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

MALATHION 123
3. HEALTH EFFECTS
within 48 hours of spraying during the Mediterranean fruit fly eradication campaign in the fall of
1989 (Dong et al. 1994).
Description of the Model. Cumulative values for malathion carboxylic acid metabolites were
simulated by the model. When simulation approximated biomonitoring estimates, the sum of the amounts
for all compartments will yield the total absorbed dose. The model assumed that a portion of the dermal
dose diffuses into the skin whereas the rest is either lost to the atmosphere or remains on the skin. The
model has seven body compartments (skin surface, skin perfused, fat, muscle, kidney-vessel rich group,
intestine, and liver) and four external compartments (air, urine, feces, and acid metabolites).
Typical kinetic and physiological parameters and constants used are listed in Table 3-6 (Rabovsky and
Brown 1993). Similar values are also given for children of different ages (Dong et al. 1994). Hydrolytic
constants were based on animal data (Mallipudi et al. 1980) and apparent Vmax was scaled by the body
weight ratio to the 0.75 power. Oxidation constants were estimated from rodent data that showed 1–2%
oxidation (Lechner and Abdel-Rahman 1986). Tissue/blood partition coefficients were estimates from
the malathion octanol/water partition coefficient (776.25). Of the total of 67 individuals who participated
in the Los Angeles biomonitoring study (30 women, 20 men, and 17 children), 11 subjects with detectable
malathion acid metabolites in their urine were included in the PBPK simulation. Urinalysis provided only
the data for malathion dicarboxylic acid. Since the model required the data on total malathion carboxylic
acid metabolites (mono- and di-carboxylic acids), this was estimated to be 3 times the amount of
dicarboxylic acid based on available measurements.
Validation of the Model. The model was later modified and applied to cases reported in Dary et al.
(1994) and cases in Wester et al. (1983). The model is designed to estimate the absorbed doses of
malathion in an exposed individual based on a single urine sample at a given time period after exposure.
The validation study revealed that most of the predictions were within 2-fold of the measured values, with
none exceeding 3-fold. The model would be more accurate with multiple samples collected within the
first 24 or 36 hours of exposure (Dong et al. 1996).
Risk Assessment. The model estimates dermal doses by using urinary metabolites collected from
exposed human populations. The doses then can be used to assess health risks of the exposure, although
elaborate risk assessment has not been published in these California epidemiological studies to which this
PBPK model has been applied.