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

MALATHION 143
3. HEALTH EFFECTS
depression in RBC cholinesterase was observed, but occurred later. No clinical signs were seen in the
volunteers. Malathion and EPN in combination seemed to have additive effects, but no potentiation was
apparent. The influence of EPN on the acute toxicity of malathion was determined in rats and dogs
(Frawley et al. 1957). Malathion doses were 0, 600, 800, 1,000, 1,250, 1,600, and 2,000 mg/kg. There
were no deaths in rats with the 600 mg/kg dose and all (10) rats died with the 2,000 mg/kg dose. Typical
cholinergic signs were seen before death. Deaths generally occurred several hours after dosing. The
combination malathion/EPN in a ratio of 25/1 showed about a 10-fold potentiation of malathion alone. In
dogs (malathion doses of 0, 25, 50, 100, 200, 500, 1,000, 2,000, and 4,000 mg/kg), there were no deaths
with 2,000 or 4,000 mg/kg malathion alone and doses of 100 mg/kg or less of EPN were not lethal.
However, a combination of 100 mg/kg malathion and 2 mg/kg EPN killed four out of four dogs, which
suggested a potentiation factor of about 50-fold. Frawley et al. (1957) also studied the effect of malathion
and the influence of simultaneous administration of EPN on blood cholinesterase activity in an 8-week
feeding study in rats. No significant change in whole blood cholinesterase activity was observed by
treatment with malathion alone. However, 500 ppm malathion (about 43.7 mg/kg/day) plus 25 ppm EPN
(which caused moderate depression of cholinesterase activity) reduced cholinesterase activity to about
30% of pretreatment values during treatment. In a 12-week feeding study in dogs, plasma cholinesterase
activity was not significantly altered by malathion (0, 25, 100, or 250 ppm), but the high dose caused
about 20% inhibition in erythrocyte activity after 6 weeks of treatment. Simultaneous administration of
EPN greatly potentiated the effect of malathion, particularly on erythrocyte cholinesterase. The high
malathion dose with 50 ppm EPN caused a maximum inhibition of about 95% after 8 weeks of treatment,
whereas 50 ppm EPN alone inhibited the enzyme by not more than 5%. Su et al. (1971) measured the
effects of carboxylesterase inhibition on the toxicity of malathion by feeding rats organophosphate
insecticides (EPN, parathion, Folex ® , TOTP, Guthion ® ) for 1 week and then administering malathion
intraperitoneally. All insecticides significantly increased the acute toxicity of malathion (reduced the
LD50) and the amount of increase was correlated with the inhibition of liver carboxylesterase (especially
the enzyme that hydrolyzes diethylsuccinate), less with inhibition of serum carboxylesterase, and poorly
with inhibition of brain, liver, and serum cholinesterase. Murphy and Cheever (1968) noted that
administration of 10 ppm dioxathion in the diet for 30 days to rats or 30 ppm ronnel for 7 days did not
significantly inhibit brain cholinesterase activity, but these diets greatly increased the inhibition of the
enzyme by a single dose of malathion. Finally, equitoxic doses (based on the LD50 values) of aldrin and
malathion or DDT plus malathion provided mutually protective action in rats, whereas synergistic effects
(more than additive) were noted when 1/3 of the LD50 values of each chlordane, parathion, and malathion
were administered to mice (Keplinger and Deichmann 1967).