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1356853 
Journal Article 
Abstract 
Dimethylarsinic acid (DMA): Results of chronic toxicity/oncogenicity studies in Fischer F344 rats and B6C3F1 mice 
Eldan, M; Arnold, LL; Van Gemert, M; Cohen, SM 
2005 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
84 
1-S 
307 
English 
Male and female Fischer F344 rats and B6C3F1 mice were treated with dietary dimethylarsinic acid (DMA) in 2-year feeding studies. Rats were treated with 2, 10, 40, or 100 ppm DMA. Mice were treated with 8, 40, 200, or 500 ppm DMA. Early in the study there was a low incidence of treatment-related mortality in male rats in the two highest dose groups (100 ppm-5/60, 40 ppm-1/60). There was no treatment- related mortality in female rats or in mice. The primary targets for DMA-induced toxicity in the rat and mouse were the urinary bladder and kidney. In the rat, treatment with DMA resulted in a dose responsive increase in urothelial cell hyperplasia at 40 and 100 ppm DMA. Bladder tumors occurred in male and female rats at 100 ppm DMA. The female rat appeared to be more sensitive to the urothelial effects of DMA. In the rat kidneys, there was an increased incidence of medullary nephrocalcinosis, medullary tubular cystic dilation, and hyperplasia of the epithelial lining of the renal papilla in both sexes at doses of 40 and 100 ppm DMA. In mice, treatment with DMA resulted in a dose-dependent increase in vacuolar degeneration of the urinary bladder epithelium without toxicity or proliferation in the 2 highest dose male groups and the 3 highest dose female groups. No treatment-related tumors were found in any mice at any dose of DMA. The NOEL in rats was assessed as 2 ppm in males and 10 ppm in females and in mice as 40 ppm in males and 8 ppm in females. Based on these studies, high doses of DMA are carcinogenic to the rat urinary bladder; DMA is not carcinogenic in the mouse. Subsequent research has demonstrated that the mode of action for the rat bladder carcinogenesis involves cytotoxicity, regenerative proliferation, and ultimately tumors.