Screening Assessment for the Challenge Ethanol, 2-(2-methoxyethoxy)-

Chemical Abstracts Service Registry Number 111-77-3

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 1. Upper-bounding estimates of daily intake of DEGME by the general population in Canada
15. Appendix 2. Upper-bounding estimates of exposure to DEGME in consumer products
16. Appendix 3. Summary of health effects information for DEGME

Synopsis

Pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Ministers of the Environment and of Health have conducted a screening assessment of ethanol, 2-(2-methoxyethoxy)- (diethylene glycol monomethyl ether, DEGME), Chemical Abstracts Service Registry Number 111-77-3. The substance DEGME was identified in the categorization of theDomestic Substances List as a high priority for action under the Ministerial Challenge. DEGME was identified as a high priority because it was considered to pose greatest potential for exposure of individuals in Canada and had been classified by the European Commission on the basis of developmental toxicity. The substance did not meet the ecological categorization criteria for persistence, bioaccumulation potential or inherent toxicity to aquatic organisms. Therefore, the focus of this assessment of DEGME relates principally to human health risks.

According to information reported under section 71 of CEPA 1999, DEGME was imported into Canada in 2006 in a quantity ranging between 1 000 000 and 10 000 000 . DEGME has various applications, including use as an additive in jet fuel and as a solvent in paints and is used in various products such as floor care products, brake fluid and some skin creams and cleansers.

Based on limited information on concentrations in environmental media and results from a survey under section 71 of CEPA 1999, exposure of the general population via the environment is expected to be low. However, exposure to DEGME by inhalation and dermal contact may occur during use of products that contain the substance. The health effects associated with exposure to DEGME are primarily developmental and reproductive toxicity and hematological effects, based on observations in experimental animals. The margins between the upper bounding estimates of dermal exposure to DEGME from consumer products, taking into consideration frequencies of use and the critical effect levels, particularly for developmental toxicity, in short-term or subchronic studies in experimental animals, may not be adequately protective. Although the margin between measured indoor air concentrations and the concentration at which no effects were observed in experimental animals (the highest concentration tested) is large, in light of the lack of an inhalation study for developmental toxicity, which appears to be the most sensitive effect, data are considered inadequate to characterize risk to health associated with exposure to DEGME by inhalation while using consumer products containing this substance.

On the basis of the potential inadequacy of the margins between conservative estimates of exposure to DEGME by dermal contact during use of consumer products and critical effect levels, particularly for developmental toxicity, in experimental animals, it is concluded that DEGME be considered a substance that is entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.

On the basis of low ecological hazard, expected releases and low environmental exposure of DEGME, 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. DEGME does not meet the criteria for persistence or bioaccumulation as set out in thePersistence and Bioaccumulation Regulations.

This substance will be included in the upcoming 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, DEGME 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 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-(2-methoxyethoxy)- (diethylene glycol monomethyl ether, referred to as DEGME), was identified as a high priority for assessment of human health risk because it was considered to present GPE and had been classified by another agency on the basis of developmental toxicity.

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

Although DEGME was determined to be a high priority for assessment with respect to human health, it did not meet the criteria for persistence, bioaccumulation potential 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.

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 October 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 Susan Griffin (US Environmental Protection Agency Region 8), 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

For the purposes of this document, this substance will be referred to as diethylene glycol monomethyl ether (DEGME).

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Physical and Chemical Properties

Table 2 summarizes the experimental and modelled physical and chemical properties of DEGME that are relevant to its environmental fate.

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Sources

DEGME does not occur naturally in the environment. It is produced by reacting ethylene oxide and methanol with an alkali catalyst (EURAR 2000).

Based on a survey conducted under section 71 of CEPA 1999, no Canadian companies reported manufacturing DEGME in a quantity greater than or equal to the 100 kg reporting threshold in 2006. However, results from the same survey and from voluntary data submitted by industry indicated that the total quantity of DEGME imported into Canada in 2006 ranged from 1 million to 10 million kilograms (Environment Canada 2008a, b). According to Chinn et al. (2007), Canadian imports of DEGME come primarily from the United States.

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Uses

According to submissions made under section 71 of CEPA 1999, the majority of DEGME is used as an additive in jet fuel (Environment Canada 2008a). It is also used as a formulant in pest control products used in various applications, including the pulp and paper industry (PMRA 2007; Environment Canada 2008a). It is used as a solvent in floor finishes, in various cleaners and degreasers and in paints (Environment Canada 2008a). In addition, DEGME is used in various other applications and settings that would not result in exposure of the general population of Canada (Environment Canada 2008a). DEGME is also used as a solvent or viscosity decreasing agent (Winter 2005; CTFA 2008) in some hairsprays, skin creams and cleansers (CNS 2008), as well as a component of fragrances (CTFA 2008). Furthermore, this substance may be used as a solvent in the manufacture of inks and can end coatings used in food contact applications. However, the potential daily intake from this latter use is considered to be negligible, as the coating is cured, resulting in evaporation of the solvent (2008 personal communication from Food Packaging Materials and Incidental Additives Section, Food Directorate, Health Canada, to Existing Substances Bureau, Health Canada; unreferenced). According to the same source, DEGME has been used in cleaners used in the food industry; however, the surfaces that come into direct contact with food must be thoroughly rinsed with potable water; as well, non-food contact surfaces (e.g., floors) must be cleaned under well-ventilated conditions. Thus, population exposure from this use is also expected to be negligible.

DEGME is also used as a chemical intermediate (Lewis 2007); as a metal solvent for mineral oil soap and mineral oil-sulfonated oil mixtures; as a solvent for dyes, nitrocellulose, resins and lacquers; for setting the twist and conditioning of yarns and cloth (EURAR 2000); as a component of hydraulic fluids (Verschueren 2001; Lewis 2007); as a solvent for solvent-based silk screen printing inks, stamp pad inks, and ballpoint and felt tip writing pen inks; as a component for pastes used in printing cellulose acetate and polyester fabrics; as a solvent and coupling agent for vat dyeing fabrics; in rust removers, aluminum brighteners and paint and varnish removers (Dow Chemical 2004); in water- and solvent-based paints and varnishes; as a component of floor cleaners, sealants and polishes; and in windshield washer fluid (EURAR 2000; HPD 2008). It is also used as a coupling agent for making miscible organic-aqueous systems and as a raw material for plasticizers (EURAR 2000). Finally, DEGME is used as a deactivator and stabilizer for agricultural formulations used before crops emerge from the soil (Dow Chemical 2004; US EPA 2006) and as a solvent for pharmaceutical manufacturing (EURAR 2000).

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Releases to the Environment

Information reported under section 71 of CEPA 1999 indicated that, in 2006, only 0.1 kg of DEGME was released to land and between 10 000 and 100 000 kg were released into water; between 10 000 and 100 000 kg were also released to air (Environment Canada 2008a). Most of the releases into air come from diffuse sources rather than from a single point source, so the resulting concentrations of DEGME in air would be low. Dispersive releases may also occur as a result of consumer and commercial uses of the substance.

Releases of DEGME are not currently reported to the National Pollutant Release Inventory (NPRI 2006) or to the US Toxics Release Inventory (TRI 2006).

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Environmental Fate

As indicated in Table 2, DEGME has a very high water solubility (1 000 000 mg/L), a moderate vapour pressure (24.0 Pa), a very low Henry's Law constant (6.59 × 10-5 Pa·m³/mol), a very low log K_ow (less than 0) and a very low log K_oc (0-0.7). These properties suggest that if DEGME were to be released into the environment, it would be expected to be found in water.

Based on its physical and chemical properties (Table 2) and the results of Level III fugacity modelling (Table 3), DEGME is expected to reside predominantly in water or in soil, depending on the compartment of release. Based on information provided above, release of this substance to soil is not typical. In addition, although there are potentially releases of DEGME to air, which could result in partitioning to soil, this substance is not persistent in soil and therefore not likely to remain in this compartment.

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Persistence and Bioaccumulation Potential

Environmental Persistence

When released into the environment, DEGME is not expected to be persistent in air, water, soil or sediment.

Modelled data for the persistence of DEGME in air and water are shown in Table 4.

Abbreviations: t½, half-life.

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 DEGME is not expected to be persistent in soil or sediment.

The weight of evidence based on the data described above indicates that DEGME does not meet the persistence criteria for air (half-life in air greater than or equal to 2 days), water or soil (half-life in water or soil greater than or equal to 182 days) or sediment (half-life in sediment 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 DEGME, presented in Table 5, indicate that DEGME does not meet the bioaccumulation criteria (bioconcentration factor (BCF), bioaccumulation factor (BAF) greater than or equal to 5000) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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Potential to Cause Ecological Harm

As indicated previously, DEGME does not meet the persistence or bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

There is modelled and experimental evidence indicating that DEGME does not cause harm to aquatic organisms at relatively low concentrations (i.e., does not exhibit acute LC₅₀/EC₅₀ values of less than or equal to 1.0 mg/L) but rather has low acute toxicity. A study on the acute aquatic toxicity of DEGME to the fish Carassius auratus resulted in an LC₅₀ of greater than 5000 mg/L (Bridié et al. 1979). This value is supported by the predictions of most models, shown in Table 6.

Environmental releases of DEGME to air and water were reported under section 71 of CEPA 1999 (see "Releases to the Environment" above). Aquatic concentrations resulting from these releases were estimated. Environment Canada's Industrial Generic Exposure Tool - Aquatic (IGETA) was employed to estimate the (worst-case) substance concentration in a generic watercourse receiving industrial effluents (Environment Canada 2008c). The generic scenario is designed to provide these estimates based on conservative assumptions regarding the amount of chemical processed and released, the number of processing days, the sewage treatment plant removal rate and the size of the receiving watercourse. However, according to the reporting company, the releases to water were actually releases to a treatment facility that is believed to remove virtually all of the substance before release into the river that receives effluent from the facility. The tool models an industrial release scenario based on loading data from sources such as industrial surveys and knowledge of the distribution of industrial discharges in the country and calculates a predicted environmental concentration (PEC). The equation and inputs used to calculate the PEC in the receiving watercourse are described in Environment Canada (2008d). Assuming a release of 6300 kg (the highest reported release to water for a facility reported under the section 71 survey), the obtained PEC was 0.7045 mg/L for point source releases.

To derive a predicted no-effects concentration (PNEC), the acute toxicity value of greater than 5000 mg/L from the Bridié et al. (1979) study cited above was divided by an assessment factor of 1000 to account for interspecies and intraspecies variability in sensitivity, to estimate a long-term no-effects concentration from a short-term LC₅₀ and to account for uncertainty in laboratory to field extrapolation. This gave a PNEC of 5 mg/L.

The resulting risk quotient (PEC/PNEC) is 0.7045/5 = 0.14. Because the risk quotient is less than 1, it is considered unlikely that industrial releases of DEGME would cause to harm to aquatic organisms.

There are also releases of DEGME to air, but the sources tend to be diffuse, and the resulting atmospheric concentrations would be low. Furthermore, the substance is not persistent in air, so it is unlikely to accumulate to levels that would cause harm to terrestrial organisms.

Based on the information available, DEGME is unlikely to be causing ecological harm in Canada.

Uncertainties in Evaluation of Ecological Risk

Quantitative structure-activity relationship (QSAR) models were used to estimate persistence and bioaccumulation. There are uncertainties associated with the use of QSAR models to estimate these characteristics. In addition, the value for K_ow, which is used as input to the QSAR models, also had to be estimated.

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Potential to Cause Harm to Human Health

Exposure Assessment

Measured concentrations of DEGME in environmental media in Canada were not available. DEGME was detected in drinking water in the United States; however, no concentration data were presented (US EPA 1984). Therefore, ChemCAN (2003) was used to predict average concentrations of DEGME in ambient air, water and soil. The amount of DEGME released and the media into which it was released were obtained from industrial data submitted through the section 71 survey (Environment Canada 2008a).

A maximum indoor air concentration of DEGME of 164 µg/m³ (mean of 0.6 µg/m³, with a detection limit of 5 µg/m³) was measured in Berlin, Germany, based on measurements from 400 rooms in 200 apartments (Plieninger and Marchl 1999). Schleibinger et al. (2001) also conducted an indoor air study in Berlin and reported a maximum indoor air concentration of 39 µg/m³ (mean of less than 5 ± 4 µg/m³, no detection limit identified) from 90 samples taken in residential homes and various public indoor environments between 1989 and 1999. The maximum value from the Schleibinger et al. (2001) study was chosen over that reported in Plieninger and Marchl (1999), as the maximum value from this latter study was much larger than the reported 95^th-percentile value of 0.4 µg/m³ and likely not a typical concentration found in indoor environments.

Appendix 1 presents upper-bounding estimates of intake of DEGME for each age group in the general population of Canada, based on the limited information listed above. The upper-bounding estimate of daily intake for the general Canadian population ranges from 6.8 µg/kg of body weight (kg-bw) per day for seniors (aged 60 years and older) to 20.5 µg/kg-bw per day for toddlers (aged 6 months to 4 years), with intakes from indoor air representing the predominant source of exposure. Exposures from ambient air, water and soil are considered negligible in comparison. These indoor air exposures likely arise as a result of the use of certain consumer products containing DEGME inside the home.

A summary of upper-bounding dermal and inhalation exposure estimates, predicted using ConsExpo software, version 4.1 (ConsExpo 2006), for users of several consumer products is presented in Tables 7 and 8, respectively. The detailed calculations for the various products, including paint, paint remover, sealants and caulking, floor cleaner, floor sealant, floor polish and brake fluid, are described in Appendix 2. A variety of other consumer products were listed in the Uses section above, such as ballpoint and felt tip pen inks and windshield washer fluid; however, insufficient data are available with which to derive estimates for all potential consumer products. In addition, these uses are expected to result in lower exposures compared with those described here.

Acute estimates are shown for products that are used infrequently (i.e., once or twice a year) throughout the year whereas chronic estimates are shown for products that are used more frequently (i.e, every day or every week).

For products used infrequently, exposure to DEGME through dermal contact is predicted to range up to approximately 11 mg/kg-bw per event (for floor sealer), whereas airborne concentrations during application could be as high as 588 mg/m³ (for paint stripper/remover). For products used more frequently, such as floor cleaners, dermal exposure is modelled to be approximately 0.19 mg/kg-bw per day, whereas airborne concentrations are predicted to be about 9 mg/m³.

DEGME is also found in some personal care products, such as skin cream, skin cleanser and hairspray (Table 9) (CNS 2008). Based on available data, aggregate dermal exposure to these products was estimated to total about 0.27 mg/kg-bw per day using the ConsExpo software, version 4.1 (ConsExpo 2006). Detailed calculations for this estimate are shown in Appendix 2. Inhalation exposure was estimated only for the hairspray scenario, as suggested by the model, and the predicted mean event concentration during use of hairspray was 0.0014 mg/m³--i.e., much lower than the concentrations from use of the products listed in Table 8.

Confidence in the exposure database is considered to be low, as only two studies were identified on concentrations of DEGME in indoor air (neither of which was from Canada), and modelling was used to determine upper-bounding estimates for ambient air, water and soil. No studies were identified regarding the presence of this substance in food. Based on the physical and chemical properties, release information and use pattern, this substance is not likely to be found in soil or food. The predicted concentrations of DEGME in environmental media presented in Appendix 1 were based on the upper end of the reporting range for releases into the environment; thus, these values likely overestimate intakes, and actual exposures are probably significantly lower. There is also low confidence in the modelled estimates of exposure from consumer products. However, as these estimates are conservative, confidence is high that actual exposure levels do not exceed these levels. In contrast, due to the possible presence of DEGME in fragrances and other personal care products in which it is used as a viscosity decreasing agent and solvent, exposure may be underestimated.

Health Effects Assessment

The available health effects information for DEGME is summarized in Appendix 3.

The European Commission has classified DEGME as a Category 3 substance, with risk phrase R63 ("possible risk of harm to the unborn child") (ESIS 2007). This classification was based on observed developmental effects, including fetal visceral and skeletal variations and/or malformations, and reduced pup survival abilities in various experimental animal species/strains after oral or dermal exposure to DEGME (EURAR 2000).

Developmental effects were observed in rodents orally exposed to DEGME. In Wistar rats, such effects included significantly increased incidence of fetal visceral variations in the thymus, delayed ossification in sternebrae and vertebrae and significantly decreased fetal body weights, in the absence of maternal toxicity, at 600 mg/kg-bw per day. At higher doses, more severe developmental effects, including significantly increased fetal resorptions, fetal visceral malformations in the cardiovascular system, higher incidence of variations in thymus and kidneys, fetal external malformations, fetal skeletal variations in ribs and vertebrae, reduced pup postnatal survival and further delayed ossification, were observed in the presence of maternal toxicity. Effects noted in dams included significantly decreased thymus weight, body weight gain and food consumption. The no-observed-(adverse-)effect levels (NO(A)ELs) for maternal toxicity and fetotoxicity were 600 and 200 mg/kg-bw per day, respectively (Yamano et al. 1993). The thymus appeared to be the most sensitive target organ in both dams and fetuses. Although the visceral malformations observed in Wistar rats were also noted in Sprague-Dawley rats following oral exposure to a comparable dose of DEGME (720 mg/kg-bw per day), more severe skeletal malformations (primarily in the ribs) were observed in the latter (Hardin et al. 1986), which suggested a strain difference. Additionally, significantly reduced pup viability was observed in orally exposed mice in the Chernoff/Kavlock assay (Schuler et al. 1984).

Dermal exposure to DEGME resulted in developmental toxicity in rabbits. At doses that did not induce maternal effects, developmental effects, including significantly delayed ossification in the fetal skull and cervical vertebrae, were observed in New Zealand White rabbits at 250 mg/kg-bw per day. At higher dose levels, a significantly increased incidence of fetal alterations, significantly delayed ossification in sternebrae and increased fetal resorptions were observed, accompanied by maternal effects, including significantly decreased red blood cell counts and packed cell volume, as well as significantly decreased body weight gain during gestation days 9-11. No developmental effects were observed at 50 mg/kg-bw per day (Dow Chemical 1983a, b; Scortichini et al. 1986).

No data on the potential developmental toxicity via inhalation exposure to DEGME were identified.

Effects on the male reproductive system induced by DEGME were observed in orally exposed rodents. Significantly reduced relative testes weights were observed at 2000 mg/kg-bw per day in a 20-day gavage study in rats (Kawamoto et al. 1990). In a 6-week gavage study in rats, testicular atrophy and altered sperm production were observed at 3600 mg/kg-bw per day, along with significantly reduced absolute and relative testes weights. No effects were observed at 900 mg/kg-bw per day (Krasavage and Vlaovic 1982). In addition, slightly reduced testicular weights were observed in mice administered 4000 mg DEGME/kg-bw per day in drinking water for 25 days (Nagano et al. 1984).

Oral administration of DEGME to experimental animals also significantly altered hematological parameters and various organ weights, such as decreased relative pituitary gland and thymus weights, along with lymphocyte depletion in the thymus cortex, and increased relative liver, kidney or heart weights (Krasavage and Vlaovic 1982; Nagano et al. 1984; Hardin et al. 1986; Kawamoto et al. 1990, 1992; Yamano et al. 1993). Upon consideration of available data, the European Commission (EURAR 2000) determined an overall oral NO(A)EL for such effects of 900 mg/kg-bw per day. No more recent data have been identified thus far to indicate any lower effect level. In the repeated dermal exposure studies in experimental animals, toxicological changes in liver and altered hematological and urinary parameters were also observed. The European Commission (EURAR 2000) established a conservative "marginal" dermal effect level (lowest dermal lowest-observed-effect level [LOEL]) of 40 mg/kg-bw per day, based on slight histopathological changes in the liver and elevated urinary calcium levels in a 13-week study in guinea pigs (Hobson et al. 1986). Additionally, effects on blood and body weight of exposed dams were observed in the above-mentioned developmental toxicity study in rabbits (lowest-observed-(adverse-)effect level [LO(A)EL] was 750 mg/kg-bw per day) (Scortichini et al. 1986). In the only available subchronic inhalation study, no exposure-related effects on body weights, organ weights, hematological analyses, clinical chemistry analyses, urinalyses and gross and histopathological examinations were observed in rats at the highest concentration tested (216 ppm, equivalent to 1060 mg/m³) for 90 days (Miller et al. 1985).

With regard to potential carcinogenicity or chronic effects of DEGME, no animal or human data are available. As to the genotoxic potential of DEGME, although the database is somewhat limited, DEGME did not show mutagenicity or clastogenicity in vitro, with or without metabolic activation, in bacteria (Ames test) (ICI 1980; BASF AG 1989) and in cultured mammalian cells (chromosomal aberration test) (Müller 1997). The European Commission stated that DEGME is not considered to be mutagenic, and the effects observed in the repeated-dose toxicity studies do not give cause for concern for its carcinogenicity (EURAR 2000).

The confidence in the toxicity dataset is moderate, as experimental data are available for developmental toxicity, reproductive toxicity, repeated-dose toxicity, genetic toxicity and acute toxicity. However, some of the studies were not performed according to current standards (EURAR 2000).

Characterization of Risk to Human Health

Based principally on the weight of evidence classification of DEGME by the European Commission as a Category 3 substance due to its developmental toxicity (ESIS 2007) and an assessment prepared by the European Union (EURAR 2000), as well as consideration of the available relevant data, the critical effects for characterization of risk to human health for DEGME are developmental and reproductive toxicity and hematological effects. Therefore, margins of exposure are derived between lowest exposure levels associated with induction of these effects and conservative estimates of population exposure to DEGME.

The principal routes of exposure to DEGME are expected to be through inhalation and dermal contact during the use of consumer products containing the substance. The maximum concentration measured in indoor air that is considered appropriate for use as a basis for characterizing risk was 39 µg/m³, based on monitoring data collected in Germany between 1989 and 1999 (Schleibinger et al. 2001). Modelling-based estimates of inhalation exposure during use of consumer products containing DEGME are much higher than this (up to 588 mg/m³ for paint remover or stripper). In experimental animal studies, no effects were observed in rats exposed to the highest concentration tested, 1060 mg/m³, for 90 days (Miller et al. 1985), and no mortality was observed in rats exposed to 200 000 mg/m³ for 1 hour or to a saturated atmosphere of DEGME for up to 8 hours (BASF AG 1960; MB Research Laboratories Inc. 1977c). A comparison between the concentration at which no effects were observed in a subchronic study, 1060 mg/m³, and the measured indoor air concentration of 39 µg/m³ results in a large margin of exposure of about 27 000. Although using some consumer products containing DEGME could result in peak levels of exposure to airborne DEGME within short time periods, in light of the lack of an inhalation study for developmental toxicity, which appears to be the most sensitive effect, data are considered inadequate for characterizing risk to health associated with exposure to DEGME via inhalation while using products containing this substance.

Dermal contact also contributes significantly to exposure to DEGME during use of some consumer products. Comparison of the highest estimate of exposure to the substance in non-cosmetic products used frequently (0.19 mg/kg-bw per day from use of floor cleaners twice a week) with a "marginal" dermal LOEL of 40 mg/kg-bw per day (EURAR 2000) for minimal effects observed in a 13-week study in guinea pigs (Hobson et al. 1986) results in a margin of exposure of about 210. For floor cleaners, less frequent use would result in lower chronic daily exposure. If the effect level for developmental toxicity is considered (i.e., LO(A)EL of 250 mg/kg-bw per day in a short-term study in rabbits; Scortichini et al. 1986) and compared with the acute per event exposure (0.68 mg/kg-bw per event), the margin of exposure for use of floor cleaners would be 370. For some other types of products used less frequently, the margins between the upper-bounding estimates of exposure to DEGME and the LO(A)EL of 250 mg/kg-bw per day for developmental effects from short-term studies would be smaller; for example, the margin between the estimated exposure of 11 mg/kg-bw per event for use of floor sealer and the LO(A)EL of 250 mg/kg-bw per day is approximately 23. For cosmetic products, based upon available data, modelled exposure estimates for use of multiple products containing the substance could reach 0.27 mg/kg bw per day (Appendix 2). Comparison of this exposure with the "marginal" LOEL of 40 mg/kg-bw per day or the LO(A)EL of 250 mg/kg-bw per day for developmental toxicity results in margins of exposure of approximately 150 or 925, respectively. In summary, the margins for dermal exposure during use of various consumer products (i.e., floor cleaners, floor sealer, latex wall paint, paint remover or stripper, caulking/sealant, floor polish and cosmetic products) may not be adequately protective of human health in light of the uncertainties in the exposure and hazard databases and the serious nature of the health effects associated with exposure to this substance (i.e., developmental toxicity).

With respect to oral exposure to DEGME, levels in drinking water and food are expected to be very low, based on available information on its properties as well as its uses and releases. Margins between predicted oral intakes in drinking water and the critical effect level in studies in orally exposed experimental animals would be very large (i.e., more than 5 orders of magnitude). Therefore, potential oral exposure to DEGME from environmental media in Canada is not expected to be of concern.

Uncertainties in Evaluation of Risk to Human Health

There is some uncertainty regarding quantification of population exposure to DEGME in the general environment, although it is expected that concentrations in environmental media are likely to be low in comparison with exposures associated with the use of consumer products. Only two German studies were identified on concentrations in indoor air, which may not reflect the Canadian situation. Estimates of exposure from the most frequently used consumer products containing DEGME were based on conservative assumptions and may overestimate actual exposure. However, there is uncertainty with some of the parameters used for the paint and floor cleaner scenarios, such as whether DEGME is actually found in consumer products at the levels presented and the frequency of use in Canada. In addition, there is also some uncertainty associated with the potential exposures from the use of multiple products containing DEGME within a short period of time. Furthermore, there is uncertainty regarding the possible presence of DEGME in fragrances and other personal care products in which it is used as a viscosity decreasing agent and solvent, and actual exposure from use of such products may be significantly greater than that presented in Appendix 2. There is some uncertainty regarding the differences in sensitivity between experimental animals and humans in view of the paucity of epidemiological data, although the critical effects observed in laboratory studies are considered likely relevant to humans, as they are consistent with those reported for other glycol ethers. In addition, there is uncertainty with respect to the carcinogenicity of DEGME due to the lack of long-term studies, although the available information from genotoxicity tests and data on other glycol ethers do not give cause for concern. As well, there is some uncertainty with regard to the potential of DEGME to induce effects via inhalation, particularly developmental effects.

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Conclusion

Based on the information presented in this screening assessment, it is concluded that DEGME 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 upon the potential inadequacy of the margins of exposure between conservative estimates of exposure to DEGME during use of consumer products via dermal contact and critical effect levels, particularly for developmental toxicity, in experimental animals, it is concluded that DEGME should be considered as a substance that is 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 DEGME does not meet the criteria in paragraph 64(a) or 64(b) of CEPA 1999, but it does meet the criteria in paragraph 64(c) of CEPA 1999. Additionally, DEGME does not meet the criteria for persistence or bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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References

[ACD] Advanced Chemistry Development. 2007. Calculated values using Advanced Chemistry Development (ACD/Labs) Software V9.04 for Solaris (c1994-2007), presented in SciFinder database, searched July 25, 2007.

[AIES] Artificial Intelligence Expert System. 2003-2005. Version 1.25. Ottawa (ON): Environment Canada. Model developed by Stephen Niculescu. Available from: Environment Canada, Existing Substances Division, New Substances Division, Ottawa, K1A 0H3.

[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. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Arnot JA, Gobas FA. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR Comb Sci [Internet] 22(3): 337-345. [restricted access] http://www3.interscience.wiley.com/journal/104557877/home_

BASF AG. 1960. Abeilung Toxilologie (unpublished data) x/284, 29.9.60, cited in VCI, BASF, Hoechst Existing substances data for the review of effects on man and environment. Band 9 1992. [cited in EURAR 2000].

BASF AG. 1989. Diethylene glycol monomethyl ether. Ames test (standard plate test and pre-incubation test with Salmonella typhimurium). Report/Project 40M0745/884379 (22.2.89). Abt. Toxikologie. BASF, Ludwigshafen, Germany [cited in ECETOC 2005].

[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. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

[BG Chemie] Die Berufsgenossenschaft der chemischen Industrie. 1995. Toxicological Evaluations. Potential Health hazards of existing Chemicals. Vol. 8. p 81-110: Diethylene glycol monomethyl ether. Springer-Verlag, Heidelberg, Germany.

[BIBRA] TNO BIBRA International Ltd. 1997. Toxicity Profile: Diethylene glycol monomethyl ether. Information and advisory service. Surrey, UK.

[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. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Boethling RS, Howard PH, Beauman JA, Larosche ME. 1995. Factors for intermedia extrapolations in biodegradability assessment. Chemosphere 30(4):741 - 752.

Bridié A, Wolff C, Winter M. 1979. The acute toxicity of some petrochemicals to goldfish. Water Research 13:623 - 626.

Browning E. 1965. Toxicity and Metabolism of Industril Solvents. Elsevier [cited in BIBRA 1997].

Bury D. 1997. Mehtyl Carbitol Solvent. Testing for sensitizing properties in the Pirbright-White guinea pig in the maximization test. Unpublished report no. 96.0683 d.d. 27-01-1997 from Hoechst marion Roussel, Preclinical Development Germany, Drug Safety, Frankfurt am Main, Germany = [cited in EURAR 2000].

Canada. 1999. Canadian Environmental Protection Act, 1999. S.C., 1999, c. 33, Canada Gazette. Part III. vol. 22, no. 3. 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. http://canadagazette.gc.ca/partII/2000/20000329/pdf/g2-13407.pdf

Canada. Dept. of the Environment, Dept. of Health. 2006. Canadian Environment 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. http://canadagazette.gc.ca/partI/2006/20061209/pdf/g1-14049.pdf

Canada, Dept. of the Environment. 2007. Canadian Environmental Protection Act, 1999: Notice with respect to Batch 3 Challenge substances. Canada Gazette, Part I, vol. 141, no. 33, p. 2379-2394. http://canadagazette.gc.ca/partI/2007/20070818/pdf/g1-14133.pdf

Carpenter CP, Smyth HF. 1946. Chemical burns of the rabbit cornea. Am J Ophthalmol 29:1363-72. [cited in ECETOC 2005].

ChemCAN [Level III fugacity model of 24 regions of Canada]. 2003. Version 6.00. Peterborough (ON): Trent University, Canadian Centre for Environmental Modelling and Chemistry. http://www.trentu.ca/academic/aminss/envmodel/models/CC600.html

Chinn H, Löchner U, Liu J, Mori H. 2007. CEH Marketing Research Report: Glycol Ethers. Chemical Economics Handbook. SRI Consulting.

[CNS] Cosmetic Notification System [Proprietary database]. 2008. Available to Health Canada, Cosmetics Division.

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

[CTFA] The Cosmetic, Toiletry, and Fragrance Association. 2008. International cosmetic ingredient dictionary and handbook. 12^th ed. Washington (DC): CTFA. [restricted access] http://www.ctfa-gov.org/

Daubert TE, Danner RP. 1989. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington (DC): Taylor and Francis.

Dow Chemical. 1954. Biochemical research laboratory. Results of range finding toxicological tests on diethylene glycol monomethyl ether. EPA/OTS 0520309. [cited in BG Chemie 1995]

Dow Chemical. 1983a. Toxicology Research Laboratory, Health and Environmental Sciences. USA. Dermal teratology methods development study in rabbits using diethylene glycol monomethl ether. Report No. EPA/OTS 0520310.

Dow Chemical. 1983b. Toxicology Research Laboratory, Health and Environmental Sciences. USA. Diethylene glycol monomethyl ether (DEGME): dermal teratology probe study in rabbits. On behalf of the Chemical Manufacturers Association. Report No. EPA/OTS 0520312.

Dow Chemical. 2004. Product information: Methyl carbitol, diethylene glycol monomethyl ether [Internet]. Midland (MI): The Dow Chemical Company. 2 p. Form No. 110-00625-0304. [cited 2007 Oct]. http://www.dow.com/PublishedLiterature/dh_005c/0901b8038005c62b.pdf?filepath=oxysolvents/pdfs/noreg/110-00625.pdf&fromPage=GetDoc

[ECETOC] European Centre for Ecotoxicology and Toxicology of Chemicals. 2005. The toxicology of glycol ethers and its relevance to man. Technical report No. 95, vol II. 4.4. Substance profile: DEGME (CAS number: 111-77-3). Brussels (BE).

[ECOSAR] Ecological Structural Activity Relationships [Internet]. 2004. Version 0.99h. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Environment Canada. 2008a. 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.

Environment Canada. 2008b. Voluntary submission of data for Batch 3 substances collected under the Chemical Management Plan Challenge initiative. Data prepared by: Environment Canada, Existing Substances Division.

Environment Canada. 2008c. Guidance for conducting ecological assessments under CEPA, 1999: science resource technical series, technical guidance module: the Industrial Generic Exposure Tool - Aquatic (IGETA). Working document. Gatineau (QC): Environment Canada, Existing Substances Division.

Environment Canada. 2008d. IGETA report: CAS RN 111-77-3, 2008-01-16. Unpublished report. Gatineau (QC): Environment Canada, Existing Substances Division.

[EQC] Equilibrium Criterion Model. 2003. Version 2.02. Peterborough (ON): Trent University, Canadian Environmental Modelling Centre. http://www.trentu.ca/academic/aminss/envmodel/models/EQC2.html_

[ESIS] European Chemical Substances Information System. [database on the Internet] 2007. Version 5. European Chemical Bureau (ECB). http://ecb.jrc.it/esis/

[EURAR] European Union Risk Assessment Report: CAS: 111-77-3: 2-(2-Methoxyethoxy)ethanol [Internet]. 2000. Luxembourg: Office for Official Publications of the European Communities. Report No.: EUR 18999 EN. [cited 2007 Oct]. 106 p. On the cover, European Commission Joint Research Centre. http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/degmereport005.pdf

[GE] GE Silicones. 2003. Material Safety Data Sheet: Caulking [Internet]. New Smyrna Beach (FL): GE Silicones, GESA Daytona Plant. [cited 2008 June]. http://www.appliednrg.com/uploads/GE_3500_CLEAR.pdf

Gingell R, Boatman RJ, Bus JS, Cawley TJ, Knaak JB, Krasavage WJ, Skoulis NP, Stack CR, Tyler TR. 1994. Chapter thirty-one: glycol ethers and other selected glycol detivatives. In Clayton GD, Clayton FE (Eds.) Patty's Ind Hyg and Toxicol. 4 th edition. Vol. II part D, p2761-2966.. New York (NY): John Wiley and Sons Inc.

Hardin BD, Goad PT, Burg JR. 1986. Developmental toxicity of diethylene glycol monomethyl ether (diEGME). Fund Appl Toxicol 6:430-439.

Health Canada. 1995. Investigating human exposure to contaminants in the environment: A handbook for exposure calculations. Ottawa (ON): Health Canada, Great Lakes Health Effects Program.

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

Hine J, Mookerjee PK. 1975. The intrinsic hydrophilic character of organic compounds. Correlations in terms of structural contributions. J Org Chem 40:292-298.

Hobson DW, D'Addario AP, Bruner RH, Uddin DE. 1986. A subchronic dermal exposure study of diethylene glycol monomethyl ether and ethylene glycol monomethyl ether in the male guinea pig. Fund Appl Toxicol 6:339-348.

[HPD] Household Products Database [database on the Internet]. 2008. Bethesda (MD): National Library of Medicine (US). [revised 2008 Apr 23; cited 2008 May]. http://hpd.nlm.nih.gov/cgi-bin/household/brands?tbl=chem&id=258&query=111-77-3&searchas=TblChemicals

[ICI] Imperial Chemical Industries PLC. 1980. Short-term carcinogen test report on methyldigol. Y00573/002. [cited in EURAR 2000].

Karaman MI, Gürdal M, ö ztürk M, Kanberoglu H. 2002. Maternal exposure to diethylene glycol monomethyl ether: a possible role in the etiology of retrocaval ureter. J Pediatr Surg 37 (8):E23.

Kawamoto T, Kodama Y. 1989. Effects of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on organ weights and hepatic metabolizing enzymes. J Toxicol Sci 14: 332 (abstract).

Kawamoto T, Matsuno K, Kayama F, Hirai M, Arashidani K, Yoshikawa M, Kodama Y. 1990. Acute oral toxicity of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether. Bull Environ Contam Toxicol 44: 602-608.

Kawamoto T, Matsuno K, Kayama F, Hirai M, Arashidani K, Yoshikawa M, Kodama Y. 1991. Induction of -GTP by ethylene glycol monomethyl ether. Toxicol Ind Health 7: 473-478. [cited in BG Chemie 1995].

Kawamoto T, Matsuno K, Kayama F, Arashidani K, Yoshikawa M, Kodoma Y. 1992. The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic -glutamyl transpeptidase. Toxicology 76: 49-57.

Kesten HD, Mulions MG, Pomerantz L. 1939. Pathologic effects of certain glycols and related compounds. Arch Pathol 27:447-65. [cited in BG Chemie 1995].

Kligman Am. 1972. Reported to RIFM. Monographs on Fragrance Raw Materials: Diethylene glycol monomethyl ether. [cited in Opdyke DLJ 1974].

[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. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Krasavage WJ, Terhaar CJ. 1981. Eastman Kodak Company. Corporate Health and Environment Laboratories, report No. TX-81-16, February 17, unpublished data. [cited in Gingell et al., 1994].

Krasavage WJ, Vlaovic MS. 1982. Comparative toxicity of nice glycol ethers: III. Six weeks repeated dose study. Health, Safety and Human factors Laboratory Report. 134780Q. Kingsport, TN : Eastman Chemical Company,. [cited in EURAR 2000].

Lewis RJ, Sr. 2007. Hawley's Condensed Chemical Dictionary. 15^th Edition. New York : Wiley-Interscience. p. 419.

MB Research Laboratories Inc. 1977a. Report on oral LD₅₀ in rats. Project number MB 77-1817. On behalf of Olin Chemicals. Report No. EPA/OTS 0516703.

MB Research Laboratories Inc. 1977b. Acute dermal toxicity in rabbits. Project number MB 77-1817. On behalf of Olin Chemicals. Report No. EPA/OTS 0516703.

MB Research Laboratories Inc. 1977c. Inhalation toxicity in rats. Project number MB 77-1817. On behalf of Olin Chemicals. Report No. EPA/OTS 0516703.

MB Research Laboratories Inc. 1977d. Report on rabbit eye irritation. Project number MB 77-1817. On behalf of Olin Chemicals. Report No. EPA/OTS 0516703.

Miller RR, Eisenbrandt DL, Gushow TS, Weiss SK. 1985. Diethylene glycol monomethyl ether 13-week vapour inhalation toxicity study in rats. Fund Appl Toxicol 5(6):1174-1179.

Müller W. 1997. Methyl carbitol solvent. In vitro mammalian chromosome aberration test in V79 Chinese hamster cells. Unpublished report no. 96.1065 dated 23-01-1997. Frankfurt am Main (DE): Hoechst AG, Hoechst Marion Roussel, Preclinical Development Germany, Drug Safety. [cited in EURAR 2000].

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 on a CD-ROM]. 2007. Issue 1. Columbus (OH): American Chemical Society, Chemical Abstracts Service. [cited 2007 Nov]. http://www.cas.org/products/cd/nci/require.html

[NHW] Department of National Health and Welfare. 1990. Present patterns and trends in infant feeding in Canada. Ottawa (ON):NHW. Catalogue No. H39-199/1990E. ISBN 0-662-18397-5. 9 p. [Cited in EHD 1998].

[NIOSH] The National Institute for Occupational Safety and Health. 1996. Registry of Toxic Effects of Chemical Substances. Cincinnati (OH). US DHHS. Silver Platter, Chem-Bank, October 1996. [cited in BIBRA 1997].

[NPRI] National Pollutant Release Inventory [database on the Internet]. 2006. Gatineau (QC): Environment Canada. http://www.ec.gc.ca/pdb/querysite/query_e.cfm

[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. http://oasis-lmc.org/?section=software

Opdyke DLJ. 1974. Monographs on fragrance raw materials: Diethylene glycol monomethyl ether. Food Cosmet Toxicol 12: 517-518.

Pastushenko TV, Golka NV, Knoderatyuk VA, Pereima VY. 1985. Study on the skin irritant and sensitizing effect of diethylene glycol monomethylether. Gig Sanit 10:80-1. [cited in BG Chemie 1995].

[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. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

[PhysProp] Interactive PhysProp Database [database on the Internet]. 2006. Syracuse (NY): Syracuse Research Corporation. [Cited 2007 Oct] http://www.syrres.com/esc/physdemo.htm

Plieninger P, Marchl D. 1999. Occurrence of ester and ether derivatives of polyvalent alcohols in indoor air of 200 Berlin households. Indoor Air 99: Proceedings of the 8 th International Conference on Indoor Air Quality and Climate vol. 4, p. 171-176.

[PMRA] Pest Management Regulatory Agency. 2007. Regulatory Note REG2007-04: PMRA list of formulants [Internet]. Ottawa (ON): Health Canada, Pest Management Regulatory Agency. http://www.pmra-arla.gc.ca/english/pdf/reg/reg2007-04-e.pdf

Reckitt Benckiser. 2004. Material Safety Data Sheet: Perk Floor Cleaner & Polish [Internet]. Parsippany (NJ): Reckitt Benckiser North America, Inc. [cited 2008 Dec]. http://msds.reckittprofessional.com/customer_services/msds/dist/05824_r.pdf

Reckitt Benckiser. 2005. Material Safety Data Sheet: Mop & Glo® Triple Action Floor Shine Cleaner [Internet]. Parsippany (NJ): Reckitt Benckiser North America, Inc. [cited 2008 Dec]. http://msds.reckittprofessional.com/customer_services/msds/dist/0041250_r.pdf

Riddick JA, Bunger WB, Sakano TK. 1985. Techniques of chemistry, vol. II. Organic solvents. 4^th ed. New York (NY): John Wiley and Sons.

[RIVM] Rijksinstituut voor Volksgezondheid en Milieu. 2006a. Cosmetics fact sheet: To assess the risks for the consumer. Updated version for ConsExpo 4 [Internet]. Bilthoven (NL): RIVM (National Institute for Public Health and the Environment). Report No.: 320104001/2006. [cited 2008 Dec]. http://www.rivm.nl/bibliotheek/rapporten/320104001.pdf

[RIVM] Rijksinstituut voor Volksgezondheid en Milieu. 2006b. Cleaning products fact sheet: To assess the risks for the consumer [Internet]. Bilthoven (NL): RIVM (National Institute for Public Health and the Environment). Report No: 320104003/2006. [cited 2008 Dec]. http://www.rivm.nl/bibliotheek/rapporten/320005003.pdf

[RIVM] Rijksinstituut voor Volksgezondheid en Milieu. 2007a. Paint products fact sheet: To assess the risks for the consumer. Updated version for ConsExpo 4 [Internet]. Bilthoven (NL): RIVM (National Institute for Public Health and the Environment). Report No: 320104008/2007. [cited 2008 Dec]. http://www.rivm.nl/bibliotheek/rapporten/320104008.pdf

[RIVM] Rijksinstituut voor Volksgezondheid en Milieu. 2007b. Do-it-yourself products fact sheet: To assess the risks for the consumer [Internet]. Bilthoven (NL): RIVM (National Institute for Public Health and the Environment). Report No.: 320104007/2007. [cited 2008 Dec]. http://www.rivm.nl/bibliotheek/rapporten/320104007.pdf

Schleibinger H, Hott U, Marchl D, Braun P, Plieninger P, Ruden H. 2001. VOC-concentrations in Berlin indoor environments between 1988 and 1999. Gefahrstoffe Reinhalt Luft 61(1-2): 26-38.

Schuler RL, Hardin BD, Niemeier RW, Booth G, Hazelden K, Piccirillo V, Smith K. 1984. Results of testing fifteen glycol ethers in a short-term in vivo reproductive toxicity assay. Environ health Perspect 57:141-6.

Scortichini BH, John-Greene JA, Quast JF, Rao KS. 1986. Teratologic evaluation of dermally applied diethylene glycol monomethyl ether in rabbits. Fund Appl Toxicol 7:68-75.

Sherwin-Williams. 2008. Material Safety Data Sheet: All surface enamel-latex high gloss, black [Internet]. Cleveland (OH): The Sherwin-Williams Company. [cited 2008 Dec]. http://www.sherlink.com/sher-link/temp/msds/640326039.pdf

Smialowicz RJ, Williams WC, Riddle MM, Andrews DL, Luebke RW. 1992. Comparative immunosuppression of various glycol ethers administered to Fischer 344 rats. Fundam Appl Toxicol 18: 621-627.

Smyth HF, Carpenter CP. 1948. Further experience with the range-finding test in the industrial toxicology laboratory. J Ind Hyg 30:63-8 [cited in ECETOC TR 95, 2005].

Smyth HF, Seaton J, Fishcher L. 1941. The single dose toxicity of some glycols and derivatives. J Ind Hyg toxicol 23:259-268. cited in EURAR 2000].

[TOPKAT] Toxicity Prediction Program [Internet]. 2004. Version 6.2. San Diego (CA): Accelrys Software Inc. http://www.accelrys.com/products/topkat/index.html

[TRI] Toxic Release Inventory Program [Internet]. 2006. Washington (DC): US Environmental Protection Agency. http://www.epa.gov/triexplorer/

Union Carbide. 1967. Data sheet, cited in NIOSH 1996. [cited in BIBRA 1997].

Union Carbide Corporation. 1984. "Methyl Carbitol: acute toxicity and primary irritancy studies" Bushy Run Research Centre. Project Report 47-1-1. Union Carbide Corporation, Danbury CT. [cited in EURAR 2000].

[US EPA] United States Environmental Protection Agency. 1984. GC/MS Analysis of organics in drinking water concentrates and advanced waste treatment concentrates: volume 1. Analysis results for 17 drinking water, 16 advanced waste treatment and 3 process blank concentrates. Research Triangle Park (NC): US Environmental Protection Agency, Health Effects Research Laboratory. 303 p. Report No. EPA-600/1-84-020a.

[US EPA] United States Environmental Protection Agency. 1986. Standard scenarios for estimating exposure to chemical substances during use of consumer products, vol 1 & 2. Washington (DC): prepared for the US EPA, Office of Toxic Substances, Exposure Evaluation Division, by Versar, Inc. Contract no. 68-02-3968.

[US EPA] United States Environmental Protection Agency. 2006. Reassessment of 3 tolerance exemptions for ethylene glycol, diethylene glycol, and the combination of diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and diethylene glycol monobutyl ether [Internet]. Washington (DC): Office of Prevention, Pesticides, and Toxic Substances. 19 p. [published 2006 Jun 29; cited 2007 Oct]. http://www.epa.gov/opprd001/inerts/glycolethers.pdf

Verschueren K. 2001. Handbook of environmental data on organic chemicals. Volume 1. 4^th Edition. New York: Wiley. p.849.

Winter R. 2005. A consumer's dictionary of cosmetic ingredients: complete information about the harmful and desirable ingredients found in cosmetics and cosmeceuticals. 6 th Edition. New York : Three Rivers Press. p. 347.

Yamano T, Noda T, Shimizu M, Moriata S, Nagahama M. 1993. Effects of diethylene glycol monomethyl ether on the pregnancy and postnatal developments in rats. Arch Environ Contam Toxicol 24(2): 228-35.

[ZEP] ZEP Commercial. 2007. Material Safety Data Sheet: Stain Resistant Floor Sealer [Internet]. Cartersville (GA): ZEP Commercial. [cited 2008 Jun]. http://www.zepcommercial.com/msds/ZU2018.pdf

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Appendix 1. Upper-bounding estimates of daily intake of DEGME by the general population in Canada

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Appendix 2. Upper-bounding estimates of exposure to DEGME in consumer products

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Appendix 3. Summary of health effects information for DEGME