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

MALATHION 86
3. HEALTH EFFECTS
Teratogenicity. Acute studies in rats found no teratogenic effects of malathion after gavage
administration of doses of 300 mg/kg/day on Gd 6–15 (Khera et al. 1978), 500 mg/kg/day on Gd 6, 10,
and 14 (Prabhakaran et al. 1993), or 800 mg/kg/day on Gd 6–15 (Lochry 1989). No teratogenic effects
were seen in rabbits given up to 100 mg/kg/day malathion on Gd 6–18 (Siglin 1985). No teratogenic
effects were observed in rats administered 50 mg/kg/day malathion for 3 months prior to mating and
during gestation (Lechner and Abdel-Rahman 1984) or in the 2-generation study by Schroeder (1990)
summarized above.
Other Effects. Administration of technical malathion (98% pure) by gavage (0, 138, 276, or 827 mg/kg)
from Gd 6 through 13 to Sprague-Dawley rats resulted in inhibition of brain cholinesterase in a dosedependent
manner both in dams and pups on postnatal day 21 (Mathews and Devi 1994). The extent of
inhibition was similar in dams and pups and was approximately 14, 37, and 47% in the low-, mid-, and
high-dose groups, respectively. Also, treatment with malathion significantly increased the activities of
carboxylesterase, glutathione-S-transferase, and cytochrome P-450 content in the liver from both dams
and pups. Malathion also reduced the glutathione content and the activities of glutathione reductase and
glutathione peroxidase and increased lipid peroxide content in the liver from both dams and pups. A
study in rabbits administered 126 mg/kg/day malathion on Gd 28–30 and killed after the last dose
reported a decrease between 54 and 79% in fetal plasma cholinesterase activity and between 60 and 66%
in fetal brain cholinesterase (Machin and McBride 1989b). An additional study in mice administered
30 or 100 mg/kg malathion (98% pure) by gavage in corn oil from day 1 to day 14 of lactation (Ld) found
that glutathione-S-transferase activity was increased in the liver from male pups from both treated groups
and in high-dose female pups (Chhabra et al. 1993). Glutathione reductase activity was increased only in
high-dose male pups. Glutathione peroxidase activity was significantly increased (dose-related) in both
dose groups of pups. These changes in pups’ liver followed the same trend as in maternal liver (see
Hepatic Effects) except for glutathione reductase activity.
Based on the available information, malathion is not a developmental toxicant when administered at doses
that do not cause maternal toxicity.
The highest NOAEL values and all reliable LOAEL values for developmental effects in each species and
duration category are recorded in Table 3-2 and plotted in Figure 3-2.