This section discusses EPA’s human health risk assessment and risk management practices and its processes for soliciting nominations and selecting chemicals for new and updated IRIS toxicity assessments. EPA’s ability to effectively implement its mission of protecting public health and the environment is critically dependent on credible and timely assessments of the risks posed by chemicals. Such assessments are the cornerstone of scientifically sound environmental decisions, policies, and regulations under a variety of statutes, such as the Safe Drinking Water Act, the Toxic Substances Control Act, and the Clean Air Act. EPA assesses the human health risks of chemicals using a model from the National Academies. This model includes four components: (1) hazard identification, (2) dose-response assessment, (3) exposure assessment, and (4) risk characterization (see fig. 1). For some, but not all chemicals, EPA conducts the first two sequential analyses of a human health risk assessment—that is, the hazard identification and dose-response assessment—under its IRIS Program. Taken together, these two steps are commonly referred to as IRIS toxicity assessments. EPA’s IRIS Program—managed by EPA’s National Center for Environmental Assessment within the Office of Research and Development—develops new IRIS toxicity assessments and updates existing IRIS toxicity assessments if revisions are warranted on the basis of newly published peer-reviewed studies. EPA program offices and regions combine information from IRIS toxicity assessments with the results from chemical exposure assessments to characterize risk, which provides information on the probability that the adverse effects described in hazard identification will occur under the conditions described in the exposure assessment. These four steps— hazard identification, dose-response assessment, exposure assessment, and risk characterization—comprise human health risk assessments, which EPA offices use to make risk management decisions. Risk management, as opposed to risk assessment, involves integrating the risk assessment information with other information—such as economic information on the costs and benefits of mitigating a risk, technological information on the feasibility of managing the risk, and the concerns of various stakeholders—to determine whether the health risks identified in a chemical risk assessment warrant EPA taking regulatory or other risk management actions. A typical IRIS toxicity assessment contains a qualitative hazard identification and quantitative dose-response assessment. The qualitative hazard identification identifies noncancer and cancer health effects that may be caused by exposure to a given chemical. For cancer effects, EPA qualitatively describes the carcinogenic potential of a chemical in a narrative that includes selecting a weight-of-evidence descriptor, ranging from “carcinogenic to humans” to “not likely to be carcinogenic to humans.” Following hazard identification, a dose-response assessment is conducted for both noncancer and cancer effects assuming adequate data are available. A quantitative dose-response assessment characterizes the quantitative relationship between the exposure to a chemical and the resultant health effects. The quantitative dose-response assessment relies on experimental data, primarily from either animal (toxicity) or human (epidemiology) studies. The noncancer dose-response assessment may include the following: an oral reference dose—an estimate (with uncertainty spanning perhaps an order of magnitude) of the daily oral exposure to a chemical that is likely to be without an appreciable risk of deleterious effects during a person’s lifetime—expressed in terms of milligrams per kilogram per day, and an inhalation reference concentration—an estimate (with uncertainty spanning perhaps an order of magnitude) of the continuous inhalation exposure to a chemical that is likely to be without an appreciable risk of deleterious effects during a person’s lifetime—expressed in terms of milligrams per cubic meter. According to EPA officials, the quantitative cancer dose-response assessment typically includes estimates of a chemical’s carcinogenic potency by both the oral and inhalation routes of exposure. For oral exposures, the “oral slope factor” is an estimated 95 percent upper bound on the increased cancer risk per increased unit of exposure (in mg/kg- day) to a chemical over a lifetime. For inhalation exposures, the “inhalation unit risk” is an estimated 95 percent upper bound on the increased cancer risk per increased unit of exposure (in µg/m in air) to a chemical over a lifetime. The toxicity values derived in both noncancer and cancer dose-response assessments—that is, the oral reference dose, inhalation reference concentration, oral slope factor, and inhalation unit risk—are often referred to as IRIS values. IRIS toxicity assessments estimate the potential health effects of lifelong (chronic) exposure to chemicals. According to the Office of Management and Budget (OMB), the IRIS Program is the only federal program that provides qualitative and quantitative assessments of both cancer risks and noncancer effects of chemicals. In addition, according to EPA’s Human Health Risk Assessment Strategic Research Action Plan, no other federal health assessment program has (1) a similar mission and scope or (2) internal and external peer review processes that are as rigorous. Specifically, the IRIS toxicity assessment process includes internal EPA review; two interagency reviews by other federal agencies and White House offices (e.g., OMB); public review and comment; and a rigorous, independent, external peer review. However, IRIS is not the only source of toxicity information available to EPA program offices and regions. For many chemicals, IRIS toxicity assessments are not available, applicable, or current; therefore, in some cases, EPA program offices and regions rely on toxicity information from other sources. Other sources include, but are not limited to the following: Toxicological Profiles and Minimal Risk Levels. The Agency for Toxic Substances and Disease Registry (ATSDR)—a federal public health agency of the U.S. Department of Health and Human Services— prepares Toxicological Profiles for hazardous substances in response to statutory requirements under the Comprehensive Environmental Response, Compensation, and Liability Act, commonly known as Superfund. ATSDR’s Toxicological Profiles typically evaluate three different exposure durations—acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). According to ATSDR’s website, during the development of toxicological profiles, if the agency determines that reliable and sufficient data exist to identify the specific health effects that result from exposure to a hazardous substance, the agency will derive Minimal Risk Levels. Minimal Risk Levels are an ATSDR estimate of daily human exposure to a hazardous substance at or below which that substance will likely not pose a measurable risk of adverse noncancerous effects—such as neurological, respiratory, and reproductive effects—over a specified time period. Minimal Risk Levels are substance-specific estimates, which according to ATSDR’s website are intended to serve as screening levels used by ATSDR health assessors and others to identify contaminants and potential health effects that may be of concern at hazardous waste sites. According to ATSDR’s website, for non-carcinogens, ATSDR adopted a practice similar to that of EPA’s oral reference dose and inhalation reference concentration. Unlike EPA’s IRIS Program, however, ATSDR does not develop quantitative cancer toxicity values. Provisional Peer Reviewed Toxicity Values (PPRTV). PPRTVs are toxicity values that EPA’s National Center for Environmental Assessment ordinarily prepares on an ongoing basis to support cleanup decisions at Superfund sites. PPRTVs are derived for chronic and subchronic exposure durations in instances where IRIS toxicity assessments are not available, and are sometimes derived for subchronic exposure durations when an IRIS toxicity assessment on chronic exposure exists. Also, while PPRTVs receive internal review by EPA scientists and external peer review by independent scientific experts, they differ from IRIS values in that they do not undergo the same rigorous process of peer review and public participation. California Environmental Protection Agency (Cal/EPA) Toxicity Assessments. Cal/EPA prepares toxicity assessments, which are peer-reviewed and provide quantitative values for both cancer and noncancer effects. According to Cal/EPA’s website, Cal/EPA’s Office of Environmental Health Hazard Assessment is responsible for developing and providing managers in state and local government agencies with toxicological and medical information relevant to managing risks and making decisions involving public health. The office develops procedures and practices for performing health risk assessments for those involved in environmental health issues, including policymakers, businesspeople, members of community groups, news reporters, and others with an interest in the potential health effects of toxic chemicals. Specifically, the office publishes “A Guide to Health Risk Assessment,” which outlines in a generalized form the four risk assessment steps in the National Academies model described above. EPA’s IRIS Program invites IRIS users to submit nominations for chemicals to be considered for new or updated IRIS toxicity assessments. The IRIS Program solicits nominations from EPA program offices and regions and other federal agencies by issuing a memorandum and solicits nominations from the public by publishing a solicitation in the Federal Register. Generally, the IRIS Program includes a list of criteria that the agency plans to use to prioritize chemicals for selection as part of the solicitation. The IRIS Program included the following criteria in its most recent 2011 nomination solicitation: (1) potential public health impact; (2) EPA statutory, regulatory, or program-specific implementation needs; (3) availability of new scientific information or methodology that might significantly change the current IRIS information; (4) interest to other governmental agencies or the public; (5) availability of other scientific assessment documents that could serve as a basis for development of an IRIS toxicity assessment; and (6) other factors such as widespread exposure to the chemical. After receiving nominations, IRIS Program staff conducts a preliminary literature search to determine whether there is sufficient information to develop toxicity values for the chemicals nominated. According to IRIS Program officials, the purpose of the literature search is to determine if there is sufficient scientific data from health studies that could be used to develop new IRIS toxicity assessments or update existing assessments. Following the preliminary literature search, the IRIS Program separates the nominated chemicals into two groups: (1) those for which health studies are available and could be used to develop or update an IRIS toxicity assessment and (2) those for which there are not enough data to develop an assessment. Next, according to IRIS Program officials, they provide EPA program offices and regions with an annotated list of chemical nominations that specifies the degree to which health studies are available for each chemical and ask for feedback regarding which chemicals are the highest priorities. After considering such feedback, the IRIS Program selects chemicals for new or updated IRIS toxicity assessments. The IRIS chemical nomination and selection process culminates in the publication in the Federal Register of the IRIS agenda— which contains, among other things, a list of chemicals for which the IRIS Program intends to initiate IRIS toxicity assessments, as well as a list of ongoing IRIS toxicity assessments. For example, the most recent IRIS agenda, published in May 2012, lists 15 IRIS toxicity assessments—with planned start dates ranging from fiscal year 2012 to fiscal year 2014—as well as a list of the 52 IRIS toxicity assessments that were already under way. According to the IRIS agenda, EPA considers its own resources and the availability of guidance, guidelines, and policy decisions in deciding when to start assessments for the selected chemicals. EPA has not done a recent evaluation of demand for IRIS toxicity assessments with input from users inside and outside the agency. EPA conducted its most recent evaluation of demand for IRIS toxicity assessments in September 2003, which included input from users inside and outside EPA, but it has not performed a similar review since that time. Without a clear understanding of current demand for IRIS toxicity assessments, EPA cannot adequately measure the program’s performance; effectively determine the number of IRIS assessments required to meet the statutory, regulatory, and programmatic needs of IRIS users; or know the extent to which unmet demand exists. EPA conducted its last evaluation of demand in 2003 at the request of Congress. In September 2000, due to concerns that EPA and state regulators were relying on potentially outdated scientific information, the Senate Committee on Appropriations requested that EPA conduct a needs assessment with public input to determine the need for increasing the annual rate of new and updated IRIS toxicity assessments.response to the Senate request, EPA conducted a needs assessment— the results of which are discussed in its September 2003 report, Needs In Assessment for U.S. EPA’s Integrated Risk Information System. According to the report, EPA estimated that 50 new or updated IRIS toxicity assessments a year were needed to meet user needs. Specifically, EPA estimated that completing 50 assessments annually would allow the agency to routinely update existing toxicity assessments in the IRIS database, as well as respond to immediate user needs for new or updated assessments. This estimate, according to the report, was based on EPA’s past experience soliciting nominations from EPA program offices and regions and information obtained through a July 2001 query of EPA program offices and regions and the public that requested information on which chemicals they considered priorities for assessment. However, based on our review of the report, we did not find sufficient support for the estimate. Specifically, the report did not describe how EPA’s past experience or its 2001 query were used to derive the report’s estimate that about 50 IRIS toxicity assessments per year were needed to meet demand. In addition, the report stated that because EPA received a small number of responses to the agency’s 2001 query, it is not clear if the responses received are necessarily representative of the broad range of IRIS users. Although EPA’s 2003 needs assessment is a decade old, EPA officials told us that the agency does not currently have plans to perform another evaluation of demand for the IRIS Program and that, due to changing conditions over the last 10 years the 2003 evaluation was not applicable to current conditions. IRIS officials stated that the IRIS Program’s primary mechanism for monitoring the needs of EPA’s program and regional offices at present is to perform outreach with EPA program offices and regions, such as holding quarterly meetings with program office representatives from each EPA program office and holding internal scoping meetings with representatives from EPA program offices and regions for certain chemicals. In response to our questions regarding current demand, IRIS Program officials told us that the annual need for IRIS toxicity assessments may likely be in the hundreds, though officials did not describe how they derived this number. We have previously reported on the need for EPA to comprehensively analyze its workload and workforce to effectively carry out its strategic goals and objectives. Specifically, in July 2011, we reported that the agency did not have a workload analysis to help determine the optimal numbers and distribution of staff among its laboratory enterprise—which is responsible for providing the scientific research, technical support, and analytical services that underpin its policies and regulations. In addition, we have previously reported that, in developing new initiatives, agencies can benefit from following leading practices for strategic planning. Congress enacted the Government Performance and Results Act (GPRA) in 1993 to improve efficiency and accountability of federal programs. We have reported that these requirements also can serve as leading practices for strategic planning at lower levels within federal agencies, such as planning for individual divisions, programs, or initiatives. Of these leading practices, it is particularly important for agencies to define strategies that address management challenges that threaten their ability to meet long-term goals—including a description of the resources needed to meet established goals. Without an evaluation of current demand for IRIS toxicity assessments that takes into account resource constraints, the IRIS Program risks not being able to develop a plan that lays out realistic goals based on current conditions. The IRIS Program’s chemical nomination and selection process, which the agency uses to gauge interest in the IRIS Program from users inside and outside of EPA, may not accurately reflect current demand for IRIS toxicity assessments. Our analysis of IRIS Program data indicates that the IRIS Program received nominations for 75 chemicals from EPA and non-EPA IRIS users in response to its most recent 2011 nomination period. However, the 75 chemicals received for the 2011 nomination period may not accurately reflect current demand for IRIS toxicity assessments. As about 1,000 new chemicals are listed for commercial use each year, demand for IRIS toxicity assessments is potentially very high, but the number of chemicals nominated may either overstate or understate actual demand. For example, it is not clear how many chemicals IRIS users did not nominate due to concerns that the IRIS toxicity assessment would not be completed in a timely manner. Officials from EPA’s Office of Water told us that even though they may need an IRIS toxicity assessment, they sometimes develop their own chemical toxicity assessments to meet their urgent or time-critical needs, such as meeting statutory deadlines. Also, given the long-standing challenges the IRIS Program has had in routinely starting new assessments, according to some EPA IRIS users, they chose not to nominate new chemicals for assessment and instead nominated chemicals that were already listed on the IRIS agenda as under way. For example, according to officials from EPA’s Office of Solid Waste and Emergency Response, due to the large number of chemicals already listed on the IRIS agenda and the IRIS Program’s limited resources, in some cases, they reiterated support for chemicals that were already listed on the agenda as under way rather than nominate new chemicals. IRIS Program officials told us that, although EPA program offices and regions and other IRIS users would like to see the IRIS Program produce more IRIS toxicity assessments each year, current resources constrain the speed at which the IRIS Program can complete them. For example, EPA issued 4 IRIS toxicity assessments in fiscal year 2012 (see fig. 2). EPA has issued from 2 to 11 IRIS toxicity assessments annually since fiscal year 2002. unable to keep up with demand for IRIS toxicity assessments, the agency had to prioritize its selection of chemicals for IRIS toxicity assessment. Furthermore, EPA has not clearly articulated under what circumstances IRIS toxicity assessments are not needed, and the IRIS Program’s process for prioritizing chemicals does not provide clarity regarding why specific chemicals are selected for assessment and others are not. According to IRIS Program officials, some chemicals may not need IRIS toxicity assessments. While the IRIS Program has developed criteria that are used to prioritize its selection of chemicals for IRIS toxicity assessment, it is not clear how it applies these criteria—including how it determines the circumstances under which program offices and regions may or may not need an IRIS toxicity assessment. As discussed earlier, the IRIS Program published its chemical selection criteria when it solicited nominations for IRIS toxicity assessment for its 2011 nomination period. However, in announcing that it had selected 15 IRIS toxicity assessments in its 2012 IRIS agenda, the IRIS Program did not explain and has not published information on, how the agency applied its selection criteria. OMB’s implementing guidance for internal control requirements for federal agencies emphasizes the need for agencies to develop policies that ensure the effectiveness and efficiency of their operations and, as part of that, emphasizes that information related to guidance should be communicated to relevant personnel at all levels within an organization and outside the agency in a relevant, reliable, and timely manner. In August 2012, IRIS Program officials told us that they were working to develop a better description of the nomination and selection process that will clarify how the agency applied the six criteria but, as of March 2013, had not done so. Consequently, for the chemicals that were nominated during the most recent 2011 nomination period, but not selected, it is not clear how many, if any, were excluded from consideration because they did not meet the IRIS Program’s selection criteria, because the IRIS Program determined that an IRIS toxicity assessment was not needed— or, alternatively, if they were not selected because of resource constraints or other reasons. EPA has not implemented an agencywide strategy for addressing the unmet needs of EPA program offices and regions when IRIS toxicity assessments are not available, applicable, or current. Specifically, EPA does not have (1) a strategy for identifying and filling data gaps that would enable it to conduct IRIS toxicity assessments for nominated chemicals that were not selected for IRIS toxicity assessment due to insufficient data and (2) agencywide guidance for addressing unmet needs when IRIS toxicity assessments are not available, applicable, or current—which is consistent with findings reported recently by EPA’s Inspector General and Science Advisory Board. EPA does not have a strategy for identifying and filling data gaps that would enable it to conduct IRIS toxicity assessments for nominated chemicals that were not selected for IRIS toxicity assessment because of insufficient scientific data from health studies. As discussed earlier, as part of the IRIS chemical nomination and selection process, IRIS Program officials separate nominated chemicals into two groups: (1) those for which sufficient scientific data from health studies exist that could be used to develop or update an IRIS toxicity assessment and (2) those for which sufficient data do not exist for developing an assessment. For example, as a part of its most recent 2011 nomination period, the IRIS Program dropped 11 of the 75 chemicals nominated from consideration because sufficient scientific data from health studies were not available to develop an IRIS toxicity assessment. One of the chemicals dropped from consideration due to insufficient data was nominated in 2005, 2007, and 2011. The chemical—iso-octane, or 2,2,4-trimethylpentane, which is a constituent of motor fuels—was nominated, according to officials with EPA’s Office of Underground Storage Tanks, within the Office of Solid Waste and Emergency Response, so that the office can determine appropriate cleanup levels for leaking underground storage tank sites. Moreover, Section 1505 of the Energy Policy Act of 2005 directed the EPA Administrator to, among other things, conduct a study on the effects on public health (e.g., the effects on children, pregnant women, minority or low-income communities, and other sensitive populations) of increased use of iso-octane and six other fuel additives as substitutes for methyl tertiary butyl ether (MTBE). While the IRIS Program prepared and issued an IRIS toxicity assessment that contained the qualitative hazard identification description of iso- octane in 2007, it was unable to derive quantitative IRIS values due to insufficient data on the chemical’s health effects in humans. According to EPA’s 2007 IRIS assessment of iso-octane, the IRIS Program did not develop quantitative estimates of noncancer and cancer risks because the studies needed to support such estimates were not available.Consequently, EPA’s Office of Underground Storage Tanks nominated iso-octane again in 2011. In response, according to IRIS Program officials, the IRIS Program evaluated the literature since the 2007 IRIS toxicity assessment was completed and determined that no new studies were available to support development of quantitative IRIS values. Therefore, iso-octane was not considered for an IRIS toxicity assessment in 2011. According to officials with the Office of Underground Storage Tanks, they meet with IRIS Program officials regularly, and the IRIS Program is aware of their need for IRIS toxicity assessments related to these chemicals. However, should officials with the Office of Underground Storage Tanks nominate iso-octane again; EPA cannot ensure that the data needed to prepare an IRIS toxicity assessment that includes quantitative IRIS values will be available and thus, allow EPA to address this unmet need. Without quantitative IRIS toxicity values for these chemicals, it is unclear how EPA will conduct a study of these chemicals on the effects on public health as required by the Energy Policy Act of 2005. The National Toxicology Program was created in 1978 as a cooperative effort to coordinate toxicology testing programs within the federal government, strengthen the science base in toxicology, develop and validate improved testing methods, and to provide information about potentially toxic chemicals to health, regulatory, and research agencies, scientific and medical communities, and the public. may also be a potential research source. Without such research—which is necessary to fill data gaps needed to develop IRIS toxicity assessments—the agency will be unable to ensure that it can respond to unmet EPA program offices’ and regions’ programmatic and public health needs in the future. EPA does not have agencywide guidance for addressing the needs of its program offices and regions when IRIS toxicity assessments are not available, applicable, or current. IRIS Program officials told us that, while there is no agencywide guidance, they work with staff from program offices and regions on a case-by-case basis to find alternatives to IRIS toxicity assessments. For example, IRIS Program officials told us that, in some cases, the Superfund Technical Support Center may be able to partially address the needs of the Office of Solid Waste or Emergency Response or regions by summarizing peer reviewed studies. In other cases, they said that they may work with the Office of Solid Waste and Emergency Response, as well as other program offices and regions, to determine if a PPRTV would meet their needs. In 2008, EPA’s Board of Scientific Counselors recommended that EPA consider using PPRTVs as an interim measure to meet its needs for some chemicals, if an IRIS toxicity assessment was not available, and recommended that well- developed PPRTVs be considered as a source of prioritization in the development of full IRIS documents. However, it is unclear how frequently program offices and regions use PPRTVs to support their statutory, regulatory, or programmatic needs—beyond their use in Superfund risk assessments—because EPA does not collect information on or have agencywide guidance on when a PPRTV, or other toxicity assessment, might be an appropriate alternative to an IRIS toxicity assessment. Without such guidance, EPA cannot ensure that it has a consistent approach for addressing the needs of program offices and regions when IRIS toxicity assessments are not available, applicable, or current. Under federal standards of internal control, agencies are to clearly document in writing internal control in management directives, administrative policies, or operating manuals and have it readily available for examination. Other non-EPA sources of toxicity information include ATSDR Minimal Risk Levels and Cal/EPA toxicity values. Although the Office of Solid Waste and Emergency Response developed the hierarchy of toxicity values specifically for the Superfund Program, officials stated that the hierarchy is generally used by all suboffices within the Office of Solid Waste and Emergency Response when IRIS toxicity assessments are not available or current. profile issues in their region because an IRIS toxicity assessment was not available. However, the officials noted that ATSDR does not develop cancer values. According to officials with the Office of Water—which is responsible for implementing, among other mandates, the Clean Water Act and Safe Drinking Water Act—they develop toxicity assessments for chemicals to meet statutory deadlines. For example, under the 1996 amendments to the Safe Drinking Water Act, every 5 years, EPA is to determine for at least five unregulated contaminants, including chemicals, whether regulation is warranted, considering those that present the greatest public health concern. Because of the limited number of IRIS toxicity assessments the IRIS Program can select and develop at one time, the Office of Water created the scheme to prioritize and nominate for IRIS toxicity assessment those chemicals that are the most controversial and high-profile, have a high economic impact, and will take more time and staff to complete. The Office of Water can then, according to officials from that office, develop its own assessments for chemicals that have less controversy surrounding them and take less time and staff to complete in order to meet some of its programmatic needs. Officials from the Office of Water told us that the office develops its own assessments for some chemicals because the IRIS Program would not be able to complete most of the needed toxicity assessments in time to meet the office’s statutory deadlines. Similarly, the Office of Pollution Prevention and Toxics, within the Office of Chemical Safety and Pollution Prevention, has developed its own toxicity assessments. The Office of Pollution Prevention and Toxics is responsible for implementing the Toxic Substances Control Act, which provides EPA with the authority to obtain more information on chemicals and to regulate those chemicals that the agency determines pose unreasonable risks to human health or the environment. In February 2012, the office announced plans to develop risk assessments on 83 chemicals. While the office has not nominated any chemicals for IRIS toxicity assessment over the past three nomination periods through the formal nomination process, according to EPA officials with the office, in developing its risk assessments, it plans to incorporate information from IRIS toxicity assessments to the extent such information is available, recent, and relevant. These officials told us that the risk assessments they are conducting in support of the Toxic Substances Control Act are often based on intermittent exposure to workers and consumers who are subject to chemicals contained in products. However, they also told us that, while the IRIS values contained in the database may not always be applicable, often other data available in the IRIS database are applicable, such as toxicity information for shorter term exposure scenarios that have long-lasting/persistent effects (e.g., development toxicity). In these cases, they said that they have used the hazard and dose-response information described in an IRIS toxicity assessment for a particular chemical to develop their own toxicity assessment. IRIS Program officials said that they are working with the Office of Pollution Prevention and Toxics and other EPA offices to find other options for assessing toxicity, such as PPRTVs, when IRIS toxicity assessments are not available, applicable, or current. While IRIS toxicity assessments may not be applicable in all situations, EPA does not have agencywide guidance that outlines the circumstances under which program offices and regions may or may not need IRIS toxicity assessments, or describes appropriate alternative sources to IRIS toxicity assessments. Our finding concerning the various approaches EPA program offices and regions use to address their need for toxicity assessments is consistent with findings reported recently by EPA’s Inspector General and Science Advisory Board. EPA’s Office of the Inspector General conducted a survey of 300 respondents from EPA program offices and regions in January 2013. The survey found that 34 percent of the 300 survey respondents indicated that they had experienced a situation in which they or their team researched a substance that was listed in IRIS but used toxicity values from another source instead of those available in IRIS. Of those respondents, 68 percent indicated that one of their top three reasons for doing so was because the alternate system source is more up-to-date with current scientific practice or other information. Additionally, 28 percent of all survey respondents indicated that they had experienced a situation in which they or their team developed their own toxicity values. However, more than a third of respondents indicated that there were no standard operating procedures or other guidance regarding how to choose a source of toxicity values for their office’s work. EPA’s Science Advisory Board has also reported on differences across the agency regarding the use of scientific information for decision making. For example, in July 2012, the Science Advisory Board reported that available resources for developing toxicity assessments, the number of scientific staff engaged in the work, and the institutional and legal framework supporting these assessments differ across the agency. The report also noted that some EPA programs and regions do not have the infrastructure required to generate all assessments needed to support their own activities and that scientists in these offices work within statutory constraints, often on an extremely short timetable and with limited budgets. Within those constraints, according to the report, they either assess available scientific information themselves or rely on the Office of Research and Development, other parts of EPA, or other federal or state agencies for the science assessments needed to support decision making. We have also reported on EPA’s fragmented and largely uncoordinated science activities. Specifically, in July 2011, we reported that EPA had not fully addressed the findings and recommendations of five independent evaluations over the past 20 years regarding long-standing planning, coordination, or leadership issues that hamper the quality, effectiveness, and efficiency of EPA’s science activities, including its laboratory operations. We recommended, among other things, that EPA establish a top-level science official with the authority and responsibility to coordinate, oversee, and make management decisions regarding major scientific activities throughout the agency, including the work of all program, regional, and Office of Research and Development laboratories.fully implemented it. In particular, while EPA expanded the responsibilities of the agency’s science advisor to coordinate, oversee, and make recommendations to EPA’s Administrator regarding the agency’s major scientific activities, as of March 2013, the agency had not given this official the authority to make management decisions regarding scientific activities across EPA as we recommended. In the absence of such authority, there is no agency mechanism for understanding and addressing the unmet needs for IRIS toxicity assessments. As a result, EPA may not be maximizing its limited resources or addressing the statutory, regulatory, and programmatic needs of EPA program offices and regions in a consistent manner. With tens of thousands of chemicals listed with EPA for commercial use in the United States and about 1,000 new chemicals listed for commercial use each year, demand for IRIS toxicity assessments is potentially very high. EPA’s IRIS Program develops new toxicity assessments and, as needed, updates information on existing toxicity assessments contained in the IRIS database. EPA has not evaluated demand for IRIS toxicity assessments with input from users inside and outside the agency since 2003, and although IRIS Program officials recognize that the 2003 estimate does not reflect current conditions, the agency does not plan to perform another evaluation of demand. Without a clear understanding of current demand for IRIS toxicity assessments, EPA cannot measure the program’s performance; determine the number of IRIS assessments required to meet the statutory, regulatory, and programmatic needs of IRIS users; or know the extent of unmet demand. The IRIS Program’s chemical nomination and selection process, which the agency uses to gauge interest in the IRIS Program from users inside and outside EPA, may not accurately reflect current demand for IRIS toxicity assessments. For example, it is not clear how many chemicals IRIS users did not nominate due to concerns that the IRIS toxicity assessment would not be completed in a timely manner. Furthermore, EPA has not clearly articulated how the IRIS Program applies the criteria it uses to prioritize the selection of chemicals for IRIS toxicity assessment—including how it determines the circumstances under which program offices and regions may or may not need an IRIS toxicity assessment. Consequently, for chemicals that are nominated, but not selected for IRIS toxicity assessment, it is not clear how many, if any, are excluded from consideration because they do not meet the IRIS Program’s selection criteria, because the IRIS Program determined that an IRIS toxicity assessment was not needed—or, alternatively, if they are not selected because of resource constraints or other reasons. EPA has not implemented an agencywide strategy for addressing the unmet needs of EPA program offices and regions when IRIS toxicity assessments are not available, applicable, or current. Specifically, EPA does not have a strategy for identifying and filling data gaps that would enable it to conduct IRIS toxicity assessments for nominated chemicals that were not selected for assessment due to insufficient data. Because EPA does not have a process in place for identifying and filling research gaps, it is unable to ensure it can respond to any unmet EPA program offices’ and regions’ programmatic and public health needs in the future. Also, EPA does not have guidance that outlines the circumstances under which program offices and regions may or may not need an IRIS toxicity assessment, or that describes appropriate alternative sources to IRIS toxicity assessments. Without guidance, EPA cannot ensure a consistent approach for addressing the needs of program offices and regions when IRIS toxicity assessments are not available, applicable, or current. We are making three recommendations to the EPA Administrator. To ensure that EPA can measure the IRIS program’s performance and determine the number of IRIS toxicity assessments required to meet the statutory, regulatory, and programmatic needs of IRIS users, we recommend that the EPA Administrator direct the Office of Research and Development to implement the following two actions without impeding the progress of ongoing assessments: Identify and evaluate demand for the IRIS Program to determine the number of IRIS toxicity assessments and resources required to meet users’ needs. Document how EPA applies its IRIS toxicity assessment selection criteria, including the circumstances under which program offices and regions may or may not need an IRIS toxicity assessment. To ensure that EPA maximizes its limited resources and addresses the statutory, regulatory, and programmatic needs of EPA program offices and regions when IRIS toxicity assessments are not available, we recommend that the EPA Administrator direct the Deputy Administrator, in coordination with EPA’s Science Advisor, to implement the following action: Once demand for the IRIS Program is determined, develop an agencywide strategy to address the unmet needs of EPA program offices and regions that includes, at a minimum: coordination across EPA offices and with other federal research agencies to help identify and fill data gaps that preclude the agency from conducting IRIS toxicity assessments, and guidance that describes alternative sources of toxicity information and when it would be appropriate to use them when IRIS values are not available, applicable, or current. We provided a draft of this report to EPA for its review and comment. EPA’s written comments and our detailed response to them are presented in appendix III. EPA also provided technical comments on our draft report, which we incorporated, as appropriate. In its written comments, EPA agreed with our findings and two of our recommendations and partially agreed with our third recommendation. Specifically, EPA agreed with our recommendations that the Office of Research and Development (1) identify and evaluate demand for the IRIS Program to determine the number of IRIS toxicity assessments and resources required to meet users’ needs and (2) document how EPA applies its IRIS toxicity assessment selection criteria, including the circumstances under which program offices and regions may or may not need an IRIS toxicity assessment. In its written comments, EPA stated that the Office of Research and Development this year will evaluate the potential future demand for IRIS toxicity assessments and the resources required to meet that demand. EPA also stated that it will better describe for internal and external stakeholders and the public the nomination and selection process for chemicals for IRIS toxicity assessments, including the rationale for not selecting nominated chemicals for IRIS assessment. With respect to our third recommendation, that EPA develop an agencywide strategy to address unmet need for IRIS toxicity assessments, in its written comments, EPA requested that we provide additional clarification and consider refining our recommendation. Specifically, EPA stated that it understood and supported the goal of developing an agencywide strategy to help identify and fill data gaps that preclude the agency from conducting IRIS toxicity assessments, but urged us to clarify more precisely the extent to which it must rely on others to conduct research to fill data gaps on IRIS chemicals. As we note in the report, IRIS Program officials told us that they do not have a process in place for filling research gaps and acknowledged that better coordination across EPA offices and with other federal research agencies, such as the Department of Health and Human Services’ National Toxicology Program, could help address this issue. We acknowledge that EPA has limited resources, which may preclude the agency from making substantial investments in research into how individual chemicals affect human health. As such, to ensure that the agency maximizes its limited resources, we have recommended that EPA develop a strategy to coordinate with other federal research agencies to help identify and fill data gaps. In this context, EPA acknowledged that it must look to other federal agencies, academic institutions, and chemical product producers to fund research into how chemicals affect human health, as we have recommended. EPA also stated, in its written comments, that the agency can and will do a more effective job to make data needs known to relevant federal agencies and nonfederal organizations that either fund or conduct chemical research. Also regarding our third recommendation that EPA develop an agencywide strategy to address unmet needs for IRIS toxicity assessments, based on technical comments provided by EPA officials prior to receiving the agency’s letter dated April 16, 2013, we refined the wording of our third recommendation. The original text recommended that EPA develop guidance that describes alternative sources of toxicity information and procedures for preparing toxicity assessments when IRIS values are not available, applicable, or current. We refined the wording of this recommendation to read: guidance that describes alternative sources of toxicity information and when it would be appropriate to use them when IRIS values are not available, applicable, or current. The revised language more accurately reflects the intent of our recommendation. In addition, in its written comments, EPA stated that it understood our interest in the agency developing guidance that describes alternative sources of toxicity information and agreed that such guidance might be helpful. However, EPA stated that the development of such guidance is best left to individual EPA programs. We disagree. In the absence of agencywide guidance that addresses unmet demand for IRIS assessments, EPA offices operate in much the same way they operated before the IRIS Program was formed to develop consensus opinions within the agency about the health effects from chronic exposure to chemicals. As we note in this report, we have previously reported on EPA’s fragmented and largely uncoordinated science activities and recommended, among other things, that EPA establish a top-level science official with the authority and responsibility to coordinate, oversee, and make management decisions regarding major scientific activities throughout the agency. Consistent with our prior report and recommendation, we believe that guidance regarding major scientific activities should also come from a top-level science official. However, as we note in our current report, EPA has not provided its Science Advisor with the authority to make management decisions regarding scientific activities across EPA as we previously recommended. Therefore, we believe that agencywide guidance should come from EPA’s Deputy Administrator in coordination with EPA’s Science Advisor. As agreed with your office, unless you publicly announce the contents of this report earlier, we plan no further distribution until 30 days from the report date. At that time, we will send copies to the Acting Administrator of EPA, the appropriate congressional committees, and other interested parties. In addition, this report will be available at no charge on the GAO website at http://www.gao.gov. If you or your staff members have any questions about this report, please contact me at (202) 512-3841 or gomezj@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. GAO staff who made key contributions to this report are listed in appendix IV. To determine the extent to which the Environmental Protection Agency (EPA) has evaluated demand for IRIS toxicity assessments, we reviewed EPA’s 2003 evaluation of demand for IRIS toxicity assessments. We also interviewed IRIS Program officials to determine whether they had conducted other evaluations of demand since 2003, how they derived the 2003 estimate, and whether that estimate reflects current conditions. Because the 2003 evaluation did not provide sufficient information on its methodology, we were unable to fully assess its estimate. We corroborated EPA officials’ assertion that the 2003 assessment no longer reflects current conditions based on our understanding of the IRIS Program. As we discussed earlier, the importance of EPA’s IRIS Program has increased over time as EPA program offices and regions have increasingly relied on IRIS toxicity assessments in making environmental protection and risk management decisions. In addition, as about 1,000 new chemicals are listed for commercial use each year, potential for changes in demand over time are likely. To determine the extent to which EPA’s process for nominating and selecting chemical for IRIS toxicity assessment accurately reflects current demand, we reviewed data provided by the IRIS Program and from the IRIS Program’s website on the number of IRIS toxicity assessments it completed annually from fiscal years 2002 through 2012. In addition, we analyzed all chemical nomination forms submitted by EPA program offices and regions to the IRIS Program from 2005, 2007 and 2011— which were the last three times that EPA solicited nominations for new and updated IRIS toxicity assessments. For additional perspective on user needs, we reviewed non-EPA IRIS users’ chemical nomination forms from 2011. To select and count the number of nominations, two analysts reviewed information EPA provided us to determine which documents to include in our analysis. We used the following inclusion and exclusion criteria to determine which documents to include in our analysis: Documents labeled as being a nomination were included while documents labeled as being another document were excluded. For example, some documents were the IRIS Program’s request for nominations or Federal Register Notices, which were not included in our analysis. In other instances, a nominating entity indicated that the chemicals were being prioritized and not nominated (i.e., they clearly stated “this is a list of our priorities”), and were not included in our analysis. We included individual nomination sheets for our analysis, but we did not include nomination cover sheets or separate documents that IRIS Program officials sent us separately from the individual nomination sheets. We did not include the nomination form if the nominating entity indicated on the form that there was no new nomination and instead was a reiteration of support for a previous nomination. In some instances, EPA program offices and regions nominated two chemicals on one nomination form or listed two chemicals together. Chemicals were counted as a single nomination if they had the same Chemical Abstracts Service (CAS) registry number and as separate nominations if they had different CAS registry numbers. According to the CAS registry website, the CAS registry is the most authoritative collection of disclosed chemical substance information, containing more than 70 million organic and inorganic substances and 64 million sequences. In cases where it was not clear to both analysts whether to include a document in our analysis, IRIS Program officials provided confirmation. While we used this methodology to determine the number of nominations in the 2005, 2007, and 2011 nomination periods, using a different methodology might result in a different number of nominations. As about 1,000 new chemicals are listed for commercial use each year, the chemicals nominated may either overstate or understate actual demand. In addition, we reviewed the IRIS Program’s processes for soliciting nominations and selecting chemicals for IRIS toxicity assessments, including the agency’s selection criteria. We also reviewed agency guidance and interviewed IRIS Program officials to better understand the chemical nomination and selection process. To determine the extent to which EPA has implemented a strategy for addressing any unmet needs of EPA program offices and regions when IRIS toxicity assessments are not available, applicable, or current, we reviewed the IRIS Program’s efforts to analyze IRIS user chemical nominations. For context, we interviewed officials from EPA’s National Center for Environmental Assessment, which manages the IRIS Program and develops IRIS toxicity assessments. For additional perspective, we interviewed officials using a standard set of questions from a nonprobability sample of three EPA program offices and one region: the Office of the Administrator, the Office of Water, the Office of Solid Waste and Emergency Response, and EPA’s Region 2. We selected these program offices and region because they submitted 78 percent of the chemical nominations to the IRIS Program during the period we reviewed—2005, 2007, and 2011. These offices and region ranked the highest in terms of the number of chemical nominations submitted, and, in some cases, nominated chemicals more than once during different nomination years. Because this is a nonprobability sample, it is not generalizable to all EPA program offices and regions, but it can provide illustrative examples of the experience of those EPA program offices and one region that nominated 78 percent of chemicals for IRIS toxicity assessment during the period we reviewed. For example, we received information from officials from these offices about how EPA program offices and one region nominate chemicals for IRIS toxicity assessment, how the IRIS Program meets the needs of these offices and region over the course of nomination periods, and what alternative toxicity assessments these offices and region turn to when IRIS toxicity assessments are not available. For a summary of approaches used by selected EPA program offices and regions to address their IRIS toxicity assessment needs, see appendix II. Separately from our nonprobability sample, we also interviewed officials from the Office of Pollution Prevention and Toxics, within the Office of Chemical Safety and Pollution Prevention, because it did not nominate any chemicals for IRIS toxicity assessment for any of the last three nomination periods. We did not evaluate the scientific content or quality of IRIS toxicity assessments. We conducted this performance audit from April 2012 to May 2013 in accordance with generally accepted government auditing standards. Those standards require that we plan and perform the audit to obtain sufficient, appropriate evidence to provide a reasonable basis for our findings and conclusions based on our audit objectives. We believe that the evidence obtained provides a reasonable basis for our findings and conclusions based on our audit objectives. According to officials at the Office of Solid Waste and Emergency Response, the office nominated 18 chemicals over the course of the 2005, 2007, and 2011 nomination periods. The Office of Solid Waste and Emergency Response provides policy, guidance, and direction for the agency’s emergency response and waste programs, including managing the Superfund Program, which responds to abandoned and active hazardous waste sites and accidental oil and chemical releases. IRIS toxicity assessments are used by the Office of Solid Waste and Emergency Response to, among other things, support mandated regulatory actions. For example, the Office of Underground Storage Tanks, within the Office of Solid Waste and Emergency Response, submitted chemicals during the 2011 nomination period to support the requirement under Section 1505 of the Energy Policy Act of 2005 that the EPA Administrator conduct a study on the effects on public health of increased use of iso-octane and six other fuel additives as substitutes for methyl tertiary butyl ether (MTBE). When IRIS toxicity assessments are not available or current, Office of Solid Waste and Emergency Response officials stated they rely on other toxicity values to meet their programmatic needs. For example, officials at the Office of Underground Storage Tanks stated that, in the absence of IRIS values, states must resort to other sources for toxicological information, and this can lead to inconsistencies state-to-state. Officials also stated that, when an IRIS toxicity assessment is not available, the office refers to a hierarchy of toxicity values to be used in performing human health risk assessments for Superfund sites. In 2003, the Office of Solid Waste and Emergency Response updated this hierarchy, which is intended to help risk assessors identify appropriate sources of toxicology information and lists the sources as: (1) IRIS toxicity values, (2) Provisional Peer Reviewed Toxicity Values (PPRTVs), and (3) other EPA and non-EPA sources of toxicity information—with priority given to those sources of information that are the most current, publicly available, and peer reviewed. Such values include the Agency for Toxic Substances and Disease Registry (ATSDR) Minimal Risk Levels and California Environmental Protection Agency (Cal/EPA) toxicity values. Although developed specifically for the Superfund Program, officials stated that this guidance is generally used by all suboffices within the Office of Solid Waste and Emergency Response. According to Region 2 officials, the region nominated 22 chemicals over the course of the 2005, 2007, and 2011 nomination periods. EPA’s Region 2 serves New Jersey, New York, Puerto Rico, the U.S. Virgin Islands, and eight tribal nations. Region 2 nominates chemicals for IRIS assessment on behalf of risk assessors throughout their region—that is, EPA and officials throughout the region, primarily at Superfund sites, that evaluate chemical risks. For example, Region 2 stated in its chemical nomination form for the 2011 nomination period that it needed IRIS toxicity assessments to support cleanup decisions for chemicals present in residential properties and in groundwater. Region 2 officials indicated that, when IRIS toxicity values are not available, they may rely on other toxicity values to meet their programmatic needs and follow the Office of Solid Waste and Emergency Response’s hierarchy of values in consultation with the IRIS Program as appropriate. Region 2 officials stated that in some cases, other organizations such as ATSDR or Cal/EPA may develop a quantitative value before the IRIS toxicity assessment is revised. In that case, the Region would consider the use of the quantitative value based on discussions with the IRIS program. According to Office of Water officials, the office nominated 23 chemicals over the course of the 2005, 2007, and 2011 nomination periods. EPA’s Office of Water is responsible for drinking water safety, and it restores and maintains oceans, watersheds, and their aquatic ecosystems. The Office of Water is responsible for implementing, among other mandates, the Clean Water Act and Safe Drinking Water Act. For example, in its chemical nomination form for the 2011 nomination period, the Office of Water stated that it needed IRIS toxicity assessments to develop regulations. The Office of Water develops assessments for chemicals it needs to meet statutory deadlines. Because of the limited number of IRIS toxicity assessments the IRIS Program can select and develop at one time, the Office of Water created the scheme to prioritize those chemicals that are the most controversial and high-profile, have a high economic impact, and will take more staff and time to complete. The Office of Water can then develop its own assessments for chemicals that have less controversy surrounding them and take less time and staff to complete in order to meet some of its programmatic needs. Officials stated that developing the office’s own assessments for some chemicals was based on the reality that the IRIS Program would not complete most of the needed toxicity assessments in time to meet the office’s statutory deadlines. According to officials at the Office of the Administrator, the office nominated 26 chemicals over the course of the 2005, 2007, and 2011 nomination periods. EPA’s Office of the Administrator provides executive and logistical support for the EPA Administrator. The office supports the leadership of EPA’s programs and activities to protect human health and the environment. An official from the Office of Policy, within the Office of the Administrator, stated that rationales for nominating chemicals varied widely—for example, the increasing or widespread exposure to a chemical or the availability of new data to develop a new or update an existing IRIS toxicity assessment. The official noted that the Office of Policy’s programmatic needs differed from other EPA offices’ needs in that it does not develop regulations or risk assessments. Instead, the office provides assistance for other EPA offices’ assessments and reviews assessments that other offices perform. In the absence of an IRIS toxicity assessment, the Office of Policy relied on the original literature, review articles, and assessments prepared by other agencies. Such values include the ATSDR Minimal Risk Levels and Cal/EPA toxicity values. An official with the Office of Children’s Health Protection, also within the Office of the Administrator, stated that most of its nominations were for chemicals that were under the Toxic Substances Control Act or the Safe Drinking Water Act and were based on children’s health concerns. The official stated that, in the absence of an IRIS toxicity assessment, the Office of Children’s Health Protection goes directly to the literature or work done by other government agencies or programs, such as the National Toxicology Program. The Office of Pollution Prevention and Toxics is responsible for implementing the Toxic Substances Control Act, which provides EPA with the authority to obtain more information on chemicals, and to regulate those chemicals that the agency determines pose unreasonable risks to human health or the environment, announced in February 2012 its plans to develop risk assessments on 83 chemicals. While the office has not nominated any chemicals for IRIS toxicity assessment over the past three nomination periods through the formal nomination process, according to EPA officials with the Office of Pollution Prevention and Toxics, in developing its risk assessments, it plans to incorporate information from IRIS toxicity assessments to the extent such information is available, recent, and relevant. Officials at the Office of Pollution Prevention and Toxics, and senior staff of the Office of Research and Development, which houses the IRIS Program, have compared the list of existing and ongoing IRIS toxicity assessments in order to share relevant literature and hazard reviews for upcoming risk assessments related to the Toxic Substances Control Act. These officials told us that the risk assessments they are conducting in support of the Toxic Substances Control Act are often based on intermittent exposure to workers and consumers who are subject to chemicals contained in products. However, they also told us that, while the IRIS values contained in the database may not always be applicable, often other data available in the IRIS database are applicable, such as toxicity information for shorter term exposure scenarios that have long-lasting/persistent effects (e.g., development toxicity). In these cases, they said that they have used the hazard and dose response information described in an IRIS toxicity assessment for a particular chemical to develop their own toxicity assessment. In addition, according to IRIS program officials, they have compared the list of chemicals for which the Office of Pollution Prevention and Toxics plans to conduct risk assessments with the list of existing and ongoing toxicity assessments and shared relevant literature and hazard reviews. IRIS program officials also said that the Office of Pollution Prevention and Toxics participates with other EPA offices in prioritizing their needs for ongoing IRIS toxicity assessments. IRIS toxicity values are generally used to estimate risks associated with continuous exposures to a pollutant in the air or water. In most cases, according to IRIS Program officials, the information used to develop the dose-response assessments is based on intermittent exposures to workers or animals in a controlled environment, and IRIS assessments include an adjustment to continuous exposure in the derivation of toxicity values. IRIS Program officials said that they are working with the Office of Pollution Prevention and Toxics and other EPA offices to find other options for assessing toxicity, such as PPRTVs, when IRIS toxicity assessments are not available, applicable, or current. The following are GAO’s comments on the letter from the Environmental Protection Agency dated April 16, 2013. 1. In this report, we do not discuss the challenges associated with suspending the development of an ongoing IRIS toxicity assessment to await new research and, therefore, our recommendations are not aimed at addressing this issue. Instead, our report is concerned with data gaps that preclude EPA from starting an IRIS assessment. However, we have addressed issues concerning suspending the development of an ongoing IRIS assessment in a prior report. Specifically, in our 2008 report on EPA’s IRIS Program, we note that, as a general rule, requiring that IRIS assessments be based on the best science available at the time of the assessment is a standard that would best support a goal of completing assessments within reasonable time periods and minimizes the need to conduct significant levels of rework. In our 2008 report, we recommended that EPA establish a policy that endorses conducting IRIS assessments on the basis of peer-reviewed scientific studies available at the time of the assessment and develop criteria for allowing assessments to be suspended to await the completion of scientific studies only under exceptional circumstances. As of the date of this report, EPA has not implemented our 2008 recommendation. 2. We have reported in the past that EPA has found many provisions of the Toxic Substances Control Act difficult to implement, and we have suggested that Congress consider making statutory changes to strengthen EPA’s authority to obtain toxicity information from the chemical industry. However, as we note in our March 2013 report on the Toxic Substances Control Act, EPA has not pursued all opportunities to obtain chemical data using its existing authorities under the law. We agree that robust collaboration between the IRIS and Toxic Substances Control Act Programs could improve EPA’s ability to develop chemical assessments in a timely manner. 3. We continue to believe that agencywide guidance is needed that describes alternative sources of toxicity information and when it would be appropriate to use them when IRIS values are not available, applicable or current. As we note in this report, we have previously reported on EPA’s fragmented and largely uncoordinated science activities and recommended, among other things, that EPA establish a top-level science official with the authority and responsibility to coordinate, oversee, and make management decisions regarding major scientific activities throughout the agency.recommendation, we believe that guidance regarding major scientific activities should also come from a top-level science official. However, as we note in our current report, EPA has not provided its Science Advisor with the authority to make management decisions regarding scientific activities across EPA as we previously recommended. Therefore, we believe that agencywide guidance should come from EPA’s Deputy Administrator in coordination with EPA’s Science Advisor. Consistent with our prior report and 4. We recognize that EPA is responsible for assessing and managing environmental risks based on many laws with different requirements and that program offices and regions may not always need IRIS toxicity assessments. However, as we note in our report, EPA has not clearly articulated under what circumstances IRIS toxicity assessments are not needed. Moreover, in cases where program offices and regions have indicated a need for an IRIS toxicity assessment, but an assessment is not available, applicable, or current, EPA does not have guidance that describes alternative sources of toxicity information and when it would be appropriate to use them. In addition to the individual named above, Diane G. LoFaro, Assistant Director; Summer Lingard-Smith; and Marie Webb made key contributions to this report. Important contributions were also made by Mark Braza, Janice Ceperich, Nirmal Chaudhary, Richard Johnson, Cynthia Norris, Aaron Shiffrin, and Kiki Theodoropoulos.

Summary: EPA created the IRIS database in 1985 to help develop consensus opinions within the agency about the health effects from chronic exposure to chemicals. The health effects information in IRIS--referred to as IRIS toxicity assessments--provides fundamental scientific information EPA needs to develop human health risk assessments. GAO was asked to review the effectiveness of EPA's implementation of its IRIS toxicity assessment process. This report determines the extent to which (1) EPA has evaluated demand for IRIS toxicity assessments from users inside and outside EPA; (2) EPA's process for nominating and selecting chemicals for IRIS toxicity assessment accurately reflects demand; and (3) EPA has implemented a strategy for addressing any unmet agency needs when IRIS toxicity assessments are not available, applicable, or current. To do this work, GAO reviewed and analyzed IRIS nomination data, among other things, and interviewed EPA officials. GAO did not evaluate the scientific content or quality of IRIS toxicity assessments. The Environmental Protection Agency (EPA) has not conducted a recent evaluation of demand for Integrated Risk Information System (IRIS) toxicity assessments with input from users inside and outside EPA. Specifically, EPA issued a needs assessment report in 2003, which estimated that 50 new or updated IRIS toxicity assessments were needed each year to meet users' needs. However, GAO did not find sufficient support for the estimate. In addition, IRIS Program officials recognize that the 2003 estimate does not reflect current conditions, but the agency does not plan to perform another evaluation of demand. Without a clear understanding of current demand for IRIS toxicity assessments, EPA cannot adequately measure the program's performance; effectively determine the number of IRIS toxicity assessments required to meet the needs of IRIS users; or know the extent of unmet demand. The IRIS Program's chemical nomination and selection process, which the agency uses to gauge interest in the IRIS Program from users inside and outside of EPA, may not accurately reflect current demand for IRIS toxicity assessments. The 75 chemicals that were nominated in response to EPA's most recent 2011 nomination period may not reflect demand for a number of reasons. For example, given the long-standing challenges the IRIS Program has had in routinely starting new assessments, according to some EPA IRIS users, they chose not to nominate new chemicals for assessment. Also, EPA has not clearly articulated how the IRIS Program applies the criteria it uses to prioritize the selection of chemicals for IRIS toxicity assessment--including how it determines the circumstances under which an IRIS toxicity assessment is or is not needed. Consequently, for chemicals that were nominated but not selected for assessment, it is not clear how many, if any, were excluded from consideration because they did not meet the IRIS Program's selection criteria because the IRIS Program determined that an IRIS toxicity assessment was not needed--or, alternatively, if they were not selected due to resource constraints or other reasons. EPA has not implemented an agencywide strategy for addressing the unmet needs of EPA program offices and regions when IRIS toxicity assessments are not available, applicable, or current. Specifically, EPA does not have a strategy for identifying and filling data gaps that would enable it to conduct IRIS toxicity assessments for nominated chemicals that are not selected for assessment because sufficient data from health studies are not available. IRIS Program officials stated that no agencywide mechanism exists for EPA to ensure that chemicals without sufficient scientific data during one nomination period will have such information by the next nomination period or even the one after that. These officials acknowledged that better coordination across EPA and with other federal agencies could help address the issue. EPA also does not have agencywide guidance for addressing unmet needs when IRIS toxicity assessments are not available, applicable, or current. In the absence of agencywide guidance, officials from select EPA offices stated that they used a variety of alternatives to IRIS toxicity assessments to meet their needs, including using toxicity information from other EPA offices or other federal agencies. GAO recommends that EPA evaluate demand for IRIS assessments; document how the agency applies its selection criteria, including the circumstances under which an IRIS toxicity assessment is or is not needed and; develop an agencywide strategy including, at a minimum, coordination across EPA offices, as well as with other federal agencies, to identify and fill data gaps, and providing guidance that describes alternative sources of toxicity information. EPA agreed with the first two recommendations and partially agreed with the third.