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

MALATHION 155
3. HEALTH EFFECTS
Malathion has been tested in oral bioassays conducted in rats (two strains) (Daly 1996a; NCI 1978,
1979a) and mice (NCI 1978; Slauter 1994). The metabolite, malaoxon, also has been tested in rats (Daly
1996b; NCI 1979b) and mice (NCI 1979b). No clear evidence of carcinogenicity for malathion was
found in the bioassays conducted by NCI (NCI 1978, 1979a), but there was evidence of liver
carcinogenicity in female Fischer-344 rats in the Daly (1996a) study and in male and female B3C6F1
mice in the Slauter (1994) study. In the two positive studies, evidence of carcinogenicity occurred at
doses that were considered excessive (EPA 2000a, 2000b). There was no evidence of carcinogenicity for
malaoxon in rats or mice (Daly 1996b; NCI 1979b), but upon reevaluation of the NCI (1979b) study, NTP
concluded that there was equivocal evidence of carcinogenicity for male and female Fischer-344 rats
based on reinterpretation of C-cell neoplasms of the thyroid (Huff et al. 1985). Further bioassays do not
seem necessary.
A recent review of the literature on pesticides and cancer by Zahm et al. (1997) identified several areas
where data gaps exist. First, improvements in exposure assessment in epidemiologic studies are needed.
Also, there is a need for validity and reliability studies of recall of pesticide use both for occupationally
and nonoccupationally exposed populations. In addition, efforts should continue to try to gain access to
information on inert ingredients of pesticide formulations since inert components are not necessarily
biologically inert. Another data gap identified is the lack of studies on migrant and seasonal farm workers
who often start exposure at an early age. The mechanism of malathion-induced carcinogenicity in
animals is not known, but it does not appear to involve mutagenicity. Additional studies investigating
noncholinergic mechanism of malathion toxicity and how these may potentially by involved in malathion
carcinogenicity would be valuable.
Genotoxicity. The genotoxicity of malathion has been investigated in many studies. Of four studies
that monitored humans exposed to malathion occupationally or by intentional ingestion of malathion
formulations, two found increased chromosomal aberrations in peripheral lymphocytes and micronuclei
(Singaravelu et al. 1998; van Bao et al. 1974), whereas the remaining two found no evidence of
micronuclei or chromosomal aberrations (Titenko-Holland et al. 1997; Windham et al. 1998). The
majority of the studies in animals were conducted in mice and showed that malathion has the capacity to
produce chromosomal changes, including chromosomal aberrations and micronuclei in bone marrow
(Abraham et al. 1997; Amer et al. 2002; Dulout et al. 1982, 1983; Giri et al. 2002; Kumar et al. 1995).
However, a negative effect for chromosomal aberrations in mouse bone marrow was reported by
Degraeve and Moutschen (1984) and a weak positive effect was reported by Dzwonkowska and Hubner
(1986) in hamster bone marrow. Effects on germ cells have been mixed. No chromosomal aberrations