SOT 2019: Q&A with Dr. Daniel Kougias

Posted on Behalf of  Daniel Kougias

Please read below for more information from Daniel Kougias on his SOT presentation.

1.      What was the title of your presentation?

The title of my presentation was "Evaluation of International Screening Values for Perfluorooctane Sulfonate (PFOS)".


2.      What was the scope of your research?

We critically evaluated international and domestic regulatory values and their corresponding methodologies, in order to gain insight into the dose-response assessment approaches that have been adopted for PFOS to date.

3.      What did you find?

A total of 5 studies from 3 distinct species (mice, rats, and monkeys) served as the basis for the regulatory values evaluated. We found large differences for the underlying reference doses (RfDs), ranging from 0.0018 to 0.3 μg/kg bodyweight/day, and that this variation originates from differences in the application of uncertainty factors, pharmacokinetic considerations, and study and point of departure selection. In particular, the lone regulatory value based on a study in mice generated the most conservative RfD, whereas in general regulatory values based on studies in rats were less conservative and those based on studies in monkeys were the least conservative. Overall, while the range of RfDs identified for determination of the regulatory values were considerable, there was a much narrower range for the point of departure in animal studies, indicating that the treatment of values after study selection is the most significant factor accounting for the large range of RfDs. In view of this, it was found that the regulatory agencies that implemented physiologically based pharmacokinetic (PBPK) modeling to obtain a human equivalent dose generally generated more conservative RfDs.

4.      What are the next steps / what other research is needed?

This critical analysis may be used to identify the best practice for the evaluation of dose-response for PFOS. Additionally, further steps can be taken to evaluate whether the effects in animals that are used to develop the various state and federal agency RfDs are sufficiently adverse or mechanistically relevant to justify using them to develop values protective of humans.

 

For more information, please contact Dr. Daniel Kougias at Daniel.Kougias@cardno.com