3
1,2-Dichloroethene1
cis-1,2-Dichloroethene
trans-1,2-Dichloroethene
Acute Exposure Guideline Levels

PREFACE

Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review and interpret relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:


AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could

1

This document was prepared by the AEGL Development Team composed of Cheryl B. Bast (Oak Ridge National Laboratory) and Chemical Manager Ernest V. Falke (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guideline reports (NRC 1993, 2001).



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3 1,2-Dichloroethene1 cis-1,2-Dichloroethene trans-1,2-Dichloroethene Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guide- line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab- lished to identify, review and interpret relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic chemicals. AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min, 1 h, 4 h, and 8 h) and are distin- guished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could 1 This document was prepared by the AEGL Development Team composed of Cheryl B. Bast (Oak Ridge National Laboratory) and Chemical Manager Ernest V. Falke (Na- tional Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances). The NAC reviewed and revised the document and AEGLs as deemed neces- sary. Both the document and the AEGL values were then reviewed by the National Re- search Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC com- mittee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guideline reports (NRC 1993, 2001). 144

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145 1,2-Dichloroethene experience notable discomfort, irritation, or certain asymptomatic, non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure. AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape. AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience life-threatening health effects or death. Airborne concentrations below the AEGL-1 represent exposure levels that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, non-sensory effects. With increasing airborne concentrations above each AEGL, there is a progres- sive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as in- fants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experi- ence the effects described at concentrations below the corresponding AEGL. SUMMARY 1,2-Dichloroethene is a flammable, colorless liquid existing in both cis- and trans- forms and as a mixture of these two isomers. It is one of a number of two carbon chlorocarbons produced in a reaction mixture resulting from proc- esses involved in the chlorination of ethylene to produce chlorinated monomers and solvents. The trans-isomer is commercially isolated by distillation and sold as a highly purified product that is used in precision cleaning of electronic equipment. The compound is a narcotic. Data on narcosis in humans, cats, rats, and mice, and systemic effects in cats, rats, and mice were available for devel- opment of AEGLs. The data were considered adequate for derivation of the three AEGL classifications. The AEGL-1 was based on human exposure to 825 ppm trans-1,2- dichloroethene for 5 min (Lehmann and Schmidt-Kehl 1936). This concentration is a no-effect-level for eye irritation. This value was divided by an uncertainty factor of 3 to protect sensitive individuals and is considered sufficient because using the default value of 10 for intraspecies variability would generate AEGL-1 values which are not supported by the total data set. (Using the full uncertainty factor of 10, yields an AEGL-1 value of 83 ppm; no effects were noted in hu- mans exposed to 275 ppm). This uncertainty factor of 3 was applied for AEGL-1 values for both the cis- and trans-isomers. Since data suggest that the cis- isomer is approximately twice as toxic as the trans-isomer with regard to narcosis and

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146 Acute Exposure Guideline Levels lethality in experimental animals, a modifying factor of 2 was applied in the derivation of the cis- isomer values only. Although the AEGL-1 point-of- departure is a NOEL for eye irritation, the use of the modifying factor is justi- fied for the cis- isomer because slight dizziness, a possible mild narcotic effect, was noted at the concentration used as starting point for the derivation of the AEGL-1. The same value was applied across the 10- and 30-min, 1-, 4-, and 8-h exposure time points since mild irritation is a threshold effect and generally does not vary greatly over time. Thus, prolonged exposure will not result in an en- hanced effect. The AEGL-2 for the 4- and 8-h time points was based on narcosis ob- served in pregnant rats exposed to 6,000 ppm of the trans- isomer for 6 h (Hurtt et al. 1993). Uncertainty factors of 3 each (total UF = 10) were applied for both inter- and intraspecies differences. The interspecies UF of 3 is considered suffi- cient because data suggest that the critical brain concentration of a halocarbon required to produce a given level of narcosis is relatively constant across species (McCarty et al. 1991). The intraspecies UF of 3 is considered sufficient because data suggest that there is little variability between vapor concentrations of anes- thetic required to produce anesthesia and age or sex of the patient (Gregory et al. 1969; de Jong and Eger 1975; Stevens et al. 1975). This total uncertainty factor of 10 was applied for AEGL-2 values for both the cis- and trans- isomers. The concentration-exposure time relationship for many irritant and systemically- acting vapors and gases may be described by Cn × t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al. 1986). To obtain conservative and pro- tective AEGL values in the absence of an empirically derived chemical-specific scaling exponent, temporal scaling was performed using n = 3 when extrapolat- ing to shorter time points and n = 1 when extrapolating to longer time points using the Cn × t = k equation. The AEGL-2 for the 10- and 30- min and 1-h time points was set as a maximum exposure level for anesthetic effects in humans (Lehmann and Schmidt-Kehl 1936). Since data suggest that the cis- isomer is approximately twice as toxic as the trans- isomer with regard to narcosis and lethality in experimental animals, a modifying factor of 2 was applied in the derivation of the cis- isomer values only. The AEGL-3 for the 4- and 8-h time points was based on a concentration (12,300 ppm) causing no mortality in rats exposed to trans-1,2-dichloroethene for 4-h (Kelly 1999). An uncertainty factor of 3 was applied for interspecies differences because rat and mouse lethality data indicate little species variability with regard to death. The interspecies UF of 3 is also considered sufficient be- cause data suggest that the critical brain concentration of a halocarbon required to produce a given level of narcosis is relatively constant across species (McCarty et al. 1991). An intraspecies UF of 3 was also applied and is consid- ered sufficient because data suggest that there is little variability between vapor concentrations of anesthetic required to produce anesthesia and age or sex of the patient (Gregory et al. 1969; de Jong and Eger 1975; Stevens et al. 1975). The total uncertainty factor of 10 was applied for AEGL-3 values for both the cis- and trans- isomers. The concentration-exposure time relationship for many irri-

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147 1,2-Dichloroethene tant and systemically-acting vapors and gases may be described by Cn × t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al. 1986). To obtain conservative and protective AEGL values in the absence of an empirically de- rived chemical-specific scaling exponent, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the Cn × t = k equation. The AEGL-3 for the 10- and 30- min and 1-h time points was set as a maximum exposure level for intracra- nial pressure, nausea, and severe dizziness in humans (Lehmann and Schmidt- Kehl 1936). Since data suggest that the cis- isomer is approximately twice as toxic as the trans-isomer with regard to narcosis and lethality in experimental animals, a modifying factor of 2 was applied in the derivation of the cis- isomer values only. The calculated values are listed in Tables 3-1 and 3-2. 1. INTRODUCTION 1,2-Dichloroethene is an extremely flammable, colorless liquid with a harsh odor, existing as both cis- and trans- forms and as a mixture (ATSDR 1996). It is one of a number of two carbon chlorocarbons produced in a reaction mixture resulting from processes involved in the chlorination of ethylene to pro- duce chlorinated monomers and solvents. The trans- isomer is commercially isolated by distillation and sold as a highly purified product that is used in preci- sion cleaning of electronic equipment. The compound reacts with alkalis to form chloroacetylene gas, reacts violently with potassium hydroxide and sodium hy- droxide, and can be combined with dinitrogen tetraoxide to form shock-sensitive explosives. Because of volatility, inhalation is the primary route of exposure of 1,2-dichloroethene to humans. Exposure may occur as the result of releases from production or use facilities, from contaminated wastewater and waste disposal sites, and from burning of polyvinyl and vinyl polymers (ATSDR 1996). In 1977, production of the cis-/trans- mixture was reported by one company as 10 to 50 million pounds and by another company as 1 to 10 million pounds (NTP 2002). The only manufacturer of the cis- isomer reported production of 0.1 to 10 million pounds; no production estimates for the trans-isomer were reported (NTP 2002). The physicochemical data for 1,2-dichloroethene are shown in Ta- ble 3-3. 2. HUMAN TOXICITY DATA 2.1. Acute Lethality 2.1.1. Case Reports An accidental fatality from occupational exposure to 1,2-dichloroethene occurred when a male rubber factory worker entered a vat containing rubber

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TABLE 3-1 Summary of AEGL Values for trans-1,2-Dichloroethene [ppm(mg/m3)] 148 Classification 10-min 30-min 1-h 4-h 8-h End Point (Reference) AEGL-1 (Nondisabling) 280 280 280 280 280 Ocular irritation in humans (1,109) (1,109) (1,109) (1,109) (1,109) (Lehmann and Schmidt-Kehl 1936) AEGL-2 (Disabling) 1,000 1,000 1,000 690 450 Narcosis in rats: 4- and 8-h (Hurtt et al. (3,960) (3,960) (3,960) (2,724) (1,782) 1993); Anesthetic effects in humans (Lehmann and Schmidt-Kehl 1936) AEGL-3 (Lethality) 1,700 1,700 1,700 1,200 620 No death in rats: 4- and 8-h (Kelly 1999); (6,732) (6,732) (6,732) (4,752) (2,455) Nausea, intracranial pressure, and dizziness in humans: 10-, 30-min, and 1-h (Lehmann and Schmidt-Kehl 1936) TABLE 3-2 Summary of AEGL Values for cis-1,2-Dichloroethene [ppm(mg/m3)] Classification 10-min 30-min 1-h 4-h 8-h End Point (Reference) AEGL-1 140 140 140 140 140 Ocular irritation in humans (Lehmann and Schmidt- (Nondisabling) (554) (554) (554) (554) (554) Kehl 1936) AEGL-2 (Disabling) 500 500 500 340 230 Narcosis in rats: 4- and 8-h (Hurtt et al. 1993); (1,980) (1,980) (1,980) (1,346) (911) Anesthetic effects in humans (Lehmann and Schmidt- Kehl 1936) AEGL-3 (Lethality) 850 850 850 620 310 No death in rats: 4- and 8-h (Kelly 1999); Nausea, (3,366) (3,366) (3,366) (2,455) (1,228) intracranial pressure, and dizziness in humans:10-, 30-min, and 1-h (Lehmann and Schmidt-Kehl 1936)

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149 1,2-Dichloroethene TABLE 3-3 Chemical and Physical Data for 1,2-Dichloroethene Parameter Data Reference Chemical Name 1,2-Dichloroethene ATSDR 1996 Synonyms 1,2-Dichloroethylene, acetylene O’Neil et al. 2001 dichloride,sym-dichloroethylene, Dioform (trade name) CAS Registry No. 540-59-0 (mixture), 156-59-2 (cis), ATSDR 1996 156-60-5 (trans) Chemical formula C2H2Cl2 O’Neil et al. 2001 Molecular weight 96.9 O’Neil et al. 2001 Physical state Liquid O’Neil et al. 2001 Odor threshold 17 ppm; ethereal, slightly acrid odor O’Neil et al. 2001 Melting/boiling/flash point -80.5°C /60.3°C /6°C (cis); ATSDR 1996 -50.0°C /48.0°C /4°C (trans) 1.2837 (cis) or 1.2565 (trans) g/cm3 Density ATSDR 1996 Solubility in water 3.5 (cis) or 6.3 (trans) g/L at 25°C ATSDR 1996 Vapor pressure 180 (cis) or 265 (trans) mm Hg at 20 °C ATSDR 1996 LogKow 1.86 (cis), 2.06 (trans) ATSDR 1996 Bioconcentration factor (BCF) ND 3.37 × 10-3 (cis) or 6.72 × 10-3 (trans) Henrys' Law constant ATSDR 1996 atm-m3/mol 1 mg/m3 = 0.25 ppm Conversion factors in air ATSDR 1996 1 ppm = 3.96 mg/m3 at 25 °C dissolved in 1,2-dichloroethene (Hamilton 1934). Symptoms of toxicity, expo- sure concentration and duration, and isomeric composition of the vapor were not reported. No other data concerning human lethality from 1,2-dichloroethene exposure were located in the available literature. 2.2. Nonlethal Toxicity 2.2.1. Case Reports Short-term inhalation experiments were conducted with “relatively” low concentrations of trans-dichloroethene (Lehmann and Schmidt-Kehl 1936). Two doctoral candidates self-administered the chemical (as a vapor) in a well insulated 10 m3 room. Using a manual sprayer and later a vaporizer (with attached oxygen tank), the chemical was uniformly distributed through the exposure chamber by means of fan and a ventilator. The concentration of trans-dichloroethene in the exposure chamber was determined analytically by determining the chlorine con- tent in the gas mixture employing the “lime method” from which the dichloro- ethene content was then calculated. Both individuals were exposed simultaneously

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150 Acute Exposure Guideline Levels in the same room. They appeared to react very similarly. Experiments lasted for 5 to 30 min. Based on concentrations of trans-dichloroethene in inspired and expired air, the authors estimated that approximately 73% of the chemical was absorbed. Exposure parameters and effects are presented in Table 3-4. 2.2.2. Epidemiologic Studies Epidemiologic studies regarding human exposure to 1,2-dichloroethene were not available. 2.3. Developmental and Reproductive Toxicity No developmental and reproductive toxicity data concerning 1,2-dichlo- roethene were identified in the available literature. 2.4. Genotoxicity No data concerning the genotoxicity of 1,2-dichloroethene in humans were identified in the available literature. 2.5. Carcinogenicity No data concerning the carcinogenicity of 1,2-dichloroethene in humans were identified in the available literature. TABLE 3-4 Effects of Inhalation Exposure to trans-1,2-Dichloroethenea Time Concentration (ppm) Effect 5 min 275 No effect 950 Slight burning of eyes 1700b Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea 2200b Severe dizziness after 5 min; intracranial pressure; nausea 10 min 825 Slight dizziness after 5 min 1200 Dizziness after 5 min; initially, slight burning of the eyes; drowsiness 30 min 1000 Dizziness after 10 min; slight burning of eyes a Two human subjects were exposed. b Symptoms persisted for 2 hours post-exposure. Source: Adapted from: Lehmann and Schmidt-Kehl 1936.

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151 1,2-Dichloroethene 2.6. Summary Only anecdotal data regarding human lethality from exposure to 1,2- dichloroethene were available, and exposure concentration, time and isomeric composition were not reported. Nonlethal exposure-response data suggest that 1,2-dichloroethene induces reversible neurological symptoms in humans. Expo- sures involved two human subjects exposed to concentrations of 275 to 2,200 ppm trans-1,2-dichloroethene/m3 for 5 to 30 min. 3. ANIMAL TOXICITY DATA 3.1. Acute Lethality 3.1.1. Mice Gradiski et al. (1978) reported a 6-h LC50 of 21,723 ppm trans-1,2- dichloroethene for female OF1SPF mice; the cause of death was not reported. Lehmann and Schmidt-Kehl (1936) exposed groups of three mice (sex and strain not specified) to cis-1,2-dichloroethene as follows: 65,000 mg/m3 (16,250 ppm) for 140 min, 70,000 mg/m3 (17,500 ppm) for 77 min, or 90,000 mg/m3 (22,500 ppm) for 66 min. All of these mice died. In the same study, groups of three mice were also exposed to the trans- isomer as follows: 75,000 mg/m3 (18,750 ppm) for 102 min, 80,000 mg/m3 (20,000 ppm) for 95 min, 105,000 mg/m3 (26,250 ppm) for 32 min, or 129,000 (32,250 ppm) mg/m3 for 30 min (see Table 3-10). All of these mice also died. 3.1.2. Rats Groups of 5 male and 5 female Crl:CD (SD)BR rats were exposed to 12,300, 22,500, 28,100, or 34,100 ppm trans-1,2-dichloroethene or 12,100, 13,500, 15,700, or 23,200 ppm cis-1,2-dichloroethene for 4 h in a 300-L stainless steel and glass chamber (Kelly 1999). The test atmospheres were gen- erated by metering liquid dichloroethene into a heated glass Instatherm flask with either a Fluid Metering pump or a Hamilton Syringe Drive. Nitrogen intro- duced into the flask swept the dichloroethene vapor into the air supply duct to the exposure chamber. The chamber concentration of dichloroethene was con- trolled by varying the amount of the metered liquid delivered to the evaporation flask. The chamber concentration of test substance was determined by gas chromatography at 15-min intervals during each exposure. Chamber airflow, temperature, and relative humidity were monitored continually. Liver, kidney, lung, and heart were examined histologically. The 4-h LC50 value was 24,100 ppm for trans-1,2 dichloroethene and 13,700 ppm for cis-1,2-dichloroethene. Data are summarized in Table 3-5.

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TABLE 3-5 Four-Hour Exposure of Rats to cis- and trans-1,2-Dichloroethene 152 Concentration (ppm) Mortality Observations trans-1,2-Dichloroethene During Exposurea After Exposure 12,300 0/10 Prostrate, decreased response followed by no Normal weight gain response to alerting stimulus, normal response 30 min after exposure 22,500 4/10 Prostrate, no response to alerting stimulus Lethargy, irregular respiration, slight weight loss (recovery time not noted) one day followed by normal weight gain 28,100 7/10 Prostrate, no response to alerting Weakness, slight to severe weight loss one day stimulus (recovery time not noted) followed by normal weight gain 34,100 10/10 Prostrate, no response to alerting stimulus — cis-1,2-Dichloroethene 12,100 0/10 Prostrate, no response to alerting stimulus Normal weight gain rate (recovery in 1 h post-exposure) 13,500 6/10 Prostrate, no response to alerting stimulus Weakness, irregular respiration, immediately after (recovery time not noted) exposure, slight to severe weight loss one day followed by normal weight gain; centrilobular fatty liver changes (2/10) 15,700 10/10 Prostrate, no response to alerting stimulus Centrilobular fatty liver changes (4/10) 23,200 10/10 Prostrate, no response to alerting stimulus — a Deaths occurred during exposure. Source: Kelly 1999. Reprinted with permission; copyright 1999, Dupont.

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153 1,2-Dichloroethene 3.1.3. Cats Cats (2/concentration) were exposed to cis-1,2-dichloroethene at concen- trations ranging from 20,000 to 114,000 mg/m3 (5,000 to 28,500 ppm) for 9 to 360 min (Lehmann and Schmidt-Kehl 1936). “Pure” chemical was obtained from I.G. Farben and was further purified by multiple fractionated distillations followed by boiling point measurements. Ambient air was suctioned from a 360- L exposure chamber utilizing a large gas valve which was rotated by means of a bucket wheel located in a water container on the same level as the valve. The experimental aerosol was produced by one of two methods: (1) either by passing a small stream of air through a Woulfsche flask containing a measured amount of chemical for a given time period and adding chemical by opening a burette or (2) by forcing a side air stream through a bulb tube containing the liquid di- chloroethene and mixing with the main air stream. The concentration of di- chloroethene in the exposure chambers was determined in one of two ways: (1) by dividing the evaporated portion of the chemical by the air volume over a spe- cific time period or (2) analytically by determining the chlorine content in the gas mixture employing the “lime method” from which the dichloroethene con- tent was then calculated. Actual concentrations achieved ranged from 98.2% to 100.7% of the nominal concentrations, suggesting reliability and accuracy in the exposure concentrations. The mean experimental ventilation rate was 1050 L/h. The exposures resulted in death at various times, ranging from 3 min to 7 days, after exposure (see Table 3-9 for details). 3.2. Nonlethal Toxicity 3.2.1. Cats Fasted cats (2/experiment) were exposed to cis- or trans-1,2-dichloro- ethene vapors in a series of experiments (Lehmann and Schmidt-Kehl 1936). “Pure” chemical was obtained from I.G. Farben and was further purified by mul- tiple fractionated distillations followed by boiling point measurements. Ambient air was suctioned from a 360 L exposure chamber utilizing a large gas valve which was rotated by means of a bucket wheel located in a water container on the same level as the valve. The experimental aerosol was produced by one of two methods: 1) either by passing a small stream of air through a Woulfsche flask containing a measured amount of chemical for a given time period and adding chemical by opening a burette or 2) by forcing a side air stream through a bulb tube containing the liquid dichloroethene and mixing with the main air stream. The concentration of dichloroethene in the exposure chambers was de- termined in one of two ways: 1) by dividing the evaporated portion of the chemical by the air volume over a specific time period or 2) analytically by de- termining the chlorine content in the gas mixture employing the “lime method” from which the dichloroethene content was then calculated. Actual concentra- tions achieved ranged from 98.2% to 100.7% of the nominal concentrations. The

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154 Acute Exposure Guideline Levels mean experimental ventilation rate was 1050 L/h. Due to the variability in re- searchers, there were some inconsistencies in observations. End points measured included equilibrium effects, lethargy, light narcosis, and deep narcosis. Effects on equilibrium were defined as swaying and difficulty in getting up and moving around. Lethargy was defined as the complete inability to move and was tested by gently lifting the head with a wooden rod. If the head fell back following removal of the rod, the cat was considered lethargic. Light narcosis was defined as the absence of extremity reflexes, and deep narcosis was defined as the ab- sence of corneal and extremity reflexes. Also observed were irritating effects on mucous membranes (eyes, nose, mouth, salivary glands) and respiratory rate. The animals were observed for at least 8 days after exposure. Respiratory rates corresponding to lethargy, light narcosis, and deep narcosis were 61, 75, and 72 breaths/min, respectively, for the trans isomer; and 85, 99, and 92 reaths/min, respectively, for the cis- isomer. Study design and observations are presented in Tables 3-6 through 3-9. 3.2.2. Rats Groups of six female SPF Wistar rats (180-200 g) were given single 8-h exposures to trans-1,2-dichloroethene vapors at 0, 200, 1,000, or 3,000 ppm (Freundt et al. 1977). Experimental concentrations were monitored by gas chro- matography, and were within 3% of the nominal concentrations. Animals were sacrificed immediately after the exposure period. The incidence of slight to se- vere fatty degeneration of hepatic lobules and Kupffer cells and pulmonary cap- illary hyperaemia and alveolar septum distention was increased in all treatment groups when compared to controls. Pneumonic infiltration and fibrous swelling and hyperemia of cardiac muscle with poorly maintained striation were observed in animals in the 3,000 ppm group. Decreased serum albumin, urea nitrogen, and alkaline phosphatase activity were observed in the 1,000 ppm group after 8 h of exposure; however, these effects are of questionable biological significance be- cause none were outside the normal range for rats. Leukocyte counts were de- creased after exposure to 200 ppm 1,2-dichloroethene for 8 h, and a decreased erythrocyte count was observed in the 1,000 ppm group after 8 h. It should be noted that the results of this study are inconsistent with the total database for 1,2-dichloroethylene and results, especially the reported pathological changes, are of questionable toxicological significance. In another study, Freundt and Macholz (1978) exposed groups of 10 fe- male Wistar rats to cis- or trans-1,2-dichloroethene at 0, 200, 600, 1,000, or 3,000 ppm for 8 h. A statistically significant (p < 0.05), dose-dependent increase in hexobarbital sleeping time and zoxazolamine paralysis time was observed in all treated groups, indicating decreased activity of the P-450 enzymes that nor- mally metabolize these compounds. The effect was observed in animals exposed to both isomers; however, the effect was more severe in rats exposed to the cis- isomer.

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175 1,2-Dichloroethene is likely that analytical measurements were not as precise as those used today. Data from animal studies are more abundant and encompass a wider range of exposure periods. More recent animal studies include greater numbers of ex- perimental animals and almost certainly improved methodology. 9. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 2003. TLVs and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. American Conference of Governmental Indus- trial Hygienists, Cincinnati, OH. ATSDR (Agency for Toxic Substances and Disease Registry). 1996. Toxicological Pro- file for 1,2-Dichloroethene. U.S. Department of Health and Human Services, Pub- lic Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. August 1996 [online]. Available: http://www.atsdr.cdc.gov/toxprofiles/tp87. pdf [accessed Oct. 23, 2008]. Barton, H.A., J.R. Creech, C.S. Godin, G.M. Randall, and C.S. Seckel. 1995. Chloro- ethylene mixtures: Pharmacokinetic modeling and in vitro metabolism of vinyl chloride, trichloroethylene, and trans-1,2-dichloroethylene in rat. Toxicol. Appl. Pharmacol. 130(2):237-247. Bruckner, J.V., D.A. Keys, and J.W. Fisher. 2004. The Acute Exposure Guideline Level (AEGL) program: Applications of physiologically-based pharmacokinetic model- ing. J. Toxicol. Environ. Health A 67(8-10):621-634. Cantelli-Forti, G., and G. Bronzetti. 1988. Mutagenesis and carcinogenesis of halo- genated ethylenes. Ann. N.Y. Acad. Sci. 534:679-693. Cerna, M., and H. Kypenova. 1977. Mutagenic activity of chloroethylenes analyzed by screening system tests [abstract]. Mutat. Res. 46(3):214-215. Costa, A.K., and K.M. Ivanetich. 1982. The 1,2-dichloroethylenes: Their metabolism by hepatic cytochrome P-450 in vitro. Biochem. Pharmacol. 31(11):2093-2102. De Ceaurriz, J., J.P. Desiles, P. Bonnet, B. Marignac, J. Muller, and J.P. Guenier. 1983. Concentration-dependent behavioral changes in mice following short-term inhala- tion exposure to various industrial solvents. Toxicol. Appl. Pharmacol. 67(3):383- 393. de Jong, R.H., and E.I. Eger. 1975. MAC expanded: AD50 and AD95 values of common inhalation anesthetics in man. Anesthesiology 42(4):384-389. DFG (Deutsche Forschungsgemeinschaft). 2002. List of MAK and BAT Values 2002. Maximum Concentrations and Biological Tolerance Values at the Workplace Re- port No. 38. Weinheim, Federal Republic of Germany: Wiley VCH. Eger, E.I., M.J. Halsey, D.D. Koblin, M.J. Laster, P. Ionescu, K. Konigsberger, R. Fan, B.V. Nguyen, and T. Hudlicky. 2001. The convulsant and anesthetic properties of cis- trans isomers of 1,2-dichlorohexafluorocyclobutane and 1,2-dichloroethy-lene. Anesth. Analg. 93(4):922-927. Filser, J.G., and H.M. Bolt. 1979. Pharmacokinetics of halogenated ethylenes in rats. Arch. Toxicol. 42(2): 123-136. Freundt, K.J., and J. Macholz. 1978. Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethylene. Toxicology 10(2):131-139. Freundt, K.J., G.P. Liebaldt, and E. Lieberwirth. 1977. Toxicity studies on trans-1,2- dichloroethylene. Toxicology 7(2):141-153.

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176 Acute Exposure Guideline Levels Gargas, M.L., P.G. Seybold, and M.E. Andersen. 1988. Modeling the tissue solubilities and metabolic rate constant (Vmax) of halogenated methanes, ethanes, and ethyl- enes. Toxicol. Lett. 43(1-3):235-256. Gargas, M.L., R.J. Burgess, D.E. Voisard, G.H. Cason, and M.E. Andersen. 1989. Parti- tion coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. Toxicol. Appl. Pharmacol. 98(1):87-99. Gargas, M.L., H.J. Clewell III, and M.E. Andersen. 1990. Gas uptake inhalation tech- niques and the rates of metabolism of chloromethanes, chloroethanes, and chloro- ethylenes in the rat. Inhal. Toxicol. 2(3):295-319. Gradiski, D., P. Bonnet, G. Raoult, and J.L. Magadur. 1978. Comparative acute inhala- tion toxicity of the principal chlorinated aliphatic solvents [in French]. Arch. Mal. Prof. Med. Trav. Secur. Soc. 39(4-5):249-257. Gregory, G.A., E.I. Eger, and E.S. Munson. 1969. The relationship between age and halo- thane requirement in man. Anesthesiology 30(5):488-491. Hamilton, A. 1934. Dichlorethylene. Pp. 217-218 in Industrial Toxicology. New York, NY:Harper and Brothers Publishers. Hanioka, N., H. Jinno, T. Nishimura, and M. Ando. 1998. Changes in hepatic cytochrome P450 enzymes by cis- and trans-1,2-dichloroethylenes in rat. Xenobiotica 28(1):41-51. Hurtt, M.E., R. Valentine, and L. Alvarez. 1993. Developmental toxicity of inhaled trans- 1,2-dichloroethylene in the rat. Fundam. Appl. Toxicol. 20(2):225-230. Kelly, D.P. 1998. trans-1,2- Dichloroethylene: 90-Day Inhalation Toxicity Study in Rats. E.I. Du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine. DuPont HL-1998-00952. Kelly, D.P. 1999. trans-1,2-Dichloroethylene and cis-1,2-dichloroethylene: Inhalation Median Lethal Concentration (LC50) Study in Rats. E.I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE. Laboratory Project ID: DuPont-2806. Lehmann, K.B., and L. Schmidt-Kehl. 1936. The thirteen most important chlorinated aliphatic hydrocarbons from the standpoint of industrial hygiene [in German]. Arch. Hyg. 116:131-268. Lilly, P.D., J.R. Thorton-Manning, M.L. Gargas, H.J. Clewell, and M.E. Andersen. 1998. Kinetic characterization of CYP2E1 inhibition in vivo and in vitro by the chloro- ethylenes. Arch. Toxicol. 72(10):609-621. McCarty, L.S., D. Mackay, A.D. Smith, G.W. Ozburn, and D.G. Dixon. 1991. Interpret- ing aquatic toxicity QSARs: The significance of toxicant body residues at the pharmacologic endpoint. Sci. Total Environ. 109-110:515-525. McCauley, P.T., M. Robinson, F.B. Daniel, and G.R. Olson. 1995. The effects of subacute and subchronic oral exposure to cis-1,2-dichloroethylene in Sprague- Dawley rats. Drug Chem. Toxicol. 18(2-3):171-184. Mortelmans, K., S. Haworth, T. Lawlor, W. Speck, B. Tainer, and E. Zeiger. 1986. Sal- monella mutagenicity tests: II. Results from the testing of 270 chemicals. Environ. Mutagen. 8(Suppl. 7):1-119. MSZW (Ministerie van Sociale Zaken en Werkgelegenheid). 2004. Nationale MAC-lijst 2004: 1,2 Dichloorethyleen. Den Haag: SDU Uitgevers [online]. Available: http://www.lasrook.net/lasrookNL/maclijst2004.ht [accessed Oct. 24, 2008]. NIOSH (National Institute of Occupational Safety and Health). 1996. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95)-1,2 Dichloroethylene. U.S. Department of Health and Human Services, Centers for

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177 1,2-Dichloroethene Disease Control and Prevention, National Institute of Occupational Safety and Health. August 1996 [online]. Available: http://www.cdc.gov/niosh/idlh/107 028.html [accessed Oct. 16, 2008]. NIOSH (National Institute of Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards: 1,2 Dichloroethylene. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute of Occupa- tional Safety and Health, Cincinnati, OH. September 2005 [online]. Available: http://www.cdc.gov/niosh/npg/npgd0195.html [accessed Oct. 16, 2008]. NRC (National Resource Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1993. Guidelines for Developing Community Emer- gency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press. NTP (National Toxicology Program). 2002. NTP Technical Report on the Toxicity Stud- ies of trans-1,2-Dichloroethylene (CAS No. 156-60-5) Administered in Microcap- sules in Feed to F344/N Rats and B6C3F1 Mice. Toxicity Report No. 55. NIH Pub- lication No. 02-4410. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health. April 2002 [online]. Available: http://ntp.niehs.nih.gov/ntp/htdocs/ST_rpts/tox055.pdf [accessed Oct. 24, 2008]. O’Neil, M.J., A. Smith, P.E. Heckelman, J.R. Obenchain, Jr., J. Gallipeau, and M.A. D’Arecca. 2001. Acetylene dichloride. Pp. 17-18 in The Merck Index: An Ency- clopedia of Chemicals, Drugs, and Biologicals, 13th Ed. Whitehouse Station, NJ: Merck and Co. Stevens, W.C., W.M. Dolan, R.T. Gibbons, A. White, E.I. Eger, R.D. Miller, R.H. DeJong, and R.M. Elashoff. 1975. Minimum alveolar concentrations (MAC) of isoflurane with and without nitrous oxide in patients of various ages. Anesthesiol- ogy 42(2):197-200. ten Berge, W.F., A. Zwart, and L.M. Appelman. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases. J. Haz- ard. Mater. 13(3):301-309. Zeiger, E., B. Anderson, S. Haworth, T. Lawlor, and K. Mortelmans. 1988. Salmonella mutagenicity tests IV. Results from the testing of 300 chemicals. Environ. Mol. Mutagen. 11(Suppl. 12):1-158.

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178 Acute Exposure Guideline Levels APPENDIX A Time-Scaling Calculations for 1,2-Dichloroethene Derivation of AEGL-1 Key study: Lehmann and Schmidt-Kehl 1936 Toxicity end point: 825 ppm, 5 min: NOEL for ocular irritation in humans Scaling: None: values were held constant across time points Uncertainty factors: 3 for intraspecies variability (trans- and cis-1,2-dichloroethene) Modifying factor: 2 for differential isomer toxicity (cis-1,2-dichloroethene only) 10-, and 30-min and 1-, 4-, and 8-h AEGL-1 825 ppm ) 3 = 275 ppm trans-1,2-dichloroethene AEGL-1 = 280 ppm cis-1,2-dichloroethene AEGL-1 = 280 ppm ) 2 = 140 ppm Derivation of AEGL-2 Key Studies: Lehmann and Schmidt-Kehl 1936 (10-, 30-, and 60-min) Hurtt et al. 1993 (4- and 8-h) Toxicity end points: Anesthetic effects in humans (10-, 30-, and 60-min) Narcosis in rats (4- and 8-h) Scaling Maximum exposure level at 10-, 30-, and 60-min (6,000 ppm)3 × 6 h = 1.3 × 1012 ppm.h (4-h) (6,000 ppm)1 × 6 h = 36,000 ppm.h (8-h) Uncertainty factors: 3 for intraspecies variability (trans- and cis- 1,2 dichloroethene; 4- and 8-h) 3 for interspecies variability (trans- and cis- 1,2-dichloroethene; 4- and 8-h) Modifying factor: 2 for differential isomer toxicity (cis-1,2-dichloroethene only) 10- and 30-min and 1-h AEGL-2 trans-1,2-dichloroethene AEGL-2 = 1,000 ppm cis-1,2-dichloroethene AEGL-1 = 1,000 ppm ) 2 = 500 ppm C3 × 4 h = 1.3 × 1012 ppm.h 4-h AEGL-2 C3 = 3.25 × 1011 ppm C = 6,875 ppm 4 h trans-1,2-dichloroethene AEGL-2= 6,868 ppm/10 = 690 ppm 4 h cis-1,2-dichloroethene AEGL-2 = 6,868 ppm/20 = 340 ppm C1 × 8 h = 36,000 ppm.h 8-h AEGL-2 C1 = 4,500 ppm

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179 1,2-Dichloroethene C = 4,500 ppm 8 h trans-1,2-dichloroethene AEGL-2 = 4,500 ppm/10 = 450 ppm 8 h cis-1,2- dichloroethene AEGL-2 = 4,500 ppm/20 = 230 ppm Derivation of AEGL-3 Key Studies: Lehmann and Schmidt-Kehl 1936 (10-, 30-, and 60-min) Kelly 1999 (4- and 8-h) Toxicity end point: Nausea, intracranial pressure, dizziness in humans (10-, 30-, and 60-min) No-effect-level for death in rats (4- and 8-h) Scaling Maximum exposure level at 10-, 30-, and 60-min (12,300 ppm)3 × 4 h = 7.44 × 1012 ppm.h (4-h) (12,300 ppm)1 × 4 h = 49,200 ppm.h (8-h) Uncertainty factors: 3 for intraspecies variability (trans- and cis- 1,2- dichloroethene; 4- and 8-h) 3 for interspecies variability (trans- and cis- 1,2-dichloroethene; 4- and 8-h) Modifying factor: 2- for differential isomer toxicity (cis-1,2-dichloroethene only) 10, and 30-min and 1-h AEGL-3 trans-1,2-dichloroethene AEGL-3 = 1,700 ppm cis-1,2-dichloroethene AEGL-3 = 1,700 ) 2 = 850 ppm C3 × 4 h = 7.44 × 1012 ppm-h 4 h AEGL-3 C3 = 1.86 × 1012 ppm C = 12,298 ppm 4 h trans-1,2-dichloroethene AEGL-3= 12,298 ppm/10 = 1,200 ppm 4 h cis-1,2-dichloroethene AEGL-3 = 12,298 ppm/20 = 620 ppm C1 × 8 h = 49,200 ppm-h 8 h AEGL-3 C1 = 6,150 ppm C = 6,150 ppm 8 h trans-1,2-dichloroethene AEGL-3 = 6,150 ppm/10 = 620 ppm 8 h cis-1,2-dichloroethene AEGL-3 = 6,150 ppm/20 = 310 ppm

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180 Acute Exposure Guideline Levels APPENDIX B Derivation Summary of AEGL Values for 1,2-Dichloroethene (trans- and cis- isomers) AEGL-1 VALUES 10 min 30 min 1h 4h 8h 280 ppm 280 ppm 280 ppm 280 ppm 280 ppm Key Reference: Lehmann, K.B., and L. Schmidt-Kehl. 1936. The thirteen most important chlorinated aliphatic hydrocarbons from the standpoint of industrial hygiene [in German]. Arch. Hyg. 116:131-268. Test Species/Strain/Number: Human subjects/2 Exposure Route/Concentrations/Durations: Inhalation: 275, 825, 950, 1000, 1200, 1700, or 2200 ppm for 5-30 min Effects: 275 ppm: No effects (5 min Total exposure) 825 ppm: Slight dizziness after 5 min (10 min exposure); determinant for AEGL-1 950 ppm: Slight burning of eyes (5 min) 1,000 ppm: Dizziness after 10 min; slight burning of eyes (30 min exposure) 1,200 ppm: Dizziness after 5 min; drowsiness; slight burning of eyes (10 min exposure) 1,700 ppm: Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea (5 min exposure) 2,200 ppm: Severe dizziness; intracranial pressure; nausea (5 min exposure) End Point/Concentration/Rationale: 825 ppm for 5 min; no effect level for eye irritation; odor present. Uncertainty Factors/Rationale: Total uncertainty factor: 3 Interspecies: Not applicable, human data used. Intraspecies: 3 - Considered sufficient because using the default value of 10 for intraspecies variability would generate AEGL-1 values which are not supported by the total data set. (Utilizing the full uncertainty factor of 10, yields an AEGL-1 value of 83 ppm; no effects were noted in humans exposed to 275 ppm). Modifying Factor: Not applicable. Animal to Human Dosimetric Adjustment: Not applicable; human data used Time Scaling: Values were held constant across time since minor irritation is a threshold effect and is not likely to increase over time. Data Quality and Research Needs: Although the values developed are considered to be protective, data are sparse due to the exposure of only two subjects.

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181 1,2-Dichloroethene AEGL-2 VALUES 10 min 30 min 1h 4h 8h 1,000 ppm 1,000 ppm 1,000 ppm 690 ppm 450 ppm Key Reference: Lehmann, K.B., and L. Key Reference: Hurtt, M.E., R. Schmidt-Kehl. 1936. The thirteen most Valentine, and L. Alvarez. 1993. important chlorinated aliphatic Developmental toxicity of inhaled trans- hydrocarbons from the standpoint of 1,2-dichloroethylene in the rat. Fundam. industrial hygiene [in German]. Arch. Appl. Toxicol. 20(2):225-230. (4- and 8- Hyg. 116:131-268. (10-, and 30-min and h) 1-h) Test Species/Strain/Number: Human Test Species/Strain/Number: rat/Crl:CD subjects/2 BR pregnant females/24/group Exposure Route/Concentrations/ Exposure Route/Concentrations/ Durations: Inhalation: 275, 825, 950, Durations: 0, 2000, 6000, or 12,000 ppm, 1000, 1200, 1700, or 2200 ppm for 5-30 6 h/d, d 7-16 of gestation min Effects: Effects: 275 ppm No effects (5 min) 2,000 ppm Clear ocular discharge 825 ppm Slight dizziness after 5 min (after single 6-h exposure) 950 ppm Slight burning of eyes (5 min) 6,000 ppm Narcosis, ocular irritation 1,000 ppm Dizziness after 10 min; slight (after single 6-h exposure) burning of eyes (30 min exposure) 1,200 ppm Ocular irritation, narcosis, 1,200 ppm Dizziness after 5 min; lethargy, decreased body weight gain drowsiness; slight burning of eyes (10 min exposure) 1,700 ppm Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea 2,200 ppm Severe dizziness; intracranial pressure; nausea (5 min exposure) End Point/Concentration/Rationale: End point/Concentration/Rationale: 1,000 ppm for 10 min; threshold for 6,000 ppm, 6 h/narcosis anesthetic effects Uncertainty Factors/Rationale: Uncertainty Factors/Rationale: Total uncertainty factor: 1 Total uncertainty factor: 10 Interspecies: Not applicable - human Interspecies: 3 data used. Intraspecies: 3 Intraspecies:1 -threshold for The interspecies UF of 3 is considered anesthetic effect sufficient because data suggest that the critical brain concentration of a halocarbon required to produce a given level of narcosis is relatively constant across species (McCarty et al. 1991). The intraspecies UF of 3 is considered (Continued)

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182 Acute Exposure Guideline Levels AEGL-2 VALUES Continued 10 min 30 min 1h 4h 8h 1,000 ppm 1,000 ppm 1,000 ppm 690 ppm 450 ppm sufficient because data suggest that there is little variability between vapor concentrations of anesthetic required to produce anesthesia and age or sex of the patient (Gregory et al. 1969; Stevens et al. 1975; de Jong and Eger 1975) Time Scaling: Cn × t = k, where the Time Scaling: Held constant at threshold for anesthetic effects exponent, n, is the conservative default of 1 (8-h) or 3 (4-h) Data Quality and Research Needs: Although recent studies are well conducted, human and animal data are in apparent conflict. AEGL-3 VALUES 10 min 30 min 1h 4h 8h 1,700 ppm 1,700 ppm 1,700 ppm 1,200 ppm 620 ppm Key Reference: Lehmann, K.B., and L. Key Reference: Kelly, D.P. 1999. trans- Schmidt-Kehl. 1936. The thirteen most 1,2-dichloroethylene and cis-1,2- important chlorinated aliphatic dichloroethylene: Inhalation Median hydrocarbons from the standpoint of Lethal Concentration (LC50) Study in Rats. industrial hygiene [in German]. Arch. E.I. du Pont de Nemours and Company, Hyg. 116:131-268. (10-, and 30- min Haskell Laboratory for Toxicology and and 1-h) Industrial Medicine, Newark, DE. Laboratory Project ID: DuPont-2806. (4- and 8-h) Test Species/Strain/Number: Human Test Species/Strain/Number: Rat/Crl:CD subjects/2 (SD)/5/sex/group Exposure Exposure Route/Concentrations/Durations: Route/Concentrations/Durations: Inhalation/ 0, 12,300, 22,500, 28,100, or Inhalation: 275, 825, 950, 1,000, 1,200, 34,100 ppm/4 h 1,700, or 2,200 ppm for 5-30 min Effects: Mortality: 275 ppm No effects (5 min) 12,300 ppm 0/10 825 ppm Slight dizziness after 5 min 22,500 ppm 4/10 950 ppm Slight burning of eyes (5 min) 28,100 ppm 7/10 1,000 ppm Dizziness after 10 min; slight 34,100 ppm 10/10 burning of eyes (30 min exposure) 1,200 ppm Dizziness after 5 min; drowsiness; slight burning of eyes (10 min exposure) (Continued)

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183 1,2-Dichloroethene AEGL-3 VALUES Continued 10 min 30 min 1h 4h 8h 1,700 ppm 1,700 ppm 1,700 ppm 1,200 ppm 620 ppm 1,700 ppm Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea 2,200 ppm Severe dizziness; intracranial pressure; nausea (5 min exposure) End Point/Concentration/Rationale: End Point/Concentration/Rationale: 1,700 ppm for 3 min; dizziness, 12,300 ppm, 4 h/NOEL for death intracranial pressure, nausea Uncertainty Factors/Rationale: Uncertainty Factors/Rationale: Total Uncertainty Factor: 1 Total Uncertainty Factor: 10 Interspecies: Not applicable - human Interspecies: 3 data used. Intraspecies: 3 Intraspecies 1 - conservative AEGL-3 An uncertainty factor of 3 was applied for end point interspecies differences because rat and mouse lethality data indicate little species variability with regard to death. The interspecies UF of 3 is also considered sufficient because data suggest that the critical brain concentration of a halocarbon required to produce a given level of narcosis is relatively constant across species (McCarty et al. 1991). The intraspecies UF of 3 is considered sufficient because data suggest that there is little variability between vapor concentrations of anesthetic required to produce anesthesia and age or sex of the patient (Gregory et al. 1969; Stevens et al. 1975; de Jong and Eger 1975). Time Scaling: Held constant across time Time Scaling: Cn × t = k, where the points; conservative AEGL-3 end point exponent n is the conservative default of 1 (8-h) or 3 (4-h) Data Quality and Research Needs: Although recent studies are well conducted, human and animal data are in apparent conflict.

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APPENDIX C 184 Category Plots for trans-1,2-Dichloroethene and cis-1,2-Dichloroethene Chemical Toxicity-All trans-1,2-Dichloroethene Human - No Effect 100000 Human - Discomfort Human - Disabling 10000 Animal - No Effect Animal - Discomfort ppm AEGL-3 Animal - Disabling 1000 AEGL-2 Animal - Partially Lethal AEGL-1 Animal - Lethal AEGL 100 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category plots for trans-1,2-dichloroethene.

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Chemical Toxicity - TSD All Data cis-1,2-Dichloroethene Human - No Effect 100000 Human - Discomfort Human - Disabling 10000 Animal - No Effect Animal - Discomfort ppm Animal - Disabling 1000 AEGL-3 Animal - Partially Lethal AEGL-2 Animal - Lethal AEGL-1 AEGL 100 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-2 Category plots for cis-1,2-dichloroethene. 185