Isobutyryl chloride

Endpoint summary

Description of key information

Oral route: The LD50 was >681 - <1000 mg/kg bw for male rats, 1100 mg/kg bw for female rats and 1000 mg/kg bw for male and female rats combined.
Inhalation route: The LC50 value was calculated to be 0.47-1.95 mg/L.
Dermal route: The LD50 was >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Value:

mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Value:

mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Value:

mg/kg bw

Additional information

Oral toxicity

In an acute oral toxicity study comparable to OECD guideline 401, rats (5/sex/dose) were given single gavage doses of 147 to 1470 mg/kg bw isobutyryl chloride in olive oil followed by a 14-day observation period (BASF AG, 1981). Clinical findings included dyspnea, agonal respiration, apathy, anomalous lying behaviour, uncoordinated movement, atonia, trembling, convulsions, bristly fur, salivation, and poor general state. Mortality occurred only at the two highest dose levels: 5/5 males and 1/5 female at 1000 mg/kg bw and 5/5 males and 5/5 females at 1470 mg/kg bw. At gross pathology, the animals that died during the test showed atrial dilatation and local acute hyperaemia of the heart, extensive haemorrhagic ulceration of the stomach with haematic contents (corrosive gastritis) and strong reddening of the intestinal mucosa with haemorrhagic contents. Animals sacrificed at the end of the observation period showed no pathological abnormalities. The LD50 was >681 - <1000 mg/kg bw for male rats, 1100 mg/kg bw for female rats and 1000 mg/kg bw for male and female rats combined.

 

In a supporting acute oral toxicity study comparable to OECD guideline 401, rats (10/sex/dose) were administered isobutyryl chloride at 204 to 2040 mg/kg bw by single dose (gavage) followed by a 7-day observation period (BASF AG, 1969). Clinical findings included calm behaviour, huddling, side- and abdominal position, piloerection, apnea, apathy, closed eyes, and mastication. In surviving animals symptoms were no longer visible after 2-6 days.

0/20 animals died at 204 mg/kg bw, 3/20 animals died at 816 mg/kg bw, 12/20 animals died at 1275 mg/kg bw, 14/20 animals died at 1632 mg/kg bw and 20/20 animals died at 2040 mg/kg bw.

At gross pathology, the animals that died during the test showed light coloured livers, dark coloured spleens, severe gastrorrhagia and blood-filled gastrointestinal tract, bloody/serous nasal discharge, general anaemia, tympanism (1 animal), and miliary necrotic lesions of the liver (1 animal). Animals sacrificed at the end of the observation period showed considerably dilated stomach and rectal discharge (2 animals), and completely filled and dilated stomachs (2 animals). The LD50 for males was 1326 mg/kg bw, for females: 1020 mg/kg bw and for males and females combined: 1122 mg/kg bw.

 

Inhalation toxicity

In an OECD 403 guideline study in which rats (5/sex/group) were exposed for 4 hours to 0.47 and 1.95 mg/L isobutyryl chloride, 1/10 animals died at the low exposure level and 9/10 animals died at the high exposure level after 14 days (BASF AG, 1989). The LC50 value was calculated to be 0.47-1.95 mg/L. Clinical signs included accelerated, intermittent and whooping respiration, apathy, restlessness, eyelid closure, nasal discharge, squatting posture and ruffled fur. In animals that died during the test, general congestion and intensified focal hyperaemia in the lungs of some animals was observed. In animals sacrificed at the end of the observation period, no pathological abnormalities were observed.

In a supporting study performed in principle as described in OECD guideline 403 (BASF AG, 1969), male and female rats were exposed to isobutyryl chloride for 3 minutes to a concentration of 12.032,3 ppm (n=12), for 10 minutes to a concentration of 12.032,3 ppm (n=6) and for 1 hour to a concentration of 200 ppm (n=12). Clinical signs included breathing difficulties, strong avoidance behaviour, irritation of mucous membranes, cloudy eyes, secretion from the eyes and agonal respiration. 10/12 animals died when exposed for 3 min to about 12032 ppm of the test substance, 6/6 animals died when exposed for 10 min to about 12032 ppm of the test substance and 0/12 animals died when exposed for 1 hour to 200 ppm of the test substance. Gross pathology of the animals which died during the study revealed pulmonary edema, emphysema and smeared snouts.

Dermal toxicity

Test groups consisting of 3 Sprague-Dawley rats/sex were treated with a single dermal application of unchanged test substance (1000 and 2000 mg/kg bw) or a 50% test substance solution in olive oil (400 mg/kg bw) in a study comparable to OECD guideline 402 (BASF AG, 1981). Exposure took place for 24 hours under occlusive conditions. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. Clinical findings included dyspnea, apathy, agitation, poor general condition, and local changes such as redness, edema, and slight spotted parchment-like necrosis to strong leather-like necrosis. No deaths occurred. The LD50 was >2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, isobutyryl chloride has to be classified for acute oral and inhalation toxicity. According to Directive 67/548/EEC, classification with Xn, R22 and T, R23 is warranted. According to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the classification is H302, Cat. 4 and H330, Cat.2.