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Toxicological Sciences 54, 481-492 (2000)
Copyright © 2000 by the Society of Toxicology

Subchronic and Chronic Toxicological Investigations on Metiram: The Lack of a Carcinogenic Response in Rodents

Jeffrey M. Charles*,1, Abraham Tobia{dagger} and Ben van Ravenzwaay{ddagger}

* Charles & Conn, LLC, Durham, North Carolina; {dagger} BASF Corporation, Research Triangle Park, North Carolina; and {ddagger} BASF Aktiengesellschaft, Ludwigshafen/Rhein, Germany

Metiram complex is a non-systemically acting fungicide of the group of ethylenebisdithiocarbamates (EBDC). The subchronic and chronic toxicity and the carcinogenic potential of metiram (containing 2% ethylene thiourea, ETU, as an intentionally added impurity) were investigated. Doses in the chronic/carcinogenicity rat study were 0, 5, 20, 80, or 320 ppm. In the carcinogenicity study in mice, diets were administered for 89 weeks (females) or 95 weeks (males) at doses of 0, 100, 300, or 1000 ppm. No oncogenic response was noted in either species. The subchronic studies in rats and mice further investigated the thyroid as a target organ. Doses of 0, 5, 80, 320, or 960 ppm were utilized in the rat study and a NOAEL of 80 ppm was established. In the subchronic mouse study, diets containing 0, 300, 1000, 3000, or 7500 ppm were utilized. A NOAEL of 300 ppm was established in this study. In summary, the findings of these studies defined the toxicity of metiram in rodents and demonstrated the lack of a carcinogenic response following chronic dietary exposure in the rat and mouse. The NOAELs that were established in these studies were consistent with the NOAELs established for thyroid toxicity/carcinogenicity in studies on ethylenethiourea (ETU).

Key Words: metiram; rat; mouse; rodent; subchronic toxicity; chronic toxicity; carcinogenicity; fungicide; dietary; T3; T4; ETU.


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