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

MALATHION 115
3. HEALTH EFFECTS
rats, however, carboxylesterase in the serum may play at least as important a role as the hepatic
carboxylesterase (Talcott 1979). In humans, carboxylesterase is essentially absent in the blood, though it
is quite active in the liver (see Section 3.5.3).
Malathion monocarboxylic acid produced by partially purified rat liver carboxylesterase in vitro and that
in the urine of male Duplin rats fed 1,500 mg/kg malathion were identified as α-monoacid, indicating that
the initial hydrolysis to monocarboxylic acid occurs strictly at the α-position in this rat strain (Chen et al.
1969).
In other strains of rats, however, both α- and β-monocarboxylic acids are found in the urine of treated
animals. In female Sprague-Dawley rats, a gavage dose of 1 mg/kg malathion yielded approximately
similar amounts of α- and β-monocarboxylic acids over 24 hours, measured both in the blood and in the
urine (Ryan and Fukuto 1985). Production of β-monocarboxylic acid and dicarboxylic acid were severely
suppressed by pretreatment with 1 mg/kg of isomalathion or O,S,S-trimethyl phosphorodithioate.
Mallipudi et al. (1980) prepared two chromatography fractions of malathion carboxylesterase from
solubilized microsomes of Sprague-Dawley rat livers. When tested with malathion as the substrate, these
enzymes yielded different ratios of α- and β-acid. With carboxylesterase in the fraction A
(50,000-60,000 dalton), fraction B (110,000–130,000 dalton), and crude homogenate, the respective ratios
were 1.5, 0.2, and 0.56. In comparison, the ratio for rat serum carboxylesterase was 1.17. In rabbit liver,
both metabolites were produced by monomeric and oligomeric forms of carboxylesterases, with ratios of
2.33 and 4.55, respectively (Lin et al. 1984a).
Matsumura's textbook (Matsumura 1985) lists the ratio of α- and β-malathion monocarboxylic acids for
pure horse liver aliesterase, rat liver microsomes, beef liver acetone powder, pig pancreas acetone
powder, pig kidney acetone powder, partially purified pig liver esterase, housefly homogenate, and
Tribolium beetle homogenate. The α/β ratio ranges from 0.07 to 5.0.
Malaoxon is hydrolyzed by a carboxylesterase, and its acute toxicity increases when this enzyme is
inhibited (Dauterman and Main 1966). The kinetics of carboxylesterase are complicated since the
substrate malaoxon inhibits carboxylesterase (Main and Dauterman 1967).
Malathion dicarboxylic acid is a major urinary metabolite of malathion, but the enzyme that yields this
metabolite by hydrolyzing the second carboxylester linkage has not been studied. In rats, the dicarboxylic