Cefic-lri Programme | European Chemical Industry Council

EMSG56-BASF: Combined Low-dose Exposures to Anti-androgenic Substances

Principal Investigator

Dr. Steffen Schneider
GV/TA – Z470, Experimental Toxicology and Ecology
67063 Ludwigshafen
Germany
Tel: +49 621 60 58144

Fax: +49 621 60 58134

Collaborators

Dr. Stephanie Melching-Kollmuss, BASF SE, DE, stephanie.melching-kollmuss@basf.com
Dr. Roland Buesen, BASF SE, DE, roland.buesen@basf.com
Dr. Hennicke Kamp, BASF SE, DE, hennicke.kamp@basf.com
Dr. Burkhard Flick, BASF SE, DE, burkhard.flick@basf.com

Prof. Dr. Mohamed Benahmed, Bâtiment Universitaire Archimed, FR, mohamed.benahmed@unice.fr

Description

Considering the available definitions of endocrine disrupting compounds (Weybridge, 1996 and WHO/IPCS, 2002) it is recommended to follow an appropriate experimental design, duration of exposure, and completeness of relevant endpoints (OECD, 2002). As expected human exposures to chemicals, pesticides, biocides, cosmetic ingredients are far below the NOAELs identified in the animal studies, combination studies reflecting these ranges of exposure could represent relevant bases for regulatory decisions with respect to mixture risk assessments. Even lower doses, corresponding to legally binding reference values (like e.g. ADIs, DNELs, RfC) would be appropriate.

This project is organized in three work packages. The androgen system has been chosen exemplarily for any endocrine system, based on the most comprehensive techniques and analyses already established in the laboratory facilities of the project team.

In addition to the workpackages, BASF is sponsoring the conduct of in-vitro studies which focus on describing the potential of a compound to interfere with the endocrine system by determining their receptor activity as well as interference with the steroidogenesis of androgens. Furthermore, downstream signal pathways of relevant receptors will be investigated.

Related Publications

Publications:

Fussell KC, Schneider S, Buesen R, Groeters S, Strauss V, Melching-Kollmuss S, van Ravenzwaay B. Investigations of putative reproductive toxicity of low-dose exposures to flutamide in Wistar rats. Arch Toxicol. 2015 Dec;89(12):2385-402.

Melching-Kollmuss S, Fussell KC, Schneider S, Buesen R, Groeters S, Strauss V, van Ravenzwaay B. Comparing effect levels of regulatory studies with endpoints derived in targeted anti-androgenic studies: example prochloraz. Arch Toxicol. 2017 Jan;91(1):143-162.

Flick B, Schneider S, Melching-Kollmuss S, Fussell KC, Gröters S, Buesen R, Strauss V, van Ravenzwaay B. Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats. Arch Toxicol. 2017 Apr;91(4):1941-1956.

Schneider S, Fussell KC, Melching-Kollmuss S, Buesen R, Gröters S, Strauss V, Jiang X, van Ravenzwaay B. Investigations on the dose-response relationship of combined exposure to low doses of three anti-androgens in Wistar rats. Arch Toxicol. 2017 Dec;91(12):3961-3989.

Presentation:

Markus Junker. Endocrine Disruptors: Industry workshop outcomes. Cefic-LRI 14th Annual Workshop, November 2012, Brussels, Belgium.

Poster:

Karma C. Fussell, Stephanie Melching-Kollmuss, Sibylle Groeters, Volker Strauss, Benazir Siddeek, Mohamed Benahmed, Markus Frericks, Bennard van Ravenzwaay and Steffen Schneider. Endocrine exposure at environmentally relevant concentrations. Cefic-LRI 14th Annual Workshop, November 2012, Brussels, Belgium.

Stephanie Melching-Kollmuß, Steffen Schneider, Karma C. Fussell, Sibylle Groeters, Volker Strauß, Benazir Siddeek, Mohamed Benahmed, Markus Frericks and Bennard van Ravenzwaay. Investigation of Flutamide at Environmentally Relevant Concentrations. 52nd Annual Meeting and ToxExpo, April2013, San Antonio, TX, USA.

Sibylle Groeters, Steffen Schneider, Karma C. Fussell, Volker Strauß, Markus Frericks, Stephanie Melching-Kollmuß, Benazir Siddeek, Mohamed Benahmed and Bennard van Ravenzwaay. Investigation of Vinclozolin at Environmentally Relevant Concentrations. 52nd Annual Meeting and ToxExpo, April2013, San Antonio, TX, USA.

Fussell Karma C., Steffen Schneider, Stephanie Melching-Kollmuß, Sibylle Groeters, Volker Strauß, Benazir Siddeek, Mohamed Benahmed, Markus Frericks and Bennard van Ravenzwaay. Endocrine Exposure at Environmentally Relevant Concentrations. 52nd Annual Meeting and ToxExpo, April2013, San Antonio, TX, USA.

Karma C. Fussell, Stephanie Melching-Kollmuss, Sibylle Groeters, Volker Strauss, Benazir Siddeek, Mohamed Benahmed, Markus Frericks, Bennard van Ravenzwaay, Steffen Schneider. Endocrine exposure at environmentally relevant concentrations. Cefic-LRI 14th Annual Workshop, November 2012, Brussels, Belgium.

Timeline: January 2011 > January 2013

LRI funding: € 600 000

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