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

MALATHION 108
3. HEALTH EFFECTS
was detected in the dialysate for up to 5 hours after application. Malathion caused a marked and long-
lasting erythema which, according to the investigators, could have been due to malathion-induced
accumulation of acetylcholine within the tissue space in quantities enough to cause visible erythema.
Reducing the skin blood flow by the addition of the vasoconstrictor noradrenaline produced an 8-fold
increase in the recovery of malathion in the dialysate, indicating significantly reduced absorption.
Other studies of dermal absorption relied on the urinary excretion of dermally-applied malathion as
evidence of dermal absorption. Although widely ranging doses employed by researchers may underlie
some of the variations, interspecies difference in absorption rates (based on urinary elimination) have
been cited by Wester and Noonan (1980) (64.6% for rabbits, 15.5% for pigs, 19.3% for monkeys, and
8.2% for humans), precluding quantitative generalization (Rabovsky and Brown 1993). Furthermore,
even in a single species, the rate of dermal absorption may vary in different skin areas. For example, in
humans, the extent of malathion absorption from the forearm was similar to that from the palm and foot,
but was less than from the abdomen and hand dorsum; absorption from the forehead and the axilla was
3–4 times more extensive than from the forearm (Maibach et al. 1971).
Urinary excretion was studied to assess percutaneous penetration of 12 pesticides, including malathion, in
humans (Feldmann and Maibach 1974). Six volunteers received 4 µg/cm 2 of 14 C-malathion (label
position unspecified) in acetone on the ventral forearms, and urinary excretion was followed over a 5-day
period. The total urinary excretion of an intravenous dose was 90.2%, and this was used to correct for the
urinary excretion of the dermal dose. Presumably reflecting the blood concentrations, urinary 14 C level
from the dermal dose reached a peak in the 4–8-hour sample and declined after 12 hours. The total
urinary excretion of the dermal dose was 8.2%.
In an effort to establish reliable methods to estimate dermal absorption from urinary excretion data, the
data of Feldmann and Maibach (1974) were reanalyzed by Thongsinthusak et al. (1999) by fitting a model
with a lag time. The model-derived maximum excretion of dermal dose predicted that 6.3%, instead of
8.2%, of the dermal dose will be eliminated via urine. The figure of 7.0% was obtained when the model
was also applied to the intravenous data of Feldmann and Maibach (1974).
In another study in humans, the effect of repeated dermal exposure on absorption was examined in male
volunteers. Tests began with a single application of 14 C-malathion (label position unspecified; mixed
with nonlabeled malathion) onto the ventral forearm skin, followed by repeated daily application of
nonlabeled malathion to the same site (Wester et al. 1983). The daily dose was 23 mg (5 mg/cm 2 over a