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

MALATHION 133
3. HEALTH EFFECTS
treatment with malathion and there were no histopathologic changes in the thyroid in the treated animals
(Ozmen and Akay 1993). The adrenal congestion reported in rats treated with malathion may be a
nonspecific effect since hyperemia and petechial hemorrhages in some organs is not an uncommon
finding following organophosphate intoxication. No such congestion was seen in the chronic studies with
much larger doses (see below).
Chronic-duration studies in rats have not observed treatment-related gross or microscopic lesions in
endocrine glands or reproductive organs (NCI 1978, 1979a), although increased relative and absolute
thyroid and parathyroid weights were seen in female rats administered 415 mg/kg/day of malathion
(97.1% pure) in the diet for 2 years (Daly 1996a); the NOAEL was 35 mg/kg/day. Similar lack of gross
or microscopic alterations in endocrine organs were reported in a chronic study in mice, but an increased
incidence of cystic endometrial hyperplasia was seen in mice administered 1,490 mg/kg/day malathion
(95% pure) for 80 weeks (NCI 1978).
Studies in male rats have demonstrated that acute exposure to malathion (40 mg/kg/day) can produce
transient testicular alterations such as a reduction in the number of Sertoli and Leydig cells (Krause 1977;
Krause et al. 1976). A higher dose of 163 mg/kg/day of malathion (unspecified purity) damaged the
seminiferous tubules and produced an abnormal pattern of Sertoli cells (Ojha et al. 1992). A considerably
higher gavage dose of 1,950 mg/kg of malathion (95% pure) given once to 8-week-old male Wistar rats
reduced the number of germinal layers and produced degeneration and necrosis of gonocytes in the
seminiferous tubules during the first 3 days after dosing and it also caused systemic toxicity
(Piramanayagam et al. 1996). Testicular effects were also reported in a 12-week study (Balasubramnian
et al. 1987b). In general, these studies suffer from incomplete reporting of the results such that no firm
conclusions can be drawn. Some studies have observed reduced number of implants in female rats at
doses (500 mg/kg/day on Gd 6, 10, and 14) that also caused maternal toxicity (Prabhakaran et al. 1993),
but no such effects were observed at even higher doses in another study in rats (800 mg/kg/day on Gd 6–
15) (Lochry 1989). No effects on implantation were reported in rabbits treated with up to 100 mg/kg/day
(Gd 6–18), but 50 mg/kg/day increased the mean number and percent resorptions (Siglin 1985).
Exposure of rats to 50 mg/kg/day malathion for periods that included mating and gestation had no
significant effects on reproductive parameters (Lechner and Abdel-Rahman 1984), and no significant
effects on reproductive performance or fertility indices were seen in a 2-generation study in rats
(Schroeder 1990). Dermal exposure of rabbits to up to 1,000 mg/kg/day of malathion for 21 days did not
induce significant changes in weight or gross or microscopical alterations in the ovaries, testes, or
epididymis (Moreno 1989).