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

MALATHION 40
3. HEALTH EFFECTS
the use of recrystallized malathion in their experiments, since, as discussed below, impurities found in
commercial formulations can greatly increase the toxicity of malathion.
Numerous studies have examined the lethality of malathion in animals, particularly the acute lethality.
Representative examples are summarized below, as well as relevant information on factors that play a role
in the acute toxicity of this pesticide.
An early study by Frawley et al. (1957) calculated an LD50 of 1,400 mg/kg for technical malathion
(98% pure) in young male Osborne-Mendel rats. Doses of 600 mg/kg caused no deaths, whereas all rats
(10 out of 10) died when administered a dose of 2,000 mg/kg (Frawley et al. 1957). Gaines (1960)
determined LD50 values of 1,375 and 1,000 mg/kg in adult male and female Sherman rats, respectively,
administered technical malathion of unspecified purity. The apparent greater susceptibility of female rats
observed by Gaines (1960) was not seen in subsequent studies by Lu et al. (1965) who reported no
significant differences in LD50 values between male and female Hooded or Wistar rats administered
malathion of 95% purity. In addition, no difference in susceptibility between strains was observed (Lu et
al. 1965).
The role that impurities (i.e., trimethyl phosphorothioate and phosphorodithioate esters, isomalathion)
play in the acute toxicity of malathion has been examined in detail in several studies. For example, in
adult Wistar rats, the LD50 of 95% pure malathion was 1/4 that of 99.6% pure malathion (925 vs.
3,697 mg/kg) (Lu et al. 1965). Similar observations have been made by others in studies in rats and mice
(Aldridge et al. 1979; Pellegrini and Santi 1972; Talcott et al. 1977; Toia et al. 1980; Umetsu et al. 1977).
Clearly, as the purity of malathion decreases (and impurities increase), the LD50 values greatly decrease
(toxicity of the malathion formulation increases). This is caused by the inherent toxicity of the impurities
and/or potentiation of malathion toxicity. Umetsu et al. (1977) reported an LD50 of 9,500 mg/kg in adult
Sprague-Dawley rats for malathion of 99.3% purity and 12,500 mg/kg for recrystallized malathion. In the
same study, the LD50 for 95% pure malathion in adult mice was 1,985 mg/kg and that for 99.3% pure
malathion was 3,000 mg/kg. Further studies demonstrated that these impurities, or contaminants of
technical malathion, inhibit the activity of serum and liver malathion carboxylesterases, which detoxify
malathion, as well as of cholinesterase, thereby increasing the toxicity of the malathion formulation
(Talcott et al. 1977, 1979b).
An additional factor that plays a role in the acute toxicity of malathion is age; young animals are more
susceptible than older animals. The single oral LD50 of 95% malathion in newborn male Wistar rats was