4-chlorobutyryl chloride

Endpoint summary

Description of key information

Acute oral toxicity indicates a moderate toxicity: in rats the oral toxicity was 1350 mg/kg bw. An older supportive study revealed an LD50 of about 1510 mg/kg bw in rats. 
In the acute inhalation toxicity study a LC50 of > 0.65 mg/l < 0.87 mg/l in male and female rats was found.

Additional information

Oral Toxicity

In an acute oral (gavage) toxicity study, comparable to OECD guideline 401, Sprague-Dawley rats (5/sex/dose) were administered 4 -chlorobutyryl chloride by gavage at 215, 1000, 1470, 2150, and 4640 mg/kg bw and followed by a 14-day observation period (BASF AG, 1980). Clinical signs included dyspnea, apathy, abnormal position, staggering, atony, pain reflexes missing, narcotic-like state, tremor, ruffled fur, exsiccation, paresis and poor general state. No mortality was observed at 215 and 1000 mg/kg bw. At 1470 mg/kg bw, 2/5 males and 4/5 females died after 14 days. At 2150 and 4640 mg/kg bw all animals died.

Findings at necropsy included acute dilatation of the heart, acute congestive hyperemia, manifold slightly broadened peripheral lobule painting in the liver, manifold hemorrhagic corrosive scab formation in the stomach, and diffuse reddened intestinal mucosa. In the sacrificed animals there were no abnormalities up to 1000 mg/kg. At 1470 mg/kg, the top of the gastro-esophageal vestibule was partly thickened and there were adhesions of the forestomach with the spleen, liver and peritoneum.

 

In a supporting acute oral toxicity study comparable to OECD guideline 401, Gassner-rats (5/sex/dose) were exposed by gavage to 4 -chlorobutyryl chloride at 200, 400, 800, 1000, 1250 and 1600 mm3/kg bw, equivalent to 252 to 2013 mg/kg bw and followed by a 14-day observation period (BASF AG, 1973). Clinical signs included dyspnea, atonia, ventral position and convulsions. Mortality occurred at 200 mm3/kg bw (1/10), and from 1000 mm3/kg bw onwards (2/10 at 1000 mm3/kg bw, 6/10 at 1250 mm3/kg bw, and 10/10 at 1600 mm3/kg bw). Findings at necropsy included dilatation of the heart, dilatation of the stomach with thin-pasty content and diffusely reddened intestine. The LD50 was calculated to be 1510 mg/kg bw for male and female animals.

Inhalation toxicity

The substance was studied as a vapour in an acute inhalation toxicity study according to OECD guideline 403 (TNO, 1992). Concentrations of 0.51, 0.65 and 0.87 mg/l were tested over a period of 4 hours with nose onyl exposure. The concentrations represent analytically determined concentrations, and the observation period was 14 days.

A moderate to severe, visually decreased breathing frequency was noted during exposure and shortly thereafter at all dose levels. Dyspnea, sniffing, and laboured breathing were noted in most animals at all dose levels throughout the 14-d observation period. In addition, closed exes, piloerection, hunched position, and dirty, wet fur were seen in several rats. Signs of poor general condition, mouth breathing, and encrustations around the nares were seen in almost all rats during the observation period. Occasional findings consisted of wounded nose, encrustations around the eyes, and wet abdominal region. In deceased rats, pale or dark, spotted and /or swollen lungs were observed which occasionally showed irregular surface or a spongy appearance. Several rats showed an air-filled stomach and/or intestines, resulting from mouth-breathing. Grayish, pale or spotted lungs were noted in several of the rats at the terminal necropsy. 8 of 10 rats exposed to 0.87 mg/l died or had to be killed in extremis during the observation period. None of the rats exposed to 0.51 or 0.65 mg/l died. Thus, the LC50 was > 0.65 mg/l < 0.87 mg/l.

In a supportive study, the respiratory tract irritancy of 4 -chlorobutyryl chloride was studied in a mouse model (Huntingdon Reseach Center, 1992). Mice were exposed nose only to vapours at concentrations of 0.15, 0.32 and 0.7 mg/l for 30 min (60 min at the highest concentration). The respiratory depression (determined as RD50 values = concentration which depresses respiration rate to 50% was calculated to be 0.3581 mg/l (early exposure phase) and 0.263 mg/l (late exposure phase).

Dermal toxicity

In accordance with column 2 of REACH Annex VIII, testing for acute dermal toxicity is not necessary as the substance is classified as corrosive to the skin according to Directive 67/548/EEC (C, R35) and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 (H314, Category 1A).

Justification for classification or non-classification

The available oral acute toxicity data warrants classification with Xn; R22 according to Directive 67/548/EEC and Cat. 4; H302 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Regarding inhalation, the substance should be classified as follows: according to Directive 67/548/EEC, classification with T, R23 is warranted and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the classification is H330, Cat. 2.