Screening Assessment for The Challenge
Ethanol, 2-ethoxy-, acetate

Chemical Abstracts Service Registry Number
111-15-9


Environment Canada
Health Canada

February 2009

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 ethanol, 2-ethoxy-, acetate (2-ethoxyethanol acetate; 2-EEA), Chemical Abstracts Service Registry Number 111-15-9. The substance 2-EEA was identified in the categorization of the Domestic Substances List as a high priority for action under the Challenge. 2-EEA was identified as a high priority because it was considered to pose greatest potential for exposure of individuals in Canada and had been classified by the European Commission on the basis of reproductive and developmental toxicity. The substance did not meet the ecological categorization criteria for persistence, bioaccumulation potential and inherent toxicity to aquatic organisms. Therefore, the focus of this assessment of 2‑EEA relates principally to human health risks.

According to data submitted in CEPA 1999 section 71 responses, 2-EEA was not manufactured in Canada in 2006 above the reporting threshold of 100 kg. The total quantity imported into Canada in the same calendar year was reported to be in the range of 10 000–100 000 kg. Its principal uses include solvents, paints, coatings and cleaning solution for industrial applications.

Population exposure to 2-EEA is expected to be predominantly via the air. Based on very limited information on concentrations in environmental media and the results of fugacity modelling, exposure in the general environment is expected to be low. 2-EEA is primarily used in industrial settings, and consumer exposure to 2-EEA is not expected to be significant. The health effects associated with exposure to 2-EEA are primarily developmental and reproductive toxicity and hematological effects, based on observations in experimental animals and exposed workers. The margins between an upper bounding estimate of concentrations in indoor air and levels associated with effects in occupationally exposed humans and experimental animals are considered to be adequately protective.

On the basis of the adequacy of the margins between conservative estimates of exposure to 2-EEA from environmental media and critical effect levels in exposed human workers and experimental animals, it is concluded that 2-EEA 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.

On the basis of low ecological hazard, expected releases and low environmental exposure of 2-EEA, it is concluded that this substance 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. 2-EEA does not meet the criteria for persistence or bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations.

This substance will be included in the upcoming Domestic Substances List inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment and, where appropriate, the performance of potential control measures identified during the risk management phase.

Based on the information available, it is concluded that 2-EEA does not meet the criteria set out in section 64 of CEPA 1999.

Introduction

The Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999) requires the Minister of the Environment and the Minister of Health to 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. Based on the results of a screening assessment, the Ministers can propose to take no further action with respect to the substance, to add the substance to the Priority Substances List (PSL) for further assessment or to recommend that the substance be added to the List of Toxic Substances in Schedule 1 of the Act and, where applicable, the implementation of virtual elimination.

Based on the information obtained through the categorization process, the Ministers identified a number of substances as high priorities for action. These include substances that

  • met all of the ecological categorization criteria, including persistence (P), bioaccumulation potential (B) and inherent toxicity to aquatic organisms (iT), and were believed to be in commerce; and/or
  • met the categorization criteria for greatest potential for exposure (GPE) or presented an intermediate potential for exposure (IPE) and had been identified as posing a high hazard to human health based on classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity.

 
The Ministers therefore published a notice of intent in the Canada Gazette, Part I, on December 9, 2006 (Canada 2006), which challenged industry and other interested stakeholders to submit, within specified timelines, specific information that may be used to inform risk assessment and to develop and benchmark best practices for the risk management and product stewardship of those substances identified as high priorities.

The substance ethanol, 2-ethoxy-, acetate (2-ethoxyethanol acetate, referred to as 2-EEA) was identified as a high priority for assessment of human health risk because it was considered to present GPE and had been classified by another agency on the basis of reproductive and developmental toxicity.

The Challenge for 2-EEA was published in the Canada Gazette on August 18, 2007 (Canada 2007). A substance profile was released at the same time. The substance profile presented the technical information available prior to December 2005 that formed the basis for categorization of this substance. As a result of the Challenge, submissions of information were received (Environment Canada 2008).

Although 2-EEA was determined to be a high priority for assessment with respect to human health, it did not meet the criteria for potential for persistence, bioaccumulation or inherent toxicity to aquatic organisms. Therefore, this assessment focuses principally on information relevant to the evaluation of risks to human health.

Under CEPA 1999, screening assessments focus on information critical to determining whether a substance meets the criteria for defining a chemical as “toxic” as set out in section 64 of the Act, where

“64. […] a substance is toxic if it is entering or may enter the environment in a quantity or concentration or under conditions that

  1. have or may have an immediate or long-term harmful effect on the environment or its biological diversity;
  2. constitute or may constitute a danger to the environment on which life depends; or
  3. constitute or may constitute a danger in Canada to human life or health.”

Screening assessments examine scientific information and develop conclusions by incorporating a weight of evidence approach and precaution as required under CEPA 1999.

This screening assessment includes consideration of information on chemical properties, hazards, uses and exposure, including the additional information submitted under the Challenge. Data relevant to the screening assessment of this substance were identified in original literature, review and assessment documents and stakeholder research reports and from recent literature searches, up to December 2007 for the exposure section of the document and up to September 2007 for the health effects section. Key studies were critically evaluated; modelling results may have been used to reach conclusions. Evaluation of risk to human health involves consideration of data relevant to estimation of exposure (non-occupational) of the general population, as well as information on health hazards (based principally on the weight of evidence assessments of other agencies that were used for prioritization of the substance). 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 incorporates input from other programs within these departments. This assessment has undergone external written peer review/consultation. Comments on the technical portions relevant to human health were received from scientific experts selected and directed by Toxicology Excellence for Risk Assessment (TERA), including John Christopher (California Department of Toxic Substances Control), Michael Jayjock (The Lifeline Group) and Joan Strawson (TERA). Comments on these sections were also received from ToxEcology Environmental Consulting Ltd. 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 risk assessment remain the responsibility of Health Canada and Environment Canada.

The critical information and considerations upon which the assessment is based are summarized below.

Substance Identity

2-Ethoxyethanol acetate (2-EEA) is the ester of 2-ethoxyethanol (2-EE) (Wenninger and McEwen 1997). Ethylene glycol monoalkyl ether acetates including 2-EEA are generally produced via esterification of the particular glycol ether with acetic acid, acetic acid anhydride or chloride (NIOSH 1991). 2-EEA is described as a colourless liquid with a mild characteristic fruity odour at room temperature and normal pressure (European Commission 2005) and is soluble in water (Nikitakis and McEwen 1990). Additional information on the identity of 2-EEA is summarized in Table 1.

Table 1. Substance identity of 2-EEA

CAS RN

111-15-9

DSL1 name

Ethanol, 2-ethoxy-, acetate

NCI2 names

Ethanol, 2-ethoxy-, 1-acetate (TSCA)
2-Ethoxyethyl acetate (EINECS)

Other names

Acetate, ethoxyethyl; Acetate, 2-ethoxyethyl; Acetic acid, 2-ethoxyethyl ester; 1-Acetoxy-2-ethoxyethane; Cellosolve acetate; 2-Ethoxy acetate; 2-Ethoxyethanol acetate; 2-Ethoxyethanol acetate ester; 2-Ethoxyethyl acetone; 2-Ethoxyethylethanoate; Ethyl cellosolve acetate; Ethyl glycol acetate; O-Ethylglycol acetate; Ethylene glycol acetate monoethyl ether; Ethylene glycol ethyl ether acetate; Ethyleneglycol monoethyl ether acetate; Ethylene glycol monoethyl ether monoacetate; Glycol monoethyl ether acetate; Oxitol acetate; Poly-Solv EE acetate

Chemical group (DSL stream)

Organics

Chemical subgroup

Esters

Chemical formula

C6H12O3

Chemical structure

Chemical structure CAS RN 111-15-9

SMILES

O=C(OCCOCC)C

Molecular mass

132.16 g/mol
1 Abbreviations: CAS RN, Chemical Abstracts Service Registry Number; DSL (, Domestic Substances List).
2 ; EINECS, European Inventory of Existing Commercial Chemical Substances; NCI, National Chemical Inventories; SMILES, simplified molecular input line entry specification; TSCA, Toxic Substances Control Act Chemical Substance Inventory.
Source: NCI 2007

Physical and Chemical Properties

Table 2 summarizes experimental and modelled physical and chemical properties of 2-EEA.

Table 2. Physical and chemical properties for 2-EEA

Property Type Value Temperature1
(°C)
Reference2

Melting point (°C)

Experimental

-61.7  

PhysProp 2006; Lewis 2007

Boiling point (°C)

Experimental

156;
156.4
 

PhysProp 2006; Budavari 1996

Relative density

 

0.9730;
0.975
20; 25

Kirk-Othmer 1980; Budavari 1996

Vapour pressure (Pa)

Experimental

270; 326.64 20; 25

Kirk-Othmer 1980; Daubert and Danner 1989

Henry’s Law constant
(Pa·m3/mol)

Experimental

3.24 × 10-4
(3.2 × 10-6
atm·m3/mol)3
25

PhysProp 2006

Log Kow (dimensionless)

Experimental

0.24  

Hüls 1989a

Log Koc
(dimensonless)

Modelled

0.32 25

PCKOCWIN 2000

1.62 25

ACD 2007

Water solubility (mg/L)

Experimental

2.47 × 105 15 - 25

Yalkowsky and Dannenfelser 1992

2.29 × 105 20

Kirk-Othmer 1980

Abbreviations: Koc, organic carbon partition coefficient; Kow, octanol–water partition coefficient.
1 The order of temperature corresponds to the order of the values.
2 The order of references corresponds to the order of the values.
3 The value in parentheses is the value originally reported in the reference.

Sources

The majority of reports noted that 2-EEA is not expected to occur naturally (IPCS 1990; European Commission 2005; NPI 2006), whereas one study reported biogenic emissions from wood species in the Mediterranean region (Peñuelas and Llusià 2001).

Anthropogenic sources of 2-EEA include manufacturing processes where the acetates are produced by standard esterification of 2-EE with acid anhydride or acid chloride and acid catalyst (Kirk-Othmer 1980).

According to data submitted in response to a survey conducted under CEPA 1999 section 71, 2-EEA was not manufactured in Canada in 2006 above the reporting threshold of 100 kg. The total quantity imported into Canada in the same calendar year was reported to be in the range of 10 000–100 000 kg (Environment Canada 2008).

All producers in the European Union ceased production of 2-EEA in 2002, and it is not expected that any production or import of this substance will start again in the future (European Commission 2006).

Uses

Glycol ethers in general have a wide range of applications, such as coupling agents for a variety of chemical specialties and as intermediates in the production of plasticizers and solvents. 2-EEA has been widely used as an industrial solvent for lacquers and varnish removers, as a blush retardant, as a solvent for nitrocellulose and in oils, resins, dyes, paints and stains. It has also been used in photographic and photolithographic processes and as a general solvent in a wide variety of cleaners (IPCS 1990). It is used in automobile lacquers to retard evaporation and impart high gloss; its primary function is to dissolve components of mixtures in both aqueous and non-aqueous systems and to keep the mixtures in solution until the final stages of evaporation (Montgomery 2000; NPI 2006). It may also be used in the production of adhesives and in the semiconductor industry (ACGIH 1991; Kim et al. 1999; NPI 2006). As a chemical intermediate, 2-EEA may be used in the synthesis of 2-ethoxyethylcyanoacrylate, which is used in low-odour cyanoacrylate adhesives (HSDB 2005).

Based on the information obtained from section 71 submissions, uses of 2-EEA in Canada include solvents, paints, coatings and cleaning solution for industrial applications (Environment Canada 2008).

2-EEA is listed among the ingredients of adhesives that may be used as components of articles intended for use in packaging, transporting or holding food in the United States (US FDA 2007). While it was also used as a solvent in the manufacture of coatings and adhesives in food packaging in Canada in the past (i.e., 15 years ago), no current known uses of this substance in food packaging are recognized in Canada (personal communication with Food Packaging Materials and Incidental Additives Section, Health Products and Food Branch, Health Canada, 2008-04-18; unreferenced).

2-EEA is listed as a solvent and viscosity-decreasing agent in the International Cosmetic Ingredient Dictionary and Handbook (Wenninger and McEwen 1997). Historically, 2‑EEA was present in an eye makeup product (30–100%) and skin moisturizer (1–3%). However, both 2-EEA and 2-EE are currently prohibited for use in cosmetic products in Canada (CNS 2008), as well as in the European Union (European Commission 1999).

Use of short straight-chain glycol ethers including 2-EEA and 2-EE has progressively decreased over the last 20 years worldwide (Johanson and Rick 1996; De Kettenis 2005; US EPA 2005). The United States Environmental Protection Agency (EPA) has indicated that there was no ongoing use of 2-EEA and 2-EE in consumer products in the United States and that notification would be required for any significant new use of these substances (US EPA 2005).

Releases to the Environment

The greatest environmental exposure from 2-EEA is a result of direct release to the atmosphere from its use as an evaporative solvent (IPCS 1990). Table 3 summarizes the environmental releases reported under the National Pollutant Release Inventory (NPRI) during the 1994–2006 period (NPRI 2007). The total on-site releases reported mainly refer to atmospheric releases. The increase in releases of 2-EEA in recent years is primarily from one company in Ontario.

Table 3. Total on-site releases of 2-EEA reported under the NPRI between 1994 and 2006

Reporting
year
Number of
reporting
companies
Total
on-site
releases
Reporting
year
Number of
reporting
companies
Total
on-site
releases
2006 2 1.4 1999 6 4.4
2005 1 1.6 1998 6 4.4
2004 2 1.8 1997 8 33
2003 3 1.5 1996 6 0.31
2002 3 0.13 1995 7 4.4
2001 4 0.12 1994 3 0.00
2000 4 0.15      

Environmental Fate

Level III fugacity modelling was performed for 2-EEA based on its physical and chemical properties (Table 2), and the results are summarized in Table 4. The results indicate that 2-EEA is expected to reside predominantly in the compartment of release.

Table 4. Results of Level III fugacity modelling (EQC 2003) for 2-EEA

  Fraction of substance partitioning to each medium (%)
Substance released to: Air Water Soil Sediment
Air (100%)

50.8

19.5

29.7

0.03

Water (100%)

0.02

99.8

0.01

0.17

Soil (100%)

0.15

21.1

78.7

0.04

Persistence and Bioaccumulation Potential

Environmental Persistence

When released into the environment, 2-EEA is not expected to be persistent in air, water, soil or sediment. Table 5 summarizes the persistence prediction based on the modelled and empirical data.

Table 5. Modelled and empirical data for persistence of 2-EEA in the environment

Fate process Data type Degradation
value
Endpoint /
Units
Reference
Atmospheric
oxidation
Modelled 0.823 t1/2 (days)

AOPWIN 2000

OH reaction
in air
Empirical 0.45

Atkinson 1989

Biodegradation
in water
Modelled 15

BIOWIN 2000 (Ultimate Survey Model)

0.915 Probability

BIOWIN 2000 (MITI Nonlinear Model)

Abbreviations: MITI, Ministry of International Trade & Industry, Japan; t½, half-life.

2-EEA reacts with sunlight and other chemicals in the atmosphere and is typically broken down to hydroesters, hydroxyacids, hydroxycarbonyls, peroxyacyl nitrates and formaldehyde (NPI 2006). High photochemical reactivity of 2-EEA has also been reported in the presence of nitrogen oxides in smog chamber tests (Yanagihara et al. 1977).

Much of the 2-EEA is expected to be deposited onto land or water by rainfall, as the gaseous 2-EEA dissolves in water upon contact (NPI 2006). It is expected to hydrolyse readily and subsequently biodegrade to carbon dioxide and water under aerobic conditions. Under anaerobic conditions, methane and carbon dioxide are the major end products (IPCS 1990). In soil, 2-EEA is broken down by bacteria (NPI 2006).

Using an extrapolation ratio of 1:1:4 for a water:soil:sediment biodegradation half-life (Boethling et al. 1995), the half-life in soil is <182 days, and the half-life in sediments is <365 days. This indicates that 2-EEA is not expected to be persistent in soil or sediment.

The weight of evidence, based on the data described above, indicates that 2-EEA does not meet the persistence criteria for air (half-life in air ≥ 2 days), water or soil (half-life in soil or water ≥ 182 days) or sediment (half-life in sediment ≥ 365 days) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

Potential for Bioaccumulation

Modelled data for the bioaccumulation potential of 2-EEA, presented in Table 6, indicate that this substance is not expected to bioaccumulate in the environment.

Table 6. Modelled data for bioaccumulation of 2-EEA in fish1

Endpoint Value wet wt
(L/kg)
Reference
BAF 1.18

Arnot and Gobas 2003 (Gobas BAF T2MTL)

BCF 1.15

Arnot and Gobas 2003 (Gobas BCF 5% T2LTL)

BCF 1.29

ACD 2007

BCF 14.37

OASIS Forecast 2005

BCF 3.16

BCFWIN 2000

Abbreviations: BAF, bioaccumulation factor; BCF, bioconcentration factor.
1 Metabolic potential of the substance was not taken into account in the modelled bioaccumulation values.

The Modified Gobas BAF middle trophic level model for fish produced a BAF value of 1.18 L/kg wet weight, indicating that 2-EEA is not likely to bioconcentrate or biomagnify in the environment. The BCF models also provide a weight of evidence to support the low bioconcentration potential of the substance.

The weight of evidence indicates that 2-EEA does not meet the bioaccumulation criteria (BCF, BAF ≥ 5000) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

Potential to Cause Ecological Harm

As noted below in the exposure assessment section for human health, concentrations of 2-EEA in air, water and soil are expected to be low.

The experimental results for aquatic toxicity summarized in Table 7 show that acute median lethal concentrations (LC50 values) were much greater than 1.0 mg/L. The experimental data therefore provide a weight of evidence indicating that 2-EEA is not highly hazardous to aquatic organisms. The range of values predicted in Table 7 indicate that 2‑EEA has low to moderate acute toxicity to aquatic organisms and that 2-EEA is unlikely to cause harm to aquatic organisms at relatively low concentrations.

Table 7. Empirical data for aquatic toxicity

Test organism Type of test Endpoint Value
(mg/L)
Daphnia Acute LC50 560
Shrimp Acute LC50 4000
Fish Acute LC50 40-197
Source: ECOTOX 2006

Reported releases of 2-EEA are predominantly to air. When released into the atmosphere 2-EEA is dispersed quickly and the resulting concentrations in air are low. Atmospheric releases from the substance from finished products containing the substance would be diffuse, from a large number of small sources rather than from a few large point sources, so the resulting concentrations of 2-EEA in air would be low. Releases to water are reported to be low, so exposure of aquatic organisms to 2-EEA would be minimal.

As indicated in the previous sections, 2-EEA does not meet the persistence or bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations (Canada 2000). Based on the information available, 2-EEA is unlikely to be causing ecological harm in Canada.

Uncertainties in Evaluation of Ecological Risk

Quantitative structure–activity relationship (QSAR) models were used to estimate persistence and bioaccumulation. There are uncertainties associated with the use of these models to estimate the ecological risk. In addition, the value for Kow, which is used as input to the QSAR models, was also estimated.

There is uncertainty about the environmental exposure to 2-EEA, but it is believed that concentrations in the various environmental media are low.

Potential to Cause Harm to Human Health

Exposure Assessment

Multimedia intake estimates were not derived in this assessment due to insufficient available data. No data were identified on concentrations of 2-EEA in environmental media in Canada except for one study in Windsor, Ontario, where the concentration of 2-EEA in ambient air was below the detection limit of 0.55–2.9 µg/m3 (OMEE 1994). Modelled estimates based on industrial releases to the atmosphere reported under NPRI in 2006 (NPRI 2007) indicate that concentrations of 2-EEA in air, water and soil are not expected to be significant (i.e., in the range of ng/m3, ng/L and ng/g, respectively) (ChemCAN 2003). Likewise, concentrations of 2-EEA in food and beverages are not expected to be significant based on available information on uses and physical and chemical properties.

The maximum concentration of 130 µg/m3 was measured in six samples of indoor air in an Italian study (De Bortoli et al. 1986), whereas in other larger studies conducted in Finland (n = 50 samples) and Germany (n = 89 samples), reported indoor air concentrations of 2‑EEA ranged up to a maximum of 5 µg/m3 only (Jungers and Sheldon 1987; Kostiainen 1995; Schleibinger et al. 2001). Thus, it is considered likely that the general population in Canada is not exposed to concentrations in indoor air greater than 5 µg/m3, the highest concentration detected in the more comprehensive surveys (Schleibinger et al. 2001). In addition, since the use of 2-EEA has declined in the United States and Europe (US EPA 2005; European Commission 2006), the higher concentrations detected in the earlier samples are likely not representative of current exposure. Danish studies have reported emission of 2-EEA from a finished product (e.g., polyvinyl chloride flooring) or during use of a product (e.g., hair dryer), which may contribute to levels of 2-EEA observed in the indoor environment (Lundgren et al. 1999; Danish Ministry of the Environment 2005).

Although only limited information is available on the presence of 2-EEA in products, available information indicates that it is used in paints (Akzo Nobel 2005), spray paints (Borden Inc. 1985, 1987), spray lubricant (Dow Corning Corporation 2007), photoresist (Injectorall Electronics Corporation 1992) and rear window defogger repair kits (Permatex, Inc. 2001). The United States Household Products Database (HPD 2007) also includes two varnishes containing 2-EEA on its ingredient listings; however, the concentration is listed as 0%. Although data were identified on the concentration of 2-EEA in yacht paint (Akzo Nobel 2005), use of this product was limited to professional use only and was not considered to be widespread enough to be appropriate for extrapolation to the general population. Likewise, all the other products were determined not to be in the Canadian marketplace or were considered to be used in limited or specialized activities. Therefore, consumer product exposure scenarios were not developed.

There is a high degree of uncertainty in the estimates of exposure, as only very limited data on concentrations of 2-EEA were identified for environmental media in Canada.

Health Effects Assessment

The available health effects information for 2-EEA is summarized in Appendix 1.

The European Commission has classified 2-EEA as a Category 2 substance with risk phrases R60 (“May impair fertility”) and R61 (“May cause harm to the unborn child”) (ESIS 2007). In addition, the International Programme on Chemical Safety has assessed the toxicity of 2-EEA, together with 2-methoxyethanol (2-ME) and its acetate (2-MEA) and 2-ethoxyethanol (2-EE), and concluded that “the major effects of concern [of these chemicals] for humans are developmental, testicular, and haematological toxicity. These are demonstrated by extensive and consistent data in animals and some human data” (IPCS 1990). Since 2-EEA is rapidly hydrolysed to 2-EE via esterases present in various tissues in the body, information on the toxicity of 2-EE is considered relevant to assessment of the acetate. In the Priority Substances List assessment prepared on 2-EE under CEPA 1999, the critical health effects were also considered to be reproductive and developmental toxicity, as well as effects on the hematological system (Environment Canada and Health Canada 2002).1

Reproductive effects were observed in mice orally exposed to 2-EEA for 5 weeks or longer. Dose-dependent testicular atrophy was observed in mice administered 2-EEA by gavage for 5 weeks, with a lowest-observed-(adverse-)effect level (LO(A)EL) of 1000 mg/kg body weight (kg-bw) per day (Nagano et al. 1979, 1984). In a continuous breeding study, there were reductions in number of litters per pair, number of pups per litter, pup viability and fetal body weight at 1860 mg/kg-bw per day and above in drinking water, whereas at a higher dose, significantly reduced fertility index, testis and epididymis weights, and sperm density were noted, as well as increased incidence of sperm abnormality. Histopathological changes in testes and epididymis were also present (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997).

Developmental effects were observed in rodents and rabbits exposed to 2-EEA via oral, dermal and inhalation administration. Following oral exposure, significantly decreased number of litters per fertile pair, reduced fetal body weights and reduced pup viability were observed in mice exposed to 1% or 2% 2-EEA in drinking water (1860 or 3000 mg/kg-bw per day, respectively) in the absence of maternal toxicity. No effects were observed in mice administered 0.5% 2-EEA (930 mg/kg-bw per day) (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997). In inhalation studies in various strains of pregnant rats and rabbits exposed to 2-EEA, there were significantly increased incidences of visceral and skeletal variations at multiple sites, increased fetal resorption, reduced fetal viability and reduced fetal body weights in the presence of maternal toxicity at 100 parts per million (ppm) (550 mg/m3) or more, for both species. No effects were observed at 50 ppm (275 mg/m3) (Tinston et al. 1983; Doe 1984; Nelson et al. 1984; Tyl et al. 1988). Rabbits were more sensitive than rats, as there was a significant increase in the number of totally resorbed litters at 200–300 ppm (1099–1649 mg/m3), whereas such effects were observed in rats only at 600 ppm (3298 mg/m3) (Nelson et al. 1984; Tyl et al. 1988). In the only available dermal developmental toxicity study, significantly increased incidence of cardiovascular and skeletal variations, increased fetal resorption and decreased fetal body weights and fetal viability were observed in rats exposed to 2-EEA at 5826 mg/kg-bw per day, the only dose tested. Maternal toxicity was also observed at this dose level (Hardin et al. 1984).

The hematological system is also a primary target of 2-EEA. Hematological effects were consistently observed in experimental animals following acute or repeated inhalation exposure. The lowest-observed-(adverse-)effect concentration (LO(A)EC) of 2-EEA in acute inhalation studies was 62 ppm (341 mg/m3), which was based on increased erythrocyte osmotic fragility in female rats (Carpenter et al. 1956). In the developmental toxicity studies described above, a concentration related decrease in the number of platelets and an elevated mean corpuscular volume were observed in rabbit dams and significantly decreased red blood cell counts, hemoglobin, hematocrit and red blood cell size as well as increased white blood cell counts were observed in rat dams at 100 ppm (550 mg/m3) or more for both species, with a no-observed-(adverse-)effect concentration (NO(A)EC) of 50 ppm (275 mg/m3) (Tyl et al. 1988). Additionally, leucopenia was observed in orally exposed mice at 1000 mg/kg-bw per day or more, but not at 500 mg/kg‑bw per day (Nagano et al. 1979, 1984).

No long-term animal bioassay conducted with 2-EEA was identified. Since 2-EEA is rapidly hydrolysed to 2-EE via esterases present in various tissues in the body (Environment Canada and Health Canada 2002), information on carcinogenicity and chronic toxicity of 2-EE is considered relevant to its acetate. One report of a chronic study was identified in which rats and mice were orally exposed to 2-EE. Although no increases in tumour incidences were noted, reporting on histopathological data was limited. However, the testes were reported to be the principal target organ in both species (Melnick 1984). Based on the analysis of available data on genotoxicity of 2-EE and 2-EEA (for the latter, the database is more limited), it was concluded in the Priority Substances assessment (Environment Canada and Health Canada 2002) that 2-EE “may have some weak potential, at most, to induce cytogenetic damage, but there is no evidence that it induces mutation.” 2-EEA did not induce gene mutation in various strains of Salmonella typhimurium (Slesinski et al. 1988; JCIETIC 2000) or in Escherichia coli (JCIETIC 2000), with or without metabolic activation. Although the clastogenicity of 2‑EEA in Chinese hamster ovary cells in vitro was enhanced by metabolic activation, 2-EEA did not induce micronuclei formation in mouse bone marrow cells in vivo (Slesinski et al. 1988).

Reproductive and developmental effects were also noted in humans exposed to glycol ethers, including 2-EEA, in occupational environments. Although exposure to 2-EEA at a time-weighted average (TWA) concentration of 0.51 ppm (2.8 mg/m3) did not affect the menstrual patterns of occupationally exposed women in a liquid crystal display manufacturing facility (Chia et al. 1997), several epidemiological investigations showed that significantly increased risks of spontaneous abortion and/or conception delays (subfertility) and congenital malformations were associated with maternal occupational exposure to glycol ether mixtures, including 2-EEA as well as 2-EE, 2-ME and 2-MEA (Gray et al. 1993, 1996; Beaumont et al. 1995; Schenker et al. 1995; Swan et al. 1995; Correa et al. 1996; Ha et al. 1996; Schenker 1996; Swan and Forest 1996; Cordier et al. 1997, 2001). However, the relative contribution of 2-EEA to these observed effects could not be elucidated, as available data indicate that 2-ME or its acetate could induce similar effects at lower exposure levels in experimental animals (Environment Canada and Health Canada 2002). In a review of these studies (Maldonado et al. 2003), it was stated that the evidence available at that time was insufficient to determine whether occupational exposure to glycol ethers causes human congenital malformations.

With respect to hematological effects, it was reported in a cross-sectional study that exposure to a geometric mean concentration of 2-EEA of 9.34 ppm (51.2 mg/m3) was associated with significant decreases in hemoglobin and hematocrit in exposed women in a silk screening shop, but not in exposed men who, on average, were exposed to lower concentrations (Loh et al. 2003). In the follow-up surveys, the hematological effects observed in the female workers were no longer significant or present after the implementation of protective measures at the workplace for 1 year or longer (Chen et al. 2007). In another cross-sectional study, hematological effects, such as increased leucopenia, were also observed in occupationally exposed men in a shipyard. The TWA level of 2-EEA at the workplace ranged from 1.76 to 3.03 ppm (9.67 to 16.65 mg/m3), with peak exposures of up to 8.12–18.27 ppm (44.6–100.4 mg/m3). The workers in this study were also exposed to other solvents, but not to other glycol ethers (Kim et al. 1999). In the only epidemiological investigation of the potential genotoxicity of 2-EEA, no cytogenic effects (sister chromatid exchange or micronuclei induction) were observed in varnish production workers who were exposed to glycol ethers, including 2-EEA, at levels up to 3.07 ppm (20.34 mg/m3) (Söhnlein et al. 1993).

Although a thorough analysis of mode of action is beyond the scope of this screening assessment, it is recognized that the systemic toxicity of 2-EEA is mediated by its principal major metabolite, 2-ethoxyacetic acid (ECETOC 2005).

The confidence in the database for reproductive and developmental toxicities and for hematological effects of 2-EEA is high, as consistent data are available from different experimental animals and by various routes of administration. These data are also supported by some epidemiological observations as well as by the toxicity information for 2‑EE and 2-ethoxyacetic acid (Environment Canada and Health Canada 2002). However, with respect to chronic effects and carcinogenicity of 2-EEA, information is limited.

Characterization of Risk to Human Health

Based on consideration of the weight of evidence–based classification of 2-EEA by the European Commission as a Category 2 substance for reproductive and developmental effects (ESIS 2007), assessments prepared by another international body (IPCS 1990) and within Health Canada (Environment Canada and Health Canada 2002), and consideration of the available relevant data, the critical effects for characterization of risk to human health for 2-EEA are reproductive, developmental and hematological toxicities. Therefore, where sufficient data are available, margins of exposure are derived between lowest exposure levels associated with induction of critical effects and estimates of population exposure to 2-EEA.

The principal source of exposure to 2-EEA for the general population is expected to be indoor air. A comparison between the concentration of 2-EEA (9.67 mg/m3) at which adverse hematological effects have been reported in workers (Kim et al. 1999) (although it is recognized that these workers were also exposed to other potentially confounding substances) and the highest concentration identified in surveys of indoor air considered most relevant to potential current exposures in Canada (5 µg/m3 [Schleibinger et al. 2001]) results in a margin of exposure of approximately 1930. Comparison of the lowest LO(A)EC (550 mg/m3) at which developmental toxicity and hematological effects were observed in experimental animals (Tyl et al. 1988) with this indoor air concentration yields a larger margin (110 000). These margins are considered adequate to account for uncertainties in the database, in light of the conservative nature of the estimates of exposure and critical effect levels in studies in humans and experimental animals.

Potential consumer products containing 2-EEA were determined not to be in the Canadian marketplace or were considered to be used in limited/specialized activities. Therefore, exposure to 2-EEA via consumer products is not expected to be significant.

Uncertainties in Evaluation of Risk to Human Health

There is some uncertainty regarding the precise magnitude of exposure to 2-EEA in the general environment, although exposures are expected to be very low. There is also uncertaintyassociated with the limited data on the environment and the presence of 2-EEA in consumer products used in Canada. Available sources of information indicate that 2-EEA is not currently used in products that would result in significant exposure of the general population.

Although quantification of differences in sensitivity to 2-EEA induced effects between laboratory animals and humans and across the population is beyond the scope of this screening assessment, it is noteworthy that hematological effects were reported in workers at concentrations lower than effect levels observed in experimental animals. There is some uncertainty with respect to the carcinogenicity potential of 2-EEA due to lack of sufficient information, although the results of genotoxicity studies as well as the primary chronic toxicity data for 2-EE do not suggest that 2-EEA is carcinogenic. Additionally, there is some uncertainty associated with the lack of a reproductive toxicity study in experimental animals exposed by inhalation (the route most relevant to population exposure); however, the available database for other endpoints observed in animals exposed by oral, dermal or inhalation routes does not suggest that effect levels for reproductive toxicity for inhaled 2-EEA would be lower than those for other effects.

Conclusion

Based upon consideration of the margins of exposure between conservative estimates of exposure to 2-EEA from environmental media and concentrations associated with developmental and hematological effects in experimental animals or exposed workers, it is concluded that 2-EEA should not be considered to be “toxic” as defined in paragraph 64(c) of CEPA 1999: i.e., 2-EEA is not a substance 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 the information presented in this screening assessment, it is concluded that 2-EEA is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term 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 therefore concluded that 2-EEA does not meet the definition of “toxic” as set out in section 64 of CEPA 1999. Additionally, 2-EEA does not meet the criteria for persistence or bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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Appendix 1. Summary of health effects information for 2-EEA (CAS RN 111-15-9)

Endpoint

Lowest effect levels1/Results

Laboratory animals and in vitro

Acute toxicity

Lowest oral LD50 (guinea pig) = 1910 mg/kg-bw (Smyth et al. 1941; Carpenter 1947)
[additional studies: LD50 = 1950–7510 mg/kg (Eastman Kodak Company 1958; Pozzani et al. 1959; Truhaut et al. 1979; Gig Sanit 1988)]

Lowest dermal LD50 (mouse) = 10 300 mg/kg-bw (Carpenter 1947)
[additional studies: LD50 = 10 500–>20 000 mg/kg-bw (Eastman Kodak Company 1958; Truhaut et al. 1979)]

Lowest inhalation LC50 (rat) = 8250 mg/m3 (Shell Chemical Co. [undated])
[additional studies: LC50 = >1.08 × 104–1.21 × 104 mg/m3 (Pozzani et al. 1959; Eastman Kodak Company 1968; Truhaut et al. 1979)]

Lowest inhalation LO(A)EC (rat, female) = 62 ppm, equivalent to 341 mg/m3, based on hemolytic effect on erythrocyte osmotic fragility (Carpenter et al. 1956)

Short-term repeated-dose toxicity

 

Lowest oral LO(A)EL (mouse) = 1000 mg/kg-bw per day (male mice, 5/group, gavage for 5 weeks), based on dose-dependent testicular atrophy and leucopenia; NO(A)EL = 500 mg/kg-bw per day (Nagano et al. 1979, 1984)
[additional study: liver weight change was observed in F1 mice in the continuous breeding study (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997)]

Lowest dermal LO(A)EL (rat) = 5826 mg/kg-bw per day (the only dose tested — pregnant rats, 18/group, 4 times daily on gestation days 7–16), based on maternal toxicity, including significantly reduced body weight gain and gravid uterus weight in dams (Hardin et al. 1984)

Lowest inhalation LO(A)EC (rat and rabbit) = 100 ppm, equivalent to 550 mg/m3 (pregnant rabbits, 24/group, 6 h/day, on gestation days 6–18; pregnant rats, 30/group, 6 h/day, on gestation days 6–15), based on maternal toxicity, including significantly reduced body weight gain, altered hematological parameters, increased absolute liver weights and clinical signs; NO(A)EC = 50 ppm, equivalent to 275 mg/m3 (Tyl et al. 1988)
[additional studies: Tinston et al. 1983; Doe 1984; Nelson et al. 1984]

Subchronic toxicity

 

Lowest inhalation LO(A)EC (rat and rabbit) = 200 ppm, equivalent to 1099 mg/m3 (2 rabbits/sex per group; 10 rats/sex per group; 4 h/day, 5 days/week for 10 months). This was the only concentration used in the study. Discrete lesions of tubular nephritis with clear degeneration of the epithelium with hyaline and granular tubular casts were observed in the kidneys of male and female rabbits and male rats but not in female rats (Truhaut et al. 1979).
[additional studies: Carpenter 1947]

Lowest oral LO(A)EL (mouse) = 2% in drinking water, equivalent to 3000 mg/kg-bw per day (Swiss CD mice, 20/sex per group, administered in drinking water for 119 days), based on significantly reduced body weights in the F0 male mice in a continuous breeding study (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997)

No dermal subchronic toxicity data identified

Chronic toxicity/ carcinogenicity

No chronic toxicity/carcinogenicity data identified

Reproductive toxicity

Lowest oral LO(A)EL (mouse) = 1000 mg/kg-bw per day (male mice, 5/group, gavage for 5 weeks), based on dose-dependent testicular atrophy; NO(A)EL = 500 mg/kg-bw per day (Nagano et al. 1979, 1984)

In a continuous breeding study (male/female mice, administered in drinking water for two generations), a LO(A)EL = 1.0%, equivalent to 1860 mg/kg-bw per day, was identified, based on reduced number of litters per pair, reduced number of pups per litter, reduced pup viability and reduced fetal body weight. At a higher dose level (3000 mg/kg-bw per day), significantly reduced fertility index and testis weights and significantly increased incidence of abnormal sperm were observed in the F0 generation, and significantly reduced epididymis weight and sperm density and prominent histopathological changes in the testes and epididymis were observed in the F1 animals. Significant liver weight changes were also observed in the F1 generation. NO(A)EL = 0.5%, equivalent to 930 mg/kg-bw per day (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997).

Developmental toxicity

Lowest oral LO(A)EL (mouse) = 1% in drinking water, equivalent to 1860 mg/kg-bw per day (male/female mice, continuous breeding study), based on significantly decreased number of litters per fertile pair and reduced fetal body weights and pup viability in the absence of maternal toxicity; NO(A)EL = 0.5% in drinking water (930 mg/kg-bw per day) (Gulati et al. 1985; Morrissey et al. 1989; Chapin and Sloane 1997)

Lowest dermal LO(A)EL (rat) = 5826 mg/kg-bw per day (the only dose tested, 18 rats/group, 4 times daily on gestation days 7–16). Significantly increased incidence of cardiovascular variation and skeletal variations in ribs and vertebrae, retarded ossification, increased fetal resorption and decreased fetal body weights and fetal viability were observed. Maternal toxicity was also observed (see above) (Hardin et al. 1984).

Lowest inhalation LO(A)EC (rat and rabbit) = 100 ppm, equivalent to 550 mg/m3 (F344 rats, 30/group, gestation days 6–15; New Zealand White rabbits, 24/group, gestation days 6–18), based on significantly increased incidence of visceral and skeletal variations in fetuses. At higher concentrations (200–300 ppm), significantly increased incidence of external variations, visceral variations (predominantly in cardiovascular and renal systems in both species and in pulmonary system in rabbits) and skeletal variations/malformation (multiple sites) in fetuses, increased fetal resorption and reduced fetal body weights and viability were observed. NO(A)EC = 50 ppm, equivalent to 275 mg/m3. Maternal toxicity was observed at 100–300 ppm (see above) (Tyl et al. 1988).
[additional studies: Tinston et al. 1983; Doe 1984; Nelson et al. 1984]

Genotoxicity and related endpoints: in vivo

Micronuclei induction
Negative results:

Genotoxicity and related endpoints: in vitro

Mutagenicity
Negative results:
Ames test in Salmonella typhimurium TA98, TA100, TA102, TA104, TA1535, TA1537 and TA1538, with and without activation (Slesinski et al. 1988; Hüls 1989b; JCIETIC 2000)

Mutation in Escherichia coli WP2uvrA/pKM101, with and without activation (JCIETIC 2000)

HGPRT locus mutation in Chinese hamster ovary (CHO) cells, with and without activation (Slesinski et al. 1988)

Sister chromatid exchange (SCE)
Negative results:
CHO cells, with and without activation (Slesinski et al. 1988)

Clastogenicity test in CHO cells (no further details), positive results with activation; weak positive results without activation (Slesinski et al. 1988)

Sensitization

Negative in guinea pig (Zissu 1995)

Irritation

Skin irritation
Rabbit:
Draize tests: slightly irritating (Zissu 1995) and negative (Truhaut et al. 1979)
EEC (European Economic Community protocol) test: Negative (Zissu 1995)
Guinea pig: slightly irritating (Eastman Kodak Company 1958; Eastman Chemical Products, Inc. 1982)

Eye irritation
Rabbit: slightly irritating (Von Oettingen and Jirouch 1931; Carpenter and Smyth 1946; Eastman Chemical Products, Inc. 1982; Kennah et al. 1989) and negative in Draize test (Truhaut et al. 1979)

Humans

Genotoxicity

No increased incidence of SCE and micronuclei induction was detected in 19 varnish production workers exposed to a glycol ether mixture, including 2-EEA, compared with 15 controls (age and smoking habits were largely matched). The 2-EEA level in the varnish workplace was in the range of 0.1–3.7 ppm, equivalent to 0.55–20.34 mg/m3 (Söhnlein et al. 1993).

Reproductive and developmental toxicity

Menstrual patterns
In a cross-sectional study of occupationally exposed women (52 exposed versus 55 referents) at a liquid crystal display manufacturing facility, no effects on menstrual patterns were noted in the exposed workers. The mean time-weighted average (TWA) concentration of 2-EEA was 0.51 ppm (range 0.15–3.03 ppm), equivalent to 2.8 mg/m3 (range 0.8–16.65 mg/m3) (Chia et al. 1997).

Spontaneous abortion
A large epidemiological study conducted in 14 US semiconductor companies, including a historical cohort (891 women aged 18–44), a prospective cohort (481 women) and a cross-sectional study (1637 women and 158 men aged 18–72), showed that an increased relative risk (RR) of spontaneous abortion was associated with parental occupational exposure to a glycol ether mixture, including 2‑ME, 2-EE and their acetates (the maximum concentration of 2-EEA was 0.708 ppm, equivalent to 3.89 mg/m3), propylene-based glycol ethers and other solvents. The RRs were significantly increased among the fabrication workers in the retrospective cohort study (RR = 1.45, 95% confidence interval [CI] = 1.02–2.06; after multivariate adjustment, RR = 1.43, 95% CI = 0.95–2.09). Exposure to glycol ethers was correlated with the incidence of spontaneous abortions when compared with non-exposed women (RR = 1.56, 95% CI = 1.02–2.31). However, in the prospective cohort study, the increased RRs of spontaneous abortion among the fabrication workers were not statistically significant (RR = 1.25, 95% CI = 0.63–1.76) (Beaumont et al. 1995; Schenker et al. 1995; Swan et al. 1995; Schenker 1996; Swan and Forest 1996).

Similar conclusions were derived from cohort studies, including a historical cohort (561 pregnancies to exposed women and 589 pregnancies to the wives of exposed men) and a prospective cohort (148 women), conducted at two IBM semiconductor manufacturing companies. Glycol ethers used at the workplace included diethylene glycol dimethyl ether and/or 2-EEA. In the historical cohort study, significantly increased RR of spontaneous abortion was observed in women who might have experienced high-level exposure (RR = 2.8, 95% CI = 1.4–5.6), and not in the wives of exposed men. In the prospective study, the RR of fetal loss was 2.5 (95% CI = 0.8–8.5) in the exposed women. The result was not significant. In addition, in the retrospective cohort study, the odds ratio (OR) of subfertility (conception delay for more than a year) was also significantly increased in those women who might have experienced high-level exposure (440 pregnancies, OR = 3.9, 95% CI = 1.4–11.4), and there was a non-significantly increased risk of subfertility in the wives of men who might have experienced high-level exposure (495 pregnancies, OR = 1.6, 95% CI = 0.6–3.8); no exposure estimates were provided (Gray et al. 1993, 1996; Correa et al. 1996).

 

Congenital malformation
In a case–control (538 cases versus 539 controls) study, there was no association between maternal exposure (occupational and/or in hobbies) to a glycol ether mixture and the occurrence of anencephaly, spinal bifida cystica, craniorachischisis and iniencephaly (neural tube defects) (Shaw et al. 1999).

In two case–control studies, increased risk of congenital malformation was associated with maternal occupational exposure to a glycol ether mixture. One was a study (984 cases versus 1134 controls) of western European workers in a wide diversity of occupational settings (Ha et al. 1996; Cordier et al. 1997); the second was a study (196 cases versus 196 controls) in the Slovak Republic (Cordier et al. 2001). No information regarding the risk specifically attributed to 2-EEA exposure was provided in these studies.

Hematological effects

A cross-sectional study was conducted in workers with high-exposure experience (n = 29: 17 males, 12 females) versus those with low/no-exposure experience (n = 56: 29 males, 27 females) at a silk screening shop. The geometric mean (GM) concentration of 2-EEA in the high-exposure group was 7.4 ppm (range 1.35–16.5 ppm), equivalent to 40.66 mg/m3 (range 7.42–90.68 mg/m3); the GM concentration for female workers was 9.34 ppm, equivalent to 51.2 mg/m3; the GM concentration for male workers was 4.87 ppm, equivalent to 26.8 mg/m3. The GM concentration in the low/no-exposure group (n = 26) was 0.07 ppm (range from undetectable to 3.62 ppm), equivalent to 0.39 mg/m3 (range from undetectable to 19.9 mg/m3). The mean values of hemoglobin and hematocrit in the female workers in the high-exposure group were significantly decreased (12 exposed versus 27 controls). No such effects were observed in exposed male workers (Loh et al. 2003). In the follow-up surveys done 1 year (11 exposed versus 24 controls) or 3 years (11 exposed versus 19 controls) after implementation of a rubber glove–wearing policy and the improvement of the ventilation system at the workplace, there were no longer any significant differences in hematological parameters between the female workers in the high-exposure group and controls. The authors stated that 2-EEA was the main component of the screen cleaning solvent; these workers may be exposed to small amounts of methyl isobutyl ketone and toluene as well (Chen et al. 2007).

Hematological effects associated with 2-EEA exposure were reported in another cross-sectional investigation among male shipyard painters with high-exposure experience (n = 30, mean years of work = 8.0 ± 5.4 [standard deviation (SD)]) or low-exposure experience (n = 27, mean years of work = 11.0 ± 0.7 [SD]), versus a control group (mainly office staff, n = 41, mean years of work = 11.0 ± 6.6 [SD]). The TWA concentration of 2-EEA in the high-exposure scenario was 3.03 ppm, equivalent to 16.65 mg/m3, with an exposure peak up to 18.27 ppm (100.4 mg/m3); the TWA concentration of 2-EEA in the low-exposure areas was 1.76 ppm (9.67 mg/m3), with an exposure peak up to 8.12 ppm (44.6 mg/m3). The occurrence of leucopenia was significantly increased in the exposure groups (6/57 = 11%). In the high exposure group, the mean white cell and granulocyte counts were significantly decreased, and the mean corpuscular volume was significantly increased, compared with the controls. The workers in the exposure groups were also exposed to other chemicals (toluene, xylene, butanol, ethyl benzene, isopropanol, ethanol, ethyl acetate, butyl acetate, methyl isobutyl ketone and nonane), but not to other glycol ethers (Kim et al. 1999).

1 LC50, median lethal concentration; LD50, median lethal dose; LO(A)EC, lowest-observed-(adverse-)effect concentration; LO(A)EL, lowest-observed-(adverse-)effect level; NO(A)EC, no-observed-(adverse-)effect concentration; NO(A)EL, no-observed-(adverse-)effect level.

Footnotes

1 An overview of the information on the health effects associated with 2-EE is presented in the Priority Substances List assessment report (Environment Canada and Health Canada 2002).