title: QSAR screening of 70,983 REACH substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the ChemScreen project.
abstract: The ChemScreen project aimed to develop a screening system for reproductive toxicity based on alternative methods. QSARs can, if adequate, contribute to the evaluation of chemical substances under REACH and may in some cases be applied instead of experimental testing to fill data gaps for information requirements. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for 70,983 REACH substances was performed. Sixteen models and three decision algorithms were used to reach overall predictions of substances with potential effects with the following result: 6.5% genotoxic carcinogens, 16.3% mutagens, 11.5% developmental toxicants. These results are similar to findings in earlier QSAR and experimental studies of chemical inventories, and illustrate how QSAR predictions may be used to identify potential genotoxic carcinogens, mutagens and developmental toxicants by high-throughput virtual screening.
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark. Electronic address: ebawe@food.dtu.dk.
authors: Eva B
authors: EB
authors: Wedebye
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors: Marianne
authors: M
authors: Dybdahl
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors: Nikolai G
authors: NG
authors: Nikolov
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors: Svava Ó
authors: SÓ
authors: Jónsdóttir
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors: Jay R
authors: JR
authors: Niemelä
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D004331:Drosophila melanogaster; D005062:European Union; D033161:Government Regulation; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D018570:Risk Assessment / Q000331:legislation & jurisprudence; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity
chemical_list: D002273:Carcinogens; D009153:Mutagens; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013723:Teratogens
keywords: Developmental toxicity; Genotoxic carcinogenicity; In silico; Mutagenicity; QSAR; REACH; Screening