Initial Submission: 90-day Subacute Oral Toxicity Study with Light Chrome Yellow in Beagle Dogs with Cover Letter dated 10/19/02

摘要

Light Chrome Yellow (C.I. Pigment Yellow; CAS No. 1344-37-2) was evaluated for subchronic toxicity in groups of purebred beagle dogs (4 /sex/group). The test material was administered in the diet of three groups at doses of 2,000, 5,000, and 20,000 ppm for 90 days, 7 days a week. Three positive control groups were fed lead carbonate at the same levels, while two additional groups served as untreated controls. Severe body weight loss was observed in animals fed 20,000 ppm light chrome yellow, while slight suppression of body weight-gain occurred at 5,000 ppm and body weight-gains were comparable to untreated controls at 2,000 ppm light chrome yellow. Lead carbonate produced severe weight-loss at both 20,000 and 5,000 ppm, while at 2,000 ppm, body weight-gain was moderate for females, slight for males. Food intake at 20,000 ppm light chrome yellow was severely depressed in all treated animals, while males only had slight depression in food intake at the 5,000 ppm level. Dogs fed 2,000 ppm light chrome yellow showed food intake levels comparable to untreated controls. Dogs fed 20,000 ppm and 5,000 pmm lead carbonate had severely depressed food intake and at 2,000 ppm, females only showed a slight decrease in food intake. Lethargy, anorexia, dehydration, and emaciation were seen initially at 5,000 and 20,000 ppm light chrome yellow and at all dietary levels of lead carbonate. These signs were followed by hyperirritability, disorientation, motor ataxia, and convulsions. Mortality occurred in dogs fed light chrome yellow at the two highest levels (6/8 at 20,000 ppm and 1/8 at 5,000 ppm), while mortalities occurred in all lead carbonate dose groups (8/8 for 20,000 ppm, 8/8 for 5,000 ppm, 3/8 for 2,000 ppm). Hematologic effects seen in the two highest light chrome yellow dose groups included a decrease in hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin. There was an increase in banded neutrophils. Blood lead concentrations were elevated in all light chrome yellow and positive control (lead carbonate) groups in a dose-related manner, as was lead content of the liver, kidney, bone, and brain tissues. However, positive controls had significantly higher lead concentrations in all tissues. Hypercellularity of bone marrow elements with a significant increase in erythrocyte precursor cells was observed in dogs at all levels of either compound. Histologic findings included focal tubular nephrosis in the kidneys of dogs at all concentrations and a significant increase in erythrocyte precursor cellsat the highest level.