Cytogenetic effects of Metalaxyl on human and animal chromosomes.
The purpose of this study was to assess the cytogenetic effects in vitro and in vivo of a commonly used fungicide, Metalaxyl. Chromosome damage in vitro, quantified by cultured human peripheral blood lymphocytes, demonstrated dose-related effects not associated with mitotic inhibition or cell death. Significant induction of chromosomal aberrations was observed with between 300 and 1000 micrograms/ml Metalaxyl in the absence of microsomal activation. Incubation in the presence of S9 mix produced less cytogenetic damage. Single i.p. injections of 75-300 mg/kg Metalaxyl had no effect on the frequency of micronuclei, detected in murine polychromatic erythrocytes. Micronuclei results were not compromised by direct evidence of cytotoxicity in the bone marrow of treated animals. The results in the present study indicated that genotoxicity of Metalaxyl was detected only in vitro and not in vivo. Available data reported that Metalaxyl was non-carcinogenic and gave negative results in a battery of genotoxicity tests. So, clastogenicity of Metalaxyl may not be evidence for DNA reactivity, but it may indicate alterations in cell homeostasis which are well implicated in the process of carcinogenesis.
Hrelia
P
P
Department of Pharmacology, University of Bologna, Italy.
Maffei
F
F
Fimognari
C
C
Vigagni
F
F
Cantelli-Forti
G
G
D000409:Alanine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004912:Erythrocytes / Q000187:drug effects; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
D005659:Fungicides, Industrial; D009153:Mutagens; C028175:metalaxyl; D000409:Alanine