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

MALATHION 88
3. HEALTH EFFECTS
for females. The combined incidences of liver adenomas and carcinomas in females were 0, 3.6, 3.6, 5.5,
and 10.9%. The incidence of hepatocellular carcinoma was not significantly increased at any dose level
in females. Because the incidence at 868 mg/kg/day was statistically significant by pair wise comparison,
there was a statistical trend, and was outside the range of both the testing facility and NTP (National
Toxicology Program) historical control databases, it was concluded that at 868 mg/kg/day, there was
evidence of carcinogenicity in female rats. A very small number of nasal tumors in males and females
and of oral cavity tumors in females was observed, but it could not be determined whether these tumors
were treatment-related or due to random occurrence. Other tumors that were considered not attributable
to treatment with malathion included thyroid follicular cell tumors and C-cell tumors observed in male
rats, pituitary tumors in females, uterine tumors, testicular tumors, and incidence of mononuclear cell
leukemia.
NCI (1978) also tested B6C3F1 mice in the 80-week dietary study. Mice were administered a diet that
provided approximately 0, 1,490, or 2,980 mg/kg/day of 95% pure malathion. There were no statistically
significant incidences of any tumors in female dosed groups when compared with those of either set of
matched or pooled controls. In males, the combined incidence of hepatocellular carcinoma and neoplastic
nodules showed a significant linear trend when either the matched controls (p=0.041) or pooled controls
(p=0.019) were used. Separately, these incidences were not statistically significantly greater in either
treated group compared with either control. The Fisher Exact test for the comparison between high-dose
(17/49) and pooled control groups had a p value of 0.031. However, the authors indicated that when
time-adjusted analysis was performed, eliminating the male mice that died before 52 weeks on study, the
following incidences resulted: matched controls, 2/9 (22%), pooled controls, 8/48 (17%), low-dose,
7/47 (15%), and high-dose, 17/49 (35%). Neither the Fisher Exact test nor the Cochran-Armitage test of
the time-adjusted incidences are significant (p>0.05) when the matched controls are used. NCI (1978)
concluded that under the conditions of the assay, there was no clear evidence of the association of the
tumor incidence with the administration of malathion in B6C3F1 mice. The NCI (1978) bioassay in
B6C3F1 mice was repeated by Slauter (1994) in a study that included four treatment levels of malathion
(96.4% pure) from 17.4 to 3,448 mg/kg/day in addition to controls. Administration of malathion had no
significant effect on mortality. Both male and female mice showed a treatment-related increase in the
incidence of hepatocellular tumors at the two highest dietary levels of malathion. In males, the percent
incidences of hepatocellular adenomas were 1.9, 7.3, 3.6, 21.8, and 94.1%; the incidences of liver
carcinomas were 0, 10.9, 5.5, 10.9, and 2.0%; the combined incidences were 1.9, 18.2, 9.1, 32.7, and
96.1%. Analysis of these data for males showed that there was a positive dose trend. The corresponding
incidences of hepatocellular adenomas for females were 0, 1.8, 0, 17, and 80.8; the incidences for liver