Review Of The Environmental Protection Agency S Draft Iris Assessment Of Formaldehyde

Formaldehyde is ubiquitous in indoor and outdoor air, and everyone is exposed to formaldehyde at some concentration daily. Formaldehyde is used to produce a wide array of products, particularly building materials; it is emitted from many sources, including power plants, cars, gas and wood stoves, and cigarettes; it is a natural product in come foods; and it is naturally present in the human body as a metabolic intermediate. Much research has been conducted on the health effects of exposure to formaldehyde, including effects on the upper airway, where formaldehyde is deposited when inhaled, and effects on tissues distant from the site of initial contact. The U.S. Environmental Protection Agency (EPA) released noncancer and cancer assessments of formaldehyde for its Intergated Risk Information System (IRIS) in 1990 and 1991, respectively. The agency began reassessing formaldehyde in 1998 and released a draft IRIS assessment in June 2010. Given the complexity of the issues and the knowledge that the assessment will be used as the basis of regulatory decisions, EPA asked the National Research Council (NRC) to conduct an independent scientific review of the draft IRIS assessment. In this report, the Committee to Review EPA's Draft IRIS Assessment of Formaldehyde first addresses some general issues associated with the draft IRIS assessment. The committee next focuses on questions concerning specific aspects of the draft assessment, including derivation of the reference concentrations and the cancer unit risk estimates for formaldehyde. The committee closes with recommendations for improving the IRIS assessment of formaldehyde and provides some general comments on the IRIS development process.

The Integrated Risk Information System (IRIS) is a program within the US Environmental Protection Agency (EPA) that is responsible for developing toxicologic assessments of environmental contaminants. An IRIS assessment contains hazard identifications and dose-response assessments of various chemicals related to cancer and noncancer outcomes. Although the program was created to increase consistency among toxicologic assessments within the agency, federal, state, and international agencies and other organizations have come to rely on IRIS assessments for setting regulatory standards, establishing exposure guidelines, and estimating risks to exposed populations. Over the last decade, the National Research Council (NRC) has been asked to review some of the more complex and challenging IRIS assessments, including those of formaldehyde, dioxin, and tetrachloroethylene. In 2011, an NRC committee released its review of the IRIS formaldehyde assessment. Like other NRC committees that had reviewed IRIS assessments, the formaldehyde committee identified deficiencies in the specific assessment and more broadly in some of EPA's general approaches and specific methods. Although the committee focused on evaluating the IRIS formaldehyde assessment, it provided suggestions for improving the IRIS process and a roadmap for its revision in case EPA decided to move forward with changes to the process. Congress directed EPA to implement the report's recommendations and then asked the National Research Council to review the changes that EPA was making (or proposing to make) in response to the recommendations. Review of EPA's Integrated Risk Information System (IRIS) Process provides an overview of some general issues associated with IRIS assessments. This report then addresses evidence identification and evaluation for IRIS assessments and discusses evidence integration for hazard evaluation and methods for calculating reference values and unit risks. The report makes recommendations and considerations for future directions. Overall, Review of EPA's Integrated Risk Information System Process finds that substantial improvements in the IRIS process have been made, and it is clear that EPA has embraced and is acting on the recommendations in the NRC formaldehyde report. The recommendations of this report should be seen as building on the progress that EPA has already made.

Formaldehyde is widely present in the environment and is one of the highest production chemicals by volume, used in manufactured goods including wood products, permanent press fabrics, and household products. It is also formed by combustion sources and is present in smoke from cigarettes and other tobacco products, and in emissions from gas stoves and open fireplaces. In carrying out its mission to protect human health, the U.S. Environmental Protection Agency (EPA) identifies and characterizes the health hazards of chemicals found in the environment through its Integrated Risk Information System (IRIS) Program, which has reviewed the human health hazards resulting from formaldehyde exposure in several assessments. This report is a continuation of guidance from the National Academies on draft IRIS assessments of formaldehyde and other aspects of the IRIS program. This report reviews the 2022 Draft Assessment with regard to its adequacy and transparency in evaluating the scientific literature, use of appropriate methods to synthesize the current state-of-the science, and presentations of conclusions that are supported by the scientific evidence. The report concludes that the 2022 Draft Assessment follows the advice of prior National Academies reports and that its findings on hazard and quantitative risk are supported by the evidence identified. However, revisions are needed to ensure that users can find and follow the methods used in each step of the assessment for each health outcome.

Introduction -- Review of the styrene profile in the National Toxicology Program 12th report on carcinogens -- Independent assessment of styrene -- Biographic Information on the Committee to Review the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens -- Statement of task of the Committee to Review the Styrene Assessment in the National Toxicology Program 12th report on carcinogens -- Review of the literature search used in the National Toxicology Program 12th report on carcinogens -- Literature search strategies used in support of the committee's independent assessment of styrene.

The US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) program develops toxicologic assessments of environmental contaminants. IRIS assessments provide hazard identification and dose-response assessment information. The information is then used in conjunction with exposure information to characterize risks to public health and may be used in risk-based decisionmaking, in regulatory actions, and for other risk-management purposes. Since the middle 1990s, EPA has been in the process of updating the IRIS assessment of inorganic arsenic. In response to a congressional mandate for an independent review of the IRIS assessment of inorganic arsenic, EPA requested that the National Research Council convene a committee to conduct a two-phase study. Critical Aspects of EPA's IRIS Assessment of Inorganic Arsenic is the report of the first phase of that study. This report evaluates critical scientific issues in assessing cancer and noncancer effects of oral exposure to inorganic arsenic and offers recommendations on how the issues could be addressed in EPA's IRIS assessment.

Over the past several years, the US Environmental Protection Agency (EPA) has been transforming the procedures of its Integrated Risk Information System (IRIS), a program that produces hazard and doseâ€'response assessments of environmental chemicals and derives toxicity values that can be used to estimate risks posed by exposures to them. The transformation was initiated after suggestions for program reforms were provided in a 2011 report from the National Academies of Sciences, Engineering, and Medicine that reviewed a draft IRIS assessment of formaldehyde. In 2014, the National Academies released a report that reviewed the IRIS program and evaluated the changes implemented in it since the 2011 report. Since 2014, new leadership of EPA's National Center for Environmental Assessment (NCEA) and IRIS program has instituted even more substantive changes in the IRIS program in response to the recommendations in the 2014 report. Progress Toward Transforming the Integrated Risk Information System Program: A 2018 Evaluation reviews the EPA's progress toward addressing the past recommendations from the National Academies.

Trichloroethylene is a chlorinated solvent widely used as a degreasing agent in industrial and manufacturing settings. It is also used as a chemical intermediate in making other chemicals and is a component of products such as typewriter correction fluid, paint removers, adhesives, and spot removers. In 2001, EPA issued a draft health risk assessment and proposed exposure standards for trichloroethylene. PA's Scientific Advisory Board (SAB) reviewed the draft and it was issued for public comment. A number of scientific issues were raised during the course of these reviews. Assessing the Human Health Risks of Trichloroethylene identifies and assesses the key scientific issues relevant to analyzing the human health risks of trichloroethylene, considering pertinent toxicologic, epidemiologic, population susceptibility, and other available information, including relevant published scientific literature, EPA's 2001 draft health risk assessment of trichloroethylene, scientific and technical comments received by EPA from public and private sources, and additional relevant information to be provided by the sponsoring agencies. This report highlights issues critical to the development of an objective, realistic, and scientifically balanced trichloroethylene health risk assessment. Guidance for hazard characterization of trichloroethylene is presented in Chapters 2 through 10. Chapter 2 provides guidance for evaluating large sets of epidemiologic data. In Chapter 3, the committee applies this guidance as an example in its evaluation of the epidemiologic data on trichloroethylene and kidney cancer, and this example should help guide evaluations of other cancer risks. Chapter 3 also assesses new information on the kidney toxicity of trichloroethylene and its metabolites and potential modes of action. Chapters 4, 5, 6, 7, and 8 evaluate the key issues regarding liver toxicity and cancer, reproductive and developmental toxicity, neurotoxicity, respiratory tract toxicity and cancer, and immunotoxicity, respectively. However, the committee's review focused on mode-of-action information to understand how trichloroethylene might affect certain processes differently in different species. Chapter 9 discusses susceptibility to trichloroethylene and its metabolites, and Chapter 10 describes important factors in considering trichloroethylene in mixtures. Physiologically based pharmacokinetic models are evaluated in Chapter 11, and guidance is provided on future directions for model development. Finally, Chapter 12 considers issues related to dose-response assessment and quantitative assessment of risk.