Garvey, Gregory J and Anderson , Janket K and Goodrum, Philip E and Tyndall, Kirby H and Cox , L Anthony and Khatami , Mahin and Montor , Jorge Morales and Schoeny , Rita S and Seed , Jennifer G and Tyagi, Rajeev K and Kirman, Christopher R and Hays , Sean M (2023) Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts. Critical Review in Toxicology , 53 (1). pp. 34-51.

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Abstract

Immunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink". The panel concluded there is moderate evidence that PFOS and PFOA are immunotoxic, based primarily on evidence from animal data. However, species concordance and human relevance cannot be well established due to data limitations. The panel recommended additional testing that includes longer-term exposures, evaluates both genders, includes other species of animals, tests lower dose levels, assesses more complete measures of immune responses, and elucidates the mechanism of action. Panel members agreed that the Faroe Islands cohort data should not be used as the primary basis for deriving PFAS risk assessment values. The panel agreed that vaccine antibody titer is not useful as a stand-alone metric for risk assessment. Instead, PFOA and PFOS toxicity values should rely on multiple high-quality studies, which are currently not available for immune suppression. The panel concluded that the available PFAS immune epidemiology studies suffer from weaknesses in study design that preclude their use, whereas available animal toxicity studies provide comprehensive dataset to derive points of departure (PODs) for non-immune endpoints. The panel recommends accounting for potential PFAS immunotoxicity by applying a database uncertainty factor to POD values derived from animal studies for other more robustly supported critical effects.

Item Type:	Article
Additional Information:	The copyright of this article belongs to taylor and Francis Online
Uncontrolled Keywords:	Immunotoxicity; PFAS; immune disorders; reference dose; risk assessment; vaccine antibody titer; weight of evidence.
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	07 Jun 2023 08:03
Last Modified:	07 Jun 2023 08:03
URI:	http://crdd.osdd.net/open/id/eprint/3083

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