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I:XTOXNET PIP - MANCOLE3 'tp://ace.orst.edu/cgi-bin/mfs/01 /pips/mancozeb.htm rats, and greater than 5000 mg/kg in rabbits [4]. It is a mild skin irritant and sensitizer, and a mild to moderate eye irritant in rabbits [4,32]. Workers with occupational exposure to mancozeb have developed sensitization rashes [ 1 ]. Chronic toxicity: No toxicological effects were apparent in rats fed dietary doses of 5 mg/kg/day in a long-term study [ 1 ]. Impaired thyroid function was observed as lower iodine uptake after 24 months in dogs fed doses of 2.5 and 25 mg/kg/day of mancozeb, but not in those dogs fed 0.625 mg/kg/day [ 1 ]. A major toxicological concern in situations of chronic exposure is the generation of ethylenethiourea (ETU) in the course of mancozeb metabolism, and as a contaminant in mancozeb production [1,33]. ETU may also be produced when EBDCs are used on stored produce, or during cooking [9]. In addition to having the potential to cause goiter, a condition in which the thyroid gland is enlarged, this metabolite has produced birth defects and cancer in experimental animals [9]• Reproductive effects: In a three -generation rat study with mancozeb at a dietary level of 50 mg/kg/day there was reduced fertility but no indication of embryotoxic effects [1,9]. In another study in which pregnant rats were exposed to mancozeb by inhalation, toxic effects on the pups were observed only at exposure levels (55 mg/m3) that were also toxic to the dams [1]. It is unlikely that mancozeb will produce reproductive effects in humans under normal circumstances. a Teratogenic effects: No teratogenic effects were observed in a three -generation rat study with mancozeb at a dietary level of 50 mg/kg/day [1]. Developmental abnormalities of the body wall, central nervous system, eye, ear, and musculoskeletal system were observed in experimental rats which were given a very high dose of 1320 mg/kg of mancozeb on the 11th day of pregnancy [25]. Mancozeb was not teratogenic to rats when it was inhaled by pregnant females at airborne concentrations of 0.017 mg/L [32]. In pregnant rats fed 5 mg/kg/day, the lowest dose tested, developmental toxicity was observed in the form of delayed hardening of the bones of the skull in offspring [9]. In view of the conflicting evidence, the teratogenicity of mancozeb is not known. • Mutagenic effects: Mancozeb was found to be mutagenic in one set of tests, while in another it did not cause mutations [9]. Mancozeb is thought to be similar to maneb, which was not mutagenic in the Ames Test [32]. Data regarding the mutagenicity are inconclusive but suggest that mancozeb is either not mutagenic or weakly mutagenic. • Carcinogenic effects: No data are available regarding the carcinogenic effects of mancozeb. While studies of other EBDCs indicate they are not carcinogenic, ETU (a mancozeb metabolite), has caused cancer in experimental animals at high doses [9,10]. Thus, the carcinogenic potential of mancozeb is not currently known. • Organ toxicity: The main target organ of mancozeb is the thyroid gland; the effects may be due to the metabolite ETU [9,10]. • Fate in humans and animals: Mancozeb is rapidly absorbed into the body from the gastrointestinal tract, distributed to various target organs, and almost completely excreted in 96 hours. ETU is the major mancozeb metabolite of toxicologic significance, with carbon disulfide as a minor metabolite [10]. Ecological Effects: Effects on birds: Mancozeb is slightly toxic to birds, with reported -day dietary LC50 values in bobwhite quail and mallard ducklings of greater than 10,000 ppm [32]. The 10 -day dietary LC50 values of 6400 ppm and 3200 ppm are reported for mallard ducks and Japanese quail, respectively [4]. • Effects on aquatic organisms: Mancozeb is moderately to highly toxic to fish and aquatic 2 of4 5/12/00 2:11 PM