title: Structural features of endocrine active chemicals--A comparison of in vivo and in vitro data.
abstract: Studies on reproductive toxicity need high numbers of test animals. Therefore, we investigated whether chemical structural features (SF) in combination with in vitro data on specific adverse outcome pathways (AOPs) may be used for predicting reproductive toxicity of untested chemicals. Using the OECD Toolbox and expert judgment, we identified 89 structure groups for 275 chemicals for which the results of prenatal developmental toxicity or multigeneration studies were present in the Fraunhofer database on Fertility and Developmental Toxicity in experimental animals (FeDTex) database. Likewise, we evaluated 220 chemicals which had been tested in reporter gene assays on endocrine ((anti)estrogenic and (anti)androgenic) properties in the CALUX(®) test battery. There was a large spread of effect levels for substances within the chemical structure groups for both, in vivo and in vitro results. The groups of highest concern (diphenyl derivatives, planar conjugated systems with fused rings, phenols and organophosphates) correlated quite well, however, between the in vivo and in vitro data on estrogenic activity. For the 56 chemicals represented in both databases, lowest effect doses in vivo correlated well with the estrogenic activity in vitro. These results suggest that a panel of assays covering relevant AOPs and data on metabolism and toxicokinetics may allow prediction of relative reproductive or development toxicity potency within the identified chemical structure groups.
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany. Electronic address: g.lewin@web.de.
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Escher
authors.affiliation: BioDetection Systems BV, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: van der Burg
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: Nelly
authors.initials: N
authors.lastname: Simetska
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Mangelsdorf
mesh_terms: D000818:Animals; D016208:Databases, Factual; D052244:Endocrine Disruptors / Q000737:chemistry* / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen
keywords: Category approach; Estrogen receptor; Predictive screening; Reproductive toxicity; Structural features; Toxicological databases