Screening Assessment for the Challenge Ethanol, 2-methoxy-, acetate

Chemical Abstracts Service Registry Number 110-49-6

Environment Canada
Health Canada

February 2009

Table of Contents

1. Synopsis
2. Introduction
3. Substance Identity
4. Physical and Chemical Properties
5. Sources
6. Uses
7. Releases to the Environment
8. Environmental Fate
9. Persistence and Bioaccumulation Potential
10. Potential to Cause Ecological Harm
11. Potential to Cause Harm to Human Health
12. Conclusion
13. References
14. Appendix I: Summary of health effects information for 2-MEA

Synopsis

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 (CAS RN) 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 (DSL) 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.

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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-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

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.

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Substance Identity

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.

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Physical and Chemical Properties

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

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Sources

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).

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Uses

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 (NPI2005).
 
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).

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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 (NPRI 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 (NPI2005).

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Environmental Fate

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 K_oc value estimated for 2-MEA.

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Persistence and Bioaccumulation Potential

Environmental Persistence

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-MEAhas also been reported in the presence of nitrogen oxides in smog chamber tests (Yanagihara et al. 1977).

Abbreviations: t½, half-life.

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 (HSDB2008).

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 less than 182 days, and the half-life in sediments is less than 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-MEAdoes not meet the persistence criteria for air (half-life greater than or equal to 2 days), water or soil (half-lives greater than or equal to 182 days) or sediment (half-life greater than or equal to 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.

The Modified Gobas BAF middle trophic level model for fish produced a BAFvalue 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 greater than or equal to 5000 L/kg) as set out in thePersistence and Bioaccumulation Regulations (Canada 2000).

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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).

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; NPRI2007).). 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, K_ow, K_oc and Henry's Law constant.

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Potential to Cause Harm to Human Health

Exposure Assessment

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-MEAwould 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") (ESIS2007). 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-MEvia 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).^Footnote1

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-bwper 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-MEhas 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-bwper 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 vitroclastogenicity 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 CEPA1999, 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.

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Conclusion

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 CEPA1999 (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 CEPA1999, but that it does meet the criteria in paragraph 64(c) of CEPA1999. Additionally, 2-MEA does not meet the criteria for persistence and bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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Appendix I: Summary of health effects information for 2-MEA (CAS RN 110-49-6)

Abbreviations: LC_LO, lowest lethal concentration; LD₅₀, median lethal dose.