Harmonization of terminology in developmental toxicology : The quest for a more precise description and a harmonized classification of fetal observations

Harmonization of terminology in developmental toxicology is a prerequisite to ensure a better risk assessmentof chemicals. As part of an international effort of the International Programme on Chemical Safety(IPCS) to harmonize terminology in developmental toxicology,workshops have taken place in Berlin since1995. This publication reports the main outcomes of the Fifth and Sixth Berlin Workshops held in 2005and 2007, respectively. The objective of the Fifth workshop was to discuss a draft international proposalfor updating the glossary of descriptive terms for fetal abnormalities put forward by Wise et al. [WiseLD, et al. Terminology of developmental abnormalities in common laboratory mammals (version 1). Teratology1997;55:249-92]. The participants were asked to classify the new external, visceral and skeletalobservations included within this newversion 2 of Terminology of Developmental Abnormalities in commonLaboratory Mammals according to the two-category scheme (malformation and variation) agreed atprevious Berlin workshops. The discussions held during the SixthWorkshop were mainly focused on thecauses of uncertainty and low agreement regarding classification of some fetal observations as malformationsor variations. Lack of precision in descriptive terms and insufficient knowledge of the postnatalconsequences of fetal observations had been identified as major causes of uncertainty and lower agreementamongevaluatorsregarding the classification of "grey zone anomalies", i.e. abnormalities that do notfit readily into one of the two categories (malformation or variation). Imprecise anatomical terms, observationterms that are too broad, lack of information on severity and the use of different terms for the samechange or different severities of the same change,were found to be the main reasons that descriptive termsare often not sufficiently precise to allow accurate classification of findings. It was agreed that provisionof additional information, including sub-location within the affected structure, more detailed descriptionof the nature of the change, in conjunction with presentation of photographs wherever possible, and agrading for severity would make descriptive terms more precise, thereby reducing misclassifications. Abetter knowledge of the adversity and postnatal consequences of fetal observationswas considered as thekey issue for achieving a substantial reduction in the number of misclassifications and grey zone anomalies.The urgent need for additional research along this line as a prerequisite for a better risk assessmentwas emphasized by the participants.