------- DISCLAIMER This report Is an external draft for review purposes only and does not constitute Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. 11 ------- PREFACE Health and Environmental Effects Documents (HEEDs) are prepared for the Office of Solid Waste and Emergency Response (OSWER). This document series Is Intended to support listings under the Resource Conservation and Recovery Act (RCRA) as well as to provide health-related limits and goals for emergency and remedial actions under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained for Agency Program Office files are evaluated as they pertain to potential human health, aquatic life and environmental effects of hazardous waste constituents. The literature searched for In this document and the dates searched are Included In "Appendix: Literature Searched." Literature search material Is current up to 8 months previous to the final draft date listed on the front cover. Final draft document dates (front cover) reflect the date the document Is sent to the Program Officer (OSWER). Several quantitative estimates are presented provided sufficient data are available. For systemic toxicants, these Include: Reference doses (RfDs) for chronic and subchronlc exposures for both the Inhalation and oral exposures. The subchronlc or partial lifetime RfO, Is an estimate of an exposure level which would not be expected to cause adverse effects when exposure occurs during a limited time Interval I.e., for an Interval which does not constitute a significant portion of the llfespan. This type of exposure estimate has not been extensively used, or rigorously defined as previous rlsfc assessment efforts have focused primarily on lifetime exposure scenarios. Animal data used for subchronlc estimates generally reflect exposure durations of 30-90 days. The general methodology for estimating subchronlc RfDs 1s the same as traditionally employed for chronic estimates, except that subchronlc data are utilized when available. In the case of suspected carcinogens, a carcinogenic potency factor, or q-j* (U.S. EPA, 1980), 1s provided. These potency estimates are derived for both oral and Inhalation exposures where possible. In addition, unit risk estimates for air and drinking water are presented based on Inhalation and oral data, respectively. An,.RfD may also be derived for the noncarclno- genlc health effects of compounds that are also carcinogenic. Reportable quantities (RQs) based on both chronic toxlclty and carclnogenldty are derived. The RQ Is used to determine the quantity of a hazardous substance for which notification Is required In the event of a release as specified under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). These two RQs (chronic toxlclty and cardnogenlclty) represent two of six scores developed (the remaining four reflect IgnltabllUy, reactivity, aquatic toxlclty, and acute mammalian toxlclty). Chemical-specific RQs reflect the lowest of these six primary criteria. The methodology for chronic toxlclty and cancer based RQs are defined In U.S. EPA, 1984 and 1986a, respectively. 111 ------- EXECUTIVE SUMMARY ds-l,2-D1chloroethy1ene Is a volatile, colorless liquid and 1s soluble In water and common polar or nonpolar organic solvents. In 1977, between 1 and 11 million pounds of cls-1,2-d1chloroethylene was produced by PPG Industries at their production facilities In Lake Charles, LA, and Ponce, Puerto R1co (TSCAPP, 1989). Recent production volume data are not avail- able. ds-1,2-D1chloroethylene 1s produced by the partial chlorlnatlon of acetylene, and 1t 1s separated from the trans-1somer by fractional distilla- tion (Stevens, 1979). ds-1,2-D1chloroethylene 1s also produced during the manufacture of other chlorinated solvents. Most cls-1,2-D1chloroethylene produced commercially Is used directly In the synthesis of other chlorinated solvents. It Is also used as a low temperature extraction solvent, a solvent for organic synthesis and as a solvent for specialty applications (Sax and Lewis, 1987; Stevens, 1979). ds-1,2-D1chloroethylene Is expected to exist almost entirely 1n the vapor phase 1n the atmosphere. Its atmospheric fate 1s expected to be dominated by the gas phase destruction by photochemlcally produced hydroxyl radicals; the half-life for this process can be estimated at 8.3 days based on an experimentally determined rate constant. Wet deposition of ds-1,2- dlchloroethylene may occur; however, any compound removed from the atmo- sphere by this process Is expected to volatilize again quickly. Neither direct photochemical degradation nor gas phase destruction by ozone or other chemical oxldants Is expected to occur to any significant extent In the atmosphere. The fate of ds-1,2-d1chloroethylene In surface water Is expected to be dominated by rapid volatilization to the atmosphere. The half-life for the volatilization of ds-1,2-d1chloroethylene from a model river Is ~3 hours. 1v ------- Although m1crob1al degradation of ds-1,2-d1chloroethylene under anaerobic conditions Is known to occur, H occurs at a slow rate. There are conflict- ing data regarding the degradation of this compound under aerobic condi- tions. It appears that some organisms are capable of degrading cls-1,2-dl- chloroethylene under aerobic conditions If suitable nutritional sources are present. The destruction of ds-1,2-d1chloroethylene 1n water by direct photolysis or by abiotic chemical degradation Is not expected to be signifi- cant. c1s-l,2-D1chloroethylene 1s not expected to bloconcentrate signifi- cantly In fish and aquatic organisms nor 1s 1t expected to adsorb to sediment and suspended organic matter. Limited experimental data on the fate of cls-1,2-d1chloroethylene In soil were located 1n the available literature. It may be highly mobile 1n soil and leach Into groundwater. c1s-l,2-D1chloroethylene will volatilize readily from the soil surface to the atmosphere. It Is expected to undergo slow microblal degradation 1n anoxlc soils and groundwater. A recent experiment Indicated that this process may also occur under aerobic conditions with certain microorganisms 1f secondary nutritional sources are available. ds-1,2-D1chloroethylene may be released to the atmosphere 1n emissions from Us production and use and from the volatilization from contaminated wastewater or from waste disposal sites, ds-1,2-Dlchloroethylene may also be released to the environment as a result of the combustion of poly(vlnyl)- chlor.lde polymers or as a result of the biological breakdown of other chlorinated solvents. Occupational exposure to c1s-l,2-dlchloroethylene may occur by Inhala- tion or dermal contact during Us manufacture, transportation or use as a solvent or chemical Intermediate. Exposure by Inhalation 1s also likely 1n areas, such as landfills, where cls-1,2-d1chloroethylene Is discarded. ------- c1s-1,2-D1ch1oroethylene has been detected In surface water, ground- water, rainwater and drinking water. Consequently, exposure to the general population can occur by drinking contaminated water. Since ds-l,2-d1- chloroethylene has been detected In tap water, exposure to the general population may occur by dermal contact or Inhalation while bathing or showering, ds-1,2-D1chloroethylene has also been detected In urban air samples. Based on an analysis of urban air levels of ds-l,2-d1chloro- ethylene (Shah and Heyerdahl, 1988), a median dally Inhalation Intake can be calculated as 3.96 yg/day. Sufficient data are not available to accurately estimate human exposure to l,2--d1chloroethylene by other routes of exposure. Pertinent data regarding the environmental toxldty of ds-l,2-d1chloro- ethylene were not located 1n the available literature cited 1n Appendix A. Pharmacok1net1c data for ds-l,2-d1chloroethylene are limited. Gas uptake studies Indicate that c1s-l,2-d1chloroethylene Is absorbed readily from the respiratory tract of rats (FUser and Bolt, 1979). Because the compound 1s neutral, low molecular weight and UpophlUc, It Is expected to be readily absorbed by any natural route of exposure (U.S. EPA, 1987a). Although tissue distribution data were not located, the highest tissue levels would be expected In the liver and kidneys (U.S. EPA, 1987a), 1f this compound behaves similarly to 1 ,l-d1chloroethylene (McKenna et al., 1978). ds-1,2-D1chloroethylene Is metabolized by hepatic cytochrome P-450 oxldases, with the formation of dlchloroacetaldehyde and dlchloroethanol (Costa and Ivanetlch, 1982). The Initial step In the metabolism probably Involves formation of a chloroethylene epoxlde that undergoes rearrangement to dlchloroacetaldehyde (Henschler, 1977; Lelbman and Ortiz, 1977). v1 ------- Metabolic elimination of ds-1,2-d1chloroethylene was described as a satur- able process, changing from a first-order to a zero-order process at 20 ppm (Fllser and Bolt, 1979). Pertinent data regarding the excretion of ds-1,2-dlchloroethylene following oral, Inhalation or dermal exposure were not located 1n the available literature dted In Appendix A. Acute Inhalation exposure of animals or humans to high concentrations of ds-1,2-d1chloroethylene vapors can produce anesthesia and narcosis (Smyth, 1937-1955; ACGIH, 1986). In rats, exposure to 16,000 ppm ds-1,2-dlchloro- ethylene for 4 hours resulted 1n death (Smyth, 1937-1955). The results of an acute oral toxlclty rat study provided biochemical evidence that ds-1,2-d1chloroethylene 1s hepatotoxlc (Jenkins et al., 1972). ds-l,2-01chloroethylene significantly elevated the activity of liver alkaline phosphatase at the 400 and 1500 mg/kg dose levels. The activities of liver glucose-6-phosphatase, liver tyroslne transamlnase and plasma alanlne transamlnase decreased at the 1500 mg/kg dose level. The systemic toxlclty resulting from subchronlc or chronic exposure to ds-l,2-d1chloroethylene, either by Inhalation or oral administration, has not been examined. Pertinent data regarding the carclnogenlclty or developmental toxlclty of ds-1,2-d1chloroethylene to animals or humans exposed by any route to this chemical were not located 1n the available literature cited In Appendix A. cls-1,2-D1chloroethylene yielded a positive result In a host-mediated assay using £. cerlvlslae 07 strains In mice (Bronzettl et al., 1984) but did not cause chromosomal aberrations or sister chromatid exchanges In Chinese hamster cells 1n vitro (Sawada et al., 1987). ------- Because of the lack of cancer data In either humans or animals, ds-1,2- dlchloroethylene was assigned to U.S. EPA we1ght-of-ev1dence group D: cannot be classified as to cardnogenldty to humans. Data were not available from which to estimate potency slope factors or to assign an RQ for cardno- genldty. Sufficient chemlcal-spedf 1c subchronlc or chronic noncancer toxlclty data were not available for derivation of RfD values for ds-l,2-d1chloro- ethylene. The RfO of 0.009 mg/kg/day for chronic oral exposure to I,l-d1- chloroethylene was adopted for subchronlc and chronic oral exposure to ds-1,2-d1chloroethylene. The Agency had previously determined that the metabolism and effects of exposure to the dlchloroethylenes are similar (U.S. EPA, 1987a,b). Using similar logic, a previously derived chronic toxlclty RQ of 1000 derived for 1,1-dlchloroethylene was adopted for ds-1,2-d1chloroethylene. ------- TABLE OF CONTENTS Page 1. INTRODUCTION 1 1.1. STRUCTURE AND CAS NUMBER 1 1.2. PHYSICAL AND CHEMICAL PROPERTIES 1 1.3. PRODUCTION DATA 2 1.4. USE DATA 2 1.5. SUMMARY 2 2. ENVIRONMENTAL FATE AND TRANSPORT 4 2.1. AIR 4 2.1.1. Reaction with Hydroxyl Radicals 4 2.1.2. Reaction with Ozone and Other Oxldants 4 2.1.3. Photolysis 4 2.1.4. Physical Removal Processes 5 2.2. WATER .- 5 2.2.1. Hydrolysis 5 2.2.2. Oxidation 5 2.2.3. Photolysis 5 2.2.4. M1crob1al Degradation 5 2.2.5. Bloconcentratlon 6 2.2.6. Adsorption 6 2.2.7. Volatilization 6 2.3. SOIL 7 2.3.1. M1crob1al Degradation 7 2.3.2. Adsorption 7 2.3.3. Volatilization 7 2.4. SUMMARY 8 3. EXPOSURE 10 3.1. WATER 10 3.2. FOOD 11 3.3. INHALATION 11 3.4. DERMAL 11 3.5. OTHER 11 3.6. SUMMARY 12 1x ------- TABLE OF CONTENTS (cent.) Page 4. ENVIRONMENTAL TOXICOLOGY 13 4.1. AQUATIC TOXICOLOGY 13 4.1.1. Acute Toxic Effects on Fauna 13 4.1.2. Chronic Effects on Fauna 13 4.1.3. Effects on Flora 13 4.1.4. Effects on Bacteria ^_ 13 4.2. TERRESTRIAL TOXICOLOGY 13 4.2.1. Effects on Fauna 13 4.2.2. Effects on Flora 14 4.3. FIELD STUDIES 14 4.4. AQUATIC RISK ASSESSMENT 14 4.5. SUMMARY 14 5. PHARMACOKINETCS 15 5.1. ABSORPTION 15 , 5.2. DISTRIBUTION 15 5.3. METABOLISM 15 5.4. EXCRETION 16 5.5. SUMMARY 16 6. EFFECTS 19 6.1. SYSTEMIC TOXICITY 19 6.1.1. Inhalation Exposure 19 6.1.2. Oral Exposure 19 6.1.3. Other Relevant Information 20 6.2. CARCINOGENICITY 21 6.2.1. Inhalation 21 6.2.2. Oral 21 6.2.3. Other^ Relevant Information 21 6.3. GENOTOXICITY 21 6.4. DEVELOPMENTAL TOXICITY 25 6.5. OTHER REPRODUCTIVE EFFECTS 25 6.6. SUMMARY 25 7. EXISTING GUIDELINES AND STANDARDS 27 7.1. HUMAN 27 7.2. AQUATIC 27 ------- TABLE OF CONTENTS (cont.) Page 8. RISK ASSESSMENT 28 8.1. CARCINOGENICITY 28 8.1.1. Inhalation 28 8.1.2. Oral 28 8.1.3. Other Routes 28 8.1.4. Weight of Evidence 28 8.1.5. Quantitative Risk Estimates 28 8.2. SYSTEMIC TOXICITY 28 8.2.1. Inhalation Exposure ... 28 8.2.2. Oral Exposure 29 9. REPORTABLE QUANTITIES 31 9.1. BASED ON SYSTEMIC TOXICITY 31 9.2. BASED ON CARCINOGENICITY 33 10. REFERENCES 34 APPENDIX A: LITERATURE SEARCHED 46 APPENDIX B: SUMMARY TABLE FOR ds-1,2-DICHLCIROETHYLENE 49 APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO C1S-1.2-DICHLOROETHYLENE 50 x1 ------- LIST OF ABBREVIATIONS AEL Adverse-effect level BCF Bloconcentratlon factor CAS Chemical Abstract Service CS Composite score PEL Frank effect level HA Health advisory HID Highest Ineffective dose Koc Son sorptlon coefficient Kow Octanol/water partition coefficient L05Q Dose lethal to 50% of recipients LOU Log dose unit LEO Lowest effective dose LOAEL Lowest-observed-adverse-effect level MED Minimum effective dose ppb Parts per billion ppm Parts per million RfD Reference dose RQ Reportable quantity RV(j Dose-rating value RVe Effect-rating value STEL Short-term exposure level TLV Threshold limit value TWA Time-weighted average UV Ultraviolet ------- 1. INTRODUCTION 1.1. STRUCTURE AND CAS NUMBER ds-l,2-D1ch1oroethylene 1s known by the synonyms els-acetylene dkhlorlde, Z-acetylene dlchlorlde, ds-1,2-d1chlorethylene and Z-l,2-d1- chlorethylene (Chemllne, 1989). The structure, CAS number, empirical formula and molecular weight are as follows: H H \ C=C \ Cl Cl CAS Registry number: 156-59-2 Empirical formula: C-HpCl- Molecular weight: 96.94 1.2. PHYSICAL AND CHEMICAL PROPERTIES ds-1,2-D1chloroethylene Is a colorless; liquid at room temperature and 1s soluble 1n water and common polar or nonpolar organic solvents (Sax and Lewis, 1987; Weast et al., 1988). It has a slight ether-Uke odor (Wlndholz et al., 1983). Selected physical and chemical properties for ds-l,2-d1- chloroethylene are given below: Melting point: -80.5°C Boiling point: 60.3°C Water solubility at 25°C: 3500 mg/a. Vapor pressure at 25°C: 215 mm Hg Log Kow: 1.86 Flash point: 6°C Conversion factors at 25°C: 1 ppm = 3.96 mg/m3; 1 mg/m3 =0.25 ppm Weast et al., 1988 Weast et al., 1988 Horvath, 1982 Stevens, 1979 Hansch and Leo, 1985 Stevens, 1979 0267d -1- 12/19/89 ------- 1.3. PRODUCTION DATA Between 1 and 11 million pounds of ds-1,2-dlchloroethylene was produced In 1977 by PPG Industries at their production facilities 1n Lake Charles, LA, and Ponce, Puerto R1co (TSCAPP, 1989). Production at the Lake Charles plant was listed as site-limited. More recent production volume data are not available. cls-1,2-D1chloroethylene Is produced by the partial chlorlnatlon of acetylene at 40°C. Separation from the trans-1somer 1s performed by fractional distillation, ds-1,2-D1chloroethylene Is also produced as a by-product of the manufacture of other chlorinated compounds (Stevens, 1979). 1.4. USE DATA ds-1,2-D1chloroethylene Is used primarily as a chemical Intermediate In the synthesis of other commercially significant chlorinated solvents. ds-1,2-D1chloroethylene Is also used as a low-temperature extraction solvent for organic materials such as dyes, perfumes, lacquers and thermo- plastics, and as a solvent for organic synthesis (Stevens, 1979; Sax and Lewis, 1987). 1.5. SUMMARY cls-1,2-D1chloroethylene 1s a volatile, colorless liquid and Is soluble In water and common polar or nonpolar organic solvents. In 1977, between 1 and 11 million pounds of cls-1,2-dlchloroethylene was produced by PPG Industries at their production facilities In Lake Charles, LA, and Ponce, Puerto R1co (TSCAPP, 1989). Recent production volume data are not avail- able. ds-1,2-D1chloroethylene 1s produced by the partial chloMnation of acetylene, and 1t 1s separated from the trans-lsomer by fractional distilla- tion (Stevens, 1979). c1s-l,2-D1chloroethylene Is also produced during the manufacture of other chlorinated solvents. Most ds-1,2-dlchloroethylene 0267d -2- 02/07/90 ------- produced commercially Is used directly In the synthesis of other chlorinated solvents. It Is also used as a low temperature extraction solvent, a solvent for organic synthesis and as a solvent for specialty applications (Sax and Lewis, 1987; Stevens, 1979). 0267d -3- 12/19/89 ------- 2. ENVIRONMENTAL FATE AND TRANSPORT 2.1. AIR The vapor pressure of ds-1,2-d1chloroethylene (215 mm Hg) at 25°C (Stevens, 1979) suggests that this compound will exist almost entirely In the vapor phase 1n the atmosphere (Elsenrelch et al., 1981). 2.1.1. Reaction with Hydroxyl Radicals. The dominant atmospheric fate process for ds-1,2-d1chloroethylene 1s expected to be destruction by the gas phase reaction with photochemlcally produced hydroxyl radicals. Experi- mental rate constants for this reaction have been determined at 2.0xlO"12 cmVmolecule-sec at 25°C (Goodman et al., 1986), Indicating a half-life of 8.3 days at an average atmospheric hydroxyl radical concentration of 5xl05 molecules/cm3. 2.1.2. Reaction with Ozone and Other Oxldants. Experimental data on the gas phase reaction of ds-1,2-d1chloroethylene with ozone, nitrate radicals or singlet oxygen Indicate that these reactions are too slow to be environ- mentally significant (Atkinson and Carter, 1984; Atkinson et al., 1987; Sanhueza and Helcklen 1975a,b). N1k1 et al. (1983) reported that the gas phase reaction of ds-1,2-dlchloroethylene with ozone was a relatively rapid reaction under controlled experimental conditions, but concluded that since free radical scavengers drastically reduce the rate of this reaction, 1t 1s not significant under atmospheric conditions. 2.1.3. Photolysis. The primary UV band for c1s-l ,2-d1chloroethylene extends from -190-240 nm (Ausubel and Wljnen, 1975). Since this compound does not adsorb significant amounts of radiation at wavelengths >290 nm, atmospheric removal by direct photolytlc degradation Is not expected to be a significant process. 0267d -4- 02/07/90 ------- 2.1.4. Physical Removal Processes. 1,2-D1chloroethylene has been found In rainwater (Kawamura and Kaplan, 1983). Wet depostlon from the atmosphere Is a likely atmospheric removal process. Any 1,2-d1chloroethylene removed from the atmosphere by this process, however, is expected to revolatHIze rapidly to the atmosphere. 2.2. WATER 2.2.1. Hydrolysis. Hydrolysis of 1,2-d1chloroethylene 1n water Is expected to be slow and should not be an environmentally significant fate process (Jaber et al., 1984; Mabey et al., 1981). 2.2.2. Oxidation. Data specific to the chemical oxidation of ds-l,2-d1- chloroethylene 1n water were not located In the available literature dted In Appendix A. By analogy to other chlorinated ethylenes, H Is not expected to be a significant process (DllUng et al., 1975). 2.2.3. Photolysis, ds-1,2-D1chloroethylene does not adsorb light 1n the environmentally significant range >290 nm (Ausubel and Wljnen, 1975); therefore, direct photochemical degradation 1n water Is not expected to be a significant fate process. 2.2.4. M1crob1al Degradation. cls-1,2-D1chloroethylene undergoes slow reductive dechlorlnatlon under anaerobic conditions. ds-1,2-D1chloro- ethylene, when Incubated with methanogenlc aquifer material obtained near a landfill, underwent mlcroblal degradation under anaerobic conditions. After 16 weeks, >98X of this compound had been removed by biological degradation (Wilson et al., 1986). When 5 mg/a of ds-1,2-dlchloroethene was added to anoxlc microcosms containing water and sediment, the half-life for removal was 88-339 days. This compound degraded to chloroethane and vinyl chloride (Barr1o-Lage et al., 1986). 0267d -5- 12/19/89 ------- c1s-l,2-D1chloroethylene has been found to resist mlcroblal attack under aerobk conditions (Fogel et al., 1986). Tabak et al. (1981), however., determined that ds-1,2-dlchloroethylene was susceptible to biological degradation, using a settled domestic wastewater Inoculum. In sediment samples obtained from a cattail marsh, 660 ppb cls-1,2-dlchloroethylene completely degraded after 50 hours under aerobic conditions with methane as a secondary nutrient source (Fogel et al., 1986). It appears that aerobic blodegradatlon of ds-1,2-dlchloroethylene may occur In the presence of suitable microorganisms and nutrients. 2.2.5. B1oconcentrat1on. A BCF of 15 can be obtained for ds-l,2-dl- chloroethylene using the linear regression equation log BCF - 0.76 log K - 0.23 (Bysshe, 1982) and the KQW reported 1n Section 1.2. This value suggests that bloaccumulatlon In fish and aquatic organisms 1s not expected to be a significant fate process. 2.2.6. Adsorption. Soil adsorption coefficients ranging from 49-254 can be estimated for ds-1,2-dlchloroethylene (Section 2.3.2.). These values suggest that this compound will not adsorb strongly to soil, therefore, It 1s not expected to adsorb significantly to sediment and suspended organic matter In aquatic systems. 2.2.7. Volatilization. An experimental Henry's Law constant of 4.08xlO~3 atm-mVmol at 24.8°C has been determined for cls-1,2-dlchloro- ethylene (Gossett, 1987). Based on this value, the estimated volatilization half-life from a model river 1 m deep, flowing at 1 m/sec with a wind velocity of 3 m/sec Is ~3 hours (Thomas, 1982). In the laboratory, the volatilization rate of ds-l,2-d1chloroethylene from a rapidly stirred solution was determined and the author estimated that the corresponding volatilization half-life from a body of water 1 m deep would be 5 hours 0267d -6- 12/19/89 ------- (D1ll1ng, 1977). It Is expected that volatilization from water to the atmosphere will be a dominant fate process. 2.3. SOIL 2.3.1. M1crob1al Degradation. Limited data on the mlcroblal degradation of ds-1,2-dlchloroethylene In soil were located 1n the available literature dted 1n Appendix A. Experimental studies have shown that cls-1,2-dlchloro- ethylene can undergo mlcroblal degradation using Inocula from groundwater microcosms (Barr1o-Lage et a!., 1986; Wilson et al., 1986); therefore, this compound may undergo biological degradation under anaerobic conditions In soil. Henson et al. (1989) reported that a mixed culture of soil organisms acclimated to chlorinated hydrocarbons completely degraded ds-1,2-dlchloro- ethylene 1n 8 days under aerobic conditions using methane gas as a nutrient. The biological degradation of ds-1,2-d1chloroethylene 1n soil, therefore, appears to be a likely fate process under both aerobic and anaerobic conditions. 2.3.2. Adsorption. A soil adsorption coefficient of 245 can be obtained using the linear regression equation log K = 0.544 log K + 1.377 (Lyman, 1982) and the K reported In Section 1.2. Using the water solubility reported In Section 1.2. 1n the regression equation log K = -0.55 log S * 3.64 {Lyman, 1982), a K of 49 Is obtained. These values suggest that ds-1,2-dlchloroethylene will be highly to moderately mobile In soil (Swann et al., 1983); therefore, cls-1,2-dlchloroethylene has the potential to leach Into groundwater. 2.3.3. Volatilization. The relatively high vapor pressure of cls-1,2-dl- chloroethylene, 215 mm Hg (Stevens, 1979), and the expectation that this compound will not adsorb strongly to soil (see Section 2.3.2.) suggest that It will readily volatilize from the soil surface to the atmosphere. 0267d -7- 02/07/90 ------- 2.4. SUMMARY ds-1,2-01chloroethylene 1s expected to exist almost entirely In the vapor phase In the atmosphere. Its atmospheric fate Is expected to be dominated by the gas phase destruction by photochemlcally produced hydroxyl radicals; the half-life for this process can be estimated at 8.3 days based on an experimentally determined rate constant. Wet deposition of cls-1,2- dlchloroethylene may occur; however, any compound removed from the atmo- sphere by this process Is expected to volatilize again quickly. Neither direct photochemical degradation nor gas phase destruction by ozone or other chemical oxldants Is expected to occur to any significant extent In the atmosphere. The fate of cls-1,2-d1chloroethylene In surface water 1s expected to be dominated by rapid volatilization to the atmosphere. The half-life for the volatilization of ds-1,2-d1chloroethylene from a model river Is -3 hours. Although mlcroblal degradation of ds-1,2-d1chloroethylene under anaerobic conditions \s known to occur. It occurs at a slow rate. There are conflict- ing data regarding the degradation of this compound under aerobic condi- tions. It appears that some organisms are capable of degrading cls-1,2-d1- chloroethylene under aerobic conditions If suitable nutritional sources are present. The destruction of cls-1,2-dlchloroethylene In water by direct photolysis or by abiotic chemical degradation 1s not expected to be signifi- cant. cls-1,2-Olchloroethylene 1s not expected to bloconcentrate signifi- cantly In fish and aquatic organisms nor Is It expected to adsorb to sediment and suspended organic matter. Limited experimental data on the fate of cls-1,2-d1chloroethylene In soil were located 1n the available literature. It may be highly mobile In soil and leach Into groundwater. cls-1,2-D1chloroethylene will volatilize 0267d -8- 12/19/89 ------- readily from the soil surface to the atmosphere. It Is expected to undergo slow mlcroblal degradation 1n anoxlc soils and groundwater. A recent experiment Indicated that this process may also occur under aerobic conditions with certain microorganisms if secondary nutritional sources are available. 0267d -9- 12/19/89 ------- 3. EXPOSURE 1,2-D1chloroethylene may be released to the atmosphere 1n emissions from Us production and use and by the volatilization from contaminated wastewater or from waste disposal sites. It can be formed from the pyroly- sls or combustion of poly(v1nyl)chlor1des and some vinyl copolymers (Mkhal, 1976; Shen, 1982). 1,2-01chloroethylene Is known to enter the environment as a result of the anaerobic breakdown of other chlorinated solvents, most notably tetrachloroethane and 1,1,2-trlchloroethylene (CUne and V1ste, 1985; Hallen et a!., 1986; Parsons et al., 1984). According to an occupational survey conducted by NIOSH (1989), 215 people are potentially exposed to 1,2-d1chloroethylene In the workplace. Occupational exposure may occur by Inhalation of 1,2-d1chloroethylene vapors or dermal contact during Us production or use. 3.1. WATER ds-1,2-D1chloroethylene has been detected 1n drinking water, ground- water and surface water. It has been qualitatively detected In the drinking water of Philadelphia, PA (Suffet et al., 1980). In a survey of drinking water supplies conducted throughout the United States, ds-1,2-d1chloro- ethylene was found 1n 16 of 466 random sites at a maximum concentration of 2.0 ppb, and 1n 38 of 479 nonrandom sites at a maximum concentration of 120 i ppb (WestMck et al., 1984). It was detected 1n samples taken from the Indian River, FL, at a concentration of 4.0-48.1 ppb {Wang et al., 1985). In groundwater surveys, ds-1,2-dlchloroethylene was detected In Nebraska (2.9 ppb maximum concentration) and Wisconsin (Goodenkauf and Atkinson, 1986; KM11 and Sonzognl, 1986). cls-1,2-D1chloroethylene has also been detected In groundwater samples obtained near sites of chlorinated organic 0267d -10- 02/07/90 ------- solvent use or hazardous waste sites (Cllne and V1ste, 1985; S1lka and Wallen, 1988; Wang et al., 1985) and In the leachate from landfills (Sabel and Clark, 1984). 3.2. FOOD Pertinent data regarding human exposure to ds-1,2-d1chloroethylene In food were not located 1n the available literature dted 1n Appendix A. 3.3. INHALATION In a recent compilation and analysis of ambient levels of volatile organic compounds In the atmosphere, Shah and Heyerdahl (1988) determined that the median dally urban level of ds-1,2-d1chloroethylene was 0.050 ppb, based on an analysis of 124 data points. The levels were below the limits of detection 1n suburban or rural areas. Given the above value, and using the average volume of air Inhaled by an adult human (20 m3), the median dally Inhalation Intake of cls-1,2-d1chloroethylene by the urban population can be calculated at 3.96 wg/day. Since ds-1,2-d1chloroethylene has been found In tap water, human exposure may occur by Inhalation of vapors that have volatilized from the water during showers and other uses of household water. / 3.4. DERMAL Pertinent data regarding dermal exposure to ds-1,2-dlchloroethylene were not located 1n the available literature, dted in Appendix A. Since ds-l,2-d1chloroethylene has been detected 1n tap water, 1t Is likely that the general population may be dermally exposed to this compound while showering or bathing with contaminated water. 3.5. OTHER Pertinent data regarding other routes of exposure to ds-1,2-dlchloro- ethylene were not located In the available literature cited 1n Appendix A. 0267d -11- 12/19/89 ------- 3.6. SUMMARY ds-l,2-D1chloroethylene may be released to the atmosphere 1n emissions from Us production and use and from the volatilization from contaminated wastewater or from waste disposal sites, ds-1,2-D1chloroethylene may also be released to the environment as a result of the combustion of poly(vlnyl)- chloMde polymers or as a result of the biological breakdown of other chlorinated solvents. Occupational exposure to ds-1,2-d1chloroethylene may occur by Inhala- tion or dermal contact during Us manufacture, transportation or use as a solvent or chemical Intermediate. Exposure by Inhalation 1s also likely 1n areas, such as landfills, where ds-1,2-d1chloroethylene 1s discarded. ds-1,2-01chloroethylene has been detected 1n surface water, ground- water, rainwater and drinking water. Consequently, exposure to the general population can occur by drinking contaminated water. Since ds-l,2-d1- chloroethylene has been detected 1n tap water, exposure to the general population may occur by dermal contact or Inhalation while bathing or showering. ds-1,2-D1chloroethylene has also been detected 1n urban air samples. Based on an analysis of urban air levels of ds-1,2-d1chloro- ethylene (Shah and Heyerdahl, 1988), a median dally Inhalation Intake can be calculated as 3.96 pg/day. Sufficient data are not available to accurately estimate human exposure to 1,2-d1chloroethylene by other routes of exposure. 0267d -12- 02/07/90 ------- 4. ENVIRONMENTAL TOXICOLOGY 4.1. AQUATIC TOXICOLOGY 4.1.1. Acute Toxic Effects on Fauna. Pertinent data regarding the effects of acute exposure of aquatic fauna to ds-1,2-d1ch1oroethylene were not located 1n the available literature cited 1n Appendix A. 4.1.2. Chronic Effects on Fauna. 4.1.2.1. TOXICITY — Pertinent data regarding the effects of chronic exposure of aquatic fauna to ds-1,2-d1chloroethylene were not located 1n the available literature dted 1n Appendix A. 4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION — Pertinent data regarding the b1oaccumulat1on/b1oconcentrat1on potential of cls-1,2-dlchloroethylene In aquatic fauna were not located In the available literature cited 1n Appendix A. 4.1.3. Effects on Flora. 4.1.3.1. TOXICITY — Pertinent data regarding the toxic effects of exposure of aquatic flora to ds-1,2-dlchloroethylene were not located In the available literature cited 1n Appendix A. 4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bloconcen- tratlon potential of ds-1,2-dlchloroethylene In aquatic flora were not located 1n the available literature dted In Appendix A. 4.1.4. Effects on Bacteria. Pertinent data regarding the effects of exposure of aquatic bacteria to ds-l,2-d1c:hloroethylene were not located In the available literature dted In Appendix A. 4.2. TERRESTRIAL TOXICOLOGY 4.2.1. Effects on Fauna. Pertinent data regarding the effects of exposure of terrestrial fauna to ds-1,2-dlchloroethylene were not located In the available literature dted 1n Appendix A. 0267d -13- 12/19/89 ------- 4.2.2. Effects on Flora. Pertinent data regarding the effects of exposure of terrestrial flora to ds-l,2-d1chloroethylene were not located In the available literature cited In Appendix A. 4.3. FIELD STUDIES Pertinent data regarding the effects of ds-1,2-d1chloroethylene on flora and fauna In the field were not located In the available literature cited 1n Appendix A. 4.4. .AQUATIC RISK ASSESSMENT Pertinent data regarding the effects of exposure of freshwater fauna and flora to ds-1,2-d1chloroethylene were not located In the available litera- ture cited In Appendix A. Acute studies with representatives from eight families of freshwater fauna and at least three chronic studies and one bloconcentratlon study with freshwater fauna and flora are needed to develop a freshwater criterion by the method of U.S. EPA/OWRS (1986). Pertinent data regarding the effects of exposure of marine fauna and flora to cls-1,2-d1chloroethylene were not located In the available litera- ture cited 1n Appendix A. Acute studies with representatives from eight families of marine fauna and at least three chronic studies and one bloconcentratlon study with marine fauna and flora are needed to develop a saltwater criterion by the method of U.S. EPA/OWRS (1986). 4.5. SUMMARY Pertinent data regarding the environmental toxlclty of ds-1,2-dlchloro- ethylene were not located In the available literature cited In Appendix A. 0267d -14- 12/19/89 ------- 5. PHARMACOKINIETICS 5.1. ABSORPTION Fllser and Bolt (1979) exposed male Wlstar rats 1n a closed Inhalation system to >500 ppm cls-1,2-d1chloroethylene and monitored the decline of the concentration 1n the gas phase to determine the equilibration of atmospheric cls-1,2-d1chloroethylene with the whole body. Concentrations of cls-1,2-dl- chloroethylene In the system declined markedly for the first 1.5 hours, Indicating rapid absorption. Data were not sufficient to estimate the rate or extent of respiratory absorption. Pertinent data regarding the gastrointestinal absorption of ds-1,2- dlchloroethylene were not located 1n the available literature dted In Appendix A. U.S. EPA (1987a), however, noted that the compound Is neutral, UpophlUc, and has low molecular weight. Thus, the chemical should be readily absorbed by any natural route of exposure. 5.2. DISTRIBUTION Pertinent data regarding tissue distribution for cls-1,2-d1chloro- ethylene following Inhalation, oral or dermal exposure of animals or humans were not located 1n the available literature dted 1n Appendix A. U.S. EPA (1987a), however, predicted that the highest levels of the compound would be located In the liver and kidney, assuming this compound behaves similarly to the structurally related 1,l-d1chloroethylene (McKenna et al., 1978). 5.3. METABOLISM Bonse et al. (1975) reported that perfuslon of the Isolated rat liver with ds-1,2-dlchloroethylene resulted 1n the production of dlchloroethanol and dlchloroacetlc acid. The Initial step 1n the metabolism of ds-l,2-d1- chloroethylene may Involve the formation of chloroethylene epoxlde, which undergoes rearrangement to form dlchloroacetaldehyde (Henschler, 1977; Lelbman and Ortiz, 1977). 0267d -15- 02/07/90 ------- According to Costa and Ivanetlch (1982), multiple forms of hepatic mlcrosomal cytochrome P-450 bind and metabolize cls-1,2-dlchloroethylene. These Investigators Identified 2,2-dlchloroethanol and dlchloroacetaldehyde in rat hepatic microsomes Incubated 1n the presence of an NADPH-generatlng system, EDTA, and cls-1,2-d1chloroethylene. 2-Chloroethanol, chloroacet- aldehyde or chloroacetlc acid were not produced In significant amounts In these Incubation mixtures. The Investigators proposed the metabolic scheme presented 1n Figure 5-1 and Indicated that the nonenzymatlc rearrangement would be expected to favor a chloride shift rather than a hydride shift. The metabolic elimination of Inhaled cls-1,2-d1chloroethylene was examined In male Wlstar rats exposed In a closed Inhalation system (Fllser and Bolt, 1979). Metabolic elimination was described as a saturable phenomenon, changing from a first-order to a zero-order process at 20 ppm. Fllser and Bolt (1980) detected acetone 1n the expired air from male Wlstar rats exposed 1n a closed Inhalation system to cls-1,2-dlchloro- ethylene. The Investigators postulated that metabolites of ds-l,2-d1- chloroethylene may Inhibit enzymes of the citric add cycle, resulting In acetonemla and the exhalation of acetone. Acetone was not considered a metabolite of ds-1,2-d1chloroethylene. 5.4. EXCRETION Pertinent data regarding the excretion of ds-1,2-dlchloroethylene following Inhalation, oral or dermal exposure of animals or humans were not located 1n the available literature cited In Appendix A. 5.5. SUMMARY Pharmacoklnetlc data for c1s-l,2-dlchloroethylene are limited. Gas uptake studies in rats Indicated that ds-1,2-dlchloroethylene Is absorbed readily from the respiratory tract (Fllser and Bolt, 1979). Because the 0267d -16- 12/19/89 ------- C IHC-CHC / \ C I HC—CHC I I«• Shift non-*nz ymIc r«orrong«minI HjO C I H2CCOCI —* C I H2CC02H •* C h I » r I d • i h I H CIjHCCHO —- C IjHCCOjH I C 12 H C C H 2 0 H FIGURE 5-1 Proposed Metabolic Scheme for the 1,2-01chloroethylenes Source: Costa and Ivanetlch, 1982 0267d -17- 12/19/89 ------- compound 1s neutral, UpophlUc, and has low molecular weight, H Is expected to be readily absorbed by any natural route of exposure (U.S. EPA, 1987a). Although tissue distribution data were not located, the highest tissue levels would be expected 1n the liver and kidneys (U.S. EPA, 1987a), If this compound behaves similarly to 1,l-d1chloroethylene (McKenna et al., 1978). ds-1,2-D1chloroethylene Is metabolized by hepatic cytochrome P-450 oxIdasBs, with the formation of dlchloroacetaldehyde and dlchloroethanol (Costa and Ivanetlch, 1982). The Initial step 1n the metabolism probably Involves formation of a chloroethylene epoxlde that undergoes rearrangement to dlchloroacetaldehyde (Henschler, 1977; Lelbman and Ortiz, 1977). Metabolic elimination of ds-1,2-d1chloroethylene was described as a satur- able process, changing from a first-order to a zero-order process at 20 ppm (Fllser and Bolt, 1979). Pertinent data regarding the excretion of ds-1,2-d1chloroethylene following oral, Inhalation or dermal exposure were not located In the available literature cited 1n Appendix A. 0267d -18- 02/07/90 ------- 6. EFFECTS 6.1. SYSTEMIC TOXICITY 6.1.1. Inhalation Exposure. 6.1.1.1. ACUTE — In an unpublished study, Smyth (1937-1955) determined that 8000 ppm ds-1,2-dlchloroethylene was not lethal to rats exposed for 4 hours. However, rats were anesthetized In 8 minutes and died within 4 hours after exposure to 16,000 ppm. Narcosis 1s a primary effect 1n animals exposed to ds-1,2-d1chloroethylene by Inhalation (Smyth, 1937-1955). ds-l,2-01chloroethylene also produces narcosis 1n humans exposed to high concentrations of this chemical (ACGIH, 1986). Freundt and Macholz (1978) showed that a single 8-hour Inhalation expo- sure to 200, 600 or 1000 ppm ds-1,2-dlchloroethylene resulted 1n signifi- cant, dose-dependent Increases In hexobart>1tal sleeping time, zoxazolamlne paralysis times and the metabolic formation of 4-am1noant1pyr1ne from amlno- pyrlne 1n adult female Wlstar rats. These Increases Indicated an Inter- action with the mixed-function oxldase system, 6.1.1.2. SUBCHRONIC -- Pertinent data regarding the toxkHy of ds-1,2-d1chloroethylene following subchronlc Inhalation exposure of animals or humans were not located 1n the available literature dted 1n Appendix A. 6.1.1.3. CHRONIC -- Pertinent data regarding the toxldty of ds-1,2- dlchloroethylene following chronic Inhalation exposure of animals or humans were not located 1n the available literature dted 1n Appendix A. 6.1.2. Oral Exposure. 6.1.2.1. SUBCHRONIC -- Pertinent data regarding the toxldty of cls-1,2-dlchloroethylene following subchronlc oral exposure of animals or humans were not located 1n the available literature dted 1n Appendix A. 0267d -19- 07/20/90 ------- 6.1.2.2. CHRONIC -- Pertinent data regarding the toxldty of ds-1,2- dlchloroethylene following chronic oral exposure of animals or humans were not located In the available literature dted 1n Appendix A. 6.1.3. Other Relevant Information. Quast et al. (1983) administered 1,l-d1chloroethylene, an Isomer of ds-1,2-d1chloroethylene, 1n drinking water to Sprague-Dawley rats for 2 years at concentrations of 0, 50, 100 and 200 ppm. Experimental groups were composed of 48 rats/sex, while 80 rats/sex formed the control group. Adjusted doses for continuous exposure were estimated by the Investigators at 0, 7, 10 or 20 mg/kg/day 1n males and 0, 9, 14 or 30 mg/kg/day In females. No statistically significant differences between treated and control groups were seen regarding survival time, body weight, food and water consumption, hematology, clinical chemistry, urlnalysls and gross pathology. Furthermore, the authors could not establish a relationship between exposure to 1 ,l-d1chloroethylene and neoplastlc changes. Females In all treated groups, however, and males 1n the highest dose group developed hepatic lesions described as "hepatocellular swelling with mldzonal fatty change." Acute LD5Q data for ds-1,2-dlchloroethylene have not been reported. Jenkins et al. (1972) evaluated the hepatotoxlclty of ds-1,2-dlchloroethylene 1n rats. Groups of three or four adult Holtzman rats were given ds-1,2-dlchloroethylene as a single dose of either 400 or 1500 mg/kg^ by gavage In corn oil. ds-1,2-D1chloroethylene significantly elevated the activity of liver alkaline phosphatase at the 400 and 1500 mg/kg doses. The activities of liver glucose-6-phosphatase, liver tyroslne transamlnase and plasma alanlne transamlnase decreased at the 1500 mg/kg dose. It should also be noted that although there 1s little data to Implicate ds-1,2-dlchloroethylene as a neurotoxlcant, 1t 1s structurally similar to trlchloroethylene which Is a neurotoxlc agent. 0267d -20- 07/20/90 ------- 6.2. CARCINOGENICITY 6.2.1. Inhalation. Pertinent data regarding the cardnogenldty of ds-l,2-d1chloroethylene following Inhalation exposure of humans or animals were not located 1n the available literature cited 1n Appendix A. 6.2.2. Oral. Pertinent data regarding the cardnogenldty of ds-l,2-d1- chloroethylene following oral exposure of humans or animals were not located In the available literature dted 1n Appendix A. 6.2.3. Other Relevant Information. Other relevant Information regarding the cardnogenldty of ds-1,2-d1chloroethylene were not located 1n the available literature dted 1n Appendix A. 6.3. GENOTOXICITY Relevant genotoxldty data for ds-l,2-d1chloroethylene are presented In Table 6-1. The pattern 1s predominantly negative 1n prokaryotes and weakly positive 1n eukaryotes. In In vitro studies 1n prokaryotes, neither ds-1,2-d1chloroethylene alone (Cerna and Kypenova, 1977) nor In a mixture with the trans- Isomer (Mortelmans et al.,, 1986) Induced reverse mutations with or without metabolic activation 1n Salmonella typhlmurlum. In the absence of activation, neither forward nor reverse mutations were Induced In Escherkhla coll K12 (Grelm et al., 1975); however, Cerna and Kypenova (1977) reported positive results with S. typhlmurlum using the host-mediated assay 1n female ICR mice. In liquid suspensions of strain 07 of Saccharo- ^ _«M.^^^^— myces cerevlslae. ds-l,2-d1chloroethylene Induced a slight but significant dose-related Increase In ade~ recomblnants 1n the presence of metabolic activation but only at one concentration In the absence of activation. In the same system, an Increase In 1lv* reverse point mutations was Induced at one concentration 1n the absence of activation (Bronzettl et al., 1984; Gain et al., 1982). The compound had sporadic effects on the number of 0267d -21- 07/25/90 ------- TABLE 6-1 Genotoxlclty Testing of cls-1,2-D1chloroethylene I rv> l\3 i Assay Reverse nutation Forward mutation Nilotic recombination Indicator Organism Salmonella typhlmurlum TA1535. TA1537, TA98. TA100 S. typhlmurlum TA9B. TA100. TA1535. TA1538. TA1950, TA1951. TA1952 S. typhlmurlum TA1950. TA1951. TA1952 Escherlchla coll K12 (gal*, arg*. nad*) E. coll K12 (5-methyl tryptophan resistance) Saccharomyces cerevlslae 07 Application liquid suspension spot test host-mediated assay In female ICR mice liquid suspension liquid suspension liquid suspension Purity (X) els-trans mixture NR NR analytical grade analytical grade 97 Concentration or Dose 33.3-3333.3 tig/plate 0.5. 5. 50 rag/plate 0.5. 1 time L050 2.9 mM 2.9 mM 40. 80. 100 mM Activating System +/- rat and hamster liver S9 NA +/- mouse liver mlcrosomal pro- tein and NADH generating system */- mouse liver mlcrosomal pro- tein and NAOH generating system »/- mouse liver mlcrosomal pro- Response Comment -/- NC Applied 0.05 ml of 1. 10. 100X per plate « Dose-effect relation- ship reported NC NC +/(*) Dose-dependent toxlclty with lower survival Reference Mortelmans et al.. 1986 Cerna and Kypenova. 1977 Cerna and Kypenova. 1977 Grelm et al. , 1975 Grelm et al.. 1975 Gall et al.. 1982; Bronzettl teln and NADH generating with S9; dose-dependent production of ade* recomblnants with S9 and at 100 mM without S9; llv* revertants at 100 mM without S9 et al.. 1984 03 O ------- 6-1 (cont.) Assay Gene conversion Indicator Application Organism S. cerevlslae 07 liquid suspension Purity Concentration Activating (X) or Dose System 97 40. 80. 100 nfl »/- mouse liver mlcrosomal pro- tein and NADH generating Response Comment -/- Dose-dependent toxldty with lower survival with S9; dose-dependent production of ade* recomblnants with S9 and at 100 mH without S9; llv* revertants at 100 mH without S9 Reference Gall 1982; et al et al.. Bronzettl .. 1984 Point mutation S. cerevlslae 07 liquid suspension 97 40. 80. 100 nfl Gene conversion S. cerevlslae 07 CO i Point mutation S. cerevlslae 07 o Sister ^ chromatld •M exchange \ o Chinese hamster fIbroblasts »/- mouse liver mlcrosomal pro- tein and NADH generating Intrasangulneous hose-mediated assay In male Swiss albino mice by gavage 97 1300 mg/kg once NA Intrasangulneous hose-mediated assay In male Swiss albino mice by gavage 97 300 mg/kg/day. 8 days «• 600 mg/kg 9th day NA cell culture 97 0.25-2 mg/mt rat liver S9. NADP -/(*) Dose-dependent toxldty with lower survival with S9; dose-dependent production of ade* recomblnants with S9 and at 100 mH without S9; llv* revertants at 100 mH without S9 (») In acute tests, trp* convertants In liver, not kidney or lung, and llv* revertants In kidney, not liver or lung: with repeated dosing, convertants In lung, liver or kidney and revertants In kidney and lung, not liver (») In acute tests, trp* convertants In liver, not kidney or lung, and llv* revertants In kidney, not liver or lung; with repeated dosing, convertants In lung, liver or kidney and revertants In kidney and lung, not liver NC Gall et al.. 1982; Bronzettl et al.. 1984 Bronzettl et al.. 1984 Bronzettl et al.. 1984 Sawada et al., 1987 ------- TABLE 6-1 (cont.) o rvi cr> Assay Chromosomal aberrations Indicator Organism Chinese hamster flbroblasts female ICR mice Application cell culture Intraperltoneal Injection Purity (X) 97 NR Concentration or Dose 0.25-2 mg/mi 0.5 x LOso. single dose Activating System rat liver S9. NADP NA Response NC Comment No significant differ- ence with a single dose Reference Sawada et al.. 1987 Cerna and Kypenova. 1977 female ICR mice Intraperltoneal Injection NR 0.167 x LD5o. 5-10 times dally NA but Increased cells with aberrations with 5 dally doses; dose- dependence seen 6 hours after 10th dose No significant differ- ence with a single dose but Increased cells with aberrations with 5 dally doses; dose- dependence seen 6 hours after 10th dose Cerna and Kypenova. 1977 NA •= Not applicable; NC « no comment; NR • not reported; ( + ) •= weakly positive in ^ O ------- trpf convertants and 11vf reverse point mutations 1n yeast of the same strain recovered from various organs In an Intrasangulneous host-mediated assay (Bronzettl et al.. 1984). In the one mammalian In vitro assay located, ds-1,2-dlchloroethylene did not Induce chromosomal aberrations or sister chromatld exchanges 1n Chinese hamster cells In vivo (Sawada et al., .1987). Ln vivo. H Induced chromosomal aberrations 1n the bone marrow of IntraperHoneally Injected mice (Cerna and Kypenova, 1977). 6.4. DEVELOPMENTAL TOXICITY Pertinent data regarding the teratogenldty of ds-l,2-d1chloroethylene were not located In the available literature cited 1n Appendix A. 6.5. OTHER REPRODUCTIVE EFFECTS Pertinent data regarding other reproductive effects of cls-1,2-dlchloro- ethylene were not located In the available literature cited In Appendix A. 6.6. SUMMARY Acute Inhalation exposure of animals or humans to high concentrations of ds-l,2-d1chloroethylene vapors can produce anesthesia and narcosis (Smyth, 1937-1955; ACGIH, 1986). In rats, exposure to 16,000 ppm ds-1,2-dlchloro- ethylene for 4 hours resulted 1n death (Smyth, 1937-1955). The results of an acute oral toxlclty study 1n rats provided biochemical evidence that ds-l,2-d1chloroethylene Is hepatotoxlc (Jenkins et al., 1972). ds-l,2-D1chloroethylene significantly elevated the activity of liver alkaline phosphatase at the 400 and 1500 mg/kg dose levels. The activities of liver glucose-6-phosphatase, liver tyroslne transamlnase and plasma alanlne transamlnase decreased at the 1500 mg/kg dose level. The systemic toxldty resulting from subchronlc or chronic exposure to ds-1,2-d1chloroethylene, either by Inhalation or oral administration, has 0267d -25- 07/25/90 ------- not been examined. It should be noted that although there Is Uttle data to Implicate ds-l,2-d1chloroethylene as a neurotoxlcant, 1t 1s structurally similar to trlchloroethylene which 1s a neurotoxlc agent. Pertinent data regarding the .< carclnogenlcHy or teratogenldty of cls-1,2-d1chloroethylene to animals or humans exposed by any route to this chemical were not located 1n the available literature cited In Appendix A. ds-1,2-D1chloroethylene yielded a positive result In a host-mediated assay using S. cerlvlslae D7 strains In mice (Bronzettl et al., 1984) but did not cause chromosomal aberrations or sister chromatld exchanges In Chinese hamster cells in vitro (Sawada et al., 1987). 0267d -26- 07/25/90 ------- 7. EXISTING GUIDELINES AND STANDARDS 7.1. HUMAN ACGIH (1989) has not adopted TLVs for ds-1,2-d1chloroethylene; however, the currently recommended TWA-TLV for the commercial mixture of the ds- and trans-lsomers Is 200 ppm (790 mg/m3), based on a no-effect level of 1000 ppm 1n animals (ACGIH, 1986). Because the no-effect level for prolonged animal Inhalation 1s -1000 ppm, ACGIH (1986) regards the TLV as sufficiently conservative and does not recommend a STEL for the mixture. OSHA (1989) also does not 11st a value for cls-1,2-dlchloroethylene but lists transi- tional and final rule limits of 200 ppm (790 mg/m3) for the commercial mixture, which Is Identical to the ACGIH (1989) recommendation. The 1-day, 10-day, longer-term and lifetime HAs recommended for cls-1,2-dlchloro- ethylene by U.S. EPA (1987a) were 4, 1, 1 and 0.07 mg/l (child), respec- tively. The longer-term HA for an adult was 3.5 mg/l. Only the 1-day advisory was computed from data generated by exposure to cls-1,2-dlchloro- ethylene; the other values were derived from experiments with 1,1-dlchloro- ethylene. 7.2. AQUATIC Guidelines and standards to protect aquatic life from exposure to ds-1,2-d1chloroethylene were not located lin the available literature cited 1n Appendix A. 0267d -27- 02/07/90 ------- 8. RISK ASSESSMENT 8.1. CARCINOGENICITY 8.1.1. Inhalation. Pertinent data regarding the cardnogenldty of Inhalation exposure of humans or animals to cls-1,2-dlchloroethylene were not located 1n the available literature cited In Appendix A. 8.1.2. Oral. Pertinent data regarding the cardnogenldty of oral exposure of humans or animals to ds-l,2-d1chloroethylene were not located In the available literature dted 1n Appendix A. 8.1.3. Other Routes. Pertinent data regarding the cardnogenldty of ds-1,2-d1chloroethylene to humans or animals exposed by other routes were not located 1n the available literature cited 1n Appendix A. 8.1.4. Weight of Evidence. Because data were not located regarding the cardnogenldty of ds-1,2-dlchloroethylene In humans or In animals, the compound Is most appropriately placed 1n U.S. EPA we1ght-of-evldence Group D: not classifiable as to human cardnogenldty (U.S. EPA, 1986b). 8.1.5. Quantitative Risk Estimates. The absence of cancer data by either the Inhalation or oral routes precludes derivation of potency slope factors for either route of exposure. 8.2. SYSTEMIC TOXICITY 8.2.1. Inhalation Exposure. 8.2.1.1. LESS THAN LIFETIME (SUBCHRONIC) ~ Pertinent data regarding the toxlclty of subchronlc Inhalation exposure to ds-1,2-dlchloroethylene were not located 1n the available literature cited In Appendix A. As discussed In Section 8.2.2.2., 1n the absence of chemical-specific data, it Is appropriate to consider deriving an RfD for ds-1,2-dlchloroethylene based on analogy to 1,1-dlchloroethylene. Inhalation data for 1,1-dlchloro- ethylene abound and have been reviewed by U.S. EPA (1986c), but no RfD has 0267d -28- 12/19/89 ------- been derived for Inhalation exposure. It Is beyond the scope of this document to evaluate the data on 1,1-dkhloroethylene to derive RfD values for Inhalation exposure to that chemical. Therefore, 1t Is not currently possible to derive an RfD for subchronlc Inhalation exposure to ds-l,2-d1- chloroethylene by analogy to 1,1-dlchloroethylene. 8.2.1.2. CHRONIC — Pertinent data regarding chronic Inhalation exposures to cls-1,2-dlchloroethylene were not located 1n the available literature dted 1n Appendix A. As discussed above, 1t Is appropriate to consider deriving an RfD for ds-1,2-d1chloroethylene based on analogy to 1,1-dlchloroethylene. The lack of an RfD for chronic Inhalation exposures to 1,1-dlchloroethylene, however, precludes derivation of an RfD for c1s-l,2-d1chloroethylene by analogy to 1 ,l-d1chloroethylene. 8.2.2. Oral Exposure. 8.2.2.1. LESS THAN LIFETIME (SUBCHRONIC) — Pertinent data regarding the toxldty of subchronlc oral exposures to ds-1,2-dlchloroethylene were not located 1n the available literature, cited In Appendix A. Chemical- specific data are not sufficient for derivation of an RfD for subchronlc oral exposures to ds-1,2-dlchloroethylene. Therefore, the chronic oral RfD of 0.009 mg/kg/day derived by 'analogy to 1,l-d1chloroethylene In Section 8.2.2.2. Is adopted as the RfD for subchronlc oral exposure to ds-l,2-dl- chloroethylene. Confidence In the key study Is medium; confidence in the data base and RfD are low, as explained 1n Section 8.2.2.2. 8.2.2.2. CHRONIC — Pertinent data regarding chronic oral exposures to ds-1,2-dlchloroethylene were not located in the available literature dted In Appendix A. Because chemical-specific data are not sufficient for derivation of an RfD, It 1s appropriate to consider data from chemicals that are structurally and tox1colog1cally similar. Structurally similar 0267d -29- 12/19/89 ------- chemicals that could be considered Include trans-1,2-d1chloroethylene and I,l-d1chloroethylene. U.S. EPA (1989) derived an oral chronic RfD of 0.02 mg/kg/day for trans-1,2-d1chloroethylene from a subchronlc drinking water rat study and an RfD of 0.009 mg/kg/day for 1 ,l-d1chloroethylene. In deriving lifetime HAs for els- and trans-1,2-d1chloroethylene (see Section 7.1.). U.S. EPA (1987a,b) evaluated data for 1,1-, ds-1,2- and trans-1,2- dlchloroethylene and concluded that the noncardnogenlc effects of these compounds are essentially Identical. Pharmacok1net1c data for the 1,1- and l,2-1somers (U.S. EPA, 1986c) Indicate that the metabolism of all three Isomers Is similar and Involves the formation of an epoxlde Intermediate. Additionally,, the proposed metabolism scheme for 1,2-d1chloroethylene by Costa and Ivanetlch (1982) postulates that a chloride shift would be favored to the exclusion of a hydride shift (see Section 5.3.). U.S. EPA (1987a,b) determined that the most conservative approach was to base derivation of the lifetime has for the c1s-l,2-1somer on analogy to 1,l-d1chloroethylene, which seems to follow a metabolic pathway very similar to the cls-1,2-1somer. Pursuing the precedent of U.S. EPA (1987a,b), the verified RfD of 0.009 mg/kg/day for chronic oral exposure to 1,1-dlchloroethylene Is adopted as the RfD for chronic oral exposure to cls-1,2-d1chloroethylene. The RfD of 0.009 mg/kg/day was based on a LOAEL of 9 mg/kg/day for liver effects In a 2-year drinking water study using rats (Quast et al., 1983). As stated by U.S. EPA (1989), confidence 1n the study 1s medium. Confidence In the data base for mixed 1,2-d1chloroethylene Is low; confidence In the RfD Is low because of the additional uncertainty associated with basing an RfD on analogy to a similar chemical. NTP (1989) Indicated that ds-1,2-dlchloroethylene has been selected for toxldty testing. These tests, when completed, may permit derivation of chemical-specific RfD values. 0267d -30- 02/07/90 ------- 9. REPORTABLE QUANTITIES 9.1. BASED ON SYSTEMIC TOXICITY The toxldty of cls-1,2-d1chloroethylene was reviewed and evaluated 1n Chapter 6. Pertinent data regarding systemic toxldty consequent to subchronlc or chronic exposure to ds-1,2-d'ichloroethylene by either oral or Inhalation exposure of humans or animals were not located 1n the available literature cited 1n Appendix A. Therefore, an RQ cannot be derived for this compound from chemical-specific data. An RQ of 1000, however, has been derived by U.S. EPA (1986c) for the other two dlchloroethylene Isomers, trans-1,2-d1chloroethylene and 1,l-d1chloroethylene. The former represents a CS of 13.8, based on fat accumulation 1n the liver and hlstologlcal alterations 1n the lungs of six rats exposed to 200 ppm trans-1,2-d1chloroethylene 8 hours/day, 5 days/week for 16 weeks (Freundt et a!., 1977). The latter represents a CS of 19.0, based on early deaths and terminations among 12 mice exposed to 55 ppm 1,l-d1chloroethylene 6 hours/day, 5 days/week for 10 months with 12 months observation (Hong et al., 1981). As discussed In Chapter 8, 1t Is appropriate, when chemical-specific data are lacking, to derive risk assessment values based on analogy to a chemical that Is structurally and lexicologically similar. To maintain consistency with the approach used 1n Chapter 8, the RQ for mixed 1,2-d1chloroethylene Isomers will be based by analogy on the 1,1-lsomer. Moreover, the key study for the l,l-1somer Is of a higher quality, since H uses more animals and Is of longer duration. Therefore, an RQ of 1000 Is recommended for cls-1,2-d'ichloroethylene, based on analogy to I,l-d1chloroethylene (Table 9-1). 0267d -31- 02/07/90 ------- TABLE 9-1 ds-1,2-D1chloroethylene Minimum Effective Dose (MED) and Reportable Quantity (RQ) Route: Inhalation Species/Sex: mice/male, female Dose*: 259 mg/day Duration: 10 months (with 12 months observation) Effect: postexposure mortality and morlbundlty RVd: 1.9 RVe: 10 CS: 19.0 RQ: 1000 Reference: Hong et al., 1981 *Equ1valent human dose 0267d -32- 12/19/89 ------- 9.2. BASED ON CARCINOGENICITY Pertinent data regarding the cardnogenlcHy of ds-1,2-d1chloroethylene In humans or In animals were not located In the available literature dted In Appendix A. Therefore, cis-1,2-dkhloroethylene Is most appropriately placed 1n U.S. EPA we1ght-of-ev1dence Group D: not classifiable as to human cardnogenlcHy (U.S. EPA, 1986b). No hazard ranking 1s assigned to chemicals In Group 0; therefore, an RQ based on cardnogenlcHy cannot be assigned. 0267d -33- 12/19/89 ------- 10. REFERENCES ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986. Documentation of the Threshold Limits Values and Biological Exposure Indices, 4th ed. Cincinnati, OH. p. 185. ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1989. Threshold Limits Values and Biological Exposure Indices for 1989-1990. p. 20. Atkinson, R. and W.P.L. Carter. 1984. Kinetics and mechanisms of gas-phase reactions of ozone with organic compounds under atmospheric conditions. Chem. Rev. 84: 437-470. Atkinson, R., S.M. Aschmann and M.A. Goodman. 1987. Kinetics of the gas- phase reactions of nitrate radicals with a series of alkynes, haloalkenes and alpha-, beta-unsaturated aldehydes. Int. J. Chem. Klnet. 19: 299-307. Ausubel, R. and M.H.J. Wijnen. 1975. Primary steps 1n the photolysis of ds-l,2-d1chloroethylene. Int. J. Chem. Klnet. 75: 739-751. Barrlo-Lage, G., F.Z. Parsons, R.S. Nassar and P.A. Lorenzo. 1986. Sequen- tial dehalogenatlon of chlorinated ethenes. Environ. Sc1. Techno!. 20: 96-99. 0267d -34- 02/07/90 ------- Bonse, G., T.H. Urban, D. Relchert, et al. 1975. Chemical reactivity, metabolic oxlrane formation and biological reactivity of chlorinated ethyl- enes In the Isolated perfused rat liver preparation. Blochem. Pharmacol. 24: 1829-1834. BronzetU, G., C. Bauer, C. Cor si, et al. 1984. Comparative genetic activ- ity of els- and trans-1,2-dlchloroethylene 1n yeast. Teratog. Cardnog. Mutagen. 4: 365-375. Bysshe, S.E. 1982. B1oconcentrat1on factor In aquatic organisms. In: Handbook of Chemical Property Estimation Methods, W.J. Lyman, W.F. Reehl and D.H. Rosenblatt, Ed. McGraw-Hill Book Co., Mew York, NY. p. 5-1 to 5-30. Cerna, M. and H. Kypenova. 1977. Mutagenlc activity of chloroethylenes analyzed by screening system tests. Mutat. Res. 46: 214-215. Chemllne. 1989. National Library of Medicine, Chemllne Database. Online 7/8/89. Cllne, P.V. and D.R. Vlste. 1985. Migration and degradation patterns of volatile organic compounds. Waste Manage. Res. 3: 351-360. Costa, A.K. and K.M. Ivanetlch. 1982. The 1,2-dlchloroethylenes: Their metabolism by hepatic cytochrome P-450 Yn vitro. Blochem. Pharmacol. 31: 2093-2102. 0267d -35- 12/19/89 ------- Crockett, P.M., B. Klllan, K.S. Crump and R.B. Howe. 1985. Descriptive Methods for Using Data from Dissimilar Experiments to Locate a No-Adverse- Toxic-Effects Region In the Dose-Duration Plane. Prepared by K.S. Crump and Company, Inc. under Contract No. 68-01-6807 for the Environmental Criteria and Assessment Office, U.S. EPA, Cincinnati, OH. Dllllng, H.L. 1977. Interphase transfer processes. II. Evaporation rates of chloromethanes, ethanes, ethylenes propanes and propylenes from dilute. aqueous solutions. Comparisons with theoretical predictions. Environ. Sd. Technol. 11: 405-409. Dllllng, W.L., N.B. Tefertlller and G.J. Kallos. 1975. Evaporation rates and reactivities of methylene chloride, chloroform, 1,1,1-trlchloroethane, trlchloroethylene, tetrachloroethylene and other chlorinated compounds In dilute aqueous solutions. Environ. Sd. Technol. 9: 833-838. Durkln, P. and W. Meylan. 1988. User's Guide for D2PLOT: A Program for Dose/Duration Graphs. Prepared by Chemical Hazard Assessment Division, Syracuse Research Corporation under Contract No. 68-C8-004 for Environmental Criteria and Assessment Office, U.S. EPA, Cincinnati, OH. Elsenrelch, S.J., B.B. Looney and J.D. Thornton. 1981. Airborne organic contaminants 1n the Great Lake ecosystems. Environ. Sd. Technol. 15: 30-38. Fllser, J.G. and H.M. Bolt. 1979. Pharmacok1net1cs of halogenated ethylenes In rats. Arch. Toxlcol. 42: 123-136. 0267d -36- 02/07/90 ------- Fllser, J.G. and H.M. Bolt. 1980. Characteristics of haloethylene-lnduced acetonemla In rats. Arch. Toxlcol. 45(2): 109-116. Fogel, M.M., A.R. Taddeo and S. Fogel. 1986. B1odegradat1on of chlorinated ethenes by a methane-utilizing mixed culture. Appl. Environ. M1crob1ol. 51: 720-724. Freundt, K.J. and J. Macholz. 1978. Inhibition of mixed functions oxldase In rat liver by trans- and ds-1,2-d1chloroethylene. Toxicology. 10: 131-139. Freundt, K.J., G.P. Llebaldt and E. L1eberw1rth. 1977. Tox1c1ty studies on trans-1,2-d1chloroethylene. Toxicology. 7: 141-153. Gain, A., C. Bauer, G. Bronzettl, et al. 1982. Genetic activity of 1,2-dlchloroethylene. A. ln_ vitro studies. Boll. Soc. Hal. B1ol. Sper. 58: 860-863. Goodenkauf, 0. and J.C. Atkinson. 1986. Occurrence of volatile organic chemicals In Nebraska groundwater. Ground Water. 24: 231-233. Goodman, M.A., E.G. Tuazon, R. Atkinson and A.M. Winer. 1986. A study of the atmospheric reactions of chloroethenes with OH radicals, In.: ACS D1v. Environ. Chem. 192nd Natl. Mtg. 26: 169-171. Gossett, J.M. 1987. Measurement of Henry's Law constant for Cl and C2 chlorinated hydrocarbons. Environ. Sd. Technol. 21: 202-208. 0267d -37- 02/07/90 ------- Grelm, H., G. Bonse, Z. Radwan, et al. 1975. MutagenlcUy In vitro and potential carclnogenldty of chlorinated ethylenes as a function of metabolic oxlrane formation. Blochem. Pharmacol. 24: 2013-2017. Hallen, R.T., 3.W. Pyne, Jr. and P.M. Molton. 1986. Transformation of chlorinated ethenes and ethanes by anaerobic microorganisms. In.: ACS D1v. Environ. Chem. 26: 344-346. Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue No. 26. Pomona College, Claremont, CA. Henschler, 0. 1977. Metabolism and mutagenlclty of halogenated oleflns: A comparison of structure and activity. Environ. Health Perspect. 21: 61-64. Henson, J.M., M.V. Yates and J.W. Cochran. 1989. Metabolism of chlorinated methanes, ethanes and ethylenes by a mixed bacterial culture growing on methane. 3. Ind. M1crob1ol. 4: 29-35. Hong, C.B., J.M. Winston, L.P. Thornburg, C.C. Lee and J.S. Woods. 1981. Follow-up study on the cardnogenlclty of vinyl chloride and vlnylldene chloride In rats and mice: Tumor Incidence and mortality subsequent to exposure. J. Toxlcol. Environ. Health. 7(6): 909-924. (CHed In U.S. EPA, 1986b) Horvath, A.L. 1982. Halogenated Hydrocarbons Solubility - M1sdb1l1ty With Water. Marcel Dekker, Inc., New York, NY. p. 496-497. 0267d -38- 02/07/90 ------- Jaber, H.M., U.R. Mabey, A.T. L1u, T.W. Chou and H.L. Johnson. 1984. Data Acquisition for Environmental Transport and Fate Screening. Prepared by the Office of Health and Environmental Assessment, Washington, DC for the Office of Solid Waste and Emergency Response, Washington, DC. EPA-600/6-84/009. NTIS PB84-243906, PB84-243955. p. 45. Jenkins, L.J., Jr., M.J. Trabulus and S.D. Murphy. 1972. Biochemical effects of 1,1-dlchloroethylene 1n rats: Comparison with carbon tetra- chloMde and 1,2-dkhloroethylene. Toxlcol. Appl. Pharmacol. 23: 501-510. Kawamura, K. and I.R. Kaplan. 1983. Organic compounds In the rainwater of Los Angeles. Environ. Scl. Technol. 17: 497-501. Krlll, R.M. and W.C. Sonzognl. 1986. Chemical monitoring of Wisconsin's groundwater. J. Am. Water Works Assoc. 78: 70-75. Lelbman, K.C. and E. Ortiz. 1977. Metabolism of halogenated ethylenes. Environ. Health Perspect. 21: 91-97. Lyman, W.J. 1982. Adsorption coefficient for soils and sediments. Jru Handbook of Chemical Property Estimation Methods, W.J. Lyman, W.F. Reehl and D.H. Rosenblatt, Ed. McGraw-Hill Book Co., New York, NY. p. 4-1 to 4-3. Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1981. Aquatic Fate Process Data for Organic Priority Pollutants. U.S. Environmental Protection Agency, Washington, DC. EPA-440/4-81-014. p. 159-160. 0267d -39- 07/25/90 ------- Mantel, N. and M.A. Schnelderman. 1975. Estimating "safe" levels, a hazardous undertaking. Cancer Res. 35: 1379-1386. McKenna, M.J., J.A. Zempel, E.O. Madrid and P.J. Gehrlng. 1978. The pharmacoklnetlcs of (14C) vinylldene chloride In rats following Inhalation exposure. Toxkol. Appl. Pharmacol. 45: 599-610. MUhal, J. 1976. ToxUHy of pyrolysls and combustion products of poly- (vlnyl chloride). F1re Mater. 1: 57-62. Mortelmans, K., S. Haworth, T. Lawlor, W. Speck, B. Talner and E. Zelger. 1986. Salmonella mutagenldty tests: II. Results from testing of 270 chemicals. Environ. Mutagen. 8(7): 1-119. N1k1, H., P.O. Maker, C.M. Savage and L.P. Breltenbach. 1983. Atmospheric ozone-olefln reactions. Environ. Sd. Techno!. 17: 312A-322A. NIOSH (National Institute for Occupational Safety and Health). 1989. National Occupational Exposure Survey (NOES) as of 3/29/89. NTP (National Toxicology Program). 1989. Management Status Report. 7/7/89. OSHA (Occupational Safety and Health Administration). 1989. 29 CFR. Part 1910. A1r Contaminants. Final Rule. p. 2933. Parsons, F., P.R. Wood and J. DeMarco. 1984. Transformations of tetra- chloroethene In microcosms and groundwater. J. Am. Water Works Assoc. 76: 56-59. 0267d -40- 07/25/90 ------- Quast, J.P., C.G. Humlston, C.E. Wade, et al. 1983. A chronic toxldty and oncogenkHy study In rats and subchronlc toxldty study 1n dogs on Ingested vlnylldene chloride. Fund. Appl. ToxUol. 3: 55-62. Sabel, G.V. and T.P. Clark. 1984. Volatile organic compounds as Indicators of municipal solid waste leachates contamination. Waste Manage. Res. 2: 119-130. Sanhueza, E. and J. Helcklen. 1975a. Reaction of atomic oxygen (3P) with dlchloroethylene. J. Photochem. 4: 1-15. Sanhueza, E. and J. Helcklen. 1975b. The oxidation of els- and trans-l,2-d1chloroethane. Int. J. Chem. K1net. 7: 589-604. Sawada, M., T. Sofunl and M. Ishldate, Jr. 1987. Cytogenlc studies on 1,1-dlchloroethylene and Us two Isomers In mammalian cells hi vitro and In vivo. Mutat. Res. 187: 157-163. Sax, N.I. and R.J. Lewis. 1987. Hawley's Condensed Chemical Dictionary, llth ed. Van Nostrand Relnhold Co., New York, NY. p. 378. Shah, J.J. and E.K. Heyerdahl. 1988. National Ambient Volatile Organic Compounds (VOCS) Data Base Update. EPA/600/3-88/010, p. 60. Shen, T.T. 1982. Estimation of organic compound emissions from waste lagoons. J. A1r Pollut. Control Fed. 32: 79-82. 0267d -41- 07/25/90 ------- Sllka, L.R. and D.A. Wallen. 1988. Observed rates of blotransformatlon of chlorinated allphatks 1n groundwater. In.: Superfund '88. Proceedings 9th National Conference, Haz. Mat. Control Res. Inst. p. 138-141. Smyth, H.F., Jr. 1937-1955. Unpublished work by Chemical Hygiene Fellow- ship, Mellon Institute, Pittsburgh, PA. (CHed 1n Smyth, 1956) Smyth, H.F. 1956. Improved communication - Hygienic standards for dally Inhalation. Am. Ind. Hyg. Assoc. Quart. 17: 129-185. Stevens, V.L. 1979. 1,2-D1chloroethylene. I_n: K1rk-0thmer Encyclopedia of Chemical Technology, 3rd ed., M. Grayson and D. Eckroth, Ed. John Wiley and Sons, New York, NY. 5: 742-745. Suffet, I.H., L. Brenner and P.R. Cairo. 1980. Gas chromatography-mass spectrometry Identification of trace organlcs In Philadelphia, PA. U.S.A. drinking waters during a two-year period. Water Res. 14: 853-867. Swann, R.L., D.A. Laskowskl, P.J. McCall, K. Vander-Kuy and H.J. Dlshburger. 1983. A rapid method for the estimation of the environmental parameters octanol/water partition coefficient, soil sorptlon content, water to air ratio and water solubility. Res. Rev. 85: 17-28. Tabak, H.H., S.A. Quave, C.I. Mashnl and E.F. Barth. 1981. B1odegradab1l- Hy studies with organic priority pollutant compounds. J. Water Pollut. Control Fed. 53: 1503-1518. 0267d -42- 07/25/90 ------- Thomas, R.G. 1982. Volatilization from water. In_: Handbook of Chemical Property Estimation Methods, W.J. Lyman, W.F. Reehl and D.H. Rosenblatt, Ed. McGraw-Hill Book Co., New York, NY. p. 15-1 to 15-34. TSCAPP. 1989. Computer print-out of non-confidential production data from TSCA Inventory OTS, CID, U.S. EPA, Washington, DC. Online: 7/8/89. U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of Health Effect Assessment Chapters of the Consent Decree Hater Criteria Documents. Federal Register. 45(231): 79347-79357. U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on Chronic ToxkUy Data. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjust- ments Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment Group, Office of Health and Environmental Assessment for the Office of Emergency and Remedial Response, Washington, DC. U.S. EPA. 1986b. Guidelines for Carcinogen Risk Assessment. Federal Register. 51(185): 33992-34003. U.S. EPA. 1986c. Health and Environmental Effects Profile for Dlchloro- ethenes. Prepared b-y the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office,, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC. 0267d -43- 07/25^90 ------- U.S. EPA. 1987a. Health Advisory Document for cls-1,2-D1chloroethylene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. p. 1-13. U.S. EPA. 1987b. Health Advisory Document for trans-l,2-01chloroethylene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. p. 1-14. U.S. EPA. 1989. Integrated Risk Information System (IRIS). Online. Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. U.S. EPA/OWRS (U.S. Environmental Protection Agency/Office of Water Regula- tions and Standards). 1986. Guidelines for Deriving Numerical National Water Quality Criteria for the Protection of Aquatic Organisms and Their Uses. U.S. EPA, Washington, DC. p. 22-58, 98. PB85-227049/XAB. Wang, T.C., R. Lenahan, M. Kanlck, et al. 1985. The removal of trkhloro- ethylene contaminated groundwater at Vero Beach, Florida. Arch. Environ. Contam. ToxUol. 14: 719-723. Weast, R.C., M.J. Astle and W.H. Beyer.. 1988. CRC Handbook of Chemistry and Physics, 69th ed. CRC Press, Inc., Boca Raton, PL. p. C-272. 0267d -44- 07/25/90 ------- Westrlck, J.J., J.W. Hello and R.F. Thomas. 1984. The groundwater supply survey. J. Am. Water Works Assoc. 76: 52-59. Wilson, B.H., G.B. Smith and J.F. Rees. 1986. Blotransformatlon .of selected aklylbenzenes and halgenated aliphatic hydrocarbons In methanogenlc aqulfler material: A microcosm study. Environ. Scl. Technol. 20: 997-1002. Wlndholz, M., Ed., et al. 1983. The Merck Index. Merck and Co., Rahway, NJ. p. 13-14. 0267d -45- 07/25/90 ------- APPENDIX A LITERATURE SEARCHED This HEED 1s based on data Identified by computerized literature searches of the following: CHEMLINE TSCATS CASR online (U.S. EPA Chemical Activities Status Report) TOXLINE TOXLIT TOXLIT 65 RTECS OHM TADS STORET SRC Environmental Fate Data Bases SANSS . AQUIRE TSCAPP NTIS Federal Register CAS ONLINE (Chemistry and Aquatic) HSDB SCISEARCH Federal Research in Progress These searches were conducted in July, 1989, and the following secondary sources were reviewed: ACGIH (American Conference of Governmental Industrial Hygienists). 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH. ACGIH (American Conference of Governmental Industrial Hygienists). 1987. TLVs: Threshold Limit Values for Chemical Substances in the Work Environment adopted by ACGIH with Intended Changes for 1987-1988. Cincinnati, OH. 114 p. Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and Sons, NY. 2878 p. Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John Wiley and Sons, NY. p. 2879-3816. 0267d -46- 02/07/90 ------- Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed.,, Vol. 2C. John Wiley and Sons, NY. p. 3817-5112. Grayson, M. and D. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo- pedia of Chemical Technology, 3rd ed. John WHey and Sons, NY. 23 Volumes. Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed. Publishing Sciences Group, Inc., Littleton, MA. 575 p. IARC (International Agency for Research on Cancer). IARC Mono- graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. IARC, WHO, Lyons, France. Jaber, H.M., W.R. Mabey, A.T. L1u, T.W. Chou and H.L. Johnson. 1984. Data Acquisition for Environmental Transport and Fate Screening. Prepared by the Office of Health and Environmental Assessment, Washington, DC. for the Office of Solid Waste, and Emergency Response, Washington, DC. EPA 600/6-84-009. NT1S PB84-243906, PB84-243955. p. 45. NTP (National Toxicology Program). 1987. Toxicology Research and Testing Program. Chemicals on Standard Protocol. Management Status. Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide Register. McGraw-Hill Book Co., NY. Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th ed. Van Nostrand Relnhold Co., NY. SRI (Stanford Research Institute). 1987. Directory of Chemical Producers. Menlo Park, CA. / U.S. EPA. 1986. Report on Status Report In the Special Review Program, Registration Standards Program and the Data Call In Programs. Registration Standards and the Data Call In Programs. Office of Pesticide Programs, Washington, DC. USITC (U.S. International Trade Commission). 1986. Synthetic Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ. 1892, Washington, DC. Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY. Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc., Rahway, NJ. Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual. British Crop Protection Council. 695 p. 0267d -47- 02/07/90 ------- In addition, approximately 30 compendia of aquatic toxldty data were reviewed, Including the following: Battelle's Columbus Laboratories. 1971. Water Quality Criteria Data Book. Volume 3. Effects of Chemicals on Aquatic Life. Selected Data from the Literature through 1968. Prepared for the U.S. EPA under Contract No. 68-01-0007. Washington, DC. Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute Toxldty of Chemicals to F1sh and Aquatic Invertebrates. Summaries of Toxldty Tests Conducted at Columbia National Fisheries Research Laboratory. 1965-1978. U.S. Dept. Interior, F1sh and Wildlife Serv. Res. Publ. 137, Washington, DC. McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed. Prepared for the Resources Agency of California, State Water Quality Control Board. Publ. No. 3-A. Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target Species. Prepared for the U.S. EPA, Washington, DC. PB-269605. Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S. EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876. 0267d -48- 12/19/89 ------- APPENDIX B Summary Table for c1s-1.2-01chloroethylene Species Inhalation Exposure Subchronlc ID Chronic ID Carclnogenlclty 10 Oral Exposure Subchronlc rat Chronic rat Carclnogenlclty ID REPOBTABLE QUANTITIES Based on chronic toxlclty: Based on Carclnogenlclty: Exposure 10 ID ID 50 ppro 1.1-dlchloroethylene In drinking water for 2 years (9 mg 1.1-dlchloroethylene/kg/day) 50 ppm 1,1-dlchloroethylene In drinking water for 2 years (9 sag 1.1-dlchlorosthylene/kg/day) J ID 1000* 10 Effect RfO or q]* ID ID ID ID 10 ID LOAEL for 0.009 liver lesions mg/kg/day* LOAEL for 0.009 liver lesions mg/kg/day* 10 ID Reference NA NA NA Quasi et al.. 1983 Quast et al.. 1983 NA Hong et al . . 1981 NA •Values derived for 1.1-dlchloroethylene adopted for 1,2-dlchloroethylene mixed Isomers based on analogy 10 - Insufficient data; NA = not applicable CD 10 ------- APPENDIX C DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO ds-1,2-OICHLOROETHYLENE C.I. DISCUSSION Dose/duration-response graphs for Inhalation and oral exposure to ds-1,2-d1chloroethylene, generated by the method of Crockett et al. (1985) using the computer software by Durkin and Meylan (1988) developed under contract to ECAO-Clnclnnatl are presented 1n Figures C-l through C-3. Data used to generate these graphs are presented 1n Section C.2. In the genera- tion of these figures, all responses are classified as adverse (FEL, AEL or LOAEL) or nonadverse (NOEL or NOAEL) for plotting. The ordlnate expresses Inhalation exposure In either of two ways. In Figure C-l, the experimental concentration, expressed as mg/m3, was multiplied by the time parameters of the exposure protocol (e.g., hours/day and days/week), and Is presented as expanded experimental concentration [expanded exp cone (mg/m3)]. In Figure C-2, the expanded experimental concentration was multiplied by the animal Inhalation rate 1n mVday and divided by the animal body weight In kg to calculate a dally dose In mg/kg/day. The dally dose was then multi- plied by the cube root of the ratio of the anlmaV.human body weight to adjust for species differences In metabolic rate (Mantel and Schnelderman, 1975). The result was multiplied by an absorption coefficient of 0.5 to adjust to an equivalent absorbed dose and then multiplied by 70 kg, the reference human body weight, to express the human equivalent dose as mg/day for a 70 kg human [human equlv dose (mg/day)]. For oral exposure, the ordlnate expresses dose as human equivalent dose. The animal dose In mg/kg/day Is multiplied by the cube root of the ratio of tbe animal :human body weight to adjust for species differences In basal metabolic rate (Mantel and Schnelderman, 1975). The result Is then multiplied by 70 kg, 0267d -50- 12/19/89 ------- 9 U 0 U X t Q t1 c t & X fc! •1800" 100 I I 8.001 (Inhalation Exposure) 0.01 HUMRN EQUIU DURflTIOH (fraction lifespan) ENVELOP METHOD Key: F . FEL L - LOAEL N . NOEL Solid line - Adverse Effects Boundary Dashed line » No Adverse Effects Boundary FIGURE C-l Dose/Duration-Response Graph for Inhalation Exposure to c1s-D1chloroethy!ene: Envelope Method (Expanded Experimental Concentration) 0267d -51- 12/19/89 ------- A > « \ 9 V •0 fi 0 u I v 1080 I I I 0.001 (Inhalation Exposure) J I e.ei HUMRN EOUIU DURRIION (fraction lifespan) ENUELOP METHOD Key: F . FEL L - LOAEL N . NOEL Solid line • Adverse Effects Boundary Dashed line - No Adverse Effects Boundary FIGURE C-2 Dose/Duration-Response Graph for Inhalation Exposure to ds-l,2-D1chloroethylene: Envelope Method (Human Equivalent Dose) 0267d -52- 12/19/89 ------- V U (!) 0 a M 0 •i 1808 i i r LI 8.001 (Oral Exposure) e.ei HUMflN EQUIU DURflTION (fraction lifespan) Key: L - LOAEL FIGURE C-3 Dose/Duration-Response Graph for Oral Exposure to ds-1,2-D1chloroethylene: Envelope Method 0267d -53- 12/19/89 ------- the reference human body weight, to express the human equivalent dose as mg/day for a 70 kg human [human equlv dose (mg/day)]. The adverse effects boundary (solid line) 1s drawn by Identifying the lowest adverse effect dose or concentration at the shortest duration of exposure at which an adverse effect occurred. From this starting point, an Infinite line 1s extended upward, parallel to the dose axis. The starting point 1s then connected to the lowest adverse effect dose or concentration at the next longer duration of exposure that has an adverse effect dose or concentration equal to or lower than the previous one. This process Is continued to the lowest adverse effect dose or concentration. From this point, a line parallel to the duration axis 1s extended Infinitely to the right. The adverse effects region lies above the adverse effects boundary. Using the envelope method, the no adverse effects boundary (dashed line) Is drawn starting with the point representing the highest no adverse effects dose or concentration. From this point, a line parallel to the duration axis Is extended to the dose or concentration axis. The starting point is then connected to the next equal or lower no adverse effect dose or concen- tration at a longer duration of exposure. When this process can no longer be continued, a line parallel to the dose or concentration axis 1s dropped to the duration axis. The no adverse effects region lies below the no adverse effects boundary. At both ends of the graph between the adverse effects and no adverse effects boundaries are regions of ambiguity. The area (1f any) resulting from Intersections of the adverse effects and no adverse effects boundaries Is defined as the region of contradiction. In the censored data method, all no adverse effect points located In the region of Contradiction are dropped from consideration, and the No Adverse effects boundary Is redrawn so that It does not Intersect the Adverse 0267d -54- 02/07/90 ------- effects boundary and no region of contradiction 1s generated. This method results In the most conservative definition of the no adverse effects region. F1gue C-l represents the dose/duration response graph of Inhalation data expressed as expanded concentration and generated by the envelope method. The boundary for the region of adverse effects 1s defined by a PEL (Rec. #1) for anesthesia In 8 minutes followed by death within 4 hours In rats Inhaling 1600 ppm cls-1,2-d1chloroethylene and a LOAEL (Rec. #3) for dose- dependent Increases 1n hexobarbHal sleeping time, zoxalamlne paralysis time and Increased formation of 4-am1noant1pyr1ne from amlnopyrlne, Indications of Interaction with the mixed function ox'idases In rats Inhaling 200 ppm. The boundary for the region of no adverse effects Is defined by a single NOEL (Rec. #2) for absence of fatalities In rats Inhaling 8000 ppm ds-1,2- dlchloroethylene. No region of contradiction was generated by overlap of the boundaries; hence, there 1s no need for use of the censored method. Figure C-2 represents the same data expressed as the human equivalent dose. Data were insufficient for the derivation of an Inhalation RfD. Figure C-3 presents the dose/duration response graph of oral data generated by the envelope method. Since there 1s only one datum (a LOAEL for Increased liver alkaline phosphatase activities 1n rats dosed once with 400 mg/kg, used to construct the graph) (Rec. #1) no boundaries can be drawn, no region of contradiction can be generated, and there Is no need for use of the censored method. Data regarding oral exposure to ds-l,2-d1- chloroethylene were Insufficient for derivation of an RfD. Adoption of the verified oral RfD for the l,l-1somer of the compound was recommended Instead. 0267d -55- 07/25/90 ------- C.2. DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS C.2.1. Inhalation Exposure. Chemical Name: CAS Number: Document Title: Document Number Document Date: Document Type: ds-1 ,2-d1chloroethylene 156-59-2 Health and Environmental ds-1 ,2-dichloroethylene NR NR HEED Effects Document on ======================== RECORD #1: Species: Sex: Effect: Route: ================ Rats NR PEL Inhalation Body Weight: Reported Dose: Converted Dose: Exposure Period: Duration Observation: Molecular Weight: Inhalation hours/day: Inhalation days/week: # Inhal. Exp. days: 0.35 kg 1600 ppm 6340 mg/m3 1 day 1 day 4.00 Comment: Citation: Comment: Citation: Number Exposed: NR Number Responses: NR Type of Effect: DEATH SHe of Effect: BODY Severity Effect: 10 Given 8000, 16,000 ppm Death within 4 hours continuous exposure. Smyth, 1937-1955 4 hours. Anesthesia In 8 minutes. after exposure. Not expanded to RECORD #2: Species: Sex: Effect: Route: Rats NR NOEL Inhalation Body Wt: Reported Dose: Converted Dose: Exposure Period: Duration Observation: Molecular Weight: Inhalation hours/day: Inhalation days/week: # Inhal . Exp. days: 0.35 kg 8000 ppm 3170 mg/m3 1 day 1 day 4.00 Number Exposed: NR Number Responses: 0 Type of Effect: Site of Effect: Severity Effect: 10 See previous record. Smyth, 1937-1955 0267d -56- 02/07/90 ------- RECORD #3: Comment: Citation: Species: Sex: Effect: Route: Rats F ema1e LOAEL Inhalation Number Exposed: 10 Number Responses: NR Type of Effect: ENZYM SHe of Effect: BODY Severity Effect: 1 Body Weight: Reported Dose: Converted Dose: Exposure Period: Duration Observation: Molecular Weight: Inhalation hours/day: Inhalation days/week: # Inhal. Exp. days: 8 NR ENZYM LIVER 1 0.35 kg 200 ppm 793 mg/m3 day day 8.00 Given 0, 200, 600, 1000 ppm, not expanded to continuous exposure. Dose-dependent Increase 1n hexobarbltal sleeping time, zoxazolamlne paralalysls time (8 rats), and Increased formation of 4-am1no-ant1pyr1ne In liver mlcrosomes (10 rats). Freundt and Macholz, 1978 C.2.2. Oral Exposure. Chemical Name: c1s-l,2-D1chloroethylene CAS Number: Document Title: Document Number: Document Date: Document Type: 156-59-2 Health and Environmental Effects Document on ds-1,2-D1chloroethylene NR NR HEED RECORD #1 Comment: Citation: Species: Sex: Effect: Route: Rats Male LOAEL Gavage Body Weight: Reported Dose: Converted Dose: Exposure Period: Duration Observation: 1 day Number Exposed: 4 Number Responses: NR Type of Effect: ENZYM SHe of Effect: LIVER Severity Effect: 1 Given 0, 400, 1500 mg/kg, single dose. liver alkaline phosphatase activity. Jenkins et al., 1972 0.35 kg 400 mg/kg/day 400 mg/kg/day 1 day Significant Increase In NR = Not reported 0267d -57- 02/07/90 ------- |