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

MALATHION 112
3.4.2.3 Dermal Exposure
3. HEALTH EFFECTS
Methoxy 14 C-malathion (5 mg) was applied in 320 µL on a 10-cm 2 area of dorsal skin of male Sprague-
Dawley rats from which hair had been clipped 24 hours before, and 8 hours after the treatment animals
were frozen in dry ice/hexane for autoradiography (Saleh et al. 1997). Electronic autoradiography
showed that 28% of the total recorded radioactivity was at the application site and 29% was distributed
over the remaining skin. Other areas with significant distribution were the small intestine (23%), large
intestine (10%), and liver (5.4%).
3.4.2.4 Other Routes of Exposure
A single dose of 2.5 mg/kg of methoxy 14 C-malathion in 0.3 mL of saline was intravenously administered
to male Sprague-Dawley rats and the whole animal was frozen in a dry ice/hexane for autoradiography
after 30 minutes (Saleh et al. 1997). As a percent of the radioactivity in sagittal sections, the highest
radioactivity was found in the liver (38%), small intestine (21%), kidney (19%), lung (11%), and urinary
tract (7%).
Another whole-body autoradiographic study with ethyl- 14 C malathion injected in the tail vein of male
Wistar rats (0.9 mg/kg) showed a rapid disposition of malathion (Muan and Nafstad 1989). Within 1–
3 minutes of dosing, label was found throughout, but was high in the kidney, liver, lung, heart, skin,
muscles, and blood. Ten minutes after the intravenous dose, the radioactivity in the liver had decreased
and the highest radioactivity was in the renal cortex, the medulla of the kidney, and the intestine. At
12 and 24 hours after dosing, radioactivity was barely detectable.
3.4.3 Metabolism
Knowledge of malathion metabolism comes from analyses of metabolites in the urine of animals and
humans exposed to malathion, in vitro biotransformation studies, and understanding of the acute mode of
action of malathion.
Malathion concurrently encounters three types of metabolic modifications in animals, one oxidative and
another hydrolytic, and the elimination of a methyl group catalyzed by glutathione (GSH) S-transferase
(Figure 3-3). The most important metabolite of the former biotransformation is malaoxon, the ultimate