The role of human volunteer studies to assess pesticide hazards from the evaluation of selected published studies

The question of the ethical and scientific acceptability of experimental studies involving human volunteers has been raised by recent debates, and has never found a clear answer. To the aim of reaching a better understanding of the advantages and the limits of these studies, the ICOH Scientific Committee on Rural Health has evaluated selected published papers to collect a better understanding of the real added value of these studies. To this aim, a PubMed search has been performed, and the papers to be evaluated have been selected based on type of study, compound addressed, and year of publication, for a total of 26 papers. For each paper the following items has been collected: author; year of publication; journal; peer review; aim of the study (absorption, distribution, metabolism and excretion –ADME); study of biological effects and/or toxicity; exposure; other, relation with pesticide authorization procedures, compound addressed, experimental design, number of groups and subjects, statistical power, approval of the ethical committee, and real need of the study to collect the requested information. Based on the evaluation carried out by our WG, it seems that most experimental studies in human volunteers, as published in the scientific literature, have not been explicitly performed to set reference values. Most of the recent studies deal with ADME rather than with toxicological effects. The problems with studies in human are the use of only one dose level and the usually relatively low number of subjects per group. For this reason, it seems that very seldom these studies are useful to set reference values, but sometime the results contribute in reducing the uncertainty of the assessments possibly help in defining a chemical-specific assessment factor. Another use of these studies might be the identification of the proper or most adequate indicators to be used in biological monitoring of exposure.