Chemical Dosimetry inBiological Monitoring of Exposure to Toxic Chemicals

Biological monitoring of exposure to chemicals has the objective of defining the so-called 'internal dose' or 'internal exposure level', and has been attempted by a variety of experimental approaches. Two categorical types of measurements can be made for this purpose: (1) measurement of concentrations of chemicals (or their metabolites) in body fluids or excreta; or (2) measurement of toxicological effects (e.g. mutation, sister chromatid exchange, chromosome aberrations, etc.) induced by chemicals in cells and tissues of exposed individuals. As the second approach is the subject of sections 3and 4, only methodology of the first category will be discussed here. Quantification of concentrations of individual chemicals or their metabolic derivatives can in principle be carried out on any biological medium that can be obtained for analysis. Thus, measurements could be made in blood, urine, faeces, expired air, adipose tissue, saliva, breast milk, semen, or samples of tissue obtained through biopsy or autopsy. A variety of analytical methodologies have been developed involving direct chemical analysis, immunological analysis, or bioassay depending upon such properties as mutagenicity of chemicals or their metabolites. With the recognition that many compounds require metabolic activation to reactive derivatives to express their toxicological effects, an additional strategy for chemical dosimetry has developed which is based upon the detection and quantitative determination of covalently bound derivatives formed between activated chemicals and cellular macromolecules such as nucleic acids and proteins. The purpose of this review is to provide a summary of currently available methodology for dosimetry applicable to the problem of assessment of human health risk posed by environmental chemicals. Some general comments are appropriate before specific methodologies are considered. Biological monitoring of exposure to chemicals may have several objectives which may in turn require specific methodological adaptations for different situations. Chemical dosimetry can be used, for example, to insure that current or past exposure does not entail an unacceptable health risk, or to detect potentially excessiveexposure before the occurrence of detectable adverse health