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

MALATHION 104
3. HEALTH EFFECTS
performed without activation, although the breakage rate was fairly slow (Griffin and Hill 1978). Studies
in various Salmonella typhimurium strains dosed with malathion reported no significant differences in
gene mutations both with and without activation (Pednekar et al. 1987; Wong et al. 1989).
Mammalian cells tested in vitro exhibited genotoxicity after malathion dosing both with and without
activation (Table 3-5). Sister chromatid exchanges were observed in human lymphoid cells and
lymphocytes, when assays were conducted with activation (Garry et al. 1990; Sobti et al. 1982). More
studies report results of tests using no activation; even without activation, malathion-associated sister
chromatid exchange occurred in human fetal fibroblasts, lymphoid cells, and lymphocytes, and Chinese
hamster ovary cells (Balaji and Sasikala 1993; Garry et al. 1990; Nicholas et al. 1979; Nishio and Uyeki
1981). Several studies in human lymphocytes report significant levels of chromosome aberrations both
with activation (Garry et al. 1990) and without activation (Balaji and Sasikala 1993; Garry et al. 1990;
Walter et al. 1980). Titenko-Holland et al. (1997) found a significant increase in micronucleated cells in
isolated human lymphocytes, whereas the genotoxic effects in whole blood cultures (although still
significant) were smaller. Pluth et al. (1996, 1998) studied the frequency of mutations in human
lymphocytes and found significantly greater mutations in cells dosed with malathion (without activation).
DNA damage and repair in human lymphocytes was investigated in one study, which showed no
significant effects of malathion (Blasiak et al. 1999). The study did find, however, that two analogues
present in commercial malathion formulations (malaoxon and isomalathion) damaged DNA in a dosedependent
manner. In a more recent study, Blasiak and Stańkowska (2001) suggested that hydrogen
peroxide and reactive oxygen species may be involved in the formation of DNA lesions induced by
malaoxon. Weak evidence of in vitro methylation of DNA bases by malathion was presented by
Wiaderkiewicz et al. (1986). Also, malathion and several impurities were able to alkylate nitrobenzylpyridine,
a synthetic substrate, but none of the impurities was mutagenic in tests in Salmonella (Imamura
and Talcott 1985).
3.4 TOXICOKINETICS
Absorption of ingested malathion is rapid, followed by efficient biotransformation and elimination,
mostly in urine. Dermally applied malathion is readily absorbed, although the fraction absorbed varies
with the site and dose. Little direct information exists for the fate of inhaled malathion. Malathion
requires for its acute toxicity the bioactivation to the ultimate neurotoxic metabolite, malaoxon. It is the
level of this metabolite at the target that determines acute toxicity. Although the liver is the richest source
of the bioactivation enzyme among various mammalian organs, the source organ of malaoxon responsible