Abstract
A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure–activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption. †Presented at the 13th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.
Highlights
The need for prediction of the toxicity of untested chemicals is still increasing
As we have developed a number of endocrine disruption (ED) models, we ran the models on the predicted positive reproductive toxicants to see whether these effects seemed like possible mechanisms of reproductive toxicity
The training set is composed of data taken from the Teratogen Information System (TERIS) and a compilation in which the US Food and Drug Administration (FDA) definitions were used to quantify risk of developmental toxicity from drugs used during pregnancy
Summary
The need for prediction of the toxicity of untested chemicals is still increasing. The tests for reproductive toxicity are among the most costly tests, requiring testing on vertebrate animals. It is estimated that approximately 30,000 chemicals will require registration [2] and that 30% of the total testing costs will be used for the development of toxicity studies [3]. Predictions from valid quantitative structure–activity relationships (QSARs) may be used to fill data gaps
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