Ethanol, 2-methoxy-, acetate
Chemical Abstracts Service Registry Number
The Ministers of the Environment and of Health have conducted a screening assessment of ethanol, 2-methoxy-, acetate (2-methoxyethanol acetate; 2-MEA), Chemical Abstracts Service Registry Number 110-49-6. The substance 2-MEA was identified in the categorization of the Domestic Substances List as a high priority for action under the Challenge. 2-MEA was identified as a high priority because it was considered to pose an intermediate 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-MEA relates principally to human health risks.
According to the information submitted under section 71 of Canadian Environmental Protection Act, 1999 (CEPA 1999), 2-MEA was not manufactured in or imported into Canada by any company at a quantity greater than the reporting threshold of 100 kg in the calendar year 2006, although some importation below this threshold was reported. Based on this information, exposure of the general population in Canada to 2-MEA is expected to be very low.
Based on available information from toxicological studies in experimental animals and epidemiological investigations in occupationally exposed populations for 2-MEA and its corresponding alcohol, 2-methoxyethanol (2-ME) (in light of the limited database on 2-MEA, the rapid conversion of the acetate to the ethanol and the common profile of effects for the two substances), the critical health effects associated with exposure are primarily developmental and reproductive toxicity (including severe and irreversible teratogenic effects), with effects being observed at very low doses, often the lowest dose tested. In addition, these substances have indicated some potential to interact with genetic material in germ cells. Thus, it cannot be precluded that there is some probability of harm at any level of exposure.
Although exposure to 2-MEA in Canada is likely to be very low, it is concluded, based principally on the non‑distinguishable hazard potential between 2-MEA and 2-ME, including reproductive and developmental effects for which there may be a probability of harm at any level of exposure, that the conclusion of the Priority Substances List assessment for 2-ME (i.e., that “on the basis principally of its high health hazard potential, 2-ME is considered to constitute a danger in Canada to human life or health” be expanded to include its acetate moiety, 2-MEA).
On the basis of low ecological hazard, very low expected releases and low environmental exposure of 2-MEA, 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-MEA 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 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-MEA meets one or more of the criteria set out in section 64 of CEPA 1999.
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-methoxy-, acetate (2-methoxyethanol acetate; referred to as 2-MEA) was identified as a high priority for assessment of human health risk because it was considered to present IPE and had been classified by another agency on the basis of reproductive and developmental toxicity.
The Challenge for 2-MEA was published in the Canada Gazette on August 18, 2007 (Canada 2007). A substance profile was released at the same time (Canada 2007b). 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-MEA 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
- have or may have an immediate or long-term harmful effect on the environment or its biological diversity;
- constitute or may constitute a danger to the environment on which life depends; or
- 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 June 2008 for the exposure section of the document and up to June 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 Glenn Talaska (University of Cincinnati), 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.
2-MEA, also known as ethylene glycol monomethyl ether acetate (EGMEA) or methyl cellosolve acetate, is an organic ester with two ether linkages in a parent chain (Table 1). At room temperature, 2-MEA is a colourless liquid with a pleasant odour (Budavari 1996; WHO 2003; Lewis 2007). It is combustible, soluble in water and miscible with common organic solvents (Budavari 1996). Additional information on the identity of 2‑MEA is summarized in Table 1.
Table 1. Substance identity of 2-MEA
Ethanol, 2-methoxy-, acetate
Ethanol, 2-methoxy-, 1-acetate (TSCA, ENCS, AICS, SWISS, PICCS, ASIA-PAC);)
Acetate, 2-methoxyethyl; Acetic acid, 2-methoxyethyl ester; 1-Acetoxy-2-methoxyethane; Acetyl methyl cellosolve; Ethyl glycol, monomethyl ether acetate; Ethylene glycol acetate monomethyl ether; Ethylene glycol methyl ether acetate; Ethylene glycol monomethyl ether acetate; Glycol monomethyl ether acetate; 2-Methoxyethanol acetate; β-Methoxyethyl acetate; Methyl cellosolve acetate; Methyl glycol acetate
|Molecular mass||118.13 g/mol|
2 Source: National Chemical Inventories (NCI). 2006: AICS (Australian Inventory of Chemical Substances); ASIA-PAC (Asia-Pacific Substances Lists); ECL (Korean Existing Chemicals List); EINECS (European Inventory of Existing Commercial Chemical Substances); ENCS (Japanese Existing and New Chemical Substances); SWISS (Swiss Giftliste 1 and Inventory of Notified New Substances); PICCS (Philippine Inventory of Chemicals and Chemical Substances).
Abbreviations: CAS RN, Chemical Abstracts Service Registry Number; DSL, Domestic Substances List; 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 2006
Physical and Chemical Properties
Table 2 summarizes experimental and modelled physical and chemical properties of 2‑MEA.
Table 2. Physical and chemical properties of 2-MEA
PhysProp 2006; Verschueren 2001
PhysProp 2006; Verschueren 2001
Henry's Law constant
2.54 × 10-2 - 2.77 × 10-1
(2.503 × 10-7 - 2.73 × 10-6
|3.1 × 10-7||20||
KOWWIN 2000; PhysProp 2006
PCKOCWIN 2000; ACD 2007
|Experimental||1.00 × 106||20||
Yalkowsky and Dannenfelser 1992
1 The order of references corresponds to the order of the values.
2 The value in parentheses is the value originally reported in the reference.
2-MEA is an anthropogenic compound and has not been found to occur as a natural product (IPCS 1990; NPI 2005). It is produced for use in manufacturing processes by esterification of 2-methoxyethanol (2‑ME) with acetic acid, acid anhydride or chloride in the presence of an acid catalyst (Kirk and Othmer 1980).
According to data submitted in CEPA 1999 section 71 responses, 2-MEA was not manufactured in Canada in the 2006 calendar year above the reporting threshold quantity of 100 kg. Some importation activities were reported at a quantity less than the reporting threshold (Environment Canada 2008).
Historically, 2-MEA was used most commonly as an industrial solvent. Applications included glues and adhesives used for bonding floor coverings and waterproof surfaces fitted to household fixtures. It was also used as a solvent for surface coatings such as paints, coatings, varnishes and lacquers for paper and leather and also for acetate adhesives (HSDB 2005; NPI 2005HSDB 2008). It has been used as a solvent in nitrocellulose, cellulose acetate, gums, resins, waxes and oils (NPI 2005). It has also been used as a solvent component in textile printing and photographic film (Verschueren 2001) as well as in nail polish and dry cleaning treatments (NPI 2005).
While some research publications have reported the use of 2-MEA as a diesel fuel additive to reduce vehicle emissions (Guo et al. 2004; Yanfeng et al. 2007), no indication of current or future commercial use of 2‑MEA for this purpose has been identified.
No current cosmetic use of 2-MEA has been notified in Canada, whereas its corresponding alcohol, 2-ME, is currently prohibited in cosmetic products and is listed on the Health Canada cosmetic hot list (CNS 2008). 2-MEA has been used in cosmetic products as a solvent and a viscosity decreasing agent, and there are still a few active suppliers of this substance noted by the Personal Care Products Council (formerly the Cosmetic, Toiletry and Fragrance Association) (CTFA 2008). However, 2-MEA as well as 2-ME are prohibited from use in cosmetics in the European Union (European Commission 1999).
In the past (i.e., 15 years ago), 2-MEA was used as a solvent in the manufacture of coatings and adhesives in food packaging. However, no current uses of this substance in food packaging are recognized in Canada (personal communication with Food Directorate, Health Products and Food Branch, Health Canada, 2008-04-18 and 2008‑05‑09; unreferenced). 2-MEA is used as a component in the formulation of a cleaner applied on food contact surfaces that are subsequently rinsed with potable water and as a cleaner on non-food contact surfaces under well-ventilated conditions in food processing plants (personal communication with Food Directorate, Health Products and Food Branch, Health Canada, 2008-06-27; unreferenced).
Use of short straight-chain glycol ethers including 2-MEA and 2-ME has progressively decreased over the last 20 years worldwide (Johanson and Rick 1996; De Kettenis 2005; US EPA 2005). The US Environmental Protection Agency (EPA) has indicated that there was no ongoing use of 2-MEA or 2-ME 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
According to data submitted in CEPA 1999 section 71 responses, no significant releases of 2-MEA were identified in the 2006 calendar year (Environment Canada 2008). In addition, no manufacture or import of 2-MEA above the reporting threshold of 100 kg was reported (although smaller quantities were reported to be imported) (Environment Canada 2008). Environment Canada’s National Pollutant Release Inventory (NPRI) data from 1994 to 2006 also indicated no reported releases of 2-MEA (NPRINPRI 2007). Therefore, total industrial releases of 2-MEA to the environment are expected to be negligible.
Internationally, 2-MEA is not listed under the US EPA Toxics Release Inventory (TRI) (TRI 2008), and a review of the Australian National Pollutant Inventory (NPI) indicated that no emissions of 2-MEA were reported for 2005 (NPI 2005).
The results of Level III fugacity modelling for 2-MEA are summarized in Table 3. The modelled predictions suggest that 2-MEA will partition predominantly to soil when it is released to air or soil. When it is released to water, it will partition predominantly to this compartment, and only a small portion will partition to other compartments. Low partitioning of 2-MEA to sediment regardless of the compartment of release is consistent with the very low log Koc value estimated for 2-MEA.
Table 3. Results of the Level III fugacity modelling (EQC Version 2003) for 2-MEA
Fraction of substance partitioning
to each medium (%)
|Substance released to:||Air||Water||Soil||Sediment|
Persistence and Bioaccumulation Potential
When released into the environment, 2-MEA is not expected to be persistent in air, water, soil or sediment. Table 4 summarizes modelled and empirical data for persistence of 2‑MEA. High photochemical reactivity of 2-MEA has also been reported in the presence of nitrogen oxides in smog chamber tests (Yanagihara et al. 1977).
Table 4. Modelled and empirical data for persistence of 2-MEA in the environment
|Fate process||Data type||
|Endpoint / Units||Reference|
|Atmospheric oxidation||Model||1.1||t1/2 (days)||
|Biodegradation in water||Model||15||t1/2 (days)||
BIOWIN 2000 (Ultimate Survey Model)
BIOWIN 2000 (MITI Nonlinear Model)
The high solubility of 2-MEA also indicates that once it is released to water, it is likely to stay in this compartment. It also biodegrades readily in water and in soil, with half-lives of 15 days. Hydrolysis half-lives in water are 391 days at pH 7 and 32 days at pH 8, suggesting that hydrolysis is not likely to be an important degradation process in water at environmentally relevant pH (HSDB 2008).
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-MEA is not expected to be persistent in soil or sediment.
The weight of evidence, based on the data described above, indicates that 2-MEA does not meet the persistence criteria for air (half-life ≥ 2 days), water or soil (half-lives ≥ 182 days) or sediment (half-life ≥ 365 days) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).
Potential for Bioaccumulation
Modelled data for the bioaccumulation potential of 2-MEA in fish as a test organism are presented in Table 5. The results indicate that this substance is not expected to bioaccumulate.
Table 5. Modelled data for bioaccumulation of 2-MEA in fish1
Value wet weight
Arnot and Gobas 2003 (Gobas BAF T2MTL)
Arnot and Gobas 2003 (Gobas BCF 5% T2LTL)
OASIS Forecast 2005
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 1.02 L/kg wet weight, indicating that this substance is not likely to bioconcentrate or biomagnify in the environment. The BCF models also provide weight of evidence to support the low bioconcentration potential of this substance.
The weight of evidence indicates that 2-MEA does not meet the bioaccumulation criteria (BCF, BAF ≥ 5000 L/kg) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).
Potential to Cause Ecological Harm
As indicated previously, 2-MEA does not meet the persistence or bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).
A study on the acute toxicity of 2-MEA to fish (Carassius auratus) resulted in a median lethal concentration (LC50) of 160 mg/L (Table 6). This concentration is considered to be of low to moderate acute toxicity, and 2-MEA is not expected to cause harm to aquatic organisms at relatively low concentrations. Devillers et al. (2002) reported a chronic reproduction value of 0.06 mg/L for Ceriodaphnia dubia. This suggests that invertebrates may be more sensitive than fish and amphibians (Xenopus laevis) to 2-MEA (Table 6).
Table 6. Empirical data for aquatic toxicity of 2-MEA in aquatic organisms
|Test Organism||Test Type||Endpoint||
|Fish||Acute||LC50||160||Bridié et al. 1979|
|50||Devillers et al. 2002|
As discussed above, no environmental releases of 2-MEA were reported under section 71 of CEPA 1999 (Environment Canada 2008) or under the NPRI (Canada 2007c; NPRI 2007).). Furthermore, the quantity of 2-MEA imported into Canada is very low and the substance is not manufactured in Canada. Therefore, based on the information available, environmental concentrations of 2-MEA are expected to be extremely low, and the substance is unlikely to be causing ecological harm in Canada.
Uncertainties in Evaluation of Ecological Risk
There are uncertainties associated with the use of quantitative structure–activity relationship (QSAR) models to estimate persistence and bioaccumulation. In addition, QSAR models were based on the estimated values for some of the key physical and chemical properties, including vapour pressure, Kow, Koc and Henry’s Law constant.
Potential to Cause Harm to Human Health
No measured concentrations of 2-MEA in Canadian environmental media were identified. According to the NPRI (2007), there has not been any significant release of 2-MEA in Canada reported since 1994. In addition, 2-MEA is not manufactured in Canada and is imported only in very small quantities, according to the section 71 submission. Therefore, this substance is not expected to be present in the environment at significant concentrations.
2-MEA has been measured at a maximum concentration of 39 µg/m3 (mean concentration of 2 ± 7 µg/m3) in 30 samples of indoor air of private and public rooms in Germany between 1988 and 1999 (Schleibinger et al. 2001). It was also detected in one of six samples of indoor air in Italy at a concentration of 4 µg/m3 (De Bortoli et al. 1986). However, it was not detected in an analysis of samples from 200 apartments in Germany, where the detection limit was 1 µg/m3 (Plieninger and Marchl 1999).
Based on its physical and chemical properties, and since it was not reported to have been released in Canada in significant amounts (cEnvironment Canada 2008), 2-MEA is not expected to be present at any significant concentrations in air, water, soil or sediment. It is also not expected to be present in food.
No submission was reported under section 71 of CEPA 1999 to indicate that 2-MEA would be present in consumer products in Canada (Environment Canada c2008). Considering that 2-MEA is used in neither the United States nor the European Union, it is not likely to be present in many Canadian consumer products. Based on its historical uses, a possible route of exposure to 2-MEA from consumer products may be inhalation of indoor air, although, in light of available information on current uses, exposures are not expected to be significant. Inhalation of 2-MEA during use of household solvent products containing the substance may be possible (NPI 2005); however, 2-MEA was not found in the US Household Products Database (HPD 2007).
Thus, the greatest potential source of exposure to 2-MEA for the general population of Canada is likely from the inhalation of indoor air, with the maximum concentration reported in earlier studies in other countries being 39 µg/m3. In light of the limited data available on concentrations in environmental media, confidence in this estimate is very low, although it is probable that exposures in Canada are below this concentration.
Health Effects Assessment
The available information on health effects associated with 2-MEA is summarized in Appendix 1.
The European Commission has classified 2-MEA 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-MEA, together with 2-ME, 2‑ethoxyethanol and its acetate, and concluded that “the major effects of concern [of these chemicals] for humans are developmental, testicular, and haematological toxicity” (IPCS 1990). Since 2-MEA is rapidly hydrolysed to 2-ME via esterases present in various tissues in the body, information on the toxicity of 2-ME is considered relevant to assessment of the acetate. In the assessment of 2-ME as a Priority Substance under CEPA 1999, the critical health effects were also considered to be reproductive and developmental toxicity, as well as effects on the hematological, immune and nervous systems (Environment Canada and Health Canada 2002).1
Testicular damage, evidenced by dose-related reductions in absolute testis weights and atrophy of the seminiferous epithelium and occasional proliferation of the Leydig cells, has been observed in mice following oral administration of 2-MEA at 500 mg/kg body weight (kg-bw) per day (lowest-observed-(adverse-)effect level [LO(A)EL]) or higher dose levels. These effects were not observed at 250 mg/kg-bw per day (no-observed-(adverse-)effect level [NO(A)EL]) (Nagano et al. 1979, 1984). In addition, 2-ME was consistently toxic to the male reproductive system in multiple species of experimental animals exposed by oral, dermal or inhalation administration (Environment Canada and Health Canada 2002). Effects on the female reproductive system, such as changes in estrous cycle and hormone levels and atrophy of female reproductive organs, have also been associated with exposure to 2-ME (Environment Canada and Health Canada 2002). The lowest oral, dermal and inhalation LO(A)ELs for 2-ME were 25 mg/kg-bw per day in rabbits, with a NO(A)EL of 12.5 mg/kg-bw per day (Foote et al. 1995; Berndtson and Foote 1997), 625 mg/kg-bw per day in rats (Feuston et al. 1989) and 30 parts per million (ppm) (93 mg/m3) in rabbits (Miller et al. 1983), respectively.
Fetal mortality was observed in mice administered 2-MEA at 1225 mg/kg-bw per day (the only dose tested) by gavage through gestation days 6–13 (Hardin et al. 1987). In addition, 2-ME has consistently induced developmental toxicity, including fetal malformations, mainly in the cardiovascular system, kidney and skeletal systems, in oral, dermal and inhalation studies in several species of experimental animals (Environment Canada and Health Canada 2002). The lowest oral effect level of 2-ME was observed at 12 mg/kg-bw per day (the lowest dose tested) in a gavage study in monkeys (Scott et al. 1989). The lowest inhalation lowest-observed-(adverse-)effect concentration (LO(A)EC) of 2-ME was identified to be 10 ppm (31 mg/m3) in rabbits, with a no-observed-(adverse-)effect concentration (NO(A)EC) of 3 ppm (9 mg/m3) (Hanley et al. 1984a, b). Effects were observed following dermal application of 2-ME at approximately 48 mg/kg-bw per day or more in rats (Hellwig 1993).
Hematological effects were observed in experimental animals after inhalation exposure, including hemolysis in female rats after 4-hour exposure to 32 ppm (154.6 mg/m3) 2-MEA (Carpenter et al. 1956) and decreases in blood pigment and red blood corpuscles in cats after 42-hour exposure to 2-MEA at 1100 mg/m3 (Gross 1938). In addition, leucopenia was observed in the short-term oral study in mice described above (Nagano et al. 1979, 1984). Impaired immune response was observed in rats orally exposed at 50 mg/kg-bw per day or more (Smialowicz et al. 1992). Although no data are available regarding the neurotoxicity of 2-MEA, 2-ME induced neurological effects were observed in rats and mice following acute or short-term inhalation exposure at concentrations of 25 ppm (78 mg/m3) or greater (Goldberg et al. 1962; Nelson et al. 1984).
No data are available with respect to the potential carcinogenicity or chronic effects of 2‑MEA or 2-ME. Limited data suggest that 2-MEA and 2-ME have weak genotoxicity potential. Although 2-MEA and 2-ME did not induce gene mutation in bacteria or yeast, both substances induced in vitro clastogenicity in mammalian cells. 2-MEA induced aneuploidy in Drosophila melanogaster and yeast, and there is some evidence that 2-ME induced deoxyribonucleic acid (DNA) damage in male germ cells in a gavage study in rats. In addition, 2-methoxyacetaldehyde (MALD), the initial metabolite of 2-MEA (after hydrolysis to 2-ME) and 2-ME, induced gene mutation in mammalian cells, and it is a more potent inducer of clastogenicity in mammalian cells as well (Bootman and May 1985; Zimmermann et al. 1985; Basler 1986; Whittaker et al. 1989; Loveday et al. 1990; Sehgal and Osgood 1990; Osgood et al. 1991; Zeiger et al. 1992; Environment Canada and Health Canada 2002).
In humans, some epidemiological investigations showed an increased risk of spontaneous abortion associated with occupational exposure to mixtures of glycol ethers, including 2‑MEA and 2-ME, in semiconductor industries (Beaumont et al. 1995; Schenker et al. 1995; Swan et al. 1995; Schenker 1996; Swan and Forest 1996). However, these data were inconclusive, as they could not elucidate the relative contribution of 2-MEA or 2-ME to the spontaneous abortion risk. The results of several epidemiological studies also suggested that increased risk of congenital malformations was associated with maternal occupational exposure to glycol ether mixtures (Gray et al. 1993; Ha et al. 1996; Cordier et al. 1997, 2001). However, in a review of available information, Maldonado et al. (2003) deemed that the evidence at the time was insufficient to determine whether occupational exposure to glycol ethers causes human congenital malformations. In addition, in a case report, congenital malformation in male reproductive organs was reported in two boys whose mother had been exposed to 2-MEA (1–2 L/day) via inhalation and dermal contact during pregnancies in an industrial laboratory (Bolt and Golka 1990). Effects on male reproductive, neuronal, hematological and immunological systems were also observed in human workers exposed to 2-MEA or 2-ME. However, these data were not conclusive due to confounding exposure factors, as all of these populations were also exposed to other chemicals (Environment Canada and Health Canada 2002).
Although a thorough analysis of the mode of induction of effects is beyond the scope of this screening assessment, it has been recognized that the generation of alkoxyacetic acid derivative is a necessary activation step to elicit both testicular and developmental effects of 2-MEA or 2-ME (IPCS 1990). 2-MEA is rapidly hydrolysed to 2-ME by esterases, and the latter is further oxidized to MALD and subsequently 2- methoxyacetic acid by dehydrogenases in humans and laboratory animals (ECETOC 2005a). Thus, on the basis of qualitatively similar kinetics and metabolism between experimental animals and humans, the effects observed in laboratory studies are considered relevant to humans, although there may be quantitative differences in sensitivity.
The confidence in the toxicity dataset for reproductive and developmental toxicity and other non-neoplastic effects associated with 2-MEA exposure is considered to be moderate. Limited data on this substance are supported by the larger dataset on the corresponding alcohol, 2-ME. However, there are some uncertainties with respect to the neoplastic potential of 2-MEA, as no long-term animal data for this substance or 2-ME are available, and there is some evidence for a weak genotoxic potential.
Characterization of Risk to Human Health
As there is no distinguishable variation with respect to the profile of toxic effects between 2-ME and 2-MEA, the two chemicals are considered to have similar intrinsic hazard potential, and, in light of the more limited database for the acetate, it is considered appropriate to incorporate information on the toxicity of 2-ME in the characterization of risk to human health for 2-MEA. The health effects associated with exposure to 2-ME and 2-MEA are primarily developmental and reproductive toxicity (including severe and irreversible teratogenic effects), with effects being observed at very low doses, often the lowest dose tested in a study. Although analysis of the mode(s) of induction of these effects is beyond the scope of this screening assessment under the Challenge, based on the observation of effects in experimental animals at low exposure levels (in some studies at the lowest doses or concentrations tested) and the genotoxicity profile of 2-MEA, 2-ME and subsequent metabolites (particularly, genetic effects induced in germ cells), it cannot be precluded at this time that interaction with genetic material, for which there may be a probability of harm at any level of exposure, may play a role. In addition, other effects, such as those on hematological, immunological and nervous systems, were also observed in experimental animals, as well as in humans exposed to 2-ME or 2-MEA along with other substances in the occupational environment.
In light of the rapid conversion of 2-MEA to 2-ME and the common profile of induced critical effects, although exposure to 2-MEA in Canada is expected to be very low, it is considered appropriate to extrapolate the conclusion reached in the PSL assessment for 2‑ME (i.e., that, “on the basis principally of its high health hazard potential, 2‑ME is considered to constitute a danger in Canada to human life or health” [Environment Canada and Health Canada 2002]) to 2-MEA.
Uncertainties in Evaluation of Risk to Human Health
The scope of this screening assessment of 2-MEA does not take into account variability across the general population. Although experimental data suggest that there may be differences in sensitivity of induction of effects between humans and experimental animals, data are insufficient to quantify these differences. In addition, there is some uncertainty with regard to the potential of 2-MEA to induce neoplastic effects.
Considering that no releases were reported under section 71 of CEPA 1999, environmental concentrations of 2-MEA are expected to be negligible. However, there is uncertainty due to the lack of adequate Canadian monitoring data. As there is evidence that the use of 2-MEA has significantly declined in other countries, it is likely that there has been similar reduction in the use of this substance in Canada. However, there is still some uncertainty regarding potential exposures via products.
Based on the information presented in this draft screening assessment, it is proposed that 2-MEA 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.
Based principally on the non-distinguishable intrinsic hazard potential between 2-ME and 2-MEA on a wide range of health effects, including reproductive and developmental endpoints for which there may be a probability of harm at any level of exposure, it is concluded that the conclusion on 2-ME under paragraph 64(c) of CEPA 1999 (Environment Canada and Health Canada 2002) should be expanded and applied to its acetate moiety, 2-MEA. Therefore, it is concluded that 2-MEA should be considered a substance that may be 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.
It is therefore concluded that 2-MEA does not meet the definition of “toxic” as set out in paragraph 64(a) or 64(b) of CEPA 1999, but that it does meet the criteria in paragraph 64(c) of CEPA 1999. Additionally, 2-MEA does not meet the criteria for persistence and bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).
[ACD] Advanced Chemistry Development. 2007. Calculated values using Advanced Chemistry Development (ACD/Labs) Software V9.04 for Solaris (© 1994-2007, presented in SciFinder database, searched July 25, 2007.
[AOPWIN] Atmospheric Oxidation Program for Windows [Estimation Model]. 2000. Version 1.91. 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
Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR Comb. Sci. 22(3):337-345.
BASF. 1966. Methoxyglykolacetat : Unpublished data (XV/334). Abt. Toxikologie (1.3.1966). BASF, Ludwigshafen, Germany. [cited in ECETOC 2005b].
Basler A. 1986. Aneuploidy-inducing chemicals in yeast evaluated by the micronucleus test. Mutat Res 174:11-3.
[BCFWIN] BioConcentration Factor Program for Windows [Estimation Model]. 2000. Version 2.15. 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
Beaumont JJ, Swan SH, Hammond SK, Samuels SJ, Green RS, Hallock MF, Dominguez C, Boyd P, Schenker MB. 1995. Historical cohort investigation of spontaneous abortion in the semiconductor health study: epidemiologic methods and analysis of risk in fabrication overall and in fabrication work groups. Am J Ind Med 28:735-750.
Berndtson WE, Foote RH. 1997. Disruption of spermatogenesis in rabbits consuming ethylene glycol monomethyl ether. Reprod Toxicol 11(1):29-36
[BIOWIN] Biodegradation Probability Program for Windows [Estimation Model]. 2000. Version 4.02. 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
Boethling RS, Howard PH, Beauman JA, and Larosche ME. 1995. Factors for intermedia extrapolations in biodegradability assessment. Chemosphere 30(4):741-752.
Bolt HM, Golka K. 1990. Maternal exposure to ethylene glycol monoethylether acetate and hypospadia in offspring. A case report. Br J Ind Med 47:352-3.
Bootman J, May K. 1985. Mutagenicity studies. Ames tests. Unpublished report. December 1985. Life Science Research, UK.
Bridié A, Wolff C, Winter M. 1979. The acute toxicity of some petrochemicals to goldfish. Water Res 13: 623–626.
Budavari S (ed.). 1996. The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 12 th Edition. Whitehouse Station, (NJ) : Merck and Co., Inc. p. 1032.
Canada. 1999. Canadian Environmental Protection Act, 1999 = Loi canadienne sur la protection de l'environnement, 1999. Statutes of Canada = Statuts du Canada, Chapter 33. Act assented to September 14, 1999. Ottawa : Queen's Printer. Available at Canada Gazette (Part III) 22(3): chapter 33. Available from: http://canadagazette.gc.ca/partIII/1999/g3-02203.pdf
Canada. 1999. Canadian Environmental Protection Act, 1999. Statutes of Canada. Ottawa: Public Works and Government Services Canada. Canada Gazette. Part III. Vol. 22, No. 3, Ch. 33. Available online at http://canadagazette.gc.ca/partIII/1999/g3-02203.pdf
Canada. 2000. Canadian Environmental Protection Act: Persistence and Bioaccumulation Regulations, P.C. 2000-348, 23 March, 2000, SOR/2000-107, Canada Gazette. Part II, vol. 134, no. 7, p. 607−612. Available from: http://canadagazette.gc.ca/partII/2000/20000329/pdf/g2-13407.pdf
Canada. Depart. of the Environment, Depart. of Health. 2006. Canadian Environmental Protection Act 1999: Notice of intent to develop and implement measures to assess and manage the risks posed by certain substances to the health of Canadians and their environment. Ottawa: Public Works and Government Services Canada. Canada Gazette. Part 1, vol. 140, no. 49, p. 4109-4116. Available from: http://canadagazette.gc.ca/partI/2006/20061209/pdf/g1-14049.pdf
Canada. Depart. of the Environment, Depart. of Health. 2007a. Canadian Environmental Protection Act, 1999: Notice of third release of technical information relevant to substances identified in the Challenge. Canada Gazette, Part I, vol. 141, no. 33., p.2375-2379. Available from:
Canada. Depart. of the Environment, Depart. of Health. 2007b. Substance Profile for The Challenge – Ethanol, 2-methoxy-, acetate (2-Methoxyethanol acetate) CAS RN 110-49-6. Available from: http://www.ec.gc.ca/substances/ese/eng/challenge/batch3/batch3_110-49-6_en.pdf
Canada. Depart. of the Environment, Depart. of Health. 2007c. Canadian Environmental Protection Act, 1999: Notice with respect to Batch 3 Challenge substances. Canada Gazette, Part I, vol. 141. no. 33, p.2379-2394. Available from: http://canadagazette.gc.ca/partI/2007/20070818/pdf/g1-14133.pdf#page=7
Carpenter CP, Pozzani UC, Weil CA, Weil CS, Nair JH, Keck GA, Smyth HF. 1956. The toxicity of butyl cellosolve solvent. AMA Arch Ind Health 14:114-31.
Carpenter CP, Smyth HF. 1946. Chemical burns of the rabbit cornea. Am J Ophthalmol 29:1363-72. [cited in ECETOC 2005b].
[CNS] Cosmetic Notification System. [Proprietary Database]. March 2008. Ottawa (ON): Health Canada.
Cordier S, Bergeret A, Goujard J, Ha MC, Aymé S, Bianchi F, Calzolari E, De Walle HEK, Knill-Jones R, Candela S, Dale I, Dananché B, de Vigan C, Fevotte J, Kiel G, Mandereau L. 1997. Congenital malformations and maternal occupational exposure to glycol ethers. Epidemiology 8:355-63.
Cordier S, Szabova E, Fevotte J, Bergeret A, Plackova S, Mandereau L. 2001. Congenital malformations and maternal exposure to glycol ethers in the Slovak Republic. Epidemiology 12:592-3.
[CTFA] The Cosmetic, Toiletry, and Fragrance Association, Inc. 2008. International Cosmetic Ingredient Dictionary and Handbook. 12th edition. Washington (DC): CFTA. Available from: http://www.cfta.gov.org
[CTFA] De Bortoli N. Knöppel H, Pecchio E, Peil A, Rogora L, Schauenburg H, Schlitt H, Vissers H. 1986. Concentrations of selected organic pollutants in indoor and outdoor air in northern Italy. Environment International 12:343-350.
De Kettenis P. 2005. The historic and current use of glycol ethers: a picture of change. Toxicol Lett 156: 5–11.
Devillers J, Chezeau A, Thybaud E, Poulsen V, Graff L, Vasseur P, Chenon P, Mouchet F, Ferrier V, Quiniou F. 2002. Toxicology Mechanisms and Methods 12:241-254.
[ECETOC] European Centre for Ecotoxicology and Toxicology of Chemicals. 2005a. The toxicology of glycol ethers and its relevance to man. Technical Report No. 95, vol. I. Brussels (BE): ECETOC.
[ECETOC] European Centre for Ecotoxicology and Toxicology of Chemicals. 2005b. The toxicology of glycol ethers and its relevance to man. Technical Report No. 95, vol. II. 4.2. Substance profile: EGMEA (CAS number: 110-49-6). Brussels (BE): ECETOC.
Environment Canada and Health Canada. 2002. Priority Substance List Assessment Report for 2-Methoxyethanol [Internet]. Ottawa (ON): Environment Canada; Health Canada. Available from: http://www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/psl2-lsp2
Environment Canada. 2008. Data for Batch 3 substances collected underCanadian Environmental Protection Act, 1999, Section71: Notice with respect to Batch 3 Challenge substances. Data prepared by: Environment Canada, Existing Substances Program.
[EQC] EQC v.2.02 model. Released May 2003. Trent University, Peterborough, Ontario. Available from: http://www.trentu.ca/academic/aminss/envmodel/
[ESIS] European Chemical Substances Information System [dataset on the Internet]. 2007. Version 5. 2-Methoxyethanol acetate, CAS No 110-49-6. European Chemical Bureau (ECB). Available from: http://ecb.jrc.it/esis/
[EC] European Commission. 1999. The rules governing cosmetic products in the European Union, Volume 1, Cosmetics legislation, Cosmetic products. Council Directive 76/768. Annex II. Euromean Commission, Enterprise Directorate-General, Pharmaceuticals and cosmetics. Available from: http://www.leffingwell.com/cosmetics/vol_1en.pdf
Feuston MH, Bodnar KR, Kerstetter SL, Grink CP, Belcak MH, Singer J. 1989. Reproductive toxicity of 2-methoxyeethanol applied dermally to occluded and nonoccluded sites in male rats. Toxicol Appl Pharmacol 100:145-61.
Foote RH, Farrel PB, Schlafer DH, McArdle MM, Trouern-Trend V, Simkin ME, Brockett CC, Giles JR, Li J. 1995. Ethylene glycol monomethyl ether effects on health and reproduction in male rabbits. Reprod Toxicol 9(6):527-39.
Goldberg ME, Haun C, Smyth HF Jr. 1962. Toxicologic implication of altered behaviour induced by an industrial vapour. Toxicol Appl Pharmacol 4:148-64. [cited in Canada 2002].
Gray RH, Corn M, Cohen R, Correa A, Hapkim R, Hou W, Shah F, Zauer H. 1993. Final report. The Johns Hopkins University retrospective and prospective studies of reproductive health among IBM employees in semiconductor manufacturing. The Johns Hopkins University. Baltimore, MD, USA. [cited in Maldonado et al. 2003].
Gross E. 1938. Methyl glycol acetate. In: Toxikologie und Hygiene der technischen Loesungsmittel. Lehmann KB, Flury F, editors. Berlin (DE): Springer-Verlag. [English version: Toxicology and hygiene of industrial solvents. King E, Smyth H, translators. Baltimore (MD): The Williams and Wilkins Company, 1943].
Guo H, Huang X, Wang X, Zhang Z. 2004. Research on a new type of oxygenate of 2-methoxyethyl acetate as a clean diesel fuel additive, Prepr. Pap.-Am. Che. Soc. Div. Pet. Chem. 49(2): 232-235.
Ha MC, Cordier S, Dananche B, Bergeret A, Mandereau L, Bruno F. 1996. Congenital malformations and occupational exposure to glycol ethers: a European collaborative case-control study. Occup Hyg 2:417-421.
Hanley TR, Young JT Jr, John JA, Rao KS. 1984a. Ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME): Inhalation fertility and teratogenicity studies in rats, mice and rabbits. Environ Health Perspect 57:7-12. [cited in Canada 2002].
Hanley TR, Yano BL Jr, Nitschke KD, John JA. 1984b. Comparison of the teratogenic potential of inhaled ethylene glycol monomethyl ether in rats, mice, and rabbits. Toxicol Appl Pharmacol 75:409-22. [cited in Canada 2002].
Hardin BD, Schuler RL, Burg JR, Booth GM, Hazelden KP, Mackenzie KM, Piccirillo VJ, Smith KN. 1987. Evaluation of 60 chemicals in a preliminary developmental toxicity test. Teratog Carcinog Mutagen 7:29-48.
Hellwig J. 1993. Study of the prenatal toxicity of 2-methoxyethanol in rats after dermal application. Unpublished report. Abstract Toxicologie. BASF AG, Ludwigshafen, Germany (No. OR53/89002). [cited in Canada 2002].
[HENRYWIN] Henry’s Law Constant Program for Microsoft Windows [Estimation Model]. 2000. Version 3.10. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: http://www.epa.gov/oppt/exposure/pubs/episuite.htm
[HPD] Household Products Database. 2007. 2-Methoxyethanol acetate. Bethesda (MD): U.S. Department of Health and Human Services, National Institutes of Health, National Library of Medicine, Toxicology Data Network. [cited 2007 Dec]. Available from: http://household products.nlm.nih.gov
[HSDB] Hazardous Substances Data Bank [database on the Internet]. 1983 – . Bethesda (MD): National Library of Medicine (US). [updated 2006 Dec 20; cited 2008 Aug. 21]. Available from: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB
[IPCS] International Programme on Chemical Safety. 1990. 2-methoxyethanol, 2-ethoxyethanol, and their acetates. Geneva (CH): World Health Organization. (Environmental Health Criteria 115). Jointly sponsored by the United Nations Environment Programme, the International Labour Organization, and the World Health Organization. Available from: http://www.inchem.org/documents/ehc/ehc/ehc115.htm
Johanson G, Rick U. 1996. Use and Use Patterns of Glycol Ethers in Sweden. Occupational Hygiene. vol.2. 105-110.
Kirk RE, Othmer DF. 1980. Encyclopaedia of Chemical Technology, 3rd Ed. Vol. 11. New York (NY): Wiley. Glycols (Ethylene and Propylene).
[KOWWIN] Octanol-Water Partition Coefficient Program for Microsoft Windows [Estimation Model]. 2000. Version 1.67. 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
Lewis RJ, Sr. 2007. Hawley's Condensed Chemical Dictionary. 15 th Edition. John Wiley & Sons. Hoboken. NJ. 530.
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(4):272-303.
Maldonado G, Delzell E, Tyl RW, Sever LE. 2003. Occupational exposure to glycol ethers and human congenital malformations. Int Arch Occup Environ Health 76(6):405-423.
Miller RR, Ayres JA, Young JT, McKenna MJ. 1983. Ethylene glycol monomethyl ether. I. Subchronic vapor inhalation study with rats and rabbits. Fundam Appl Toxicol 3:49-54.
[MITI] Ministry of International Trade & Industry. 1992. Biodegradation and Bioaccumulation Data of Existing Chemicals Based on the CSCL Japan. Chemical Products Safety Division; Basic Industries Bureau, Ministry of International Trade & Industry, Tokyo (JA): Chemicals Inspection & Testing Institute.
Nagano K, Nakayama E, Koyano M, Oobayashi H, Adachi H, Yamada T. 1979. Testicular atrophy of mice induced by ethylene glycol mono alkyl ethers. Sanyo Igaku (Jap J Ind Health) 21:29-35 [in Japanese].
Nagano K, Nakayama E, Oobayashi H, Nishizawa T, Okuda H, Yamazaki K. 1984. Experimental studies on toxicity of ethylene glycol alkyl ethers in Japan. Environ Health Perspect 57:75-84.
[NCI]. National Chemical Inventories [database. American Chemical Society, Chemical Abstract Service. Cited November 2007]. On a CD-Room. 2007. Issue I. Columbus (OH). Available from: http://pubchem.ncbi.nlm.nih.gov/
Nelson BK, Brightwell WS, Burg JR, Massari VJ. 1984. Behavioural and neurochemical alternations in the offspring of rats after maternal or paternal inhalation exposure to the industrial solvent 2-methoxyethanol. Pharmacol Biochem Behav 20:269-79.
[NPI] National Pollutant Inventory. 2005. Substance Fact Sheet. 2-Methoxyethanol Acetate. Australian Government. Department of the Environment and Water Resources. [cited January 2008] Available from: http://www.npi.gov.au/database/substance-info/profiles/56.html
[OASIS Forecast] Optimized Approach based on Structural Indices Set [Internet]. 2005. Version 1.20. Bourgas (BG): Bourgas Prof. Assen Zlatarov University, Laboratory of Mathematical Chemistry. Available from:
Osgood C, Zimmering S, Mason J. 1991. Aneuploidy in Drosophila II. Further validation of the FIX and ZESTE genetic test systems employing female Drosophila. melanogaster. Mutat Res 259:147-63.
[PCKOCWIN] Organic Carbon Partition Coefficient Program for Windows [Estimation Model]. 2000. Version 1.66. 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
[PhysProp] Interactive PhysProp Database [database on the Internet]. 2006. Syracuse (NY): Syracuse Research Corporation. Cited 2006 March. Available from: http://www.syrres.com/esc/physdemo.htm
Plieninger P, Marchl D. 1999. Proceedings of the 8th international conference on indoor air quality and climate. Vol. 4. Edinburgh, Scotland. Aug 8–13. London: Construction Research Communications LTP.
Schenker MB. 1996. Reproductive health effects of glycol ether exposure in the semiconductor industry. Occup Hyg 2:367-72.
Schenker MB, Gold EB, Beaumont JJ, Eskenazi B, Hammond SK, Lasley BL, McCurdy SA, Samuels JJ, Saiki CL, Swan SH. 1995. The association of spontaneous abortion and other reproductive effects with work in the semiconductor industry. Am J Ind Med 2(6):639-659.
Schleibinger H, Hott U, Marchl D, Braun P, Plieninger P, Ruden H. 2001.
VOC-concentrations in Berlin indoor environments between 1988 and 1999. Gefahrstoffe Reinhaltung der Luft. 61(1-2):26-38.
Scott WJ, Fradkin R, Wittfoht W, Nau H. 1989. Teratologic potential of 2-methoxyethanol and transplacental distribution of its metabolite, 2-methoxyacetic acid, in non-human primates. Teratology 39(4):363-373. [cited in Canada 2002].
Sehgal A, Osgood C. 1990. Rapid and efficient of chemically-induced aneuploidy using Drosophila females. Env Mol Mut 15:53-4. [Abstract].
Shaw GM, Velie EM, Katz EA, Morland KB, Schaff DM, Nelson V. 1999. Maternal occupational and hobby chemical exposures as risk factors for neural tube defects. Epidemiology 10:124-9.
Smialowicz RJ, Williams WC, Riddle MM, Andrews DL, Luebke RW Copeland CB. 1992. Comparative immunosuppression of various glycol ethers orally administered to Fischer 344 rats. Fundam Appl Toxicol 18:621-7.
Smyth H, Seaton J, Fisher L. 1941. The single doses toxicity of some glycols and derivatives. J Ind Hyg Toxicol 23:259-68.
Swan SH, Beaumont JJ, Hammond SK, VonBehren J, Green RS, Hallock MF, Woskie SR, Hines CJ, Schenker MB. 1995. Historical cohort study of spontaneous abortion among fabrication workers in the semiconductor health study: agent-level analysis. Am J Ind Med 28:751-769.
Swan SH, Forest W. 1996. Reproductive risks of glycol ethers and other agents used in semiconductor manufacturing. Occup Hyg 2:373-85.
[TRI] Toxics Release Inventory [database on the Internet]. 2008. TRI Explorer 4.7. Washington (DC): US Environmental Protection Agency. [cited 2007 Dec]. Available from: http://www.epa.gov/triexplorer/
[US EPA] US Environmental Protection Agency. 2005. Federal Register Environmental Documents. Volume 70, number 228. November 29, 2005. Rules and Regulations. 71401-71406. Avaliable from: http://www.epa.gov/EPA-TOX/2005/November/Day-29/t23421.htm
Verschueren K. 2001. Handbook of Environmental Data on Organic Chemicals. 4th ed. New York (NY): Van Nostrand Reinhold Co. p. 1115.
Whittacker 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.
[WHO] World Health Organization. 2003. International Chemical Safety Card: 2-Methoxyethyl acetate. ICSC: 0476. Available from: http://www.cdc.gov/niosh/ipcsneng/neng0476.html.
Yalkowsky SH, Dannenfelser RM. 1992 The Aquasol Database of Aqueous Solubility. Fifth Edition, Tucson (AZ): Univ Az, College of Pharmacy.
Yanagihara S, Shimada I, Shinoyama E, Chisaka P, Saito K. 1977. Photochemical reactivities of hydrocarbons. Proceeding of the Fourth International Clean Air Congress. p. 472-477.
Yanfeng G, Shenghua L, Hejun G, Tiegang H, Longbao Z. 2007. A new diesel oxygenate additive and its effects on engine combustion and emissions. Applied Thermal Engineering 27(1):202-207.
Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. 1992. Salmonella mutagenicity tests. V. Results from the testing 311 chemicals. Environ Mol Mutagen 19 (s 21):2-141.
Zimmermann FK, Mayer VW, Scheel I, Resnick MA. 1985. Acetone, methylethylketone, ethylacetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy in Saccharomyces cerevisiae. Mutat Res 149(3):339-51.
Appendix 1: Summary of health effects information for 2-MEA (CAS RN 110-49-6)
|Endpoint||Lowest effect levels1/Results|
|Laboratory animals and in vitro|
Lowest oral LD50 (guinea pig) = 1250 mg/kg-bw (Smyth et al. 1941)
Lowest dermal LD50 (rabbit) = 5250–5560 mg/kg-bw (Kirk-Othmer 1980)
Lowest inhalation LCLO (guinea pig and cat) = 22 000 mg/m3 (3 h) (Gross 1938)
Lowest inhalation LO(A)EC (female rat) = 32 ppm, equivalent to 154.6 mg/m3 (4 h), based on hemolysis; NO(A)EC = 16 ppm (77.3 g/m3) (Carpenter et al. 1956)
Short-term repeated-dose toxicity
Lowest oral LO(A)EL (rat) = 50 mg/kg-bw per day (the lowest dose tested, 6 male rats/dose, 2 days), based on dose-related suppression of the antibody plaque-forming cell response to trinitrophenyl-lipopolysaccharide; at higher dose levels, reduced hemagglutination titres were observed (Smialowicz et al. 1992)
Lowest inhalation LO(A)EC (cat) = 1100 mg/m3 (in total 42 hours, no further details), based on decrease in blood pigment and red blood corpuscles (Gross 1938)
No dermal short-term repeated-dose studies identified
No subchronic toxicity data identified
Chronic toxicity/ carcinogenicity
No chronic toxicity/carcinogenicity data identified
Genotoxicity and related endpoints: in vivo
Genotoxicity and related endpoints: in vitro
Saccharomyces cerevisiae D61.M, with and without activation (Zimmermann et al. 1985)
Sister chromatid exchange
Malsegregation and aneuploidy induction
Lowest oral LO(A)EL (mouse) = 500 mg/kg-bw per day (5 male mice/dose, 5 weeks, gavage); NO(A)EL = 250 mg/kg-bw per day, based on dose-related reductions in absolute testis weights and atrophy of the seminiferous epithelium and occasional proliferation of the Leydig cells (Nagano et al. 1979, 1984)
Effects at 1225 mg/kg-bw per day by gavage (the only dose tested); pregnant mice exposed on gestation days 6–13; no viable fetus born from 31 litters; dam appeared to be unaffected (Hardin et al. 1987)
No sensitization data available
Reproductive and developmental toxicity
Spontaneous abortion risk
Three studies showed that increased risk of congenital malformation was associated with maternal occupational exposure to a glycol ether mixture, including a case–control 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); a historical cohort study of US workers in the semiconductor industry (Gray et al. 1993) and a case–control study (196 cases versus 196 controls) in the Slovak Republic, similar to the study reported by Cordier et al. (1997) (Cordier et al. 2001). No information regarding the risk specifically associated with 2-MEA exposure was provided in these studies.
1 An overview of the information on the health effects associated with 2-ME is presented in the Priority Substances List assessment report (Canada 2002).
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