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

MALATHION 126
3. HEALTH EFFECTS
muscarinic cholinergic receptors include nausea, vomiting, abdominal cramps, diarrhea, tightness of the
chest, incontinence, miosis, and breathing difficulty. The action on nicotinic receptors in the somatic
motor endplates at the skeletal muscles leads to muscle fasciculations, generalized muscle weakness,
cramping, flaccid or rigid paralysis, and ataxia. Bradycardia or tachycardia with accompanying decrease
or increase in blood pressure may occur depending on the relative impact of cholinergic stimulation on
the muscarinic parasympathetic neurons or on the nicotinic neurons that innervate the heart. Effects on
cholinergic neurons in the central nervous system also yield a variety of effects including mental
confusion, insomnia, headache, convulsions, coma, and depression of respiratory centers.
Which effects may dominate depends on the sensitivity of the target enzyme at various synapses and the
level of the ultimate toxic molecule, malaoxon, which may be produced at or near the nerve from
malathion or transported from the site of malathion activation such as the liver, lung, or kidney.
Generation and distribution of malaoxon is poorly understood, but undoubtedly depends on the route of
exposure to malathion.
3.5.1 Pharmacokinetic Mechanisms
No special feature has been found in the absorption of malathion, which most likely undergoes passive
diffusion. Barrier function of the epidermis may be reduced when the skin is washed, as shown by the
increased absorption of 14 C-labeled malathion (Bucks et al. 1985). Adjuvants in malathion formulation
may also affect the rate of dermal absorption since different patterns of 14 C distribution were observed
between unformulated and formulated malathion (Abou Zeid et al. 1993). No information was located in
the literature regarding pharmacokinetic factors in inhalation and ingestion of malathion.
Distribution of absorbed malathion among components in the skin has been modeled and analyzed
experimentally (Chang et al. 1994). Although this analysis revealed a high affinity compartment that
serves as a reservoir for malathion in circulation, it has not clarified a variation in the percent absorption
of widely ranging dermal doses. In the only autoradiographic study of distribution of malathion (Saleh et
al. 1997), a suggestion has been made that the entire skin, rather than merely the site of dermal
application, may serve as a reservoir of dermally applied malathion, but the conclusion has not been
validated by others. The role of blood proteins in the distribution of absorbed malathion or its active
metabolite malaoxon has not been examined.