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EC number: 236-670-8 | CAS number: 13463-40-6
BASF (1995) reported a 28-day inhalation toxicity study. Male and female rats were offered vapour concentrations of 0.1 ppm = ca. 0.8 mg/m3 (test group 4), 0.3 ppm = ca. 2 mg/m3 (test group E), 1 ppm = ca. 8 mg/m3 (test group 1), 3 ppm = ca. 24 mg/m3 (test group 2) and 10 ppm = ca. 81 mg/m3 (test group 3). The frequency of treatment was 5 days per week and 6 hours per day (totally up to 20 exposures). The following findings were obtained: One exposure to 10 ppm (test group 3) caused 100% lethality and 2 exposures to 3 ppm (test group 2) 50% lethality (3 male and 2 female animals) during a period of 4 days. In test group 3 (10 ppm) the animals showed symptoms of respiratory distress and irritation as well as reduced general state. Pathological examinations revealed signs of irritation in the upper respiration tract and severe lung damage. In some animals lymphocyte depletion of the spleen occurred.
In test group 2 (3 ppm) the surviving animals showed accelerated respiration up to study day 9. No influence on body weight development was seen in the post-exposure observation period. No substance-related changes in hematological or clinico-chemical parameters occurred. The same kind of lung damage as in test group 3 was found during pathological examination in the animal that died or were sacrificed prematurely. The surviving animals still showed increased absolute and relative lung weights and some histopathologic changes in the lungs at the end of the study period.
No substance-related clinical signs and findings or influence on body weight development were seen in test groups 4, E and 1. No substance-induced effects on hematological and clinicochemical parameters occurred besides a slight but mostly statistically significant elevation of CO-hemoglobin levels which is not considered as of toxicologial relevance. Pathological evaluation also did not reveal any morphological alterations besides a slight but statistically significant increase in absolute and relative lung weights of the male animals of test group 1 ppm. The NOAEC was found to be 2 mg/m3 (= 0.3 ppm).
The above-mentioned BASF study was based on an older investigation of Gage (1970). Male and female rats were offered daily (5.5 h/d) vapour concentrations of 15 ppm (2 days) or 7 ppm (18 days). In the high dose group, 4 rats died within 3 - 4 days; lethargy, respiratory difficulties, formation of 0.2 - 0.4% carboxyhemoglobin, lung edema, and congestion was observed. In the low dose group, no signs of toxicity were observed; organs appeared to be normal. The NOAEC was found to be 55 mg/m3.
Classification proposal regarding EU criteria: R48/23. GHS criteria: Cat. 1
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