On January 11, 2021, scientists collaborating in the European human biomonitoring initiative (HBM4EU) published a study in Reproductive Toxicology showing that lipophilic chemical mixtures from the human placenta exhibited effects on thyroid function and showed estrogen and androgen receptor activation.

The multinational team led by Andrea Rodríguez-Carrillo extracted 24 placenta samples and tested the resulting xenobiotic chemical mixtures in one in vivo and four in vitro bioassays for estrogen, androgen, and thyroid effects. Different biological pathways were affected simultaneously, however, most extracts had shown estrogenic activity and affected thyroid function in vitro.

According to the researchers, these results indicate that fetuses may be exposed to complex mixtures of synthetic chemicals which may negatively influence their healthy development. Furthermore, this study elucidates how extracting chemical mixtures from human samples and their subsequent testing for bioactivity in a combination of both in vitro and in vivo bioassays can help to identify chemicals or combinations of chemicals that most strongly affect the observed mixture toxicity. This approach is also known as effect-based testing. A previous study led by Paulo Indiveri already identified 13 compounds including benzophenone (CAS 119-61-9) in chemical extracts of placenta tissue, and it found the chemical mixtures exhibited androgenic activity.

The authors conclude: “The use of this combined approach together with the information provided by additional biomarkers of effect (e.g. hormone levels, biochemical parameters, etc.) would help to strengthen the weight of evidence in observational studies linking chemical exposures to health outcomes.”

HBM4EU will end this year but funding is expected to continue under the next EU research framework program, Horizon Europe.

Humans are exposed to a large number of man-made chemicals on a daily basis, many of which occur in complex mixtures. However, in many cases, the effects on human health, especially unborn life, remain unclear. Within the HBM4EU project, the researchers aim to link the presence of chemical mixtures to effects on human health by running several complementary biomarkers assays.


Andrea Rodríguez-Carrillo et al (June 2020). “Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas.” Reproductive Toxicology

Paulo Indiveri et al (August 2014 ). “Analytical methodology for the profiling and characterization of androgen receptor active compounds in human placenta.” Reproductive Toxicology