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EXTOXNET PIP -DINOSEB Page 2 of 4 reported dermal LD50 of 80 to 200 mg/kg in rabbits and 200 to 300 mg/kg in guinea pigs [1,29]. Dinoseb did not cause skin irritation in rabbits [29]. Inhalation of dusts and sprays may be irritating to the lungs and eyes, and may cause serious illness; direct skin contact may cause irritation,yellow stains,burns, and dermatitis, and more serious effects in humans [29]. In one fatal incident, a farm worker was using a backpack hand-held sprayer that leaked dinoseb onto his body and penetrated his skin [29]. Symptoms in persons receiving accidental exposure include fatigue, thirst, sweating, insomnia,weight loss, headache, flushing of the face,nausea, abdominal pain, and occasional diarrhea [29]. In one case, some of these persisted for several months following exposure [29]. . Chronic toxicity: Dinoseb interferes with cellular conversion of food molecules(such as glucose) into useable energy for the body [83]. Specifically, it disturbs the production of adenosine triphosphate(ATP) in the mitochondria of the cells, ATP being the molecule that provides energy for all cellular activities [83]. This may account for many of the toxic effects caused by dinoseb. Dietary levels of about 25 mg/kg/day caused marked food refusal and some deaths after five or more doses [29]. Lower doses (5 to 20 mg/kg/day) caused statistically significant decreases in growth [29]. Some formulations of dinoseb may cause anemia-like effects,jaundice, and increased excretion of hemoglobin-related compounds (coproporphyrinuria) [29]. e Reproductive effects: Dinoseb is reported to adversely affect reproduction in rats and mice at levels that are commonly found among occupational workers. Decreased sperm count and abnormal sperm shape were observed in male rats and mice after 3 weeks at low exposure levels (about 10 mg/kg/day) for 30 days [84]. In a separate study,rats were exposed to relatively small quantities of dinoseb through their diet for a total of 22 weeks. Effects such as decreased fertility, slow weight gain, and poor survival of newborns appeared to be related to this pesticide [85]. Because of the adverse effects observed in laboratory animals at low chronic exposure levels, it is believed that dinoseb may cause decreased fertility or sterility in humans [83]. o Teratogenic effects: Low levels of dinoseb fed to rats and rabbits caused birth defects in the fetuses of exposed females [8]. When dinoseb was administered to pregnant mice, its breakdown products were found in the embryos. However, no teratogenic effects were noted. Various tests of mice and rats fed or injected with small amounts of dinoseb (around 10 mg/kg/day)have shown maternal toxicity, decreased fetal body weights and changes in fetal development [29]. In some studies of mice, oral doses to pregnant mothers caused an increased death rate in the exposed animals but caused no fetal damage [8]. Other studies indicate that dinoseb is a stronger teratogen when injected than when ingested. At low feeding levels the compound was responsible for skeletal deformities and neurological problems in newborn rats [83]. Based on the data, dinoseb may produce teratogenic effects in humans. . Mutagenic effects: Dinoseb was not mutagenic or genotoxic in laboratory studies performed using eukaryotic cells (the type found in mammals and other higher order species) [29,83]. This evidence suggests that mutagenic effects in humans due to dinoseb exposure are unlikely. . Carcinogenic effects: Dinoseb didn't cause significant increases in tumors when administered to two strains of mice at the maximum tolerated dose over a period of 18 months [29]. While not carcinogenic to male mice, it was found to be carcinogenic to female mice in another study [83]. The compound caused liver cancer in these animals at moderate to high doses [83]. The evidence regarding the carcinogenic potential of dinoseb is currently inconclusive. ® Organ toxicity: Dinoseb has the potential to damage the eye. It may also affect the immune system, liver,kidneys, and spleen [29]. ® Fate in humans and animals: Dinoseb is readily absorbed through the skin, gastrointestinal tract, and lung surface [29]. Esters of dinoseb are rapidly transformed into dinoseb,which is the active toxicant [29]. The chemical is excreted in the urine and feces and is metabolized in the liver. Breakdown products are found in the liver, kidneys, spleen, blood, and urine [29]. Dinoseb can also pass through the placenta into the fetus of experimental animals. http://extoxnet.orst.edu/pips/dinoseb.htm 3/24/2008