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

MALATHION 71
3. HEALTH EFFECTS
hormones, were measured in 22 patients. Of eight hormones, adrenocorticotropic hormone (ACTH),
cortisol, and prolactin (PRL) levels were significantly higher shortly after poisoning than 3 days after
appropriate treatment had been provided; blood levels of all three hormones had decreased by about 50%
3 days after treatment. Follicle-stimulating hormone (FSH) levels were slightly, but not significantly
lower before treatment (by 20.5%) than after treatment. In addition, seven patients showed transient
lowering in thyroid hormone levels (low fT3, fT4) and thyroid-stimulating hormone (TSH) before
treatment. The toxicological significance of these findings is unknown.
Relatively little information is available on the endocrine effects of malathion after oral exposure in
animals. Increased pituitary gland weight and serum prolactin levels and decrease pituitary levels of
prolactin were reported in male Wistar rats administered approximately 225 mg/kg/day of malathion for
6 days (Simionescu et al. 1977). An intermediate-duration study found congestion in the zona reticularis
of the adrenal glands from rats treated by gavage with 10 mg/kg/day of malathion (94% pure) for
15 weeks (Ozmen and Akay 1993). Serum cortisol and aldosterone levels were increased at
10 mg/kg/day, but not at 100 mg/kg/day. Serum T4, T3, testosterone, and 17β-estradiol levels were not
significantly affected by treatment with malathion and there were no histopathologic changes in the
thyroid in the treated animals (Ozmen and Akay 1993).
A chronic-duration study in Osborne-Mendel rats did not reveal gross or microscopical lesions in the
adrenal glands, thyroid, or parathyroid from rats administered 0, 359, or 622 mg/kg/day malathion
(95% pure) in the diet for 80 weeks (NCI 1978). However, cysts of the pituitary were seen more often in
treated males (0% in controls, 28% incidence in low-dose, and 22% in the high-dose) than in controls.
Since only one high-dose female showed this lesion, the authors (NCI 1978) did not consider the lesion
treatment-related. In the bioassay with Fischer-344 rats, there were no significant treatment-related
lesions in endocrine organs during treatment with up to 332 mg/kg/day malathion (95% pure) in the diet
for 103 weeks (NCI 1979a). Similar results were obtained in B6C3F1 mice administered up to
2,980 mg/kg/day malathion in the diet for 80 weeks (NCI 1978). Increased relative and absolute thyroid
and parathyroid weights were seen in female Fischer-344 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.
The limited information available does not suggest that endocrine organs are direct targets for malathion
toxicity. The adrenal congestion reported by Ozmen and Akay (1993) in rats treated with 10 mg/kg/day
malathion may be a nonspecific effect since hyperemia and petechial hemorrhages in some organs is not