EPA issues new chemicals decision framework to assess eye irritation and corrosion
The EPA has issued a decision framework to be used when assessing eye irritation and corrosion hazards for new chemicals under the Toxic Substances Control Act. The framework supports EPA’s mandate to develop and implement alternative test methods and strategies, or new approach methodologies (NAMs), that do not require vertebrate animal testing for assessing risk of injury to health or the environment.
Regulatory background on new chemicals under TSCA
- On June 22, 2016, the Frank R. Lautenberg Chemical Safety for the 21st Century Act was signed into law, amending the 1976 Toxics Substances Control Act (TSCA). TSCA manages risks from existing chemicals that are listed on the TSCA Chemicals Inventory, as well as risks from new chemicals. Chemicals not listed on the Inventory are considered new chemical substances.
- Section 5 of TSCA requires that anyone who plans to manufacture or import a new chemical substance must provide notice to EPA before initiating these activities (if not exempt). Exclusions are for substances that are managed by another agency or regulation, such as tobacco, drugs, munitions, food additives, cosmetics, pesticides, or nuclear materials. In addition, a chemical may be excluded if it is formed during manufacture or import of an article, manufactured solely for export or formed incidentally by a reaction, or is a mixture, impurity, naturally occurring material, a byproduct, or a non-isolated material. Other exemptions include a substance that is manufactured in small quantities for research or development, or in an amount less than 10,000 kg each year; has low environmental release and low human exposure (LoREX); will be used solely for test marketing; or if the substance is a polymer.
- If none of these exemptions or exclusions applies, a premanufacture notice (PMN) must be submitted to EPA at least 90 days prior to the manufacture or import. The PMN must contain the chemical identity, structure and formula, process diagram and description, production volume, byproducts and impurities, intended use, environmental release, disposal practices, human exposure, and existing available test data on the effect to human health or the environment.
- EPA groups PMN chemicals with shared toxicological properties into 56 chemical categories. The categories (acid chlorides, boron compounds, esters, persistent bioaccumulative and toxic (PBTs), etc.) are listed alphabetically and provide a definition of the category, hazard concerns, general testing strategy, occupational exposure controls (if relevant) and references. These categories accumulate data from past decisions which submitters and reviewers can utilize to facilitate reviews. While the categories do save resources for chemical reviews, risk management must then be developed along with possible actions to control potential risks, which is a heavy lift for the agency. The most recent version of the document listing the categories is from 2010.
- The New Chemicals Division (NCD) of the Office of Chemical Safety and Pollution Prevention (OCSPP) administers the New Chemicals Program (NCP). Statistics for the NCP may be reviewed here. The office conducts risk assessments as part of the new chemicals review process and determines whether new chemicals present unreasonable risks. NCD conducts both human health and ecological risk assessments. The new chemicals review process under the Lautenberg amendments contains 14 steps that include risk assessment. The process begins with a pre-screen, leading to chemistry review, hazard meetings, and scoping meetings.
- In 2018, EPA published its Strategic Plan to promote the development and implementation of alternative test methods within TSCA. The Strategic Plan has three core components: (1) identifying, developing, and integrating NAMs for TSCA decisions; (2) building confidence that the NAMs are scientifically reliable and relevant for TSCA decisions; and (3) implementing the reliable and relevant NAMs for TSCA decisions. The plan includes a list of alternative test methods and strategies, or NAMs.
- NAMs refer to any technology, methodology, approach (including computational/in silico models like QSARs), or a combination that can be used to provide information on chemical hazard and risk assessment that avoids the use of intact animals. For the purposes of TSCA, EPA recognizes NAMs as encompassing any “alternative test methods and strategies to reduce, refine, or replace vertebrate animals.” EPA maintains a list of NAMs that includes representative NAMs that EPA may consider. The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) also maintains a list of alternative methods accepted by U.S. agencies.
Decision framework for hazard identification of eye irritation and corrosion
- On January 9, the EPA published a new decision framework supporting NCP under TSCA. The objective of the document is to provide a decision framework for NCP to facilitate the identification of eye irritation or corrosion hazards for new chemical substances. The decision-making process is based on the prioritization of reproducible human-relevant data utilizing methods that use human cells or tissues known to be sensitive. The review process accepts data from studies approved by the Organization for Economic Co-operation and Development (OECD), EPA, or NICEATM. Other studies are outside the scope of this decision framework. NCP does not encourage the use of in vivo eye irritation testing using live rabbits.
- NCP uses three categories to identify new chemicals for their eye irritation potential: corrosive, irritating, and nonirritating. The flow chart of the decision framework provides the parameters and the prioritization of data.
- The first decision is to prioritize data by completing scientific quality assessments of all available data and their applicability to evaluating human eye irritation or corrosion potential.
- The second decision evaluates prioritized data derived from new chemical substances or from one or more appropriate analogues and their relevance to eye irritation/corrosion endpoint and to humans. NCP prioritizes reproducible data from human cell or tissue methods. If this data is available, the framework moves to determine if all three categories (corrosive, irritating, nonirritating) can be identified utilizing certain test methods (OECD test method TG 492B). If only two can be identified, test methods OECD TG 492 or OECD TG 494 are utilized.
- The framework moves on to the third decision concerning nonhuman tests including reproducible data from in chimico, in vitro and/or ex vivo test methods. Numerous OECD test methods are utilized depending on the hazard identification capability.
- If there is no data from eye irritation/corrosion, data from assessments of skin irritation/corrosion may be considered (Decision 4). Tests use all human cells or tissue, mixed human and nonhuman cells or tissue, or all nonhuman. If none of these is available, physicochemical properties, structural alerts, or other relevant data from the TSCA NCP Chemical Categories document may be utilized.
- Table 3 provides all methods and the principles of the tests. It also contains the applicability domain and limitations, as well as categorization and outcome type (full spectrum or binary).
- This new decision framework is an effort by OCSPP to improve NCD’s decision-making process when assessing eye irritation and corrosion. The decision framework is nonbinding on the agency and outside parties. If necessary, EPA can utilize other decision-making processes to assess eye irritation or corrosion without providing notice.
- In August 2023, AgencyIQ analyzed EPA’s Office of the Inspector General’s (OIG) report on the New Chemicals Division operating processes. The scathing report’s conclusion was its title, “The EPA Lacks Complete Guidance for the New Chemicals Program to Ensure Consistency and Transparency in Decisions.”
- According to the OIG, despite a plethora of NCD guidance documents, many are outdated and may not be facilitating NCD’s new chemical assessments, resulting in the agency’s failure to meet the 90-day PMN deadline. According to NCP statistics, 517 TSCA section 5 notices and other applications are currently under review; many which must be reviewed within 90 days. Meanwhile, application for exemptions have between 30- and 60-day review periods.
- EPA proposed updates to New Chemicals Regulations under TSCA in May 2023. The proposal includes amendments that would require notices are complete when submitted. This would reduce the “re-work” of risk assessments. Once finalized, the changes proposed would help reduce the length of time that new chemical notices are under review. The final rule is expected in April 2024.
To contact the author of this piece, please email Patricia Iscaro.
To contact the editor of this piece, please email Scott Stephens.