ARCHIVED - Draft Assessment for Ethylene Glycol

Canadian Environmental Protection Act, 1999

Priority Substances List Assessment Report
Follow-up to the State of Science Report, 2000

Environment Canada
Health Canada

December 2007

Update:

Publication of Final Decision on the Assessment of a Substance -- Ethylene Glycol, CAS No. 107-21-1

And

Follow-up to the State of Science Report, 2000 - Ethylene Glycol, April 2010

Table 1: Chemical and physical properties of ethylene glycol
Table 2: Ethylene glycol releases from all reporting sources (NPRI 1994 - 2005)
Table 3: Untreated ethylene glycol releases, by compartment, all sources (NPRI, 1994 - 2005)
Table 4: Ethylene glycol releases from airports
Table 5: Summary statistics of concentrations of ethylene glycol in stormwater released from Canadian airports in selected years
Table 6: Direct toxicity risk quotients for exposure of algae to ethylene glycol
Table 7: Direct toxicity risk quotients for exposure of amphibians to ethylene glycol
Table 8: Indirect toxicity risk quotients for exposure of aquatic biota to ethylene glycol
Table 9: Upper-bounding estimates of daily intake of ethylene glycol by the general population of Canada
Table 10: Upper-bounding estimates of daily intake of ethylene glycol by a highly exposed population in the immediate vicinity of an industrial point source
Table 11: Upper-bounding estimates of exposure to ethylene glycol from use of consumer products
Table 12: Benchmark dose (BMD) values for key toxicity studies: Gaunt et al. (1974), Depass et al. (1976), Neeper-Bradley et. al. (1995), Cruzan et al. (2004) and ACC (2005)
Table 13: Maternal and developmental effects in CD-1 mice from nose-only exposure to ethylene glycol during gestation days 6-15 (Tyl, et al. 1995)
Table 14: Concentration of ethylene glycol in groundwater sampled at Canadian airports
Table 15: Concentrations of total glycol sampled at selected monitoring stations of Canadian airports for the 2004/2005 deicing season

Figure 1: Chemical Structure of Ethylene Glycol
Figure 2: Frequency Distribution of Glycol Concentrations in Airport Stormwater
Figure 3: Untreated Glycol Releases -- All Sources

ADAF

aircraft de-icing and anti-icing fluids

ATAC

Air Transport Association of Canada

ACC

American Chemistry Council

BMD₀₅

benchmark dose₀₅

CAS

Chemical Abstracts Service

CCME

Canadian Council of Ministers of the Environment

CCSPA

Canadian Consumer Speciality Products Association

CEPA 1999

Canadian Environmental Protection Act, 1999

COM

calcium oxalate monohydrate

CTV

critical toxicity value

DO

dissolved oxygen

EEV

estimated environmental value

ENEV

estimated no-effect value

F-344

Fischer 344 rats

GA

glycolic acid

GMP

glycol mitigation plan

GOMP

glycol operational management plan

HPT

human proximal tubule

kg-bw

kilogram-body weight

95% LCL

lower 95% confidence limit

LOAEL

lowest-observed-adverse-effect level

LOEL

lowest-observed-effects level

NOAEL

no-observed-adverse-effect level

NOEL

no-observed-effect level

OX

oxalic acid

PT

proximal tubule

PTSs

proximal tubular segments

PSL2

second Priority Substances List

PBPK

physiologically-based pharmacokinetic model

SoS Report

State of the Science; short for “Canadian Environmental Protection Act, 1999: Priority Substances List State of the Science Report for Ethylene Glycol”

TC

tolerable concentration

TI

tolerable intake

USEPA

United States Environmental Protection Agency

Ethylene glycol was included on the Priority Substances List (PSL) under the Canadian Environmental Protection Act (CEPA) to assess the potential environmental and human health risks posed by the exposure to ethylene glycol in consumer products and the environment.

In December 2000, the second Priority Substances List (PSL2) assessment of ethylene glycol was formally suspended due to the uncertainties associated with the human effect and exposure data set. At the same time, a state of the science report (Environment Canada and Health Canada 2000) on ethylene glycol was released, providing an in depth review of the toxicity and exposure information related to human health and the environment. The essential information needed to complete the PSL2 assessment was identified and acquired during the subsequent seven years.

Ethylene glycol is primarily used as a component of de-icer and anti-icer/antifreeze fluid used in aircraft de-icing and anti-icing operations, and as an anti-freeze component in motor vehicles. It is also used in manufacturing polyester products. Ethylene glycol is present as a slow-evaporating solvent and/or freeze-thaw stabilizer in latex paints. Ethylene glycol can also be used in a variety of other products such as floor and wall adhesives, brake fluid, automotive wax/polish and floor wax/polish. In 2001, approximately 1440 kt of ethylene glycol were manufactured in Canada by three companies in Alberta. Most Canadian glycol production is destined for export.

With regard to the environment, the highest reported releases of ethylene glycol to the environment are to land from aircraft deicing/anti-icing operations, with subsequent release to the aquatic environment. However, in recent years, management practices at Canada’s major airports have improved with the installation of new ethylene glycol application and mitigation facilities or improvements to existing ones.

The direct comparison of exposure concentrations measured in the aquatic environment with the estimated no-effect values (ENEVs) suggests that adverse effects are unlikely when consideration is given to the seasonal nature of releases, ambient temperatures, metabolic rates and duration of exposure. Furthermore, examination of potential indirect effects through oxygen depletion suggests a low potential for concentrations of dissolved oxygen (DO) to drop to levels of concern. As such, it is proposed that ethylene glycol 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 constitutes, or may constitute a danger to the environment on which life depends.

With regard to human health, upper-bounding estimates of daily intake of ethylene glycol by the general population of Canada, and by a highly exposed population in the immediate vicinity of an industrial point source, are well below tolerable intake (TI), derived based on a Benchmark Dose calculated for non-neoplastic renal effects in animals and an uncertainty factor. "Tolerable intake" is the level of intake to which it is believed a person may be exposed daily over a lifetime without deleterious effect. However, conservative estimates of short-term indoor air concentrations that individuals, including children, may be exposed to from use of certain consumer products containing this substance (latex paint), exceeds the Tolerable Concentration (the concentration to which it is believed a person may be exposed without deleterious effect) considered appropriate for short-term exposures. The Tolerable Concentration was based on a no-observed-adverse-effect-level for developmental effects in animals and an uncertainty factor. Given the uncertainties in estimates of short-term concentrations that individuals, including children, may be exposed to, and the nature of the health effect, it is considered appropriate to apply precaution when characterizing risk. It is proposed, therefore, that ethylene glycol is entering the environment in a quantity or concentration or under conditions that may constitute a danger to human life or health.

Based on the information available for human health and the environment, it is thus proposed that ethylene glycol be considered "toxic" as defined in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999).

Additional characterization of the range and distribution of concentrations of ethylene glycol in certain consumer products (latex paint) currently available in Canada, as well as human exposure (inhalation, dermal contact) to ethylene glycol from use of these consumer products is considered a priority for risk management. Furthermore, information to reduce uncertainty regarding absorption of ethylene glycol through the skin from use of consumer products containing this substance would be valuable. Further information on interspecies and intraspecies toxicokinetics and toxicodynamics would be useful in determining whether data-derived values could replace components of the interspecies and intraspecies uncertainty factors.

Ethylene glycol was added in 1995 to the second Priority Substances List (PSL2) under the Canadian Environmental Protection Act (CEPA) to assess the potential environmental and human health risk posed by the exposure to ethylene glycol in the environment and consumer products.

The PSL2 assessment of ethylene glycol was formally suspended in December 2000 due to the uncertainties associated with the human effect and exposure data set. At the same time, a state of the science report (SoS report) (Environment Canada and Health Canada 2000) on ethylene glycol was released, providing an in-depth review of the available toxicity and exposure information related to human health and the environment. A large number of uncertainties were identified in the SoS Report and Health Canada was unable to determine whether EG was toxic or capable of becoming toxic to the general population in Canada. The SoS Report stated that information on concentrations of ethylene glycol present in consumer products in Canada, dose-response results for renal effects of ethylene glycol based on a chronic animal study, and information on the intake of ethylene glycol by individuals living in the vicinity of industrial point sources were essential for the completion of the human health assessment. Furthermore, the SoS Report concluded that harmful environmental effects were unlikely to result from exposure to ethylene glycol in Canada.

However, effects related to the depletion of dissolved oxygen (DO) levels in receiving waters were possible near some Canadian airports a very small percentage of the time under conditions of maximum loading. It was therefore recommended that efforts to reduce releases of ethylene glycol during aircraft deicing/anti-icing operations continue to be strengthened with the aim of reducing further the instances when ethylene glycol concentrations in stormwaters exceed the CEPA Part IV guideline of 100 mg total glycol/L.

The essential information needed to complete the PSL2 health assessment was identified and acquired during the ensuing seven years, and is included in this report.

External peer-review of a draft of the human health component of this document was coordinated by Toxicology Excellence in Risk Assessment (TERA). In addition, Dr. Douglas C. Wolf, U.S. Environmental Protection Agency provided expert advice on endpoint selection for key dietary toxicity studies. Mike Walker, Health Canada,provided biostatistical expertise. External peer-review of a draft of the ecological component of this document was undertaken by Saleem Sattar, Manager, Environmental Protection, Environmental Programs, Transport Canada and by Jonathan Farley, Manager, Environmental Protection, Client and Internal Services, Transport Canada.

• 2.1 Identity and Physical/Chemical Properties
• 2.2 Entry Characterization
• 2.2.1 Production, Importation and Use
• 2.2.2 Sources and Releases
• 2.3 Environmental Fate

2.1 Identity and Physical/Chemical Properties

Ethylene glycol (CAS No. 107-21-1) belongs to the simplest group of organic chemicals of the chemical family of glycols, which are characterized by two hydroxyl (OH) groups at adjacent positions in a hydrocarbon chain (see Figure 1).

Figure 1: Chemical Structure of Ethylene Glycol

The physical and chemical properties of ethylene glycol, also known as monoethylene glycol and 1,2-ethanediol, are presented in Table 1. Ethylene glycol is a clear, colourless, odourless, relatively non-volatile, viscous liquid (Nielsen et al., 1993). It has a sweet taste and imparts a warming sensation to the tongue when swallowed (Beasley and Buck, 1980). Ethylene glycol has a relatively low vapour pressure (7-12 Pa at 20°C) (Verschueren, 1983; Howard, 1990) and a low Henry's Law constant of 5.8 × 10^-6 to 6.0 × 10^-3 Pa·m³/mol (Hine and Mookerjee, 1975; Howard, 1990). It is completely miscible in water (Canada, 1985; Budavari et al., 1989). It is very hygroscopic and will absorb up to 200% of its weight in water at 100% relative humidity (Budavari et al., 1989). The octanol/water partition coefficient of ethylene glycol is very low (i.e., log K_ow = -1.36) (Verschueren, 1983; Budavari et al., 1989; Howard, 1990).

2.2 Entry Characterization

2.2.1 Production, Importation and Use

In 2001, there were three companies (in four locations, all in Alberta) manufacturing ethylene glycol in Canada: Alberta & Orient Glycol (Prentiss, AB), Dow Chemical Canada (in Fort Saskatchewan, AB and Prentiss, AB), and Shell Chemical (in Scotford AB) (CIS, 2003). The total annual production in 2001 from these three companies was 1,440 kilotonnes (kt): 350 kt for Alberta & Orient Glycol, 650 kt for the two Dow Chemical plants combined and 440 kt for Shell Chemical (CIS, 2003). Currently there are two companies manufacturing ethylene glycol in Canada: Dow Chemical Canada (marketed by MEGlobal) and Shell Chemicals Canada Ltd (CIS, 2006). More recent data were not identified, however, it was estimated that production capacity would remain the same in 2004 (CIS, 2003).

Canada imported 7.34 kt of ethylene glycol from the United States in 2001. In total, 956 kt of ethylene glycol (mono-, di and tri-) was exported in the same year (CIS 2003).

In Canada in 2001, most of the ethylene glycol used was for anti-freeze mixtures and deicing fluids, accounting for 83 kt (49% of the domestic demand) (CIS 2003). This amount has decreased since 1999 (CIS 2003). The amount of ethylene glycol used for the production of polyethylene terephthalate (resin and fibre) has increased since 1999 and was 52 kt (30% of the domestic demand) in 2001 (CIS 2003). The amount of ethylene glycol used for oil and gas processing has remained at 12 kt (7% of the domestic demand) (CIS 2003). The remaining 21 kt of ethylene glycol (12.5% of the domestic demand) was used in miscellaneous industrial applications such as solvents (CIS 2003).

Ethylene glycol is present as a slow-evaporating solvent and/or freeze-thaw stabilizer in latex paints (US EPA 1986; NLM 2007). It is noteworthy that information indicates a trend in Canada towards substitution of ethylene glycol in paint formulations with other solvents/stabilizers (ICI Canada 2007). Ethylene glycol can also be used in a variety of other products such as floor and wall adhesives, brake fluid, automotive wax/polish and floor wax/polish (NLM 2007; Flick 1986 and in US EPA 1986).The quantities used in Canada for such products are unknown.

Ethylene glycol may also be present in pharmaceutical products as a residual solvent. It is classified by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) as a Class 2 solvent or a solvent that is to be limited in pharmaceutical products (ICH 1997). The concentration limit of 620 ppm of ethylene glycol in pharmaceutical products has been set by both the ICH and the United States Pharmacopoeia (ICH 1997; USPC 2007).

2.2.2 Sources and releases

Table 2 presents data from the National Pollutant Release Inventory (NPRI) on total industrial annual volumes of releases of ethylene glycol from all reporting sources from 1994 to 2005. While there are year-to-year fluctuations, total releases generally increased and untreated releases dropped.

Annual volumes of untreated releases from all reporting sources of ethylene glycol to air, water and land for the period 1994 to 2005 are shown in Table 3. Since peaking in 1997 at 4698 tonnes, total untreated releases have trended downwards, reaching 2263 tonnes in 2005. While both air and land releases continue to show a downward trend, releases to water have increased fivefold since 2000.

Releases to Air

The amount of untreated ethylene glycol released to air has gone down since 1995 (Table 3). While petrochemical manufacture is still the biggest contributor (144 tonnes, or 49%), significant amounts are also released by conventional oil and gas extraction (85 tonnes, or 29%), as well as from the paint and coating industry (20 tonnes, or 7%), resin and synthetic rubber manufacturing (11 tonnes, or 4%), and petroleum refineries (10 tonnes, or 3.5%) (NPRI, 2005).

Other contributing industrial activity includes motor vehicle brake and motor manufacturing, printing and iron ore mining. Together these account for approximately 7% of the total releases to air (NPRI 2005). Use of consumer products containing ethylene glycol may also contribute to releases to air.

Releases to Water

Releases (untreated) to water have gone up significantly since 1994. Releases then were reported at 91 tonnes, mostly from the paper products and the primary steel industry sectors. A sharp increase in releases occurred in 2003 and continued increases were reported up to 2005. Total 2005 releases to water were reported as 572 tonnes, with oil and gas accounting for 446 tonnes (78%). The paper products sector, including pulp mills, reported a significant drop. While this sector was previously reported as the biggest contributor of releases to water, it accounted for only 8 tonnes (1.4%). Iron and steel mills accounted for 44 tonnes (8%) in 2005.

As indicated in the SoS Report, ethylene glycol is used in large volumes for aircraft deicing/anti-icing practices and these volumes are reportedly released to land; however, airport collection facilities and drainage systems may divert substantial quantities to the aquatic environment. This point is discussed further in Appendix D.

Releases to Land

National Pollutant Release Inventory (NPRI) data show that land releases are the biggest component of total untreated releases in 2005. For that year, scheduled air transportation and support activities for air transport account for 95% of untreated releases to land. Although these volumes are reported as released to land, airport collection facilities and drainage systems may divert substantial quantities to the aquatic environment. Other sources of untreated releases to land include chemical pulp mills, diamond mines and cement manufacturing.

Since 2000, several major federal airports have built and/or improved their glycol handling facilities. These include the following locations:

• Ottawa Macdonald-Cartier International: A new biological treatment facility was opened in 2003.
• Toronto Pearson International: The Central Deicing Facility (CDF), built in 1998, was expanded in 1999-2000. Three additional deicing pads were built in 2004. An on-site glycol recycling facility was commissioned in 2005 (GTAA 2005).
• Winnipeg James Armstrong Richardson International: A central deicing facility was opened in 2005. Aeration to Truro Creek, one of two receiving water bodies for airport runoff, was started in 2001.
• • Edmonton International: A subsurface-flow (SSF) wetland facility was commissioned in 2000–2001 to treat ethylene glycol-containing aircraft deicing/anti-icing fluids (ADAFs) on-site.
• Vancouver International: work began on a new deicing pad in 2005 and the pad was operational in 2006.
• Montréal-Trudeau: extensive improvements have been made since 2000, including a new enlarged deicing pad.

Total releases of ethylene glycol from airport operations for the years 1998 to 2005 are shown in Table 4. As can be seen, there is an increase in total releases from 4577 tonnes in 1998 to 6745 tonnes in 2005. This was due to an increase in the amount of ethylene glycol that was either recycled or disposed of. The term "disposal" indicates that the glycol received some form of treatment before being either released or sent to a municipal wastewater treatment system.

For the same 1998 to 2005 period, untreated releases of ethylene glycol dropped from 2450 tonnes to 1232 tonnes. This represents a decrease of 50%. For the same period, the fraction of ethylene glycol that was released with no treatment compared with the total amount of releases (including recycling and disposal) declined steadily from 53% in 1998 to 18% in 2005.

Releases Underground

Table 3 shows that, compared with 1994, when underground injections (mostly on-site) amounted to 77 tonnes, some 93 tonnes were disposed of in this manner in the 2005-reporting year. There was a peak of 422 tonnes injected underground in the 2000 reporting year. The natural gas industry in western Canada is the biggest user of this type of disposal method (NPRI 2005).

2.3 Environmental Fate

The SoS Report revealed that, once released into the environment, ethylene glycol partitions mainly into surface water or groundwater. It does not bioaccumulate or persist in the environment, primarily due to biodegradation. Half-lives are estimated to typically range from 0.35 to 3.5 days in air, 2 to 12 days in water, 4 to 24 days in groundwater and 2 to 12 days in soil, but may exceed these ranges, depending on environmental conditions. Ethylene glycol has been found to biodegrade rapidly in the aquatic environment and therefore has the potential to induce depletion of the dissolved oxygen (DO) in receiving waters.

• 3.1 CEPA 1999 64(a): Environment
• 3.1.1 Environmental Exposure
• 3.1.2 Environmental Effects
• 3.1.3 Risk Quotient Calculations
• 3.1.4 Characterization of Ecological Risk
• 3.1.5 Uncertainties in Evaluation of Ecological Risk
• 3.1.6 Proposed Conclusion
• 3.2 CEPA 1999 64(c): Human Health
• 3.2.1 Population Exposure
• 3.2.2 Hazard Characterization
• 3.2.3 Exposure Response Analysis
• 3.2.4 Risk characterization
• 3.2.5 Proposed Conclusion
• 3.2.6 Uncertainties and Degree of Confidence in Human Health Risk Characterization
• 3.3 Conclusion
• 3.4 Considerations for Follow-up

3.1 CEPA 1999 64(a): Environment

3.1.1 Environmental Exposure

Given that releases from airports (releases to land, with subsequent movement to receiving waters) are by far the largest releases of ethylene glycol in Canada, and that those releases occur over a limited part of the year (as opposed to industrial releases that occur over the whole year), the highest environmental exposures are expected in the winter and spring in receiving waters adjacent to airports. The ecological assessment therefore focuses on potential exposure resulting from releases from airports.

Figure 2 illustrates the distribution of 3254 individual measurements of ethylene glycol sampled in stormwater at airports across Canada over the combined 2003-2004 and 2004-2005 deicing seasons. Key percentiles in this distribution and the breakdown by season are summarized in Table 5. Generally, mean glycol concentrations measured over these two years were very similar to the 1997 to 1999 data (as reported in the 2000 State of the Science (SoS) Report).

Figure 2: Frequency Distribution of Glycol Concentrations in Airport Stormwater

3.1.2 Environmental Effects

The critical toxicity values presented in the State of the Science (SoS) Report (Environment Canada and Health Canada 2000), namely the IC₂₅ of 3268 mg/L for the green alga Selenastrum capricornutum and the subchronic toxicity value of 4732 mg/L for the amphibian Xenopus laevis, still represent the most sensitive measurements of toxicity of ethylene glycol to aquatic organisms. Using IC₂₅ of 3268 mg/L from the most conservative algae test results as the critical toxicity value (CTV) and applying an application factor of 5 to account for interspecies variability and laboratory to field extrapolation, the estimated no-effect value (ENEV) of 654 mg/L is obtained. As well, using 4732 mg/L as a CTV and applying an application factor of 10 to account for the fact that the amphibian study used a non-native species and for uncertainty in laboratory to field extrapolation, the subchronic ENEV becomes 473 mg/L.

3.1.3 Risk Quotient Calculations

Aquatic Biota - Direct Effects

Based on the most recent available data from all airports for the 2004-2005 season, the levels of ethylene glycol in effluent streams are below 136 mg/L 99% of the time and below 200 mg/L 99.5% of the time from the over 1728 measurements taken (Table 5), with the reported maximum of 2560 mg/L measured in the spring of 2005. The concentrations of ethylene glycol in effluent streams, measured from all of the airports, for the most recent 2004-2005 season were below 100 mg/L 97.6% of the time.

Natural dilution of effluents occurs in the receiving waters and must be considered in calculating the risk to aquatic organisms. The level of dilution varies with each location; therefore, a generic and conservative dilution factor of 10 is applied. The effluent concentrations are assumed to be reduced by one order of magnitude--that is, the isolated maximum effluent concentration of 2560 mg/L referred to above becomes 256 mg/L in the receiving waters.

It is assumed that under worst-case conditions, high levels of ethylene glycol will be found in the effluent for a period of several days.

Conservative risk quotients for the most recent 2004-2005 season presented in Table 6 and Table 7 are all less than 1.0; however, the conservative risk quotients using the highest reported concentration for the 1997-1998 and 1998-1999 seasons were very close to 1.0 (0.99) for amphibians and 0.71 for algae.

Risk quotients at the 95th and 99th percentile values for the two comparison periods are quite comparable in the case of both algae and amphibians. At the maximum recorded values, the risk quotient is of course lower, again for both algae and amphibians.

Aquatic Biota - Indirect Effects

For characterization of risk from indirect effects, the input parameters applied to the Streeter-Phelps oxygen sag model (Streeter and Phelps, 1925) include the assumption of complete ice cover and therefore no re aeration, a dilution factor of 10, an initial DO concentration of 12.4 mg/L and concentrations of ethylene glycol in stormwater (maximums and percentiles) released from 32 airports during the 1997-1998 and 1998-1999 seasons. Oxygen deficit quotients are provided in Table 8. This table has been updated to include comparative data from the latest available Transport Canada Airport Glycol Monitoring Report for the 2003-2004 and 2004-2005 seasons.

From the quotients presented in Table 8, depletion of oxygen below the Canadian Council of Ministers of the Environment (CCME) guideline of 9.5 mg/L is not expected to occur, based on the 99th percentile of effluent releases. However, the potential for oxygen depletion appears to exist when the analysis assumes the worst-case maximum levels for both pre- and post-2000 Transport Canada data. The worst-case risk quotient for the 1997-1999 season was 16.1, whereas for the 2003-2005 period it was lower at 9.1.

Results of a separate probabilistic modeling study that used maximum loadings from individual airport facilities during the 1997-1998 or 1998-99 season and assumed complete ice cover, predicted that DO levels below the CCME DO guideline would occur about 17% of the time under worst-case conditions (Parker 1999). In a more recent study, using actual geophysical and precipitation data from several major Canadian airports, it was shown that ethylene glycol could reduce oxygen levels below the CCME guideline in the airports’ receiving watercourses, even under some conditions of no ice cover, especially at higher concentrations (> 500 mg/L) (Chaulk 2003). It should be pointed out that concentrations of 500 mg/L or higher represent less than 0.5% of recently recorded values at these airports, thus indicating a very low probability for this scenario.

Terrestrial Wildlife - Direct Effects

The SoS Report (Environment Canada and Health Canada 2000) reported the following toxicity information, which is pertinent to the potential effects of ethylene glycol on terrestrial wildlife. Ethylene glycol poisoning is common among domestic animals and has been reported in cats, pigs, poultry, wildlife and calves (Kersting and Nielsen 1965; Riddell et al. 1967; Black 1983; Amstrup et al. 1989). Ethylene glycol is a slow-acting poison. Even after a massive dose, an animal will be unaffected for 0.5-2 hours post-exposure (Penumarthy and Oehme 1975; Oehme 1983; Beasley 1985; Grauer and Thrall 1986). The oral toxicity of ethylene glycol varies among species. Cats were reported to be the most susceptible to poisoning (Osweiler et al. 1985). The reported lethal dose for cats is only 1.5 mL/kg-bw (1650 mg/kg-bw) (Black 1983), whereas for dogs it is 4.2-6.6 mL/kg-bw (4620-6600 mg/kg-bw) (Beasley and Buck 1980; Oehme 1983; Grauer and Thrall 1986). Osweiler et al. (1985) reported a lethal dose of 2-4 mL/kg-bw (2200-4400 mg/kg-bw) in cats, 4-5 mL/kg-bw (4400-5500 mg/kg-bw) in dogs and 7-8 mL/kg-bw (7700-8800 mg/kg-bw) in poultry. Mallard ducks (Anas platyrhynchos) exposed orally to ethylene glycol demonstrated adverse toxic effects (lowest-observed-effect dose, or LOED) at 2.3 mL/kg-bw (2530 mg/kg-bw) (Stowe et al. 1981). A no-observed-effect level (NOEL) for orally dosed ducks at 1221 mg/kg-bw and reported lethal doses for poultry at approximately 8000 mg/kg-bw were reported in CA/ICCA (2000).

For the assessment of very short-term exposure to ethylene glycol, applying an assessment factor of 10 to the LD50 for cats of 1650 mg/kg-bw, to account for interspecies and intraspecies variability in sensitivity, gives an ENEV of 165 mg/kg-bw. The 99th-percentile concentration in stormwater runoff from airports from all data from the 1997-1999 seasons is 200 mg/L. Therefore, an animal would have to drink its own weight of stormwater runoff in a short period of time in order to attain the ENEV dose of 165 mg/kg-bw. Assuming a dilution factor of 10, an animal would have to drink about 10 times its own weight of water from a receiving stream in order to attain the ENEV dose.

Elevated concentrations of ethylene glycol in receiving waters may persist for several days. In a 16-week study with rats, the lowest-observed-effect level, based on increased incidence of calcium oxalate crystals, was 150 mg/kg-bw/day (Cruzan et al. 2004). Dividing this value by an assessment factor of 10, to account for interspecies and intraspecies variability in sensitivity, gives an ENEV of 15 mg/kg-bw/day. A 1-kg animal would have to drink about 75 mL/day of airport stormwater runoff containing 200 mg ethylene glycol/L, or 7.5% of its body weight per day, to attain this ENEV. Assuming a dilution factor of 10, an animal would have to drink about 75% of its own weight of water per day from a receiving stream in order to attain the ENEV dose.

Given that a 70-kg human drinks about 3 kg of water per day, or about 4% of his or her body weight and extrapolating this to other species and considering that high levels of ethylene glycol occur for only a few days at a time, it is unlikely that terrestrial wildlife would be harmed by drinking water from receiving waters in the vicinity of airports for a period of time ranging from a few days to several weeks.

3.1.4 Characterization of Ecological Risk

Ethylene glycol is not persistent in air, water or soil and does not accumulate in organisms. The substance has a low inherent toxicity; that is, it causes adverse effects in organisms only at relatively high doses or concentrations.

With respect to releases of ethylene glycol from all sources, as reported to the National Pollutant Release Inventory (NPRI), there is a general downward trend both in total amounts of untreated releases and in the fraction of untreated releases relative to total releases (including disposed of or recycled releases). Based on data from Table 3, the following graph shows the downward trend in total untreated releases from all sources.

Figure 3: Untreated Glycol Releases -- All Sources

The largest portion of untreated releases of ethylene glycol is to land, with 95% of those releases originating from airports. Much of the ethylene glycol released subsequently moves to watercourses, such that airports are ultimately the greatest source to water as well. For airports, improved management practices have led to increases in the amounts of ethylene glycol that are treated or disposed of, such that the proportion of untreated glycol to total glycol releases has steadily declined from 53% in 1998 to 18% in the 2005 reporting year.

Based on extensive monitoring data from airports, the risk quotients for effects in freshwater ecosystems indicate that ethylene glycol concentrations likely do not exceed concentrations associated with effects, based on the 99th percentile glycol concentration measured at airports for both direct and indirect effects. Examination of potential indirect effects through oxygen depletion suggests a low potential for dissolved oxygen (DO) levels to drop below the Canadian water quality guideline value (9.5 mg/L DO) under very infrequent maximal loding conditions. It is thus expected that direct or indirect effects are unlikely, especially when consideration is given to the seasonal and transient nature of the releases, the short duration of exposure, and the low ambient temperatures and metabolic rates at the periods of maximum release.

3.1.5 Uncertainties in Evaluation of Ecological Risk

As reported in the SoS Report (Environment Canada and Health Canada 2000), there is a lack of measurement data for ethylene glycol in the ambient environment. However, a large data set of measurements of ethylene glycol in effluents from Canadian airports provides a very good indication of the concentrations being released. Because the conditions of the receiving waters can be highly variable across Canada, some conservative assumptions, including the use of a dilution factor of 10, have been applied in estimating concentrations in waterways. It is expected that an adequate estimate of the concentrations of ethylene glycol in the receiving waters has been obtained.

The use of deicing and anti-icing fluids at airports across Canada will vary from year to year and from region to region, depending on climatic factors. Through control programs by Transport Canada, the Air Transport Association of Canada and local airports and airlines, including the implementation of glycol mitigation plans and glycol operational management plans at the major airports in Canada, the amounts of untreated ethylene glycol being released to the ambient environment have been declining over the past years, and in particular since 2000 with improvements in glycol application and control methods.

While this assessment addressed the potential ecological impacts of ethylene glycol, it is recognized that, while ethylene glycol is the principal ingredient in airplane deicing and anti-icing formulations in Canada, other constituents can be present and can increase the toxicity of the formulation. For example, some deicing formulations can be three to ten times more toxic to certain organisms than ethylene glycol alone (Pillard 1995).

Based on the present analyses, harmful ecological effects are unlikely to result from exposure to ethylene glycol in Canada. Similarly, effects related to reductions in concentrations of dissolved oxygen are unlikely. However, concentrations could reach levels of concern near some Canadian airports a very small percentage of the time under conditions of maximum loading. Continued monitoring of stormwater effluents and receiving waters at airports would permit ongoing determination of the occurrence or frequency of such occasional high releases.

3.1.6 Proposed Conclusion

Based on the information presented and using a weight of evidence approach, it is therefore proposed that ethylene glycol 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 it constitutes or may constitute a danger to the environment on which life depends.

3.2 CEPA 1999 64(c): Human Health

3.2.1 Population Exposure

The following presentation is limited to identifying recent data considered critical to the quantitative estimation of the exposure to ethylene glycol for various age groups in the general population of Canada and, hence, to an assessment of “toxic” under paragraph 64(c) of the Canadian Environmental Protection Act, 1999 (CEPA 1999).

The Environmental Monitoring and Reporting Branch of the Ontario Ministry of Environment (formerly the Ontario Ministry of Environment and Energy) used Trace Atmospheric Gas Analyzer (TAGA) 6000 units to carry out several mobile air monitoring surveys in Windsor, Ontario in 1991 and 1992 (OMEE 1994b). The surveys were performed in order to determine the concentrations of certain substances in air that are not usually measured in routine monitoring programs (OMEE 1994). Ethylene glycol was measured during the 1992 survey that focused on determining concentrations of industrial chemicals found in areas where the general population could be exposed, such as in city parks and near schools (OMEE 1994). Levels of ethylene glycol ranged from < 1 µg/m³ to 75 µg/m³ (detection limit of 1 µg/m³) (OMEE 1994). Based on the maximum value, the upper-bounding estimates of intake for ambient air range from 1.9 to 5.6 µg/kg-bw/day and are shown in Table 9.

Zhu et al., (2004) developed an analytical method for measuring ethylene glycol and propylene glycol in indoor air. This Canadian study involved sampling 9 residential homes (2 apartments and 7 single detached houses), 1 attached residential garage, 1 office and 2 laboratories. The samples were collected from an area that had no industrial point source releases nearby. Ethylene glycol was detected in all locations with levels from the residences (including the attached garage) ranging from 2.0 to 223 µg/m³ and levels from the office and laboratories, ranging from 1.9 to 4.4 µg/m³ (method detection limit of 0.07 µg/m³). Hodgson et al. (2000) sampled indoor air in 11 newly built houses (4 manufactured and 7 site-built houses) in the eastern and southeastern United States. Levels of ethylene glycol were measured at least one month after the completion of the house and ranged from < 23.4-1247 µg/m³. Latex paint was indicated as a source of ethylene glycol emissions. It is noteworthy that in a study of ethylene glycol emission rates from carpets (possibly from an adhesive), the emission rate decreased from 949 µg/m²/h to less than 50 µg/m²/h (detection limit) in 28 days (Wilke et al. 2002).

Based on the maximum value found in residences from the Canadian study (Zhu et al. 2004), the upper-bounding estimates of daily intake from indoor air ranges from 39 to 117 µg/kg-bw/day and are shown in Table 9.

As no new data on levels of ethylene glycol in food or food packaging were identified, it is assumed that the level of ethylene glycol intake through food has not changed since the publication of the 2000 SoS Report. This source of intake is summarized in Table 9 and Table 10.

Upper-bounding estimates of total daily intake of ethylene glycol for the general Canadian population range from 53 µg/kg-bw/day in adults (60+ years) to 157 µg/kg bw/day in children (0.5-4 years), as shown in Table 9. For each age group, indoor air is the primary source of exposure.

Sciences International, Inc. was commissioned by the Ethylene Glycol Panel of the American Chemistry Council to characterize potential exposures of the general population to ethylene glycol near an ethylene-glycol manufacturing plant located in Red Deer, Alberta, Canada (Sciences International, Inc. 2003). The purpose of this study was in part to respond to the need for more research on exposure to humans located near point source releases, which was an uncertainty identified in the SoS Report.

Sciences used ISC PRIME (Industrial Source Complex Plume Rise Model Enhancements), a site-specific air dispersion model, to estimate potential human exposure to ethylene glycol. The model incorporated ethylene glycol emission data acquired from the facility, as well as five years of meteorological data (Sciences International, Inc. 2003). The predicted maximum 24-hr concentration at nearby residences was 154 µg/m³ (60 ppb). Based on this output, the upper-bounding estimates of daily intake from ambient air ranges from 3.82 in adults (60+ years) to11.55 µg/kg-bw/day (0.5 - 4 years) for individuals living near point sources (Table 10).

The intake values from exposure to soils located near a point source remain the same as those reported in the SoS Report.

Upper-bounding estimates of daily intake of ethylene glycol for a highly exposed population in the immediate vicinity of an industrial point source range from 57 µg/kg bw/day in adults (60+ years) to 191 µg/kg-bw/day in children (0.5-4 years), as shown in Table 10. For most age groups, the present estimation is approximately two to three times higher than the estimate presented in the SoS Report. Indoor air is the primary source of exposure for all age groups living in the vicinity of a point source.

In the SoS Report, the highest exposure to the general population was considered to be from dermal exposure to ethylene glycol from use of tub and tile cleaners. Dermal exposure estimates were also derived for latex paints, floor polish/wax and auto polish/wax. According to the Canadian Consumer Specialty Products Association (CCSPA) (2002), tub and tile cleaners found in the Canadian market do not contain ethylene glycol. CCSPA (2007) has also confirmed that floor polish/wax products containing ethylene glycol are for use in commercial and institutional settings and are not for consumer use. Therefore, the daily intake of ethylene glycol through dermal exposure is considered to be mainly from auto polish/wax and latex paints. The estimates of exposure to adults from dermal contact to these consumer products were 0.56 and 1.9 mg/kg-bw/day, respectively (Table 11)

Inhalation exposure to consumer products was not estimated in the SoS Report; however, based on the levels identified in indoor air from Zhu et al., (2004) and Hodgson et al. (2000), it was determined that this route of exposure should be investigated. Table 11 shows air concentration estimates from use of latex paint. Using the US EPA's Wall Paint Exposure Model (WPEM), the highest 8-hr average concentration for a do-it-yourself painter painting a room with latex paint was 22 mg/m³ ethylene glycol, whereas the highest 8-hr average concentration for the occupants of the home being painted was 9.6 mg/m³ ethylene glycol (Table 11). The highest concentrations are predicted to occur approximately 1.5 days after painting has commenced, and it is therefore very likely that other occupant scenarios (e.g., child sleeping or playing in a freshly painted room) could result in higher exposures than the one presented.

Although, CCSPA (2007) has confirmed that floor polish/wax products containing ethylene glycol are restricted to commercial and institutional settings, inhalation exposure to occupants of these facilities is possible and was therefore investigated using the ConsExpo model developed by The National Institute for Public Health and the Environment (RIVM, 2006). The mean event concentration while applying floor polish in a residential setting was 2.09 mg/m³ (see Table 11) and is considered an upper-bounding estimate of the concentrations that occupants may be exposed to. It was considered that auto polish/wax is used primarily outdoors and inhalation exposure would be negligible (US EPA 1986).

In the SoS Report, exposure estimates from use of consumer products were derived through amortization of daily exposures over a one-year period, taking event frequency into account. However, it is noted in the SoS Report that for developmental and reproductive effects, peak exposure during product use may be a more appropriate basis for comparison. As such, daily exposure estimates are considered the most appropriate exposure metric for the current assessment.

3.2.2 Hazard Characterization

A number of studies have been reported in the period following the release of the SoS Report, in addition to studies conducted to address uncertainties identified in the SoS Report. Recent mammalian in vitro and in vivo toxicity studies and human studies are presented below for the hazard characterization of ethylene glycol.

An acute immunotoxicity study conducted by Zabrodskii and Germanchuck (2000) observed higher E. coli-induced mortality among ethylene-glycol-exposed mice than among controls. In human acute toxicokinetic studies, when male volunteers were exposed to labelled ethylene glycol through inhalation for 4 hrs, 100% uptake was reported. The half-life of labelled ethylene glycol and glycolic acid was 2.1-2.6 and 2.6-2.9 hr, respectively (Carstens et al. 2002, 2003).

In short-term toxicity studies, when Wistar and Sprague-Dawley rats were exposed to 1050 mg/kg-bw/day of ethylene glycol through drinking water for 42 and 28 days respectively, both strains showed increased urinary oxalate and renal calculi (Huang et al. 2000, 2002, 2003; Green et al. 2005). Khan et al. (2002) conducted a similar study using Sprague-Dawley rats with an exposure period of 8 weeks. Crystal deposition in the kidneys was present in all treated animals. In another study, when mice were orally administered 2200 mg/kg-bw ethylene glycol for 7 days, decreased body weight was reported (Mohanasundari et al. 2005).

A new 16-week subchronic (Cruzan et al. 2004) and a 12-month chronic (ACC 2005) dietary study on rats are now available to further characterize the repeat dose toxicity of ethylene glycol to mammals. To further investigate strain differences in toxicity, the subchronic toxicity study (Cruzan et al. 2004) was conducted using both Wistar and Fischer 344 (F-344) rats. When rats were exposed to 0, 50, 150, 500 and 1000 mg/kg bw/day ethylene glycol for 16 weeks under identical dietary exposure conditions, the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) for both strains were reported as 150 and 500 mg/kg-bw per day respectively. At the LOAEL, increased incidence of calcium oxalate crystals was reported for both strains. However, Wistar rats were more sensitive to ethylene glycol at higher doses than were F-344 rats. The ethylene glycol sensitivity of Wistar rats at 500 mg/kg-bw/day was comparable to that of F-344 rats at 1000 mg/kg-bw per day.

Toxicokinetic studies showed significant strain difference in oxalic acid levels in the kidney at an ethylene glycol dosage level of 500 mg/kg-bw/day and above. At the end of a 16-week exposure period, the oxalic acid levels in kidney tissues of F-344 rats at 500 and 1000 mg/kg-bw/day were 32.92 and 20 616 µg/g respectively, whereas in Wistar rats these levels were 33 108 and 100 812 µg/g respectively (Cruzan et al. 2004). There was a clear strain difference in elimination of oxalic acid in urine. Wistar rats exposed to 500 and 1000 mg/kg-bw/day had 21 and 14 times less elimination in urine respectively compared to that of F-344 rats.

The chronic toxicity study (ACC 2005) with male Wistar rats is considered a key study for the human health risk assessment of ethylene glycol. When rats were exposed to 0, 50, 150, 300 and 400 mg/kg-bw/day in their diet for 12 months, the NOAEL was 150 mg/kg-bw/day, and the LOAEL was 300 mg/kg-bw per day based on renal toxicity (e.g., crystal nephropathy). The highest dose exceeded the maximum tolerable dose (MTD), as all the surviving rats had to be euthanized before the scheduled termination due to excessive weight loss.

In the same study, the renal clearance of oxalic acid in Wistar rats was compared with F 344 rats. A significantly higher renal clearance was present in young F 344 rats (6.06 mL/min/kg-bw) compared to that of Wistar rats (3.8 mL/min/kg-bw). There was no age difference in renal clearance of oxalic acid among Wistar rats.

When blood, urine and kidney samples were analysed for ethylene glycol metabolites, oxalic acid level in kidneys showed a rapid and non-linear increase. At 0, 50, 150, 300 and 400 mg/kg-bw per day, the oxalic acid levels were 5.31, 16.07, 8.72, 6561 and 18 789 µg/g respectively.

Elimination of ethylene glycol followed a linear dose-response relationship, whereas elimination of glycolic acid (GA) was linear up to 150 mg/kg-bw/day and increased non linearly at 300 mg/kg-bw per day. Urinary elimination of oxalic acid was similar to control animals across all the doses.

Poldelski et al. (2001) exposed isolated mouse proximal tubular segments (PTSs) to ethylene glycol or its main metabolites (glycolate, glycoaldehyde, glyoxylate or oxalate) for 15 or 60 minutes and cell injury was measured by the percentage of lactate dehydragenase (LDH) release, LDH destruction, adenosine triphospate (ATP) depletion or membrane phospholipid degradation. Only glyoxalate and glycoaldehyde resulted in significant ATP depletion and LDH release causing cytotoxicity. Ethylene glycol, glycolate and oxalate were not injurious to PTSs. The authors concluded that glyoxalate and glycoaldehyde are the principle metabolites responsible for ethylene-glycol-induced nephrotoxicity. In contrast, Guo et al. (2005) showed using in vitro studies with human proximal tubule (HPT) cells that calcium oxalate monohydrate (COM) dose-dependently increased the LDH release while glycolic acid, glyoxylic acid or glycoaldehyde did not increase LDH release at any pH levels tested (pH 6, 6.5, 7 or 7.4). The results of this study suggest that COM, not the other metabolites of ethylene glycol, is toxic to HPT cells at the relevant concentrations.

In other in vitro studies (Guo and McMartin 2005), the toxicity of oxalate and calcium oxalate monohydrate (COM) to rat proximal tubular (PT) cells and human proximal tubular (HPT) cells was investigated. COM, not oxalate ion, caused the cytotoxicity in HPT cells, assessed by the release of LDH and percentage of cell death. Similar results were observed in Wistar and F-344 rat PT cells exposed to oxalate and COM. This study also indicated that HPT cells are less sensitive to COM-induced cytotoxicity compared to rat PT cells. McMartin and Wallace (2005) indicate that inhibition of mitochondrial respiratory function in PT cells by COM crystals is an important factor for the renal toxicity of ethylene glycol. These in vitro findings of COM toxicity are in agreement with the findings of Cruzan et al. (2004).

In a recent developmental toxicity study, Carney et al. (2001, 2002) observed maternal toxicity and fetal malformations when pregnant rats were exposed to ethylene glycol through a subcutaneous bolus injection. In another study, developmental toxicity was observed in mice when exposed to 11 090 mg/kg-bw/day ethylene glycol through oral gavage during GD 7-14 (Schuler et al. 1984).

Following Wistar rat whole embryo (on GD 9.5-11.5) cultures exposed to ethylene glycol and its metabolites (glycoaldehyde, glycolic acid, glyoxale, glyoxylic acid and oxalic acid), the LOAELs for developmental toxicity were reported as 200 mM for ethylene glycol and 3 mM for glycolic acid. Decreased growth parameters (protein content and crown-rump length) were reported at LOAEL (Klug et al. 2001). Previous investigations have shown that the ethylene-glycol-induced developmental toxicity is caused by the intermediate metabolite glycolic acid (Carney et al. 1999, 2001).

In a toxicokinetic study, when ethylene glycol was administered orally to pregnant and non-pregnant Sprague-Dawley rats, the pregnancy status did not have any impact on the pharmacokinetic parameters of ethylene glycol and its metabolites. Abnormal embryos were observed at ethylene glycol exposure levels of 1000 mg/kg-bw/day and above. The LOAEL for developmental toxicity was 1000 mg/kg-bw per day. The peak blood glycolic acid level at LOAEL was as high as 363 µg/g or 4.8 mM (Pottenger et al., 2001).

In a metabolism study, Booth et al. (2004) exposed rat, rabbit and human liver slices to ethylene glycol. Rat liver slices produced approximately 10 times higher levels of glycolic acid compared to rabbit liver slices. The glycolic acid was not detected in human liver. Human liver tissues were also more efficient in further metabolising glycolic acid to glyoxylic acid. Therefore, there is less chance for accumulation of glycolic acid in human than in experimental animals.

Physiologically based pharmacokinetic models have been developed for ethylene glycol and its metabolite, glycolic acid, in rats and humans (Corley et al. 2005a, b).

In humans, (Leth and Gregersen 2005, Krenova and Pelclova 2005, Huttner et al. 2005, Caravati et al. 2005, Morfin and Chin 2005) severe metabolic acidosis, elevated serum anion and osmolar gap and calcium oxalate crystalalluria were observed in individuals with acute exposures to large quantities of ethylene glycol. The pathological examination of renal tissues showed wide-spread necrosis of the tubular epithelium and deposition of oxalate crystals in the proximal and distal tubules and collecting ducts. Oxalate crystals appeared in tissues including brain, heart, kidney and lungs. Lethality was observed among individuals who ingested approximately 1.43 ml/kg-bw of ethylene glycol.

3.2.3 Exposure Response Analysis

Chronic Exposure

Table 12 presents the benchmark dose₀₅ (i.e. the dose estimated to cause a 5% increase in incidence over the background response rate; BMD₀₅) and the corresponding 95% lower confidence limit (BMDL₀₅) for key toxicity studies presented in the SoS Report (Environment Canada and Health Canada 2000) and the current follow-up report.

The following model, which describes the probability of the occurrence of the given health effect, was used to derive the BMD₀₅ from the dose-response data:

where d is dose, k is the number of dose groups in the study, P(d) is the probability of the animal developing the effect at dose d and q_i<0, i=1,...,k and d₀ are parameters to be estimated.

The models were fit to the data using THRESH (Howe 1995) and the BMD₀₅s were calculated as the dose D which satisfies

A chi-square lack of fit test was performed for each of the model fits. The degrees of freedom for this test are equal to k minus the number of q_is whose estimates are non-zero. A p-value of less than 0.05 indicates a significant lack of fit. The BMDL₀₅ is defined as the lower 95% confidence limit on the BMD₀₅.

The BMD₀₅ of 120 mg/kg/day, based on incidence of crystal nephropathy in male Wistar rats exposed to ethylene glycol for 12 months through diet (ACC 2005), was considered the most appropriate for use in establishing the tolerable intake (TI). The primary reason for selecting the 12-month study over the 16-week study (Cruzan et al. 2004) is to reduce the uncertainty associated with less-than-chronic exposure. Furthermore, the results of the chronic study indicate that the kidney lesions are not progressing over long-term exposure. The BMDL₀₅ value for this end point was less than twofold lower than the central estimate of the BMD₀₅; the latter, therefore, was used in the calculation of TI.

In the chronic study (ACC 2005), renal changes were reported in terms of crystal nephropathy only. In contrast, the provisional TI reported in the SoS Report was established based on the BMD₀₅ for incidence of total tubular damage (i.e., oxalate crystals in kidney, dilated tubules, protein casts) in a subchronic study (Gaunt et al. 1974). Incidence of crystal nephropathy is a more compound-specific histopathological effect, which is considered adverse. For comparison purposes, the BMD₀₅ for incidence of exclusive oxalate crystal formation in the kidney (as opposed to total tubular damage) from Gaunt et al. (1974) is 173.4 mg/kg/day (95% LCL 67.3 mg/kg-bw/day). Similarly, the BMD₀₅ from the 16-week study (Cruzan et al. 2004) is 161 mg/kg-bw/day based on incidence of crystal nephropathy (95% LCL of 72 mg/kg/day).

Based on the BMD₀₅ of 120 mg/kg-bw/day, the tolerable intake (TI) has been derived as follows:

where:

120 mg/kg-bw/day is the BMD₀₅ for the incidence of compound-induced crystal nephropathy in male Wistar rats after dietary exposure to ethylene glycol for 12 months (ACC, 2005) and

100 is the uncertainty factor (x10 for interspecies variation, x10 for intraspecies variation). Regarding the factors for interspecies and intraspecies variation, available data remain inadequate to further address toxicokinetic and toxicodynamic aspects of components of uncertainty with data-derived values. The additional uncertainty factor of 10x, which was applied to account for less-than-chronic exposure in the SoS Report, is no longer warranted given the availability of a chronic study in the sensitive rat strain.

Short-term Inhalation Exposure

The nose-only inhalation study conducted by Tyl et al. (1995) in CD-1 mice was considered the most appropriate study from which to derive a tolerable concentration. Table 13 presents the maternal and developmental effects of inhalation exposure to ethylene glycol during gestation days 6 to15. Maternal toxicity was limited to a slight increase (7%, p < 0.05) in relative kidney weight at 2505 mg/m³, without evidence of cytotoxicity. The increased absolute maternal kidney weight at 360 mg/m³ was considered a NOEL since no other adverse effect was reported. At 2505 mg/m³, developmental toxicity, including reduced fetal body weight per litter, increased incidence of fused ribs and skeletal variations, were observed. Therefore, the NOAEL for developmental toxicity was 779 mg/m³. This NOAEL is the most appropriate end point upon which to derive a tolerable concentration (TC).

where:

779 mg/m³ is the developmental NOAEL in mice (Tyl et al. 1995) and

100 is the uncertainty factor (x 10 for interspecies variation, x 10 for intraspecies variation)

3.2.4 Risk characterization

Chronic Exposure Scenario

The above estimated tolerance intake (TI) for chronic exposure remains protective for potential developmental effects. New information on developmental effects (Schuler et al. 1984; Pottenger et al. 2001) does not indicate a different developmental hazard profile than the one presented in the SoS Report. In the SoS Report, TIs for this end point were derived based on i) the NOAEL for developmental effects in mice (i.e., 500 mg/kg bw/day) divided by an uncertainty factor of 100; and ii) the NOEL of 150 mg/kg-bw/day in the same mice study divided by an uncertainty factor of 100. These values exceed the TI, based on renal effects, of 1.2 mg/kg-bw per day.

Based on the information available, upper-bound estimates of daily intake of ethylene glycol for the general population of Canada (up to 157 ug/kg-bw per day; Table 9), and for a highly exposed population in the immediate vicinity of an industrial point source (up to 191 ug/kg-bw per day; Table 10), are well below the TI of 1.2 mg/kg-bw per day.

Short-term Inhalation Exposure Scenario

The estimated air concentrations from the use of latex paint, both for do-it-yourself painters (22 mg/m³) and for occupants, including children, of a residence being painted (9.6 mg/m³) exceed the tolerable concentration (TC) (7.79 mg/m³). The highest 8-hr average exposure concentration to which a painter would be exposed is approximately threefold greater than the TC. The highest 8-hr average exposure for an occupant of a residence being painted also exceeds the TC. Exposure to ethylene glycol from latex paints is expected to be even greater as a result of dermal contact with these products, which will contribute to the overall exposure.

According to CCSPA (2007) floor polish/wax products containing ethylene glycol are only used in commercial and institutional settings and are not for consumer use. Dermal exposure is therefore not of concern; however, it is possible that the general population may be exposed to ethylene glycol via inhalation in institutional settings. The upper bounding estimate used to represent this route of exposure (2.09 mg/m³) is below the TC (7.79 mg/m³) and is not, therefore, of concern. It was considered that auto polish/wax is used primarily outdoors and inhalation exposure would be negligible. (Note: As the dermal exposure estimate from use of auto polish/wax is below the TI, this consumer product scenario is not of concern.)

3.2.5 Proposed Conclusion

Based upon upper-bounding estimates of short-term inhalation exposure to ethylene glycol to individuals, including children, from use of certain consumer products (latex paints), it is proposed, therefore, that ethylene glycol is entering the environment in a quantity or concentration or under conditions that may constitute a danger to human life or health. Therefore, it is proposed that ethylene glycol is "toxic" to human health as defined in paragraph 64(c) of the Canadian Environmental Protection Act, 1999 (CEPA 1999).

3.2.6 Uncertainties and Degree of Confidence in Human Health Risk Characterization

There is low confidence in the estimated total daily intake values for the general population based on the limited data available. In the SoS Report, limitations of the available data precluded development of upper-bounding estimates of daily intake of ethylene glycol by the general population. In the current assessment, additional data, albeit limited, permitted derivation of upper-bounding estimates of daily intake of ethylene glycol. However, the intakes from ambient air and from indoor air are each based on a single Canadian study with insufficient samples to ensure representativeness of the Canadian population. No monitoring data for drinking water and soils were not identified. No new data on levels of ethylene glycol from food or food packaging were also not identified either and this remains an area of uncertainty.

There is moderate confidence in the estimated intake in the vicinity of point sources. The computer air dispersion model (ISC PRIME) is considered to provide a reliable indication of ambient air concentrations of ethylene glycol at the dwelling and property boundary in the vicinity of industrial point sources. With respect to indoor air, it is possible that the indoor air intake value for those residents living near the vicinity of a point source is underestimated as these values were measured in dwellings not located near industrial point sources. There is a high degree of certainty that the estimates of intake from ingestion of soil by a population exposed due to its proximity to a source of discharge to the atmosphere are upper-bounding.

Overall, there is low to moderate confidence in the estimates of exposure to ethylene glycol from use of consumer products. Based on the information provided by CCSPA (2002), there is high confidence that tub and tile cleaners do not contain ethylene glycol and that floor polish/waxes containing ethylene glycol are targeted to commercial and institutional uses (CCSPA, 2002, 2007). However, there is uncertainty about occupant exposures following commercial and institutional uses. There is also some uncertainty regarding the appropriateness of using the ConsExpo residential floor polish scenario to represent potential inhalation exposures to ethylene glycol to occupants of institutional settings. Additionally, data on Canadian-specific ranges and distributions of concentrations in the various products were not available. No additional information to characterize absorption through the skin was identified; however, the assumption of complete absorption is considered conservative. As noted in the SoS Report, estimated daily intakes by dermal absorption of ethylene glycol from use of consumer products would be several orders of magnitude less than the values presented in Table 11 if skin permeability were taken into account. However, available data on the permeability of of human skin to ethylene glycol are currently inadequate as a basis for confident estimation of exposure (Environment Canada and Health Canada 2000). There is moderate confidence in the exposure estimates via the inhalation route from latex paint using the US EPA's Wall Paint Exposure Model. The model is relatively robust and has incorporated results of chamber tests involving ethylene glycol (US EPA 2001). This model was designed specifically to model indoor air concentrations and exposures from painting applications and is intended for use by industry product developers as well as health and safety officials (US EPA 2001). The highest air concentrations are predicted to occur approximately 1.5 days after painting has commenced, and it is therefore very likely that other occupant scenarios (e.g., child sleeping or playing in a freshly painted room) could result in higher exposures than the one presented. Furthermore, children have a higher breathing-rate-to-body-weight ratio than adults and intake following exposure to ethylene glycol in air will be proportionally higher for children than for adults. As such, it is considered appropriate to apply precaution when characterizing risk of exposure to ethylene glycol.

The degree of confidence in the database on toxicity that serves as the basis for development of the TI for ethylene glycol remains moderate. Confidence that the TI developed on the basis of renal effects is protective of other adverse effects of ethylene glycol, such as developmental effects, also remains moderate. The lack of data on progression of renal lesions following chronic exposure in the most sensitive animal model was an area of considerable uncertainty identified in the SoS Report. This has been addressed through conduct of a 12-month study in Wistar rats. It is considered that the chronic study used to derive BMD₀₅ has comprehensively covered the renal histopathology as renal tissues are the primary target sites for ethylene glycol toxicity. Furthermore, the study was conducted on the strain of rats most sensitive to ethylene glycol (Wistar rats).

There is limited confidence in the database used to derive the tolerable concentration for the short-term exposure scenario. It should be noted that the mice are less sensitive to ethylene-glycol-induced toxicity then are the rats. The degree of difference in sensitivity between mice and humans is a considerable area of uncertainty. Furthermore, interpretation of restrained nose-only inhalation studies can be complicated by confounding factors such as stress associated with restraint and ingestion exposure to test material deposited on the face.

3.3 Conclusion

Based on the information presented and using a weight of evidence approach, it is therefore proposed that ethylene glycol 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 constitutes or may constitute a danger to the environment on which life depends.

Based upon the upper-bounding estimates of short-term inhalation exposure to ethylene glycol to individuals, including children, from use of certain consumer products (latex paints), it is proposed, therefore, that ethylene glycol is entering the environment in a quantity or concentration or under conditions that may constitute a danger to human life or health. Therefore, ethylene glycol is considered “toxic” to human health as defined in paragraph 64(c) of the Canadian Environmental Protection Act, 1999 (CEPA 1999).

3.4 Considerations for Follow-up

Additional characterization of the range and distribution of concentrations of ethylene glycol in certain consumer products (i.e. latex paints) currently available in Canada and human exposure (inhalation, dermal contact) to ethylene glycol from use of these consumer products is considered a clear priority as a basis for risk management. Furthermore, information to reduce uncertainty regarding the absorption of ethylene glycol through the skin from use of consumer products containing ethylene glycol would be valuable. Further information on interspecies and intraspecies toxicokinetics and toxicodynamics would be useful in determining whether data-derived values could replace components of the interspecies and intraspecies uncertainty factors.

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Notes: All releases in tonnes. "Untreated Releases" does not include underground injection.

Source: NPRI 2005. All releases are in tonnes.

¹ Quotient is derived by dividing the EEV by the ENEV (654 mg/L).

¹ Quotient is derived by dividing the EEV by the ENEV (473 mg/L).

¹ Oxygen deficit is the application of the Streeter and Phelps (1925) oxygen sag model to provide the number of mg O₂/L below the saturation point of 13.1 mg O₂/L and resulting from the assumed EEV in the receiving water.
² The quotient represents the ratio between the calculated oxygen deficit and the minimal oxygen deficit of 3.6 mg/L needed to meet the cold-water CCME freshwater guideline of 9.5 mg/L, assuming a water temperature of 4°C.

¹ Assumed to weigh 7.5 kg, to breathe 2.1 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
² Assumed to weigh 15.5 kg, to breathe 9.3 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
³ Assumed to weigh 31.0 kg, to breathe 14.5 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
⁴ Assumed to weigh 59.4 kg, to breathe 15.8 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
⁵ Assumed to weigh 70.9 kg, to breathe 16.2 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
⁶ Assumed to weigh 72.0 kg, to breathe 14.3 m3 of air per day (EHD 1998) and to consume food items at average daily rates indicated in EHD (1998).
⁷ The Ontario Ministry of Environment (formerly the Ontario Ministry of Environment and Energy) measured levels of ethylene glycol at 12 different public areas located in Windsor, Ontario in 1992 (OMEE 1994b). The maximum concentration (75 µg/m³) was used to calculate the upper-bounding estimate of exposure for ambient air. Canadians are assumed to spend 3 hours outdoors each day (EHD 1998).
⁸ Zhu et al. (2004) measured levels of ethylene glycol in nine residential homes (two apartments and seven single detached houses), one attached residential garage, one office and two laboratories. The maximum concentration observed in a residential home (223 µg/m³) was used to calculate the upper-bounding estimate of exposure. Canadians are assumed to spend 21 hours indoors each day (EHD 1998).
⁹ Refer to the State of the Science Report on ethylene glycol (Environment Canada and Health Canada 2000) for more details on the values of ethylene glycol that may be found in food and beverages.
¹⁰ Concentrations of ethylene glycol in Canadian drinking water or elsewhere were not identified.
¹¹ Background concentrations of ethylene glycol in Canadian soils or elsewhere were not identified.

¹ Assumed to weigh 7.5 kg, to breathe 2.1 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 30 mg of soil per day (EHD 1998).
² Assumed to weigh 15.5 kg, to breathe 9.3 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 100 mg of soil per day (EHD 1998).
³ Assumed to weigh 31.0 kg, to breathe 14.5 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 65 mg of soil per day (EHD 1998).
⁴ Assumed to weigh 59.4 kg, to breathe 15.8 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 30 mg of soil per day (EHD 1998).
⁵ Assumed to weigh 70.9 kg, to breathe 16.2 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 30 mg of soil per day (EHD 1998).
⁶ Assumed to weigh 72.0 kg, to breathe 14.3 m³ of air per day, to consume food items at average daily rates indicated in EHD (1998), and to ingest 30 mg of soil per day.(EHD 1998).
⁷ Based on the maximum 24-hr average concentration (154 *g/m³) predicted in ambient air in a nearby residences located outside of outer property boundary of an ethylene glycol manufacturing facility in Red Deer, Alberta, Canada (Sciences International, 2003). Canadians are assumed to spend 3 hours outdoors each day (EHD 1998). These values are likely underestimated as they do not take into account the higher levels of ethylene glycol expected to be found in indoor air of residences located near the vicinity of an industrial point source.
⁸ Zhu et al. (2004) measured levels of ethylene glycol in nine residential homes (two apartments and seven single detached houses), one attached residential garage, one office and two laboratories. The maximum concentration observed in a residential home (223 µg/m³) was used to calculate the upper-bounding estimate of exposure. Canadians are assumed to spend 21 hours indoors each day (EHD 1998).
⁹ Refer to the State of the Science Report For Ethylene Glycol from 2000 for more details on the values of ethylene glycol that may be found in food and beverages.
¹⁰ Based on the maximum reported concentration (4290 mg/kg) in soil near an industrial point source of discharge (AEP 1996).

¹ Assume this activity would be done outdoors and therefore inhalation exposure to ethylene glycol would be negligible (US EPA, 1986).

* These data were originally modeled in 1999 using a multistage model with a threshold term (d0), which was standard practice at the time. The current practice is to omit the threshold term since the resulting BMDs are more conservative.

The critical information for the hazard characterization was obtained from the rat dietary studies conducted by the Ethylene Glycol Research Task Force of the American Chemistry Council; this information was submitted under Section 71(1)(c) of CEPA 1999. The critical information related to exposure assessment among the general population in Canada was obtained from a letter issued by the Canadian Consumer Speciality Product Association (CCSPA). Additional information was obtained from a study report prepared for the American Chemistry Council; the report consisted of an assessment of estimated human exposure to ethylene glycol in the vicinity of an ethylene glycol manufacturing facility and was used to quantify the level of ethylene glycol to which the people living close to manufacturing facilities were exposed.

A comprehensive literature search was conducted of monitoring data in Canada and/or elsewhere (from January 2000 to January 2007) and toxicological studies in animals and humans (from January 2000 to August 2006) to identify critical new data for the assessment of the human health risk. A search was conducted by chemical name or CAS registry number in the following databases: HSDB (Hazardous Substances Data Bank), TOXLINE, Pubmed, Current Contents (SilverPlatter database), ChemIDplus, IRIS (Integrated Risk Information System), TERA (Toxicology Excellence for Risk Assessment), CCRIS (Chemical Carcinogenesis Research Information System), GENE?TOX, DART/ETIC (Developmental and Reproductive Toxicology / Environmental Teratology Information Centre), IARC (International Agency for Research on Cancer), IUCLID, US EPA (United States Environmental Protection Agency), WHO (World Health Organization) database, Patty's Toxicology database, BIBRA International, OECD (Organisation for Economic Co-operation and Development) database, NPRI 2005 (National Pollutant Release Inventory), Syracuse Research Corporation's Environmental Fate Database, NAPS (National Air Pollutant Surveillance) database, Dow Chemical website, Shell Chemicals website, MEGlobal website, Camford Information Services Product Profiles (2003), and the Pest Management Regulatory Agency (Health Canada) website. A general search was also conducted using the Google search engine.

Updates since January 2000 were obtained through a search of the SciFinder and Cyberus databases. In addition, on-line searches were done through Google Scholar and Google. Updated information on ethylene glycol releases were obtained from the NPRI (National Pollutant Release Inventory). The latest available data at the time of writing was for the 2004-2005 winter season. Airport glycol release information was obtained from Transport Canada's annual Airport Glycol Monitoring Program reports, up to and including 2004-2005.

Management of ethylene glycol at Canadian airports was discussed at some length in the State of the Science Report (Environment Canada and Health Canada, 2000). Some recent improvements in the handling and release of ethylene glycol have been mentioned in the present report.

Data on groundwater concentrations of ethylene glycol are very limited, but some pre 2000 measurements were taken at Calgary International, Charlottetown, Montréal International (Dorval and Mirabel) and Ottawa Macdonald-Cartier International airports. These data are summarized in Table 14 below, along with data obtained from the Edmonton International Airport.

Table 15 presents concentrations of total glycol at selected monitoring stations at Canadian airports for the 2004-2005 deicing season.

¹ For many airports, "total glycol" values have been reported; however, none of the airports listed used other glycols. All samples taken in the immediate vicinity of deicing operations and at shallow depth were excluded. The "detection limit" (DL) is equivalent to minimum values in all cases.