SLIM project in the "Volkskrant"

SLIM publications
The 'SLIM' consortium has published some of it's relevant findings in four recent scientific publications (see references below). During the project, data was collected from hundreds of chemicals in two specific databases. One contained data relating to toxicity effects on embryonic development and one database contained data on carcinogenic potential of chemicals. The papers and the results were mentioned in the Scientific Pages of the Dutch newspaper "Volkskrant" on March 18th, 2017.   

Scientific merits lead to adaptation in legislation
The four papers published all refer to data from one of these two databases. The results bring us a step closer to to the replacement and reduction of the use of animals for toxicological evaluation of chemicals. This could mean that in the majority of cases, performing tests with both rats and rabbits does not provide addionial information on the reproductive toxicity potential of medicines. The results in this paper will lead to a refinement of the current legislation, probably before the end of 2017. 

Two papers focus on reproductive toxicity of chemicals. The results indicate that for 2 out of 3 medicines, rats are equally sensitive as rabbits in showing effects of compounds on the embryonic development and reproduction.

The other two papers concern data-driven research on the carcinogenic potential of chemicals. The data presented in the paper show that acute (relatively short) exposure of animals to compounds is predictive for inducing carcinogenicity. This could mean that the amount cases where animals are exposed to chemicals for two years could be reduced by approximately 40-60%. The same information can be extracted from studies in rats that have been exposed for half a year. Pharmokinetic and pharmocodynamic studies are necessary to  supplement the data for an adequate evaluation. Reseanably, this could lead to adaptations to the international carcinogenicity testing guidelines.      

Scientific papers
P. T. Theunissen, S. Beken, B. K. Beyer,W. J. Breslin, G. D. Cappon, C. Chen, G. Chmielewski, L. De Schaepdrijver, B. Enright, J. E. Foreman, W. Harrouk, K. W. Hew, A. M. Hoberman, J. Y. Hui, T. B. Knudsen, S. B. Laffan, S. L. Makris, M. Martin, M. E. McNerney, C. L. Siezen, D. J. Stanislaus, J. Stewart, K. E. Thompson, B. Tornesi, G. Weinbauer, S. Wood, J. W. Van derLaan and A. H. Piersma. Comparison of rat and rabbit embryo–fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects. Critical Reviews in Toxicology. (accepted August 2016; Published October 2016)

P. T. Theunissen, S. Beken, B. K. Beyer,W. J. Breslin, G. D. Cappon, C. Chen, G. Chmielewski, L. De Schaepdrijver, B. Enright, J. E. Foreman, W. Harrouk, K. W. Hew, A. M. Hoberman, J. Y. Hui, T. B. Knudsen, S. B. Laffan, S. L. Makris, M. Martin, M. E. McNerney, C. L. Siezen, D. J. Stanislaus, J. Stewart, K. E. Thompson, B. Tornesi, G. Weinbauer, S. Wood, J. W. Van derLaan and A. H. Piersma. Comparison of rat and rabbit embryo–fetal developmental toxicity data for 379 pharmaceuticals: on systemic dose and developmental effects. Critical Reviews in Toxicology. (accepted August 2016; Published October 2016)

R.A. Woutersen, A.E. Soffers, E.D. Kroese, C.A. Krul, J.W. van der Laan, J. van Benthem J, Luijten M. Prediction of carcinogenic potential of chemicals using repeated-dose (13-week) toxicity data. Regul Toxicol Pharmacol. 81 (2016) 242 - 249 (accepted September 2016; Published September 2016)

J.W. van der Laan, W. H. Buitenhuis, L Wagenaar, A. E. Soffers, E. P. van Someren, C. A. Krul and R. A. Woutersen. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties. Frontiers in Medicine. (accepted September 2016; Published October 2016)