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.