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

MALATHION 147
3. HEALTH EFFECTS
intestinal motility is greatly increased. Gastric lavage may be performed with the care to prevent
aspiration, as organic solvent vehicles may precipitate pneumonitis. Treatment of inhaled
organophosphates is mostly supportive as respiratory distress is a common effect of poisoning; intubation
may be necessary to facilitate control of secretions.
3.11.2 Reducing Body Burden
No information was located regarding reducing the body burden of malathion, or organophosphates,
following exposure. As mentioned in Section 3.4, malathion is eliminated relatively rapidly, such that
short-term exposures will not result in accumulation of the pesticide.
3.11.3 Interfering with the Mechanism of Action for Toxic Effects
The following information has been extracted from the texts listed above. Administration of atropine and
pralidoxime (2-PAM) seems to be a universally accepted treatment for organophosphate poisoning. It
should be mentioned, however, that glycopyrrolate, a quaternary ammonium compound, has also been
used instead of atropine (Bardin and Van Eeden 1990). Unlike atropine, glycopyrrolate does not cross the
blood-brain barrier and, therefore, has fewer central nervous system effects. Atropine is a competitive
antagonist at muscarinic receptor sites and since it crosses the blood-brain barrier, it also treats the central
nervous system effects. Atropine is particularly helpful in drying excessive secretions especially from the
tracheobronchial tree. Atropine does not antagonize nicotinic effects; therefore, 2-PAM is needed for
treatment of muscle weakness and respiratory depression. Most texts recommend an initial dose of 1–
2 mg for an adult and 0.05 mg/kg for children, preferably by the intravenous route. This may be repeated
every 15–30 minutes until signs of atropinization occur. 2-PAM is a quaternary amine oxime that can
reverse the phosphorylation of acetylcholinesterase and thereby restore activity. It may also prevent
continued toxicity by detoxifying the organophosphate molecule and has an anticholinergic effect
(Carlton et al. 1998). 2-PAM and other oximes function by nucleophilic attack on the phosphorylated
enzyme; the oxime-phosphonate is then split off, leaving the regenerated enzyme. 2-PAM should be
administered as soon as the diagnosis is made. The initial dose is 1–2 g for adults and 25–50 mg/kg for
children administered intravenously over 30–60 minutes. The dose can be repeated in 1 hour and then
every 8–12 hours until clinical signs have diminished and the patient does not require atropine. Some
patients may require multiple doses, as enzyme regeneration depends on plasma levels of the