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

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MALATHION 77<br />

3. HEALTH EFFECTS<br />

serum IgG or IgM levels; however, <strong>malathion</strong> (11.5 mg/kg/day) significantly attenuated the normal<br />

increase in IgG level that occurs after administration of the antigens tetanus toxoid <strong>and</strong> ovalbumin. The<br />

IgM fraction after antigen stimulation was not affected. Antibody titers against tetanus toxoid <strong>and</strong><br />

ovalbumin were significantly decreased in high-dose rats throughout the study <strong>and</strong> in the mid-dose rats<br />

after 22 weeks. The MMI response in ovalbumin immunized rats was significantly decreased in mid- <strong>and</strong><br />

high-dose rats in a time-related manner. Rats exposed to <strong>malathion</strong> <strong>and</strong> immunized with ovalbumin or<br />

tetanus toxoid showed a significant decrease in LMI response especially with the high dose <strong>and</strong> at longer<br />

times with the mid-level dose. Mild lymphoid depletion of the spleen was described in another<br />

intermediate-duration study in rats treated with 130 mg <strong>malathion</strong>/kg/day <strong>for</strong> 6 weeks, whereas marked<br />

depletion occurred at 390 mg/kg/day (Piramanayagam <strong>and</strong> Manohar 2002).<br />

Male Hissar mice received <strong>malathion</strong> (approximately 4.2, 10.5, or 21 mg/kg/day) in the diet <strong>for</strong> 3–<br />

12-weeks (Banerjee et al. 1998). Mice exposed to 10.5 mg/kg/day <strong>malathion</strong> <strong>for</strong> 12 weeks <strong>and</strong><br />

immunized with SRBC showed a significant decrease in relative spleen weight. There was no significant<br />

change in thymus weight. Malathion did not significantly alter levels of IgG or IgM. Exposure to<br />

21 mg/kg/day <strong>for</strong> 3 weeks did not alter primary antibody titer against SRBC, but significantly decreased<br />

the secondary antibody titer against SRBC throughout the experiment. Serum antibody titer to ovalbumin<br />

was also decreased in high-dose mice after 8 weeks of exposure to <strong>malathion</strong>. Exposure to the high-dose<br />

<strong>for</strong> 3 weeks caused a reduction in the PFC response only after secondary immunization, but exposure to<br />

10.5 or 21 mg/kg/day <strong>for</strong> more than 6 weeks caused a dose-related decrease in PFC response after both<br />

primary <strong>and</strong> secondary immunization. Exposure to <strong>malathion</strong> (mid- <strong>and</strong> high-dose) produced a marked<br />

decrease in the MMI response to ovalbumin <strong>and</strong> tetanus toxoid immunization. In male New Zeal<strong>and</strong><br />

rabbits treated by gavage with 0.5 or 2.5 mg/kg/day <strong>malathion</strong> <strong>for</strong> 21 days, there was no significant effect<br />

on serum IgG or IgM levels. High-dose rabbits showed a significant decrease in antibody titer to<br />

ovalbumin after 7 <strong>and</strong> 11 weeks of primary immunization (5 <strong>and</strong> 9 weeks after secondary immunization,<br />

or 3 <strong>and</strong> 7 weeks after tertiary immunization) with the antigen. No effect was seen with the low-dose.<br />

Rabbits exposed to <strong>malathion</strong> <strong>for</strong> 15 weeks <strong>and</strong> immunized with ovalbumin or tetanus toxoid showed a<br />

significant decrease in LMI response after 7 weeks of antigen.<br />

The effects of a commercial <strong>malathion</strong> <strong>for</strong>mulation (50% <strong>malathion</strong>) on the immune system of female<br />

SJL/J mice was investigated by Johnson et al. (2002). The mice were gavaged with 0, 0.018, 7.2, or<br />

180 mg of <strong>malathion</strong>/kg on alternate days <strong>for</strong> 28 days. Malathion did not stimulate cholinergic activity as<br />

monitored by the lack of significant change in brain acetylcholinesterase activity. The only significant<br />

effect observed was a significant enhancement of the primary IgM response to SRBCs when the response

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