Assays in Endocrine Safety Pharmacology

Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009

“…Repeated administration (at least 7 days) is generally required to reach a steady state for the response and adaptation of hormone dependent organs (Sandow, 2006). At least two doses are necessary for a sufficient effect size and to achieve a biologically relevant (and statistically significant), difference between treated groups and control group.…”

Drug safety testing paradigm, current progress and future challenges: an overview

“…Early compound profiling by in vitro safety pharmacology can flag for receptor-, enzyme-, transporter-and channel-related liabilities of compounds and interprets these data in conjunction with absorption, distribution, metabolism and excretion (ADME) and toxicity characteristics, determined either in vitro or in vivo. Useful review of the appropriate use of safety pharmacology assays and their predictive value has been provided elsewhere (Guth et al, 2004;Whitebread et al, 2005;Sandow, 2006;Baldrick, 2008a;Valentin and Hammond, 2008;Cavero, 2009;Valentin et al, 2009;Gintant, 2011;Leishman et al, 2012;Hamdam et al, 2013;Parkinson et al, 2013). Table 4 enlists the various tests available for screening compounds for cardiovascular, central nervous and respiratory system-related liabilities.…”