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

MALATHION 137
3. HEALTH EFFECTS
woman who used a hair lotion containing 0.5% malathion during the 11 th and 12 th weeks of pregnancy
and gave birth to a severely malformed child was described by Lindhout and Hageman (1987). The
malformations resembled amyoplasia congenita, a condition in which skeletal muscle is almost
completely replaced by fatty tissue. Although the causal link is difficult to establish, the mother and
father were healthy and had two other children who were healthy. Studies in animals suggest that
malathion is not a developmental toxicant at doses that do not induce maternal toxicity (Khera et al. 1978;
Lochry 1989; Machin and McBride 1989a; Schroeder 1990; Siglin 1985). However, a study by Kalow
and Marton (1961) found increased neonatal mortality (days 7 and 21 after birth) in rats following
maternal exposure to 240 mg/kg/day malathion (95% pure) in the diet for at least 5 months starting before
mating, but no information was provided regarding maternal effects.
There is no information regarding possible transgenerational effects of malathion in humans. A study in
male mice treated with 300 mg/kg of malathion (>99% pure) intraperitoneally did not observe an increase
in chromosome aberrations in spermatogonia (Degraeve and Moutschen 1984). In the same study, the
investigators also conducted a dominant lethal mutation assay and found that the frequency of pre- and
postimplantation fetal lethality was not significantly increased over the control level. Salvadori et al.
(1988) treated male mice dermally with multiple doses of 500 mg/kg/day of commercial malathion
(unspecified purity) and found a significant increase in chromosome aberrations in primary
spermatocytes. Malathion (250 mg/kg/day) also produced an increase in univalent chromosomes (lacking
centromeres). However, as mentioned in Section 3.3, the significance of results of Salvadori et al. (1988)
has been questioned by some investigators.
There is no information regarding the pharmacokinetics of malathion in children or regarding the
nutritional factors that may influence the absorption of malathion. A PBPK simulation of exposure to
malathion during an urban pesticide application estimated that the highest dermally absorbed dose for
adults and children (14–34 kg) were 1.3 and 0.4 mg, respectively (Dong et al. 1994). Analysis of urine
samples from humans exposed to malathion suggests the involvement mainly of phase I metabolic
enzymes in the biotransformation and elimination of malathion. The specific P-450 isozymes involved in
phase I metabolism are not known, and thus, no conclusions can be drawn based on general differences in
isozymes activities between adults and children. The hydrolysis of malathion/malaoxon to the
biologically-inactive α-monoacids is catalyzed by carboxylesterases and at least in rats, the activities of
these enzymes in various tissues increase postnatally, which explains in part the greater susceptibility of
young animals to the acute toxicity of malathion compared to older ones (Brodeur and DuBois 1967; Lu
et al. 1965; Mendoza 1976; Mendoza and Shields 1976, 1977). No information was located regarding