Health risk assessment of Endocrine Disrupters – focus on bisphenol A and development of methodology

During the past decades there have been an increasing number of reports of chemicals with endocrine disrupting properties and associations between exposure to such substances and endocrine-related health effects in the general population as well as in wildlife. Endocrine disrupting compounds (EDCs) have lately been identified as substances of very high concern that should be phased out in new EU legislations for e.g. chemicals, plant protection products and biocides. There is thus an increased pressure on regulatory agencies to be able to efficiently and reliably identify, test and risk assess EDCs.

However, risk assessment of EDCs has proven complicated, in part due to the complex toxicity exhibited by hormonally active substances, but also because there are currently no generally agreed upon criteria within the EU or internationally that direct how to specifically identify compounds with endocrine disrupting properties.

This research aims at identifying how scientific uncertainties concerning the toxicity of EDCs can be reduced or handled to make health risk assessments of EDCs more transparent, systematic, and reliable. Literature studies are conducted that investigate the risk assessment process for EDCs within different regulatory frameworks in the EU, as well as the underlying toxicity data available to risk assessors and how the use of all available toxicity data can be improved. The much debated EDC bisphenol A (BPA) is used for a case study.

Regulatory toxicity testing of EDCs is hampered by the lack of standardized test methods with international regulatory acceptance that are adequate to identify and evaluate EDC toxicity. We have shown that non-standard research studies, i.e. studies not conducted according to standardized test guidelines, fill data gaps and contribute information that could be particularly important for the identification and risk assessment of EDCs. However, non-standard studies are often criticized for having methodological limitations or being insufficiently reported, limiting their use in regulatory risk assessment. Regulatory agencies commonly give more weight to standard than non-standard studies in risk assessment of BPA, despite the growing amount of research indicating that toxic effects at low doses are overlooked.

A framework of criteria and guidelines intended to enable transparent and systematic evaluation of non-standard research studies, as well as guidance for how to report in vivo research to meet the requirements for regulatory risk assessment, have been proposed. These tools are freely available online ( and intended to facilitate the use of non-standard research studies in regulatory risk assessment and hopefully improve the reliability of risk assessment conclusions for EDCs.

This project is a collaboration with the Department of Environmental Science and Analytical Chemistry (ACES) at Stockholm University (Drs Anna Beronius, Marlene Ågestrand, MSc Linda Molander and Professor Christina Raudén).

Contact person

Annika Hanberg, Professor


Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union.
Beronius A, Rudén C, Hanberg A, Håkansson H
Regul. Toxicol. Pharmacol. 2009 Nov;55(2):111-22

Risk to all or none? A comparative analysis of controversies in the health risk assessment of Bisphenol A.
Beronius A, Rudén C, Håkansson H, Hanberg A
Reprod. Toxicol. 2010 Apr;29(2):132-46

The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A: implications for toxicity testing.
Beronius A, Johansson N, Rudén C, Hanberg A
Toxicology 2013 Sep;311(1-2):13-26

Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals: a proposal to improve evaluation criteria and reporting.
Beronius A, Molander L, Rudén C, Hanberg A
J Appl Toxicol 2014 Jun;34(6):607-17

Bridging the gap between academic research and regulatory health risk assessment of Endocrine Disrupting Chemicals.
Beronius A, Hanberg A, Zilliacus J, Rudén C
Curr Opin Pharmacol 2014 Dec;19():99-104

Beronius A, A Hanberg (2013) Is it possible to determine thresholds for the effects of endocrine disruptors? – A summary of scientific argumentation from 15 relevant publications on endocrine disruption”. Report commissioned by the Swedish Chemicals Agency: KemI PM 2/13.

Beronius A, A Hanberg (2012) Low-dose effects of Bisphenol A identification of points of departure for the derivation of an alternative reference dose”. Report commissioned by the Swedish Chemicals Agency: KemI PM 8/12, September 2012.

Beronius A, A Hanberg, C Rudén (2010) Background paper on the risk assessment of bisphenol A for WHO, 2010.