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

MALATHION 89
3. HEALTH EFFECTS
carcinomas were 1.8, 0, 3.7, 1.9, and 3.8%; and the combined incidences were 1.8, 1.8, 3.7, 18.9, and
84.6%. As with males, there was a positive dose trend. Examination of the nasal tissues showed no
evidence of carcinogenic response. It was concluded that there was evidence of carcinogenicity in both
sexes at the two highest doses tested, 1,476 and 2,978 mg/kg/day for males and 1,707 and
3,448 mg/kg/day for females.
The active metabolite of malathion, malaoxon, also has been tested for carcinogenicity in rats and mice.
In the NCI (1979b) study, male and female Fischer-344 rats were administered malaoxon in the diet
(approximately 0, 41, and 82 mg/kg/day) and to male and female B6C3F1 mice (approximately 0, 91, and
182 mg/kg/day) for 103 weeks. The only possibly carcinogenic response seen was the incidence of C-cell
adenomas and carcinomas of the thyroid among treated female rats. However, comparison of the
incidences in treated rats with historical controls precluded relating the incidence of the tumors seen in the
study to administration of malaoxon. NCI (1979b) concluded that under the conditions of the study,
malaoxon was not carcinogenic to Fischer-344 rats or B6C3F1 mice. A more recent study in male and
female Fischer-344 rats administered one of three dietary levels of malaoxon in the range of 1–
141 mg/kg/day for 103 weeks found no treatment-related neoplasia (Daly 1996b).
In response to increased concern about the widespread use of malathion in agriculture, the NTP, in
consultation and agreement with NCI, reevaluated the histopathology of the NCI studies on malathion in
Osborne-Mendel rats (NCI 1978) and Fischer-344 rats (NCI 1979a), and of malaoxon on Fischer-344 rats
(NCI 1979b). The results of the reevaluation confirmed the original conclusions of NCI regarding the
lack of carcinogenicity of malathion in rats (Huff et al. 1985), and slightly modified the original
interpretation for the C-cell neoplasms of the thyroid in the malaoxon study by concluding that there was
equivocal evidence of carcinogenicity for male and female Fischer-344 rats (Huff et al. 1985).
CEL values from each reliable study in each species and duration category are recorded in Table 3-2 and
plotted in Figure 3-2.
3.2.3 Dermal Exposure
As stated in the introduction to Section 3.2.1, Inhalation Exposure, occupational exposure to malathion
involves mostly exposure by the inhalation and dermal routes, but the contribution of each specific route
is impossible to ascertain, especially if it is not known whether or not workers were using protective
clothing or masks. This section includes summaries of studies in which direct skin contact was explicitly