§ 30.5 - What requirements apply to the EPA's use of dose-response data underlying pivotal science?

§ 30.5 What requirements apply to the EPA's use of dose-response data underlying pivotal science?

(a) When promulgating a significant regulatory action or developing influential scientific information that relies on dose-response data, the Agency shall follow best practices to evaluate potential links between exposure to a pollutant, contaminant, or substance and the effect and the nature of the dose-response relationship.

(b) The EPA will use the following factors to assess the quality of studies identified in the systematic review: soundness, applicability and utility, clarity and completeness, uncertainty and variability, and evaluation and review. The EPA will rely on the highest quality, most relevant studies in determining the potential for hazard due to exposure to a pollutant, contaminant, or substance. Where there is convincing and well-substantiated evidence of a relationship between exposure and effect, the EPA will identify those studies based on the exposure situation being addressed, the quality of the studies, the reporting adequacy, and the relevance of the endpoints that would inform a dose-response assessment for those effect endpoints. From the subset in the preceding sentence, the specific dose-response studies or analyses that drive the requirements, quantitative analyses, or both of an EPA significant regulatory action or influential scientific information will be identified as pivotal science.

(c) The EPA shall give greater consideration to pivotal science where the underlying dose-response data are publicly available in a manner sufficient for independent validation. The Agency shall also give greater consideration to pivotal science based on dose-response data that include confidential business information, proprietary information or personally identifiable information if these data are available through restricted access in a manner sufficient for independent validation. For pivotal science where there is no access to dose-response data, or access is limited, the Agency may still consider these studies but will give them lesser consideration unless the Administrator grants an exemption under § 30.7. The Agency will identify the pivotal science that was given lesser consideration and provide a short description of why lesser consideration was given.

(d) In determining the degree of consideration to afford pivotal science for which the dose-response data are not available for independent validation, the EPA shall consider the following factors and any other relevant factors, as applicable:

(1) The quality of the study relative to other studies for which the dose-response data are available;

(2) The extent to which there are other studies for which the dose-response data are available;

(3) The sensitivity of the conclusions in the significant regulatory action or influential scientific information based on the use of the study;

(4) The extent to which the study is fit for the purpose or intended use relative to other pivotal science for which the dose-response data are available;

(5) The use of exposures or doses in a range and duration that is relevant for the intended use and that minimizes the need for extrapolations;

(6) The extent to which the study is supported by other scientific evidence;

(7) The extent to which the study accounted for unique scientific considerations;

(8) The extent to which the study minimizes the use of defaults and assumptions, uses appropriate and strong statistical methods, and includes a robust representation of uncertainty and confidence intervals; and

(9) The study's consideration of a broad range of parametric dose-response or concentration-response models, a robust set of potential confounding variables, nonparametric models that incorporate fewer assumptions, various threshold models across the dose or exposure range, and models that investigate factors that might account for spatial heterogeneity.

(e) The EPA shall also describe critical assumptions and methods used in its dose-response assessment and shall characterize the variability and uncertainty of the assessment. The EPA shall evaluate the appropriateness of using default assumptions on a case-by-case basis. The EPA shall clearly explain the scientific basis for critical assumptions used in the dose-response assessment that the EPA relied on for the significant regulatory action or influential scientific information.

(f) Where the Agency is making dose-response data publicly available, it shall do so in a fashion that is consistent with law, protects privacy, confidentiality, confidential business information, and is sensitive to national security. Dose-response data is considered “publicly available in a manner sufficient for independent validation” when it includes the information necessary for the public to understand, assess, and reanalyze findings and may include, for example:

(1) Data (data would be made available subject to access and use restrictions);

(2) Associated protocols necessary to understand, assess, and extend conclusions;

(3) Computer codes and models involved in the creation and analysis of such information;

(4) Recorded factual materials; and

(5) Detailed descriptions of how to access and use such information.

(g) The provisions of this section apply to dose-response data underlying studies that are pivotal science, regardless of who funded or conducted the studies. The Agency shall make all reasonable efforts to explore methodologies, technologies, and institutional arrangements for making such data available before it concludes that doing so in a manner consistent with law and protection of privacy, confidentiality, national security is not possible.