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

MALATHION 107
3. HEALTH EFFECTS
Interplay of such factors was analyzed in a direct study of dermal absorption employing the isolated
perfused porcine skin flap (IPPSF) and revealed modest rates of absorption. Percutaneous absorption
kinetics for the 14 C-labeled insecticides including malathion were examined in viable epidermis and
dermis with a functional microcirculation (Chang et al. 1994). Measured venous flux values during the
8-hour perfusion were fitted to the 4-compartment pharmacokinetic model, and rate constants were
estimated. The model yielded estimates of rate constants for surface-to-skin (transitional), skin
(transitional)-to/from-skin (reservoir), skin (transitional)-to/from-vascular, and vascular-to-effluent
compartments. Absorption, defined as cumulative flux of radioactivity appearing in the venous perfusate
for malathion, was 1.29% of the applied dose in 8 hours.
In contrast, very rapid dermal absorption was observed in a study involving succinyl 14 C-malathion
applied to 7–8-week-old female Duplin ICR mice. The dermal dose of 1 mg/kg was rapidly absorbed
(5.5% in 1 minute, 13% in 5 minutes, 23% in 15 minutes, 25% in 60 minutes, 67% in 8 hours, and 98% in
48 hours) (Shah et al. 1981). Of 14 pesticides examined, malathion showed the slowest absorption rate,
with an absorption half-life of 130 minutes.
Dary et al. (2001) used a factorial design of three factors, vehicle, the source of the chemical (technical
grade 95% pure vs. 50% emulsifiable concentrate), and exposure duration (0.5 vs. 1 hour) to examine
dermal penetration of 14 C-malathion through the skin of rats. Penetration of malathion was detected by
instant electronic autoradiography. The result showed no significant interactions between the factors,
penetration was influenced solely by the vehicle; malathion was found to penetrate the stratum corneum
and the underlying layers of the skin more efficiently from an aqueous vehicle than from an organic
solvent. The portion of the applied dermal dose that was absorbed into the system amounted to a mean
total of 6.0±1.0% for the various groups studied.
The rate of percutaneous absorption of malathion in human skin in vivo was measured using
microdialyisis probes in 31 healthy volunteers (Boutsiouki et al. 2001). The authors also examined the
relationship between tissue levels of malathion and changes in local skin blood flow. An aqueous
solution of malathion was applied to the volar surface of the forearm at a concentration of 2.5 mg/cm 2 .
Malathion was detected in the dialysate collected from the perfused probes within 30 minutes of
application to the skin and the concentration increased to reach a steady state of 50 ng/mL at 3 hours.
There was no significant further increase up to 5 hours of continuous exposure. The total amount of
malathion recovered was relatively low, approximately 71 ng. No malaoxon could be detected in the
dialysate at any time. When a commercial aqueous solution of 0.5% malathion was applied, no malathion