Estimation of dermal absorption using the exponential saturation model.

Estimates of dermal absorption are used in exposure assessment to calculate the internal dose of persons contacting pesticides and are a critical part of risk assessments. An exponential saturation model with lag time was validated against a classic dermal absorption study of 12 pesticides administered to human volunteers. The model gave dermal absorption estimates consistent with reported values in the literature. Moreover, this model gave more realistic estimates of the percentage of dermal absorption for some pesticides, which have special properties. In most submitted dermal absorption studies in animals, especially rats, "bound" skin residues (BSR) at treated skin sites were generally high when animals were sacrificed more than 24 h after the dose was administered. The direct addition of the total BSR as an absorbed dose would likely overestimate actual dermal absorption. From a well-conducted dermal absorption study, this model can be utilized to estimate maximum excretion of the administered dermal dose as a result of further absorption of bioavailable BSR. Resulting dermal absorption estimates are appropriate for regulatory purposes in the risk assessment of pesticides because they take into account the bioavailability of BSR while at the same time the estimates are not overly conservative.

Determination of atrazine metabolites in human urine: development of a biomarker of exposure.

Enzyme-linked immunosorbent assays (ELISAs) are reported for the detection of atrazine and its principle metabolite in human urine. The ELISAs can be used with crude urine or following extraction and partial purification by methods described in this report. GC, MS, and HPLC techniques were used to confirm and complement the ELISA methods for qualitative and quantitative detection of urinary metabolites. A series of samples from workers applying this herbicide confirmed a mercapturic acid conjugate of atrazine as a major urinary metabolite. The mercapturate was found in concentrations at least 10 times that of any of the N-dealkylated products or the parent compound. Atrazine mercapturic acid was isolated from urine using affinity extraction based upon a polyclonal antibody for hydroxy-s-triazines and yielded products sufficiently pure for structure confirmation by MS/MS. In a pilot study monitoring applicators, a relationship between cumulative dermal and inhalation exposure and total amount of atrazine equivalents excreted over a 10-day period was observed. On the basis of these data, we propose that an ELISA for the mercapturate of atrazine could be developed as a useful marker of exposure.