toxicological profile for malathion - Agency for Toxic Substances and ...

MALATHION 87
3.2.2.7 Cancer
3. HEALTH EFFECTS
No studies were located regarding cancer in humans following oral exposure to malathion, but several
bioassays have been conducted to examine the carcinogenicity of malathion in animals.
NCI (1978) did an 80-week study in Osborne-Mendel rats administered malathion (95% pure) in the diet
at approximate doses of 0, 359, and 622 mg/kg/day. In addition to a matched controls group, the study
used pooled controls, which included controls used in assays for other pesticides. Most tissues and
organs were examined microscopically from animals that died early, and at the end of the study. Higher
incidences of proliferative lesions in the thyroids were observed in treated rats compared with matched
controls. No statistically dose-related trends of differences from controls (either matched or pooled) were
found for C-cell (parafollicular cells) or follicular cell adenomas or carcinomas in male rats. In females,
the combined incidence of follicular cell adenoma and carcinoma in the high-dose group was 4/49 (8%)
versus none in either set of controls. The Cochran-Armitage test indicated a significant positive linear
trend (p=0.026) in incidence using pooled controls, but the Fisher Exact test was not significant. No other
tumor appeared in the rats at any site in statistically significant incidences. It was concluded that under
the conditions of the assay, there was no evidence of carcinogenicity attributable to malathion in Osborne-
Mendel rats. A study was also conducted in Fischer-344 rats administered malathion (95% pure) in the
diet at approximate dose levels of 0, 166, or 332 mg/kg/day for 103 weeks (NCI 1979a). Administration
of malathion resulted in a variety of neoplasms in both control and dosed animals, with the exception of
adrenal pheochromocytomas in male rats, which not believed to be compound-related. The incidences of
adrenal pheochromocytomas were 2/49 (2%), 11/48 (23%), and 6/49 (12%) in controls, low-dose, and
high-dose rats, respectively. The result of the Fisher Exact test for the low-dose group relative to the
controls was significant (p=0.006), but the high-dose group was not. The result of the Cochran-Armitage
test also was not significant. A lower incidence of leukemia and of carcinomas of the pituitary was
observed in male rats, which according to the authors, may have accounted for the shorter survival of the
dosed animals compared to controls. The conclusion was that under the conditions of the study,
malathion was not carcinogenic for Fischer-344 rats of either sex, but females may have not received the
maximum tolerated dose.
More recent information is provided by a study by Daly (1996a), also in Fischer-344 rats, that used a
wider dose range. In this 2-year study, four dose levels of 2–868 mg/kg/day were used in addition to
controls. Administration of malathion (97.1% pure) significantly increased mortality in males at
359 mg/kg/day and in both sexes at the highest dose levels, 739 mg/kg/day for males and 868 mg/kg/day