The ReProTect Feasibility Study, a novel comprehensive in vitro approach to detect reproductive toxicants.
ReProTect is a project within the 6th European Framework Program which has developed alternative methods aimed to reduce or replace animal experimentation in the field of reproductive toxicology. In its final year, a ring trial, named the "Feasibility Study", was conducted, in which 10 blinded chemicals with toxicologically well-documented profiles were analyzed by employing a test battery of 14 in vitro assays. EC(50) (half maximal effective concentration) or equivalent endpoints were determined and the test compounds were ranked relative to chemicals previously assayed in the tests of the battery. This comparative analysis together with a weight of evidence approach allowed a robust prediction of adverse effects on fertility and embryonic development of the 10 test chemicals in vivo. 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. 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
Barbara
B
Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Tübingen, Germany.
Weimer
Marc
M
Bremer
Susanne
S
van der Burg
Bart
B
Cortvrindt
Rita
R
Freyberger
Alexius
A
Lazzari
Giovanna
G
Pellizzer
Cristian
C
Piersma
Aldert
A
Schäfer
Wolfgang R
WR
Seiler
Andrea
A
Witters
Hilda
H
Schwarz
Michael
M
D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D000818:Animals; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D023381:Endpoint Determination; D005240:Feasibility Studies; D005298:Fertility / Q000187:drug effects; D066298:In Vitro Techniques; D012098:Reproduction / Q000187:drug effects*
D052244:Endocrine Disruptors