Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – 1,1-Dichloroethylene

1,1-DCE has been detected only infrequently in drinking water in Canada. In a 1979 national survey of 30 municipal drinking water supplies, 1,1-DCE was found in only one treated water supply at a mean concentration of <1 µg/L and a maximum concentration of 20 µg/L.^{Footnote 4} In a 1981 to 1982 survey of drinking water in the lower Great Lakes, 1,1-DCE was detected in one of the 10 municipal supplies, in treated water but not in the untreated supply, at a trace level (<0.1 µg/L).^{Footnote 5} In an Alberta survey conducted from 1978 to 1985, 1,1-DCE was detected in one of 29 municipal drinking water supplies, at a maximum concentration of 1.4 µg/L.^{Footnote 6} Between 1987 and 1994, none of 1900 samples from 300 municipal surface water and groundwater supplies within Alberta contained 1,1-DCE at a concentration above the detection limit of 1 µg/L.^{Footnote 7} 1,1-DCE was not found in surveys conducted in 1985 and 1986 on 40 municipal supplies in the Atlantic region^{Footnote 8} or of 18 supplies in Quebec.^{Footnote 9} In a 1987 survey of the Lemieux Island treatment plant in Ottawa, conducted by the Ontario Ministry of the Environment, 1,1-DCE was not detected in 36 samples taken at the treatment plant or at two distribution sites.^{Footnote 10} In a 1985 to 1988 survey of water supplies in the four Atlantic provinces, 1,1-DCE was not detected in raw or treated drinking water samples taken from 151 sampling stations; the minimum quantifiable limit ranged from 0.5 to 1.0 µg/L.^{Footnote 11Footnote 12Footnote 13Footnote 14} In a 1981 survey of surface water samples taken from Lake Ontario, 1,1-DCE was detected (detection limit 0.09 µg/L) in 11 of 82 samples taken; concentrations ranged from trace to 3.5 µg/L. Maximum concentrations were generally near 0.19 µg/L.^{Footnote 15} Because of its volatility, there is potential for exposure in the home to airborne 1,1-DCE released from tap water.

The leaching of solvents into groundwater is a potential source of 1,1-DCE contamination. The presence of 1,1-DCE in 43% of the groundwater samples at the Gloucester, Ontario, landfill site (concentrations ranged from 0.9 to 60 µg/L) sampled in 1988 is thought to have resulted from the degradation of tetrachloroethylene and 1,1,1-trichloroethane, as 1,1-DCE is a known degradation product of these two compounds and was not known to have been disposed of at the site.^{Footnote 16} Ambient air sampling for 1,1-DCE was carried out by Environment Canada yearly between 1988 and 1990.^{Footnote 17} In 1988, 1,1-DCE was detected in only two of 21 samples (maximum concentration 0.1 µg/m³) taken from five sites in two cities between October and December. In 1989 and 1990, sampling was carried out at 17 sites in 10 cities. 1,1-DCE was detected in 17% (n = 503; maximum concentration 0.4 µg/m³) and 3% (n = 750; maximum concentration 0.5 µg/m³) of the samples in 1989 and 1990, respectively. 1,1-DCE was detected in a survey of ambient air in Windsor and at Walpole Island, Ontario.^{Footnote 18} The mean 1,1-DCE concentration was <0.1 µg/m³ in samples taken between July 1987 and October 1990 in Windsor and in samples taken between January 1988 and October 1990 at Walpole Island; maximum concentrations were 0.3 µg/m³ and 0.2 µg/m³ for Windsor and Walpole Island, respectively. In a limited study, Chan et al.^{Footnote 19} found that concentrations of 1,1-DCE in ambient air in Canada were highest in November/December (3.2 µg/m³).

Chan et al.^{Footnote 19} also detected 1,1-DCE in the indoor air of a small number of Canadian homes. Average indoor concentrations were 8.4 µg/m³ and 8.8 µg/m³ for sampling done in November/December and February/ March, respectively; a maximum concentration of 77 µg/m³ was detected. 1,1-DCE has been identified in indoor air samples (both residences and offices) as well as in commuting automobile air samples collected in metropolitan Toronto.^{Footnote 20} In a small number of home and office samples, the mean concentrations of 1,1-DCE were 5.4 µg/m³ and 5.0 µg/m³, respectively; maximum concentrations were 9.0 µg/m³ and 20.2 µg/m³, respectively. The average concentrations of 1,1-DCE in the air in five commuter vehicles (two private automobiles and three public transit vehicles, one to two hours each way) in the morning and evening were 4.3 µg/m³ and 3.6 µg/m³, respectively; mean concentrations in ambient air were 0.4 µg/m³ at both times.

There are no Canadian or U.S. data on exposure to 1,1-DCE via food, and it is therefore not possible at this time to estimate average intake from food. However, residual 1,1-DCE monomer is known to be present in food packaging materials. Concentrations of 1,1-DCE ranging from <0.2 to 26.2 ppm (mg/kg) have been reported in various household and industrial films used for food packaging.^{Footnote 21Footnote 22} 1,1-DCE was not detected in snacks, cheese or baked goods, but it was present in the outer layers of cooked meat products at concentrations ranging from 5 to 10 ppb (µg/kg)^{Footnote 22} and in potato chips at 26 ppb and 34 ppb after 48 and 90 days, respectively.^{Footnote 23} 1,1-DCE has been detected in composite samples of clams from The Rigolets, a pass between the Mississippi River (U.S.A.) and the Gulf of Mexico, at a concentration of 4.4 ppb wet weight.^{Footnote 24} The factors that govern migration of 1,1-DCE into food include the type of food packaged, the original concentration of the monomer in the packaging, the storage temperature and the length of time of contact during storage.^{Footnote 23} This was demonstrated in a study in which potato chips were packaged and stored in film containing 1,1-DCE at 0.4, 0.8 or 1.2 mg/m² for 48 or 90 days.^{Footnote 25} The data indicated that the 1,1-DCE concentration was highest in the food product packaged in film with the highest original 1,1-DCE content and with the longest storage time.

It has been estimated in the United Kingdom that the maximum possible intake of 1,1-DCE from food as a result of the use of packaging materials containing the monomer is no more than 1 µg/d per person.^{Footnote 26} If a 1,1-DCE concentration of 0.5 µg/L in drinking water is assumed, the estimated intake would be less than 1 µg/d for an adult consuming 1.5 L of drinking water per day. The concentrations of 1,1-DCE found in both ambient and indoor air would result in a higher intake of 1,1-DCE from air than from either food or drinking water. It is therefore probable that less than 10% of total 1,1-DCE intake is normally ingested in drinking water.

Analytical Methods and Treatment Technology

1,1-DCE may be detected by purge and trap gas chromatography followed by flame ionization detection or mass spectroscopy.^{Footnote 4Footnote 5} Based on its similarity to seven other volatile organics, its minimum practical quantitation limit (PQL) is 5 µg/L.^{Footnote 27} Available data indicate that concentrations of 1,1-DCE are not reduced significantly during conventional drinking water treatment processes.^{Footnote 4Footnote 5Footnote 27} Removal of 90 to 95% of 1,1-DCE, to levels below 1 µg/L, may be achieved using packed tower aeration or granular activated carbon.

Health Effects

Mammals readily absorb 1,1-DCE after either inhalation or ingestion; dermal absorption is also assumed to occur.^{Footnote 28Footnote 29} 1,1-DCE is rapidly distributed to the tissues following oral or inhalation exposure, with preferential accumulation in the liver, kidneys and lungs. Elimination occurs primarily via urine and exhaled air.^{Footnote 30} Complete absorption was observed in fasted and fed male rats given a single oral 1,1-DCE dose of 200 mg/kg bw in mineral oil, corn oil or aqueous Tween-80.^{Footnote 31} The total amount of 1,1-DCE exhaled was not affected by the magnitude of the dose administered, nor was the initial rapid-phase exhalation half-time of 1,1-DCE. In contrast, however, the later slow phase of 1,1-DCE exhalation was predictably affected by the administrative vehicle, with ^t½ values increasing in the following order: Tween-80 < corn oil < mineral oil.

1,1-DCE is metabolized to a reactive intermediate via the mixed-function oxidase (MFO) pathway, which is saturable at relatively low doses, irrespective of the route of administration.^{Footnote 32} Inhalation studies in rats exposed to 150 ppm 1,1-DCE for two hours demonstrated a metabolic threshold for the MFO pathway.^{Footnote 29Footnote 33Footnote 34} Metabolic thresholds were also observed in small male rats orally dosed at 25 mg/kg bw and in female rats at 100 mg/kg bw.^{Footnote 32} By analogy with the proposed mechanism for other chlorinated ethylenes,^{Footnote 35} the metabolism of 1,1-DCE has been suggested to produce an epoxide, presumed to be a transient unstable intermediate. The epoxide would readily conjugate with glutathione by glutathione-S-transferase, be hydrolysed by epoxide hydratase or react with nucleophilic centres. Thus, depletion of glutathione, by pretreatment with inhibitors such as diethyl maleate or by fasting, would decrease the potential of the rat to detoxify the reactive intermediates.

In support of this hypothesis, hepatotoxicity has been found to increase in glutathione-depleted animals, which suggests that detoxification of the intermediate metabolite occurs mainly through glutathione conjugation.^{Footnote 32} As well, a reduced rate of 1,1-DCE metabolism and an increase in 1,1-DCE toxicity have been observed in fasted rats receiving oral doses of 1,1-DCE. The effects of an oral 1,1-DCE dose of 50 mg/kg bw on fed, fasted and hyperthyroid (T₄) male rats were reported by Kanz et al.^{Footnote 36} The differences observed in body temperature (hypothermia in fasted rats), serum glucose concentrations (hypoglycaemia in fed and T₄ rats; hyperglycaemia in fasted rats) and hepatic glutathione and glutathione transferase (decreased in both fasting and T₄ rats) were indicative of different pathways or mechanisms of toxicity in fasted and hyperthyroid rats. Liver injury was found to be minimal in fed rats, moderate in fasted rats and intermediate in T₄ rats. Chieco et al.^{Footnote 31} found that liver injury was only slight in fed animals regardless of vehicle of administration; however, liver injury in fasted rats was moderate (Tween-80) to massive (mineral oil and corn oil).

Oral LD₅₀ values (olive or corn oil) of 1510 to 1800 mg/kg bw and 1500 mg/kg bw have been determined for male and female rats, respectively.^{Footnote 37Footnote 38} In mice, Jones and Hathway^{Footnote 39} reported LD₅₀ values of 194 mg/kg bw in females and 217 mg/kg bw in males. Bronchial injury in mice and hepatic damage in rats have been reported following acute exposure to 1,1-DCE.^{Footnote 32Footnote 40} In an abstract, Quast et al.^{Footnote 41} described a study in which Sprague-Dawley rats were exposed to 1,1-DCE in their drinking water at concentrations of 0, 60, 100 or 200 ppm for 90 days, equivalent to concentrations of 0, 6, 10 or 19 mg/kg bw per day in males and 0, 8, 13 or 26 mg/kg bw per day in females. The only effect observed was reversible minimal hepatocellular cytoplasmic vacuolation reported in several rats (sex not stated) in the 200 ppm dose group. In a 13-week study by the National Toxicology Program (NTP),^{Footnote 42} rats and mice (10 per sex per dose) were administered 1,1-DCE at 0, 5, 15, 40, 100 or 250 mg/kg bw per day by gavage in corn oil, five times a week. In both species, the liver was identified as the target organ, with fatty metamorphosis, congestion, centrilobular or cellular necrosis, hepatocytomegaly, fibrosis or focal areas of cellular alteration being observed. 1,1-DCE (99.5% purity) was administered in peanut oil incorporated into gelatin capsules to beagle dogs (four per sex per dose) at doses of 0, 6.25, 12.5 or 25 mg/kg bw per day for 97 days.^{Footnote 43} Necropsy and histopathological examination did not reveal any exposure-related changes in tissues.

Although a few epidemiological studies involving 1,1-DCE have been reported, interpretation of the data is confounded by concomitant exposure to vinyl chloride. In the only study reported where vinyl chloride was not used as a copolymer, Ott et al.^{Footnote 44} examined the mortality and health of 138 employees exposed to 1,1-DCE and reported no findings that were statistically related or individually attributable to 1,1-DCE exposure. The International Agency for Research on Cancer^{Footnote 45} concluded that this study was not adequate to permit an assessment of human carcinogenicity, noting that 27 workers were lost to follow-up but considered to be alive in the analyses, 55 individuals had less than 15 years since first exposure and only five deaths had been observed.

In the only study to date to report carcinogenicity, Maltoni et al.^{Footnote 23}exposed Swiss mice (either 30 or 60 per sex per dose; 100 per sex in the control group) to 1,1-DCE by inhalation at doses of 0, 10, 25, 50, 100 or 200 ppm, four hours per day, four to five days per week for 52 weeks. A second 25 ppm treatment group (120 per sex; 90 per sex for controls) was added to further assess the carcinogenicity at 25 ppm. In both studies, following the 52-week dosing, the mice were allowed to survive either until spontaneous death or until 126 weeks. Excesses in mortality were reported in mice exposed to 50, 100 and 200 ppm. An increase in kidney adenocarcinomas (significance not stated) in male mice, a rare tumour in mice, was observed in the 25 and 50 ppm dose groups. Incidences using corrected values (animals alive when first kidney adenocarcinoma was observed) were 0/54, 0/24, 3/21, 2/18, 0/13 and 0/1 for the 0, 10, 25, 50, 100 and 200 ppm dose groups and 0/66 and 25/98 for the second control and 25 ppm dose groups. A kidney adenocarcinoma was also reported in a female mouse in the larger 25 ppm group.

Several carcinogenicity studies in which 1,1-DCE was orally administered have yielded negative results. Groups of 50 male and 50 female rats were administered 1,1-DCE in olive oil by gavage for 52 weeks at doses of 0, 0.5, 5, 10 or 20 mg/kg bw per day, four to five days per week, and allowed to survive until spontaneous death. There was no evidence of treatment-related or dose-related effects from exposure to 1,1-DCE by gavage.^{Footnote 23}The authors stated that the lack of neoplastic response in the study was difficult to assess and may have been due to the animal system, the route of administration or the level of the daily dose used in the experiment.

In the most adequate study to date to investigate carcinogenicity via the oral route using the most appropriate vehicle of administration, 1,1-DCE (99.5% purity) was incorporated into the drinking water of groups of male and female Sprague-Dawley rats (48 per sex per dose) for two years.^{Footnote 43}Time-weighted average daily dose levels were 0, 7, 10 or 20 mg/kg bw for males and 0, 9, 14 or 30 mg/kg bw for females. No treatment-related effects on mortality, body or organ weights or haematological, urinary or clinical chemistry end points were observed. Histopathological examination showed no exposure-related neoplastic changes in rats of any treatment group; however, a minimal amount of hepatocellular swelling with mid-zonal fatty change was observed in females at all dose levels and was significant in males in the 20 mg/kg bw per day dose group only. A dose-related trend for females was not stated; in males, however, a "trend towards increased hepatic changes" was observed in the 10 mg/kg bw per day dose group.

There was no evidence of carcinogenicity of 1,1-DCE in an investigation by the NTP.^{Footnote 42}Doses of 0, 1 or 5 mg/kg bw per day in corn oil were administered by gavage, five days per week for 104 weeks, to groups of 50 male and 50 female F344/N rats. Similarly, doses of 0, 2 or 10 mg/kg bw per day were administered to B6C3F₁/N mice. There was an increased incidence of liver necrosis (focal, multifocal or diffused) in high-dose male mice and low-dose female mice and chronic renal inflammation in high-dose rats of both sexes. Increased tumour incidences (lymphoma only; lymphoma or leukaemia) in low-dose female mice were not considered to be treatment-related, as these effects were not observed in high-dose female mice, in male mice or in rats. It should be noted that 12 control and 10 low-dose male rats were accidentally killed during week 82 of the study, which may have compromised the sensitivity of the male rat study. Under the conditions of the bioassay, 1,1-DCE administered by gavage was not carcinogenic for F344/N rats or B6C3F₁/N mice of either sex. The NTP noted, however, that the use of a maximum tolerated dose in the oral dose study had not been clearly demonstrated, as indicated by the absence of compound-related effects on survival or clinical signs of toxicity, and that carcinogenicity had been associated with inhalation exposure to 1,1-DCE.^{Footnote 23}1,1-DCE was administered by stomach tube (150 mg/kg bw in olive oil) as a single dose to 24 female BD IV rats on day 17 of gestation, and weekly doses of 50 mg/kg bw were administered to the 89 male and 90 female progeny for 120 weeks.^{Footnote 37}Controls, receiving olive oil only, followed the same dosing schedule. Litter sizes, pre-weaning mortality and survival rates were similar in exposed and control groups. There was no significant difference between exposed and control rats in the total number of tumour-bearing animals, although there were increases in the incidence of some tumours at certain sites. Non-significant increases in tumours observed in treated males and females but not in vehicle controls included a squamous cell carcinoma of the stomach (male), liver cell carcinomas (one male; two females), a seminoma (male), a rectal adenomatous polyp (male), a liver cell adenoma (female) and a carcinoma and adenoma of the salivary gland (female). Hyperplastic liver nodules were significantly increased (p = 0.04) in both sexes of treated progeny (2/81 males; 6/80 females) and in 2/23 treated dams, but not in controls. The authors concluded that there was "limited evidence of carcinogenicity," although additional study was required. It was also stated that the maximum tolerated dose was not reached, as indicated by a lack of obvious toxic effects in the dosed animals.

Footnote 1

1,1-DCE has been mutagenic in several reverse gene mutation assays using Salmonella typhimurium, Escherichia coli K12 and Saccharomyces cerevisiae D7, only in the presence of metabolic activation,^{Footnote 46Footnote 50} and in a mouse host-mediated microbial assay with S. cerevisiae D7 following gavage of 1,1-DCE in corn oil.^{Footnote 50}Negative results have been obtained in both rat and mouse dominant lethal studies.^{Footnote 51Footnote 52} Several in vivo and in vitro mammalian cytogenetic studies have failed to produce any significant positive results. Drevon and Kuroki^{Footnote 53} reported no increases in 8-azaguanine-resistant and ouabain-resistant colonies in Chinese hamster V79 cells exposed for five hours to 1,1-DCE in desiccators. In a more recent in vitro study, Sawada et al.^{Footnote 54} reported a weak but significant increase in the incidence of sister chromatid exchanges and a dose-dependent induction of chromosomal aberrations observed in the Chinese hamster cell line (CHL), but only in the presence of S9 activation. In in vivo mammalian studies, Quast et al.^{Footnote 55} observed no adverse effects (chromatid or chromosomal aberrations) of femoral bone marrow cells of Sprague-Dawley rats exposed to 25 or 75 ppm 1,1-DCE via inhalation for six months. A micronucleus test in the liver and blood of fetuses of ddY mice treated with 1,1-DCE was also negative; there was also no increase in the frequency of micronucleated erythrocytes in bone marrow.^{Footnote 54}Positive findings of increases in chromosomal aberrations in bone marrow cells of Chinese hamsters have, however, been reported by Hofmann and Peh^{Footnote 56} and Zeller and Peh.^{Footnote 57}

Sawada et al.^{Footnote 54}also examined the role of cytochrome P-450 in the metabolic activation of 1,1-DCE. The results indicated that the induction of chromosomal aberrations was inhibited by the addition of metyrapone and glutathione; tests of two metabolites of 1,1-DCE, chloroacetyl chloride and chloroacetic acid, were also negative. The authors concluded that the findings were compatible with the hypothesis that 1,1-DCE oxide may be the active genotoxic metabolite, although mutagenicity testing of this compound has not been reported because stabilized 1,1-DCE oxide is difficult to obtain.

Developmental effects of 1,1-DCE have not been demonstrated. Murray et al.^{Footnote 58} exposed pregnant rats to 1,1-DCE in their drinking water at doses of 0 or 200 ppm (equivalent to 40 mg/kg bw per day) on days 6 to 15 of gestation. There was a significant increase in the mean fetal crown-rump length in the litters of exposed rats, but no evidence of toxicity to the dams or their offspring. The authors concluded that, under the conditions of the experiment, 1,1-DCE was not teratogenic to rats.

Nitschke et al.^{Footnote 59} investigated the fertility of male and female Sprague-Dawley rats (F₀: 10 males and 20 females) and neonatal toxicity in a three-generation, six-litter study in which animals were exposed to 0, 50, 100 or 200 ppm 1,1-DCE continuously in their drinking water. Calculated doses were equivalent to approximately 0, 7, 14 or 29 mg/kg bw per day in the F₀ adults.^{Footnote 60} Histopathological examination was conducted on tissues of rats that had been exposed in utero, during lactation and post-weaning. Dose-related mild hepato-cellular fatty changes were observed, as well as an accentuated hepatic lobular pattern that was reversible in adult rats. There was no evidence that fertility was affected by exposure to 1,1-DCE, although low fertility rates were observed in both treatment and control groups. Observations of six sets of litters throughout the three generations suggested that the reproductive capacity had not been affected.

Classification and Assessment

1,1-DCE is mutagenic with metabolic activation in in vitro assays and weakly genotoxic in some in vivo studies. The mutagenicity of 1,1-DCE in vitro requires the use of S9 from metabolically induced mouse or rat liver. S9 from uninduced liver does not seem to be effective. These results are a clue to the rather specific conditions that are required to produce a positive result in vivo. Effects are seen only in hamsters that have a unique pattern of P-450 metabolism, whereas a number of other in vivo studies in mice are negative. The positive host-mediated result in mice may be due to detection of a weak effect by this rather specialized assay resulting from low levels of metabolites present in the mouse. The limited metabolic conditions under which mutagenic effects are seen support the finding of limited tissue-specific carcinogenicity.

Available epidemiological data are inadequate for assessment of the carcinogenicity of 1,1-DCE in humans. There has been some evidence, in one study, of increased kidney tumour (adenocarcinomas) incidence in male mice exposed to 1,1-DCE by inhalation.^{Footnote 23} The compound was not, however, carcinogenic in several (including one adequate) bioassays by the ingestion route. Limiting factors with the Maltoni study^{Footnote 23} include less-than-lifetime exposure, lack of a clear dose-response relationship and no indication of statistical significance for the observed tumours. Studies using orally administered 1,1-DCE have yielded negative results, although small increases in liver tumour incidence have also been observed in rats and offspring of exposed mothers in a limited bioassay by Ponomarkov and Tomatis.^{Footnote 37} The evidence for the carcinogenicity of 1,1-DCE is, therefore, considered to be limited, and the compound has been classified in Group IIIB (possibly carcinogenic to humans).

For compounds classified in Group IIIB, the acceptable daily intake (ADI) is usually derived on the basis of division of a no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) by an uncertainty factor that takes into account the limited evidence of carcinogenicity. For 1,1-DCE, however, no adequate studies by the oral route that resulted in adverse effects were identified.

Therefore, a LOEL (lowest-observed-effect level) of 9 mg/kg bw per day, based on mid-zonal fatty changes in the liver observed in female rats, and an additional uncertainty factor of 10 for use of a LOEL instead of a NOAEL were used to derive the ADI as follows:

 

 

where:

• 9 mg/kg bw per day is the LOEL for mid-zonal fatty changes in the liver of female rats, observed in the two-year study with the most appropriate route and vehicle of administration (i.e., drinking water)^{Footnote 43}
• 3000 is the uncertainty factor (×10 for interspecies variation; ×10 for intraspecies variation; ×10 for use of a LOEL; and ×3 for limited evidence of carcinogenicity, based on an inhalation study using a different species [mouse] and with a different target organ [kidney], in view of the fact that studies by the oral route are negative).

It should be noted that the effect level on which the ADI was derived is similar to that for the same effects observed in the reproductive study by Nitschke et al.^{Footnote 59}

Rationale

1,1-DCE is a known degradation product of tetrachloroethylene and 1,1,1-trichloroethane, which are common groundwater contaminants. Because 1,1-DCE is classified in Group IIIB, the maximum acceptable concentration (MAC) for 1,1-DCE in drinking water is derived from the ADI as follows:

 

 

where:

• 0.003 mg/kg bw per day is the ADI, as derived above
• 70 kg bw is the average body weight of an adult
• 0.10 is the proportion of total 1,1-DCE intake considered to be ingested in drinking water (see "Exposure" section)
• 1.5 L/d is the average daily consumption of drinking water for an adult.

References