Hematological and Genotoxic Effects of Subchronic Oral Exposure to a Mancozeb‐Based Fungicide in Female Mice

ABSTRACT

The extensive use of pesticides in modern agriculture has raised increasing concerns regarding the potential biological effects of repeated exposure to pesticide residues and commercial formulations. Mancozeb is a widely used ethylene‐bis‐dithiocarbamate fungicide; however, information on its hematological and genotoxic effects following repeated oral exposure remains limited, particularly in female models. In this study, we investigated the hematological, genotoxic, welfare‐related, and morphometric effects of subchronic oral exposure to the commercial mancozeb‐based formulation Dithane NT in female Swiss mice. The experimental dose of 200 mg/kg/day was defined as a subchronic oral exposure level for the mammalian assay and was interpreted in relation to available mammalian toxicological and regulatory benchmarks. The Artemia salina assay was used only as a preliminary ecotoxicological screening tool for the commercial formulation and was not applied as a direct interspecies dose‐conversion model. Animals were orally exposed to mancozeb for 30 consecutive days, followed by evaluation of hematological parameters, erythrocyte osmotic fragility, micronucleus frequency in bone marrow erythrocytes, body parameters, and welfare monitoring. Subchronic oral exposure to mancozeb induced a significant increase in micronucleus frequency in bone marrow erythrocytes, indicating a genotoxic response. Hematological evaluation indicated preservation of erythrocyte‐related parameters, leukocyte counts, and erythrocyte membrane stability. Morphometric assessment showed a selective increase in gastrocnemius muscle weight in exposed animals, whereas the remaining evaluated body parameters were not significantly altered. Welfare monitoring identified clinical impairment in a subset of exposed animals, including one euthanasia event before terminal sample collection. Overall, these findings demonstrate that subchronic oral exposure to a mancozeb‐based formulation induces genotoxic damage and a selective morphometric alteration in female mice, even in the absence of overt hematological toxicity.