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

MALATHION 136
3. HEALTH EFFECTS
are significant differences in the responses between children and adults. A case report of aplastic anemia
in a 12-year-old child following inhalation of malathion fumes after fumigation of a home was described
by Reeves et al. (1981), but this case seems to be unique and there is no evidence that malathion was the
causal agent. A population-based case-control study in California found no significant association
between the use of household pesticides during pregnancy and the risk of pediatric brain tumors (Pogoda
and Preston-Martin 1997).
It is not known whether or not children are more susceptible than adults to malathion toxicity. However,
as previously mentioned, young animals are more susceptible to malathion than older animals. The single
oral LD50 of 95% pure malathion in newborn male Wistar rats was 124.1 mg/kg, whereas in preweaning
(14–16 days old) and adult (3–4 months) rats, LD50 values were 386.8 and 925.4 mg/kg, respectively (Lu
et al. 1965). This difference was also observed for 4-day cumulative LD50 values (Lu et al. 1965).
Similar findings were reported by Brodeur and DuBois (1967) and by Mendoza (1976) and Mendoza and
Shields (1976, 1977) who also observed that the decrease in susceptibility more or less paralleled
increases in the activities of esterases in various tissues. For example, using acetylthiocholine as
substrate, a single dose of 8,000 mg/kg of malathion inhibited brain esterase by 85% in 18-day-old pups,
while in 1-day-old pups, the same degree of inhibition was achieved with a dose of only 500 mg/kg
(Mendoza and Shields 1977). More recent in vitro studies of Mortensen et al. (1998) showed that
acetylcholinesterase activity in the rat brain increases during postnatal development and reaches a
maximum at about 40 days of age, but the Km, substrate profiles, and in vitro sensitivities to selected
organophosphates were not different in young versus adult animals.
There is limited information regarding developmental effects of malathion in humans. A study of
children born to women exposed to malathion via aerial spraying found some positive (and significant)
associations for some anomalies, but the anomalies that occurred more frequently than expected did not
represent a biologically consistent pattern (Grether et al. 1987). No significant association was found
between low birth weight and increasing exposure to malathion. An additional study involving the same
type of exposure found a statistically significant association between incidence of gastrointestinal
anomalies in offspring and exposure to malathion during the second trimester of pregnancy (OR=4.14;
CI=1.01, 16.6) (Thomas et al. 1992). No significant associations were observed for intrauterine growth
retardation or other congenital defects reportable by the California Birth Defects Monitoring Program.
García et al. (1998) compared paternal pesticide exposures between offspring with congenital
malformations and controls. In a subgroup of 14 individuals exposed to malathion, regression analysis
showed no significant associations with outcomes after adjusting for confounding factors. A case of a