Human in vivo studies of non-pharmaceutical products

Two principal types of human in vivo studies with non-pharmaceuticals can b e distinguished: (1) human metabolism studies are used for identification o f target metabolites which can subsequently be used in biological monitorin g studies. Furthermore, they allow extrapolation from excretion of metaboli te(s) to exposure to the parent compound on the basis of an understanding o f human pharmacokinetics. (?) Pharmacodynamic or effect studies are restric ted to the study of acute and inherently reversible changes and are most li kely to improve risk assessment in the following areas: neurobehavioural ef fects (e.g, alcohol, organic solvents), alterations in biochemical markers (e.g. cholinesterase inhibition following organophosphate exposure) and top ical effects (e.g, skin irritancy). Ethical considerations al e of prime im portance 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-benefi t analysis and provisions for appropriate ethical review. The welfare of th e 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 participat ing 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. (C) 2001 El sevier Science Ireland Ltd. All rights reserved.