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Testing for departures from additivity in mixtures of perfluoroalkyl acids (PFAAs)
Citation:
Carr, C., A. Watkins, Cynthiaj Wolf, B. Abbott, C. Lau, AND C. Gennings. Testing for departures from additivity in mixtures of perfluoroalkyl acids (PFAAs). TOXICOLOGY. Elsevier Science Ltd, New York, NY, 306:169-75, (2013).
Impact/Purpose:
Availability of information regarding potential for additivity of PFAAs in mixtures is critically important for risk assessors who are concerned with the ability of compounds to affect human health and impact ecological systems. It is clear that exposures are not to single compounds, but to mixtures of the PFAAs. This paper presents the results from data collected using the design from Carr, et a!. along with subsequent analyses that were performed to classify the relationships among mixtures of PFAAs.
Description:
This study is a follow-up to a paper by Carr, et al. that determined a design structure to optimally test for departures from additivity in a fixed ratio mixture of four perfluoroalkyl acids (PFAAs) using an in vitro transiently-transfected COS- 1 PPARa reporter model with an NHANES-based mixing ratio. Availability of information regarding potential for additivity of PFAAs in mixtures is critically important for risk assessors who are concerned with the ability of the compounds to affect human health and impact ecological systems. It is clear that exposures are not to single compounds, but to mixtures of the PFAAs. This paper presents the results from the data collected using the design from Carr, et a!. along with subsequent analyses that were performed to classify the relationships among mixtures of PFAAs. A non-linear logistic additivity model was employed to predict relative luciferase units (RLU), an indicator of PPARO activation. The results indicated a less than additive relationship among the four PFAAs. To determine if the possible “antagonism” is from the competition among or between carboxylates and sulfonates, four different binary mixtures were also studied. There was a less than additive relationship in all four binary mixtures. These findings are generally similar to two other reports of interfering interactions between PFAAs in mixtures. The most conservative interpretation for our data would be an assumption of additivity (and lack of a greater than additive interaction), with a potential for antagonistic interactions.