A weight of evidence approach relies on assessing all available information and weighing data by considering relevance and quality. For example, observation of an adverse effect in an animal (in vivo) study would be given greater weight than responses observed in cells in isolation (in vitro).
Numerous test methods – from in vitro studies at the cellular level to whole animals – have been developed to assess the potential of substances to interact with components of the endocrine system. Responses detected in vitro do not necessarily represent adverse effects nor predict toxicity in humans because these test systems do not include complete physiological systems, such as those present in whole animals. Laboratory animal studies provide the most relevant data for evaluating adverse effects on endocrine-sensitive tissues or reproductive capacity.
To determine whether a substance has the capacity to cause adverse effects via interactions with the endocrine system and whether the risk of exposure to that substance is significant, a weight of evidence evaluation is necessary. Such an evaluation will typically consider the following types of information:
The weight-of-evidence approach should use objective criteria for assessing the quality and reliability of available studies, integrating all relevant data, understanding of the mode of action and identifying relevant exposures in order to provide a strong and science-based determination of potential risk. When the weight of evidence is used consistently and uniformly by regulators,, it enables them to best assess the potential health and environmental effects of chemical substances, including crop protection products.
 United States Environmental Protection Agency. 2010. Weight of evidence guidance: evaluating results of EDSP tier 1 screening to identify candidate chemicals for tier 2 testing. http://www.epa.gov/endo
 Lamb JC, Boffetta P, Warren FG, Goodman JE, Hentz KL, Rhomberg LR, Staveley J, Swaen G, Van Der Kraak G, Williams A. 2014. Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals – 2012. Regul Toxicol Pharm. 69 (2014) 22-40.
 European Food Safety Authority Scientific Committee. 2013. Scientific Opinion on the hazard assessment of endocrine disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment. EFSA Journal 11(3):3132.
 United States Environmental Protection Agency. July 1999. Review of the Endocrine Disruptor Screening Program by a Joint Subcommittee of the Science Advisory Board and Scientific Advisory Panel. EPA-SAB-EC-99-013. http://www.epa.gov/scipoly/sap