Reproductive Toxicology 27 (2009) 8–13 Contents lists available at ScienceDirect Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox Harmonization of terminology in developmental toxicology: The quest for a more precise description and a harmonized classification of fetal observations  article info Keywords: Classification Grey zone anomalies Malformation Variation Developmental toxicology Reproductive toxicology Harmonization Terminology abstract Harmonization of terminology in developmental toxicology is a prerequisite to ensure a better risk assess- ment of 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 since 1995. This publication reports the main outcomes of the Fifth and Sixth Berlin Workshops held in 2005 and 2007, respectively. The objective of the Fifth workshop was to discuss a draft international proposal for updating the glossary of descriptive terms for fetal abnormalities put forward by Wise et al. [Wise LD, et al. Terminology of developmental abnormalities in common laboratory mammals (version 1). Ter- atology 1997;55:249–92]. The participants were asked to classify the new external, visceral and skeletal observations included within this new version 2 of Terminology of Developmental Abnormalities in com- mon Laboratory Mammals according to the two-category scheme (malformation and variation) agreed at previous Berlin workshops. The discussions held during the Sixth Workshop were mainly focused on the causes of uncertainty and low agreement regarding classification of some fetal observations as malfor- mations or variations. Lack of precision in descriptive terms and insufficient knowledge of the postnatal consequences of fetal observations had been identified as major causes of uncertainty and lower agree- ment among evaluators regarding the classification of “grey zone anomalies”, i.e. abnormalities that do not fit readily into one of the two categories (malformation or variation). Imprecise anatomical terms, obser- vation terms that are too broad, lack of information on severity and the use of different terms for the same change or different severities of the same change, were found to be the main reasons that descriptive terms are often not sufficiently precise to allow accurate classification of findings. It was agreed that provision of additional information, including sub-location within the affected structure, more detailed description of the nature of the change, in conjunction with presentation of photographs wherever possible, and a grading for severity would make descriptive terms more precise, thereby reducing misclassifications. A better knowledge of the adversity and postnatal consequences of fetal observations was considered as the key issue for achieving a substantial reduction in the number of misclassifications and grey zone anoma- lies. The urgent need for additional research along this line as a prerequisite for a better risk assessment was emphasized by the participants. 1. Background In the first Berlin Workshop, held in 1995, the International Fed- eration of Teratology Societies (IFTS) terminology of developmental abnormalities in laboratory animals was discussed, and a first ver- sion of the IFTS glossary of descriptive terms was published [1]. The focus of the second Workshop, held in 1998, was the classi- fication of fetal observations. After weighing the advantages and disadvantages of classification, it was agreed that classification of observations can be useful for risk assessment. A classification sys- tem based on only two categories, malformations and variations, was then advanced [2]. During the third Workshop, held in 2000, the experts discussed the results of a survey on the classifica- tion of skeletal anomalies as malformations or variations that had  Main outcomes of the 5th and 6th Workshops on the Terminology in Develop- mental Toxicology, Berlin, 2005 and 2007. been sent to developmental toxicologists [3]. The term “grey zone anomalies” was used for those abnormalities that did not fit read- ily into one of the two categories (malformation or variation) [3]. In the fourth workshop, held in 2002, the discussion was focused on the results of a similar survey on classification of external and soft tissue anomalies [4]. In both surveys, a high agreement was reached among evaluators regarding classification of most anoma- lies described by IFTS glossary terms. The discussion during the third and fourth workshops was focused on terms for which there was disagreement or uncer- tainty regarding classification. Fetal observations described by these terms were thereafter referred to as “grey zone anomalies”. Among the possible reasons for lower agreement among evaluators on classification of terms as malformation or variation, the atten- dees of both workshops identified imprecise descriptive terms, insufficient knowledge of the postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity as key factors. 0890-6238/$ – see front matter doi:10.1016/j.reprotox.2008.12.001