Human in vivo studies of non-pharmaceutical products

Two principal types of human in vivo studies with non-pharmaceuticals can be distinguished: (1) human metabolism studies are used for identification of target metabolites which can subsequently be used in biological monitoring studies. Furthermore, they allow extrapolation from excretion of metabolite(s) to exposure to the parent compound on the basis of an understanding of human pharmacokinetics. (2) Pharmacodynamic or effect studies are restricted to the study of acute and inherently reversible changes and are most likely to improve risk assessment in the following areas: neurobehavioural effects (e.g. alcohol, organic solvents), alterations in biochemical markers (e.g. cholinesterase inhibition following organophosphate exposure) and topical effects (e.g. skin irritancy). Ethical considerations are of prime importance and, as a minimum, any human study must comply with the principles of the Declaration of Helsinki. The protocol should include scientifically sound objectives, a justification of subject numbers, a formal risk-benefit analysis and provisions for appropriate ethical review. The welfare of the individual participating in the study must be paramount. Informed consent has to be obtained and subjects must be free to withdraw from the study at any time. Compensation should be given for the inconvenience of participating in the study, but never for undergoing risk. Provided these conditions are met, human volunteer studies can be a powerful tool in risk assessment and risk management of exposure to non-pharmaceutical products.