Endocrine disrupting effects of PFCs: in vitro profiling and effect in rats exposed during development to a PFC plus/minus background exposure to a mixture of known endocrine disrupters

Perfluorinated compounds (PFC) are a diverse group of synthetically produced compounds, with the unique ability to repel water as well as oil - a property making them ideal for multiple purposes in a variety of consumer and industrial products. PFCs have been measured in the environment, as well as in human blood, urine and milk. Due to their long half-life in humans, there is a risk that exposure to these compounds can cause adverse effects. However, except for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), there is a large data gap regarding toxicological information on PFCs. The specific aims of this project are to
• Perform a broad toxicological in vitro profiling of various PFCs to pinpoint critical endocrine activities
• Knowledge building with regards to existing in vitro and in vivo data on endocrine and reproductive toxicity effects of PFCs to be used for selecting the specific PFC and for the planning of dose levels and endpoints for in vivo studies
• Investigate endocrine disrupting effects of developmental exposure to a PFC in experimental animal studies. The focus is adverse effects early and late in life, mixture effects, markers for adverse outcome pathways, as well as potential for non-monotonic dose response and low dose effects
• Provide knowledge relevant for evaluating the current principles for risk assessment of endocrine disrupters with regards to mixture effects, non-monotonic dose-response and low dose effects.
The results of the in vitro profiling of endocrine activity of PFCs is expected to be of value for regulatory considerations on the need for in vivo studies as well as regulatory considerations on how to group PFCs for cumulative risk assessment.
The new in vivo data on effects and mode of action of the tested PFC will be of major importance for risk assessment for the specific PFC as well as for this class of compounds in general. If the PFC induces endocrine disrupting effects during development at low doses, this may - together with the critical persistency of PFCs in humans – highlight the need for more PFC studies, and also be an important knowledge with regards to considerations of regulatory actions. The study of potential mixture effects of the PFC with a mixture of known endocrine disrupters is expected to provide further knowledge of relevance for regulatory considerations of grouping of substances for cumulative risk assessment.