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

MALATHION 157
3. HEALTH EFFECTS
No information was available regarding reproductive effects in animals following inhalation exposure to
malathion. Acute studies in male animals, mainly rats, administered malathion orally have reported
transient alterations in spermatogenesis and alterations in the seminiferous tubule epithelium (Krausse
1977; Krausse et al. 1976; Ojha et al. 1992; Piramanayagam et al. 1996), but none of these studies
assessed reproductive function. A 12-week gavage study also reported reversible testicular alterations in
rats given 45 mg/kg/day malathion (Balasubramanian et al. 1987b), but no morphological alterations were
seen in the reproductive organs from male rats or mice in chronic bioassays (NCI 1978, 1979a). An
intermediate-duration dermal study in male and female rabbits did not observe any significant gross or
microscopic alterations in the reproductive organs following application of up to 1,000 mg/kg/day of
malathion 6 hours/day, 5 days/week for 3 weeks (Moreno 1989). Malathion was not a reproductive
toxicant when administered to females at doses that did not induce maternal toxicity (Lechner and Abdel-
Rahman 1984; Mathews and Devi 1994; Prabhakaran et al. 1993; Siglin 1985). A 2-generation study in
rats found no significant effects on reproductive performance, fertility indices, and gestation length
(Schroeder 1990). The only significant finding in a chronic bioassay was an increased incidence of cystic
endometrial hyperplasia in mice treated with approximately 1,490 mg/kg/day of malathion for 80 weeks
(NCI 1978). The overall evidence in animals suggests that malathion is not a reproductive toxicant, but
the less than optimal quality of some studies do not allow drawing a firm conclusion. The issue of
testicular toxicity should be further explored in studies in animals exposed at various ages including
exposure in utero and later tested for reproductive performance. Also, studies examining standard semen
and sperm parameters in adult animals would provide valuable information. These studies should be
conducted by the oral route of exposure since this route is the most relevant for exposure of the general
population and there is no evidence suggesting that the toxicity of malathion is route-specific.
Developmental Toxicity. Data on developmental effects of malathion in humans are limited. Two
studies conducted in California after aerial spraying of malathion did not find consistent or significant
developmental effects in the offspring from women who were pregnant during the spraying (Grether et al.
1987; Thomas et al. 1992). Some positive associations were found in the former study between exposure
and some anomalies, but no biologically consistent pattern was observed. Thomas et al. (1992) found a
significant association for gastrointestinal anomalies and second trimester exposure, but the
gastrointestinal tract is completely developed by the second trimester. An additional study of paternal
exposure to malathion found no significant association between exposure and congenital malformations
(García et al. 1998). No information was found regarding developmental effects in humans following
oral exposure to malathion. The only data after dermal exposure are from Lindhout and Hageman (1987),