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

MALATHION 120
3. HEALTH EFFECTS
agricultural workers (mixers and applicators) evaluated dermal exposure to malathion by monitoring
urinary dimethyl phosphorothioic acid and O,O-dimethyl phosphorodithioate (Fenske 1988). Urinary
metabolites monitored for 3 days following exposure showed that applicators excreted 17% of the applied
dose estimated by fluorescent tracer technique, and mixers 23%.
3.4.4.4 Other Routes of Exposure
In a poisoning case involving suicidal intravenous injection of about 1.8 g of malathion, serum
concentration of malathion in the range of 0.029–0.349 µg/ml between 6 and 24 hours postinjection
indicated a half-life of ≤ 2.89 hours for serum malathion (Lyon et al. 1987).
A single dose of 2.5 mg/kg of methoxy 14 C-malathion in 0.3 mL of saline was intravenously administered
to male Sprague-Dawley rats and the whole animal was frozen in a dry ice/hexane for autoradiography
after 30 minutes (Saleh et al. 1997). As a percent of the recorded radioactivity of sagittal sections, the
small intestine contained 21% of the radioactivity and the urinary tract contained 7%, leading the authors
to conclude that the bile is a major route of excretion.
3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models
Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and
disposition of chemical substances to quantitatively describe the relationships among critical biological
processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry
models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of
potentially toxic moieties of a chemical that will be delivered to any given target tissue following various
combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based
pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to
quantitatively describe the relationship between target tissue dose and toxic end points.
PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to
delineate and characterize the relationships between: (1) the external/exposure concentration and target
tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al.
1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can
be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from