Methyl chloroformate

Endpoint summary

Description of key information

Methyl chloroformate is very toxic after inhalation, being the relevant route of exposure. The substance is toxic to harmful after oral administration depending on the vehicle.  Dermal toxicity of methyl chloroformate is low . 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

40 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

60 mg/m³

Additional information

Oral

In a study comparable to OECD TG 401, Sprague-Dawley rats (2/sex/dose) received 15.61, 23.41, 35.12, 52.67, 79.01 or 118.5 mg/kg bw methylchloroformate by gavage. The oral LD₅₀value was determined to be 40 mg/kg bw. Animals that died exhibited burns and hemorrhage of the stomach, and some blood in the intestines.  No gross pathologic changes were noted in animals that survived to study termination (Lazzara 1975).

In another study comparable to OECD TG 401, Sprague-Dawley rats (5/sex/dose) were given 147, 215, 464, 681, or 2150 mg/kg bw methylchloroformate in olive oil by gavage. All animals receiving 681 or 2150 mg/kg bw died. Mortalities were 6/10, 3/10, and 1/10 after a dose of 464, 215 and 147 mg/kg bw, respectively. The calculated oral LD₅₀value was 313 mg/kg bw (95 % CL = 229 – 427). Dyspnea, apathy, staggering, tremors, piloerection, and poor general state were observed at all dose levels. Reddened intestinal mucosa and gastric hemorrhage were observed in several animals that died. A thickened forestomach wall and abdominal adhesions were noted in the surviving animals at necropsy (BASF AG, 1981).

 

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 methylchloroformate. methylchloroformate was severely irritating and corrosive to the skin. At all dose levels tested,erythema, severe edema, burns, subdermal hemorrhages, necrosis, and escharosis were observed. No animals died and thus, the dermal LD₅₀was determined to be greater than 3,038 mg/kg bw (Lazzara, 1975).

 

inhalative

In an inhalation study comparable to OECD TG 403,Sprague-Dawley rats (10/sex/dose) were exposed by whole-body inhalation for 4 hours to 0.006, 0.053, 0.120 or 0.130 mg/L methylchloroformate vapor (analytical concentration). No mortality was observed at 0.006 mg/L. At 0.053 mg/L, 8/20 animals died. Bloody nasal discharge and dyspnoea were observed. All animals exposed to 0.120 mg/L died and 17/20 exposed to 0.130 mg/L died. At necropsy, edema was noted in the lungs of the deceased animals. A hydrothorax was noted in several deceased cases (BASF, 1980c). The LC₅₀was determined to be 0.06 mg/L/4h.

In another inhalation study [OECD TG 403], Fischer 344 rats (5/sex/dose) were exposed by whole-body inhalation for 1 hour to 0.07, 0.36, 0.48, 0.58 or 0.61 mg/L methylchloroformate vapor (analytical concentration). Rats exposed to 0.07 mg/L or 0.36 mg/L survived to study termination. At 0.48 mg/L, 7/10 animals died. All animals exposed to higher concentrations died. Bloody discharge from the ocular, oral and/or genital regions was noted in animals exposed to 0.36 mg/L or higher concentrations. Dyspnea was observed in all rats exposed to 0.48 mg/L or higher concentrations. Survivors were generally free of symptoms by day 6 after exposure. At necropsy, hyperemia and edema were noted in the lungs of two of the deceased animals (Fisher, 1981a). The LC₅₀was calculated to be 0.46 mg/L/1h.

In an OECD TG 403 study, Wistar rats (5/sex/dose) were exposed by whole-body inhalation for 4 hours to 35, 45, 57, or 73 ppm methylchloroformate vapor (analytical concentration) (Hoechst, 1986). Mortality occurred at 57 ppm (8/10) and 73 ppm (10/10). No animals died at concentrations up to 45 ppm. Signs of respiratory irritation (gasping and accelerated, irregular and jerky respiration) were noted. Necropsy of deceased rats confirmed this observation with findings of dark red haemorrhagic lungs filled with liquid. Lungs with dark red foci were observed at necropsy in a few of the animals sacrificed at the end of the study. The 4-hr LC₅₀values for males and females were 51 ppm (0.2 mg/L) and 53 ppm (0.21 mg/L), respectively (Hoechst, 1986).

Justification for classification or non-classification

Methyl chloroformate is classified according to Annex I of EU Regulation 67/548 as very toxic by inhalation and harmful via the oral and dermal route (R26; R21; R22). According to Annex VI of EU Regulation 1272/2008 an acute inhal. tox cat 1; acute dermal tox cat 4; acute oral tox cat 2 is proposed.