Registration Dossier

Administrative data

Description of key information

Isopropyl chloride is associated with low acute toxicity in rats following oral exposure. An oral LD50 value greater than 2000 mg/kg body weight was reported in male and female Wistar rats in a study performed according to test guidelines and in compliance with Good Laboratory Practice (Sterner and Chibanguza, 1990). No deaths occurred over the 14-day observation period, and no clinical signs of toxicity were noted. Body weight gains were normal in all animals and no test-article related findings were reported at necropsy.

Isopropyl chloride is associated with low acute toxicity in rats following dermal exposure. A dermal LD50 value greater than 2000 mg/kg body weight was reported in male and female Wistar rats in 2 studies performed according to test guidelines, one which was conducted in compliance with good laboratory practice (Sterner and Chibanguza, 1989); Chibanguza, 1990). No animals died, and no abnormal clinical signs of toxicity were reported. In addition, all animals showed normal body weight gain, and there were no signs of dermal reactions, and no test-article related findings at necropsy.  

Isopropyl chloride is associated with low acute toxicity in rats following inhalation exposure. The inhalation LC50 for isopropyl chloride in male and female Sprague-Dawley rats was determined to be greater than 6.54 mg/L in a study performed to test guidelines and in compliance with good laboratory practice.  No animals died during the study period, and gross macroscopic inspection at necropsy did not reveal any test-related adverse effects. Pfenning (1989) reported that 5 male and 5 female Wistar rats died after 1 hour of exposure to an exceedingly large concentration (133 g per cubic meter) of isopropyl chloride vapor. Gross necropsy revealed hyperemic lungs in all animals.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Additional information

Acute Toxicity: Oral

 

The potential acute oral toxicity of isopropyl chloride was assessed in Wistar rats in a study performed according to OECD Guideline for the Testing of Chemicals No. 401 and in compliance with Good Laboratory Practice (Sterner and Chibanguza, 1990). Groups of 5 male and 5 female Wistar rats were orally administered 2000 mg isopropyl chloride/kg body weight in oleum arachidis (vehicle) by gavage. The animals were observed for 14 days after administration and body weights were taken at days 0, 7, and 14. Animals were observed for clinical signs of toxicity 20 minutes and 1, 2, 3, 6, and 24 hours following administration and once daily until day 14. Animals were necropsied after the observation period. No deaths occurred over the 14-day observation period, and no clinical signs of toxicity were noted. Body weight gains were normal in all animals and no test-article related findings were reported at necropsy. Therefore, the oral LD50 for isopropyl chloride in male and female rats was determined to be greater than 2000 mg/kg body weight.

Isopropyl chloride was not classified as acutely toxic following oral exposure according to CLP criteria.

 

Acute Toxicity: Dermal

 

The potential acute dermal toxicity of isopropyl chloride was assessed in Wistar rats in a study performed according to OECD Guideline for the Testing of Chemicals No. 402 and in accordance with good laboratory practice (Chibanguza, 1990). Isopropyl chloride in oleum arachidis (vehicle) was applied for 24 hours to 5 male and 5 female rats at 2000 mg/kg body weight. The test substance was applied to the shaved backs of the animals and covered with a porous gauze dressing and Elastoplast®. After 24 hours, the dressing was removed, and the animals were observed for clinical signs of toxicity 20 minutes and 1, 2, 3, 6, and 24 hours afterwards, and once daily thereafter. Dermal irritation was evaluated daily according to a scheme based on the Draize method. Body weights were recorded on day 0, 7, and 14. Animals found dead and animals surviving till the end of the 14-day observation period were necropsied and gross pathological examinations were performed. No animals died, and no abnormal clinical signs of toxicity were reported. In addition, all animals showed normal body weight gain and there were no signs of erythema or edema, and no test-article related findings at necropsy. Therefore, the dermal LD50 for isopropyl chloride in male and female rats was determined to be greater than 2000 mg/kg body weight.

Isopropyl chloride was not classified as acutely toxic following dermal exposure according to CLP criteria.

 

The results of Chibanguza (1990) are supported by results reported by Sterner and Chibanguza (1989) for the acute dermal toxicity of isopropyl chloride. In the latter study, the potential acute dermal toxicity of isopropyl chloride was assessed in Wistar rats according to OECD Guideline for the Testing of Chemicals No. 402. Isopropyl chloride in oleum arachidis (vehicle) was applied to 5 male and 5 female rats at a dose of 2000 mg/kg body weight for 24 hours with an occlusive dressing. The animals were observed for 14 days and necropsy was performed on all animals after the administration period. There were no mortalities, no adverse clinical signs, and no adverse findings at necropsy. The dermal LD50 in male and female rats was determined to be greater than 2000 mg kg body weight. 

Isopropyl chloride was not classified as acutely toxic following dermal exposure according to CLP criteria.

 

Acute Toxicity: Inhalation

 

The potential acute inhalation toxicity of isopropyl chloride was assessed in Sprague-Dawley rats in a study performed according to OECD Guideline for the Testing of Chemicals No. 403 and in compliance with good laboratory practice (Leuschner, 1990). Groups of 5 male and 5 female rats were exposed to 1.94 or 6.54 mg isopropyl chloride vapour /L for 4 hours via nose-only exposure in test chambers. During the exposure, continuous analysis of the atmosphere was performed. The animals were observed for clinical signs of toxicity throughout exposure and daily for 14 days thereafter. Necropsy was performed at the end of the observation period. No animals died during the study period, and gross macroscopic inspection at necropsy did not reveal any test-related adverse effects. Therefore, the inhalation LC50 for isopropyl chloride in male and female rats was determined to be greater than 6.54 mg/L. Isopropyl chloride was not classified as acutely toxic following inhalation exposure according to CLP criteria.

 

Pfenning (1989) also examined the potential acute inhalation toxicity of isopropyl chloride in Wistar rats in a study performed according to OECD Guideline for the Testing of Chemicals No. 403 and in compliance with good laboratory practice. Five male and 5 female rats were exposed to 133 g per cubic meter of isopropyl chloride vapour for 7 hours via whole-body exposure in test chambers. The animals’ activity was increased for a short time, but within 10 minutes all animals were deeply narcotized. All animals died within 1 hour and gross necropsy revealed hyperemic lungs in all animals. Classification under CLP criteria could not be performed based on the results of this study.

Justification for classification or non-classification

Acute Toxicity, oral: According to Title I, Article 4, paragraph 3 of Regulation (EC) No 1272/2008, “if a substance is subject to harmonised classification and labelling in accordance with Title V through an entry in Part 3 of Annex VI, that substance shall be classified in accordance with that entry, and a classification of that substance in accordance with Title II shall not be performed for the hazard classes or differentiations covered by that entry.” According to Part 3 of Annex VI, the substance meets the criteria for category 4 classification as acutely toxic by oral exposure.

 

Acute Toxicity, dermal: According to Title I, Article 4, paragraph 3 of Regulation (EC) No 1272/2008, “if a substance is subject to harmonised classification and labelling in accordance with Title V through an entry in Part 3 of Annex VI, that substance shall be classified in accordance with that entry, and a classification of that substance in accordance with Title II shall not be performed for the hazard classes or differentiations covered by that entry.” According to Part 3 of Annex VI, the substance meets the criteria for category 4 classification as acutely toxic by dermal exposure.

 

Acute Toxicity, inhalative: According to Title I, Article 4, paragraph 3 of Regulation (EC) No 1272/2008, “if a substance is subject to harmonised classification and labelling in accordance with Title V through an entry in Part 3 of Annex VI, that substance shall be classified in accordance with that entry, and a classification of that substance in accordance with Title II shall not be performed for the hazard classes or differentiations covered by that entry.” According to Part 3 of Annex VI, the substance meets the criteria for category 4 classification as acutely toxic by inhalative exposure.

However, test data reported in this section indicate no need for classification according to regulation EC No 1272/2008 as acute oral and dermal toxicity results reported as LD50 are greater 2000 mg/kg bw and the acute inhalative toxicity study showed no mortality at the highest tested concentration of 6.54 mg/l. Consequently, a self-classification is proposed in section 2 for GHS for assessment.

Specific Target Organ Toxicity– Single Exposure: The submission substance did not exhibit significant toxic effects arising from a single exposure. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.8.