Innovative Methodological Approaches to Study Replacement Chemicals’ Effects on Health: Flame Retardants and Bisphenol S

June 20, 2019
12:00 pm US Eastern Time

Slides & Resources


Karine Audouze. Combining Artificial Intelligence and Systems Biology for Bisphenol S Toxicity Evaluation.

Lola Bajard. Use of mechanistic information to evaluate the hazard and predict health effects of replacement flameretardants.


Karine Audouze

Carvaillo JC, Barouki R, Coumoul X, Audouze K. Linking Bisphenol S to Adverse Outcome Pathways Using a Combined Text Mining and Systems Biology Approach.
Environ Health Perspect, 2019.

Jiang L, Audouze K, Romero Herrera JA, Ängquist LH, Kjærulff SK, Izarzugaza JMG, Tjønneland A, Halkjær J, Overvad K, Sørensen TIA, Brunak S. Conflicting associations between dietary patterns and changes of anthropometric traits across subgroups of middle-aged women and men. Clin Nutr, 2019

Barouki R, Audouze K, Coumoul X, Demenais F, Gauguier D. Integration of the human exposome with the human genome to advance medicineBiochimie, 2018.

Barouki R, Melén E, Herceg Z, Beckers J, Chen J, Karagas M, Puga A, Xia Y, Chadwick L, Yan W, Audouze K, Slama R, Heindel J, Grandjean P, Kawamoto T, Nohara K. Epigenetics as a mechanism linking developmental exposures to long-term toxicity. Environ Int, 2018.

Lola Bajard

Ankley, G. T., Bennett, R. S., Erickson, R. J., Hoff, D. J., Hornung, M. W., Johnson, R. D., … Villeneuve, D. L. (2010). Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environmental Toxicology and Chemistry, 29(3), 730–741. https://doi.org/10.1002/etc.34

Bajard, L., Melymuk, L., & Blaha, L. (2019). Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and Adverse Outcome Pathways. Environmental Sciences Europe, 31(1), 14. https://doi.org/10.1186/s12302-019-0195-z

Judson, R. S., Houck, K. A., Kavlock, R. J., Knudsen, T. B., Martin, M. T., Mortensen, H. M., … Dix, D. J. (2010). In vitro screening of environmental chemicals for targeted testing prioritization: The toxcast project. Environmental Health Perspectives, 118(4), 485–492. https://doi.org/10.1289/ehp.0901392

Van der Veen, I., & de Boer, J. (2012). Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis. Chemosphere, 88(10), 1119–1153. https://doi.org/10.1016/j.chemosphere.2012.03.067

AOPwiki. https://aopwiki.org/

Scientists are developing new, innovative approaches to study health outcomes of different replacement chemicals. From flame retardants (FR) to bisphenol S (BPS), scientists are utilizing new tools to access the biological pathways and exposures to these replacement chemicals. Dr. Karine Audouze and Dr. Lola Bajard highlighted their methodologies and health impacts observed in their studies of new FR and BPS.    

In a new study, Dr. Audouze and colleagues used an integrative approach that combined a new tool called AOP-helpFinder and systems biology to assess the association between bisphenol S (BPS) and obesity. During the webinar Dr. Audouze discussed how she sought to identify associations from available sources of information between BPS and components of adverse outcome pathways (AOPs), that include molecular initiating event (MIE), key event (KE) and adverse outcome (AO). AOP-helpFinder is a hybrid tool based on text mining, that is used to identify and extract co-occurrence of terms, and graph theory to quantify the co-occurrence and prioritize them. The use of such computational approaches was illustrated with the finding associating BPS and obesity.

During this webinar Dr. Bajard presented her novel approach to researching chemicals replacing brominated diphenyl ester (PBDEs) and hexabromocyclododecane (HBCDD), which were restricted from use in flame retardants (FRs).To comply with flammability standards, FRs are used in most consumer products and people are chronically exposed to these chemicals. Many diverse chemicals are being used as replacements for PBDEs and HBCDD, and information regarding their health effects, especially to humans, is very limited. In Dr. Bajard’s study, she and her colleagues collected in vivotoxicological data (research papers and reports from agencies), and in vitro results from ToxCast, for a list of 52 replacement FRs. They found that the information currently available is insufficient to evaluate the hazard for most of the FRs used as replacement. For 9 FRs, substantial information indicates some toxicological concern but direct evidence of their health effects on humans is almost absent. For these 9 FRs, they then used mechanistic information from the Adverse Outcome Pathway (AOP)-wiki to optimize and rationalize the information collected, and predict their potential effects on human health. This led them to identify several plausible mechanisms of toxicity, providing mechanistic support for several potential health effects related to neurotoxicity, hepatotoxicity and decrease in male fertility. However, with one exception, they did not find evidence for complete toxicity pathways leading from molecular interaction to adverse health outcome, revealing important gaps that should be addressed in future research.

Featured Speakers

Karine Audouze is Associate Professor in Systems biology and Bioinformatics bioinfo at Université de Paris. She is responsible on the Systems Toxicology axis, under the MetaTox team at Inserm U1124. Her main research interest is in the development of computational systems biology and predictive toxicology models to investigate the effects of exposure to environmental chemicals on human health. Her teaching activities are complementary to her scientific skills (from chemoinformatics to bioinformatics). She is the principal investigator of the European H2020 project OBERON, and the ANR project CREATIvE.


Lola Bajard is a scientist working at the Research Centre for Toxic Compounds in the Environment (Recetox) of Masaryk University (MU) in Brno, Czech Republic. Before joining Recetox in 2017, Lola Bajard acquired a solid background on molecular regulation of key processes of embryo development and cancer progression. She got her PhD at the Pasteur Institute in Paris, working on muscle development in the mouse embryo. Later she obtained a Marie curie and an HSFP grant to support her research on the formation of precursors of vertebrae in the zebrafish embryo, at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden. She then joined the Central European Institute of Technology (Ceitec) of MU in Brno, studying the tumor suppressor Axin1. Her current research is part of the European project HBM4EU (Human biomonitoring for Europe), a joint effort of 28 countries, that aims at generating evidence of the actual exposure of citizens to chemicals and the possible health effects in order to support policy making. She is particularly interested in mechanistic-based toxicology and how this can be used to prioritize and predict health effects of novel chemicals, in a global effort of reducing animal testing. Her project is focused on novel flame retardants used as replacement for the polybrominated diphenyl ethers (PBDEs) that were banned after being included into the Stockholm convention on POPs.

This webinar was moderated by Jerry Heindel, PhD, founder and director of Commonweal's Healthy Environment and Endocrine Disruptor Strategies (HEEDS). It lasted for 45 minutes and was recorded for our call and webinar archive.