The French approach to deriving toxicity reference values: An example using reprotoxic effects

Abstract

Following the French health and environment action plan, the French Agency for Environmental and Occupational Health and Safety set up a workgroup to standardise a method of deriving toxicity reference values (TRVs). Over the last few decades, there has been increasing concern about the effect of exposure to chemicals on reproductive function, leading the group to take an interest in reprotoxic effects. This article presents the recommendations of the workgroup regarding specific reprotoxic effects. Abnormal development of foetuses and infants, together with impairment of reproduction were considered to be critical effects. Where critical windows of exposure were concerned, quantitative analysis suggested the need for several types of toxicity reference value, as a function of exposure duration: reprotoxic effects may result from acute or chronic exposure at any time of life, whilst developmental effects may occur after exposure during the pregnancy or during the lactation period. The choice of a critical study is based on epidemiological or toxicological quality criteria. The working group recommends the use of the benchmark dose approach in estimating the critical dose. Finally, the working group considered the application of uncertainty factors typically used to take into account the variability between animal and human, between different individuals, and the availability of the data.