Document MZEx1gkkbZZBYeQG7xOwdwky

Harch 31, 198 7 I. INTRODUCTION TETRACHLOROT}fLEN (PCX) Health Advisory - Office of Drinking Water O.s. Environmental Protection Agency ( The Health Advisory (HA) Program, sponsored by the Office of Drinking Water (ODW), provides Information on the health effects, analytical method ology and treatment technology that would be useful in dealing with the contamination of drinking water* Health Advisories describe nonregulatory concentrations of drinking water contaminants at which adverse health effects would not be anticipated to occur over specific exposure durations. Health Advisories contain a margin of safety to protect sensitive members of the population. Health Advisories serve as Informal technical guidance to assist Federal, State and local officials responsible for protecting public health when emergency spills or contamination.situations occur. They are not to be construed as legally enforceable Federal standards* Hie HAa are subject to change as new information becomes available* Health Advisories are developed for One-day, Ten-day, Longer-term (approximately 7 years, or 10% of an individual's lifetime) and Lifetime exposures based on data describing noncarclnogenic end-points of toxicity. Health Advisories do not quantitatively incorporate any potential carcinogenic risk from such exposure. For those substances that are known or probable human carcinogens, according to the Agency classification scheme (Group A or 5), Lifetime HAs are not recommended. Hie chemical concentration values for Group. A or B carcinogens are correlated with carcinogenic risk estimates by employing a cancer potency (unit risk) value together with assumptions for Lifetime exposure and the consumption of drinking water* The cancer unit risk is -usually derived from the linear multistage model with 95% upper confidence limits. This provides a lew-dose estimate of cancer risk to humans that is considered unlikely to pose a carcinogenic risk in excess of the stated values. Excess cancer risk estimates may also be calculated using the One-hit, Weibull, Logit or Problt models. There Is no current understanding of the biological mechanisms involved in cancer to suggest that any one of these models is able to predict risk more accurately than another. Because each model is based on differing assumptions, the estimates that are derived can differ by several orders of magnitude. 304 NGC36691 -2- Thts Health Advisory (HA) is based on Information presented In the Office of Health and Environmental Assessment Criteria Document (CD) for Tetrachloroethylene (U.S. EPA, 1985a). Individuals desiring further informa tion on the toxicological data base or rationale for risk characterization should consult the CD. The CD Is available for a fee. from the National Technical Information Service, U.S. Department of Commerce, 5265 Port Royal Rd., Springfield, VA, 22161. The toll-free number la (800) 336-4700; in the Washington, D.C. area: (703) 487*4650. II. GENERAL INFORMATION AND PROPERTIES CAS So. 127-18-4 Structural Formula Cl - C * C - Cl .I I Cl Cl Synonyms PCE, Perchloroethylene, 1,1,2,2-Tetrachloroethylene, Perc Uses Solvent for many organic substances In drycleaning processes Metal degreaser Intermediate in the synthesis of certain fluorocarbons In the textile industry (Puller, 1976) Properties (Verschueren,. 1977? Torkelsen and Rowe, 1981? Windholz, 1983) Chemical Formula Molecular Weight Physical State Boiling Point Melting Point Density Vapor Pressure Specific Gravity Water Solubility Log Octanol/Water Partition Coefficient Taste Threshold Odor Threshold (water) 1 ppm in air Conversion Factor C2C14 165.85 . liquid 121.2C -- -- 19 mm Eg 1.623 150 mg/L (25*C) 2.86 -- 300 ug/L 6.78 mg/m^ -- _ 305 NGC36692 Tetrachloroethylene -3- March 31, 1987 ,Occurrence * Tetrachloroethylene (PCE) is a synthetic chemical with no natural sources. * Production of PCE was 550 million pounds in 1982 (0.S. ITC, 1983). * The majority of PCE is not consumed during its various uses, but is released directly to the atmosphere. Tetrachloroethylene that does not evaporate during use becomes heavily contaminated with grease and oil and la disposed of in the forma of solid and liquid wastes. During disposal, PCE .is dischrarged directly to land and surface water. Sfcs'.'se metal and fabric cleaning industries are widely dispersed, PCE releases occur nationwide. * PCE released to air degrades In a matter of days or weeks. PCE released to water degrades slowly; volatilization appears to be the major transport process for removal of PCE from aquatic systems (U.s. EPA, 1979). It Is very mobile In soil and readily migrates to ground water. In ground water# where volatilization does not occur# PCE remains for months or years. Under certain conditions# PCE in ground water has been reported to degrade to trichloroethylene and then to dlchloroethylene and vinyl chloride (Parsons et al., 1984; Vogel arid McCarty, 1985), * Tetrachloroethylene is ubiquitous in the air with levels in the ppt to ppb range. It Is also a common contaminant In ground and surface waters with higher levels found in ground water. Surveys of drinking water supplies'have found that' 3% of all public systems derived from well water contain PCE levels of 0.5 ug/L or higher. A small number of systems (0.7%) have levels higher than 5 ug/L. Public systems derived from surface water have also been found to contain tetrachlorethylerre but at lower levels. 0 The major sources of exposure to tetrachloroethylene are from contami nated water and to a lesser extent air. Tetrachloroethylene has been .reported to occur in some, foods in the'ppm range, but food is considered only, a minor source of exposure (U.S. EPA, 1983). PHARMACOKINETICS Absorption 0 Single oral doses of (S^CD-PCE were absorbed completely when admini stered to rats at a concentration of 189 mg/kg (Daniel# 1963) as were doses of (14c)-PCE administered to mice at a dose of 50.0 mgAg (Schu mann et al., 1980).* * Human volunteers at rest absorbed about 25 percent of PCE admini stered by inhalation exposure at 72 or 144 ppo over a four-hour period. The compound initially was absorbed rapidly, with decreasing uptake as exposure continued. Absorption was determined' by measuring PCE and its metabolites (trichloroethanol,' trichloroacetic acid) in exhaled air, blood and urine (Monster, 1979; Monster et al., 1979; Monster and Houtkooper, 1979). 306 NGC36693 Distribution -4- ' Once In the bloodstream, PCE tends to distribute to body fat. In human tissue at autopsy, ratios of fat to liver concentrations are greater than 6:1 (McConnell et al., 1975), The fat to blood ratio Is about 90 and the half-life for saturation of the fat to 50% of its equilibrium concentration is about 25 hours (Monster, 1579). * In rats exposed via inhalation, PCE levels rise sore or less continu ously with duration of exposure in brain, lungs, and fat, but tend to level off in blood and liver after a 3-hour exposure. Brain cerebrum concentrations of PCE exceed blood levels by about four-fold, and brain cerebellum by about three-fold, independent of the duration of exposure (Savolainen et al., 1977). Metabolism Only small amounts of PCE (less than 4% of the estimated absorbed dose) are metabolized - and excreted as trichloroacetic acid in humans (Ogata et al., 1971; Fernandez et al., 1976)* 0 Oxidative metabolism Is proposed to proceed via an epoxide intermediate which can lead to the major metabolite, trichloroacetic add. (U.S. EPA, 1985a). In humans, PCE is metabolized to trichloroethanol, trichloroacetic acid and unidentified chlorinated products (Ikeda and Ohtsuji, 1972? Ikeda, 1977). * Workers exposed occupationally reached a plateau rate of urinary metabolite excretion (measured as total trichloro-coopounds) when the. workplace air concentrations of PCE approached 100 ppm. Metabolite ' excretion did not increase when air concentrations rose to 400 ppm (Ikeda et al,, 1972). Excretion 9 PCE itself is eliminated primarily via the lungs. The respiratory half-life for PCE elimination has. been estimated at 6.5 to 70 hours (Stewart et al., 1970; Ikeda and Imamura, 1973). 0 Trichloroacetic acid, as a metabolite of PCE, is eliminated with a half-life of 144 hours via the urine (Ikeda and Imamura, 1973). IV. HEALTH EFFECTS Humans * Liver, kidney, and CNS effects have been observed in humans occupationally exposed to tetrachloroethylene (U.S. EPA, 1985a). Hookworm trsitr.gr.t with oral PCE was prevalent in the 1920s and 1930s In India and the Pacific Islands. Thousands of individuals received oral doses of approximately 0.15 mL/kg (Kendrick, 1929) or a total dose of about 4 mL for adults (Fernando et al., 1939). No-effect levels for oral exposure cannot be derived from these clinical reports. * 307 NGC36694 Tetrachloroethylene -5- although they suggest that PCE is relatively nontoxic by the oral route at these doses* Stewart et al. (1974) exposed 19 volunteers to PCE (20'to 150 ppm) for a 5-week period and noted deleterious effects (decreased odor perception, diminished response on the modified Romberg test) at 100 ppm but not at 20 ppm* Animals Short-term Exposure 9 In mice,. the 24-hour DD5QS/LC50B cures 8*8 to 10*8 g/kg by the oral route (Wenzel and Gibson, 1951), 5,200 ppm with 4 hours inhalation exposure (Frtberg et al*, 1955) and 4*7 gAg lntraperitoneal (Klaassen and Plaa, 1966)* 9 In rats, the 24-hour LE>soa/LC503 are 13 SA? oral (Smyth et al*, -1969) and 4,000 ppm with four hours inhalation ea^osure (Carpenter- et al., 1949). 9 Single oral gavage doses of 2,158 agAg PCS to rabbits' resulted In a 50% Increase in serum lipoprotein levels and mild transient elevations ct serum enzymes (alkaline phosphatase, SGOT, SGPT) which were indica tive of liver daaage (Fujii, 1975). * A dose-response related Increase in fatty Infiltration of the livers of mice was observed after four hours of' exposure to-200 to 5,000 ppm (140Q to 20,000 mg/m3) via inhalation (Kylin et al*, 1963)* Decreased hepatic ATP and increased total lipid and.triglyceride levels were observed in mice exposed to 800 ppm PCS In air for three hours (Ogata et al., 1966). 9 Schumann, et al. (1980) administered.tetrachloroethylene in corn oil ' to rats and mice via gavage for 11 consecutive days at does .of 100, 250, 500 and 1000 mgA?* For mice, histopathologieal changes (centrilobu- lar swelling) were observed at ali dose levels and Increased body weight/ liver weight ratios -were observed at doses of 250 mg/kg/day and higher. Rats were more resistant with toxicity (increased liver weight and serum enzyme levels) apparent only at the highest dose* A LOAEL of 100 mgAs/day was identified based on histopathologieal changes in mice.. .. Donger-term Exposure -' 9 Rats were exposed to 70, 230 or 470 ppm PCE (470, 1600, or 3200 mg/m3) by inhalation 8 hours/day, 5 days/week for 150 days* Mo significant changes were observed at 70 ppm; renal and liver congestion and swelling were observed at 230 and 470 ppm (Carpenter,' 1937)* 9 Rats, rabbits and monkeys were exposed via inhalation to PCE at 400 ppm (2700 mg/a3) 7 hours/day, 5 days/week for up to 179 days (Rowe, et al., 1952). Histopathologieal examination of the liver, kidney and spleen revealed no significant changes at this exposure' level* 3 02 NGC36695 -6- 4 Guinea pigs showed a dose dependent Increase In liver weight and fatty infiltration of the liver when exposed to 100, 200 or 400 ppm (680, 1400, or 2700 mg/m3) for up to 169 exposures over 236 days (Rowe et al., 1952). Kylin et al. (1965) observed fatty infiltration in livers of mice exposed to 200 ppm (1400 ng/m3), 4 hours/day, 5 days/week for 8 months. * In a study by Buben and O'Flaherty (1985), male Sviss-Cox mice were exposed to tetrachloroethylene in corn oil via gavage at doses of 0, 20, 100, 200, 500, 1000, 1500, and 2000 ag/kg, 5 days/week for 6 weeks. Liver toxicity was evaluated by several parameters Including liver weight /body weight ratio, hepatic triglyceride concentrations, OKA content, hlstopathologlcal evaluation and serum enzyme levels. Increased liver triglycerides were first observed in mice treated with 100 mg/k?** Liver weight/body weight ratios were significantly higher than controls for th 100 mgA9 group, and slightly higher than controls in the 20 mg/kg group. A K0AEL of 20 mgAs/day was identified based on the absence of hepatotoxtc effects. e Toxic nephropathy was observed in mice exposed to 386 and 1072 mgAg In corn oil via gavage, 5 days/week, for 78 weeks (NCI, 1977). Reproductive Effects Rabbits showed liver enzyme changes and renal function alterations following 200 to 30.0 ppm exposures (1400 to 20,000 mg/m3), 4 hours/day, 5 days/week for 9 weeks (Brahcaccio et al., 1971; Mazza, 1972). Pregnant rats exposed to 300 ppm PCE (20,000 mg/m3) for 1 hours/day, on days 6 through 15 of gestation had 4 to 5% reduction in body weight and twice the number of resoprtions per implantation compared with controls (Schwetz et al. (1975). Developmental Effects ? Schwetz et al. (1975) assayed'for reproductive and developmental effects in rats and mice exposed to 300 ppm PCE (20,000 mg/m3.) by inhalation for 7 hours/day on gestational days 6 through 15. Pregnant mice exhibited a significant increase in the mean relative liver weights and their fetuses weighed significantly less than controls. In the mouse pups, significant subcutaneous edema, delayed skull ' ossification and t^he presence of split stemebrae were observed. Offspring of rats exposed to PCE (900 ppm [6100 mg/m3J, days 7-13 of gestation; 900 ppm, days 14-20 of gestation; 100 ppm [680 mg/m3], days 14-20 of gestation) were evaluated with respect to brain histopathoiogy and biochemistry and several behavioral parameters. No significant differences were found between controls and the 100 ppm dose group. Differences In neurotransmitter levels and some altera tions on behavioral tests were noted in the 900 ppm dose groups. 309 \ NGC36696 Tetrachloroethylene -7- warcn ji, 50 > Mutageniclty 0 Several mutagenicity studies have been performed on PCS which -employ the Ames Salwionella/microsome test or modifications of this test* Most tests reveal little or no evidence of mutagenic activity by PCS except at concentrations which result in greater than 90% bacterial' toxicity (U.S. EPA, 1985a). ' Carcinogenicity * PCE containing stabilisers was concluded by NCI (1977) to be a liver carcinogen In B6C3F^ mice administered 386 to 1,072 mgAg by gavage for 78 weeks. No conclusion concerning the effects on Osborne-Mendel rats administered 471 to 949 mg/k? by gavage could be made because of high mortality rates (median survival for treated animals was less than 60 weeks compared to greater than 88 weeks for controls). 0 Zn the NTP (1985) inhalation bioassay, rats and alee of both sexes were exposed to 0, 200 and 400 ppm (rats) and 0, 100 and 200 ppm (mice) tetrachloroethylene. Male rats exhibited a significantly Increased Incidence of mononuclear cell leukemia, and an increased Incidence of renal tubular adenomas/carcincnas (combined). PCE induced hepatocellular carcinomas In male and female mice at both doses. * Classification of PCE as carcinogenic in the rat is. contro versial. The Science Advisory Board's Halogenated Organics Subcommittee (U.S. EPA, 1987) has questioned the relevance of mononuclear leukemia to. .man, a species not susceptible to this type of leukemia, and the validity of combining renal adenomas/carcinomas to achieve statistical significance to the results. V, QUANTIFICATION OF. TOXICOLOGICAL EFFECTS Health Advisories (HAs) are generally determined for One-day, Ten-day, Longer-term (approximately 7 years) and Lifetime exposures If adequate data are available that identify a sensitive noncarclnogenic end point of toxicity. The HAs for noncarcinogenic toxicants are derived, using the following formulas r *>OAEL) * .(bit? B ____ m/l (___ Lug/t) (OF) x (_____L/day) . where; NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level in mg/ks hw/day. aw assumed body weight of a child (10 kg) or an adult (70 kg)* UF * uncertainty factor (10, 100 or 1,000), in accordance with NAS/0DW guidelines. ____ L/day assumed daily water consumption of a child 311 NGC36697 -8- Ona-day Health Advisory The available studies were not considered sufficient for derivation of a One-day HA. It is recommended that the value for the Ten-Day HA, 2 mg/1, be used at this time as a conservative estimate for the One-Day HA. Ten^day Health Advisory Hepatotoxiclty in mice exposed to tetrachloroethylene was selected, as the basis for calculating the Ten-day HA value. Schumann at al. (1980) administered PCS in corn oil to rats and mice via gavage for 11 consecutive days at doses of 0, 100, 250, 500. and 1000 mg/kg. For mice, histopathological changes (centrllobular hepatocellular swelling) were observed In all treated animals,' and.lnereased liver.weight/body weight ratios were observed in animals exposed to doses of 250 mg/k9'and higher. The lowest dose, 100 ng/kq/6ay, represents the LOAEL for the study; This value Is consistent with the estimated LOAEL (based on altered hepatic lipid and triglyceride content) of 160 mg/kS/day for mice exposed to 200 ppm for 4 hours (Kylln et al, 1963; see appendix), and could be used as the basis fbr the Ten-Day Health Advisory with the Application of an uncertainty factor of 1000. This uncertainty factor is in accordance with NAS/0DW guidelines for derivation of the HA based on a LOAEL from an animal study. Data from longer-term studies indicates that an uncer tainty factor of 1000 may be overly conservative in this case. Buben and O'Flaherty (1985) treated mice with doses ranging from 20 to 2000 mg/kg, 5 days/week for 6 weeks and observed a slight.increase in liver weight .in mice, treated with 20 mg/kgr et 100 mg/kg, increases were significantly different from controls. From this study,, a dose of 20 ag/kg was.identified as a N0AEL and 100 mg/kg was identified as a LOAEL. Basing the Ten-day HA on the H0AEL of 20 mg/kg with an uncertainty factor of 100 Is consistent with the protection of humans from the CNS effects observed by Stewart et al. (1980) at 100 ppm fof 7 hours (approximately 20 mg/kg, see appendix). The value was calculated as follows: Ten-day HA = <2,P, ,w9/*?/day> tlQ (100) (1 L/day) * 2.0 mg/L * 2,000 ug/L *' ' where: 20 mg/kg/day NOAEL based on the absence of effects on liver weight of mice exposed to tetrachloroethylene .via gavage. 10 kg = assumed body weight of child. 100 uncertainty factor, chosen in accordance with NAS/ODW guidelines for use of -a NOAEL from an animal study. I L/day = assumed daily water consumption for a child. 311 NGC36698 Tetrachloroethylene March 31, 198? Longer-term. Health Advisory The study by Suben and O'Flaherty was also selected as the basis for the longer-term HA* Lifetime carcinogenicity bioassays did not provide an indication of toxicity at the low dose range (NCI, 1977; KU-, 1985). The NOAEL of 20 agAg/day and the LOAEL of 100 mgAs/day Identified in the study by Buben and O'Flaherty are consistent with estimates of LOAELs from inhalation studies. A LOAEL of 63 mgAg/day (based on increased liver height and fatty infiltration of the liver) was estimated from chronic exposure of guinea pigs to 100 ppm for 7 faours/day. (Rove et &!., 1952; see appendix)# and a LOAEL of 160 mgAg/day (based on fatty infiltration of the liver) from mice exposed to 200 ppm for 4 hours (Kylln et al, 1965). The Longer-term HA value for a 10-kg child was calculated as follows; Longer-term HA a (20 mg/kq/day){5/7)(10 kg) , 1*4 mg/L 1400 ug/L (100) (1 L/day) where; 20 ntg/kg/day * NOAEL based on the absence of effecta on liver weight for mice exposed to tetrachloroethylene via gavage. 5/7 * factor to convert 5 day/week, exposure to daily exposure. 1 0 kg assumed weight of child* 1 00 ' 1 L/day * ' uncertainty factor chosen in accordance wi'th NAS/ODW. guidelines for used of a NOAEL from an animal study. a assumed, water consumption for a 10 kg child. The Longer-term HA value for a 70-kg adult was calculated as follows: Longer-term where: 20 mg/kg/day NOAEL based on the absence of effects on liver weight for mice exposed to tetrachloroethylene via gavage. 5/7 * factor to convert 5 day/week exposure to daily exposure. 100 * uncertainty factor, chosen in accordance with NAS/ODW guidelines for use of a NOAEL from art animal study. 70 kg * assumed weight of adult. 2 L/day assumed water consumption for 70 kg adult. 312 NGC36699 -1 0- Lifetlme Health Advisory The Lifetime HA represents that portion of an individual's total exposure that Is attributed to drinking water and is considered protective of noncarcinogenic adverse health effects over a lifetime exposure* The Lifetime HA is derived in a three step process* Step 1 determines the Reference Dose (RfD), formerly called the Acceptable Daily intake (ADZ)* She RfD is an esti mate of a daily exposure to the human population that is. likely to be without appreciable risk of deleterious effects over a lifetime, and is derived from the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level (DWEL) can.be determined (Step 2)* A DWEL is a medium-specific (i.e., drinking water) lifetime exposure level, assuming 100% exposure from that medium, at which adverse, noncarclnogenic health effects would not be expected to occur* The DWEL is derived from the multiplication of the RfD by the assumed body weight of an adult and divided by the assumed dally water consumption of an adult* The Lifetime HA is determined in Step 3 by factoring in other sources of exposure, the relative source contribution (RSC). Ihe RSC from drinking water Is based on actual exposure data or, if data are not available, a value of 20% is assumed for synthetic organic chemicals and a value of 10% Is assumed for inorganic chemicals* . If the contaminant is classified as a Group A or B carcinogen, according to the Agency's classification scheme of carcinogenic potential (U.S* EPA, 1986), then caution should be exereised in assessing the risks associated with lifetime exposure to this chemical* No suitable chronic oral or lifetime oral studies were located in the literature to serve .as .the basis for the Lifetiae. HA value*' .NOAELs were not identified in the NCI (1977) study in which LOAELs were identified at high doses (386 mg/kg/day, mice, 471 mg/kg/day, rats)* The NTP (1983) study in which lower doses were tested has not been validated* Approximate NOAELs and LOAELs calculated from chro.nic and lifetime inhalation studies give less conservative estimates of toxic doses' than the six-week oral study, of Buben and O'Flaherty (1985), LOAEL estimates of 63 mgAg/day for guinea pigs "exposed to 100 ppm,. 7 hrs/day (Rowe et al., 1952), 400 mg/kg/day for rats exposed to 475 ppm for 7 hr/day (Carpenter, 1937) and 160 mg/kg/day for mice exposed to 100 ppm for 6 hr/day (NTP, 1985) are consistent with the NOAEL of 20 mgAg/day and LOAEL of 100 mgAg/day identified in the study by Buben and O'Flaherty. In this study, mice were treated with doses of '20 t.o 2000 mgAg/day, 5 days/week for 5 weeks* A slight increase in liver weight was observed at 20 mgA9? ab 100 ngAg? liver weight and hepatic triglyceride levels were significantly Increased over controls. Using the NOAEL of 20 gAg/day and an uncertainty factor of 1000 consistent with the use of data from less than lifetime studies, the Reference dose and DWEL were calculated as follows: Step 1: Determination of the Reference Dose (RfD) Reference Dose ir'y. mgAg/day ) (5/7) - 0*0143 mgAg/day 1000 3/ a/ r where: 20 mgAg/day NOAEL based on the absence of effects in liver weight for mice exposed to tetrachloroethylene via gavage* 313 i NGC36700 Te trachloroe thyle ne -11- March 31, 19S~ 5/7 factor to convert 5 day/week exposure, to daily exposure. 1000 * uncertainty factor, chosen in accordance with NAS/ODW guidelines for.use with a NOAEL from an animal study of less-thah-lifa time duration. Step 2s Determination of the Drinking. Water Equivalent Level (DWEL) DWEL ------- N where: t0.0143 mg/kg/day) (70 Jcg) (2 L/day) * o.5 * 500 uc/L 0.0143 mg/kg/day = RfD. 70 kg = assumed body weight of an adult. 2 L/day assumed daily water consumption of an adult. Step 3.- Determ!nation of the Lifetime Health Advisory A lifetime HA is not recommended for PCS because of its classification as group B2: probable human carcinogen (US EPA, 1986). The estimated excess cancer risk associated with lifetime exposure to drinking water containing tetrachloroethylene at 500 ug/L is approximately 1 x 10"'^. This estimate., represents the upper 95% confidence limit from extrapolations prepared by EPA's Carcinogen Assessment Group using the linearized, multistage model. The actual risk is unlikely to. exceed this value, but there is considerable uncertainty as to the accuracy of risks calculated by this methodology. Controversy surrounds the classification of PCE. The Science Advisory Board, Halogenated Organics Subcommittee has recommended a classification of `Group C: possible human carcinogen (U.S. EPA, 1987). This committee concluded that the animal evidence of carcinogenicity was limited and questioned-grouping rat renal adenoraas/carcinomas for statistical analysis and- extrapolating mouse mononuclear cell .leukemia, to man, a species which is not susceptible to this.`.type of leukemia. In contrast to group B2 carcinogens for which no lifetime HA values are recommended, lifetime ,KA values are' calculated for group C carcinogens as follows; Lifetime HA - 500 ug/L x 20% = 10 Ug/L 10 where: '500 ug/L * DWEL. 20% assumed relative source contribution from water. 10 - additional uncertainty factor per ODW policy to account for possible carcinogenicity. 314 NGC36701 -12- Evaluation of Carcinogenic Potential ------- The National Academy of Sciences (NAS, 1977, 1980) and EPA's Carcinogen Assessment Group (Anderson, 1983) have calculated drinking water con centrations that would be estimated to increase the risk by one excess cancer per million (10"6) and per one hundred thousand (10~5). Assuming consumption of 2 liters of water/day by a 70 kg adult over a 70 year lifetime, HAS calculated drinking water concentrations of 3.5 ug/L and 35 ug/L for 10"6 and'10"5 risks, respectively. CAG calculated concen trations of 66, 6.6 and 0.7 ug/L for 10**^, 10"^ and 10"^ risks, respectiveiy. Each group employed the linearized, non-threshold multistage model, extrapolating from data obtained in the 1977 NCI bioassay in mice. The linear multistage model is only one method of estimating carcino genic risk. It is possible to estimate carcinogenic risk with the probit, logit or Weibull models, but for PCE the data are inadequate for calculating reasonable risk estimates using these techniques. While recognized as Statistically alternative approaches, the range of risks described by using any of these modelling approaches has little biological significance unless data can be used to support the selection of'one model over another. In the interest of consistency of approach and in providing an upper bound on the potential cancer risk, the Agency has recommended use of the linearized multistage approach. IARC (1979) stated that there is limited evidence to conclude that it is a carcinogen in mice, and placed it in Group 3.- The US EPA Carcinogen Assessment Group (CAG) classified tetrachloiroethylene ' in Group E2i Probable human-carcinogen (U.S. EPA, 1986). This classifica tion has been questioned by the Science Advisory Board, Halogenated Organics Subcommittee, which has recommended a classification of Group C: Possible human carcinogen (U.S. EPA, 1987). .VI. OTHER CRITERIA, GUIDANCE AND STANDARDS 0 The World. Health Organization has recommended a tentative guideline value of 10 ug/L for PCE in drinking water, based on carcinogenic properties (WHO, 1984). The National Academy of Sciences (NAS,.1980) calculated 24-hour and 7-day SNARLS. The 24-hour SNARL was 172 mg/L, based on a 490 mgAg LOAEL following i;p. administration, a 100-fold uncertainty factor, and a 70 kg adult drinking 2 L/day of drinking water. A 7-day SNARL of 24.5 mg/liter was calculated by dividing the 24-hour SNARL by seven. VII. ANALYTICAL METHODS Analysis of tetrachloroethylene is by a purge-and-txap gas chromato graphic procedure used for the determination of volatile organohalides in drinking water (U.S. EPA, 1985b). This method calls for the 315 NGC36702 Te trachloroe thylene -13 March 31, 195? bubbling of an inert gas through the -sample and trapping tetrachloroethylene on an adsorbant material* The adsorbent material is heated to drive off the tetrachloroethylene onto a gas chromatographic column. This method is applicable to the measurement of tetrachloroethylene over a concentration range of 0.03,to 1500 ug/L. Confirmatory analysis for tetrachloroethylene is by mass spectrometry (U.S. EPA, 1985c). The detection limit for confirmation by mass spectrometry is 0.-3 ug/L. VIII. TREATMENT TECHNOLOGIES ' Treatment technologies vhich will remove te trachloroe thyiene from water include granular activated carbon adsorption (GAC), aeration and boiling. Dobbs and Cohen (1980) developed adsorption curves for several organic chemicals including PCE. . It was reported that Filtrasorb 300 'carbon exhibited adsorptive capacities of 51 mg, 14 mg, 3.9 mg and 1 .V-mg PCE/gm carbon at equilibrium concentration of 1,000, 100,- 10 and 1 mg/L respectively. USEPA-DV7R.D installed pilot-scale adsorptiion columns in New Jersey and Rhode Island. In Rhode Island, a Filtrasorb 400 GAC column maintained a concentration of PCE below 0.1 mg/L for 11 weeks of operation and below for 20 weeks of operation in the effluent, given an influent concentration that ranged from 600 to 2,5.00 mg/L (Love and Eilers, 1982). In New Jersey, PCE concentration ranging from 60 to 205 mg/L.were reduced to less than 0.1 mg/L by ' GAC over a 58-week study period (Love and Ellers, 1982). 6 PCE- is amenable to aeration on the basis of its Henry's -Law Constant of 1,100 atm (Kavanaugh and Trussell, 1980). In a pilot-scale packed tower aeration study, removal efficiencies of 72 to 99.8% for PCE were achieved using air-to-water ratios of 5-80, respectively (ESE, 1985). " In diffused-air aeration pilot-scale studies .using either spiked Cincinnati tap water (17-1,025 mg/L PCE) or actual PCE contaminated New Jersey groundwater (94 nig/L PCE), diffused aeration removed-90% of PCE at an air-to-water ratio of 4 for the latter and 98+% for the Cincinnati water at air-to-water ratios of 8, 16 and 20 {Love and Eilers, 1962). 0 Air stripping is an effective, simple and relatively inexpensive process for removing PCE and other volatile organics from water. However, use of this process then transfers the contaminant directly to the air stream. When considering use of air stripping as a treat ment process, it is suggested that careful consideration be given to the overall environmental occurrence, fate,-route of exposure and various otrcer hazards associated with the chemical. 316 NGC36703 -1 4- IX, REFERENCES Anderson, E,L. 1963. Draft memo to Frederic A. Eidsness, Jr., entitled "Latest Cancer Risk Rate Estimates," March 22, Brancaccio, A,, V. Mazza and R, DiPaolo, 1971, Renal function in experi mental tetrachloroethylene poisoning. Folia Med. (Maples). 54:233-237, Bub.en, J.A., and E, 0*Flaherty, 1985, Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchioroethylene: a dose-effect study, Tox. Appl, Pharm. 78:105-122, Carpenter, C.P. 1937. the chronic toxicity of tetrachloroethylene, J, 2nd, Hyg, Toxicol. 19:323-326. Carpenter, C.P., H.F. Smyth, Jr. and O.C, Fozzanl. 1949, The assay of acute vapor toxicity and the grading and interpretation of results on 96 chemical compounds. J, Ind. Hyg, Toxicol. 31:343-346, Cerna, N., and H. Kypenova. 1977. v Mutagenic activity of chloroethylenes analyzed by screening system tests, Mut. Res, 46 (3):214-215. Daniel, J.W. 1963* The metabolism of 36Cl-iabelied trichloroethylene-and tetrachloroethylene in the rat. Blochea. Pharmacol. 12:795--802. Dobbs, R.A., and J.M. Cohen. 1980. Carbon adsorption isotherms for toxic organics. EPA 600/8-80-023, Office of Research and Development, MERL, Wastewater Treatment Division, Cincinnati, Ohio, ESE, 1985, Environmental Science and Engineering, Draft technologies and costs for the removal of volatile organic chemicals from potable water supplies. No. 84-912-0300, Prepared for U,S, EPA, Science and Technology Branch, CSD, ODW, Washington, D.C, Federal Register* 1986. Guidelines for carcinogen risk assessment. 51 (185): 33992 - 34003. September 24.* Fernandez, J,, E. Guberan and J, Caperos, 1976, .Experimental human exposures to tetrachloroelJiylene vapor and elimination in breath after Inhalation.' Am. Ind. Hyg. Assoc. J. 37:43-150, Fernando, P.B., M. D'Silva, G.K.B. Stork and G.R, Slnnatamby, 1939, Tetra chloroethylene in the treatment of hookworm disease, with special reference to toxicity. Indian J. Med. Res. 26:759-783. Friberg, L., B, Kylin and A, Nystrom. 1953, Toxicities of trichloroethylene and tetrachloroethylene and Fujlwara's pyridine-alkali reaction. Acta Pharmacol, et Toxicol, 9:303-312, Fujii, T. 1975, The variation in the liver function of rabbits after admini stration of chlorinated hydrocarbons. Jap, J. Ind. Health, 17:61-68, 317 NGC36704 Tetrachloroethylene -15- Fiiller, B.B. 1 976. Air pollution assessment of tetrachloroethylene MTR-7143, McLean, Virginia, Mitre Corporation. EPA Contract Mo, 68-02-1495. Hake, C.L., and R.D. Stewart. 1977. Human exposure to tetrachloroethylene: Inhalation and skin contact. Environ'. Health Perspect. 21:231-238. Xkeda, M. 1977. Metabolism of trichloroethylene and tetrachloroethylene in human subjects. Environ. Health Perspect. 21/t239-245. Xkeda, M., and T. Imamura. 1973. Biological half-life of trichloroethylene and tetrachloroethylene In human subjects. Int. Arch. Arbettsmed. 31:209-224. Xkeda, M., and. H. Ohtsuji. 1972. A comparative study of the excretion of Fujlwara reaction--positive substances in urine of humans and rodents given trlchloro- or tetrachloro- derivatives of ethane and ethylene. Brit. J. Ind.. Med 29:99-104. Xkeda, M., H. Ohtsuji, T. Imamura and Y. Komoike. 1972. Orlnary excretion of total trlchloro compounds, triehloroethanol and trichloroacetic acid as a measure of exposure to trichloroethylene and tetrachloroethylene. Brit. J. Ind. Med. 29:328-333. XARC. 1979. International Agency for Research on Cancer. XARC monographs ' on the evaluation of the- carcinogenic risk of chemicals to man. Some monomer', plastic and synthetic elastomes and acrolein. 19:377-401 Xavanaugh, M.C., and R.R. Trussell. 1980. Design of aeration towers to strip volatile contaminants from drinking water. JAWWA. Kendrick, J.F. 1929. The treatment of hookworm disease with, tetrachloro ethylene. Amer. J. Trop. Med. 9:483-488. Xlaassen, C.D., and G.L. Plaa. 1966. Relative effects of various chlorinated hydrocarbons on liver and kidney function In mice. Toxicol. Appl. Pharma col.' 9:139-151. Kylin, B, H. Reichard, I. Sumegi and -S. Yllner* 1963. Hepatotoxicity of inhaled trichloroethylene, tetrachloroethylene and chloroform. Single exposure. Acta Pharmacol. Toxicol. 20:16-26. Kylin, 3., I. Sumegi and S. Yllner. 1965. Hepatotoxiclty of inhaled tri chloroethylene and tetrachloroethylene. Long-term exposure. Acta Pharma col, Toxicol. 22:379-385. Love, O.T., Jr., and R.G. Ellers. 1982. Treatment of drinking water containing trichloroethyle/iS end related industrial solvents. JAWWA.. ,, Margard, W. 1978. In vft.ro bioassay of chlorinated hydrocarbon solvents. Battelle Laboratories, Unpublished proprietary document for Detrex Chemical Industries. July. `` 318 NGC36705 -1 6- Mazza, V. 1972* Enzymatic changes In experimental tetrachloroethylene poison ing. Folia Med- 55{9-10):373-381. McConnell, G., D.M. Ferguson and C.R, Pearson. 1975. Chlorinated hydrocarbons and the environment. Endeavor. 34:13-18. Monster, A.C. 1979. Difference in uptake, elimination and metabolism in exposure to trichloroethylene, 1,1,1 --trichloroethane, and tetrachloro-- ethylene. Int. Arch. Occup. Environ. Health. 42:311-317. Monster, A.C., <3. Boersmaand H. Steenveg. 1979. Kinetics of tetrachloro ethylene In volunteers: Influence of exposure concentration and work load. Int. Arch. Occup. Environ, Health. 42:303-309. Monster, A.C., and J.M. Houtkooper. 1979* Estimation of Individual uptake of trichloroethylene, 1,1,1-trlchloroethane and tetrachloroethylene from biological parameters. Znt. Arch. Occup. Environ. Health. 42:319-323. NAS. 1977. National Academy of Sciences. Drinking Hater and Health. Volume 1. National Academy Press. Washington, D.C. NAS. 1980. National Academy of Sciences. Drinking Hater and Health. Volume 3. National Academy Press. Washington, D.C. NCI. 1977. National Cancer Institute. Bioassay of tetrachloroethylene for possible `carcinogenicity. DHEW Publication No. NIH 77-813, U.S. Depart ment of HEW, PHS, National Institute of Health, National Cancer Institute PS-272 950, NTIS. NTP. 1983. Bioassay on tetrachloroethylene in female B6C3Fj mice. Draft. NTP. 1985. NTP technical report on the toxicology and carcinogenesis studies on tetrachloroethylene (perchloroethylene). NTP, Research Triangle Park, NC. Nelson, B.K., B.J. Taylor, J.V. Setzer and R.W. Hornung. 1979. Behavioral teratology of perchloroethylene in rats. J.' Environ. Pathol. Toxicol. 3:233-250. Ogata, M., Y, Takatsuka, K. Tomokuni and K Murol. 1971. Excretion of organic chlorine compounds in the urine of persons exposed to vapors of trichloroethylene and tetrachloroethylene. Brit. J. Ind. Med. 28:386-391. Ogata, M,, K, Tomokuni and S. Watanabe. 1968. ATP and lipid contents in the itver of mice after inhalation of .chlorinated hydrocarbons. Ind. Health. 6:116-119. Parsons, F., P.R. Wood and J. DeMarco. 1984. Transformation of tetrachioroethene and trtchloroethene in microcosms and groundwater, JAWWA. 26(2):56f. Rowe, V.K., DD. KcColll.ster, H.C. Spencer, E.M. Adams and D.D. Irish. 1952. Vapor toxicity of tetrachloroethylene for'laboratory animals and human subjects. AMA Arch. Ind. Hyg. Occup. Med. 5:566-579. 319 NGC36706 Tetrachloroethyiene -17- narcn a r Savolalnen, H., P. Pfaffii, M. Tengen and H, Vainlo. 1977. Biochemical and behavioral effects of inhalation exposure to tetrachloroethylene and diehloromethane. J. Neuropathol. Exp. Neurol. 36(6):941-949. Schumann, A.M., J.F. Quest and P.G. Watanabe. 19S0. The pharmacokinetics and nacxomolecular interactions of perchloroethyiene in mice and rats as related to oncogenicity. Toxicol. Appl. Pharmacol. . 55:207-219. Schwetz, B.A., B.X.J'. Leong and P.J. Geftring. 1975. The effect of maternally inhaled trichloroethylene, perchloroethyiene, methyl chloroform, and methylene chloride on embryonal and fetal development in mice and rats. Toxicol. Appl. Pharmacol. 32*84-96. Smyth, H.F., Jr., C.S. Weil, J.S. West and C.P. Carpenter. 1969. An explora tion of joint toxic action* Twenty-seven industrial chemicals intubated in rats in all possible pairs. Toxicol. Appl. Pharmacol. 14*340-347. Stewart, F-.D,* E.D, Barretta, H.C. Dodd and T.R.- Torkelson. 1970, Expert- mental human exposure to tetrachloroethylene. Arch. Environ. Health. 20:224-229. " Stewart, R.D., H.H. Gay, D.S. Erley, C.L. Hake and A.W. Schaffer. 1961. Human exposure to tetrachloroethylene vapor. Arch. Environ. Health. 20:516-522. Stewart, R.D., C.L. Hake, H.V. Forster, A.J. Lebrun, J.F. Peterson and A. Wu. 1974. Tetrachloroa-thylene: Development of a biologic standard for the industrial worker by breath analysis. Report' No. NIOSH-MCOW-ENUM-PCE-74-6, Medical College of Wisconsin, Milwaukee, Wisconsin. Torkelson, T;R., and V.X. Rowe. 1981. Halogenated aliphatic hydrocarbons. In; Industrial Hygiene and Toxicology. 3rd ed. Vol. 2B. John Wiley and Sons, New York. p. 3561. VmS *, .EPA. 1979. U.S. Environmental Protection Agency. Water Related Environmental Fate of 129 Priority Pollutants, Office of Water Planning and Standards, EPA-440/4-79-029, December 1979. U.S. EPA. 1983, U.S. Environmental Protection Agency. Tetrachloroethylene occurrence in drinking water, food, and air. Office of Drinking Water. U.S. EPA. 1985a. U.S. Environmental Protection Agency. Health Effects Criteria Document for Tetrachloroethylene. Criteria and Standards . Division, Office of Drinking-Water. Washington, D.C, April. - U.S. EPA.. 19S5b. U.S. Environmental Protection Agency. Method 502.1. Volatile Halogenated Organic Compounds in Water by Purge and Trap. Gas Chromato graphy. Environmental Monitoring and Support Laboratory, Cincinnati, Ohio -45266. ' U.S. EPA. 1985c. U.S. Environmental Protection Agency. Method 524.1. Volatile Organic Compounds in Water by Purge and Trap Gas Chromatography/Mass Spectrometry. Environmental Monitoring and Support Laboratory, Cincinnati, Ohio 45268. 320 NGC36707 xetracnioroethyiene -18- March 31t 198 U.S. EPA. 1986. U.S. Environmental Protection Agency. Addendum to the Health Assessment Document for Tetrachloroethylene (Perchloroethylene). Office of Health and Environmental Assessment. External Review Draft. April* U.S. EPA. 1987. u.s. Environmental Protection Agency. Science Advisory Board's Environmental Health Committee, Halogenated Organics Subcommittee Report. - Memo from N. Nelson and R.A. Griesemer to Lee M* Thomas, Janu ary 27, 1987. U.S. ZTC. 1983. U.S. International Trade Commission. Synthetic organic chemicals United States production, 1983. USITC Publication 1422. Washington, D.C, 20436. Verschueren, K. 1977. Handbook of Environmental Data on Organic Chemicals. 2nd ed. Van Nostrand Reinhold Company. New York. p. 580-582... Vogel, T., and P McCarty. 1985. Biotransformation of tetrachloroethylene to trichloroethylene, dichloroethylene, vinyl chloride, and carbon dioxide under methanogenic conditions. Appl, Environ. Microbiol. 49(5). Wenzel, D.G., and R.D. Gibson. 1951* A study of the toxicity and anthelminthic activity of n-butylidene chloride. J. Pham. Pharmacol. .3:169-176. WHO. 1984. World Health Organization. Guidelines for Drinking Water Quality. Volume I. Geneva. ISBN 9241541687. Windholz, M. 1983. The Merck Index, 10th ed. Merck and Co., Inc. Rahway, New Jersey, p. 1315. 321 NGC36708 Tetrachloroethylene -19 March 31, 1987 Appendix Estimation of absorbed dose based on inhalation exposure Species Approx. Approximate weight minute vol. (kq) (liter/min) Human 70.0 10.0 Guinea pig 0.50 0.222 Rat 0.25 0.132 Mouse 0.025 0.024 / Time of Approximate [PCE] Exposure dose (ppm) . (hr/d&y) (m<r/kqr/day)a Reference 100 7 20 Stewart et al, 1977 100 7 63 Rowe et al. 1952 200 400 230 470 100 200 200 6 6 8 8 6 6 _4 130 260 200 400 120 230 160 Savolainen et al, Savolainen et al, Carpenter, 1937 Carpenter, 1937 1977 1977 NTP, 1985 NTP, 1985 Xylin, 1963i, 1965 aDose [PCEfmg/L)J[min. vol.(L/hr33[Time(hr/day))f50% absorption3/rbw(*9)) . where: [PCECmg/L) twin. vol.(L/hr)] [PCEtppirO] x {6.78 mg/m3 - ppm) x (1 L/1000 m3) [min. vol.(L/min)) x (60 min/hr) 3 99 NGC36709