In vitro and in vivo studies demonstrate non-mutagenicity of the herbicide metolachlor

Abstract

The herbicide metolachlor was evaluated for genotoxic potential. Metolachlor did not induce micronuclei in mice, however at 40 mg/kg it significantly decreased the percentage of polychromatic erythrocytes, which is a cytotoxic effect. Metolachlor did not induce chromosomal aberrations in human lymphocytes in vitro, but 2.0 mug/ml culture medium resulted in cytotoxicity, decreasing the mitotic index significantly. The indirect exposure test was carried out by adding plasma from metolachlor-pretreated rats to the human lymphocyte cultures. There was no indication of clastogenicity by metolachlor metabolites. On the other hand, plasma of cyclophosphamide-pretreated rats had a significant clastogenic effect<br>O herbicida metolachlor foi avaliado quanto ao seu potencial genotóxico. Em camundongos não houve indução de micronúcleos nos eritrócitos policromáticos de medula óssea; entretanto, com a dose mais forte de 40 mg/kg peso por 48 h, observaram-se efeitos citotóxicos através da queda acentuada na porcentagem de eritrócitos policromáticos em relação aos normocromáticos. O metolachlor também não induziu aberrações cromossômicas em linfócitos humanos quando tratados in vitro, porém na concentração de 2,0 mig/ml de meio ocorreu queda no índice mitótico, demonstrando a toxidez do tratamento. Para se estudar os efeitos genotóxicos de possíveis metabolitos do metolachlor, ratos Wistar foram tratados com duas doses de 50 mg/kg com um intervalo de 24 h. Uma hora após o último tratamento, seus plasmas foram coletados através de punção cardíaca e adicionados às culturas de linfócitos humanos. Os resultados também demonstraram efeitos citotóxicos mas não de mutagenicidad

Characterization of the photodegradation products of metolachlor: structural elucidation, potential toxicity and persistence

“…No mutagenicity was observed for metolachlor and its degradation products though the software simulation. This observation is in agreement with the literature data which indicates that metolachlor does not induce gene mutation …”

Mutagenic impact on fish of runoff events in agricultural areas in south-west France

“…Based on data from the literature, the genotoxicity of the molecules detected in higher concentrations during spring flood remains unclear. Clements et al (1997) showed induction of DNA damage in Rana catesiana tadpoles exposed by immersion to a commercial formulation of metolachlor (Dual-960E) at 0.272 mg L −1 , but Grisolia and Ferrari (1997) concluded to non-mutagenicity in mice after injection of metolachlor at concentrations up to 40 mg kg −1 . No genotoxicity associated with exposure to isoproturon was detected, either in the mouse bone-marrow micronucleus test (Gebel et al, 1997) or by the comet assay and the chromosomal aberration test in Chinese Hamster ovary cells (Vigreux et al, 1998).…”

Cancer incidence and metolachlor use in the Agricultural Health Study: An update

“…24 In human lymphocytes, metolachlor has not been found to induce sister chromatid exchanges. 25 Whether metolachlor produces a clastogenic response in human lymphocytes is unclear, with both positive 20 and negative 26 reports.…”

“…24 In human lymphocytes, metolachlor has not been found to induce sister chromatid exchanges. 25 Whether metolachlor produces a clastogenic response in human lymphocytes is unclear, with both positive 20 and negative 26 reports. The findings from this update of the cohort are similar to those in the earlier report on cancer incidence and metolachlor use 6 for rectal cancer, with nonsignificant elevations in all Table 2.…”