title: Screening for potential endocrine disruptors in fish: evidence from structural alerts and in vitro and in vivo toxicological assays.
abstract: BACKGROUND
  The European chemicals' legislation REACH aims to protect man and the environment from substances of very high concern (SVHC). Chemicals like endocrine disruptors (EDs) may be subject to authorization. Identification of (potential) EDs with regard to the environment is limited because specific experimental assessments are not standard requirements under REACH. Evidence is based on a combination of in vitro and in vivo experiments (if available), expert judgement, and structural analogy with known EDs.
  
  
  OBJECTIVE
  The objectives of this study are to review and refine structural alerts for the indication of potential estrogenic and androgenic endocrine activities based on in vitro studies; to analyze in vivo mammalian long-term reproduction studies with regard to estrogen- and androgen-sensitive endpoints in order to identify potential indicators for endocrine activity with regard to the environment; to assess the consistency of potential estrogenic and androgenic endocrine activities based on in vitro assays and in vivo mammalian long-term reproduction studies and fish life-cycle tests; and to evaluate structural alerts, in vitro assays, and in vivo mammalian long-term reproduction studies for the indication of potential estrogenic and androgenic endocrine disruptors in fish.
  
  
  RESULTS
  Screening for potential endocrine activities in fish via estrogenic and androgenic modes of action based on structural alerts provides similar information as in vitro receptor-mediated assays. Additional evidence can be obtained from in vivo mammalian long-term reproduction studies. Conclusive confirmation is possible with fish life-cycle tests. Application of structural alerts to the more than 33,000 discrete organic compounds of the EINECS inventory indicated 3585 chemicals (approx. 11%) as potential candidates for estrogenic and androgenic effects that should be further investigated. Endocrine activities of the remaining substances cannot be excluded; however, because the structural alerts perform much better for substances with (very) high estrogenic and androgenic activities, there is reasonable probability that the most hazardous candidates have been identified.
  
  
  CONCLUSIONS
  The combination of structural alerts, in vitro receptor-based assays, and in vivo mammalian studies may support the priority setting for further assessments of chemicals with potential environmental hazards due to estrogenic and androgenic activities.
authors.affiliation: Analytical Laboratory, Bahnhofstr. 1, 24816 Luhnstedt, Germany.
authors.forename: Monika
authors.identifier: 0000-0002-1305-2235
authors.initials: M
authors.lastname: Nendza
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wenzel
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Auf dem Aberg 1, 57392 Schmallenberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany ; 30161 Hannover, Germany.
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany.
authors.forename: Nelly
authors.initials: N
authors.lastname: Simetska
authors.affiliation: German Environment Agency UBA, Wörlitzer Platz 1, 06844 Dessau-Roßlau, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Stock
authors.affiliation: German Environment Agency UBA, Wörlitzer Platz 1, 06844 Dessau-Roßlau, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Arning
keywords: Androgen; EINECS; Endocrine; Estrogen; Priority setting; QSAR; REACH; SVHC; Structural analogy