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

MALATHION 76
3. HEALTH EFFECTS
class of compound and the necessity for a metabolism system should be determined for each parameter
assessed.
The mechanism of malathion-induced macrophage activation has been examined in more detail in recent
studies. Using a wide range of doses, Rodgers and Ellefson (1992) observed that peritoneal cells from
mice treated with a single dose of 0.25 mg/kg of malathion exhibited an increased respiratory burst
activity, as measured by hydrogen peroxide production following stimulation with PMA; there was also
an increase in the percentage of degranulated mast cells. The authors suggested that malathion-induced
degranulation of mast cells and subsequent release of mast cell inflammatory mediators such as histamine
(Rodgers and Xiong 1997b) or arachidonic acid metabolites and tumor necrosis factor (Rodgers and
Xiong 1997a) may increase macrophage function. Increased serum levels of histamine occurred in both
rats and mice after administration of malathion, and the increase was maximum 4 hours after a dose of
10 mg/kg (Rodgers and Xiong 1997b). In rats, lower and higher doses produced smaller increases,
whereas in mice, a significant but smaller increase occurred 8 hours after dosing with 700 mg/kg
malathion. Degranulation of mast cells associated with the small intestine was seen in mice after
administration of as low as 0.1 mg/kg/day of malathion for 14 days (Rodgers and Xiong 1997d) or
90 days (Rodgers and Xiong 1997c), but differences in tissue sensitivities were apparent. Rodgers and
Ellefson (1992) speculated that degranulation of mast cells by malathion may be accomplished by
inhibition of an esterase on the surface of the mast cell. Administration of malathion (300 mg/kg) to mast
cell-deficient mice reduced macrophage function; however, exposure of mast cell-deficient mice
reconstituted with bone marrow-derived mast cells from wild-type mice resulted in enhanced macrophage
function and the production of circulating IgM, but not IgG antibodies to SRBC on days 3 and 5 after
immunization (Rodgers et al. 1996). This suggested that the presence of mast cells is necessary for the
increase in macrophage function and humoral immunity observed after the administration of malathion.
Intermediate-duration studies by Banerjee et al. (1998) provide comparative information on the effects of
non-cholinergic doses of malathion on the humoral and cell-mediated immune responses in rats, mice,
and rabbits. Humoral immune responses were assessed by measuring IgM and IgG concentrations,
antibody titer against antigens (SRBC, tetanus toxoid, ovalbumin), and splenic plaque forming cells
(PFC). The cell-mediated immune (CMI) response was studied by using the leucocyte migration
inhibition (LMI) and macrophage migration inhibition (MMI) tests. Male Wistar rats were treated with
malathion (>99% pure) in the diet (approximately 2.3, 5.8, or 11.5 mg/kg/day) for 8–22 weeks. There
was no effect on thymus weight, but relative spleen weight was significantly decreased at 22 weeks in the
mid- and high-dose rats that were immunized with ovalbumin or tetanus toxoid. There was no effect on