Letter to the editor about the article “Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts” by Garvey et al. (2023)

This letter is written regarding the recently published paper, Garvey et al. (2023).

“Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts,” doi:10.1080/10408444.2023.2194913.

I am writing to correct inaccuracies in the information about the use of immune system effects as the critical endpoints for toxicity factors (Reference Doses [RfDs]; Minimal Risk Levels [MRLs]) for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) that Garvey et al. attributed to my publication, Post (2021).

Garvey et al. state:

Currently, there are few examples of use of immune endpoints as critical effects for deriving toxicity values (e.g. RfDs). Some regulatory agencies have used other critical effect endpoints (e.g. developmental) to derive toxicity values for PFOA and PFOS, often accounting for the immune endpoint in the database uncertainty factor. (see review in Post 2021)

The statement by Garvey et al. (2023) that few toxicity factors for PFOA and PFOS are based on immune endpoints does not accurately reflect the information presented in Post (2021). Specifically, Table 3 of Post (2021) shows that of the eight states whose drinking water guidelines and RfDs for PFOS were reviewed, most (six) states used an immunological endpoint as the critical effect for their PFOS RfDs, one state used a database uncertainty factor to account for potentially more sensitive effects (specified in the state’s supporting documentation as immune system effects), and one state did not derive its own RfD but rather used the RfD based on developmental effects developed by the U.S. Environmental Protection Agency in 2016. Additionally, Post (2021) discusses that the European Food Safety Authority’s (EFSA CONTAM Panel 2020) Tolerable Daily Intake for PFOA, PFOS, and two other long-chain PFAS is based on immune system effects (decreased antibody response to vaccination) in breastfed children.

Post (2021) also discusses that the Agency for Toxic Substances and Disease Registry (ATSDR 2021) did not use immune system effects as the primary basis for its PFOS MRL (analogous to an RfD), but instead incorporated a modifying factor (i.e. uncertainty factor) of 10 to account for potentially more sensitive immune effects. However, while not discussed in Post (2021) due to the journal’s manuscript length limitations, ATSDR (2021) concluded that immune system effects are more sensitive endpoints for PFOS toxicity than the developmental effects used as the primary basis for the PFOS MRL. ATSDR (2021) states that immune system effects were not used as the primary basis for the PFOS MRLs because the toxicokinetic parameters needed for MRL development were not available for the strains of mice used in the immunotoxicity studies. Based on measured serum PFOS levels, ATSDR (2021) then developed an “alternative” PFOS MRL based on immunotoxicity that is numerically very close to the primary MRL. The consistency in the primary and alternative MRLs indicates that the primary MRL based on developmental effects, which includes a modifying factor of 10, is protective for immune system toxicity.

It is also noted that Garvey et al. does not cite Pachkowski et al. (2019) a highly relevant peer-reviewed publication on the derivation of an RfD for PFOS based on an immune endpoint (for which I am a co-author). Pachkowski et al. (2019) conclude that decreased plaque forming cell response to a foreign antigen in mice caused by PFOS “is a valid indicator of immunosuppression and is an adverse effect that is relevant to the human health risk from PFOS exposure,” and that “this conclusion is consistent with and supported by epidemiologic evidence for immunosuppression.”

Thank you for the opportunity to clarify the information that Garvey et al. (2023) attributed to my publication, Post (2021), about the use of immune system effects as the basis for toxicity factors for PFOS.

Declaration of interest

The author provides scientific support to the New Jersey Department of Environmental Protection (NJDEP) on PFAS issues. She is also a member of the New Jersey Drinking Water Quality Institute (NJ DWQI), an advisory body to NJDEP that recommended the Maximum Contaminant Levels for PFOA and PFOS that were adopted by NJDEP. The views expressed in this letter are those of the author and do not necessarily represent the views or policies of the NJDEP or the NJ DWQI. This letter was written as part of the author’s work at the New Jersey Department of Environmental Protection.