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Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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).

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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 susceptible 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 susceptible 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 progressive 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 infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience 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 processes 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 development 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 humans 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

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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 justified 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 enhanced effect.

The AEGL-2 for the 4- and 8-h time points was based on narcosis observed 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 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; 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 protective AEGL values in the absence of an empirically derived 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-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 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). An intraspecies UF of 3 was also applied and 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; 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-

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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 derived 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 intracranial 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 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 reacts with alkalis to form chloroacetylene gas, reacts violently with potassium hydroxide and sodium hydroxide, 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 Table 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

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-1 Summary of AEGL Values for trans-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

End Point (Reference)

AEGL-1 (Nondisabling)

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

Ocular irritation in humans (Lehmann and Schmidt-Kehl 1936)

AEGL-2 (Disabling)

1,000 (3,960)

1,000 (3,960)

1,000 (3,960)

690 (2,724)

450 (1,782)

Narcosis in rats: 4- and 8-h (Hurtt et al. 1993); Anesthetic effects in humans (Lehmann and Schmidt-Kehl 1936)

AEGL-3 (Lethality)

1,700 (6,732)

1,700 (6,732)

1,700 (6,732)

1,200 (4,752)

620 (2,455)

No death in rats: 4- and 8-h (Kelly 1999); 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 (Nondisabling)

140 (554)

140 (554)

140 (554)

140 (554)

140 (554)

Ocular irritation in humans (Lehmann and Schmidt-Kehl 1936)

AEGL-2 (Disabling)

500 (1,980)

500 (1,980)

500 (1,980)

340 (1,346)

230 (911)

Narcosis in rats: 4- and 8-h (Hurttet al. 1993); Anesthetic effects in humans (Lehmann and Schmidt-Kehl 1936)

AEGL-3 (Lethality)

850 (3,366)

850 (3,366)

850 (3,366)

620 (2,455)

310 (1,228)

No death in rats: 4- and 8-h (Kelly 1999); Nausea, intracranial pressure, and dizziness in humans: 10-, 30-min, and 1-h (Lehmann and Schmidt-Kehl 1936)

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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 dichloride,sym-dichloroethylene, Dioform (trade name)

O’Neil et al. 2001

CAS Registry No.

540-59-0 (mixture), 156-59-2 (cis), 156-60-5 (trans)

ATSDR 1996

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);

−50.0°C /48.0°C /4°C (trans)

ATSDR 1996

Density

1.2837 (cis) or 1.2565 (trans) g/cm3

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

 

Henrys' Law constant

3.37 × 10−3 (cis) or 6.72 × 10−3 (trans) atm-m3/mol

ATSDR 1996

Conversion factors in air

1 mg/m3 = 0.25 ppm

1 ppm = 3.96 mg/m3 at 25 °C

ATSDR 1996

dissolved in 1,2-dichloroethene (Hamilton 1934). Symptoms of toxicity, exposure 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 content in the gas mixture employing the “lime method” from which the dichloroethene content was then calculated. Both individuals were exposed simultaneously

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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-dichloroethene 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

1 000

Dizziness after 10 min; slight burning of eyes

aTwo human subjects were exposed.

bSymptoms persisted for 2 hours post-exposure.

Source: Adapted from: Lehmann and Schmidt-Kehl 1936.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
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. Exposures 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 generated by metering liquid dichloroethene into a heated glass Instatherm flask with either a Fluid Metering pump or a Hamilton Syringe Drive. Nitrogen introduced into the flask swept the dichloroethene vapor into the air supply duct to the exposure chamber. The chamber concentration of dichloroethene was controlled 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.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-5 Four-Hour Exposure of Rats to cis- and trans-1,2-Dichloroethene

Concentration (ppm)

Mortality

Observations

trans-1,2-Dichloroethene

 

 

During Exposurea

After Exposure

12,300

0/10

Prostrate, decreased response followed by no response to alerting stimulus, normal response 30 min after exposure

Normal weight gain

22,500

4/10

Prostrate, no response to alerting stimulus (recovery time not noted)

Lethargy, irregular respiration, slight weight loss one day followed by normal weight gain

28,100

7/10

Prostrate, no response to alerting stimulus (recovery time not noted)

Weakness, slight to severe weight loss one day 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 (recovery in 1 h post-exposure)

Normal weight gain rate

13,500

6/10

Prostrate, no response to alerting stimulus (recovery time not noted)

Weakness, irregular respiration, immediately after 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

aDeaths occurred during exposure.

Source: Kelly 1999. Reprinted with permission; copyright 1999, Dupont.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
3.1.3.
Cats

Cats (2/concentration) were exposed to cis-1,2-dichloroethene at concentrations 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 dichloroethene and mixing with the main air stream. The concentration of dichloroethene 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 specific time period or (2) analytically by determining the chlorine content in the gas mixture employing the “lime method” from which the dichloroethene content 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-dichloroethene vapors in a series of experiments (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 dichloroethene and mixing with the main air stream. The concentration of dichloroethene 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 specific time period or 2) analytically by determining the chlorine content in the gas mixture employing the “lime method” from which the dichloroethene content was then calculated. Actual concentrations achieved ranged from 98.2% to 100.7% of the nominal concentrations. The

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

mean experimental ventilation rate was 1050 L/h. Due to the variability in researchers, 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 absence 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 chromatography, and were within 3% of the nominal concentrations. Animals were sacrificed immediately after the exposure period. The incidence of slight to severe fatty degeneration of hepatic lobules and Kupffer cells and pulmonary capillary 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 because none were outside the normal range for rats. Leukocyte counts were decreased 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 female 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 normally 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.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-6 Sublethal Effects in Cats Exposed to trans-1,2-Dichloroethene for 22-248 Minutesa

Concentration [mg/m3 (ppm)]

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

72,000 (18,000)

348

7-8

37-43

320-340

330-345

86,400 (21,600)

213

4

22-23

152-157

206-210

110,000 (27,500)

75

3-5

8-9

20-21

69-70

147,000 (36,750)

23

1-3

5

7-9

14-18

189,200 (47,300)

22

1

3

5

12-13

aLehmann and Schmidt-Kehl 1936. Two animals/exposure (1 male and 1 female; or 2 males); body weight 2.05-4.05 kg. Symptoms of irritation (salivation, licking, sneezing, and eye blinking) occurred immediately and after several minutes. Following deep narcosis, corneal reflexes returned after a few minutes to ½ h. One animal died (exposure not given).

bTime in minutes after initiation of exposure when effect was observed.

TABLE 3-7 Sublethal Effects in Cats Exposed to trans-1,2-Dichloroethene for 10-390 Minutesa

Concentration (mg/m3 (ppm)

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

43,000 (10,750)

390

57-60

325-390

Absent

Absent

52,000 (13,000)

360

18-21

100-115 (spasms)

Absent

Absent

97,000 (24,250)

163

19

18-19 (spasms)

Absent

No data

101,500 (26,250)

268

2-3

16-18 (spasms)

172-192 (spasms in 1 male)

238-268

117,000 (29,250)

188

Instantly-2 min

3-10 (cough spasms)

27-83

178-188

129,000 (32,250)

129

3-4 (spasms)

6-14 (spasms)

40-100

87-158

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

Concentration (mg/m3 (ppm)

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

136,000 (34,000)

136

No data

4-5

21-42

127-132

138,000 (34,500)

50

Immediately (1 male)

6-9

19-21 (spasms in 1 female)

49-50

158,500 (39,500)

15

No data

4-6

11-12

14-15 (spasms)

191,000 (47,750)

10

5

3-9 (spasms in 1 male)

7-10

9-12

aLehmann and Schmidt-Kehl 1936. Two cats/exposure (1 male and 1 female, or 2 males); body weight 2.1-4.5 kg. Symptoms of irritation (salivation, licking, coughing, biting) occurred immediately and after several minutes. Vomiting occurred in 2 animals. Following deep narcosis, corneal and leg reflexes returned after a few minutes. Three animals died (exposure not given). Spasms (convulsions) affected extremities, chewing muscles, and diaphragm, but were not severe.

bTime after initiation of exposure when effect was observed.

TABLE 3-8 Sublethal Effects in Cats Exposed to cis-1,2-Dichloroethene for 17-288 Minutesa

Concentration (mg/m3 (ppm))

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

38,200 (9550)

288

60

121-165

238-265

246-285

39,600 (9900)

225

18-61

40-27

140-142

155-224

42,200 (10,500)

162

1 (1 male)

22-46

56-57

153-161

42,500 (10,625)

210

absent

43-65

55-65

141-210

50,600 (12,650)

117

2-6

13-22

32-35

72-114

56,300 (14,075)

66

5

14-17

25-26

64-66

61,400 (15,350)

26

3-5

12-15

16-19

24-25

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

76,000 (19,000)

24

5

10-11

13

16-19

100,000 (25,000)

17

2.5-5

7-8

9-10

12-13

aLehmann and Schmidt-Kehl 1936. Two cats/exposure (1 male and 1 female, or 2 males); body weight 2-3.2 kg. Symptoms of irritation (salivation, licking, sneezing) occurred immediately and after several minutes. Vomiting occurred in 2 animals. Following deep narcosis, corneal and leg reflexes returned after a few minutes, and ability to walk after a few minutes to ½ h. Three animals died (exposure not given).

bTime after initiation of exposure when effect was observed.

TABLE 3-9 Cats Exposed to cis-1,2-Dichloroethene for 9-360 Minutesa

Concentration [mg/m3 (ppm)]

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

20,000 (5000)

360

120-180, head and leg spasms

Absent after 360 min

Absent after 360 min

Absent after 360 min, 1 died after 2 d

35,000 (8750)

234

120, leg spasms

122-126

125-171, scratching

230-232,1 died

42,000 (10,500)

48

7

17

20

48, 1 died after 3 min

48,000 (12,000)

105

No data

12-44

15-68

27-104, 1 died after 1 d

49,000 (12,500)

122

7

37-69

72-88

90-121, 1 died after 5 d

53,000 (13,250)

118

8

17-30, spasms

21-60, restless, nystagmus

118-124,1 died after 2 d

62,000 (15,500)

49

6

10-17

4-20

12-48, both died on first d

64,000 (16,000)

37

No data

17-21

26

36-31

68,000 (17,000)

25

5, restless, scratching and biting

7-12, Leg spasms

17-22

21-23

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

Concentration [mg/m3 (ppm)]

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Light Narcosis (min)b

Deep Narcosis (min)b

77,000 (19,250)

25

Restless

6, spasms

8-9

13-24, 1 died after 7 d

98,000 (24,500)

20

3-5

8-10

11-18

12-20

114,000 (28,500)

9

No data

3-4

5

7-9, 1 died

aLehmann and Schmidt-Kehl 1936. Two cats/exposure (1 male and 1 female, or 2 males); only one male cat was exposed to 42 mg/L for 48 min; body weight 2.2-4.6 kg.

bTime after initiation of exposure when effect was observed.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

Hurtt et al. (1993) exposed groups of 24 pregnant Crl:CD BR rats to trans-1,2-dichloroethene at 0, 2,000, 6,000, or 12,000 ppm in 150-L square, pyramidal, stainless steel and glass exposure chambers 6 h/d on days 7-16 of gestation. The test atmosphere was generated by vaporization of the dichloroethene from glass, gas-washing bottles placed in temperature-regulated water baths and the vaporized test material was swept into 3-neck glass mixing flasks. Filtered, conditioned dilution air was added to the mixing flasks at 30 L/min to sweep vapors into the exposure chamber. The chamber concentration of test substance was determined by gas chromatography at 30-min intervals during each exposure. Chamber airflow, temperature, and relative humidity were monitored continually. Decreased body weight gain was observed in dams exposed at 12,000 ppm, and decreased maternal food consumption was observed in dams exposed at 6,000 and 12,000 ppm. Narcotizing effects were observed in dams exposed at 6,000 and 12,000 ppm. Signs of eye irritation were observed immediately following exposure(s). At 2,000 ppm, 13/24 animals exhibited a clear ocular discharge and 3/24 exhibited periocular wetness. At 6,000 ppm, 22/24 had ocular discharge and 17/24 had periocular wetness, and at 12,000 ppm all 24 dams showed both ocular discharge and periocular wetness. Alopecia, lethargy and salivation were observed in dams exposed to 12,000 ppm. An increase in the mean number of resorptions per litter was observed at 6,000 and 12,000 ppm; however, the values were within historical control ranges. A decrease in mean combined female fetal weight was observed at 12,000 ppm. No other fetal effects were observed.

In a subchronic exposure study, groups of 15 male and 15 female Crl:CD (SD)BR rats were exposed to trans-1,2-dichloroethene (99.9% pure) at 0, 200, 1,000, or 4,000 ppm for 6 h/d, 5 d/wk for 90 days in a 1,400-L stainless steel and glass chamber (Kelly 1998). The test atmospheres were generated by metering liquid dichloroethene into a heated glass Instatherm flask with either a Fluid Metering pump or a Hamilton Syringe Drive. Nitrogen introduced into the flask swept the dichloroethene vapor into the air supply duct to the exposure chamber. The chamber concentration of dichloroethene was controlled 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. No treatment-related effects on body weight, body weight gain, food consumption, clinical signs, clinical chemistry, hematology, gross or microscopic pathology or liver cell proliferation were observed.

In a 14-week feeding study, groups of 10 male and 10 female F344/N rats were fed diets with microcapsules containing trans-1,2-dichloroethene (NTP 2002). Dietary concentrations of microencapsulated trans-1,2-dichloroethene at 3,125, 6,250, 12,500, 25,000 and 50,000 ppm resulted in average daily doses of 190, 380, 770, 1,540, and 3,210 mg/kg for male rats and 190, 395, 780, 1,580, and 3,245 for female rats. Groups of 10 rats/sex served as untreated and vehicle controls. There was no treatment-related mortality. Mean body weights of males

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

in the 50,000 ppm group were decreased approximately 6% (p ≤ 0.01) compared to vehicle controls. On day 21 and at week 14, there were slight decreases (p ≤ 0.05 or 0.01) in hematocrit values, hemoglobin concentrations, and erythrocyte counts in males and females in the 25,000 and 50,000 ppm groups. At week 14, these effects were also noted in males in the 6250 and 12,500 ppm groups. Liver weights were increased up to 10% (p ≤ 0.05 or 0.01) in females in the 6250 ppm group and higher compared to vehicle controls, and kidney weights were decreased approximately 22% (p ≤ 0.05) in males in the 25,000 and 50,000 ppm groups. No treatment-related gross or microscopic lesions were noted.

In another oral study, McCauley et al. (1995) administered cis-1,2-dichloroethene by gavage in corn oil to groups of 10 male and 10 female Sprague-Dawley rats. Doses were 1.0, 3.0, 10.0, and 22.0 mmol/kg/day for 14-days or 0.33, 1.00, 3.00, or 9.00 mmol/kg/day for 90 days. There were no treatment-related deaths or histopathlogical lesions noted. Increased relative liver weights (p ≤ 0.05) were noted in both sexes and all doses tested in the 14-day study (up to 19% increase) and at 1.0 mmol/kg and above in the 90-day study (up to 26% increase).

3.2.3.
Mice

Three mice (sex not given)/experiment were exposed to either cis- or trans 1,2-dichloroethene vapors (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 136 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 determined 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 determining the chlorine content in the gas mixture employing the “lime method” from which the dichloroethene content was then calculated. Actual concentrations achieved ranged from 98.2% to 100.7% of the nominal concentrations. The mean experimental ventilation rate was 1050 L/h. Observations included effects on equilibrium (described as swaying), lethargy (described as the inability to move), and loss of foot reflexes. Also observed were irritating effects on mucous membranes (eyes, nose, mouth, salivary glands) and respiratory rate. Data are summarized in Tables 3-10 and 3-11.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-10 Effects in Mice Exposed to cis-1,2-Dichloroethene for 66-150 Minutesa

Concentration [mg/m3(ppm)]

Time (min)

Effects on Equilibrium (min)b

Lethargy (min)b

Loss of Reflex (min)b

Death/Recovery

27,000 (6750)

150

13

91

86 (2 mice)

Recovery in 3-19 min

40,000 (10,000)

150

7

11

24

Recovery in 10 min

50,000 (12,500)

149

5

9

19

Recovery in 10 min

65,000 (16,250)

140

3

6

9

All died in 75-140 min

70,000 (17,500)

77

1

3

5

All died in 55-77 min

90,000 (22,500)

66

1

3

4

All died in 24-66 min

aLehmann and Schmidt-Kehl 1936. 3 animals/exposure; sex not given; body weight 17-25 g; time at which effect occurred is average for 3 mice. At the beginning of exposure, the animals became restless and excited. After a few min, they assumed a side position which occurred almost simultaneously with a loss of reflexes at the higher concentrations. The respiratory rate was usually in the range of 150-180 breaths/minute, but occasionally reached as high as 300. Fewer spasms were seen in animals exposed to the cis- isomer compared to the trans- isomer. None of the animals that survived the exposure period, died later. Recovery occurred rapidly.

bTime after initiation of exposure when effect was observed.

TABLE 3-11 Mice Exposed to trans-1,2-Dichloroethene for 30-155 Minutesa

Concentration (mg/m3[ppm])

Time (min)

Effects on Equilibrium (min)b

Decreased Activity, Lethargy (min)b

Loss of Reflex (min)b

Death/Recovery

45,000 (11,250)

155

19

115

155

Recovery in 5-10 min

50,000 (12,500)

135

15

110

119

Recovery in 5 min

58,000 (14,500)

110

14

48

94

Recovery in 10 min

67,000 (16,750)

132

10

20

57

Recovery in 25 min

75,000 (18,750)

102

10

18

44

All died in 121-142 min

80,000 (20,000)

95

5

9

19

All died in 66-92 min

105,000 (26,250)

32

4

8

16

All died in 21-32 min

129,000 (32,250)

30

3

6

11

All died in 11-28 min

aLehmann and Schmidt-Kehl 1936. 3 Animals/exposure; sex not given; body weight 17-25 g; times at which effect occurred is average for 3 mice. There was no remarkable irritation of mucous membranes; initially the animals were quiet. Shortly before lethargy set in, spasmodic jumping and rapid respiration were observed. Cyanosis occurred during narcosis.

bTime after initiation of exposure when effect was observed.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

In another study, DeCeaurriz et al. (1983) exposed groups of 10 male Swiss OF1 mice weighing 20 to 25 g to 0, 1582, 1720, 2194, or 2485 ppm 1,2-dichloroethene (99%) vapors for 4 h.. Differences in mean total duration of immobility between control and experimental groups were measured over a 3 min period after exposure in a behavioral despair swimming test. Immobility was defined as cessation of struggling to get out of the water (suggesting prolongation of escape-directed behavior). A dose-related decrease, ranging from 23 to 71%, in mean duration of immobility was observed in exposed animals when compared to controls. Data are summarized in Table 3-12.

In a 14-week feeding study, groups of 10 male and 10 female B6C3F1 mice were fed diets with microcapsules containing trans-1,2-dichloroethene (NTP 2002). Dietary concentrations of microencapsulated trans-1,2-dichloroethene at 3,125, 6,250, 12,500, 25,000 and 50,000 ppm resulted in average daily doses of 480, 920, 1,900, 3,850, and 8,065 mg/kg for male mice and 450, 915, 1,830, 3,760, and 7,925 mg/kg for female mice. Groups of 10 mice/sex served as untreated and vehicle controls. There was no treatment-related mortality. Mean body weight gain of females in the 12,500, 25,000, and 50,000 ppm groups was decreased approximately 4-7% (p ≤ 0.01) compared to vehicle controls. There were no effects on hematology parameters or organ weights, and no treatment-related gross or microscopic lesions were noted.

3.3.
Developmental and Reproductive Toxicity

Hurtt et al. (1993) exposed groups of 24 pregnant Crl:CD BR rats to trans-1,2-dichloroethene at 0, 2,000, 6,000, or 12,000 ppm for 6 h/day on days 7-16 of gestation. This study was previously described in section 3.2.2. No other developmental and reproductive data concerning 1,2-dichloroethene were identified.

TABLE 3-12 Immobility in Mice Exposed to 1,2-Dichloroethene Vapors for 4 Hoursa

Concentration [mg/m3(ppm)]

Time (h)

Duration of Immobility (s ± SE)

Percent Change from Control

Control

Exposed

6,265 (1,582)

4

79.2±10.0

60.6±7.4

−23

6,811 (1,720)

4

94.5±6.5

51.7±8.3b

−45

8,776 (2,194)

4

79.2±10.0

33.9±6.6b

−57

9,840 (2,485)

4

94.0±9.0

26.9±6.2b

−71

aDeCeaurriz et al. 1983.

bSignificantly different from control, p < 0.05.

Source: DeCeaurriz et al. 1983. Reprinted with permission; copyright 1983, Toxicology and Applied Pharmacology.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
3.4.
Genotoxicity

Neither trans-, cis-, or cis- and trans-1,2-dichloroethene were mutagenic in Salmonella typhimurium strains TA97 (cis- isomer only), TA98, TA100, TA1535, or TA1537, with or without metabolic activation (Mortelmans et al. 1986; Zeiger et al. 1988; NTP 2002). In CHO cells in vitro, cis-1,2-dichloroethene induced sister chromatid exchanges (SCEs) in the absence of metabolic activation; results were equivocal with S9. The cis- and trans- mixture induced increases in SCE frequency in cultured CHO cells with and without metabolic activation; however, the trans-isomer was negative in this assay (NTP 2002). Neither isomer nor the isomeric mixture included chromosomal aberrations in CHO cells with or without metabolic activation (NTP 2002). In vivo genotoxicity studies, trans-1,2-dichloroethene was negative in a mouse bone marrow chromosomal aberration assay (Cerna and Kypenova 1977; NTP 2002), in host-mediated gene mutation assays in S. typhimurium and in gene mutation and gene conversion assays in Saccharomyces cerevisiae (Cerna and Kypenova 1977; Cantelli-Forti and Bronzetti 1988). cis-1,2-Dichloroethene was positive in a mouse bone marrow chromosomal aberration assay (Cerna and Kypenova 1977), and in host-mediated gene mutation assays in S. typhimurium and S. cerevisiae (Cerna and Kypenova 1977; Cantelli-Forti and Bronzetti 1988). Results were equivocal for the cis- isomer in a gene conversion assay in S. cerevisiae (Cerna and Kypenova 1977; Cantelli-Forti and Bronzetti 1988).

3.5.
Carcinogenicity

No data concerning the carcinogenicity of 1,2-dichloroethene were identified in the available literature.

3.6.
Summary

Lethal toxicity data are limited. Four-hour LC50 values of trans-1,2-dichloroethene at 24,100 ppm and cis-1,2-dichloroethene at 13,700 ppm have been reported in rats. No-effect-levels for death for 4-h of exposures were 12,300 ppm for trans-1,2-dichloroethene and 12,100 ppm for cis-1,2-dichloroethene (Kelly 1999). A 6-h LC50 of trans-1,2-dichloroethene at 21,723 ppm has been reported in OF1SPF mice (Gradiski et al. 1978). Also, deaths were observed, following a progression of narcotic effects, in both cats and mice exposed to various regimens of 1,2-dichloroethene (Lehmann and Schmidt-Kehl 1936). Nonlethal toxicity data indicate that 1,2-dichloroethene has a narcotic effect and that the cis- isomer is more potent than the trans- isomer with respect to narcosis (Lehmann and Schmidt-Kehl 1936). Narcotic observations indicated a progression from equilibrium effects, followed by lethargy, light narcosis (loss

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

of limb reflex, maintenance of corneal reflex), finally deep narcosis (loss of corneal reflex), and in some cases, as indicated above, death. Narcotic effects were also observed in pregnant rats exposed to trans-1,2-dichloroethene at 6,000 and 12,000 ppm, and dose-related ocular irritation was observed in pregnant rats exposed at 2,000, 6,000, and 12,000 ppm. Decreased fetal weight was observed in offspring of these rats exposed to trans-1,2-dichloroethene at 12,000 ppm (Hurtt et al. 1993). No treatment-related effects were noted in a 90-day study in rats repeatedly exposed to trans-1,2-dichloroethene at 4,000 ppm (Kelly 1998).

4.
SPECIAL CONSIDERATIONS

4.1.
Absorption, Distribution, Metabolism and Disposition

Blood:air partition coefficients, as well as liquid:air and tissue: air partition coefficients for both cis- and trans-1,2-dichloroethene have been reported. The cis-1,2-dichloroethene blood:air partition coefficient was reported as 9.58 and the trans-1,2-dichloroethene blood:air partition coefficient as 6.04. Gargas et al. (1988, 1989) also determined liquid:air and tissue:air partition coefficients for both isomers using 0.9% saline, olive oil, rat blood, rat liver, rat muscle and rat fat tissue. The reported partition coefficients for cis-1,2-dichloroethene are: rat blood:air = 21.6; saline:air = 3.25; olive oil:air = 278; fat:air = 227, liver:air = 15.3, and muscle:air = 6.09. Partition coefficients for trans-1,2-dichloroethene were reported as follows: rat blood:air = 9.58; saline:air = 1.41; olive oil:air = 178; fat:air = 148, liver:air = 8.96, and muscle:air = 3.52. The higher blood:air partition coefficient of the cis- isomer compared with the trans- isomer is likely a major factor in the more rapid and more extensive uptake of the cis- isomer into the systemic circulation and in the greater narcotic potency of the cis- isomer.

No data were located concerning the distribution of cis- or trans-1,2-dichloroethene by any route in any species.

1,2-Dichloroethene is metabolized by the hepatic mixed function oxidase system; it binds to the active site of the cytochrome P450 isoform, CYP2E1, resulting in inhibition of its own metabolism (Costa and Ivanetich 1982; Barton et al. 1995; Hanioka et al. 1998; Lilly et al. 1998). Both the cis- and trans- isomer are metabolized by CYP2E1 to an epoxide intermediate that covalently binds to proteins, forming S-methylcysteine amino acid adducts (NTP 2002). The epoxide intermediate is then transformed to 2,2-dichloroacetaldehyde by spontaneous rearrangement, which is then converted to 2,2-dichloroethanol and 2,2-dichloroacetate by cytolsolic and/or mitochondrial aldehyde and alcohol dehydrogenases (Costa and Ivanetich 1982; ATSDR 1996). The aldehyde formed from the cis- isomer yields primarily dichloroethanol with small concentrations of dichloroacetate, while the trans- isomer yields primarily dichloroacetate with only small amounts of dichloroethanol.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

cis-1,2-Dichloroethene has a 4-fold greater rate of turnover in hepatic microsomes when compared to the trans- isomer. The elimination of 1,2 dichloroethene follows zero-order kinetics above the metabolic saturation point and first-order kinetics below the saturation point. The cis- isomer has been shown to have a higher rate of first-order clearance than the trans- isomer (ATSDR 1996).

Inhalation pharmacokinetics were studied in male Wistar rats exposed to cis- or trans-1,2-dichloroethene using a closed inhalation chamber and analyzed with a nonphysiologically constrained, two-compartment model (Filser and Bolt 1979). The zero-order Vmax elimination rate for the cis- isomer was 0.67 mg/h·kg, and the value for the trans- isomer was 2.4 mg/h·kg. The authors suggested that the low maximal velocities were due to inactivation of CYP450 by reactive epoxy intermediates. Gargas et al. (1990) conducted a study to compensate for enzyme inhibition-resynthesis, and determined Vmax values of 3 mg/h·kg for the cis- isomer and 2.49 mg/h·kg for the trans- isomer.

4.2.
Mechanism of Toxicity

1,2-Dichloroethene metabolites modify the heme moiety of cytochrome P-450, resulting in loss of both cytochrome P-450 and heme. The modification may account for the in vivo and in vitro inhibition of metabolism of other cytochrome P-450 substrates by 1,2-dichloroethene. A suicide enzyme inhibition-resynthesis model has been used to describe the metabolism of 1,2-dichloroethene, meaning that the cytochrome P-450 may inactivate itself and enhance the toxicity of other xenobiotics detoxified by the mixed function oxidase system (Gargas et al. 1990). The CYP2E1-catalyzed oxidation of 1,2-dichloroethene to an epoxide, 2,2-dichloroacetaldehyde, and 2,2-dichloroethanol represents metabolic activation. Each of these metabolites is cytotoxic, and collectively, they may be responsible for the hepatic centrilobular fatty degeneration observed in animal studies after 1,2-dichloroethene administration (Lehmann and Schmidt-Kehl 1936; Kelly 1999). The more rapid and extensive metabolism of the cis- isomer and the more extensive production of dichloroethanol and its unstable predecessors from the cis- isomer are consistent with this isomer’s greater ability to affect the liver (Kelly 1999).

At high concentrations, 1,2-dichloroethene possesses anesthetic properties similar to other chlorinated ethenes. Eger et al. (2001) identified a MAC (minimum alveolar concentration) of 0.0183% ± 0.0031% for trans-1,2-dichloroethene and a MAC of 0.0071% ± 0.0006% for cis-1,2-dichloroethene for induction of anesthesia in rats. These data suggest that the cis- isomer is approximately 2.5-times more potent than the trans- isomer with regard to anesthesia induction. Data presented in this document suggest that the cis- isomer is approximately twice as effective as the trans- isomer in producing narcosis and with regard to lethality. Kelly (1999) reported 4-h LC50 rat values of 24,100 ppm and 13,700 ppm for trans- and cis-1,2-dichloroethene, respectively. Rats exposed to trans-1,2-dichloroethene at 12,300 ppm recovered from a lack of

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

stimulus response in approximately 30 min, whereas, rats exposed to the cis-isomer at 12,100 ppm took approximately 1 h to recover from similar effects (Kelly 1999). In general, it took animals exposed to the trans- isomer 2 to 3 times longer to lose equilibrium than when exposed to the same concentration of the cis- isomer. For example, data in Tables 3-10 and 3-11 indicate that mice exposed to 50,000 mg/m3 of the cis- isomer lost equilibrium in 5 min, whereas it took 15 min for mice exposed to the trans- isomer to lose equilibrium. Similarly, cats exposed to of the cis- isomer at 53,000 mg/m3 lost equilibrium in 8 min, whereas it took 18-21 min for cats exposed to the trans- isomer at 52,000 mg/m3 to lose equilibrium (data from Tables 3-7 through 3-9).

4.3.
Other Relevant Information
4.3.1.
Species Variability

Interspecies Variability

trans-1,2-Dichloroethene inhalation lethality data suggest little species variability between rats and mice. Gradiski et al. (1978) reported a 6-h LC50 of 21,723 ppm for mice. (However, no experimental details were available for this study.). (Kelly 1999) reported a 4-h LC50 of 24,100 ppm for rats.

McCarty et al. (1991) have shown that for acute exposures the critical brain concentration of halocarbons required to produce a given level of narcosis is relatively constant across species.

Intraspecies Variability

de Jong and Eger (1975) compared the MAC (minimum alveolar concentration) of nine anesthetics required to induce adequate anesthesia in 50% (AD50) or 95% (AD95) of patients. The ratios of AD95:AD50 ranged from 1.1 to 1.4, suggesting a steep concentration-response curve in the vapor concentration required to produce anesthesia.

Gregory et al.(1969) examined the MAC (minimum alveolar concentration) of halothane required to induce anesthesia in 8 age groups (0-0.5 years, 0.5-2.5 years, 2.5-6 years, 7-11 years, 12-18 years, 19-30 years, 31-55 years, and 70-96 years). The number of patients per age group ranged from 8 to 24. The MAC was found to be the highest in newborns (1.08%) and lowest in the elderly (0.64%). These data suggested relatively little intraspecies variability with regard to age.

Stevens et al. (1975) also found little variability with regard to age when comparing MAC of isoflurane required for anesthesia. The MAC were 1.28% ± 0.01 for age range 19-30 years, 1.15% ± 0.06 for age range 32-55 years, and 1.05%±0.05 for age over 55 years.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
4.3.2.
Physical and Chemical Properties

1,2-Dichloroethene is highly flammable and will produce toxic fumes of hydrogen chloride when burning. It also forms explosive hazards when combined with metals and alloys and will detonate by heat, impact, or friction when mixed with nitric acid (ATSDR 1996).

4.3.3.
Concurrent Exposure Issues

No information was located concerning exposure to 1,2-dichloroethene in conjunction with other chemicals that might be found concurrently in the workplace or environment. However, as previously described, 1,2-dichloroethene is metabolized by and may inhibit cytochrome P-450. Thus, 1,2-dichloroethene may potentiate the toxicity of compounds that are normally detoxified through cytochrome P-450 dependent metabolism and may antagonize the toxicity of compounds that are activated by cytochrome P-450. Ethanol in alcoholic beverages induces CYP2E1, and isozyme involved in the metabolic activation of 1,2-dichloroethene and other halocarbons, and thus may enhance the metabolic activation and increase liver toxicity of chlorinated hydrocarbons, including 1,2-dichloroethene. Also, as previously described in section 3.2.2, Freundt and Macholz (1978) observed prolonged hexobarbital sleeping time and zoxazolamine paralysis time in rats treated with 1,2-dichloroethene, suggesting that 1,2-dichloroethene may inhibit P-450 catalyzed detoxification of other chemicals.

4.4.
Temporal Extrapolation

The concentration-exposure time relationship for many irritant and systemically-acting vapors and gases can be described by the relationship Cn × t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al. 1986). Data were unavailable for an empirical derivation of n in the equation, Cn × t = k. In the absence of chemical specific data, an n of 3 will be applied to extrapolate to shorter time periods, and an n of 1 will be applied to extrapolate to longer time periods, to provide AEGL values that would be protective of human health (NRC 2001).

Although use of an exponent ‘n’ of 1 for extrapolating from shorter-term to longer-term time points may often overestimate risks for volatile organic compounds (VOCs) (Bruckner et al. 2004), this approach is considered appropriate for 1,2-dichloroethylene. For most well-metabolized VOCs, such as trichloroethylene, blood concentrations rapidly attain near steady-state during inhalation exposures. As a consequence, adverse effects typically increase only modestly with time for the longer exposure periods (once steady-state is reached). However, cis- and trans-1,2-dichloroethylene are distinctive in that they are suicide inhibitors (the trans- isomer is a more potent suicide inhibitor

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

than the cis- isomer) (Lilly et al. 1998). As a result, blood and brain concentrations of 1,2-dichloroethylene should continue to increase during prolonged exposures, rather than reaching near steady-state. The parent compounds are responsible for producing the CNS depression.

Furthermore, although Barton et al. (1995) published a model that was used to predict interactions between trans-1,2-dichloroethylene and other halocarbons, it has not been validated for humans; and thus was not used for time scaling of this chemical.

5.
RATIONALE AND AEGL-1

5.1.
Human Data Relevant to AEGL-1

Human data indicate that trans-1,2-dichloroethene at a concentration of 275 ppm for 5 min had no effect, a concentration of 825 ppm caused slight dizziness after 5 min, and slight eye irritation was observed at a concentration of 950 ppm for 5 min (Lehmann and Schmidt-Kehl 1936). The odor threshold is 17 ppm (ATSDR 1996).

5.2.
Animal Data Relevant to AEGL-1

Signs of dose-related ocular irritation were observed in pregnant rats exposed to trans-1,2-dichloroethene at 2,000, 6,000, and 12,000 ppm for 6 h/day during days 7-16 of gestation (Hurtt et al. 1993). The irritation was observed immediately following exposures. At 2,000 ppm the ocular irritation was considered minor and thus consistent with the definition of AEGL-1, because 13 of 24 animals exhibited clear-eye discharge, but only 3 of 24 animals exhibited periocular wetness. If significant discharge were occurring, a greater number of animals would be expected to exhibit periocular wetness.

5.3.
Derivation of AEGL-1

Since human data are available, they will be used to derive AEGL-1 values. The NOEL for eye irritation of 825 ppm was used as the point of departure (Lehmann and Schmidt-Kehl 1936). 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 humans exposed to 275 ppm). The values were held constant across the 10- and 30-min, 1-, 4-, and 8-h exposure time points since mild irritantancy is a threshold effect and generally does not vary greatly over time. Thus, prolonged exposure will not result in an enhanced effect. The animal data previously described

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

in this report (Section 4.2) suggest that the cis- isomer is approximately twice as toxic as the trans- isomer with regard to narcosis and lethality in experimental animals. Therefore, 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 justified 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 values for AEGL-1 are given in Table 3-13 (trans- isomer) and Table 3-14 (cis- isomer).

6.
RATIONALE AND AEGL-2

6.1.
Human Data Relevant to AEGL-2

Human data indicate that a concentration of 1,000 ppm trans-1,2-dichloroethene caused dizziness in two subjects after 10 min (Lehmann and Schmidt-Kehl 1936). Higher concentrations caused greater dizziness, drowsiness, burning of the eyes, intracranial pressure, and nausea.

6.2.
Animal Data Relevant to AEGL-2

Narcosis was observed in pregnant rats exposed to trans-1,2-dichloroethene at 6,000 and 12,000 ppm for 6 h/day during days 7-16 of gestation (Hurtt et al. 1993). Cats exposed to trans-1,2-dichloroethene at 43,000 mg/m3 (10,750 ppm) exhibited effects on equilibrium after 57 min and lethargy after 325 min of exposure, while cats exposed to cis-1,2-dichloroethene at 20,000 mg/m3 (5,000 ppm) exhibited head and leg spasms after 120 min (Lehmann and Schmidt-Kehl 1936). Mice exposed to trans-1,2-dichloroethene at 45,000 mg/m3 (11,250 ppm) exhibited effects on equilibrium after 19 min, lethargy after 115 min, and loss of reflex after 155 min of exposure, while mice exposed to cis-1,2-dichloroethene at 27,000 mg/m3 (6,750 ppm) exhibited effects on equilibrium after 13 min, lethargy after 91 min, and loss of reflex after 82 min of exposure (Lehmann and Schmidt-Kehl 1936). The total exposure times of mice for the trans- and cis- isomers were 155 and 150 min, respectively. The trans-exposed mice recovered 5-10 min after the end of the exposure period, and the cis-exposed mice recovered within 3-19 min after exposure.

TABLE 3-13 AEGL-1 for trans-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-1

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-14 AEGL-1 for cis-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-1

140 (554)

140 (554)

140 (554)

140 (554)

140 (554)

6.3.
Derivation of AEGL-2

The narcosis observed in the well-conducted study of pregnant rats exposed to the trans- isomer at 6,000 ppm was used to derive AEGL-2 values for the 4- and 8-h time points. Uncertainty factors of 3 each (total UF = 10) were applied for both inter- and intraspecies differences. The interspecies UF of 3 is 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; de Jong and Eger 1975; Stevens et al. 1975). This total uncertainty factor of 10 was applied to 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 protective AEGL values in the absence of an empirically derived 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 10-, 30-, and 60-min values extrapolated with n=3 would be 1,400 ppm for 10- and 30-min and 1,100 ppm for 1-h. However, these values are within the range of exposure times and concentrations in which healthy adult humans responded with symptoms reaching a level of severe dizziness (Lehmann and Schmidt-Kehl 1936). Dizziness was seen in humans after exposure at 1,000 ppm for 10 min, and the exposure lasted for 30 min. Therefore, the 10-min, 30-min, and 1-h values were set as maximum exposure values of 1,000 ppm for anesthetic effects in humans.

The animal data previously described in this report (section 4.2) suggest that the cis- isomer is approximately twice as toxic than the trans- isomer with regard to narcosis and lethality in experimental animals. Therefore, a modifying factor of 2 was applied in the derivation of the cis- isomer values only.

The values for AEGL-2 are given in Table 3-15 (trans- isomer) and Table 3-16 (cis- isomer).

TABLE 3-15 AEGL-2 for trans-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-2

1,000 (3,960)

1,000 (3,960)

1,000 (3,960)

690 (2,724)

450 (1,782)

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-16 AEGL-2 for cis-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-2

500 (1980)

500 (1,980)

500 (1,980)

340 (1,346)

230 (911)

7.
RATIONALE AND AEGL-3

7.1.
Human Data Relevant to AEGL-3

Although there has been a report of a human fatality associated with accidental exposure to 1,2-dichloroethene, the exposure concentration and duration are not known (Hamilton 1934). Dizziness, intracranial pressure, and nausea were observed in two human subjects exposed to 1,700 ppm trans-1,2-dichloroethene for 5 min (Lehmann and Schmidt-Kehl 1936).

7.2.
Animal Data Relevant to AEGL-3

Four-hour rat LC50 values of 24,100 ppm and 13,700 ppm were reported for trans- and cis-1,2-dichloroethene, respectively (Kelly 1999). In the same study, no deaths were reported for 4-h exposures at 12,300 ppm for the trans-isomer and at 12,100 ppm for the cis- isomer (Kelly 1999). No histopathologic changes were noted in the liver, heart, kidney, or lungs in any of the rats in the Kelly (1999) study. Exposure of cats to cis-1,2-dichloroethene at concentrations ranging from 5,000 to 28,500 ppm for 9 to 360 min resulted in death at various times after exposure (Lehmann and Schmidt-Kehl 1936). Varying degrees of equilibrium effects, lethargy, light narcosis, and/or deep narcosis were observed in cats prior to death. Decreases in combined and mean female fetal weight were observed in pregnant rats exposed to trans-1,2-dichloroethene at 12,000 ppm for 6 h/day on days 7-16 of gestation. In another study, female Wistar rats exhibited severe fatty degeneration of hepatic lobules and kupffer cells, pulmonary capillary hyperemia, alveolar septum distention, pneumonic infiltration, and fibrous swelling and hyperemia of cardiac muscle with poorly maintained striation after exposure to trans-1,2-dichloroethene at 3,000 ppm for 8 h (Freundt et al. 1977). However, these pathology data are contradicted by a recent study showing no treatment-related effects in rats exposed to trans-1,2-dichloroethene at up to 4,000 ppm for 6 h/day, 5 days/week for 90 days (Kelly 1998).

7.3.
Derivation of AEGL-3

The concentration (12,300 ppm) causing no death in rats exposed to trans-1,2-dichloroethene for 4 h was used as the basis of AEGL-3 for the 4- and 8-h time points. An uncertainty factor of 3 was applied for interspecies differences because rat and mouse lethality data indicate little species variability with regard

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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). An intraspecies UF of 3 was also applied and 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; 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 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 protective AEGL values in the absence of an empirically derived 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 10-, 30-, and 60-min values extrapolated with n = 3 are 3,500, 2,500, and 2,000 ppm respectively. However, these values are within the range of exposure times and concentrations in which healthy humans responded with severe dizziness. Dizziness, intracranial pressure, and nausea were observed at 1,700 ppm. Therefore, the 10-, 30-, and 60-min values were set at 1,700 ppm because healthy adult humans exposed for 5 min to 1,700 ppm experienced dizziness, intracranial pressure (unspecified) and nausea which persisted for ½ hour after exposure (Lehmann and Schmidt-Kehl 1936). Similar effects were seen with exposures of humans to 2,200 ppm for 5 min which resulted in severe dizziness, intracranial pressure (unspecified) and nausea which persisted for ½ hour after exposure. The animal data previously described in this report (Section 4.2) suggest that the cis- isomer is approximately twice as toxic than the trans- isomer with regard to narcosis and lethality in experimental animals. Therefore, a modifying factor of 2 was applied in the derivation of the cis- isomer values only. (Although the concentration causing no death observed in the cis- isomer rat experiment could be used to derive AEGL-3 values for this isomer, the approach of dividing the trans- values by 2 was chosen to be consistent with the AEGL-1 and AEGL-2 derivations.).

The values for AEGL-3 are given in Table 3-17 (trans- isomer) and Table 3-18 (cis- isomer).

8.
SUMMARY OF AEGLS

8.1.
AEGL Values and Toxicity End Points

The derived AEGL values for various levels of effects and durations of exposure are summarized in Table 3-19 (trans- isomer) and Table 3-20 (cis-isomer). AEGL-1 values were based on a NOEL for ocular irritation in humans. AEGL-2 values were based on narcosis in rats (4- and 8-h) or anesthetic effects

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

in humans (10-, 30-, and 60-min). AEGL-3 values were based on a no-effect-level for death in rats (4- and 8-h) or dizziness, intracranial pressure, and nausea in humans (10-, 30-, and 60-min).

8.2.
Other Exposure Criteria

Other standard and guidance levels are listed in Table 3-21.

TABLE 3-17 AEGL-3 for trans-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-3

1,700 (6,732)

1,700 (6,732)

1,700 (6,732)

1,200 (4,752)

620 (2,455)

TABLE 3-18 AEGL-3 for cis-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-3

850 (3,366)

850 (3,366)

850 (3,366)

620 (2,455)

310 (1,228)

TABLE 3-19 Relational Comparison of AEGL Values for trans-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-1 (Nondisabling)

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

280 (1,109)

AEGL-2 (Disabling)

1,000 (3,960)

1,000 (3,960)

1,000 (3,960)

690 (2,724)

450 (1,782)

AEGL-3 (Lethality)

1,700 (6,732)

1,700 (6,732)

1,700 (6,732)

1,200 (4,752)

620 (2,455)

TABLE 3-20 Relational Comparison of AEGL Values for cis-1,2-Dichloroethene [ppm (mg/m3)]

Classification

10-min

30-min

1-h

4-h

8-h

AEGL-1 (Nondisabling)

140 (554)

140 (554)

140 (554)

140 (554)

140 (554)

AEGL-2 (Disabling)

500 (1,980)

500 (1,980)

500 (1,980)

340 (1,346)

230 (911)

AEGL-3 (Lethality)

850 (3,366)

850 (3,366)

850 (3,366)

620 (2,455)

310 (1,228)

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

TABLE 3-21 Extant Standards and Guidelines for 1,2-Dichloroethene

Guideline

Exposure Duration

10-min

30-min

1-h

4-h

8-h

 

Trans- isomer

AEGL-1

280 ppm

2,80 ppm

280 ppm

280 ppm

280 ppm

AEGL-2

1,000 ppm

1,000 ppm

1,000 ppm

690 ppm

450 ppm

AEGL-3

1,700 ppm

1,700 ppm

1,700 ppm

1,200 ppm

620 ppm

 

cis- isomer

AEGL-1

140 ppm

140 ppm

140 ppm

140 ppm

140 ppm

AEGL-2

500 ppm

500 ppm

500 ppm

340 ppm

230 ppm

AEGL-3

850 ppm

850 ppm

850 ppm

620 ppm

310 ppm

IDLH (NIOSH)a

1,000 ppm

 

 

 

 

REL-TWA (NIOSH)b

 

 

 

 

2,00 ppm

PEL-TWA (OSHA)c

 

 

 

 

2,00 ppm

TLV-TWA(ACGIH)d

 

 

 

 

2,00 ppm

MAK (Germany)e

 

 

 

 

2,00 ppm

MAC (The Netherlands)f

 

 

 

 

2,00 ppm

aIDLH (immediately dangerous to life and health, National Institute of Occupational Safety and Health) (NIOSH 1996) represents the maximum concentration from which one could escape within 30 min without any escape-impairing symptoms, or any irreversible health effects. The IDLH for 1,2-dichloroethene is based on acute inhalation toxicity data in humans.

bREL-TWA (recommended exposure limits–time weighted average, National Institute of Occupational Safety and Health ) (NIOSH 2005) is defined analogous to the ACGIH TLV-TWA.

cPEL-TWA (permissible exposure limits–time-weighted average, Occupational Health and Safety Administration) (NIOSH 2005) is defined analogous to the ACGIH TLV-TWA, but is for exposures of no more than 10 h/d, 40 h/wk.

dTLV-TWA (Threshold Limit Value–time-weighted average, American Conference of Governmental Industrial Hygienists,) (ACGIH 2003) is the time-weighted average concentration for a normal 8-h workday and a 40-h workweek, to which nearly all workers may be repeatedly exposed, day after day, without adverse effect.

eMAK (maximale rbeitsplatzkonzentration [maximum workplace concentration], German Research Association) (DFG 2002) is defined analogous to the ACGIH TLV-TWA.

fMAC (maximaal aanvaarde concentratie [maximal accepted concentration] Dutch Expert Committee for Occupational Standards, The Netherlands) (MSZW 2004) is defined analogous to the ACGIH TLV-TWA.

8.3.
Data Quality and Research Needs

Data from human studies are sparse. Exposure times are short-term, ranging from only 5 to 30 min. Furthermore, the only quantitative human data are from 1936, and although the study appears to be thorough and well described, it

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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 experimental animals and almost certainly improved methodology.

9.
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Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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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 chloroethylenes. Arch. Toxicol. 72(10):609-621.

McCarty, L.S., D. Mackay, A.D. Smith, G.W. Ozburn, and D.G. Dixon. 1991. Interpreting 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. Salmonella 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

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

Disease Control and Prevention, National Institute of Occupational Safety and Health. August 1996 [online]. Available: http://www.cdc.gov/niosh/idlh/107028.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 Occupational 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: National Academy Press.

NRC (National Research Council). 1993. Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press.

NTP (National Toxicology Program). 2002. NTP Technical Report on the Toxicity Studies of trans-1,2-Dichloroethylene (CAS No. 156-60-5) Administered in Microcapsules in Feed to F344/N Rats and B6C3F1 Mice. Toxicity Report No. 55. NIH Publication 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 Encyclopedia 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. Anesthesiology 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. Hazard. 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.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

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

4-h AEGL-2

C3 × 4 h = 1.3 × 1012 ppm.h

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

8-h AEGL-2

C1 × 8 h = 36,000 ppm.h

C1 = 4,500 ppm

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

 

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

4 h AEGL-3

C3 × 4 h = 7.44 × 1012 ppm-h

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

8 h AEGL-3

C1 × 8 h = 49,200 ppm-h

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

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

APPENDIX B
Derivation Summary of AEGL Values for 1,2-Dichloroethene (trans- and cis- isomers)

AEGL-1 VALUES

10 min

30 min

1 h

4 h

8 h

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.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

AEGL-2 VALUES

10 min

30 min

1 h

4 h

8 h

1,000 ppm

1,000 ppm

1,000 ppm

690 ppm

450 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. (10-, and 30-min and 1-h)

Key Reference: 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. (4- and 8-h)

Test Species/Strain/Number: Human subjects/2

Test Species/Strain/Number: rat/Crl:CD BR pregnant females/24/group

Exposure Route/Concentrations/Durations: Inhalation: 275, 825, 950, 1000, 1200, 1700, or 2200 ppm for 5-30 min

Exposure Route/Concentrations/Durations: 0, 2000, 6000, or 12,000 ppm, 6 h/d, d 7-16 of gestation

Effects:

275 ppm No effects (5 min)

825 ppm Slight dizziness after 5 min

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

2,200 ppm Severe dizziness; intracranial pressure; nausea (5 min exposure)

Effects:

2,000 ppm Clear ocular discharge (after single 6-h exposure)

6,000 ppm Narcosis, ocular irritation (after single 6-h exposure)

1,200 ppm Ocular irritation, narcosis, lethargy, decreased body weight gain

End Point/Concentration/Rationale: 1,000 ppm for 10 min; threshold for anesthetic effects

End point/Concentration/Rationale: 6,000 ppm, 6 h/narcosis

Uncertainty Factors/Rationale:

Total uncertainty factor: 1

Interspecies: Not applicable - human data used.

Intraspecies:1 -threshold for anesthetic effect

Uncertainty Factors/Rationale:

Total uncertainty factor: 10

Interspecies: 3

Intraspecies: 3

The interspecies UF of 3 is 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

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

10 min

30 min

1 h

4 h

8 h

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: Held constant at threshold for anesthetic effects

Time Scaling: Cn × t = k, where the 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

1 h

4 h

8 h

1,700 ppm

1,700 ppm

1,700 ppm

1,200 ppm

620 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. (10-, and 30- min and 1-h)

Key Reference: 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. (4- and 8-h)

Test Species/Strain/Number: Human subjects/2

Test Species/Strain/Number: Rat/Crl:CD (SD)/5/sex/group

Exposure Route/Concentrations/Durations: Inhalation: 275, 825, 950, 1,000, 1,200, 1,700, or 2,200 ppm for 5-30 min

Exposure Route/Concentrations/Durations: Inhalation/ 0, 12,300, 22,500, 28,100, or 34,100 ppm/4 h

Effects:

275 ppm No effects (5 min)

825 ppm Slight dizziness after 5 min

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)

Mortality:

12,300 ppm 0/10

22,500 ppm 4/10

28,100 ppm 7/10

34,100 ppm 10/10

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

10 min

30 min

1 h

4 h

8 h

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: 1,700 ppm for 3 min; dizziness, intracranial pressure, nausea

End Point/Concentration/Rationale: 12,300 ppm, 4 h/NOEL for death

Uncertainty Factors/Rationale:

Total Uncertainty Factor: 1

Interspecies: Not applicable - human data used.

Intraspecies 1 - conservative AEGL-3 end point

Uncertainty Factors/Rationale:

Total Uncertainty Factor: 10

Interspecies: 3

Intraspecies: 3

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 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 points; conservative AEGL-3 end point

Time Scaling: Cn × t = k, where the 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.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×

APPENDIX C
Category Plots for trans-1,2-Dichloroethene and cis-1,2-Dichloroethene

FIGURE C-1 Category plots for trans-1,2-dichloroethene.

FIGURE C-1 Category plots for trans-1,2-dichloroethene.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
FIGURE C-2 Category plots for cis-1,2-dichloroethene.

FIGURE C-2 Category plots for cis-1,2-dichloroethene.

Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
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Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
×
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Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Page 181
Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Page 182
Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Page 183
Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Page 184
Suggested Citation:"3 1,2-Dichloroethene." National Research Council. 2010. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8. Washington, DC: The National Academies Press. doi: 10.17226/12770.
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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 8 Get This Book
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This book is the eighth volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals, and reviews AEGLs for acrolein, carbon monoxide, 1,2-dichloroethene, ethylenimine, fluorine, hydrazine, peracetic acid, propylenimine, and sulfur dioxide for scientific accuracy, completeness, and consistency with the NRC guideline reports.

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