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.
Gradient is presenting at the SETAC North America 45th Annual Meeting, taking place October 20-24, 2024, in Fort Worth, Texas.
Gradient Senior Environmental Scientist and Geologist Dr. Qian Zhang will be presenting at the 2024 RemTEC & Emerging Contaminants Summit, October 15-17, 2024 in Westminster, CO.
US FDA recently held a public meeting to introduce a two-pronged, fit-for-purpose process for post-market assessment of chemicals in food to be implemented by the agency’s newly established Human Foods Program (HFP).
On September 25, 2024, the US Food and Drug Administration (US FDA) held a public meeting on its proposal to develop an enhanced systematic process for post-market assessment of chemicals in food under the newly established Human Foods Program (HFP). In this meeting, US FDA provided additional details regarding the process outlined in its recent discussion paper and an opportunity for external stakeholder comments.
To date, US FDA has conducted its post-market assessment of chemicals in food on an ad hoc basis, centering its activity around regulatory petitions or resubmissions, issues of great public interest or inquiry, and potential topics identified by US FDA experts. In addition, most of the agency’s work in this capacity has not been publicized unless there was a regulatory action. In the public meeting, US FDA acknowledged that the increasing number of state-level restrictions and questions surrounding the adequacy of current pre-market systems have prompted the agency, in part, to develop this enhanced approach for post-market assessment.
In its proposal, US FDA outlines an approach that aims to leverage artificial intelligence (AI) to monitor and identify “signals,” which are then triaged and addressed in a fit-for-purpose manner. This two-pronged process includes assessments that are both focused (relatively limited in scope) and comprehensive (complex and resource intensive), and the agency intends to publish scientific assessments and/or conclusions from both assessment types. In addition, US FDA notes that the process should allow for flexibility to address chemicals with varying levels of pre-market activity, including generally recognized as safe (GRAS) substances, food and color additives, food contact substances, and environmental contaminants.
Gradient scientists are at the forefront of the toxicological assessment of food ingredients and contaminants, including conducting weight-of-evidence reviews, providing regulatory comments, and overseeing ingredient vulnerability assessments. To discuss this issue further, please contact:
Charlotte Marsh, M.S., CPPS
Senior Toxicologist
Charlotte.Marsh@gradientcorp.com
Ari Lewis, M.S.
Principal
Ari.Lewis@gradientcorp.com
Julie Goodman, Ph.D., DABT, FACE, ATS
Principal
Julie.Goodman@gradientcorp.com
California’s Toxic-Free Medical Devices Act prohibits the use of intentionally added DEHP in IV solution containers and tubing products beginning January 1, 2030.
California recently passed the Toxic-Free Medical Devices Act (AB 2300), prohibiting the use of di-(2-ethylhexyl) phthalate (DEHP) in almost all intravenous (IV) solution containers and tubing. The bill also prohibits replacing DEHP with eleven other specified ortho-phthalates, including benzyl-butyl phthalate (BBP), di-isononyl phthalate (DINP), and di-n-octyl phthalate (DNOP). The ban on intentionally added ortho-phthalates for IV containers starts on January 1, 2030, six months ahead of similar European Union (EU) restrictions; the ban on IV tubing starts on January 1, 2035. Unintentionally added DEHP, i.e., DEHP in an IV solution container or IV tubing product that is not used for functional or technical effect on the product, may be present at a quantity at or above 0.1 percent weight per weight (w/w).
List of Banned Ortho-phthalates (Including DEHP):
Exemptions to the Ortho-phthalates Ban Include:
Timeline of the Ortho-phthalates Ban:
Choosing the Right Alternatives
Do you need help selecting potential alternatives to satisfy California and EU requirements? Gradient’s experts specialize in alternative assessments comparing the hazards, performance, and regulatory trend of alternatives to prevent regrettable substitutions. When choosing the right alternative, it is also important to consider degradation products under clinical and harsh extraction solvent conditions to minimize safety concerns.
Our colleagues at Cambridge Polymer Group offer holistic thinking on material selection. For example, downstream sterilization techniques dictate upstream material selection, but this is often overlooked until the very end. Choice of starting material must be driven by the anticipated end-use, and often this is influenced by forces out of the designer’s control, such as the regulatory bans being discussed here.
“Selecting the right alternatives goes beyond engineering and performance. It requires holistic evaluations of biological safety and material regulatory trends, all tailored to your device and manufacturing processes.”
Medical Device Approval
A DEHP-free reformulation will require pre-approval from US FDA and/or updates to the product’s design history file. Gradient’s team of medical device experts can help with the biological evaluation and toxicological risk assessment from the material change. In addition, Cambridge Polymer Group can offer material selection consulting support, as well as testing, including chemical characterization.
Gradient Contacts:
Jiaru Zhang, M.P.H., DABT
Principal Scientist
Jiaru.Zhang@gradientcorp.com
Joel M. Cohen, Sc.D., DABT
Principal
Joel.Cohen@gradientcorp.com
Lindsey Borton, M.P.H.
Principal
Lindsey.Borton@gradientcorp.com
Cambridge Polymer Group Contact:
Gavin Braithwaite
CEO
gavin@campoly.com
Cambridge Polymer’s Additive Analysis Services
Gradient Principal Ari Lewis will be presenting at the 2024 Society for Chemical Hazard Communication (SCHC) Annual Meeting, September 24-26, 2024 in Charlotte, NC.
Gradient Principal Dr. Tom Lewandowski will be presenting on a panel at the 2024 Prop. 65 Annual Conference in San Francisco, CA on September 23, 2024.