Page 1 of 2 EPA’s Approach for Considering Other Scie ntifically Relevant Information (OSRI) under the Endocrine Disrupt or Screening Program March 26, 2009

This paper was developed by EPA to provide guidance to EPA staff and managers who will be reviewing the responses to Tier 1 Orders issued under the Endocrine Disruptor Screening Program (EDSP), and may also be of interest to parties considering whether to submit other scientifically relevant information to EPA. This paper provides general guidance and is not binding on either EPA or any outside parties, and t he use of language such as "will," "is," "may," "can" or "should" in this paper does not connote any requirement for either EPA or any outside parties. As such, EPA may depart from the guidance where circumstances warrant and without prior notice, and this guidance is not otherwise in tended to limit anyone’s submission of or citation to other scientifically relevant information. Anyone may provide other scientifically relevant information and the Agency will assess the information on a case-by-case basis to determine whether the information can be used to satisfy part or all of the Tier 1 Order, and/or otherwise inform the Tier 1 determination. EPA will respond to the submitter in writing and will make its determination publicly available.

General EPA understanding of what OSRI is:

“Other scientifically relevant informa tion” is information that informs the
determination as to whether the substance may have an effect that is similar to an effect produced by a substance that interacts with the estrogen, androgen, and/or thyroid hormonal systems (e.g., information that identifies substances as having the potential to interact with the estrogen, androgen, and/or thyroid system(s); information demonstrating whethe r substances have an effect on the functioning of the endocrine system). OSRI may either be func tionally equivalent
to information obtained from the Tier 1 assays—that is, data from assays that perform the same function as EDSP Tier 1 assays—or may include data that provide information on a potential consequ ence or effect that could be due to effects on the estrogen, andr ogen or thyroid systems.

Discussion of OSRI in general:

• Anyone may submit OSRI, not ju st Test Order recipients.

• Rather than simply describing the otherscientifically relevant information the submitter wishes EPA to consider, EPA encourages submitters to provide the information itself or to cite the publicat ion or a reference number for information previously submitted to EPA, as these will make the greatest amount of information available for the Agency to consider , in the shortest time frame.

• Information may receive di fferent weights in a weight of evidence judgment that evaluates the totality of the evidence.

• The quality of the informati on will weigh heavily in EPA’s evaluation. For examples of some of the factors EPA may cons ider when evaluating the quality of information, please see the Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Info rmation Disseminated by the Environmental Protection Agency (available at:
http://epa.gov/quality/informationguidelines/d ocuments/EPA_InfoQualityGuidelines.pdf ) and thePage 2 of 2 EPA Assessment Factors Guidance (available at:
http://www.epa.gov/OSA/spc/pdfs/assess2.pdf ).

• Factors that EPA may consider include sens itivity, specificity, confidence in the conclusions, and applicability of conclusions across taxa.

• Judgments will be made considering all fact ors, not just apparent similarity of endpoints and effects. Such factors may include route of admin istration, duration of dosing, rationale for the dose leve ls chosen, frequency of dosing, age at exposure, species, test system , vehicle used, number of test units, variability of data, other factors, and whet her the final data set available to the Agency provides a basis for conclusions about the potentia l for interaction with the endocrine system in both mammalian and non-mammalian systems.

• As a general matter, EPA thinks that the following types of studies may contain information that the EPA would be likely to regard as scientifically relevant
information: studies that corre spond to the assays in Tier 1 or Tier 2; metabolism studies; or other vertebrate or invertebrate toxicity studies, including, but not limited to, developmental toxicity tests, carci nogenicity tests, toxicogenomic data, and reproductive toxicity tests. Other ty pes of studies may also be considered scientifically relevant. For instance, testing conducted under 40 CFR Part 158 data requirements to support a pesticide regist ration may be considered by EPA. The weight any study carries in a weight of evidence judgment may depend on whether the protocol meets information qualit y and scientific standards, and evaluates relevant and necessary endocrine related endpoints.

Relationship to the Tier 1 Orders:

• The Agency’s consideration of OSRI is in itiated when someone su bmits the OSRI.

• EPA will evaluate the OSRI, in combinati on with any other available information,
and determine the extent to which the OSRI satisfies the Tier 1 Order.

• Some OSRI may be sufficient to satisfy part or all of the Ti er 1 Order. For example, the OSRI may have been submitt ed to only address a particular part of the Tier 1 Order.

• EPA encourages submitters to provide a cogent and complete rationale for why they believe the OSRI is sufficient to sa tisfy part or all of the Tier 1 Order.

• Decisions about whether the OSRI satisfie s part or all of the Tier 1 Order will be based on the weight of evidence from a ll relevant information available.

• Judgments about whether the OSRI satisfies part or a ll of the Tier 1 Order will generally consider the dataset as a whole for the subject chemical. In general, it may in some cases be possible to determi ne that a particular chemical has the potential to interact with the endocrine syst em and therefore could proceed to Tier
2 even if Tier 1 data are lim ited. However, if only so me of the Tier 1 data are available, there may not be sufficient informa tion to determine that some of the Tier 2 data are not necessary. For example, if, based on the weight of available information, EPA were able to determine that it has sufficient data to know that Tier 2 testing is needed due to estrogen-relat ed effects, EPA may be able to determine that additional Tier 1 data on androgen and thyroid systems is not needed to satisfy the Tier 1 Order. However, depending on the result s, more complete Tier 1 data might allow EPA to determi ne that not all of the Tier 2 testing is necessary.