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.

Alterações histológicas dos rins e expressão das metalotioneínas e das proteínas de choque térmico em ratos Wistar após exposição ao fungicida tirame

“…A diminuição de peso está de acordo com os resultados obtidos em outros trabalhos, nos quais também foi observada redução de peso nos animais em crescimento alimentados com dietas contendo diferentes ditiocarbamatos, designadamente tirame (Dalvi, 1988;Guitart et al, 1996) e zirame (Enomoto et al, 1989).…”

“…Contracoloração com hematoxilina de Mayer. (Suzuki et al, 2000(Suzuki et al, , 2001, atividade anti-angiogênica (Marikovsky, 2002) e formação de quelatos com o cobre e o zinco, elementos essenciais como cofatores para várias enzimas (Dalvi, 1988). Funcionalmente, as MTs atuam principalmente como reguladoras da homeostase de metais nos tecidos e também como um potente antioxidante que protege as células ou os tecidos dos danos oxidativos.…”

“…Além disso, é usado como ingrediente de sabões, bronzeadores e sprays antissépticos, como aditivo em óleos lubrificantes e como acelerador de vulcanização de borracha (Mariano et al, 2008). Efeitos tóxicos e tumorigênicos foram observados em diferentes espécies animais expostas ao tirame (Dalvi, 1988;Maita et al, 1991) e inúmeros testes indicam que é genotóxico (Crebelli et al, 1992;Hemavathi e Rahiman, 1996). Embora a Environmental Protection Agency (EPA) e a World Health Organization (WHO) tenham considerado o tirame como ligeiramente tóxico, sua persistência no ambiente não é ainda bem conhecida.…”

Chromosomal aberrations in cultured human lymphocytes treated with the fungicide, Thiram

“…Thiram was found to induce malsegregation in fungi (Upshall and Johnson, 1981), excisable DNA lesions in bacteria (Crebelli et al, 1992), and also apoptosis in neuronal-like pheochromocytoma cells (Sook Han et al, 2003), chick chondrocytes (Rath et al, 1995), and Chinese hamster cells (Grosicka et al, 2005). Other examples of the consequences determined by treating Chinese hamster cells with Thiram are point mutations at the hypoxanthine-guanine phosphoribosyl transferase locus (Paschin and Bakhitova, 1985), increased CAs (Mosesso et al, 1994), cellular reduced glutathione (GSH) depletion, and protein and membrane lipid peroxidation (LPO) (Grosicka et al, 2005).…”

Major Degradation Pathway of Thiuram in Tap Water Processed by Oxidation with Sodium Hypochlorite

“…Thiuram, bis(dimethylthiocarbamoyl) disulfide, is a thiocarbamate fungicide that has been widely used for the protection of seeds and vegetable crops and as an accelerator and vulcanization agent in the rubber industry. It has been reported that plate incorporation assays with Salmonella typhimurium demonstrated direct mutagenecity of thiuram in TA100 (Crebelli et al, 1992;Franekic et al, 1994). The Integrated Risk Information System has set up the toxicological constant of thiuram at 0.005 mg/kg/day, and Smith (1996) has established the risk-based concentration of thiuram in tap water at 180 µg/L.…”