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

MALATHION 78
3. HEALTH EFFECTS
was expressed per viable spleen cells or per spleen; the increases appeared similar with the three doses
tested and no dose-response was apparent. Malathion did not affect splenic cellularity or the viability of
the splenocytes. Furthermore, lymphocyte blastogenesis was not affected and there was no significant
effect on Con A- or phytohemagglutinin-induced T-lymphocyte proliferation or LPS-induced
B-lymphocyte proliferation.
Chronic-duration studies in rats administered up to approximately 622 mg/kg/day of malathion for
80 weeks (NCI 1978) or 332 mg/kg/day for 103 weeks (NCI 1979a) or in mice given up to approximately
2,980 mg/kg/day for 80 weeks (NCI 1978) reported no significant treatment-related alterations in the
gross or microscopical appearance of lymph nodes or the spleen; no functional immunological end points
were evaluated in these studies.
Overall, the findings in animal studies suggest that malathion has at least a modulatory effect on some
immune parameters and that this can occur at relatively low doses. However, as Rodgers and Ellefson
(1992) stated, the physiological significance of alterations in respiratory burst and mast cell degranulation
of the magnitude observed are unknown. Nevertheless, these findings could explain the symptoms of
rashes and irritation of mucous membranes reported by individuals following exposure to malathion and
suggest that these responses may be systemic in nature rather than localized. Results from animal studies
also warned about extrapolating data obtained from in vitro studies to in vivo situations (Rodgers and
Ellefson 1990) and from one animal species to another (Banerjee et al. 1998).
3.2.2.4 Neurological Effects
Several reports of accidental or intentional ingestion of malathion formulations, some with fatal
consequences, were located. In all cases, the patients showed many of the characteristic signs of
organophosphate poisoning (i.e., excessive salivation, lacrimation, abdominal cramps and diarrhea,
pupillary constriction, nausea, respiratory distress, fasciculations). Cholinesterase levels were measured
in many of these cases. Both RBC cholinesterase and plasma cholinesterase activity levels ranged from
undetectable to 70–90% inhibition shortly after poisoning (Choi et al. 1998; Dive et al. 1994; Jušić and
Milić 1978; Lee and Tai 2001; Matsukawa et al. 1997; Namba et al. 1970; Sudakin et al. 2000). Doses of
malathion could be estimated to have been between 214 and 2,000 mg/kg, but dose-response relationships
could not be established with this set of studies. Treatment with cholinesterase-reactivating agents
reversed the enzyme inhibition to various degrees in some but not all cases.