Bioassay of 3-Nitropropionic Acid for Possible Carcinogenicity (CAS No. 504-88-1)
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Chemical Formula: C3H5NO4
3-Nitropropionic acid was selected for testing for carcinogenic activity because it was known to demonstrate varying degrees of toxicity in man and animals, and because its use in food preparations and its identification as a contaminant in foods suggested there was a possibility of long-term human exposure.
A bioassay of 3-nitropropionic acid (95% pure) for possible carcinogenicity was conducted by administering the test chemical by gavage to Fischer 344 rats and B6C3F1 mice.
Groups of 50 rats and 50 mice of each sex were administered 3-nitropropionic acid at one of the following doses by gavage 5 days per week. For male rats, the doses were 0.425 or 0.85 mg/animal/day; for females, they were 0.6 or 1.2 mg/animal/day. For both sexes of mice, the doses were 0.375 or 0.75 mg/animal/day. The rats were administered the chemical for 110 weeks and the mice for 104 weeks. The controls consisted of 50 untreated rats and 50 untreated mice of each sex. All surviving rats were killed at 111 weeks and all surviving mice at 104 or 105 weeks.
Mean body weights and mortality of the dosed animals were not markedly affected by 3-nitropropionic acid under the conditions of this bioassay, indicating that the maximum tolerated dose may not have been reached. The various clinical signs observed were common to both dosed and control groups.
In rats, the combination of neoplastic nodule of the liver and hepatocellular carcinoma occurred in the males with a significant dose-related trend (P=0.010) and with a higher incidence (P=0.012) in the high-dose group of animals than in the controls (controls 0/49, low-dose 3/50, high-dose 6/49). All but one of these tumors were neoplastic nodules. In the females, only two neoplastic nodules occurred, one in each of the dosed groups. Biliary hyperplasia occurred at a higher incidence in the dosed males than in the corresponding controls (controls 19/50, low-dose 32/50, high-dose 36/50), but the incidence of this lesion in the dosed females was not increased as compared with controls. There was also a dose-related trend (P=0.033) in the incidence of pancreatic islet-cell adenoma in the male rats (controls 4/49, low-dose 6/50, high-dose 11/50); however, direct comparisons of incidences in the dosed and control groups were not statistically significant. The historical incidence of pancreatic islet-cell adenoma among 100 control Fischer 344 rats at the laboratory was 7/100 (7%). In addition, focal myocardial fibrosis was observed at a higher incidence in dosed rats than among controls (males: controls 1/4, low-dose 17/49, high-dose 24/48; females: controls 2/48, low-dose 9/46, high-dose 9/50).
In mice, each type of neoplasm found in the dosed and control mice has been encountered previously as a spontaneous lesion. No specific tumor was found to occur at a statistically significantly higher incidence among dosed mice than among the respective control groups.
It is concluded that under the conditions of this bioassay, there was an elevated incidence of hepatocellular neoplasms, primarily benign, and of islet-cell adenomas of the pancreas in male Fischer 344 rats receiving 3-nitropropionic acid as compared with controls; however, there was no conclusive evidence that 3-nitropropionic acid was carcinogenic in these animals. The chemical was not carcinogenic in female rats or in male or female B6C3F1 mice.
Synonyms: b-nitropropionic acid; hiptagenic acid
Levels of Evidence of Carcinogenicity:
Report Date: 1978