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1000
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Abstract/Summary
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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated ziram to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect is inflammation, squamous metaplasia, hyperplasia, and necrosis of cartilage in the larynx of rats after 28‐day inhalation exposure to 0.3 mg/m3. From the NOAEC of 0.1 mg/m3 a MAK value of 0.01 mg/m3 for the inhalable fraction has been established. With the critical effect being local, ziram has been classified in Peak Limitation Category I. An excursion factor of 2 has been established as acute irritation is not expected if twice the MAK value is exceeded. In one of three oral carcinogenicity studies in mice a significantly increased incidence of lung tumours was observed but coincided with a Sendai virus infection, therefore, this finding cannot unequivocally be regarded as substance‐induced. In one of three oral carcinogenicity studies in rats a significantly increased incidence of thyroid C‐cell carcinomas in male F344 rats was observed. As these tumours were not reproduced in other studies using higher doses and higher‐purity ziram and may have an incidence of up to 33% in untreated F344 rats, C‐cell carcinomas in male F344 rats are regarded as an isolated finding and have not resulted in the classification of ziram in one of the categories for carcinogenic substances. Ziram did not demonstrate any mutagenicity in rats or mice or clastogenicity in mice. The NOAEL for developmental toxicity accompanied by maternal toxicity was 16 mg/kg body weight and day in rats and 7.5 mg/kg body weight and day in rabbits, corresponding to ziram concentrations of 24 or 19 mg/m3. The NOAEL for developmental neurotoxicity was 12 mg/kg body weight and day, corresponding to 18 mg/m3. Thus, there is a sufficiently large margin between levels that cause developmental toxicity or developmental neurotoxicity and the MAK value of 0.01 mg ziram/m3 I has been classified in Pregnancy Risk Group C. Ziram shows a skin sensitizing potential in animals, which is also supported by the clinical and experimental findings obtained with the structurally closely‐related zinc diethyldithiocarbamate. Ziram has been labelled with “Sh” (for substances which cause sensitization of the skin), but not with “Sa” (for substances which cause sensitization of the airways). Dermal absorption of ziram is low and does not contribute significantly to systemic toxicity.
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