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

MALATHION 75
3. HEALTH EFFECTS
studies, particularly in rats and mice. When assessing effects on the immune system, it became apparent
that a distinction had to be made between a direct action of the pesticide on any component of the
immune system and responses that may be mediated indirectly by the pesticide-induced cholinergic
stimulation and resulting stress. An early study by Casale et al. (1983) sought to investigate this specific
issue. Administration of a single gavage dose of 720 mg/kg of malathion (95% pure) to C57BL/6N mice
significantly suppressed the primary IgM response following immunization with sheep red blood cells
(SRBC). This dose of malathion, which caused moderate to severe cholinergic signs, also decreased
relative spleen weight and the number of viable cells per spleen. When malathion was given in four daily
doses of 240 mg/kg/day, a regimen that did not produce cholinergic signs, it did not suppress the primary
IgG response to SRBC. Furthermore, results of experiments with a cholinomimetic agent suggested that
cholinergic stimulation played a major role in malathion-induced suppression of the primary immune
response (Casale et al. 1983).
It is interesting that other studies that used almost the same dose level (715 mg/kg) of malathion
(>99% pure) in the same strain of mice did not observe any clinical signs of cholinergic poisoning or
reduction of total acetylcholinesterase activity in plasma, but still observed alterations in some immune
parameters (Rodgers et al. 1986). In this study, the single 715 mg/kg dose of malathion had no effect on
the generation of a cytotoxic T lymphocyte (CTL) response to alloantigen by splenocytes, increased the
ability of splenocytes to generate a response to SRBC 5 days after malathion treatment, significantly
increased the proliferative response to concanavalin A (Con A) and lipopolysacchraride (LPS), and did
not alter thymic lymphocyte number. In contrast, 14 days of daily treatments with 143 mg/kg of
malathion had no effect on the response to SRBC or the mitogenic responses to Con A or LPS, but
significantly decreased thymic lymphocyte number. This set of experiments pointed out the differences
between results from single and repeated dosing. Further studies by Rodgers and coworkers showed that
in vitro exposure of splenocytes to malathion resulted in a suppression of the proliferative response to
Con A and LPS (Rodgers and Ellefson 1990). However, treatment with malathion activated with a crude
liver system capable of regenerating reduced nicotinamide adenine dinucleotide phosphate (NADPH)
resulted in an unchanged proliferative response. Rodgers and Ellefson (1990) also showed that
administration of single doses of 715 or 900 mg/kg malathion to mice significantly elevated respiratory
burst activity, a measure of macrophage activation of peritoneal leukocytes following stimulation with
12-phorbol 13-myristate acetate (PMA). However, no such elevation was evident after treatment of the
cells in vitro, unless malathion had been metabolically activated with the NADPH-regenerating system.
Rodgers and Ellefson (1990) concluded that in order for the effects of a compound on the immune
response to be examined following in vitro exposure, the applicability of this type of exposure to that