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tory animals have yielded negative results. In one of the more extensive studies, which was carried out by the FDA, rats were administered sodium arsenite at concentrations up to 250 ppm or sodium arsenate at concentrations up to 400 ppm in the diet for 2 years. No increases in tumors were observed (Byron et al. 1967). A similar negative finding was noted in beagles maintained on diets containing sodium arsenate or sodium arsenite at 5-125 ppm for 2 years; however, the high dose proved to be lethal (Byron et al. 1967). In another study, rats were administered lead arsenite at concentrations of 463 or 1,850 ppm (arsenic at approximately 400 ppm) or sodium arsenite at a concentration of 416 ppm in the diet (based on body weight and food consumption data, equivalent to approximately 18-20 mg/kg of body weight per day) for 29 months with some indication of toxicity, but no increase in tumorigenicity when compared with controls (Kroes et al. 1974). In a study of 20 Cynomolgus monkeys, arsenic was administered by mouth as sodium arsenate at a dose of 0.1 mg/kg per day, 5 days per week, for 15 years. None of the animals developed malignant tumors (Thorgeirsson et al. 1994).

Animal studies on the carcinogenicity of arsenic administered via drinking water have also been conducted. In rats, sodium arsenite administered at a concentration of 5 mg/L for a lifetime did not cause an increase in tumors (Schroeder et al. 1968). The authors calculated that the concentration was equivalent to a dose of 0.38 mg/kg of body weight per day. Although some evidence of arsenic accumulation was found in the animals, it had no effect on survival (Schroeder et al. 1968). In a similar study, rats received sodium arsenate at a concentration of 5 mg/L (approximately 350 µg/kg of body weight per day) for a lifetime and had no indication of tumorigenicity (Kanisawa and Schroeder 1969). In a shorter study examining the effect of arsenic on mammary tumors, Schrauzer and Ishmael (1974) administered sodium arsenite to mice at 10 mg/L in drinking water for 16 weeks. The incidence of mammary tumors was lower in the tested animals (27%) than in the controls (82%). However, they found that arsenic increased the size of spontaneous mammary tumors. In a study, which has not yet been peer reviewed and is available only in abstract form, Ng et al. (1998) reported preliminary results indicating that the administration of sodium arsenate in drinking water (0.500 mg/L) to C57B1/6J and metallothionein knock-out mice for up to 26 months caused tumors of the gastrointestinal tract, lungs, liver, spleen, bone, skin, reproductive system, and eye. No tumors were observed in the control groups of the study.

Several animal studies have examined the interaction of arsenic with other chemicals to determine if it might be acting as a promoter rather than as an initiator of tumors. Baroni et al. (1963) administered arsenic trioxide as a 0.01 % solution in drinking water or sodium arsenate by skin application (two

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