Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 8 (2010) / Chapter Skim
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3 1,2-Dichloroethene
3 1,2-Dichloroethene
Pages 144-185
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From page 144... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 145... ...
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.
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From page 146... ...
. 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.
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From page 147... ...
. 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.
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From page 148... ...
(2,455) Nausea, intracranial pressure, and dizziness in humans: 10-, 30-min, and 1-h (Lehmann and Schmidt-Kehl 1936)
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From page 149... ...
, 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.
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From page 150... ...
TABLE 3-4 Effects of Inhalation Exposure to trans-1,2-Dichloroethenea Time Concentration (ppm) Effect 5 min 275 No effect 950 Slight burning of eyes 1700b Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea 2200b Severe dizziness after 5 min; intracranial pressure; nausea 10 min 825 Slight dizziness after 5 min 1200 Dizziness after 5 min; initially, slight burning of the eyes; drowsiness 30 min 1000 Dizziness after 10 min; slight burning of eyes a Two human subjects were exposed.
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From page 151... ...
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.
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From page 152... ...
13,500 6/10 Prostrate, no response to alerting stimulus Weakness, irregular respiration, immediately after (recovery time not noted) exposure, slight to severe weight loss one day followed by normal weight gain; centrilobular fatty liver changes (2/10)
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From page 153... ...
Farben and was further purified by multiple fractionated distillations followed by boiling point measurements. Ambient air was suctioned from a 360L 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.
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From page 154... ...
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.
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TABLE 3-7 Sublethal Effects in Cats Exposed to trans-1,2-Dichloroethene for 10-390 Minutesa Concentration Time Effects on Lethargy Light Narcosis Deep Narcosis (mg/m3 (ppm)
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From page 156... ...
TABLE 3-8 Sublethal Effects in Cats Exposed to cis-1,2-Dichloroethene for 17-288 Minutes Concentration Time Effects on Equilibrium Lethargy Light Narcosis Deep Narcosis (mg/m3 (ppm)
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From page 157... ...
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 2 h.
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From page 158... ...
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.
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From page 159... ...
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.
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From page 160... ...
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.
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From page 161... ...
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.
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From page 162... ...
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.
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From page 163... ...
. In vivo genotoxicity studies, trans-1,2-dichloroethene was negative in a mouse bone marrow chromosomal aberration assay (Cerna and Kypenova 1977; NTP 2002)
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From page 164... ...
, 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.
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From page 165... ...
. 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)
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From page 166... ...
(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.
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From page 167... ...
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)
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From page 168... ...
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)
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From page 169... ...
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.
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From page 170... ...
. 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.
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From page 171... ...
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.
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From page 172... ...
. 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.
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From page 173... ...
(2,455) TABLE 3-20 Relational Comparison of AEGL Values for cis-1,2Dichloroethene [ppm (mg/m3)
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From page 174... ...
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
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2004. The Acute Exposure Guideline Level (AEGL)
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. NIOSH (National Institute of Occupational Safety and Health)
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From page 177... ...
2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 178... ...
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)
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From page 179... ...
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)
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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)
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From page 181... ...
1,200 ppm Ocular irritation, narcosis, 1,200 ppm Dizziness after 5 min; lethargy, decreased body weight gain drowsiness; slight burning of eyes (10 min exposure) 1,700 ppm Dizziness after 3 min; slight burning of eyes; intracranial pressure; nausea 2,200 ppm Severe dizziness; intracranial pressure; nausea (5 min exposure)
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From page 182... ...
28,100 ppm 7/10 1,000 ppm Dizziness after 10 min; slight 34,100 ppm 10/10 burning of eyes (30 min exposure) 1,200 ppm Dizziness after 5 min; drowsiness; slight burning of eyes (10 min exposure)
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From page 183... ...
Intraspecies: 3 Intraspecies 1 - conservative AEGL-3 An uncertainty factor of 3 was applied for end point interspecies differences because rat and mouse lethality data indicate little species variability with regard to death. The interspecies UF of 3 is also considered sufficient because data suggest that the critical brain concentration of a halocarbon required to produce a given level of narcosis is relatively constant across species (McCarty et al.
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From page 184... ...
APPENDIX C 184 Category Plots for trans-1,2-Dichloroethene and cis-1,2-Dichloroethene Chemical Toxicity-All trans-1,2-Dichloroethene Human - No Effect 100000 Human - Discomfort Human - Disabling 10000 Animal - No Effect Animal - Discomfort ppm AEGL-3 Animal - Disabling 1000 AEGL-2 Animal - Partially Lethal AEGL-1 Animal - Lethal AEGL 100 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category plots for trans-1,2-dichloroethene.
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From page 185... ...
Chemical Toxicity - TSD All Data cis-1,2-Dichloroethene Human - No Effect 100000 Human - Discomfort Human - Disabling 10000 Animal - No Effect Animal - Discomfort ppm Animal - Disabling 1000 AEGL-3 Animal - Partially Lethal AEGL-2 Animal - Lethal AEGL-1 AEGL 100 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-2 Category plots for cis-1,2-dichloroethene.
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