CHEMICAL 

ASSESSMENTS

An Agencywide 

Strategy May Help 

EPA Address Unmet 

Needs for Integrated 

Risk Information 

System Assessments

Report to the Chairman, Committee on 

Environment and Public Works, 

U.S. Senate

May 2013

GAO-13-369

United States Government Accountability Office

GAO
United States Government Accountability Office

Highlights of GAO-13-369, a report to the 

Chairman, Committee on Environment and 

Public Works, U.S. Senate 

May 2013 

CHEMICAL ASSESSMENTS 

An Agencywide Strategy May Help EPA Address

Unmet Needs for Integrated Risk Information 

System Assessments 

Why GAO Did This Study

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.

What GAO Recommends

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. 

What GAO Found

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. View GAO-13-369. For more information, 

contact J. Alfredo Gómez at (202) 512-3841 or 

gomezj@gao.gov. 
Page i GAO-13-369 Chemical Assessments

Letter 1 

Background 5

EPA’s Most Recent Evaluation of Demand for IRIS Toxicity 

Assessments Is a Decade Old 12

EPA’s Chemical Nomination and Selection Process May Not 

Accurately Reflect Current Demand for IRIS Toxicity 

Assessments 15

EPA Has Not Implemented an Agencywide Strategy for Addressing 

Unmet Needs for IRIS Toxicity Assessments 18

Conclusions 26

Recommendations for Executive Action 27

Agency Comments and Our Evaluation 28

Appendix I Scope and Methodology 31

Appendix II Summary of Approaches Used by Select EPA Program Offices 

and Regions to Address Toxicity Assessment Needs 34

Appendix III Comments from the Environmental Protection Agency 39

Appendix IV GAO Contact and Staff Acknowledgments 44

Figures

Figure 1: National Academies’ Risk Assessment Model Used by 

EPA 6

Figure 2: Number of IRIS Toxicity Assessments EPA Issued, Fiscal 

Years 2002 to 2012 16

Contents 
Page ii GAO-13-369 Chemical Assessments

Abbreviations

ATSDR Agency for Toxic Substances and Disease Registry

Cal/EPA California Environmental Protection Agency

CAS Chemical Abstracts Service

DIPE diisopropyl ether

EPA Environmental Protection Agency

ETBE ethyl tertiary butyl ether

GPRA Government Performance and Results Act of 1993

IRIS Integrated Risk Information System

MTBE methyl tertiary butyl ether

OMB Office of Management and Budget

PART Program Assessment Rating Tool

PPRTV Provisional Peer Reviewed Toxicity Value

TAME tertiary amyl methyl ether

TBA tertiary butyl alcohol

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Page 1 GAO-13-369 Chemical Assessments

United States Government Accountability Office 

Washington, DC 20548

May 10, 2013

The Honorable Barbara Boxer

Chairman

Committee on Environment and Public Works

United States Senate

Dear Madam Chairman:

The Environmental Protection Agency’s (EPA) Integrated Risk 

Information System (IRIS)—a database integral to the agency’s mission 

of protecting human health and the environment—contains EPA’s 

scientific position on the potential human health effects that may result 

from exposure to various chemicals in the environment.1 EPA created the 

IRIS database in 1985 to help it develop consensus opinions within the 

agency about the health effects from chronic exposure to chemicals and 

currently includes information on more than 550 chemicals. The health 

effects information in the IRIS database—referred to as IRIS toxicity 

assessments—provides fundamental scientific information EPA needs to 

develop human health risk assessments on particular chemicals.2 These 

human health risk assessments, in turn, provide the foundation for EPA’s 

risk management decisions, such as whether EPA should establish air 

and water quality standards to protect the public from exposure to 

particular toxic chemicals. EPA’s IRIS Program develops new IRIS 

toxicity assessments and, as needed, updates information in existing IRIS 

toxicity assessments contained in the IRIS database.3

 

1

Under its IRIS Program, EPA (1) identifies a chemical’s toxicity, or hazardous properties, 

which are the potential noncancer and cancer human health effects of exposure to a 

chemical, and (2) assesses the dose-response relationship between exposure to a 

chemical and the resultant health effects, which describes the magnitude of hazard for 

potential noncancer effects and increased cancer risk.

The importance of 

2

A human health risk assessment characterizes the nature and magnitude of health risks 

to humans from exposure to chemical contaminants that may be present in the 

environment. IRIS toxicity assessments are used along with other information to prepare 

human health risk assessments. Toxicity represents the degree to which a chemical is 

harmful. In this report, the terms toxicity and hazard are used synonymously.

3

According to IRIS Program officials, new assessments are added to the IRIS database 

after an evaluation of the available scientific literature, and existing assessments are 

revised based on an evaluation of new studies that have been published since the original 

assessment was completed. 

 
 

Page 2 GAO-13-369 Chemical Assessments

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, 

state and local environmental programs, as well as some international 

regulatory bodies, rely on IRIS toxicity assessments in managing their 

environmental protection programs.

Although the information in the IRIS database is a critical primary 

component of EPA’s capacity to support scientifically sound decisions, 

policies, and regulations, we have reported previously on EPA’s difficulty 

producing timely, credible IRIS toxicity assessments. Specifically, in 

March 2008, we reported that the IRIS database was at serious risk of 

becoming obsolete because EPA had not been able to (1) keep its 

existing assessments current or (2) complete assessments of the most 

important chemicals of concern.4 Further, we reported that because EPA 

staff time continued to be dedicated to completing ongoing assessments, 

EPA’s ability to both keep existing assessments (at that time more than 

540) up to date and initiate new assessments was limited. We also 

reported that, although the number of program staff quadrupled from 8 to 

37 and program funding increased from $1.7 million to $9.6 million for 

fiscal years 2000 to 2007, EPA had on average completed about five 

assessments annually during this period. For these and other reasons, in 

2009 we added EPA’s processes for assessing and controlling toxic 

chemicals to our list of areas at high risk for waste, fraud, abuse, and 

mismanagement or in need of broad-based transformation.5

In December 2011, we reported, among other things, that EPA’s initial 

productivity gains under the May 2009 revised process had not been 

sustained and that the agency continued to face challenges in 

implementing the IRIS Program.

In response 

to our 2008 report and subsequent high-risk designation, EPA revised its 

IRIS toxicity assessment process in May 2009.

6

 

4

GAO, Chemical Assessments: Low Productivity and New Interagency Review Process 

Limit the Usefulness and Credibility of EPA’s Integrated Risk Information System, 

For example, from May 2009 through 

GAO-08-440 (Washington, D.C.: Mar. 7, 2008).

5

GAO, High-Risk Series: An Update, GAO-09-271 (Washington, D.C.: Jan. 22, 2009). 

This high-risk area addresses EPA’s implementation of the IRIS Program, as well as 

implementation of the Toxic Substances Control Act.

6

GAO, Chemical Assessments: Challenges Remain with EPA’s Integrated Risk 

Information System Program, GAO-12-42 (Washington, D.C.: Dec. 9, 2011).
 

Page 3 GAO-13-369 Chemical Assessments

September 2011, EPA completed 20 IRIS toxicity assessments—more 

than doubling the total productivity it achieved during the two fiscal years 

immediately preceding the adoption of the revised process. However, 16 

of these toxicity assessments were completed in the first year and a half 

of implementing the revised process, and productivity fell sharply during 

fiscal year 2011, with EPA issuing 4 IRIS toxicity assessments. We 

reported that, even if EPA were to overcome the significant productivity 

difficulties it has experienced in recent years and met its goal of 

completing 40 assessments in fiscal year 2012, it was not clear that this 

level of productivity would meet the needs of IRIS users inside and 

outside EPA.7

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. In this context, you asked us to review the 

effectiveness of EPA’s implementation of its IRIS toxicity assessment 

process. Our objectives were to determine 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 needs of 

EPA program offices and regions when IRIS toxicity assessments are not 

available, applicable, or current.

We noted that beyond EPA’s ongoing assessments, and 

some that were on hold, the demand for additional IRIS toxicity 

assessments was unclear.

To determine the extent to which EPA has evaluated demand for IRIS 

toxicity assessments, we reviewed EPA’s 2003 evaluation of demand for 

IRIS toxicity assessments. We also interviewed officials at the National 

Center for Environmental Assessment, which manages the IRIS Program 

and develops IRIS toxicity assessments (henceforth IRIS Program 

officials). Specifically, we interviewed these 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. We reviewed the report to determine its basis for estimating 

 

7

For purposes of this report, “IRIS users” represent EPA program offices and regions and 

non-EPA entities that submit chemical nominations to the IRIS Program. Such non-EPA 

entities include other federal agencies, White House offices, and the public.
 

Page 4 GAO-13-369 Chemical Assessments

IRIS demand and the number of assessments it needed to conduct in 

order to meet demand.

To determine the extent to which EPA’s process for nominating and 

selecting chemicals for IRIS toxicity assessments 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 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 the IRIS Program solicited 

nominations for new and updated IRIS toxicity assessments.8

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 IRIS Program officials. 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.

For 

additional perspective on user needs, we reviewed non-EPA IRIS users’ 

chemical nomination forms from 2011. In addition, we reviewed the IRIS 

Program’s processes for soliciting nominations and selecting chemicals 

for 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.

9

 

8

According to IRIS Program documents, the IRIS Program solicits opinions from EPA 

offices, other federal agencies, and the public on an annual basis. However, since 2004, 

the IRIS Program has solicited nominations from IRIS users three times: in 2004, 2006, 

and 2010. In their nomination forms, IRIS users send EPA the names of chemicals and 

the reasons for requesting that IRIS toxicity assessments be developed or updated, 

among other information. In 2004, the IRIS Program solicited nominations only from EPA 

program offices and regions. In 2006 and 2010, the IRIS Program solicited nominations 

from all IRIS users. The IRIS Program refers to these nomination periods as being for 

fiscal years 2005, 2007, and 2011, which are the years we also refer to in this report.

We 

9

We interviewed officials both at the Office of Policy and the Office of Children’s Health 

Protection, which are suboffices within the Office of the Administrator. We also received a 

written response from the Office of Underground Storage Tanks, which is a suboffice 

within the Office of Solid Waste and Emergency Response.
 

Page 5 GAO-13-369 Chemical Assessments

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 chemical 

nominations 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.

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. A more detailed description of our scope and 

methodology can be found in appendix I. For a summary of approaches 

used by selected EPA program offices and regions to address their unmet 

needs regarding IRIS toxicity assessments, see appendix II.

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.

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.

Background
 

Page 6 GAO-13-369 Chemical 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.10

Figure 1: National Academies’ Risk Assessment Model Used by EPA

This model includes four components: (1) hazard 

identification, (2) dose-response assessment, (3) exposure assessment, 

and (4) risk characterization (see fig. 1).

 

10The National Academies comprise four organizations: the National Academy of 

Sciences, the National Academy of Engineering, the Institute of Medicine, and the 

National Research Council. EPA uses the model that was initially outlined in the 1983 

National Academies’ National Research Council, Risk Assessment in the Federal 

Government (commonly known as the Red Book). The National Research Council’s 

subsequent 2009 report presented by the National Academies in Science and Decisions: 

Advancing Risk Assessment (Washington, D.C.: The National Academies Press, 2009) 

reiterated this process. This publication is also known as the Silver Book.

EPA’s Human Health Risk 

Assessment and Risk 

Management Practices
 

Page 7 GAO-13-369 Chemical Assessments

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.11

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 

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.

 

11Exposure represents the magnitude, frequency, and duration of contact with a chemical.
 

Page 8 GAO-13-369 Chemical Assessments

from “carcinogenic to humans” to “not likely to be carcinogenic to 

humans.”12

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/kgday) 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/m3 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.

 

12According to IRIS Program officials, one of the following five descriptors is selected 

based on the extent of human and animal data available: (1) “carcinogenic to humans,” (2) 

“likely to be carcinogenic to humans,” (3) “suggestive evidence of carcinogenic potential,” 

(4) “inadequate information to assess carcinogenic potential,” or (5) “not likely to be 

carcinogenic to humans.” 
 

Page 9 GAO-13-369 Chemical Assessments

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.13 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.14

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.15

• 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.

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:

16

 

13OMB, Fiscal Year 2006 Program Assessment Rating Tool (PART) assessment of EPA’s 

Human Health Risk Assessment Program.

 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 

14EPA Office of Research and Development, Human Health Risk Assessment Strategic 

Research Action Plan 2012-2016, EPA 601/R-12/007, June 2012.

15EPA decides the type of independent peer review an IRIS toxicity assessment will 

undergo. The peer reviews are conducted by (1) a peer review panel assembled by an 

EPA contractor, (2) EPA’s Science Advisory Board, or (3) the National Academies. 

1642 U.S.C. § 9604 (i)(3).
 

Page 10 GAO-13-369 Chemical Assessments

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.17

• 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.18

• 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 

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.

 

17Toxicity values are a numerical expression of a substance’s exposure-response

relationship that is used in risk assessments.

18The specific definition for each exposure duration category may vary depending on the 

source of the toxicity value being used. In general, subchronic is used to describe periods 

of repeated exposure by the oral, dermal, or inhalation route for more than 30 days up to 

approximately 90 days in laboratory animals or 10 percent of the life span in humans.
 

Page 11 GAO-13-369 Chemical Assessments

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.19

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 

 

19The IRIS Program also included these criteria, with slight variation, for the 2005 and 

2007 nomination solicitations.

EPA’s Process for 

Soliciting Nominations and 

Selecting Chemicals for 

New and Updated IRIS 

Toxicity Assessments
 

Page 12 GAO-13-369 Chemical Assessments

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.20 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.21

 

20Of the 15 IRIS toxicity assessments listed in the 2012 IRIS agenda, 7 were updates of 

assessments already in the IRIS database. Of the 52 IRIS toxicity assessments that were 

already under way, 34 were updates of assessments already in the IRIS database.

In 

response to the Senate request, EPA conducted a needs assessment—

the results of which are discussed in its September 2003 report, Needs 

21S. Rep. No. 106-410 at 90 (2000).

EPA’s Most Recent 

Evaluation of Demand 

for IRIS Toxicity 

Assessments Is a 

Decade Old
 

Page 13 GAO-13-369 Chemical Assessments

Assessment for U.S. EPA’s Integrated Risk Information System.

22

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.23 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.24

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 

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.

 

22EPA, Needs Assessment for U.S. EPA’s Integrated Risk Information System

(Washington, D.C.: September 2003).

23For example, the report called for developing a schedule for updating potentially 

outdated assessments at least once every 10 years and updating some every 5 years.

24EPA received responses from 10 EPA program offices, 7 EPA regions, and 22 public 

and private organizations. Non-EPA respondents included the U.S. Army, state agencies, 

industries, trade organizations, public interest and nonprofit organizations.
 

Page 14 GAO-13-369 Chemical Assessments

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.25 In addition,

we have previously reported that, in developing new initiatives, agencies 

can benefit from following leading practices for strategic planning.26

Congress enacted the Government Performance and Results Act (GPRA) 

in 1993 to improve efficiency and accountability of federal programs.27 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.28

 

25GAO, Environmental Protection Agency: To Better Fulfill Its Mission, EPA Needs a More 

Coordinated Approach to Managing Its Laboratories, 

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 

GAO-11-347 (Washington, D.C.: July 

25, 2011).

26GAO, Environmental Protection: EPA Should Develop a Strategic Plan for Its New 

Compliance Initiative, GAO-13-115 (Washington, D.C.: Dec. 10, 2012); GAO, 

Environmental Justice: EPA Needs to Take Additional Actions to Help Ensure Effective 

Implementation, GAO-12-77 (Washington, D.C.: Oct. 6, 2011).

27We have reported in the past that, taken together, the strategic planning elements 

established under GPRA and associated OMB guidance, and practices identified by GAO 

provide a framework of leading practices in federal strategic planning. For example, see 

GAO, Executive Guide: Effectively Implementing the Government Performance and 

Results Act, GAO/GGD-96-118 (Washington, D.C.: June 1, 1996); GAO, Tax 

Administration: IRS Needs to Further Refine Its Tax Filing Season Performance 

Measures, GAO-03-143 (Washington, D.C.: Nov. 22, 2002); and GAO, Managing for 

Results: Strengthening Regulatory Agencies’ Performance Management Practices, 

GAO/GGD-00-10 (Washington, D.C.: Oct. 28, 1999).

28Leading practices in federal strategic planning include defining mission and goals, 

defining strategies that address management challenges and identify resources needed to 

achieve goals, ensuring leadership involvement and accountability, involving stakeholders, 

coordinating with other federal agencies, and developing and using performance 

measures.
 

Page 15 GAO-13-369 Chemical Assessments

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.

EPA’s Chemical 

Nomination and 

Selection Process 

May Not Accurately 

Reflect Current 

Demand for IRIS 

Toxicity Assessments
 

Page 16 GAO-13-369 Chemical Assessments

Figure 2: Number of IRIS Toxicity Assessments EPA Issued, Fiscal Years 2002 to 

2012

Note: EPA’s Integrated Risk Information System (IRIS) contains toxicity assessments that provide 

fundamental scientific information EPA needs for assessing the risks chemicals pose to human health 

(i.e., develop human health risk assessments). 

In addition, as we reported in December 2011, EPA fell short of its 

productivity goal in fiscal year 2011—completing 4 of the 20 IRIS toxicity 

assessments it had originally planned to complete that year.29 Similarly, in 

completing 4 IRIS toxicity assessments in fiscal year 2012, EPA fell short 

of its fiscal year 2012 goal of completing 40 assessments. Given the 

challenges the IRIS Program has experienced issuing IRIS assessments, 

for many chemicals, the IRIS Program is not fulfilling the goal of providing 

a common scientific foundation for decision making within EPA 

programs—which is the stated purpose of an IRIS toxicity assessment 

according to EPA’s strategic planning document for human health risk 

assessment research.30

 

29

Instead, because the IRIS Program has been 

GAO-12-42. EPA originally planned to issue 20 IRIS toxicity assessments in fiscal year 

2011: 4 were issued, 1 was dropped, 2 were given “TBD”—to be determined—completion 

dates, and 13 were added to the fiscal year 2012 completion goal, bringing it to 40 

assessments. 

30EPA Office of Research and Development, Human Health Risk Assessment Strategic 

Research Action Plan 2012-2016, EPA 601/R-12/007, June 2012.
 

Page 17 GAO-13-369 Chemical Assessments

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.31

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.32

 

31As discussed earlier, EPA’s IRIS Program was originally created to develop consensus 

across the Agency regarding health effects resulting from chronic exposures to chemicals. 

IRIS Program officials have recently told us that IRIS no longer formally requires Agency 

consensus for its assessments, but consensus is still sought and often achieved through 

the existing Agency review process.

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—

32OMB, Memorandum to the Chief Financial Officers, Chief Operation Officers, Chief 

Information Officers, and Program Managers, December 21, 2004.
 

Page 18 GAO-13-369 Chemical Assessments

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.33 One of the chemicals dropped from 

consideration due to insufficient data was nominated in 2005, 2007, and 

2011.34

 

33As discussed earlier, the IRIS Program has not published information on how the 

agency applied its selection criteria but, upon request, provided us with information 

regarding chemicals dropped from consideration due to insufficient data.

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 

342,2,4-Trimethylpentane (iso-octane).

EPA Has Not 

Implemented an 

Agencywide Strategy 

for Addressing Unmet 

Needs for IRIS 

Toxicity Assessments

EPA Does Not Have a 

Strategy for Identifying 

and Filling Data Gaps
 

Page 19 GAO-13-369 Chemical Assessments

appropriate cleanup levels for leaking underground storage tank sites.35

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).36

While the IRIS Program prepared and issued an IRIS toxicity assessment 

that contained the qualitative hazard identification description of isooctane 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 

 

35According to EPA’s website, 2,2,4-trimethylpentane is released to the environment 

through the manufacture, use, and disposal of products associated with the petroleum and 

gasoline industry. During an accident, 2,2,4-trimethylpentane penetrated the skin of a 

human which caused necrosis of the skin and tissue in the hand and required surgery. No 

other information is available on the acute (short-term) effects in humans. Irritation of the 

lungs, edema, and hemorrhage has been reported in rodents acutely exposed by 

inhalation and injection. No information is available on the chronic (long-term), 

reproductive, developmental, or carcinogenic effects of 2,2,4-trimethylpentane in humans. 

Kidney and liver effects have been observed in rats chronically exposed via gavage 

(experimentally placing the chemical in the stomach) and inhalation.

3642 U.S.C. § 7545(b)(4). These substances are (1) ethyl tertiary butyl ether (ETBE); (2) 

tertiary amyl methyl ether (TAME); (3) diisopropyl ether (DIPE); (4) tertiary butyl alcohol 

(TBA); (5) ethanol; (6) iso-octane (2,2,4-trimethylpentane); and (7) alkylates. According to 

EPA’s website, MTBE is a fuel additive made by combining methanol and isobutylene and 

has been used since 1979 in the United States as an octane-enhancing replacement for 

lead. According to the website, the use of MTBE in gasoline sold in the United States has 

virtually ceased in recent years. According to IRIS Program officials, ETBE, TAME, DIPE, 

TBA, and ethanol are currently on the IRIS agenda in the draft development step. The 

ETBE assessment is being revised because important new data became available after 

the external peer review. New schedules for ETBE and TBA were posted on the IRIS 

website in February 2013. Taking into account the complexity of the ethanol dataset, IRIS 

Program officials told us that they are considering various approaches to conducting the 

ethanol assessment and will revisit the priority of the ethanol assessment in fiscal year 

2013. Alkylates were added to the IRIS agenda in 2007 but were withdrawn in 2012 

because there are multiple chemicals in this class, many with limited databases. If 

individual alkylates with sufficient data to support an IRIS assessment are nominated in 

the future, the IRIS Program will consider these nominations individually.
 

Page 20 GAO-13-369 Chemical Assessments

the studies needed to support such estimates were not available.37

IRIS Program officials told us that no mechanism exists for EPA to ensure 

that chemicals without sufficient health studies during one nomination 

period will have those data gaps filled by the next nomination period or 

even the one after that. As discussed earlier, as part of its solicitation 

process, the IRIS Program circulates an annotated list of chemical 

nominations that specifies the degree to which health studies are 

available for each chemical. However, 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.

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.

38

 

37According to EPA’s 2007 IRIS assessment on iso-octane, no subchronic or chronic oral 

or inhalation studies were identified that demonstrated a dose-response effect that could 

be used to determine the noncarcinogenic risk for iso-octane and no studies were 

available on the carcinogenic effects of iso-octane on which to base a cancer assessment.

Other agencies within the Department of Health and Human Services 

38The 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.
 

Page 21 GAO-13-369 Chemical Assessments

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.39 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.40 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 welldeveloped PPRTVs be considered as a source of prioritization in the 

development of full IRIS documents.41

 

39According to officials at the Office of Solid Waste and Emergency Response, summaries 

of toxicity literature are more useful than no information about toxicity of a particular 

chemical, but typically the summaries do not completely address the needs of the program 

offices of regions.

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 

40PPRTVs are developed for EPA’s Superfund program and, therefore, the Superfund 

program determines the chemicals that are nominated for development. Other EPA 

program offices are not included in the nomination process in the same fashion as they 

are for the IRIS nomination process. However, once a PPRTV is posted to the Office of 

Solid Waste and Emergency Response’s Superfund website, they are publicly available.

41EPA Board of Scientific Counselors, Review of the Office of Research and 

Development’s Human Health Risk Assessment Program at the U.S. Environmental 

Protection Agency: Final Report, April 1, 2008.

EPA Does Not Have 

Agencywide Guidance for 

Addressing Unmet Needs
 

Page 22 GAO-13-369 Chemical Assessments

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.42

In the absence of agencywide guidance, officials from the three EPA 

program offices and one region we met with said they used a variety of 

different approaches to meet their needs when an IRIS toxicity 

assessment was not available or current. That is, EPA offices operate in 

much the same way as they operated before the IRIS Program was 

formed to develop consensus opinions within the agency about the health 

effects from chronic exposure to chemicals. For example, when IRIS 

toxicity assessments are not available or current, Office of Solid Waste 

and Emergency Response officials stated that their office refers to a 

hierarchy of toxicity values it established to perform 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 in order of preference as: (1) IRIS toxicity values, (2) 

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.43

 

42GAO, Standards for Internal Control in the Federal Government, 

Similarly, 

Region 2 officials told us that they generally follow the Office of Solid 

Waste and Emergency Response’s hierarchy of values to guide their 

decisions regarding other toxicology sources to meet their needs when an 

IRIS toxicity assessment is not available. For example, Region 2 officials 

told us that there are a number of chemicals for which their office has 

used PPRTVs and values from ATSDR and Cal/EPA to address high–

GAO/AIMD-00-21.3.1

(Washington, D.C.: November 1999).

43Other 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.
 

Page 23 GAO-13-369 Chemical Assessments

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 
 

Page 24 GAO-13-369 Chemical Assessments

often based on intermittent exposure to workers and consumers who are 

subject to chemicals contained in products.44 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).45

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 

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.

 

44This focus is consistent with the fact that media-specific environmental laws such as the 

Clean Air Act and Clean Water Act are available to limit the concentration of contaminants 

in water or the ambient air, and the Toxic Substances Control Act requires EPA to defer 

action to such other laws if the agency determines that it can use them to adequately 

address a given risk. However, information on such continuous exposures is still critical for 

regulation under the Toxic Substances Control Act. For example, to promulgate a rule 

under section 6 of the Toxic Substances Control Act, EPA must have information on, 

among other things, the effects of the chemical on human health and the magnitude of 

human exposure to the chemical.

45IRIS toxicity values are generally used to estimate risks associated with continuous 

exposures to a pollutant in the air or water. In most cases, the information used to develop 

the dose-response assessments is based on intermittent exposures to workers or animals 

in a controlled environment. IRIS assessments include an adjustment to continuous 

exposure in the derivation of toxicity values.
 

Page 25 GAO-13-369 Chemical Assessments

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.46 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.47

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 

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.

 

46EPA’s Science Advisory Board is a federal advisory committee established by Congress 

in 1978 with a broad mandate to advise the agency on technical matters.

47Science Advisory Board, Science Integration for Decision Making at the U.S. 

Environmental Protection Agency, EPA-SAB-12-008 (Washington, D.C.: July 6, 2012).
 

Page 26 GAO-13-369 Chemical Assessments

laboratories.48 While EPA agreed with our recommendation, it has not 

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 

 

48GAO-11-347. 

Conclusions
 

Page 27 GAO-13-369 Chemical Assessments

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.

Recommendations for 

Executive Action
 

Page 28 GAO-13-369 Chemical Assessments

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 

Agency Comments 

and Our Evaluation
 

Page 29 GAO-13-369 Chemical Assessments

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 
 

Page 30 GAO-13-369 Chemical Assessments

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.

49 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.

Sincerely yours,

J. Alfredo Gómez

Director, Natural Resources and Environment

 

49GAO-11-347. 
Appendix I: Scope and Methodology

Page 31 GAO-13-369 Chemical Assessments

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.1

• Documents labeled as being a nomination were included while 

documents labeled as being another document were excluded. For 

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:

 

1

According to IRIS Program documents, the IRIS Program solicits opinions from EPA 

offices, other federal agencies, and the public on an annual basis. However, since 2004, 

the IRIS Program has solicited nominations from IRIS users three times: in 2004, 2006, 

and 2010. In 2004, the IRIS Program solicited nominations only from EPA program offices 

and regions. In 2006 and 2010, the IRIS Program solicited nominations from all IRIS 

users. The IRIS Program refers to these nomination periods as being for fiscal years 

2005, 2007, and 2011, which are the years we also refer to in this report.

Appendix I: Scope and Methodology
Appendix I: Scope and Methodology

Page 32 GAO-13-369 Chemical Assessments

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 
Appendix I: Scope and Methodology

Page 33 GAO-13-369 Chemical Assessments

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 2.2

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 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.

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.

 

2

We interviewed officials both at the Office of Policy and the Office of Children’s Health 

Protection, which are suboffices within the Office of the Administrator. We also received a 

written response from the Office of Underground Storage Tanks, which is a suboffice 

within the Office of Solid Waste and Emergency Response.
Appendix II: Summary of Approaches Used by 

Select EPA Program Offices and Regions to 

Address Toxicity Assessment Needs 

Page 34 GAO-13-369 Chemical Assessments

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.1 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).2

 

1

The Office of Solid Waste and Emergency Response has suboffices including the Office 

of Underground Storage Tanks, which submitted separate nominations (inclusive of the 18 

chemicals) to the IRIS Program.

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 

2

42 U.S.C. § 7545(b)(4). These substances are (1) ethyl tertiary butyl ether (ETBE); (2) 

tertiary amyl methyl ether (TAME); (3) diisopropyl ether (DIPE); (4) tertiary butyl alcohol 

(TBA); (5) ethanol; (6) iso-octane (2,2,4-trimethylpentane); and (7) alkylates. According to 

EPA’s website, MTBE is a fuel additive made by combining methanol and isobutylene and 

has been used since 1979 in the United States as an octane-enhancing replacement for 

lead. According to the website, the use of MTBE in gasoline sold in the United States has 

virtually ceased in recent years. According to IRIS Program officials, ETBE, TAME, DIPE, 

TBA, and ethanol are currently on the IRIS agenda in the draft development step. The 

ETBE assessment is being revised because important new data became available after 

the external peer review. New schedules for ETBE and TBA were posted on the IRIS 

website in February 2013. Taking into account the complexity of the ethanol dataset, IRIS 

Program officials told us that they are considering various approaches to conducting the 

ethanol assessment and will revisit the priority of the ethanol assessment in fiscal year 

2013. Alkylates were added to the IRIS agenda in 2007 but were withdrawn in 2012 

because there are multiple chemicals in this class, many with limited databases. If 

individual alkylates with sufficient data to support an IRIS assessment are nominated in 

the future, the IRIS Program will consider these nominations individually.

Appendix II: Summary of Approaches Used 

by Select EPA Program Offices and Regions 

to Address Toxicity Assessment Needs

Office of Solid Waste and 

Emergency Response
Appendix II: Summary of Approaches Used by 

Select EPA Program Offices and Regions to 

Address Toxicity Assessment Needs 

Page 35 GAO-13-369 Chemical Assessments

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.3 Officials also told us 

that there are number of high-profile chemicals where the office has used 

PPRTVs and values from ATSDR and Cal/EPA, because an IRIS toxicity 

assessment is not available. However, officials noted that ATSDR does 

not develop cancer values.

 

3

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.

EPA Region 2
Appendix II: Summary of Approaches Used by 

Select EPA Program Offices and Regions to 

Address Toxicity Assessment Needs 

Page 36 GAO-13-369 Chemical Assessments

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.4

 

4

The Office of the Administrator has suboffices including the Office of Policy and the 

Office of Children’s Health Protection, which each submitted separate nominations 

(inclusive of the 26 chemicals) to the IRIS Program. 

 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 

Office of Water

Office of the Administrator
Appendix II: Summary of Approaches Used by 

Select EPA Program Offices and Regions to 

Address Toxicity Assessment Needs 

Page 37 GAO-13-369 Chemical Assessments

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 

Office of Pollution 

Prevention and Toxics
Appendix II: Summary of Approaches Used by 

Select EPA Program Offices and Regions to 

Address Toxicity Assessment Needs 

Page 38 GAO-13-369 Chemical Assessments

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. 
Appendix III: Comments from the 

Environmental Protection Agency

Page 39 GAO-13-369 Chemical Assessments

Appendix III: Comments from the 

Environmental Protection Agency

Note: GAO comments 

supplementing those in 

the report text appear at 

the end of this appendix.
Appendix III: Comments from the 

Environmental Protection Agency

Page 40 GAO-13-369 Chemical Assessments

See comment 3.

See comment 2.

See comment 1.
Appendix III: Comments from the 

Environmental Protection Agency

Page 41 GAO-13-369 Chemical Assessments

See comment 4.
Appendix III: Comments from the 

Environmental Protection Agency

Page 42 GAO-13-369 Chemical Assessments

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,1

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,

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

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 

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.

 1 GAO-08-440. 

2

GAO, Toxic Substances: EPA Has Increased Efforts to Asses and Control Chemical but Could 

Strengthen Its Approach, GAO-13-249 (Washington, D.C.: Mar. 22, 2013).
Appendix III: Comments from the 

Environmental Protection Agency

Page 43 GAO-13-369 Chemical Assessments

activities throughout the agency.

3

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.

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. 

 3

GAO-11-347. 
Appendix IV: GAO Contact and Staff 

Acknowledgments

Page 44 GAO-13-369 Chemical Assessments

J. Alfredo Gómez, (202) 512-3841 or gomezj@gao.gov

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.

Appendix IV: GAO Contact and Staff 

Acknowledgments 

GAO Contact 

Staff 

Acknowledgments 

(361369)
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