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

MALATHION 102
3. HEALTH EFFECTS
of 240 mg/kg (all aberrations except gaps) and 2,400 mg/kg (all aberrations) (Dzwonkowska and Hubner
1986). Results were not significant at intervening doses. Dulout et al. (1982) observed a significantly
higher number of micronucleated cells in mice at single intraperitoneal doses of 120 and 240 mg/kg, but
not at the highest dose of 480 mg/kg. No differences were observed after dermal administration. After
10 days of gavage dosing with 0.2 µg/kg/day, mice spermatocytes had slower rates of meiotic cell
division than controls (Hoda et al. 1993). Another study showed no significant numbers of chromosome
aberrations in bone marrow or spermatogonia and no dominant lethal mutations after a single
intraperitoneal dose of 300 mg/kg was administered to mice (Degraeve and Moutschen 1984).
Administration of single intraperitoneal doses of malathion in the range of 2.5–10 mg/kg to mice resulted
in significant dose-dependent increases in the frequency of chromosome aberrations in bone marrow cells
and sperm abnormalities, but did not affect the total sperm count (Giri et al. 2002). A study in male mice
treated dermally with multiple doses of 500 mg/kg/day of commercial malathion (unspecified purity)
found a significant increase in chromosome aberrations in primary spermatocytes (Salvadori et al. 1988).
Malathion (250 mg/kg/day) also produced an increase in univalent chromosomes (lacking centromeres).
However, the significance of results of Salvadori et al. (1988) has been questioned by some investigators
who noted that “while higher frequencies of spermatocytes containing univalents were observed in both
sex chromosomes and autosomes in malathion-exposed mice, the statistical strength of the effect was
stronger in the sex chromosomes, diminishing the significance of the effect” (Flessel et al. 1993). It was
also pointed out that “the reported increase in univalents among the sex chromosomes exhibited a positive
dose-response relationship, whereas the increase among the autosomes did not.”
In vivo studies in Drosophila are more equivocal (Table 3-4). Kumar et al. (1995) did observe increased
failure of eggs to hatch after untreated females were mated with treated males, assumed to be due to
dominant lethal mutations. The study also found increased sex-linked recessive lethal mutations.
Another study, however, showed no differences in sex-linked recessive lethal mutations, although this test
used a Drosophila strain selected for increased malathion resistance (Velázquez et al. 1987). Results of
the wing spot test, which can test genotoxic activity without exogenous metabolic activation, were
negative (Osaba et al. 1999).
Results from in vitro studies are summarized in Table 3-5. Assays in bacteria show conflicting results.
Shiau et al. (1980) observed some mutagenicity of malathion without metabolic activation in one strain of
Bacillus subtilis (and greater mutagenicity with activation) and weak DNA damaging potential in several
B. subtilis strains. In another study, purified colicinogenic plasmid E1 DNA from malathion-treated
Escherichia coli was found to have significantly more breaks than DNA from control bacteria in a test