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XTOXNET PIP-HEXAZINONE Page 2 of increased liver weights in mice [29]. • Reproductive effects: Female rats, fed moderate to high doses (up to 150 mg/kg) over two generations, showed no effects on reproduction or milk production,but only reduced offspring weight [15,29]. Available evidence suggests that hexazinone is unlikely to cause reproductive effects in humans. • Teratogenic effects: Pregnant female rats receiving doses up to 100 mg/kg/day during gestation, and rabbits receiving up to 125 mg/kg/day, evidenced no fetal abnormalities [15]. Teratogenic effects were observed in rats only at maternal doses greater than 400 mg/kg/day during gestation [15]. It is unlikely that hexazinone would pose a teratogenic effects in humans under normal conditions. • Mutagenic effects: Hexazinone showed no mutagenic activity in the Ames assay and tests using Chinese hamster ovary cell cultures [15]. In living animal tests, no changes in chromosomal structure occurred. In other laboratory analysed of its capacity to induce genetic disruption, results were inconclusive [15]. The evidence suggests hexazinone is either slightly or nonmutagenic. • Carcinogenic effects: Rats, mice, and dogs have been tested for 1 to 2 years on diets containing up to 500 mg/kg. Hexazinone was not carcinogenic in rats, and was only carcinogenic in mice at dietary levels of over 300 mg/kg. At these levels in mice, liver adenomas were observed [15]. These studies suggest that hexazinone is unlikely to be carcinogenic to humans under normal circumstances. • Organ toxicity: Target organs affected in lab animals by chronic hexazinone exposure include the liver. • Fate in humans and animals: Hexazinone is fairly rapidly processed and excreted by animal systems. Rats typically excrete hexazinone almost completely within 3 to 6 days,the majority in urine [30]. Long-term exposure does not diminish this rapid processing and elimination; rats given prior exposure for 2 weeks excreted almost all of the product within 3 days [30]. Less than 1% of the parent hexazinone was detected in urine and feces. There does not appear to be any significant tissue accumulation [30]. Dairy cows given small amounts of hexazinone in their diets for 30 days had no detectable residues in milk, fat, liver,kidney, or lean muscle,but did have minute amounts of a hexazinone metabolite in their milk [30]. Lactating goats given small amounts of hexazinone for 5 days also had small amounts of the compound in their milk and livers [30]. Ecological Effects: • Effects on birds: Hexazinone is slightly to practically nontoxic to birds. The acute oral LD50 of hexazinone in bobwhite quail is 2258 mg/kg [15]. The 5-to 8-day dietary LC50 in bobwhite quail and mallard ducklings is greater than 10,000 ppm [15]. • Effects on aquatic organisms: Hexazinone is slightly toxic to fish and other freshwater organisms. Some of the reported 96-how LC50 values include: rainbow trout, 320 mg/L; bluegill, 370 mg/L; fathead minnow, 274 mg/L [6,15]. The 48-hour LC50 for hexazinone in the water flea, Daphnia magna, is 151 mg/L [15]. The bioconcentration factor in bluegill sunfish is only seven times the ambient water concentration, indicating very low bioaccumulation in fish [30]. • Effects on other organisms: Hexazinone is nontoxic to honey bees. The herbicide is toxic to larch trees (Larix spp.), and should not be used for weed control in forested areas [6]. Environmental Fate: • Breakdown in soil and groundwater: Hexazinone is of moderate to high persistence in the soil environment. Measured field half-lives range from less than 30 to 180 days, with a representative value of about 90 days [31]. Hexazinone is broken down by soil microbes,which release carbon dioxide in the process [15]. Sunlight may also break down the compound via photodegradation [31]. The rate of breakdown under natural field conditions will depend on many site-specific variables, including sunlight, rainfall, soil type, and rate of application. Hexazinone does not evaporate to any appreciable extent from soil [31]. Hexazinone is very poorly adsorbed to soil particles,very soluble in water, and slowly degraded, so it is likely to be mobile in most soils and has the potential to contaminant groundwater. • Breakdown in water: Photodecomposition, biodegradation, and dilution are the prime mechanisms for loss of hexazinone activity in aquatic systems [15]. • Breakdown in vegetation: Hexazinone is readily absorbed in the root zone and translocated throughout the