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

MALATHION 163
3. HEALTH EFFECTS
Defining the source of malaoxon responsible for the acute neurotoxicity of malathion will be critical to
our understanding of human hazards. The source may not be a single organ (as was discovered for
parathion) (Nakatsugawa 1992). Although the detoxification of malathion is mainly set by
carboxylesterase, other biotransformation enzymes assume a much greater role when carboxylesterase is
suppressed. Since the suppression occurs to varying degrees with all commercial formulations, there is
also a need to define the nature and significance of the phosphatases and GSH S-transferase involved in
the metabolism of malathion and malaoxon. Human hazards from malathion will be better understood
through further studies of absorption of malathion. Here again, studies of absorption in isolation from the
influence of carboxylesterase may reveal clearer data. In addition, relationships between physical
properties such as partition coefficients and absorption of chemicals were explored in early literature
without clear conclusions. The reported lack of clear correlation in early literature (Ahdaya et al. 1981;
Shah et al. 1981), for example, may need to be reexamined. The technique employed seems inadequate to
estimate such physical parameters accurately, relying on near-background level counts to estimate the
concentration in the oil phase. More reliable partition coefficients have been published. Meaningful
distribution studies may only be possible when better metabolic data and techniques have been secured.
When the levels of malathion and malaoxon are obscured by the rapid metabolism, more data on just the
distribution of both the parent insecticide and metabolites would reveal little additional information.
Comparative Toxicokinetics. Absence of carboxylesterase in human blood is a conspicuous
departure from the rat model, which has most often been employed. Comparative studies involving
volunteers, rats, mice, and perhaps other mammals may reveal useful patterns. Interestingly, fairly wide
differences between rats and mice are already apparent. Umetsu et al. (1977) tested the acute oral toxicity
of malathion samples in female Sprague-Dawley rats and Swiss white mice fasted 6 hours before dosing.
For a technical malathion, the LD50 for the rat was 1,500 mg/kg and for mice was similar at 1,850 mg/kg.
For a 99.3% pure malathion, the LD50 values were 9,500 mg/kg for rats and 3,000 mg/kg for mice. For a
sample purified by recrystallization, the respective values were 12,500 and 3,600 mg/kg. Comparison
seems valid since all tests were done during the course of a single study using the same source of animals.
Comparative data for metabolism, particularly for carboxylesterases in various tissues in various species
against malathion and malaoxon will contribute greatly to our understanding of potential toxic effects on
humans.
Methods for Reducing Toxic Effects. There is good information on the procedures used to limit
absorption and to interfere with the mechanism of action of organophosphates, including malathion, after
acute exposures (Aaron and Howland 1998; Carlton et al. 1998; Osmundsen 1998). However, no