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

MALATHION 160
3. HEALTH EFFECTS
Lee and Tai 2001; Matsukawa et al. 1997; Monje Argiles et al. 1990; Namba et al. 1970; Ramu et al.
1973). As an organophosphate pesticide, malathion inhibits the activity of the enzyme
acetylcholinesterase as well as that of plasma cholinesterase. The inhibition of acetylcholinesterase at
various levels within the nervous system produces a characteristic set of signs and symptoms including
respiratory distress, bradycardia, increased bronchial secretions, excessive salivation, lacrimation,
pupillary constriction, fasciculations, abdominal cramps, and diarrhea (Aaron and Howland 1998; Carlton
et al. 1998; Osmundson 1998). Most of these signs and symptoms have been observed in the cases listed
above. In addition, abnormal electromyographic findings were reported in some studies of documented
ingestion of malathion (Crowley and Johns 1966; Dive et al. 1994; Monje Argiles et al. 1990). A study of
controlled administration of malathion in capsules to volunteers identified a NOAEL and LOAEL for
inhibition of plasma cholinesterase of 0.23 and 0.34 mg/kg/day, respectively (Moeller and Rider 1962),
and these findings were used to derive an intermediate oral MRL for malathion. Studies of workers
exposed to several pesticides have also documented inhibition of plasma and RBC cholinesterase, and in
some cases, the degree of enzyme inhibition has been correlated with the presence or absence of clinical
signs (Ernest et al. 1995; Peedicayil et al. 1991; StDlberg et al. 1978). Information is lacking on potential
effects of long-term, low-level exposure to malathion as well as on potential long-term effects of acute
high exposure to malathion. This information can only be obtained from evaluation of cohorts exposed
only to malathion, but data from subjects exposed to a few organophosphates would also be helpful.
Studies in animals support the findings in humans. In addition to measurements of cholinesterase
activity, a few studies have examined the effects of malathion on neurobehavioral parameters. An acute
study that tested a functional observation battery in rats reported increased motor activity 21 days after a
single gavage dose of 2,000 mg/kg of malathion (88% pure) (Ehrich et al. 1993), whereas a similarly
designed study found decreased motor activity 14 days after dosing with 2,000 mg/kg malathion
(96.4% pure) (Lamb 1994a). Similar inconsistencies were seen between two 90-day feeding studies (Desi
et al. 1976; Lamb 1994b). Further studies are needed to clarify these inconsistencies. Chronic-duration
studies have reported inhibition of plasma and RBC cholinesterase activity in both rats (Daly 1996a) and
mice (Slauter 1994) and body tremors in female mice after 70 weeks of dosing with approximately
2,980 mg/kg/day of malathion (NCI 1978). Should additional chronic studies be conducted, microscopic
examination of nervous tissues from both peripheral and central nervous system may be conducted. Also,
a subgroup of animals could be tested for possible subtle neurobehavioral alterations of long-term, lowlevel
exposure. Finally, pilot studies should be designed to evaluate possible neurodevelopmental effects
of gestational and lactational exposure to malathion.