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

MALATHION 17
2. RELEVANCE TO PUBLIC HEALTH
muscarinic receptors results in ocular effects (miosis, blurred vision), gastrointestinal effects (nausea,
vomiting, abdominal cramps, diarrhea), respiratory effects (excessive bronchial secretions, chest
tightness, bronchoconstriction), cardiovascular effects (bradycardia, decreased blood pressure), effects on
exocrine glands (increased salivation, lacrimation), and effects on the bladder (incontinence). At the level
of parasympathetic and sympathetic autonomic nicotinic receptors, acetylcholine will induce tachycardia
and increase blood pressure. At the neuromuscular junction, excess acetylcholine will induce muscle
fasciculations, cramps, diminished tendon reflexes, muscle weakness in peripheral and respiratory
muscles, ataxia, and paralysis. Finally, overstimulation of brain cholinergic receptors will lead to
drowsiness, lethargy, fatigue, headache, generalized weakness, dyspnea, convulsions, and cyanosis.
The signs and symptoms described above have been documented in almost all of the cases of accidental
or intentional ingestion of high amounts of malathion and in cases of dermal intoxication. Lethal doses
can be estimated from case reports to have been between 350 and 2,000 mg/kg. These dose levels usually
inhibited plasma and RBC cholinesterase activities to levels ranging from undetectable to 10–30% of
normal. Studies of workers exposed to a combination of pesticides, including malathion, have shown
decreases between 10 and 50% in both plasma and RBC cholinesterase activities. In general, plasma
cholinesterase activity can be inhibited by 20–25% without significant physiological consequences.
Studies also have shown that the rate of decrease of RBC cholinesterase correlates better with appearance
of symptoms than the absolute value reached after exposure. It was found that plasma cholinesterase
activity in workers who exhibited cholinergic symptoms and signs was 17% lower than in workers
without symptoms and signs. Similar findings were reported in another study (Ernest et al. 1995). No
cholinergic signs were seen in a study in which the activities of RBC and plasma cholinesterase varied
less than 10% between pre- and postexposure. A study in volunteers exposed to 85 mg/m 3 of a malathion
aerosol for 2 hours/day over a 42-day period observed no clinical signs and no significant inhibition of
plasma or RBC cholinesterase activity over the study period. In an additional study of volunteers orally
administered 0.34 mg malathion/kg/day for 56 days, there was a maximum depression of 25% in plasma
cholinesterase approximately 3 weeks after cessation of treatment. A similar depression in RBC
cholinesterase was observed, but occurred later. Administration of 0.11 mg malathion/kg/day for 32 days
or 0.23 mg/kg/day for 47 days did not produce any significant depression of plasma or RBC
cholinesterase activity. No clinical signs were seen in the volunteers. As detailed in Section 3.2,
numerous studies in animals exposed to malathion by any route have shown inhibition of plasma, RBC,
and brain cholinesterase activities.