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

MALATHION 41
3. HEALTH EFFECTS
124.1 mg/kg, whereas in preweaning (14–16 days old) and adult (3–4 months) rats, oral LD50 values were
386.8 and 925.4 mg/kg, respectively (Lu et al. 1965). This difference was also observed for 4-day
cumulative LD50s (Lu et al. 1965). Similar findings were reported by Mendoza (1976) and Mendoza and
Shields (1976) who also observed that the decrease in susceptibility more or less paralleled increases in
the activities of esterases in various tissues. For example, using acetylthiocholine as substrate, a single
dose of 8,000 mg/kg of malathion inhibited brain esterase by 85% in 18-day-old pups, while in 1-day-old
pups, the same degree of inhibition was achieved with a dose of only 500 mg/kg.
In dogs, single doses of up to 4,000 mg/kg of 98% pure malathion in a gelatin capsule were not lethal,
although the observation period was not indicated (Frawley et al. 1957). In rabbits, a single dose of
1,200 mg/kg of 95% pure malathion killed five out of six animals 6 hours after dosing; there were no
deaths with 600 mg/kg (Weeks et al. 1977). In all of the species examined, death was preceded by signs
of cholinergic stimulation such as salivation, respiratory distress, tremors, and convulsions.
Deaths in animals also have been reported in intermediate-duration studies. In a 6-week dietary study,
five out of five male and female Osborne-Mendel rats administered approximately 2,816 mg/kg/day
technical malathion (95% pure) died by week 3 (NCI 1978); no deaths were reported at 1,408 mg/kg/day.
Deaths were also observed among male and female Fischer-344 rats administered approximately
1,399 mg/kg/day technical malathion, but not at #700 mg/kg/day in a 13-week feed study (NCI 1979a).
Also, 4 out of 10 male, but no female B6C3F1 mice died following dietary administration of
approximately 6,432 mg/kg/day of technical malathion for 3 weeks (NCI 1978); no deaths occurred with
approximately 3,216 mg/kg/day malathion or less.
Significant increased mortality was observed among male Fischer-344 rats administered approximately
166 mg/kg/day of technical malathion (95% pure) in the diet for 2 years (NCI 1979a). A more recent
bioassay reported a significant increase in deaths not attributed to cancer among male Fischer-344 rats
given approximately 359 mg/kg/day technical malathion (97.1% pure) or higher doses (Daly 1996a). No
significant increase in mortality was seen in the females that received up to 868 mg malathion/kg/day
(Daly 1996a).
The LOAEL values for death in each species and duration category are recorded in Table 3-2 and plotted
in Figure 3-2.