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Provisional Peer-Reviewed Toxicity Values (PPRTVs)

Basic Information About Provisional Peer-Reviewed Toxicity Values (PPRTVs)

Learn About Provisional Peer-Reviewed Toxicity Values

1. What are PPRTVs?

EPA’s PPRTV Program supports the Agency’s mission to protect human health and the environment by identifying and characterizing the health hazards of, and providing an important source of toxicity information and toxicity values for, chemicals of concern to the Superfund Program.

PPRTV assessments are developed in response to requests from EPA’s Superfund Program to the Superfund Health Risk Technical Support Center (STSC) within EPA’s Office of Research and Development’s (ORD’s) National Center for Environmental Assessment (NCEA). PPRTVs are derived after a review of the relevant scientific literature and using Agency methodologies, practices, and guidance for the development of toxicity values (e.g., oral reference doses (RfDs), inhalation reference concentrations (RfCs), provisional oral slope factors (p-OSF), and provisional inhalation unit risks (p-IUR)).

All PPRTV assessments receive internal review by EPA scientists and external peer review by independent scientific experts. For additional information on the methodologies used, please refer to Guidance & Tools. PPRTV assessments are eligible to be updated as requested by the Agency to incorporate new data or methodologies that might impact the science and decisions used to derive provisional toxicity values, and are revised as appropriate.

2. Who develops PPRTVs?

PPRTVs are assessments developed by scientists in ORD’s National Center for Environmental Assessment (NCEA) and the Human Health Risk Assessment (HHRA) National Research Program who are recognized internationally for their expertise in toxicology, epidemiology, biology, chemistry, and statistics.

3. What types of PPRTVs are derived?

PPRTV assessments provide the following provisional toxicity values for health effects resulting from chronicHelpchronicUsed to describe recurring symptoms or disease. or subchronic exposureHelpsubchronic exposureRepeated exposure by the oral, dermal, or inhalation route for more than 30 days, up to approximately 10% of the life span in humans (more than 30 days up to approximately 90 days in typically used laboratory animal species). [See also longer-term exposure.] to chemicals, they are typically grouped as noncancer assessments and cancer assessments.

Noncancer Assessments

The following terms describe the types of values that are derived:

Provisional Reference Dose (p-RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral (ingested) exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious health effects during a lifetime. It can be derived from a NOAELHelpNOAELThe highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse or precursors of adverse effects. (no observed adverse effect level), LOAELHelpLOAELThe lowest exposure level at which there are biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. (lowest observed adverse effect level), or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used.

Provisional Reference Concentration (p-RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious health effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used.Help

RfC An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments. [Durations include acute, short-term, subchronic, and chronic and are defined individually in this glossary].Cancer Assessments

Cancer descriptors characterize the chemical as:

  • Carcinogenic to Humans
  • Likely to Be Carcinogenic to Humans
  • Suggestive Evidence of Carcinogenic Potential
  • Inadequate Information to Assess Carcinogenic Potential
  • Not Likely to Be Carcinogenic to Humans

The following terms describe the types of values that are derived:

Provisional oral slope factor HelpOral slope factor An upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime oral exposure to an agent. This estimate, usually expressed in units of proportion (of a population) affected per mg/kg-day, is generally reserved for use in the low-dose region of the dose-response relationship, that is, for exposures corresponding to risks less than 1 in 100. (p-OSF): An estimate of the increased cancer risk from oral exposure to a dose of 1 mg/kg-day for a lifetime. The OSF can be multiplied by an estimate of lifetime exposure (in mg/kg-day) to estimate the lifetime cancer risk.

Provisional inhalation unit riskHelpunit riskThe upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/L in water, or 1 µg/m³ in air. The interpretation of unit risk would be as follows: if unit risk = 2 × 10⁻⁶ per µg/L, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per liter of drinking water. (p-IUR): An estimate of the increased cancer risk from inhalation exposure to a concentration of 1 µg/m3 for a lifetime. The IUR can be multiplied by an estimate of lifetime exposure (in µg/m3) to estimate the lifetime cancer risk.

Screening Assessments

Screening values are derived when the data do not meet all requirements for deriving a provisional toxicity value. They can be screening subchronic and chronic p-RfDs and p-RfCs, as well as screening p-OSFs and p-IURs. Screening PPRTVs are derived using the same methodologies and undergo the same development and review processes (i.e., internal and external peer review, etc.) as provisional values; however, the screening values are presented in an appendix and characterized such that users of screening PPRTVs are made aware that there is more uncertainty associated with these screening values than for the values presented in the main body of a PPRTV assessment.

4. Under what circumstances are screening PPRTVs derived?

When some useful human or animal toxicity data are available for a chemical, but…

  • The data are published in non peer-reviewed sources.
  • The data are published and peer-reviewed, but have associated uncertainties such as:
    • The composite Uncertainty Factor is greater than 3,000.
    • The principal study is not comprehensive (e.g., few or one endpoint examined).
    • Other: the principal study has a small number of animals tested, poor study design, incomplete reporting, etc.
  • When no useful human or animal toxicity data are available for a chemical…
    • An expert-driven read-across approach can be applied.

5. What is an expert-driven read across approach?

An expert-driven read across approach is defined as:

  • A framework designed to address data gaps for chemicals with limited in vivo toxicity information for quantitative human health risk assessment (for additional information, see journal article by Wang et al., 2012).
  • Relies on the identification of three main types of potential analogues (structural, metabolic/toxicokinetic, and toxicity).
  • A weight-of-evidence (WoE) approach is applied for the selection of a final/best surrogate chemical based on structural, metabolic/toxicokinetic, and toxicity similarity.
  • The point of departure (POD) for the chosen surrogate is used to derive screening PPRTVs for the target chemical of concern

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Guidance & Tools

EPA follows Agency guidance in developing PPRTV assessments. Key guidelines, technical documents and a EPA tools used by the PPRTV Program for developing assessments are listed below. Additional Agency guidance, models and tools are available at EPA's Risk Assessment website.

EPA Guidance Documents

On this page:


EPA Guidance Documents

EPA Cancer Guidelines

EPA Risk Assessment Guidelines

EPA Science Policy Council Guidelines

Other Guidance Documents and Technical Panel Reports

References Cited in Older Assessment Documents but Superseded by More Recent Guidance

Relevant Scientific Journal Articles

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Tools

Benchmark Dose Software (BMDS)

Benchmark dose (BMD) modeling is EPA’s preferred approach for deriving points of departure (PODs) used to develop toxicity values in PPRTV assessments. Use of BMD modeling involves fitting a set of mathematical models to dose-response data from human and animal studies. EPA’s benchmark dose software (BMDS) was designed to facilitate the application of BMD methods in dose-response assessment.

Health and Environmental Research Online (HERO)

HERO is a searchable database of more than 1.6 million scientific studies and other references used to support the development of EPA assessments like the Provisional Peer-Review Toxicity Value (PPRTV) assessments. Each HERO record provides detailed bibliographic information with associated project pages for some of the more recent PPRTV assessments.

Integrated Risk Information System(IRIS)

IRIS is a searchable database of more than 500+ chemical assessments and other references used to support the development of EPA assessments. Each IRIS chemical landing page provides the available toxicity values, assessment status details, and a history of supporting documents. The IRIS database is used as a reference for the application and practice of current risk assessment methodologies to ensure consistency across PPRTV assessments and other NCEA products.

Regional Screening Levels (RSLs)

The RSL tables provide comparison values for residential and commercial/industrial exposures to soil, air, and tapwater (drinking water). The unified use of the RSLs, to screen chemicals at Superfund sites, promotes national consistency. The RSLs tables include risk-based screening levels, calculated using the latest toxicity values, default exposure assumptions and physical and chemical properties, and a calculator where default parameters can be changed to reflect site-specific risks. PPRTV assessments are a significant source of toxicity values for the RSL tables.

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PPRTV Process for Developing Assessments

Before beginning to develop a draft PPRTV assessment in response to the Superfund Program’s request, the PPRTV Program undertakes an internal chemical scoping process to characterize the needs for an assessment.  A Scoping team screens available data and prioritizes chemicals on an annual basis to develop the list for PPRTV development.This diagram illustrates the process the PPRTV program undergoes to produce an assessment.Click to enlarge this image.

  • Two NCEA scientists internally review the draft PPRTV assessment, and it is revised based on the comments received.
  • The draft PPRTV assessment undergoes a letter external peer review by three independent experts in toxicology and human health risk assessment.
  • The PPRTV Program revises the assessment to address external peer review comments. They also prepare a written response-to-comment document.
  • The final PPRTV assessment is posted to the PPRTV website.

Note: To learn more about the historical development of the PPRTV Process see the history of PPRTVs.

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History of the Provisional Peer-Reviewed Toxicity Values Program

Important milestones include:

  • 2018 - EPA  migrated the PPRTV website and database from the Oak Ridge National Laboratory (ORNL) server to the EPA website.
  • 2008 - EPA began developing screening PPRTVs for chemicals when the data do not meet all requirements for deriving a toxicity value.
  • 2004 - EPA's PPRTV assessments were made available to Superfund sites and risk assessors via a limited accessibility website managed by ORNL.
  • 1998 - EPA began developing PPRTV assessments to support a growing need for toxicity values for the Superfund Program. Within the same year, the Superfund Health Risk Technical Support Center (STSC) was also established to provide the resources needed to manage the PPRTV development process.

Provisional Peer-Reviewed Toxicity Values (PPRTVs)