Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 20 (2016) / Chapter Skim
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Appendix D Acute Exposure Guideline Levels for Selected Chloroformates
Appendix D Acute Exposure Guideline Levels for Selected Chloroformates
Pages 160-173
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From page 160... ...
No deaths occurred in rats repeatedly exposed to methyl chloroformate at 3.1 ppm and only histopathologic changes in the nasal turbinates and lesions of the larynx were found. Larynx lesions were the only finding in rats exposed at 1.01 ppm for 6 h/day, 5 days/week for 4 weeks (BASF 1993)
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From page 161... ...
= 47.8 ppm Concentration Male mortality Female mortality 35 ppm 0/5 0/5 45 ppm 0/5 0/5 57 ppm 5/5 3/5 73 ppm 5/5 5/5 Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 Intraspecies: 3 The effects of the chloroformates result from the direct-acting corrosive effects of the chemicals on the airways, in the absence of other systemic effects. Supporting information for this mode of action comes from observations of nasal irritation and respiratory effects (pulmonary congestion, pulmonary edema, and increased lung weights)
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From page 162... ...
Effects: Male rat LC50 = 145 ppm; female rat LC50 = 170 ppm Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 Intraspecies: 3 The effects of the chloroformates result from the direct-acting corrosive effects of the chemicals on the airways, in the absence of other systemic effects. Supporting information for this mode of action comes from observations of respiratory effects (e.g., lung congestion, edema, and emphysema)
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From page 163... ...
Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 Intraspecies: 3 The effects of the chloroformates result from the direct-acting corrosive effects of the chemicals on the airways, in the absence of other systemic effects. Supporting information for this mode of action comes from observations of nasal irritation and respiratory effects (pulmonary inflammation, pulmonary edema, and emphysema)
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From page 164... ...
AEGL-2 Values for n-Propyl Chloroformate 10 min 30 min 1h 4h 8h 3.7 ppm 3.7 ppm 3.0 ppm 1.9 ppm 1.3 ppm Data adequacy: Sparse data set on n-propyl chloroformate. Chemical-specific data were insufficient to derive AEGL-2 values because of uncertainties in the quality of the available data.
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From page 165... ...
Furthermore, interspecies and intraspecies uncertainty factors of 3 were also used in determining the AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate, and the resulting AEGL values were considered protective when compared with chemical-specific, repeated-exposure data on these analogs. (Continued)
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From page 166... ...
Additionally, mouse RD50 data suggest that two chemicals have similar toxicity; the RD50 values from studies in male Swiss-Webster mice were 97 ppm for isobutyl chloroformate and 117 ppm for sec-butyl chloroformate (Carpenter 1982d)
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From page 167... ...
differences among species and individuals are unlikely to play a major role in direct-acting irritation or corrosion at the portal-of-entry (respiratory tract)
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From page 168... ...
February 15, 1990. Test species/Strain/Sex/Number: Rat; Sprague Dawley; 5 males and 5 females per group Exposure route/Concentrations/Durations: Inhalation; 18.6 or 84.6 ppm for 4 h End point/Concentration/Rationale: No deaths occurred at 18.6 ppm Effects: No deaths at 18.6 ppm; 5/10 rats died at 84.6 ppm Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 Intraspecies: 3 The effects of the chloroformates result from the direct-acting corrosive effects of the chemicals on the airways, in the absence of other systemic effects.
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From page 169... ...
AEGL-2 Values for Phenyl Chloroformate 10 min 30 min 1h 4h 8h 0.24 ppm 0.24 ppm 0.19 ppm 0.12 ppm 0.06 ppm Data adequacy: In the absence of specific data on phenyl chloroformate to derive AEGL-2 values, estimates were made by dividing the AEGL-3 values by 3. This calculation is used to estimate a threshold for irreversible effects if a chemical has a steep concentration-response curve (NRC 2001)
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From page 170... ...
. Furthermore, interspecies and intraspecies uncertainty factors of 3 were also used in determining the AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate, and the resulting AEGL values were considered protective when compared with chemicalspecific, repeated-exposure data on these analogs.
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From page 171... ...
. Furthermore, interspecies and intraspecies uncertainty factors of 3 were also used in determining the AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate, and the resulting AEGL values were considered protective when compared with chemical-specific, repeated-exposure data on these analogs.
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From page 172... ...
AEGL-2 Values for Ethyl Chlorothioformate 10 min 30 min 1h 4h 8h 1.0 ppm 1.0 ppm 0.80 ppm 0.50 ppm 0.25 ppm Data adequacy: In the absence of specific data on ethyl chlorothioformate to derive AEGL-2 values, estimates were made by dividing the AEGL-3 values by 3. This calculation is used to estimate a threshold for irreversible effects if a chemical has a steep concentration-response curve (NRC 2001)
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From page 173... ...
. Intraspecies: 3, because the observed LC50s for ethyl chlorothioformate and ethyl chloroformate were similar Modifying factor: No applicable Animal-to-human dosimetric adjustment: Insufficient data Time scaling: Cn × t = k; default values of n = 3 for extrapolating to shorter durations and n = 1 for extrapolating to longer durations (NRC 2001)
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