Further in vitro and in vivo mutagenicity assays with thiram and ziram fungicides: bacterial reversion assays and mouse micronucleus test.

Abstract

The fungicides thiram and ziram have been assayed in a battery of nine bacterial strains of different genetic specificity. The results obtained suggest the induction of excisable DNA lesion(s), and indicate similar mutability of strains with AT or GC base pairs at target sites. This mutagenic profile is clearly distinct from that of oxidative mutagens, and it does not support the proposed role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in bacteria. Furthermore, the bone marrow micronucleus test has been carried out in B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5-50 mg/kg) and ziram samples (2.5-10 mg/kg in males, and 5-20 mg/kg in females). Thiram produced a significant increase of micronucleated PCEs in male mice sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase was detected in treated females. Ziram, tested in a lower range of doses because of its higher toxicity, resulted negative in both sexes. Both the acute toxicity and the ratio polychromatic/normochromatic erythrocytes indicated some sex specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1 mouse.