Chemical Formula: C10 H19 O6 PS2
Malathion is an organophosphorus insecticide and acaricide first synthesized in the United States in 1952. Malathion primarily affects the nervous system by inhibition of cholinesterase activity and subsequent accumulation of acetylcholine. However, it has a low mammalian toxicity. Malathion is approved for a wide variety of uses as an insecticide and acaricide on field crops, fruits, nut trees, vegetables, livestock, agricultural premises, and land. Tolerances for residues of malathion have been established on many of these products.
A bioassay of technical-grade malathion for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered malathion at one of two doses for 80 weeks, then observed for 33 weeks. Time-weighted average doses were 4,700 or 8,150 ppm. Matched controls consisted of groups of 15 untreated rats of each sex; pooled controls consisted of the matched controls combined with 40 untreated male and 40 untreated female rats from similar bioassays of four other test chemicals. All surviving rats were killed at 108-113 weeks.
Groups of 50 mice of each sex were administered malathion at one of two doses, either 8,000 or 16,000 ppm, for 80 weeks, then observed for 14 or 15 weeks. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls consisted of the matched controls combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 94 or 95 weeks.
Mortality in either rats or mice was not significantly related to the administration of malathion. Sufficient numbers of animals were at risk in the dosed and control groups of rats and mice of each sex for development of late-appearing tumors.
In female rats, three follicular-cell carcinomas and one follicular-cell adenoma of the thyroid occurred in the high-dose group, and three follicular-cell hyperplasias occurred in the low-dose group. The incidence of these tumors showed a statistically significant (P=0.026) dose-related trend; however, the results of the Fisher exact test for direct comparison between the dosed and control groups were not significant. More dosed males than dosed females had either tumors or hyperplasia of the follicular cells of the thyroid; however, because of the higher incidence of tumors among the male controls, none of the results of the statistical tests were significant. These thyroid tumors were notconsidered to be associated with the administration of malathion.
In male mice, hepatocellular carcinoma occurred at the following incidences: matched controls 2/10, pooled controls 5/49, low-dose 7/48, high-dose 11/49. In addition, neoplastic nodules occurred in 3/49 pooled-control and 6/49 high-dose animals. When the combined incidence of these neoplasms in the dosed animals was compared with that of the pooled controls, the dose-related trend was P=0.019 and the direct comparison of the high-dose group with the control group was P=0.031. Thus, none of the direct comparisons of dosed groups with controls were significant using the Bonferroni criteria. In addition, the historical controls from this laboratory had several control groups with incidences of 35-40% hepatocellular carcinoma, rates which are comparable with the incidence of this tumor in the dosed male mice of the present study. Thus, these liver tumors are not considered to be associated with the administration of malathion. The incidences of liver tumors in dosed females were not statistically significant when compared with that in control animals.
It is concluded that under the conditions of this bioassay, there was no clear evidence of the association of the tumor incidence with the administration of malathion to Osborne-Mendel rats or B6C3F1 mice.
Note: Malathion was subsequently studied by administration in feed to F344 rats (See TR-192, reported 1979).
Report Date: 1978