_ August, 1987 820K88103 DACTHAL Health Advisory Office of Drinking Water U.S. Environmental Protection Agency -_— ! O I. INTRODUCTION 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. The HAs 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 noncarcinogenic 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 B), Lifetime HAs are not recommended. The 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 low-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 Probit 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. ------- Dacthal August, 1987 -2- II. GENERAL INFORMATION AND PROPERTIES CAS No. 1861-32-1 Structural Formula cu CK CQgCHa ^c, V^ci COjCHs Dimethyl tetrachloroterephthalate Synonyms Uses e 2,3,5,6-Tetrachlorodimethyl-1,4-benzenedicarboxylic acid; DCPA; Chlorothal; Dacthalor; DAC; DAC-4; DAC-893; DCP (Meister, 1983). 0 Selective pre-emergence herbicide used to control various annual grasses in turf, ornamentals, strawberries, certain vegetable transplants, seeded vegetables, cotton, soybeans and field beans (Meister, 1983). Properties (Meister, 1983; Windholz et al., 1983; CHEMLAB, 1985) Chemical Formula Molecular Weight Physical State (25°C) Boiling Point Melting Point Density (°C) Vapor Pressure (258C) Specific Gravity Water Solubility (25°C) Log Octanol/Water Partition Coefficient Taste Threshold Odor Threshold Conversion Factor C10H604C14 331.99 Crystals 156°C 5,000 mg/L 4.15 (calculated) Occurrence 0 Dacthal has been found in 462 of 1,818 surface water samples analyzed and in 33 of 615 ground water samples (STORET, 1987). Samples were collected at 551 surface water locations and 576 ground water locations, ------- Dacthal August, 1987 -3- and dacthal was found in eight states. The 85th percentile of all nonzero samples was 0.39 ug/L in surface water and 0.05 ug/L in ground water sources. The maximum concentration found was 8.74 ug/L in surface water and 0.05 ug/L in ground water. Environmental Fate 0 In aqueous solutions, dacthal is stable to photolysis with a half- life of greater than one week. -Dacthal is stable to soil photolysis (Registrant CBI data). 0 Soil metabolism of dacthal proceeds with a half-life of greater than 2-3 weeks. Degradation rate is affected by temperature. No degra- dation of dacthal has been observed in sterile soils (half-life of 1,590 days) (Registrant CBI data). 0 Degradation products of dacthal include monomethyltetrachlorotere- phthalate (MTP) and tetrachloroterephthalic acid (TTA) (Registrant CBI data). 0 TTA has been shown to be very mobile in soils whereas dacthal is not (Registrant CBI data). III. PHARMACOKINETICS Absorption 0 Hazleton Laboratories (no date) reported that humans receiving single oral doses of dacthal (25 or 50 mg) excreted up to 6% of the 25 mg dose in urine as metabolites over a 3-day period. Approximately 12% of the 50 mg dose was metabolized and excreted over a similar time period. The data indicated that up to 12% of a 50 mg dose could be absorbed in humans. 0 Skinner and Stallard (1963) reported that following administration of single oral doses of dacthal (100 or 1,000 mg/kg) by capsule to dogs, 90 and 97% of the administered doses were eliminated as the parent compound in the feces by 24 and 96 hours, respectively. Approximately 3% of dacthal was converted to the monoethylester of tetrachloro- t«rephthalic acid (DAC 1449). Two percent was eliminated in the urine and 1% in the feces. Less than 1% (0.07%) of DAC 1449 was converted to tetrachloroterephthalic acid (DAC 954), which was also excreted in the urine. The results indicated that dacthal was absorbed poorly (about 3%) from the gastrointestinal tract of dogs. Distribution 0 Skinner and Stallard (1963) reported that following a single oral dose of dacthal (100 or 1,000 mg/kg) to dogs, there was no storage of dacthal in the kidneys, liver or fat. However, DAC 954 was found in the kidneys. The authors also reported that no dacthal was found in the kidneys or liver of dogs that had been administered dacthal-T at ------- Dacthal August, 1987 10,000 ppm (250 mg/kg/day) in the diet for two years. The kidneys, liver and fat contained DAC 1449, while the kidneys contained DAC 954 only. Both dacthal and DAC 1449 were found in the fat of dogs treated with 10,000 ppm. Metabolism Hazleton Laboratories (no date) reported that humans who took single oral doses of dacthal (25 or 50 mg) converted 3 to 4% of the dose to DAC 1449 within 24 hours. After 3 days, approximately 6% of the 25 mg dose and 11% of the 50 mg dose were converted to DAC 1449. At either dose, less than 1% was converted to DAC 954 in the 1- or 3-day time period. Skinner and Stallard (1963) reported that in dogs administered single oral doses of dacthal, small amounts were converted to DAC 1449 (3%) or DAC 954 (0.07%). Hazleton and Dieterich (1963) reported similar results when dogs were administered dacthal (10,000 ppm; 250 mg/kg bw) in the diet for 2 years. Excretion In human studies (Hazleton Laboratories, no date), 6% of a single 25 mg oral dose was excreted in urine as DAC 1449 and 0.5% as DAC 954 over a three-day period. Approximately 11% of the 50 mg dose was converted to DAC 1449 and 0.6% was converted to DAC 954. The parent compound was not found in the urine at either dose. Skinner and Stallard (1963) reported that following the administra- tion of a single oral dose (100 or 1,000 mg/kg) to dogs, 90 and 97% was eliminated unchanged in the feces at 24 hours and 96 hours, respectively. Approximately 3% was converted to DAC 1449; of this 3%, 2% was eliminated in the urine and 1% in the feces. IV. HEALTH EFFECTS Humans Hazleton Laboratories (no date) reported that dacthal, administered as single 25 mg or 50 mg oral doses to each of six volunteer subjects, did not cause any observable effects. Assuming 70 kg body weight, these amounts correspond to doses of 0.36 or 0.71 mg/kg. Hemograms, liver, kidney and urine analyses from the six human volunteers were normal. Animals Short-term Exposure 0 The acute oral LD5Q for male and female rats was reported to be greater than 12,500 mg/kg (Wazeter et al., 1974a). ------- Dacthal ' August, 1987 -5- 0 The acute oral LD50 for male and female beagle dogs was reported to be greater than 10,000 mg/kg (Wazeter et al., 1974b). 0 Keller and Kundzin (1960) administered pure dacthal to weanling male Sprague-Dawley rats (10/dose) in the diet for 28 days at dose levels of 0, 0.0082, 0.0824 or 0.824%. Based upon body weight and compound consumption data provided by the investigators, these dietary levels correspond to approximately 0, 7.6, 78.6 or 758 mg/kg/day. Following treatment, no effects on growth, food consumption, survival, body weights, organ weights, gross pathology and histopathology were observed. This study identifies a NOAEL of 758 mg/kg/day (the highest dose tested). 0 Keller (1961) reported that oral administration (by capsule) of 800 mg/kg/day of DCPA (% a.i. unknown) to beagle dogs (two/sex) for 28 days resulted in loss of body weight, reduced appetite, increased liver weight and liver to body weight ratio, centrilobular liver congestion and degeneration. Dermal/Ocular Effects 0 The acute dermal LD50 value for albino rabbits was reported to be greater than 10,000 mg/kg (Elsea, 1958). He also reported that dacthal, when applied to rabbit skin, did not cause irritation or sensitization. 0 Johnson et al. (1981) applied dacthal (2,000 mg/kg) for 24 hrs to shaved intact or abraded back or flank skin of New Zealand rabbits (five/sex) in a paste form. Desquamation (which ranged from very slight to slight) and very slight erythema were observed. There was no macroscopic or microscopic pathology noted, and dacthal caused no signs of irritation or sensitization. 0 A single application of 3.0 mg of dacthal to the eyes of albino rabbits produced a mild degree of irritation that subsided completely within 24 hours following treatment (Elsea, 1958). Long-term Exposure 0 Wazeter et al. (1977) fed CD rats (15/sex/dose) disodium dacthal in the diet for 90 days at dose levels of 0, 50, 500, 1,000 or 10,000 ppm. Based upon compound consumption and body weight data provided by the authors, these dietary levels are approximately 0, 3.6, 36.4, 74 or 732 mg/kg/day for males and 0, 4.2, 43.2, 82.3 or 856 mg/kg/day for females. General behavior, appearance, body weight, food con- sumption, ophthalmoscopic evaluation, hematology, clinical chemistry, urinalysis, gross pathology and histopathology were comparable for treated and control groups. A NOAEL of 10,000 ppm (732 mg/kg/day for males and 856 mg/kg/day for females, the highest dose tested) was identified for this study. 0 Hazleton and Dieterich (1963) fed beagle dogs (four/sex/dose) dacthal in the diet at 0, 100, 1,000 or 10,000 ppm for two years. Based upon ------- Dacthal August, 1987 -6- body weight and food consumption data provided in the report, these dietary levels are approximately 0, 2.6, 17.7 or 199 mg/kg/day for males and 0, 3, 20.7 or 238 mg/kg/day for females. Physical appearance, behavior, food consumption, hematology, biochemistry, urinalysis, organ weight, organ-to-body weight ratio, gross pathology and histopathology were comparable in treated and control groups at all dose levels. A NOAEL of 10,000 ppm (199 mg/kg/day for males and 238 mgA9/day for females; the highest dose tested) was identified for this study. e Paynter and Kundzin (1963) fed albino rats (35/sex/dose; 70/sex for controls) dacthal in the diet for 2 years at 0, 100, 1,000 or 10,000 ppm. Based on food consumption and body weight data provided in the report, these dietary levels correspond approximately to 0, 5, 50 or 500 mg/kg/day. Physical appearance, behavior, hematology, biochemistry, organ weights, body weights, gross pathology and histo- pathology of treated and control animals were monitored. After 3 months at 10,000 ppm, slight hyperplasia of the thyroid was reported in both sexes. After 1 year, increased hemosiderosis of the spleen of females occurred at 10,000 ppm and there were slight alterations in the centrilobular cells of the liver of both sexes. Kidney weights were increased significantly in males fed 10,000 ppm at the end of the 2-year study. Based on these data, a NOAEL of 1,000 ppm (50 mgA9/day) was identified. Reproductive Effects 0 Paynter and Kundzin (1964) conducted a two-generation study using albino rats. Animals (8 males/16 females) were fed dacthal in the diet at dose levels of 0, 0.1 or 1.0% for 24 weeks, prior to mating. Assuming that 1 ppm in the diet of rats is equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of 0, 50 or 500 mg/kg/day. This study reported an evaluation of data collected on the second parental generation (P^) and through weaning of the first litter (F2a). The authors reported that a second litter (F2t>) was n°t obtained. Following treatment, the following indices were evaluated; fertility, gestation, live births and lactation. Since the fertility index was 37% (6/16) at the 1% dose, 75% (12/16) at the 0.1% dose, and only 19% (3/16) in controls, no conclusions could be reached. The lactation index for the 0.1% group was significantly lower than controls. No oth^r adverse reproductive effects were observed. 0 Hazleton (1963) performed a one-generation reproduction study in albino rats. Animals were given dacthal in the diet at 0, 1,000 or 10,000 ppm in the diet. Assuming that 1 ppm in the diet of rats is equivalent to 0.05 mg/kg/day (Lehman, 1959), this corresponds to doses of about 0, 50 or 500 mg/kg/day. No effects were detected on fertility, gestation, number of live births or lactation. Based on this information a NOAEL of 10,000 ppm (500 mg/kg/day; the highest dose tested) was identified. ------- Dacthal August, 1987 « -7- Developmental Effects^ 0 Powers (1964) fed pregnant New Zealand rabbits (six/dose) dietary levels of dacthal-T (0, 1,000 or 10,000 ppm) on days 8 to 16 of gestation. Assuming that 1 ppm in the diet of rabbits is equivalent to 0.03 mg/kg/day (Lehman, 1959), this corresponds to about 0, 30 or 300 mg/kg/day. Following treatment, fetal toxicity (number of live/dead or resorptions), maternal effects (appearance, behavior, body weight) and visceral and skeletal anomalies were evaluated. No adverse effects were observed at any dose level tested, This study identified a developmental NOAEL of 300 mg/kg/day (the highest dose tested). Mutagenicity 0 No significant increase in mutation frequency was observed in Droso~ phila melanogaster larvae that had been fed media containing 0.1 to 10 mM dacthal (Paradi and Lovenyak, 1981). 0 Dacthal had no mutagenic activity in Salmonella assays (Microbiological Associates, 1977a), in in vivo cytogenetic tests (Microbiological Associates, 1977b), in DNA repair tests (Microbiological Associates, 1977c) or in dominant lethal tests (Microbiological Associates, 1977d). Carcinogenicity 0 Paynter and Kundzin (1963) fed albino rats (35/sex/dose; 70/sex for controls) dacthal-T for 2 years at dose levels of 0, 100, 1,000 or 10,000 ppm. Based upon compound consumption and body weight provided in the report, these dietary levels correspond approximately to 0, 5, 50 or 500 mg/kg/day. Based on gross and histologic examination, neo- plasms of various tissues and organs were similar in type, localization, time of occurrence, and incidence in control and treated animals. 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 noncarcinogenic end point of toxicity. The HAs for noncarcinogenic toxicants are derived using the following formula: HA = (NOAEL or LOAEL) x (BW) . /L ( /r} (UP) x ( L/day) where: NOAEL or LOAEL * No- or Lowest-Observed-Adverse-Effect-Level in mg/kg bw/day. BW = assumed body weight of a child (10 kg) or an adult (70 kg). ------- Dacthal , August, 1987 -8- UF » uncertainty factor (10, 100 or 1,000), in accordance with NAS/ODW guidelines. L/day «• assumed daily water consumption of a child (1 L/day) or an adult (2 L/day). One-day Health Advisory No information was found in the available literature that was suitable for deriving a One-day HA. The study in humans by Hazleton Laboratories (no date) was not selected since only low doses (0.36 or 0.71 mg/kg) were tested, and longer-term studies in animals suggest the no-effect level may be much higher. It is, therefore, recommended that the Ten-day HA value for the 10-kg child (75 mg/L; calculated below) be used at this time as a conservative estimate of the One-day HA. Ten-day Health Advisory The 28-day feeding study in rats by Keller and Kundzin (1960) has been selected to serve as the basis for determination of the Ten-day HA. In this study, no adverse effects on growth, organ weight, food consumption, gross pathology or histopathology were detected at 758 mg/kg/day. The Ten-day HA for the 10-kg child is calculated as follows: Ten-day HA = (758 mg/kg/day) (10 kg) = 75 /L (75 000 ug/L) (100) (1 L/day) where: 758 mg/kg/day = NOAEL, based on absence of effects on growth, organ weight, food consumption, gross pathology or histopathology in rats fed dacthal for 28 days. 1 0 kg = assumed body weight of a child. 100 = uncertainty factor, chosen in accordance with NAS/ODW guidelines for use with a NOAEL from an animal study. 1 L/day = assumed daily water consumption of a child. Longer-term Health Advisory No appropriate data were available for the calculation of a Longer-term HA. Therefore, it is recommended that the modified DWEL, adjusted for a 10-kg child (5 mg/L), be used at this time as a conservative estimate for a Longer- term HA. Lifetime 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 noncar- cinogenic adverse health effects ove-r a lifetime exposure. The Lifetime HA ------- Dacthal August, 1987 -9- is derived in a three step process. Step 1 determines the Reference Dose (RfD), formerly called the Acceptable Daily Intake (ADI). The 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, noncarcinogenic health effects would not be expected to occur. Ihe DWEL is derived from the multiplication of the RfD by the assumed body weight of an adult and divided by the assumed daily 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). The 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, 1986a), then caution should be exercised in assessing the risks associated with lifetime exposure to this chemical. The 2-year study in rats by Paynter and Kundzin (1963) has been selected to serve as the basis for determination of the Lifetime HA value for dacthal. This study identified a NOAEL of 50 mg/kg/day, based on absence of effects on appearance, behavior, hematology, blood chemistry, organ weight, body weight, gross pathology and histopathology in male rats. The LOAEL was 500 mg/kg/day, based on thyroid hyperplasia, histological changes in the liver and increased kidney weights. Using this study, the Lifetime HA is derived as follows: Step 1: Determination of the Reference Dose (RfD) RfD = .(..50 mg/kg/day) . 0.5 mg/kg/day where: 50 mg/kg/day = NOAEL, based on absence of toxic effects in rats exposed to dacthal in the diet for two years. 100 = uncertainty factor, chosen in accordance with NAS/ODW guidelines for use with a NOAEL from an animal study. Step 2: Determination of the Drinking Water Equivalent Level (DWEL) DWEL = (0.5 mg/kg/day) (70 kg) = 17.5 mg/L (17,500 ug/L) (2 L/day) ------- Dacthal August, 1987 -10- where: 0.5 mg/kg/day « RfD. 70 kg = assumed body weight of an adult. 2 L/day = assumed daily water consumption of an adult. Step 3: Determination of the Lifetime Health Advisory Lifetime HA * (17.5 mg/L) (20%) = 3.5 mg/L (3,500 ug/L) where: 17.5 mg/L « DWEL. 20% = assumed relative source contribution from water. Evaluation of Carcinogenic Potential 0 Paynter and Kundzin (1963) fed dacthal to rats for 2 years and reported no evidence of carcinogenic effects at dose levels up to 10,000 ppm (450 mg/kg/day for males and 555 mg/kg/day in females). • This study is limited in that the relatively small numbers of animals used (35/sex/dose; 70/sex for controls) and the removal of animals (10/sex/dose; 20/sex for controls) for interim sacrifice may have resulted in there being too few animals available for observation of late-developing tumors. e The International Agency for Research on Cancer has not evaluated the carcinogenic potential of dacthal. 0 Applying the criteria described in EPA's guidelines for assessment of carcinogenic risk (U.S. EPA, 1986a), dacthal may be classified in Group D: not classified. This category is for substances with inade- quate animal evidence of carcinogenicity. VI. OTHER CRITERIA, GUIDANCE AND STANDARDS • The U.S. EPA has established residue tolerances for dacthal in or on raw agricultural commodities that range from 0.5 ppm to 15.0 ppm (U.S. EPA, 1985). VII. ANALYTICAL METHODS 0 Analysis of dacthal is by a gas chromatographic (GC) method applicable to the determination of certain chlorinated pesticides in water samples (U.S. EPA, 1986b). In this method, approximately 1 liter of sample is extracted with methylene chloride. The extract is concen- trated and the compounds are separated using capillary column GC. Measurement is made using an electron-capture detector. The method ------- Dacthal August, 1987 -11- detection limit has not been determined for dacthal, but it is estimated that the detection limits for analytes included in this method are in the range of 0.01 to 0.1 ug/L. VIII. TREATMENT TECHNOLOGIES 0 Reverse osmosis (RO) is a promising treatment method for pesticide- contaminated waters. As a general rule, organic compounds with molecular weights greater than 100 are candidates for removal by RO. Larson et al. (1982) report 99% removal efficiency of chlorinated pesticides by a thin-film composite polyamide membrane operating at a maximum pressure of 1,000 psi and a maximum temperature of 113°F. More operational data are required, however, to specifically determine the effectiveness and feasibility of applying RO for the removal of dacthal from water. Also, membrane adsorption must be considered when evaluating RO performance in the treatment of dacthal-contaminated drinking water supplies. ------- Dacthal August, 1987 -12- IX. REFERENCES CHEMLAB. 1985. The Chemical Information System, CIS, Inc., Bethesda, MD. Elsea, J.R.* 1958. Acute oral administration; acute dermal application; acute eye application. Unpublished study. MRID 00045823. Hazleton Laboratories, Inc.* Undated. Oral administration - humans. ODW Document No. 0036. Hazleton, L.N., and W.H. Dieterich.* 1963. Two-year dietary feeding - dogs. Final Report. Unpublished study. MRID 00083584. Hazleton Laboratories, Inc.* 1963. Reproduction study - albino rats. ODW Document No. 0032. Johnson, D., J. Myer and A. Olafsson.* 1981. Acute dermal toxicity (LD50) study in albino rats. Unpublished study. MRID 00110553. Keller, J.G. 1961 «,* 28-day oral administration - dogs. Unpublished study. MRID 00083573. Keller, J.G., and M. Kundzin.* 1960. Twenty-eight day dietary feeding study in rats. Unpublished study. MRID 00083571. Larson, R.E., P.S. Cartwright, P.K. Eriksson and R.J. Petersen. 1982. Appli- cations of the FT-30 reverse osmosis membrane in metal finishing operations. Paper presented in Tokohama, Japan. Lehman, A.J. 1959. Appraisal of the safety of chemicals in foods, drugs and cosmetics. Published by the Association of Food and Drug Officials of the United States. Meister, R., ed. 1983. Farm Chemicals Handbook. Willoughby, OH: Meister Publishing Company. Microbiological Associates.* 1977a. Activity of DTX-0003 in the Salmonella/ microsomal assay for bacterial mutagenicity. ODW Document No. 0029. Microbiological Associates.* 1977b. The activity of DTX-77-0006 in the in vivo cytogenetic assay in rodents for mutagenicity. ODW Document No. 0029? Microbiological Associates.* 1977c. Activity of DTX-77-0005 in a test for differential inhibition of repair deficient and repair competent strains of Salmonella typhimurium. ODW Document No. 0029. Microbiological Associates.* 1977d. Activity of DTX-77-0004 in the dominant lethal assay in rodents for mutagenicity. ODW Document No. 0029. Paradi, E., and M. Lovenyak. 1981. Studies on genetical effect of pesticides in Drosophila melanogaster. Acta Biol. Sci. Hung. 32:119-122. ------- Dacthal August, 1987 -13- Paynter, O.E. , and M. Kundzin.* 1963. Two year dietary administration - rats. Final Report. MRID 00083577. Paynter, O.K., and M. Kundzin.* 1964. Reproductive study - rats. Unpublished study. MRID 00053082. Powers, M.B. 1964.* Reproductive study - rabbits. Unpublished study. MRID 00053088. Skinner, W.A. , and D.E. Stallard.* 1963. Dacthal animal metabolism studies. ODW Document No. 0033. STORET. 1987. U.S. EPA. 1985. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 180.185. July 1, 1985. pp. 280-281. U.S. EPA. 1986a. U.S. Environmental Protection Agency. Guidelines for carcinogen risk assessment. Fed. Reg. 51 ( 185) : 33992-34003. Septem- ber 24. U.S. EPA. 1986b. U.S. Environmental Agency. U.S. EPA Method #2 - Determina- tion of chlorinated pesticides in ground water by GC/ECD, January 1986 draft. Available from U.S. EPA's Environmental Monitoring and Support Laboratory, Cincinnati, OH. Wazeter, F.X., E.I. Goldenthal and W.P. Dean.* 1974a. Acute oral toxicity male and female rats. Unpublished study. MRID 00031873. Wazeter, F.X., E.I. Goldenthal and W.P. Dean.* 1974b. Acute oral toxicity in beagle dogs. Unpublished study. MRID 00031873. Wazeter, F.X., E.I. Goldenthal et al.* 1977. Ninety-day toxicity study in rats. ODW Document No. 0029. Windholz, M. , S. Budavari, R.F. Blumetti and E.S. Otterbein, eds. 1983. The Merck Index--an Encyclopedia of Chemicals and Drugs, 10th ed. Rahway, NJs Merck and Company, Inc. Confidential Business Information submitted to the Office of Pesticides Programs. ------- |