The ReProTect Feasibility Study, a novel comprehensive in vitro approach to detect reproductive toxicants

ReProTect is a project within the 6th European community Framework Program for Research, Technological Development and Demonstration, which has developed alternative methods aimed to reduce or replace animal experimentation in the field of reproductive toxicology. In the final year of the project, a ring trial, named the ¿Feasibility Study¿, was conducted, in which 10 blinded chemicals with toxicologically well-documented profiles, selected by independent experts, were analyzed by employing a test battery of 14 in vitro assays, mostly having been developed or optimized in ReProTect. The data generated on the 10 blinded test compounds by the in vitro assays were used to predict the presence or absence of reproductive toxicity in vivo. EC50 (half maximal effective concentration) or equivalent endpoints were determined in each of the assays and the test compounds were then ranked relative to chemicals previously assayed in the tests of the selected test battery. The comparison of the activities (EC50-values) of the test agents with that of reference chemicals with known mode of action and integrating the information from all 14 tests, allowed a robust prediction of the adverse effects on fertility and embryonic development of the 10 test chemicals. Moreover, a weight of evidence approach, integrating information from different assays, enhanced the predictive power. In summary, the vast majority of the predictions made based on the in vitro results turned out to be correct when compared to the whole animal data. Importantly, two negative control chemicals, devoid of any reproductive toxicity in the animal assay, were also negative in our in vitro test battery. The procedure used here, a nearest neighbor analysis coupled with a weight of evidence approach, may guide future activities in the field of alternative toxicity testing

SCHENK Barabara;  WEIMER Marc;  BREMER Susanne;  VAN DER BURG Bart;  CORTVRINDT Rita;  FREYBERGER Alexius;  LAZZARI Giovanna;  PELLIZZER Cristian;  PIERSMA Aldert;  SCHAEFER Wolfgang;  SEILER Andrea;  WITTERS Hilda;  SCHWARZ Michael; 

2010-10-19

PERGAMON-ELSEVIER SCIENCE LTD

JRC57418

0890-6238,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC57418,   

10.1016/j.reprotox.2010.05.012,