Gradient scientists recently published an article evaluating the available research on dermal absorption of PFOA and recommend provisional values for exposure to PFOA in water or soil. This analysis may be relevant to certain other PFAS in other exposure media, such as consumer products.
The article, “Evaluating Dermal Absorption of Perfluorooctanoic Acid (PFOA) and Implications for Other Per- and Polyfluoroalkyl Substances (PFAS)” was published in the peer-reviewed journal Regulatory Toxicology and Pharmacology. Gradient scientists evaluated the available studies quantifying the rate and extent of dermal absorption of PFOA, a PFAS chemical that has been used to make products resistant to water, heat, and stains. This study advances the scientific understanding of dermal exposure to PFAS and is the first publication of its type.
The Gradient authors evaluated the reliability and physiological relevance of the limited number of studies directly measuring dermal absorption kinetics of PFOA in human skin. Further, the authors assessed whether the reported kinetic parameters were measured under appropriate conditions relevant to typical environmental exposures in humans (for example, using appropriate doses, solvents, experimental pH). From this evaluation, the authors identified the most appropriate values for use as absorption factors to estimate dermal exposures to PFOA from soil and water. These values are considered provisional for use in PFOA soil and water exposure assessments until more data become available.
By applying the recommended absorption factors, the Gradient authors estimated PFOA exposures from soil and water in children via both dermal and ingestion routes. Overall, results from this study indicate low dermal absorption of PFOA from soil and water compared to the ingestion pathway. The Gradient authors conclude that low dermal absorption is likely for other PFAS with similar physicochemical properties to PFOA (for example, chain length and functional group composition). These findings, and the recommended dermal absorption factors, can be considered for estimates of dermal absorption for PFAS with similar characteristics in other exposure media. For example, this study could be of use in estimating dermal absorption of certain PFAS from consumer products, such as textiles, cosmetics, and personal care products.
Read the article here.
If you have any questions regarding the article, please contact:
Andrew Yeh, Ph.D., DABT
Senior Toxicologist
Andrew.Yeh@gradientcorp.com
Robyn Prueitt, Ph.D., DABT
Principal
Robyn.Prueitt@gradientcorp.com
Barbara Beck, Ph.D., DABT, ATS, AAAS Fellow
Principal
Barbara.Beck@gradientcorp.com
Gradient is presenting at the Society of Risk Analysis (SRA) 2024 Annual Meeting, taking place December 8-12, 2024, in Austin, Texas.
Dr. Tom Lewandowski was featured recently in Inside EPA’s Inside TSCA, commenting on the contributions industry can make to help improve US EPA’s approach to alternatives assessment under TSCA.
Dr. Tom Lewandowski was featured in the November 20, 2024, edition of Inside EPA’s Inside TSCA, which provides news and analysis on the Toxic Substances Control Act (TSCA). The article summarizes a webinar co-presented with lawyer Sarah Amick of the law firm Wiley Rein on the status of alternatives assessment under different regulatory programs. In particular, the article addresses some concerns that US EPA’s TSCA process has failed to fully analyze and identify suitable alternatives for some chemicals undergoing regulatory review. The article notes that industry groups are challenging TSCA assessments, stating that the US EPA’s current approach to alternatives assessment merely scratches the surface in determining if alternatives for a certain chemical “are available,” leaving a need for more comprehensive information regarding the suitability of an alternative as an effective substitute for a chemical’s various uses.
Dr. Lewandowski highlighted alternatives assessment requirements and programs under TSCA and in states such as California and Washington, and emphasized the benefits of industry in leading, or at least providing technical input on, regulatory-driven alternatives assessments. Responding to a question from Inside TSCA, he stated, “greater attention on whether an alternative can actually perform is going to be worthwhile and that’s where industry has a lot to contribute . . . especially for complex products, or products with complex uses. The folks in industry are the ones that have the knowledge about whether something works and why, right? I think that’s where the EPA process could be improved, to get that sort of input on the performance side of things.”
Read the article here.
For more information on Gradient’s alternatives assessment and TSCA services, please reach out to Gradient.
Contact:
Tom Lewandowski, Ph.D., DABT, ERT, ATS
Principal
Tom.Lewandowski@gradientcorp.com
Dr. Alex Gauthier and Ms. Charlotte Marsh have been certified as a Diplomate of the American Board of Toxicology.
Congratulations, Alex and Charlotte!
ECHA identifies four new hazard categories for endocrine-disrupting chemicals in its updated guidance on the classification, labelling, and packaging of substances and mixtures (CLP).
On November 13, the European Chemicals Agency (ECHA) published an updated version of its Guidance on the Application of the CLP Criteria to address the new hazard classes for endocrine disruption (ED) and PMT/vPvM[1] properties. The guidance identifies four new hazard categories for endocrine-disrupting chemicals, including “known or presumed” (Category 1) and “suspected” (Category 2) endocrine disruptors for human health or the environment. The guidance describes the criteria for classification, and advocates for the use of a weight-of-evidence approach informed by expert judgment and considering all available relevant information.
For the ED hazard classes, the criteria involve an evaluation of endocrine activity, adverse effects, and a biologically plausible link via mode-of-action analyses. Assessment of endocrine activity may involve mechanistic information from in vitro and in vivo studies, as well as results from in silico models. The guidance provides example ED classifications for human health and environmental hazards based on estrogen, androgen, thyroid, and steroidogenic (EATS) and non-EATS modalities.
For existing substances placed on the European Union (EU) market before May 1, 2025, classification and labeling for the new endpoints is mandatory starting November 2026. For mixtures placed on the EU market before May 1, 2026, classification and labeling for the new endpoints is mandatory starting May 1, 2028. The mandatory deadlines are earlier for new substances and mixtures placed on the market after May 1, 2025, and May 1, 2026, respectively.
For more than two decades, Gradient scientists have been at the forefront of the topic of endocrine-disrupting chemicals, including:
Timeline to Adopt New EU Hazard Classes
To discuss preparing for the requirements of this regulation, please feel free to contact Gradient.
Contact:
Ari S. Lewis, M.S.
Principal
Tim Verslycke, Ph.D.
Principal
Charlotte Marsh, M.S., CPPS
Senior Toxicologist
Gradient Senior Toxicologist Dr. Alex Gauthier will be presenting at the ACT 2024 Annual Meeting, November 17-20, 2024 in Austin, TX.
“Weight-of-Evidence Carcinogenicity Assessment of GLP-1RA Drugs.” A. Gauthier, M. Khazaee, I. Mohar
Gradient Principal Scientist Dr. Isaac Mohar will be presenting at the Pharma Ed Resources, Inc. Extractables & Leachables West 2024 Summit, November 13-14, 2024 in La Jolla, CA.
“Qualification of Extractables and Leachables for Combination Products.” I. Mohar, E. Hill (BA Sciences)
Join Trends authors in a webinar expanding on their articles in the Fall 2024 issue on energy and the environment. Topics include challenges in evaluating PM2.5 toxicity, environmental and community impacts of large data centers, and potential human health and environmental risks of carbon dioxide capture chemicals. You can read the full issue of Trends here.
A recently published commentary authored by Gradient scientists evaluates the epidemiology, experimental animal, and mechanistic evidence behind the IARC’s recent PFOA and PFOS cancer classifications.
In November 2023, the International Agency for Research on Cancer (IARC) finalized its evaluation of the carcinogenicity of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), classifying PFOA as Group 1 (“carcinogenic to humans”) and PFOS as Group 2B (“possibly carcinogenic to humans”). Gradient scientists recently published a commentary on this evaluation, in which they assessed the epidemiology, experimental animal, and mechanistic evidence used as the basis for IARC’s conclusions.
Specifically, the commentary addresses IARC’s approach for considering mechanistic evidence in assessments of potential carcinogenicity. The mechanistic evidence for PFOA and PFOS was used to upgrade IARC’s classifications for these substances to higher carcinogenicity categories than were initially determined from the epidemiology and experimental animal evidence. For example, PFOA was initially classified as Group 2A (“probably carcinogenic to humans”) based on limited epidemiology evidence and sufficient experimental animal evidence, but was upgraded to Group 1 after consideration of mechanistic evidence. Similarly, PFOS was initially classified as Group 3 (“not classifiable as to its carcinogenicity”) based on inadequate epidemiology evidence and limited experimental animal evidence, but was upgraded to Group 2B after consideration of mechanistic evidence. The Gradient authors demonstrated that IARC’s approach did not consider the quality, external validity, and relevance of the mechanistic evidence and concluded that IARC’s approach for evaluating mechanistic evidence did not constitute a systematic or robust mechanistic assessment of carcinogenicity. Further, the authors concluded that IARC overstated the available evidence for the carcinogenicity of PFOA and PFOS.
The commentary goes on to discuss that the classification of a substance as carcinogenic to humans by IARC, or other agencies, does not consider how much exposure to the substance is needed to cause cancer and, therefore, does not necessarily indicate that the substance will cause cancer at human-relevant exposure levels and pose a public health concern.
Read the commentary here: “Commentary: Understanding IARC’s PFOA and PFOS Carcinogenicity Assessments“
Gradient is presenting at the ISES 2024 Annual Meeting, taking place October 20-24, 2024, in Montreal, Canada.