Summary
This report contains updated values for n-propyl chloroformate, isopropyl chloroformate, ethyl chlorothioformate, as well as the AEGL values for the other 9 chloroformates included in the Interim Acute Exposure Guideline Levels (AEGLs) for Selected Chloroformates. A summary of these AEGL values is presented in Table S-1. AEGL-1 values were not derived for any chloroformate because of insufficient toxicity data. No acute inhalation data consistent with the definition of AEGL-2 were available. Therefore, the AEGL-2 values for all chloroformates were calculated by taking a three-fold reduction in the AEGL-3 values. That approach is consistent with recommendations in the Standing Operating Procedures for Developing AEGLs for estimating a threshold for irreversible effects (NRC 2001). AEGL-3 values were based on lethality data on the individual chloroformates, although the toxicity data for chloroformates were sparse. Respiratory effects associated with direct-acting irritation and corrosion (nasal irritation, pulmonary inflammation, pulmonary edema, and emphysema and associated lethality) have been observed in humans and animals for several of the chloroformates. Interspecies and intraspecies uncertainty factors of 3 (for a total uncertainty factor of 10) were used for calculating the AEGL values for the chloroformates. Those values were chosen because pharmacodynamic variability is probably minimal (within a factor of 3) for irritants and because metabolic (pharmacokinetic) 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). The AEGL values for n-propyl chloroformate were determined on the basis of structural similarity to isopropyl chloroformate, and the AEGL values for isobutyl chloroformate and sec-butyl chloroformate were determined on the basis of structural analogy to n-butyl chloroformate.
REFERENCE
NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Substances. Washington, DC: National Academy Press.
TABLE S-1 AEGL Values for Selected Chloroformatesa
| Classification | 10 min | 30 min | 1 h | 4 h | 8 h |
|---|---|---|---|---|---|
| Methyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 4.0 ppm (16 mg/m3) | 2.8 ppm (11 mg/m3) | 2.2 ppm (8.6 mg/m3) | 1.4 ppm (5.5 mg/m3) | 0.70 ppm (2.7 mg/m3) |
| AEGL-3 (lethal) | 12 ppm (47 mg/m3) | 8.5 ppm (33 mg/m3) | 6.7 ppm (26 mg/m3) | 4.2 ppm (16 mg/m3) | 2.1 ppm (8.2 mg/m3) |
| Ethyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 2.9 ppm (13 mg/m3) | 2.0 ppm (8.8 mg/m3) | 1.6 ppm (7.0 mg/m3) | 0.40 ppm (1.8 mg/m3) | 0.20 ppm (0.88 mg/m3) |
| AEGL-3 (lethal) | 8.8 ppm (39 mg/m3) | 6.1 ppm (27 mg/m3) | 4.8 ppm (21 mg/m3) | 1.2 ppm (5.3 mg/m3) | 0.60 ppm (2.6 mg/m3) |
| Isopropyl chloroformate and n-propyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 3.7 ppm (19 mg/m3) | 3.7 ppm (19 mg/m3) | 3.0 ppm (15 mg/m3) | 1.9 ppm (9.5 mg/m3) | 1.3 ppm (6.5 mg/m3) |
| AEGL-3 (lethal) | 11 ppm (55 mg/m3) | 11 ppm (55 mg/m3) | 9.1 ppm (46 mg/m3) | 5.7 ppm (29 mg/m3) | 3.8 ppm (19 mg/m3) |
| Allyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 1.3 ppm (6.4 mg/m3) | 0.87 ppm (4.3 mg/m3) | 0.70 ppm (3.4 mg/m3) | 0.18 ppm (0.88 mg/m3) | 0.09 ppm (0.44 mg/m3) |
| AEGL-3 (lethal) | 3.8 ppm (19 mg/m3) | 2.6 ppm (13 mg/m3) | 2.1 ppm (10 mg/m3) | 0.53 ppm (2.6 mg/m3) | 0.26 ppm (1.3 mg/m3) |
| n-Butyl chloroformate, isobutyl chloroformate, and sec-butyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 4.0 ppm (22 mg/m3) | 2.8 ppm (33 mg/m3) | 2.2 ppm (27 mg/m3) | 0.57 ppm (6.7 mg/m3) | 0.28 ppm (3.3 mg/m3) |
| AEGL-3 (lethal) | 12 ppm (68 mg/m3) | 8.4 ppm (100 mg/m3) | 6.7 ppm (80 mg/m3) | 1.7 ppm (20 mg/m3) | 0.83 ppm (10 mg/m3) |
| Benzyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 1.2 ppm (8.7 mg/m3) | 1.2 ppm (8.7 mg/m3) | 0.97 ppm (6.7 mg/m3) | 0.63 ppm (4.3 mg/m3) | 0.31 ppm (2.2 mg/m3) |
| AEGL-3 (lethal) | 3.7 ppm (26 mg/m3) | 3.7 ppm (26 mg/m3) | 2.9 ppm (20 mg/m3) | 1.9 ppm (13 mg/m3) | 0.93 ppm (6.5 mg/m3) |
| Phenyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 0.24 ppm (1.5 mg/m3) | 0.24 ppm (1.5 mg/m3) | 0.19 ppm (1.2 mg/m3) | 0.12 ppm (0.77 mg/m3) | 0.06 ppm (0.38 mg/m3) |
| AEGL-3 (lethal) | 0.72 ppm (4.6 mg/m3) | 0.72 ppm (4.6 mg/m3) | 0.57 ppm (3.6 mg/m3) | 0.36 ppm (2.3 mg/m3) | 0.18 ppm (1.2 mg/m3) |
| 2-Ethylhexyl chloroformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 1.2 ppm (9.5 mg/m3) | 1.2 ppm (9.5 mg/m3) | 0.97 ppm (7.7 mg/m3) | 0.60 ppm (4.7 mg/m3) | 0.30 ppm (2.4 mg/m3) |
| AEGL-3 (lethal) | 3.6 ppm (28 mg/m3) | 3.6 ppm (28 mg/m3) | 2.9 ppm (23 mg/m3) | 1.8 ppm (14 mg/m3) | 0.91 ppm (7.2 mg/m3) |
| Ethyl chlorothioformate | |||||
| AEGL-1 (nondisabling) | NRb | NRb | NRb | NRb | NRb |
| AEGL-2 (disabling) | 1.0 ppm (5.1 mg/m3) | 1.0 ppm (5.1 mg/m3) | 0.80 ppm (4.0 mg/m3) | 0.50 ppm (2.6 mg/m3) | 0.25 ppm (1.3 mg/m3) |
| AEGL-3 (lethal) | 3.0 ppm (15 mg/m3) | 3.0 ppm (15 mg/m3) | 2.4 ppm (12 mg/m3) | 1.5 ppm (7.6 mg/m3) | 0.75 ppm (3.8 mg/m3) |
aTreatment of people exposed to chloroformates should consider that pulmonary edema frequently occurs, but its symptoms may not manifest for several hours after exposure and may be aggravated by physical exertion.
bNR, not recommended. Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects.
