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Abstract for TR-033

Bioassay of Tetrachlorvinphos for Possible Carcinogenicity

CASRN: 961-11-5
Chemical Formula: C10H9Cl4O4P
Synonyms/Common Names: 2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate
Report Date: 1978



Tetrachlorvinphos is an organophosphorous pesticide introduced in 1966 byShellDevelopment Company. It is registered for use against various pests of fruits,vegetables, ornamental plants, forest trees, and livestock, and for use onagricultural premises, agricultural equipment, and recreational areas.

A bioassay of technical-gradetetrachlorvinphos for possible carcinogenicity was conducted by administeringthe test chemical in feed to Osborne-Mendelrats and B6C3F1 mice.

Groups of 50 rats of each sex were administered tetrachlorvinphos at one oftwodoses for 80 weeks, then observed for 31 additional weeks. Time-weightedaverage doses were either 4,250 or 8,500 ppm. Matched controls consistedofgroups of 10 untreated rats of each sex; pooled controls, used for statisticalevaluation, consisted of the matched controls combined with 45 untreatedmaleand 45 untreated female rats from similar bioassays of four other testchemicals. All surviving rats were killed at 111 weeks.

Groups of 50 mice of each sex were administered tetrachlorvinphos at one oftwodoses, either 8,000 or 16,000 ppm, for 80 weeks, then observed for 12additional weeks. Matched controls consisted of groups of 10 untreated miceofeach sex; pooled controls, used for statistical evaluation, consisted of thematched controls combined with 40 untreated male and 40 untreated femalemicefrom similar bioassays of four other test chemicals. All surviving mice werekilled at 90-92weeks.

The mean body weights of the treated rats and mice were generally lowerthanthose of the matched controls; however, the mortality rate was affectedadversely by tetrachlorvinphos only in the male rats. Survival of all groupsof rats and mice was adequate for meaningful statistical analyses of theincidence of tumors, except for a matched-control group of female rats forwhich the survival was abnormally low.

In rats, C-celladenoma of the thyroid showed a significant dose-related trend in thefemales,using pooled controls (controls 1/46, low-dose2/50, high-dose7/46, P=0.013), and by direct comparison, an increased incidence in thehigh-dose group (P=0.027). High incidences of C-cellhyperplasia in treated males and females further indicated a chemical-relatedeffect on proliferative lesions of the thyroid. Cortical adenoma of theadrenal also showed a significant dose-relatedtrend in the females, using pooled controls (controls 0/50, low-dose2/49, high-dose5/50,P=0.017), and by direct comparison, an increased incidence in thehigh-dosegroup (P=0.022). Hemangioma of the spleen occurred in male rats at asignificantly higher incidence in the low-dosegroup than in the pooled controls (controls 0/52, low-dose4/48, P=0.049); however, neither the incidence in the high-dosegroup (0/47) nor the test result for dose-relatedtrend was statistically significant.

In mice, hepatocellular carcinoma in males showed a highly significantdose-relatedtrend, using either matched controls (controls 0/9, low-dose36/50, high-dose40/50, P<0.001) or pooled controls (controls 5/49, P<0.001). Thisfinding was supported by direct comparisons of low-and high-dosegroups of males with matched-or pooled-controlgroups, which showed highly significant increases in incidences of the tumorinthe treated groups in all instances (P<0.001). In females, the incidence ofhepatocellular carcinoma was not significant; however, the incidence ofneoplastic nodule was significantly higher in both the low-and high-dosegroups than in the pooled controls (controls 1/48, low-dose14/49, P<0.001; high-dose9/47, P=0.007), using pooled controls for tests for both doses. Because ofthis higher incidence in the low-dosegroup than in the high-dosegroup, there was a significant departure from linear trend (P=0.006).

Granulomatous lesions of the liver were found in high proportions in bothtreated rats and treated mice, but none were found in matched controls.

It is concluded that under the conditions of this bioassay, the administration of technical-gradetetrachlorvinphos in Osborne-Mendel rats was associated with proliferativelesions of the C cells of the thyroid and cortical adenomas of the adrenal infemales. In female B6C3F1 mice, the incidence of neoplastic nodule of theliver was associated with treatment, and in male mice tetrachlorvinphos wascarcinogenic, causing hepatocellular carcinoma of the liver.

Levels of Evidence of Carcinogenicity:
Male Rats: Negative
Female Rats: Positive
Male Mice: Positive
Female Mice: Positive