Workshop Report 14 – Use of Markers for Improved Retrospective Exposure Assessment in Epidemiology Studies

Abstract

WR 14 : Use of Markers for Improved Retrospective Exposure Assessment in Epidemiology Studies | February 2009

The workshop addressed the question of whether new analytical and molecular techniques would allow the identification of biomarkers of historical exposure to chemicals. This would allow epidemiological researchers to use objective and quantitative data in place of surrogates of exposure such as data from questionnaires. The criteria for these biomarkers to be useful are: sensitivity to low levels of the chemical or the change induced; stability of the biomarker inside the exposed individual and specificity of the change that allows it to be unambiguously attributed to the exposure.

The techniques available from classical analytical methods to genomics and proteomics are all capable of extreme sensitivity. However, while the requirement for sensitivity is met by the methods discussed, the other two criteria are currently not attained at a feasible level.

In particular the biological matrices which can be readily obtained are turned over rapidly in the living organism. Red blood cells remain for a matter of months and other tissues are impractical to sample. At a sub-cellular level addition products (adducts) to DNA and proteins in cell populations with longer biological half lives may be useful. Certain adducts, notably adducts to histones, are potentially longer lasting.

The ?omics? (metabonomics, proteomics, genomics), have promise, but are subject to large interindividual variation in part due to environmental factors.

In conclusion, no single one of the techniques described can be used in the field to valid historical exposure. Exceptions to this require that the exposure window be relatively recent and the marker is present as an adduct to a macromolecule. The workshop identified several areas where research held the promise of improving on this situation, although it seems unlikely that a general approach would be rapidly forthcoming.