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

MALATHION 80
3. HEALTH EFFECTS
approximately 3 weeks after cessation of treatment. A similar depression in RBC cholinesterase was
observed, but occurred later. No clinical signs were seen in the volunteers in phase three. The NOAEL
of 0.23 mg/kg/day was used to derive an intermediate-duration oral MRL of 0.02 mg/kg/day.
Many studies have evaluated the effects of oral administration of malathion on neurological end points in
animals. End points examined include activity of plasma, RBC and/or brain cholinesterase as an indicator
of potential neurological effects, neurophysiological effects, occurrence of clinical signs, and
morphological effects. Some representative examples are summarized below.
Effects on Cholinesterase Activity. In rats, single dose studies have reported 37% inhibition for plasma
cholinesterase after a dose of 500 mg/kg malathion (96% pure) (Enan 1983) and 11–48% inhibition in
female rats administered a range of 500–2,000 mg/kg malathion (96.4% pure) (Lamb 1994a), although
the magnitude of the inhibition was not dose-related. Also, no significant inhibition was detected in male
rats with that same dose range (Lamb 1994a). A 34% inhibition was reported for RBC cholinesterase in
female rats given 1,000 mg/kg malathion and 39% with 2,000 mg/kg (Lamb 1994a). Brain cholinesterase
appears much less susceptible, as a 2,000 mg/kg dose of malathion had no significant effect on the
enzyme activity in either male or female rats (Lamb et al. 1994a). However, a 2,000 mg/kg dose of
88% pure malathion decreased brain cholinesterase activity 44%, suggesting a possible role for malathion
impurities. A similar pattern can be seen in intermediate-duration studies in rats. For example, Lamb
(1994b) found that in female rats (effects were similar in males), a dose of 395 mg/kg/day malathion
(96.4% pure) for 90 days caused a 15–30% decrease in plasma cholinesterase activity, a 49–53% decrease
in RBC cholinesterase, and a 12–20% decrease in brain cholinesterase; no significant effects were seen at
4 mg/kg/day. Similar observations were made by Husain et al. (1987) in a 32-day study. In a chronicduration
study, after 24 months of treatment, plasma and RBC were inhibited 12–29% with doses
between 29 and 35 mg/kg/day malathion, whereas brain cholinesterase was only inhibited 1–3% (Daly
1996a); the NOAEL was 2 mg/kg/day for males and 3 mg/kg/day for females. The NOAEL for males
was used to derive a chronic-duration oral MRL of 0.02 mg/kg/day.
Acute studies in mice also suggest that brain cholinesterase is less susceptible than plasma or RBC
cholinesterase to inhibition by malathion, but the differential susceptibility seems to be less marked than
in rats. For example, a single dose of 720 mg/kg of malathion (only dose level tested) diminished the
activities of plasma, RBC, and brain cholinesterase by 41, 47, and 36%, respectively, 6 hours after
treatment (Casale et al. 1983). The corresponding percent inhibition after four doses of 240 mg/kg/day
was 47, 59, and 15% (Casale et al. 1983). The same trend was seen in an 18-month study in mice in