Ethyl chloroformate

Endpoint summary

Description of key information

The 1-hr LC50 values for males and females were 0.84) mg/L and 0.89 mg/L, respectively (--> 4h LC50 = 0.43 mg/L). 
Ethylchloroformate is toxic at inhalative exposure. The dermal LD50 value was greater than 2280 mg/kg bw. The oral LD50 value of ethylchloroformate is in the range of 205- 614 mg/kg bw. 

Additional information

ORAL:

Ethylchloroformate in water by gavage was administered at 80, 100, 125, 160, 200, 250, 320 or 400 µl/kg bw to 10 Wistar rats/sex/dose. The study was comparable to an OECD TG 401 oral toxicity study. All animals of the two highest dose groups died. No males died receiving a dose of EtCF up to 125 µl/kg bw. However, 2/10 females died in the lowest dose group. The oral LD₅₀value was estimated to be approximately180 µL/kg (205 mg/kg bw based on a density of 1.14 g/cm³ at 20°C). Animals that died exhibited hemorrhage of the stomach and the gastrointestinal tract. No gross pathologic changes were noted in animals that survived to study termination (BASF AG, 1970).

In another oral toxicity study comparable to OECD TG 401, Wistar rats (10/sex/dose) were given 400, 600, 1000, or 1600 mg/kg bw Ethylchloroformate in sesame oil by gavage. Mortalities were 7/10, 9/10, and 10/10 after a dose of 600, 1000 and 1600 mg/kg bw, respectively. All animals in the lowest dose group survived. The calculated oral LD₅₀value was 614 mg/kg bw (95 % CL = 521- 724). Clinical signs were not reported. There were no findings at the necropsy of the surviving animals; however, a reddened gastrointestinal tract was found in animals that died (Hoechst, 1975).

DERMAL:

In a dermal toxicity study equivalent to OECD TG 402, 0.5, 1.0, or 2.0 ml Ethylchloroformate/kg bw was applied to 2 male rabbits per dose(strain not reported). No animals died but the substance was corrosive in all doses. The dermal LD₅₀value was greater than 2280 mg/kg bw (Griscom, 1972).

INHALATION:

Five F344 rats per sex/dose were exposed by inhalation to 0 (room air), 0.21, 0.68, 0.80, 1.09 or 1.20 mg/L Ethylchloroformate vapor (60 min does equivalent concentrations) for 1 hour in a study comparable to OECD TG 403. All rats exposed to 0.21 mg/L or room air survived. All rats exposed to 1.09 and 1.20 mg/L died within 24 hours of exposure. Dyspnea or gasping, salivation, ocular and nasal discharge, and inactivity were seen in rats exposed to more than 0.21 mg/L. For the affected dose groups, most rats recovered by day 6 or 7. At necropsy, red discoloration of the lungs was noted in several rats that died as well as in two females sacrificed at the end of the study. Hydrotorax was observed in deceased animals in the two highest dose groups. No lesions were observed in tissues of rats exposed to 0.21 mg/L or in control animals. There was no mention of lesions in tissues other than the lungs or thoracic cavity. The 1-hr LC50 values (analytical with 95% confidence intervals) for males and females were 0.84 (0.73 - 0.96) mg/L and 0.89 (0.77 - 1.03) mg/L, respectively (Fisher 1981). According to EC/1272/2008 Annex I, 3.1.2.1.b the 4h-LC50 value is calculated for vapour by dividing by factor 2: 4h-LC50 = 0,43 mg/L.

Justification for classification or non-classification

Ethylchloroformate has to be classified as toxic at inhalative exposure (R26; acute inhal.tox. cat 1) and harmful via the oral route (R22;acute oral tox cat 3) according to the classification criteria given in EU Regulation 67/548 and EU regulation 1272/2008. Oral toxicity is believed to be a secondary effect of the caustic properties of the substance

No classification is warranted for ethylchloroformate toxicity via the dermal route.