individual soldiers; and distinguishing the types of herbicides used. The section entitled ''Development of the Exposure Reconstruction Model'' in the Appendix (p. 46) discusses this in greater detail.
Biomarkers of exposure require the ability to measure a chemical in a biologic specimen—that is, urine, blood, tissue, organs, hair, and the like. If biomarkers of exposure are chosen as a dose index, such as serum TCDD, then the quantitative relations between the marker and herbicide exposure and its limitations must be discussed. For example, individual clearance rates of TCDD are variable, so low serum TCDD may not equate to low past exposure. There are also other sources of TCDD intake, such as diet, so current high TCDD levels may not necessarily indicate high past exposure. Finally, TCDD was a highly variable constituent of the herbicides used in Vietnam, and some herbicides did not contain TCDD; therefore, TCDD may not be a good marker for all types of herbicide exposure. Additional information on biomarkers is provided in the Appendix.
VALIDATION OF EXPOSURE ASSESSMENT APPROACHES
Validation of the exposure assessment approach developed will be a critical part of the proposal. The committee recognizes that retrospective exposure assessment of herbicide exposures among Vietnam War veterans may, at best, be semiquantitative or rank ordered. Because we have a generally poor understanding of the sources and magnitudes of exposures to herbicides that occurred in Vietnam more than 25 years ago, the predicted levels of exposure to individual veterans are likely to be imprecise. Thus, applicants should discuss the anticipated sources and magnitudes of uncertainty in their model predictions. Attention should also be paid to the role that quantitative or semiquantitative data might play in the validation of exposure predictions in a pilot study.
The best method for validation is not obvious and is left to the researchers to propose, critique, and defend. The limitations and uncertainties associated with the validation method—such as those discussed previously for serum TCDD levels—should be addressed.
Respondents are encouraged to consider other alternative approaches to the validation process.
EVALUATION CRITERIA
The purpose of the research to be sponsored under the RFP is to develop exposure assessment models for use in epidemiologic studies of Vietnam veterans. Proposals of models for which the relevance to Vietnam veterans is unclear will not be further evaluated. The proposals will be assessed based on
