2-ethylhexyl chloroformate

Endpoint summary

Description of key information

2 Ethylhexanoylchloride is of low toxicity via the oral and dermal route of exposure. LD50 values are 5420 mg/kg (oral) and > 3038 mg/kg (dermal).

The substance is however very toxic after inhalation. LC50 = 0.27 mg/L/4h.

 

Additional information

oral

In an OECD TG 401 study, Sprague-Dawley rats (5/ sex/dose) were administered 215, 464, 1000, 2610, 4640, 5000, 6810, or 8250 mg/kg bw 2 ethylhexanoylchloroformate by gavage (vehicle; olive oil). None of the rats exposed to doses up to and including 2610 mg/kg bw died. Two of ten animals and 3/10 animals died after receiving a dose of 4640 and 5000 mg/kg bw, respectively. Nearly all animals receiving a higher dosage died (9/10 at 6810 mg/kg bw and 10/10 at 8250 mg/kg bw). Necropsy of deceased animals revealed chemical burns in the stomach. The calculated oral LD₅₀value was 5420 mg/kg bw (95% CL = 4913-6050 mg/kg bw) (BASF, 1980).

 

In an supporting study the LD50 was about 6000 mg/kg bw/d, however, mortality was observed at doses of 3200 mg/kg bw/d and higher (BASF 1968).

 

In another study comparable to OECD TG 401, Sprague-Dawley rats (2/sex/dose) were administered 400, 600, 800, 900, 1350, 2025, 3038, 4556, 6834, or 10,250 mg/kg bw 2 ethylhexanoylchloroformate by gavage (no vehicle). None of the rats exposed to doses up to and including 2025 mg/kg bw died or exhibited any signs of toxicity. Three out of 4 exposed to 3038 and 4556 mg/kg bw died within 6-22 hours after treatment. All four animals exposed to 6834 or 10250 mg/kg bw died within 4-22 hours after treatment. Animals treated with 3038 mg/kg or higher exhibited hypoactivity, ptosis, muscular weakness, prostration and/or convulsions within 30 minutes to 4 hours of treatment.Necropsy of deceased animals chemical burns in the stomach, hemorrhaged lungs and mottled, discolored livers. Chemical burns in the stomach were observed in all animals (surviving or deceased) treated with 1350 mg/kg and higher. The calculated oral LD₅₀value wass 3038 mg/kg bw (+/- 436.9 mg/kg) (Quinn & Paa, 1975).

 

Inhalative

Crl:CD(SD)IGS BR rats (5/sex/concentration) were exposed (whole body) to 0.18, 0.42, 0.76, 2.22, or 3.84 mg/L ethylhexanoylchloroformate (vapor; analytical concentrations) for 4 hours in an OECD TG 403 study. None of the animals exposed to 0.18 mg/L died. At 0.42 mg/L group, 3 males died during exposure and 1 male and 3 females were found dead on Day 1. Mortality in this dose group was 4/5 males and 3/5 females. Nine of ten animals exposed to 0.76 mg/L died during exposure or within the first day following exposure. All animals in the 2.22 and 3.84 mg/L groups died during exposure. The 4-hr LC₅₀value was 0.38 mg/L. A concentration-dependent increase in respiration rate (up to gasping) during exposure was observed in all animals. Animals in the 0.18 mg/L group were normal by day 3. The other surviving animals appeared normal by day 5. Gross findings in animals that died following exposure included dark red lungs, mottled lungs and/or ocular opacity. At the scheduled necropsy, dark red lungs and mottled lungs were noted in some females exposed to 0.18 mg/L (Henson, 2002).

 

In another OECD TG 403 study, Wistar rats (10/sex/concentration) were exposed (whole body) to 0.18, 0.21, 0.27, or 0.37 mg/L ethylhexanoylchloroformate (vapor; measured) for 4 hours. None of the animals exposed to 0.18 mg/L died. Mortality occurred at the higher concentrations as follows: 5/20 (0.21 mg/L), 9/20 (0.27 mg/L), and 20/20 (0.37 mg/L). The overall 4-hr LC₅₀value was 0.27 mg/L. No effects were noted at the two lower concentrations. After exposure to 0.27 mg/L and/or higher, forced breathing/gasping, reddish nasal discharge, nasal encrustation, and staggering were observed. Surviving animals recovered within 2-6 days. Gross pathology revealed pulmonary emphysema in all found dead animals, and pneumonia in 2 females that were found dead. There were no pathological findings in animals that were sacrificed (BASF AG, 1985).

 

dermal

In a study comparable to OECD TG 402, New Zealand White rabbits (2/sex/dose) were dermally treated with 600, 900, 1,350, 2,025 or 3,038 mg/kg bw of 2-ethylhexanoylchloroformate. The test material was severely irritating/corrosive to the skin. One male exposed to 3,038 mg/kg bw died at 12 days. There were no other deaths. The dermal LD₅₀ was greater than 3,038 mg/kg bw. Focal hemorrhages in the lung as well as red lungs at > 900 mg/kg bw suggest an inhalation co-exposure (Quinn & Paa, 1975).

 

Justification for classification or non-classification

2-Ethylhexanoylchloride is very toxic via the inhalative route according to the classification criteria laid down in EU Regulation 1272/2008 (acute inhal. Cat 1).

No classification is warranted concerning the oral and dermal rout of exposure as classification criteria of EU Regulation 1272/2008 are not met.