Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks.
Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.
Abdo
K M
KM
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC 27709.
Elwell
M R
MR
Montgomery
C A
CA
Thompson
M B
MB
Thompson
R B
RB
Prejean
J D
JD
D000818:Animals; D001151:Arsenic / Q000378:metabolism*; D020261:Arsenic Poisoning; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D012406:Roxarsone / Q000008:administration & dosage / Q000633:toxicity*; D012737:Sex Factors; D013045:Species Specificity
D012406:Roxarsone; D001151:Arsenic