Technical guidance document on risk assessment, Part II. Ispra (IT): European Commission, Joint Research Centre. Report No.: EUR 20418 EN/2.

[ECOSAR] Ecological Structure Activity Relationships Class Program for Windows. 2008. Version 1.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Eggert T, Bødker J, Hansen OC. 2002. Chemical ingredients in candles sold in Danish retail shops. Survey of Chemical Substances in Consumer Products, No. 6 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/4DBF68B7-77DD-4D13-8911-B42581EBACCC/0/lys_uk.pdf

Egmose K, Pors J. 2005. Survey of chemical substances in textile colorants. Survey of Chemical Substances in Consumer Products, No. 58 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www2.mst.dk/Udgiv/publications/2005/87-7614-677-4/pdf/87-7614-678-2.pdf

Engelund B, Sørensen H. 2005. Mapping and health assessment of chemical substances in shoe care products. Survey of Chemical Substances in Consumer Products, No. 52 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/A0B7B547-8403-410F-906E-DF2A2E336F07/0/52.pdf

Engelund B, Höglund L, Skjødt D. 2003. Mapping of stain removers. Survey of Chemical Substances in Consumer Products, No. 43 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/D1C06F0C-0F52-4EC0-A859-91FF1E1F9849/0/43.pdf

Environment Canada. 2004. Data collected under Canadian Environmental Protection Act, 1999,Section 71. Notice with respect to certain substances on the Domestic Substances List (DSL). Data compiled by: Environment Canada, Program Development and Engagement Division.

Environment Canada. 2006.  Wastewater section.  Database of wastewater treatment systems on federal properties; restricted access.

Environment Canada. 2011a. National Pollutant Release Inventory, online facility-reported data for acetone for years 1997, 1998, 2009. [cited 2011 Dec 15]. Available from: www.ec.gc.ca/pdb/websol/querysite/query_e.cfm

Environment Canada. 2011b. National Air Pollution Surveillance (NAPS) program, monitoring data for years 2000–2009. Ottawa (ON): Environment Canada, Analysis and Air Quality Division.

 [EQC] Equilibrium Criterion Model. 2003. Version 2.02. Peterborough (ON): Trent University, Canadian Centre for Environmental Modelling and Chemistry. Available from: www.trentu.ca/academic/aminss/envmodel/models/EQC2.html

[EPI Suite].  Estimation Programs Interface Suite for Microsoft Windows [Estimation Model]. 2008. Version 4.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuitedl.htm

Ernstgård LE, Gullstrand E, Johanson G, Löf A. 1999. Toxicokinetic interactions between orally ingested chlorzoxazone and inhaled acetone or toluene in male volunteers. Toxicol Sci 48:189–196. [cited in Mörk and Johanson 2006].

European Commission. 1997. Evaluation of VOC emissions from building products--solid flooring materials. European Collaborative Action: Indoor Air Quality & Its Impact on Man. Environment and Quality of Life. Luxembourg: Office for Official Publications of the European Communities. Report No.: 18.

European Commission. ©2000a. IUCLID Dataset, acetone, CAS No. 67-64-1 [Internet]. Year 2000 CD-ROM edition. [place unknown]: European Commission, European Chemicals Agency. [created 2000 Feb 18;. Available from: http://esis.jrc.ec.europa.eu/index.php?PGM=dat

European Commission. ©2000b. IUCLID Dataset, propano1, CAS No. 67-63-0. [Internet]. Year 2000 CD-ROM edition. [place unknown]: European Commission, European Chemicals Agency. [created 2000 Feb 18;. Available from: http://esis.jrc.ec.europa.eu/index.php?PGM=dat

[FAO/WHO] Food and Agriculture Organization of the United Nations/World Health Organization. 1998. Evaluation of certain food additives. Fifty-first report of the Joint FAO/WHO Expert Committee on Food Additives. Geneva (CH): World Health Organization. (WHO Technical Report Series 891). Available from: http://whqlibdoc.who.int/trs/WHO_TRS_891.pdf

Feilberg A, Tønning K, Jacobsen E, Hemmersam AG, Søborg I, Cohr K-H. 2008. Survey and health assessment of possible health hazardous compounds in proofing sprays. Survey of Chemical Substances in Consumer Products, No. 98. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www2.mst.dk/udgiv/publications/2008/978-87-7052-837-5/pdf/978-87-7052-838-2.pdf

Fenner K, Scheringer M, MacLeod M, Matthies M, McKone TE, Stroebe M, Beyer A, Bonnell M, Le Gall A, Klasmeier J, Mackay D, Pennington DW, Scharenberg B, Wania F. 2005. Comparing estimates of persistence and long-range transport potential among multimedia models. Environ Sci Technol 39:1932–1942.

Feron VJ, De Groot AP, Spanjers MT, Til HP. 1973. An evaluation of the criterion “organ weight” under conditions of growth retardation. Food Cosmet Toxicol 11:85–94.

Feys M, Tobback P, Maes E. 1980. Volatiles of apples (var. ‘Schone van Boskoop’); isolation and identification. J Food Technol 15:485–492.

Freeman AE, Weisburger EJ, Weisburger JH, Wolford RG, Maryak JM, Huebner RJ. 1973. Transformation of cell cultures as an indication of the carcinogenic potential of chemicals. J Natl Cancer Inst 51(3):799–807. [cited in WHO 1998].

Freeman JJ, Hayes EP. 1985. Acetone potentiation of acute acetonitrile toxicity in rats. J Toxicol Environ Health 15:609–621. [cited in ATSDR 1994; WHO 1998].

Friedrich U, Nass G. 1983. Evaluation of a mutation test using S49 mouse lymphoma cells and monitoring simultaneously the induction of dexamethasone resistance, 6-thioguanine resistance and ouabain resistance. Mutat Res 110:147–162. [cited in Morgott 2001].

Fukabori S, Nakaaki K, Tada O. 1979. [On the cutaneous absorption of acetone]. J Sci Labour 55:525–532 (in Japanese). [cited in ATSDR 1994; US EPA 2003].

Gamis AS, Wasserman GS. 1988. Acute acetone intoxication in a pediatric patient. Pediatr Emerg Care 4:24–26. [cited in ATSDR 1994; WHO 1998].

Gehly EB, Heidelberger V. 1982. The induction of Ouar mutations in nontransformable CVP3SC6 mouse fibroblasts. Carcinogenesis 3:963–967. [cited in Morgott 2001].

Geiss O, Giannopoulos G, Tirendi S, Barrero-Moreno J, Larsen BR, Kotzias D. 2011. The AIRMEX study--VOC measurements in public buildings and schools/kindergartens in eleven European cities: statistical analysis of the data. Atmos Environ 45:3676–3684.

Geller I, Gause E, Kaplan H, Hartmann RJ. 1979a. Effects of acetone, methyl ethyl ketone and methyl isobutyl ketone on a match-to-sample task in the baboon. Pharmacol Biochem Behav 11:401–406.

Geller I, Hartmann RJ, Randle SR, Gause EM. 1979b. Effects of acetone and toluene vapors on multiple schedule performance of rats. Pharmacol Biochem Behav 11:395–399. [cited in ATSDR 1994].

Gierczak T, Burholder JB Jr, Bauerle S, Ravishankara AR. 1998. Photochemistry of acetone under tropospheric conditions. Chem Phys 231:229–244.

Girman JR, Hadwen GE, Burton LE, Womble SE, McCarthy JF. 1999. Individual volatile organic compound prevalence and concentrations in 56 buildings of the Building Assessment Survey and Evaluation (BASE) Study. In: Proceedings of the 8th International Conference on Indoor Air Quality and Climate. Indoor Air 2:460–465.

Giroux D, Lapointe G, Baril M. 1992. Toxicological index and the presence in the workplace of chemical hazards for workers who breast-feed infants. Am Ind Hyg Assoc J 53:471–474.

Glensvig D, Ports J. 2006. Mapping of perfume in toys and children’s articles. Survey of Chemical Substances in Consumer Products, No. 68 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www2.mst.dk/Udgiv/publications/2006/87-7052-018-6/pdf/87-7052-019-4.pdf

Glowa JR, Dews PB. 1987. Behavioral toxicology of volatile organic solvents: IV. Comparisons of the rate-decreasing effects of acetone, ethyl acetate, methyl ethyl ketone, toluene, and carbon disulfide on schedule-controlled behavior of mice. J Am Coll Toxicol 6(4):461–469. [cited in ATSDR 1994; WHO 1998; Morgott 2001].

Goldberg MD, Johnson HE, Pozzani UC, Smyth HF Jr. 1964. Effect of repeated inhalation vapors of industrial solvents on animal behavior: I. Evaluation of nine solvent vapors on pole-climb performance in rats. Am Ind Hyg Assoc J 25:369–375.

Goldstein AH, Schade GW. 2000. Quantifying biogenic and anthropogenic contributions to acetone mixing ratios in a rural environment. Atmos Environ 34:4997–5006.

Gorsuch JW, Kringle RO, Robillard KA. 1990. Chemical effects on the germination and early growth of terrestrial plants. In: Wang W, Gorsuch JW, Lower WR, editors. Plants for toxicity assessment. Philadelphia (PA): American Society for Testing and Materials. p. 49–58. Report No.: ASTM STP 1091.

Graedel TE, Hawkins DT, Claxton LD. 1986. Atmospheric chemical compounds: sources, occurrences and bioassay. Orlando (FL): Academic Press. p. 263. [cited in HSDB 1983– ].

Graham DG. 2000. Letter to the editor: Critical analysis of Mitran et al. (1997). Neurotoxicity associated with occupational exposure to acetone, methyl ethyl ketone, and cyclohexanone.Environ. Res. 73,181–188. Environ Res A 82:181–183.

Grampella C, Catenacci G, Garavaglia L, Tringali S. 1987. Health surveillance in workers exposed to acetone. In: Proceedings of the 7th International Symposium on Occupational Health in the Production of Artificial Organic Fibres, Wolfheze, the Netherlands. p. 137–141. [cited in ACC 2003].

Grannas AM, Shepson PB, Guimbaud C, Sumner AL, Albert M, Simpson W, Dominé F, Boudries H, Bottenheim J, Beine HJ, Honrath R, Zhou X. 2002. A study of photochemical and physical processes affecting carbonyl compounds in the Arctic atmospheric boundary layer. Atmos Environ 36(15–16): 2733–2742. 

Grey TC, Shrimpton H. 1967. Volatile components of raw chicken breast muscle. Br Poult Sci 8:23–33. [cited in WHO 1998].

Grove JK, Stein OR. 2005. Polar organic solvent removal in microcosm constructed wetlands. Water Res 39:4040–4050.

Haggard HW, Greenberg LA, Turner JA. 1944. The physiological principles governing the action of acetone together with determination of toxicity. J Ind Hyg Toxicol 26:133–151. [cited in ATSDR 1994].

Hallare A, Nagel K, Köhler H-R, Triebskorn R. 2006. Comparative embryotoxicity and proteotoxicity of three carrier solvents to zebrafish (Danio rerio) embryos. Ecotoxicol Environ Saf 63:378–388.

Han T, Han Y-S, Park CY, Jun YS, Kwon MJ, Kang S-H, Brown MT. 2008. Spore release by the green alga Ulva: a quantitative assay to evaluate aquatic toxicants. Environ Pollut 153:699–705.

Hansen J, Hansen OC, Pommer K. 2004. Release of chemical substances from tents and tunnels for children. Mapping of Chemical Substances in Consumer Products, No. 46 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec]. Available from: www.mst.dk/NR/rdonlyres/26E770C9-2FFB-4059-BD1B-139D6D373C85/0/46.pdf

Hansen PL, Tønnig K, Pommer K, Malmgren B, Hansen OC, Poulsen M. 2006. Survey and health risk assessment of products for treatment of sports injuries and pains. Survey of Chemical Substances in Consumer Products, No. 79 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec]. Available from: www2.mst.dk/Udgiv/publications/2006/87-7052-318-5/pdf/87-7052-319-3.pdf

Hansen OC, Eggert T. 2003. Survey, emission and evaluation of volatile organic chemicals in printed matter. Survey of Chemical Compounds in Consumer Products, No. 36 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/C2C6FC89-9584-4757-A286-B6D6DFCB571A/0/36.pdf

Hatch GG, Mamay PD, Ayer ML, Casto BC, Nesnow S. 1983. Chemical enhancement of viral transformation in Syrian hamster embryo cells by gaseous and volatile chlorinated methanes and ethanes. Cancer Res 43:1945–1950. [cited in Morgott 2001].

Health Canada. 1994. Human health risk assessment for priority substances. Ottawa (ON): Health Canada. Available from: www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/contaminants/approach/approach-eng.pdf

Health Canada. 1995. Investigating human exposure to contaminants in the environment: a handbook for exposure calculations. Ottawa (ON): Health Canada.

Health Canada. 1998. Exposure factors for assessing total daily intake of priority substances by the general population of Canada. Unpublished report. Ottawa (ON): Health Canada, Environmental Health Directorate.

Health Canada. 1999. Q3C: Impurities: guideline for residual solvents. International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) / Therapeutic Products Programme guideline [Internet]. Ottawa (ON): Health Canada, Therapeutic Products Programme. Available from: www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ich/qual/q3c-eng.php

Health Canada. 2003. GL-18--Impurities: residual solvents in new veterinary medicinal products, active substances and excipients [Internet]. Ottawa (ON): Health Canada, Veterinary Drugs Directorate. [cited 2012 Apr]. Available from: www.hc-sc.gc.ca/dhp-mps/vet/legislation/guide-ld/vich/guide-ligne-eng.php

Health Canada. 2007. Evidence for quality of finished natural health products [Internet]. Ottawa (ON): Health Canada, Natural Health Products Directorate. Available from: www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/eq-paq-eng.php

Health Canada. 2010a. Windsor exposure assessment study (2005–2006): data summary for volatile organic compound sampling. Ottawa (ON): Health Canada. 85 p.

Health Canada. 2010b. Regina indoor air quality study (2007): data summary for volatile organic compound sampling. Ottawa (ON): Health Canada. 164 p.

Health Canada. 2011. Halifax indoor air quality study (2009): data summary for volatile organic compound sampling [draft]. Ottawa (ON): Health Canada. 37 p.

Health Canada. 2012a. Lists of permitted food additives [Internet]. Ottawa (ON): Health Canada. [cited 2013 Jan 17]. Available from: www.hc-sc.gc.ca/fn-an/securit/addit/list/index-eng.php

Health Canada. 2012b. Recommended default values for personal care product exposure scenarios. Unpublished report. Ottawa (ON): Health Canada, Safe Environments Directorate, Existing Substances Risk Assessment Bureau.

Heatherbell DA, Wrolstad RE, Libbey LM. 1971. Carrot volatiles.1. Characterization and effects of canning and freeze drying. J Food Sci 36:219–224.

Heavner DL, Morgan WT, Ogden MW. 1996. Determination of volatile organic compounds and respirable suspended particulate matter in New Jersey and Pennsylvania homes and workplaces. Environ Int 22(2):159–183.

Herman MI, Glass T, Howard SC. 1997. Case records of the LeBonheur Children’s Medical Center: a 17-month-old girl with abdominal distension and portal vein gas. Pediatr Emerg Care 13:237–242. [cited in US EPA 2003].

Hiatt MH, Pia JH. 2004. Screening processed milk for volatile organic compounds using vacuum distillation/gas chromatography/mass spectrometry. Arch Environ Contam Toxicol 46:189–196.

Hill EF, Heath RG, Spann JW, Williams JD. 1975. Lethal dietary toxicities of environmental pollutants to birds. Washington (DC): US Department of the Interior, Fish and Wildlife Service. (Special Scientific Report--Wildlife No. 191). p. 1–2, 8, 47.

Hinrichsen LL, Anderson HJ. 1994. Volatile compounds and chemical changes in cured pork: role of three halotolerant bacteria. J Agric Food Chem 42:1537–1542.

Holden HE, Stoll RE, Spalding JW, Tennant RW. 1998. Hemizygous Tg.AC transgenic mouse as a potential alternative to the two-year mouse carcinogenicity bioassay: evaluation of husbandry and housing factors. J Appl Toxicol 18(1):19–24.

Howard WL. 2011. Acetone [Internet]. In: Kirk-Othmer Encyclopedia of Chemical Technology, online version. [cited 2011 Dec 6]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/0471238961.0103052008152301.a01.pub3/abstract [restricted access]

Howard PH, Sage GW, Jarvis WF, Gray DA. 1990. Acetone. In: Handbook of Environmental Fate and Exposure Data for Organic Chemicals, Volume II, pp. 9-18. Lewis Publishers, Inc. New York, NY.

Howard PH, Boethling RS, Jarvis WF, Meylan WM, Michalenko EM, editors. 1991. Handbook of environmental degradation rates. Chelsea (MI): Lewis Publishers. p. 97–98.

[HPD] Household Products Database [database on the Internet]. 1993– . Bethesda (MD): National Library of Medicine (US). [cited 2011 Oct]. Available from: http://householdproducts.nlm.nih.gov/

[HSDB] Hazardous Substances Data Bank [database on the Internet]. 1983– . Bethesda (MD): National Library of Medicine (US). [revised 2007 Nov 10; cited 2011]. Available from: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

Hutchinson TH, Shillabeer N, Winter MJ, Pickford, DB. 2006. Acute and chronic effects of carrier solvents in aquatic organisms: a critical review. Aquat Toxicol 76:69–92.

[IARC] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. 1999. Isopropanol. IARC Monogr  Eval Carcinog Risks Hum 71:1027–1036. Available from: http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-45.pdf

[ICH] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2009. ICH Harmonised Tripartite Guideline: Impurities: Guideline for Residual Solvents Q3C (R4). Geneva (CH): ICH.

Ishidate M Jr, Sofuni T, Yoshikawa K, Hayashi M, Nohmi T, Sawada M, Matsuoka A. 1984. Primary mutagenicity screening of food additives currently used in Japan. Food Chem Toxicol 22:623–636. [cited in Morgott 2001].

Iversen OH, Ljunggren S, Olsen WM. 1988. The early effects of a single application of acetone and various doses of 7,12-dimethylbenz(α)anthracene on CD-1 and hairless mouse epidermis: a cell kinetic study of so-called initiation and complete carcinogenesis (initiation plus promotion) in chemical skin tumor induction. Acta Pathol Microbiol Immunol Scand 27(Suppl):7–80. [cited in ATSDR 1994; WHO 1998; Morgott 2001].

Jacob DJ, Field BD, Jin E, Bey I, Li Q, Logan JA, Yantosca RM, Singh HB. 2002. Atmospheric budget of acetone. J Geophys Res 107(D10):5-1–5-17.

Jelnes JE. 1988. Semen quality in workers producing reinforced plastic. Reprod Toxicol 2:209–212.

Kane LE, Domboske R, Alarie Y. 1980. Evaluation of sensory irritation from some common industrial solvents. Am Ind Hyg Assoc J 41:451–455.

Kawai T, Yasugi T, Mizunuma K, Horiguchi S, Iguchi H, Ikeda M. 1992. Curvi-linear relation between acetone in breathing zone air and acetone in urine among workers exposed to acetone vapor. Toxicol Lett 62:85–91. [cited in US EPA 2003].

Kimura ET, Ebert DM, Dodge PW. 1971. Acute toxicity and limits of solvent residue for sixteen organic solvents. Toxicol Appl Pharmacol 19:699–704.

Kinlin TE, Muralidhara R, Pittet AO, Sanderson A, Walradt JP. 1972. Volatile components in roasted filberts. J Agric Food Chem 20:1021–1028.

Klasmeier J, Matthies M, MacLeod M, Fenner K, Scheringer M, Stroebe M, Le Gall AC, McKone TE, van de Meent D, Wania F. 2006. Application of multimedia models for screening assessment of long-range transport potential and overall persistence. Environ Sci Technol 40:53–60.

Klimisch HJ, Andreae M, Tillmann U. 1997. A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul Toxicol Pharmacol 25:1–5.

[KOCWIN] Organic Carbon Partition Coefficient Program for Windows [Estimation Model]. 2008. Version 2.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Krasavage WJ, O’Donoghue JL, DiVincenzo GD. 1982. Ketone. In: Clayton GD, Clayton FE, editors. Patty’s industrial hygiene and toxicology, vol. 2C. 3rd ed. New York (NY): John Wiley & Sons. p. 4709–4800. [cited in ATSDR 1994; Morgott 2001].

Krill RM, Sonzogni WC. 1986. Chemical monitoring of Wisconsin’s groundwater. J Am Water Works Assoc 78(9):70–75.

Kubinski H, Gutzke GE, Kubinski ZO. 1981. DNA-cell binding (DCB) assay for suspected carcinogens and mutagens. Mutat Res 89:95–136. [cited in WHO 1998].

Ladefoged O, Hass U, Simonsen L. 1989. Neurophysiological and behavioral effects of combined exposure to 2,5-hexanedione and acetone or ethanol in rats. Pharmacol Toxicol 65:372–375.

Lake RS, Kropko ML, Pezzutti MR, Shoemaker RH, Igel HJ. 1978. Chemical induction of unscheduled DNA synthesis in human skin epithelial cell cultures. Cancer Res 38:2091–2098. [cited in ATSDR 1994].

Lang RJ. 1989. Modeling the movement of trace gases in municipal solid waste landfills [thesis]. Davis (CA): University of California. 215 p. [cited in Brosseau and Heitz 1994].

Lankas GR. 1979. Effect of cell growth rate and dose fractionation on chemically-induced ouabain-resistant mutations in Chinese hamster V79 cells. Mutat Res 60:189–196. [cited in Morgott 2001].

Larsen JJ, Lykkegaard M, Ladefoged O. 1991. Infertility in rats induced by 2,4-hexanedione in combination with acetone. Pharmacol Toxicol 69:43–46.

Latt SA, Allen J, Bloom SE, Carrano A, Falke E, Kram D, Schneider E, Schreck R, Tice R, Whitfield B, Wolff S. 1981. Sister-chromatid exchanges: a report of the GENE-TOX program. Mutat Res 87:17–62. [cited in Morgott 2001].

Laursen J, Trap L. 2002. Mapping and exposure of chemical substance in Christmas sprays. Survey of Chemical Substances in Consumer Products, No. 19 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/9BFA1182-5BBF-4A80-A02F-DCEDBF0E2ED0/0/19.pdf

LeBlanc GA, Surprenant DC. 1983. The acute and chronic toxicity of acetone, dimethylformamide, and triethylene glycol to Daphnia magna (Straus). Arch Environ Contam Toxicol 12:305–310.

Lillehaug JR, Djurhuus R. 1982. Effect of diethylstilbestrol on the transformable mouse embryo fibroblast C3H/10T1/2C18 cells. Tumor promotion, cell growth, DNA synthesis, and ornithine decarboxylase. Carcinogenesis 3:797–799. [cited in Morgott 2001].

Line DE, Wu J, Arnold JA, Jennings GD, Rubin AR. 1997. Water quality of first flush runoff from 20 industrial sites. Water Environ Res 69:305–310.

Liu W, Zhang J, Korn LR, Zhang L, Weisel CP, Turpin B, Morandi M, Stock T, Colome S. 2007. Predicting personal exposure to airborne carbonyls using residential measurements and time/activity data. Atmos Environ 41:5280–5288.

[LNHPD] Licensed Natural Health Products Database [database on the Internet]. 2011. Ottawa (ON): Health Canada. [cited 2011]. Available from: http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/index-eng.jsp

Loretz LG, Api AM, Barraj LM, Burdick J, Dressler WE, Gettings SD, Han Hsu H, Pan YHL, Re TA, Renskers KJ, Rothenstein A, Scrafford CG, Sewall C. 2005. Exposure data for cosmetic products: lipstick, body lotion, and face cream. Food Chem Toxicol 43: 279-291.

Loretz LG, Api AM, Babcock L, Barraj LM, Burdick J, Cater KC, Jarrett G, Mann S, Pan YHL, Re TA, Renskers KJ, Scrafford CG. 2008. Exposure data for cosmetic products: facial cleanser, hair conditioner, and eye shadow. Food Chem Toxicol 46:1516–1524.

Loveday KS, Anderson BE, Resnick MA, Zeiger E. 1990. Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. V: Results with 46 chemicals. Environ Mol Mutagen 16:272–303. [cited in Morgott 2001].

Lovegren NV, Fisher GS, Legendre MG, Schuller WH. 1979. Volatile constituents of dried legumes. J Agric Food Chem 27:851–853.

Maarse H, Visscher CA. 1989. Volatile compounds in food--Qualitative and quantitative data. 6th ed. Zeist (NO): TNO-CIVO Food Analysis Institute.

Mackay D, Di Guardo A, Paterson S, Cowan CE. 1996. Evaluating the environmental fate of a variety of types of chemicals using the EQC model. Environ Toxicol Chem 15:1627–1637.

MacLeod AJ, Pieris NM. 1984. Comparison of the volatile components of some mango cultivars. Phytochemistry 23(2):361–366.

Malmgren-Hansen B, Olesen S, Pommer K, Winther Funch L, Pedersen E. 2003. Emission and evaluation of chemical substances from selected electrical and electronic products. Survey of Chemical Substances in Consumer Products, No. 32 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/F6F58F52-2D13-48DC-B7B2-71A58387AC57/0/32.pdf

Marquis O, Millery A, Guittonneau S, Miaud C. 2006. Solvent toxicity to amphibian embryos and larvae. Chemosphere 63:889–892.

Mashbitz LM, Sklianskaya RM, Urieva FI. 1936. The relative toxicity of acetone, methylalcohol and their mixtures: II. Their action on white mice. J Ind Hyg Toxicol 18:117–122.

Mast TJ, Evanoff JJ, Rommereim RL, Stoney KH, Weigel RJ, Westerberg RB. 1988. Inhalation developmental toxicology studies: teratology study of acetone in mice and rats: final report. Research Triangle Park (NC): US Department of Health and Human Services, National Toxicology Program. 260 p. Report No.: PNL-6768 (prepared by Pacific Northwest Laboratory). [cited in ATSDR 1994].

Matsushita T, Yoshimune A, Inoue T, Yamaka S, Suzuki H. 1969a. [Experimental studies for determining the maximum permissible concentrations of acetone: I. Biological reactions in one-day exposure to acetone.] Sangyo Igaku 11:477–485 (in Japanese). [cited in WHO 1998; NRC 2005].

Matsushita T, Goshima E, Miyagaki H, Maeda K, Takeuchi Y, Inoue T. 1969b. [Experimental studies for determining the MAC value of acetone. 2. Biological reaction in the “six-day exposure” to acetone.] Sangyo Igaku 11:507–515 (in Japanese). [cited in ATSDR 1994; WHO 1998; NRC 2005].

McCann J, Choi EE, Yamasaki BN, Ames BN. 1975. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci USA 72:5135–5139. [cited in WHO 1998].

McCarroll NE, Keech BH, Piper CE. 1981. A microsuspension adaptation of the Bacillus subtilisrec”assay. Environ Mutagen 3:607–616. [cited in Morgott 2001].

McGregor DB, Edwards I, Riach CG, Cattanach P, Martin R, Mitchell A, Caspary WJ. 1988. Studies of an S9-based metabolic activation system used in the mouse lymphoma L5178Y cell mutation assay. Mutagenesis 3:485–490. [cited in Morgott 2001].

Meyrahn H, Pauly J, Schneider W, Wameck P. 1986. Quantum yields for the photodissociation of acetone in air and an estimate for the life time of acetone in the lower troposphere. J Atmos Chem 4:277–291. [cited in WHO 1998].

Mishra NK, Wilson CM, Pant KJ, Thomas FO. 1978. Simultaneous determination of cellular mutagenesis and transformation by chemical carcinogens in Fischer rat embryo cells. J Toxicol Environ Health 4:79–91. [cited in Morgott 2001].

Mitran E. 2000. Reply to the editor. Environ Res 82:184–185.

Mitran E, Callender T, Orha B, Dragnea P, Botezatu G. 1997. Neurotoxicity associated with occupational exposure to acetone, methyl ethyl ketone, and cyclohexanone. Environ Res 73:181–188.

Montelius J, Boman A, Wahlkvist H, Wahlberg JE. 1996. The murine lymph node assay: search for an alternative, more adequate vehicle than acetone/olive oil (4:1). Contact Dermatitis 34:428–430.

Mookherjee BD, Deck RE, Chang SS. 1965. Relationship between monocarbonyl compounds and flavour of potato chips. J Agric Food Chem 13(2):131–134.

Morgott DA. 2001. Acetone. In: Bingham E, Cohrssen B, Powell CH, editors. Patty’s toxicology, vol. 6. 5th ed. New York (NY): John Wiley & Sons.

Mörk AK, Johanson G. 2006. A human physiological model describing acetone kinetics in blood and breath during various levels of physical exercise. Toxicol Lett 164(1):6–15.

Nakamura A, Momma J, Sekiguchi H, Noda T, Yamano T, Kaniwa M, Kojima S, Tsuda M, Kurokawa Y. 1994. A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test. Contact Dermatitis 31:72–85.

Nakamura SI, Oda Y, Shimada T, Oki I, Sugimoto K. 1987. SOS-inducing activity of chemical carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002: examination with 151 chemicals. Mutat Res 192:239–246. [cited in Morgott 2001].

[NCI] National Chemical Inventories [database on a CD-ROM]. 2006. Issue 1. Columbus (OH): American Chemical Society, Chemical Abstracts Service. Available from: www.cas.org/products/cd/nci/index.html

Nelson KW, Ege JF Jr, Ross M, Woodman LE, Silverman L. 1943. Sensory response to certain industrial solvent vapors. J Ind Hyg Toxicol 25:282–285. [cited in NRC 2005].

Nelson PE, Hoff JE. 1969. Tomato volatiles: effect of variety, processing and storage time. J Food Sci 34:53–57.

[NHPID] Natural Health Products Ingredients Database [database on the Internet]. 2011. Ottawa (ON): Health Canada. [cited 2011]. Available from: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/search-rechercheReq.do

[NHW] Dept. of National Health and Welfare (CA). 1990. Present patterns and trends in infant feeding in Canada. Ottawa (ON): Department of National Health and Welfare. NHW Cat. No. H39-199/1990E. [cited in Health Canada 1998].

Nielsen J, Niemann AL, Mikkelsen J, Hansen MK. 2003. [Chemical substances in spray paint.] Survey of Chemical Substances in Consumer Products, No. 45 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency (in Danish). Available from: www2.mst.dk/udgiv/publikationer/2004/Kortlaegning/045_eksponering_af_kemiske_stoffer_i_spraymaling.pdf

Nilsson N. 2007. Analysis of chemical substances in balloons. Survey of Chemical Substances in Consumer Products, No. 89 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www2.mst.dk/Udgiv/publications/2007/978-87-7052-662-3/pdf/978-87-7052-664-7.pdf

Nilsson N, Staal Jensen M. 2003. Survey and assessment of chemical substances in hobby adhesives. Survey of Chemical Substances in Consumer Products, No. 29 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/EAF240E2-E152-4E56-BD41-D447CACA9BB7/0/29.pdf

Nilsson NH, Pedersen S, Hansen PL, Christensen I. 2004. Survey and liberation of chemical substances in joint sealants. Survey of Chemical Substances in Consumer Products, No. 38 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/E440A7B6-6B50-4185-8499-A61AA28B5654/0/38.pdf

Nilsson NH, Malmgren-Hansen B, Bernth N, Pedersen E, Pommer K. 2006. Survey and health assessment of chemical substances in sex toys. Survey of Chemical Substances in Consumer Products, No. 77 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec]. Available from: www2.mst.dk/udgiv/publications/2006/87-7052-227-8/pdf/87-7052-228-6.pdf

Norppa H, Hemminki K, Sorsa M, Vainio H. 1981. Effect of monosubstituted epoxides on chromosome aberrations and SCE in cultured human lymphocytes. Mutat Res 91:243–250. [cited in WHO 1998].

[NRC] National Research Council. 2005. Acetone. Interim acute exposure guideline levels (AEGLs). For NAS/COT Subcommittee for AEGLs. Interim 1: 07/2005. Available from: www.epa.gov/opptintr/aegl/pubs/tsd200.pdf

[NTP] National Toxicology Program (US). 1988. Inhalation developmental toxicology studies: teratology study of acetone in mice and rats: final report. Research Triangle Park (NC): US Department of Health and Human Services, National Toxicology Program. Report No.: PNL-6768 (prepared by Pacific Northwest Laboratory). 260 p. [cited in ATSDR 1994.]

[NTP] National Toxicology Program (US). 1991. Toxicity studies of acetone in F344/N rats and B6C3F1 mice (drinking water studies). Research Triangle Park (NC): US Department of Health and Human Services, National Toxicology Program. 38 p. (Technical Report No. 3; NIH Publication No. 91-3122).

Nylén D, Borling P, Sørensen H. 2004. Mapping of chemical substances in animal care products. Survey of Chemical Substances in Consumer Products, No. 44 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency [cited 2011 Dec 8]. Available from: www.mst.dk/NR/rdonlyres/65B2994E-8862-48D7-A891-F4F3850AB7E9/114900/Surveyno44.pdf

[NYSDOH] New York State Department of Health. 2005. Study of volatile organic chemicals in air of fuel oil heated homes [Internet]. [cited 2011 Nov 25]. Available from: www.health.ny.gov/environmental/indoors/air/docs/fuel_oil.pdf

O’Brien AK, Reiser RG, Gylling H. 1997. Spatial variability of volatile organic compounds in streams on Long Island, New York and in New Jersey. West Trenton (NJ): US Geological Survey. (Fact Sheet FS-194-97).

[OECD] Organisation for Economic Co-operation and Development. 1999. SIDS Initial Assessment Report for SIAM 9: Acetone: CAS RN 67-64-1. Geneva (CH): United Nations Environment Programme (UNEP) Publications. Available from: http://webnet.oecd.org/HPV/UI/handler.axd?id=db15a09e-0f1a-47e7-bf99-f04e69a1b26f

[OECD] Organisation for Economic Co-operation and Development. 2002. SIDS Initial Assessment Report for SIAM 6: 2-Propanol: CAS RN 67-63-0. Geneva (CH): United Nations Environment programme (UNEP) Publications. Available from: http://webnet.oecd.org/HPV/UI/handler.axd?id=668b6b61-3645-491e-a423-1a7100bc6598

[OECD] Organisation for Economic Co-operation and Development. 2009. Manual for the assessment of chemicals. Annex 1: Guidance for completing a SIDS dossier [Internet]. Paris (FR): OECD, Environment Directorate. [cited 2011 Jul]. Available from: www.oecd.org/chemicalsafety/risk-assessment/36045066.pdf

Oglesby FL, Williams JL, Fassett DW. 1949. Eighteen-year experience with acetone. Paper presented at the Annual Meeting of the American Industrial Hygiene Association, Detroit, MI. [cited in OECD 1999].

[OMOE] Ontario Ministry of the Environment. 2003. Municipal sewage treatment data compiled in Excel spreadsheet.  Restricted access..

Ontario. 2009. Toxics Reduction Act, 2009. S.O. 2009, Chapter 19. Last amended 2010, c. 16, Sched. 7, s. 5. Available from: www.e-laws.gov.on.ca/html/statutes/english/elaws_statutes_09t19_e.htm

Oser BL, Ford RA. 1973. Recent progress in the consideration of flavouring ingredients under the food additives amendment. 6. GRAS substances. Food Technol 27:64–67.

Otson R, Williams DT, Bothwell PD. 1982. Volatile organic compounds in water at thirty Canadian potable water treatment facilities. J Assoc Off Anal Chem 65(6):1370–1374.

Ott MG, Skory LK, Holder BB, Bronson JM, Williams PR. 1983a. Health evaluation of employees occupationally exposed to methylene chloride: general study design and environmental considerations. Scand J Work Environ Health 9 (Suppl 1):1–7. [cited in Morgott 2001].

Ott MG, Skory LK, Holder BB, Bronson JM, Williams PR. 1983b. Health evaluation of employees occupationally exposed to methylene chloride: mortality. Scand J Work Environ Health 9(Suppl 1):8–16. [cited in Morgott 2001].

Ott MG, Skory LK, Holder BB, Bronson JM, Williams PR. 1983c. Health evaluation of employees occupationally exposed to methylene: clinical laboratory evaluation. Scand J Work Environ Health 9(Suppl 1):17–25.

Park HY, Koprowska I. 1968. A comparative in vitro and in vivo study of induced cervical lesions of mice. Cancer Res 28:3236–3240.

Peden VH. 1964. Determination of individual serum “ketone bodies,” with normal values in infants and children. J Lab Clin Med 63:332–343.

Pellizzari ED, Hartwell TD, Harris BSH, Waddell RD, Whitaker DA, Erickson MD. 1982. Purgeable organic compounds in mother’s milk. Bull Environ Contam Toxicol 28:322–328. [cited in ATSDR 1994].

Personal Care Products Council. 2011. wINCI [online version of the International Cosmetic Ingredient Dictionary & Handbook]. [cited 2011 Oct]. Available from: http://webdictionary.personalcarecouncil.org/jsp/Home.jsp

Peterson AR, Landolph JR, Peterson H, Spears CP, Heidelberger C. 1981. Oncogenic transformation and mutation of C3H/10T 1/2 clone 8 mouse embryo fibroblasts by alkylating agents. Cancer Res 41:3095–3099. [cited in Morgott 2001].

Pienta RJ. 1980. Transformation of Syrian hamster embryo cells by diverse chemicals and correlation with their reported carcinogenic and mutagenic activities. In: deSerres FJ, Hollaender A, editors. Chemical mutagens: principles and methods for their detection. New York (NY): Plenum. p. 175–202. [cited in Morgott 2001].

Plaa GL, Hewitt WR, Du Souich P, Caille G, Lock S. 1982. Isopropanol and acetone potentiation of carbon tetrachloride–induced hepatotoxicity: single versus repetitive pretreatments in rats. J Toxicol Environ Health 9:235–250. [cited in ATSDR 1994].

Platen H, Schink B. 1989. Anaerobic degradation of acetone and higher ketones via carboxylation by newly isolated denitrifying bacteria. J Gen Microbiol 135:883–891.

Plumb RH Jr. 1991. The occurrence of appendix IX organic constituents in disposal site ground water. J Ground Water Monit Rev 11:157–164.

Pollard S, Adams JA. 1988. Artificially induced metamorphosis acetone in Acris gryllus. Arch Environ Contam Toxicol 17:419–428.

Poulsen PB, Jensen AA, Hoffmann L. 2002. [Survey of chemical substances in hairstyling products.] Survey of Chemical Substances in Consumer Products, No. 18. Copenhagen (DK): Danish Environmental Protection Agency (in Danish). Available from: www2.mst.dk/udgiv/publikationer/2002/Kortlaegning/018_Kortl%c3%a6gning_af_kemiske_stoffer_i_h%c3%a5rstylingsprodukter.pdf

Quarles JM, Sega MW, Schenley CK, Ljinsky W. 1979. Transformation of hamster fetal cells by nitrosated pesticides in a transplantation assay. Cancer Res 39:4525–4533. [cited in Morgott 2001].

Raleigh RL, McGee WA. 1972. Effects of short, high-concentration exposures to acetone as determined by observation in the work area. J Occup Med 14:607–610. [cited in US EPA 2003; NRC 2005].

Ramu A, Rosenbaum J, Blaschke TF. 1978. Disposition of acetone following acute acetone intoxication. West J Med 129:429–432. [cited in ATSDR 1994; WHO 1998; US EPA 2003].

Rathbun RE, Tai DY. 1987. Vapor pressures and gas-film coefficients for ketones. Chemosphere 18:69–78.

Rathbun RE, Stephens DW, Shultz DJ, Tai DY. 1982. Fate of acetone in water. Chemosphere 11:1097–1114.

Rathbun RE, Stephens DW, Schultz DJ, Tai DY. 1988. Fate of acetone in an outdoor model stream in southern Mississippi. J Hydrol 104:181–209. [cited in HSDB 1983– ].

Rathbun RE, Stephens DW, Tai DY. 1991. Fate of acetone in an outdoor model stream with a nitrate supplement, southern Mississippi, USA. J Hydrol 123:225–242.

Rathbun RE, Stephens DW, Tai DY. 1993. Bacterial degradation of acetone in an outdoor model stream. Environ Pollut 79:153–182.

Reichard GA Jr, Haff AC, Skutches CL, Paul P, Holroyde CP, Owen OE. 1979. Plasma acetone metabolism in the fasting human. J Clin Invest 63(4):619–626. [cited in ATSDR 1994].

Rengstorff RH, Petrali JP, Sim VM. 1972. Cataracts induced in guinea pigs by acetone, cyclohexanone, and dimethyl sulfoxide. Am J Optom Arch Am Acad Optom 49:308–319.

Rengstorff R, Petrali J, Sims V. 1976. Attempt to induce cataracts in rabbits by cutaneous application of acetone. Am J Optom Physiol Optics 53:41–42.

Riddick JA, Bunger WB, Sakano TK. 1986. Organic solvents: physical properties and methods of purification. In: Techniques of chemistry, vol. 2. 4th ed. New York (NY): Wiley-Interscience. p. 336–337.

Ritter L. 1999. Acetone. An assessment prepared at the request of National Pollutant Release Inventory, Environment Canada. Guelph (ON): University of Guelph, Canadian Network of Toxicology Centres.

Roberts BL, Dorough HW. 1984. Relative toxicities of chemicals to the earthworm Eisenia foetida. Environ Toxicol Chem 3:67–78.

Rosculet G, Rickard M. 1968. Isolation and characterization of flavor components in beer. Am Soc Brew Chem Proc 1968:203–213.

Rossman TG, Molina M, Meyer L, Boone P, Klein CB, Wang Z, Li F, Lin WC, Kinney PL. 1991. Performance of 133 compounds in the lambda prophage induction endpoint of the Microscreen assay and a comparison with S. typhimurium mutagenicity and rodent carcinogenicity assays. Mutat Res 260:349–367. [cited in Morgott 2001].

Roudabush RL, Terhaar CJ, Fassett DW, Dziuba SP. 1965. Comparative acute effects of some chemicals on the skin of rabbits and guinea pigs. Toxicol Appl Pharmacol 7:559–565.

Rustung E, Koren F, Föyen A. 1931. Über Aufnahmeund von Aceton im Organismus von Kaltblütern. Biochem Z 242:366–376. [cited in OECD 1999].

Sabel GV, Clark TP. 1984. Volatile organic compounds as indicators of municipal solid waste leachate contamination. Waste Manage Res 2(2):119–130.

Safronov GA, Nevmerzhitsky NS, Tiunov LA, Tiunova LV. 1993. Comparative acute inhalation toxicity of aliphatic aldehydes and ketones according to exposure time. Curr Topics Toxicol 1:47–51. [cited in Morgott 2001].

Sakai A, Sato M. 1989. Improvement of carcinogen identification in BALB/3T3 cell transformation by application of a 2-stage method. Mutat Res 214:285–296. [cited in ATSDR 1994; Morgott 2001].

Sakata M, Kikuchi J, Haga M, Ishiyama N, Maeda T, Ise T, Hikita N. 1989. Disposition of acetone, methyl ethyl ketone and cyclohexanone in acute poisoning. J Toxicol Clin Toxicol 27:67–77. [cited in ATSDR 1994; WHO 1998].

Satoh T, Omae K, Nakashima H, Takebayashi T, Matsumura H, Kawai T, Nakaza M, Sakurai H. 1996. Relationship between acetone exposure concentration and health effects in acetate fiber plant workers. Int Arch Occup Environ Health 68:147–153.

Schaper M, Brost MA. 1991. Respiratory effects of trimellitic anhydride aerosols in mice. Arch Toxicol 65:671–677.

Scheringer M, MacLeod M, Wegmann F. 2006. Manual: The OECD POV and LRTP Screening Tool. Version 2.0 [Internet]. Zurich (CH): Swiss Federal Institute of Technology. Software distributed at OECD/UNEP Workshop on Application of Multimedia Models for Identification of Persistent Organic Pollutants, Ottawa, Canada, May 31–June 2, 2006. [cited Dec 2011]. Available from: www.sust-chem.ethz.ch/docs/Tool2_0_Manual.pdf

Scholl HR, Iba MM. 1997. Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat: interactions and effects of route of exposure. Xenobiotica 27:265–277. [cited in US EPA 2003].

Schubert U, Wisanowsky L, Kull U. 1995. Determination of phytotoxicity of several volatile organic compounds by investigating the germination pattern of tobacco pollen. J Plant Physiol 145:514–518.

Seeber A, Kiesswetter E, Vangala RR, Blaszkewicz M, Golka K. 1992. Combined exposure to organic solvents: an experimental approach using acetone and ethyl acetate. Appl Psychol Int Rev 41:281–292.

Serjeant EP, Dempsey B. 1979. Ionisation constants of organic acids in aqueous solution. New York (NY): Pergamon. (IUPAC Chemical Data Series No. 23). p. 989. [cited in HSDB 1983– ].

Shahidi F, Rubin L, D’Souza LA. 1986. Meat flavor volatiles: a review of the composition, techniques of analysis, and sensory evaluation. CRC Crit Rev Food Sci Nutr 24:141–243.

Siek TJ, Lindsay RC. 1970. Semiquantitative analysis of fresh sweet-cream butter volatiles. J Dairy Sci 53:700–703.

Sifniades S, Levy AB, Bahl H. 2011. Acetone [Internet]. In: Ullmann’s Encyclopedia of Industrial Chemistry, online version. [cited 2011 Dec 14]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14356007.a01_079.pub3/full [restricted access]

Sina JF, Bean CL, Dysart GR, Taylor VI, Bradley MO. 1983. Evaluation of the alkaline elution/rat hepatocyte assay as a predictor of carcinogenic/mutagenic potential. Mutat Res 113:357–391. [cited in Morgott 2001].

Singh HB, Kanakidou M, Crutzen PJ, Jacobs DJ. 1995. High concentrations and photochemical fate of oxygenated hydrocarbons in the global troposphere. Nature 378:50–54.

Singh KP, Yoon HL, Ratner S, Reiners JJ. 1996. Modulation of the development of humoral immunity by topically applied acetone, ethanol and 12-O-tetradecanoylphorbol-13-acetate. Fundam Appl Toxicol 33:129–139. [cited in Woolhiser et al. 2003].

Smyth HF Jr, Carpenter CP, Weil CS, West JS. 1962. Range-finding toxicity data: List VI. Am Ind Hyg Assoc J 23:95–107.

Soden KJ. 1993. An evaluation of chronic methylene chloride exposure. J Occup Med 35:282–286. [cited in ACC 2003].

Sollman T. 1921. Studies of chronic intoxications on albino rats. II. Alcohols (ethyl, methyl and “wood”) and acetone. J Pharmacol Exp Ther 16:291–309. [cited in Morgott 2001].

Solomon SJ, Schade GW, Kuttippurath J, Ladstatter-Weissenmayer A, Burrows JP. 2008. VOC concentrations in an indoor workplace environment of a university building. Indoor Built Environ 17(3):260–268.

Spencer PS, Bischoff MC, Schaumburg HH. 1978. On the specific molecular configuration of neurotoxic aliphatic hexacarbon compounds causing central-peripheral distal axonopathy. Toxicol Appl Pharmacol 44:17–28.

[SRD] Source Ranking Database [database on the Internet]. 2004. Version 4.0. Washington (DC): US Environmental Protection Agency. [updated 2004 Apr; cited 2011 Nov]. Available from: www.epa.gov/oppt/exposure/pubs/srd.htm

[SRI] Stanford Research Institute. 2011. Chemical economic handbooks--Acetone [Internet]. [cited 2011 Dec 1]. Available from: www.sriconsulting.com/WP/Public/Reports/acetone/ [restricted access]

Steinemann AC, MacGregor IC, Gordon SM, Gallagher LG, Davis AL, Ribeiro DS, Wallace LA. 2011. Fragranced consumer products: chemicals emitted, ingredients unlisted. Environ Impact Assess Rev 31(3):328–333.

Stewart RD, Hake CL, Wu A, Graft SA, Forster AV, Keeler WH, Lebrun AJ, Newton PE, Soto RJ. 1975. Acetone: development of a biologic standard for the industrial worker by breath analysis. Cincinnati (OH): National Institute for Occupational Safety and Health. Report No.: NTIS PB82-172917. 80 p.

Stocco C, MacNeill M, Wang D, Xu X, Guay M, Brook J, Wheeler AJ. 2008. Predicting personal exposure of Windsor, Ontario residents to volatile organic compounds using indoor measurements and survey data. Atmos Environ 42:5905–5912.

Suflita JM, Mormile MR. 1993. Anaerobic biodegradation of known and potential gasoline oxygenates in the terrestrial subsurface. Environ Sci Technol 27(5):976–978.

Takeoka GR, Flath RA, Guntert M, Jennings W. 1988. Nectarine volatiles: vacuum steam distillation versus headspace sampling. J Agric Food Chem 36:553–560.

Tanii H, Tsuji H, Hashimoto K. 1986. Structure–toxicity relationship of monoketones. Toxicol Lett 30:13–17.

[TaPL3] Long Range Transport and Persistence Level III model [Internet]. 2003. Version 3.0. Peterborough (ON): Trent University, Canadian Centre for Environmental Modelling and Chemistry. Available from: www.trentu.ca/academic/aminss/envmodel/models/TaPL3.html

Targowski SP, Klucinski W. 1983. Reduction in mitogenic response of bovine lymphocytes by ketone bodies. Am J Vet Res 44:828–830. [cited in Morgott 2001].

Taskinen H, Kyyrönen P, Hemminki K, Hoikkala M, Lajunen K, Lindbohm ML. 1994. Laboratory work and pregnancy outcome. J Occup Med 36:311–319. [cited in Morgott 2001].

Tates AD, Kriek E. 1981. Induction of chromosomal aberrations and sister chromatid exchanges in Chinese hamster cells in vitro by some proximate and ultimate carcinogenic arylamide derivatives. Mutat Res 88:397–410. [cited in Morgott 2001].

Taylor A, Smith DE, Palmer VJ, Shepard D, Padhye N, Morrow F. 1993. Relationships between acetone, cataracts, and ascorbate in hairless guinea pigs. Ophthalmic Res 25(1):30–35.

Thomas RG (1982) Volatilization from water. In: Lyman WJ, Reehl WF, & Rosenblatt DH ed. Handbook of chemical property estimation methods. New York, McGraw-Hill, chapter 15, pp 15/1-15/34. [cited in WHO 1998].

Tsai K-P, Chen C-Y. 2007. An algal toxicity database of organic toxicants derived by a closed-system technique. Environ Toxicol Chem 26(9):1931–1939.


[US EPA] US Environmental Protection Agency. 1975. Preliminary assessment of suspected carcinogens in drinking water. Interim report to Congress (June 1975). Washington (DC): US EPA.

[US EPA] US Environmental Protection Agency. 1980. Planning workshops to develop recommendations for a ground water protection strategy. Appendices. Washington (DC): US EPA. Report No.: NTIS PB81-122624. [cited in Burmaster 1982].

[US EPA] US Environmental Protection Agency. 1988. Superfund record of decision: Summit National, OH. First remedial action. Washington (DC): US Environmental Protection Agency. Report No.: EPA/ROD/R05-88/068 (NTIS PB89 225908/AS). [cited in ATSDR 1994].

[US EPA] US Environmental Protection Agency. 1993.  Wildlife Exposure Factors Handbook, Volume I.  Office of Health and Environmental Assessment, Office of Research and Development.  EPA/600/R-93/187.  Washington, D.C. 

[US EPA] US Environmental Protection Agency. 1994. Lower Rio Grande Valley, Environmental Monitoring Study. Report to the community on the pilot project. Dallas (TX): US EPA, Office of Research & Development, Region 6 Office (Texas region) and Region 9 Office (Arizona and California).

[US EPA] US Environmental Protection Agency. 2003. Toxicological review of acetone in support of summary information of the Integrated Risk Information System (IRIS). Washington (DC): US EPA. Report No.: EPA/635/R-03/004. Available from: www.epa.gov/iris/toxreviews/0128tr.pdf

[US EPA] US Environmental Protection Agency. 2011. Exposure factors handbook: 2011 edition. Chapter 16: Activity factors [Internet]. Washington (DC): US EPA, National Centre for Environmental Assessment, Office of Research and Development. Available from: www.epa.gov/ncea/efh/report.html

[US EPA] US Environmental Protection Agency. 2012. TRI Chemical List Changes (1987–2012) [Internet]. [cited 2012 Nov 26]. Available from: www.epa.gov/tri/trichemicals/

[US FDA] US Food and Drug Administration. 2011. Everything Added to Food in the United States (EAFUS) Database [Internet]. [cited 2011 Nov 22]. Available from: www.accessdata.fda.gov/scripts/fcn/fcnNavigation.cfm?rpt=eafusListing&displayAll=true

[USGS] US Geological Survey. 2007. Concentration data for anthropogenic organic compounds in ground water, surface water, and finished water of selected community water systems in the United States, 2002–05 [Internet]. [cited 2011 Nov]. Available from: http://water.usgs.gov/nawqa/swqa/

Van Duuren BL, Loewngart G, Seidman I, Smith AC, Melchione S. 1978. Mouse skin carcinogenicity tests of the flame retardants tris(2,3-dibromopropyl)phosphate, tetrakis(hydroxymethyl)phosphonium chloride, and polyvinyl bromide. Cancer Res 38:3236–3240. [cited in ATSDR 1994; Morgott 2001].

Van Straten S, Maarse H. 1983. Volatile compounds in food--Quantitative data. 5th ed. Zeist (NL): TNO-CIVO Food Analysis Institute.

Vasavada HA, Padayatty JD. 1981. Rapid transfection assay for screening mutagens and carcinogens. Mutat Res 91:9–14. [cited in Morgott 2001].

Vasvári G, Szilágyi I, Bencsura Á, Dóbé S, Bérces T, Henon E, Canneaux S, Bohr F. 2001. Reaction and complex formation between OH radical and acetone.  Phys Chem Chem Phys 3(4):551-555.

[VICH] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products. 2000. Impurities: residual solvents in new veterinary medicinal products, active substances and excipients. Brussels (BE): VICH.

Vogt-Nielsen K, Hagedorn-Rasmussen P. 2007. A mapping of products and material used within live role-play. Survey of Chemical Substances in Consumer Products, No. 85 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec 8]. Available from: www2.mst.dk/Udgiv/publications/2007/978-87-7052-553-4/pdf/978-87-7052-554-1.pdf

Von der Hude W, Scheutwinkel M, Gramlich U, Fissler B, Basler A. 1987. Genotoxicity of three-carbon compounds evaluated in the SCE test in vitro. Environ Mutagen 9:401–410. [cited in Morgott 2001].

Von der Hude W, Behm C, Gürtler R, Basler A. 1988. Evaluation of the SOS chromotest. Mutat Res 203:81–94. [cited in Morgott 2001].

Waggy GT, Conway PA, Hansen JL, Blessing RL. 1994. Comparison of 20-d BOD and OECD closed-bottle biodegradation tests. Environ Toxicol Chem 13(8):1277–1280.

Wang G, Maranelli G, Perbellini L, Raineri E, Brugnone F. 1994. Blood acetone concentration in “normal people” and in exposed workers 16 h after the end of the shift. Int Arch Occup Environ Health 65:285–289. [cited in US EPA 2003].

Ward JM, Quander R, Devor D, Wenk ML, Spangler EF.1986. Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies. Environ Health Perspect 68:81–89.

Weast RC, Lide DR, editors. 1989. Handbook of chemistry and physics. 70th ed. Boca Raton (FL): CRC Press.

Weisel CP, Zhang JJ, Turpin BJ, Morandi MT, Colome S, Stock TH, Spektor DM, Korn L, Winer A, Kwon J, Meng QY, Zhang L, Harrington R, Liu W, Reff A, Lee JH, Alimokhtari S, Mohan K, Shendell D, Jones J, Farrar L, Maberti S, Fan T. 2005. Relationships of indoor, outdoor, and personal air (RIOPA). Part I. Collection methods and descriptive analyses. Res Rep Health Eff Inst 130(1):1–127.

Weisel CP, Mokhtaris S, Sanders, PF. 2008. Indoor air VOC concentrations in suburban and rural New Jersey. Environ Sci Technol 42:8231–8238.

Whittaker SG, Zimmermann FK, Dicus B, Piegorsch WW, Fogel S, Resnick MA. 1989. Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae--An interlaboratory study. Mutat Res 224:31–78. [cited in Morgott 2001].

[WHO] World Health Organization, International Programme on Chemical Safety. 1998. Acetone. Geneva (CH): World Health Organization. (Environmental Health Criteria 207). [cited 2011 Nov]. Available from: www.inchem.org/documents/ehc/ehc/ehc207.htm

[WHO] World Health Organization, International Programme on Chemical Safety. 1990. 2-Propanol. Geneva (CH): World Health Organization. (Environmental Health Criteria 103). [cited 2011 Nov]. Available from: www.inchem.org/documents/ehc/ehc/ehc103.htm

Wigaeus E, Holm S, Astrand I. 1981. Exposure to acetone: uptake and elimination in man. Scand J Work Environ Health 7:84–94. [cited in ATSDR 1994; US EPA 2003].

Wigaeus E, Löf A, Nordqvist M. 1982. Distribution and elimination of 2-[14C]-acetone in mice after inhalation exposure. Scand J Work Environ Health 8:121–128. [cited in ATSDR 1994; US EPA 2003].

Williams AA, Lewis MJ, Tucknott OG. 1980. The neutral volatile components of cider apple juices. Food Chem 6:139–151.

Windholz M, editor. 1989. Acetone. In: The Merck Index--An Encyclopaedia of Chemicals, Drugs and Biologicals. 11th ed. Whitehouse Station (NJ): Merck & Co., Inc.

Witterseh T. 2004. Emission of chemical substances from products made of exotic wood. Mapping of Chemical Substances in Consumer Products, No. 49 [Internet]. Copenhagen (DK): Danish Environmental Protection Agency. [cited 2011 Dec]. Available from: www.mst.dk/NR/rdonlyres/AA1FFDA1-D5E0-4BF8-B4DF-B69A23E5471F/0/49.pdf

Wolfe TA, Demirel T, Baumann ER. 1986. Adsorption of organic pollutants on montmorillonite treated with amines. J Water Pollut Control Fed 58:68–76.

Wood GM, Boettcher PJ, Kelton DF, Jansen GB. 2004. Phenotypic and genetic influences on test-day measures of acetone concentration in milk. J Dairy Sci 87:1108–1114.

Woolhiser MR, Anderson PK, Waechter JM. 2003. Acetone: 4-week drinking water immunotoxicity study in CD-1 mice. Study ID: 021126. Unpublished study by Dow Chemical Company, Midland, MI.

Woolhiser MR, Houtman CE, Waechter JM. 2006. Acetone in drinking water does not modulate humoral immunity in mice as measured by the antibody, plaque-forming cell assay. Int J Toxicol 25(5):333–339.

Wu AHB, editor. 2006. Tietz clinical guide to laboratory tests. 4th ed. Philadelphia (PA): Saunders.

Wysocki CJ, Dalton P, Brody M, Lawley HJ. 1997. Odor and irritation thresholds for acetone in acetone-exposed factory workers and control (occupationally-nonexposed) subjects.Am Ind Hyg Assoc J 58:704–712.

Yadav AS, Vashishat RK, Kakar SN. 1982. Testing endosulfan and fenitrothion for genotoxicity in Saccharomyces cerevisiae. Mutat Res 105:403–407. [cited in Morgott 2001].

Zakova N, Zak F, Froelich E, Hess R. 1985. Evaluation of skin carcinogenicity of technical 2,2-bis-(p-glycidyloxyphenyl)-propane in CF1 mice. Food Chem Toxicol 23:1081–1089.

Zarani F, Papazafiri P, Kappas A. 1999. Induction of micronuclei in human lymphocytes by organic solvents in vitro. J Environ Pathol Toxicol Oncol 18(1):21–28. [cited in ATSDR 2011].

Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. 1992. Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environ Mol Mutagen 19(Suppl 21):2–141. [cited in Morgott 2001].

Zhu J, Newhook R, Marro L, Chan C. 2005. Selected volatile organic compounds in residential air in the city of Ottawa, Canada. Environ Sci Technol 39:3964–3971.

Zimmerman RE, Goodkind ME. 1981. Landfill recovery. Part I: Environmental impacts. Chicago (IL): Gas Research Institute. Report No.: GRI-80/0084 (Oct.). 100 p. [cited in Brosseau and Heitz 1994].

Zimmermann FK, Mayer VW, Scheel I, Resnick MA. 1985. Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy in Saccharomyces cerevisiae. Mutat Res 149(3):339–351. [cited in WHO 1998].

Footnotes

Footnote 1

A determination of whether one or more of the criteria of section 64 are met is based upon an assessment of potential risks to the environment and/or to human health associated with exposures in the general environment. For humans, this includes, but is not limited to, exposures from ambient and indoor air, drinking water, foodstuffs and the use of consumer products. A conclusion under CEPA 1999 is not relevant to, nor does it preclude, an assessment against the hazard criteria specified in the Controlled Products Regulations, which are part of the regulatory framework for the Workplace Hazardous Materials Information System for products intended for workplace use. Similarly, a conclusion based on the criteria contained in section 64 of CEPA 1999 does not preclude actions being taken under other sections of CEPA 1999 or other Acts.

Return to footnote[1]referrer

Footnote 2

The conversion factor is based on the molar volume of an ideal gas and is 1 ppm = 2.374 mg/m3 for acetone at STP.

Return to footnote[2]referrer

Footnote 3

Intakes were calculated according to reference values in Health Canada (1994).

Return to footnote[3]referrer

Footnote 4

Some assessments cite this study as NTP (1988).

Return to footnote[4]referrer

Footnote 5

Extragestational weight gain is the actual maternal body weight gain during pregnancy and is defined as the maternal body weight at sacrifice minus gravid uterine weight minus maternal body weight on gestation day 0.

Return to footnote[5]referrer

Footnote 6

The accumulation of alpha2u-globulin (a2u-g), a low-molecular-weight protein, in the male rat kidney initiates a sequence of events that appears to lead to renal tubule tumor formation

Return to footnote[6]referrer

Date modified: