Evaluation of EPA’s Tier 1 Endocrine Screening Battery and recommendations for improving the interpretation of screening results

Borgert, Christopher J.; Mihaich, Ellen; Quill, Terry F.; Marty, M. Sue; Levine, Steven L.; Becker, Richard A.

doi:10.1016/j.yrtph.2011.01.003

Cited by 61 publications

(29 citation statements)

References 24 publications

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“…Borgert et al (2011b) has described three tiers of scientific validity. To be considered established scientific facts, scientific data must minimally conform to three tenets underpinning the basic language of science that enables trustworthy measurement of the natural world (Gori 2009).…”

Section: Discussionmentioning

confidence: 99%

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Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice

McCarty¹,

Borgert

Mihaich³

2012

Environ Health Perspect

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Background: There is an ongoing discussion on the provenance of toxicity testing data regarding how best to ensure its validity and credibility. A central argument is whether journal peer-review procedures are superior to Good Laboratory Practice (GLP) standards employed for compliance with regulatory mandates.Objective: We sought to evaluate the rationale for regulatory decision making based on peer-review procedures versus GLP standards.Method: We examined pertinent published literature regarding how scientific data quality and validity are evaluated for peer review, GLP compliance, and development of regulations.Discussion: Some contend that peer review is a coherent, consistent evaluative procedure providing quality control for experimental data generation, analysis, and reporting sufficient to reliably establish relative merit, whereas GLP is seen as merely a tracking process designed to thwart investigator corruption. This view is not supported by published analyses pointing to subjectivity and variability in peer-review processes. Although GLP is not designed to establish relative merit, it is an internationally accepted quality assurance, quality control method for documenting experimental conduct and data.Conclusions: Neither process is completely sufficient for establishing relative scientific soundness. However, changes occurring both in peer-review processes and in regulatory guidance resulting in clearer, more transparent communication of scientific information point to an emerging convergence in ensuring information quality. The solution to determining relative merit lies in developing a well-documented, generally accepted weight-of-evidence scheme to evaluate both peer-reviewed and GLP information used in regulatory decision making where both merit and specific relevance inform the process.

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Section: Discussionmentioning

confidence: 99%

“…The technical and policy challenges have proved formidable. Despite considerable effort, standard technical definitions have remained controversial and the widespread use of generally accepted testing protocols has proven to be a substantial challenge that is not yet resolved (Borgert et al 2011b). …”

mentioning

confidence: 99%

Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice

McCarty¹,

Borgert

Mihaich³

2012

Environ Health Perspect

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“…However the assay is not designed to identify substances that affect steroidogenesis due to effects on the hypothalamus or pituitary gland. Furthermore, without a correction for significant cytotoxicity there is a high likelihood of confounding results and erroneous identification as a chemical with potential to inhibit steroidogenesis (Borgert et al, 2011). In the OECD validation study for test guideline 456, there was a high degree of consistency between laboratories of the fold changes in T synthesis caused by different androgen agonists and antagonists, and there was a low number of false negatives or false positives with respect to in vivo changes to T levels (Hecker et al, 2011).…”

Section: Mie4: Lh Antagonismmentioning

confidence: 99%

Towards a non-animal risk assessment for anti-androgenic effects in humans

Dent

Carmichael

Jones

et al. 2015

Environment International

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Toxicology testing is undergoing a transformation from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches that could be used to develop a non-animal safety assessment for anti-androgenic effects in humans, with a focus on the molecular initiating events (MIEs) that human disorders indicate critical for normal functioning of the hypothalamus-pituitary-testicular (HPT) axis. In vitro test systems exist which can be used to characterize the effects of test chemicals on some MIEs such as androgen receptor antagonism, inhibition of steroidogenic enzymes or 5α-reductase inhibition. When used alongside information describing the pharmacokinetics of a specific chemical exposure, these could be used to inform a pathways-based safety assessment. However, some parts of the HPT axis such as events occurring in the hypothalamus or pituitary are not well represented by accepted in vitro methods. In vitro tools to characterize perturbations in these events need to be developed before a fully integrated model of the HPT axis can be described. Knowledge gaps also exist which prevent us from using in vitro data to predict the type and severity of in vivo effect(s) that could arise from a given level of in vitro anti-androgenic activity. This means that more work is needed to reliably link an MIE with an adverse outcome. However, especially for chemicals with low anti-androgenic activity, human exposure data can be used to put in vitro mode of action data into context for risk-based safety decision-making.

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“…Using this approach, compounds that operate by a specific MOA should affect a number of primary endpoints indicative of this MOA; for example, if a compound is estrogenic through binding to the estrogen receptor, primary indica-3 Workshop Session II: Practical applications of Tier 1 data 3.1 Plenary presentations the second session focused on the use of relevant information from the current eDSP tier 1 screening battery to inform: 1) how to stage Tier 1 screening assays in a more efficient manner; 2) how to use tier 1 and OSRI to identify potential modes of action; and 3) how to incorporate available information into a weight of evidence (WOe) assessment for evaluating potential interactions with endocrine pathways. General principles of WOe and the ePA's WOe document for evaluating tier 1 endocrine results were presented and an information framework was introduced that can be used for WOe assessments and/ or differentiating potential MOAs (Borgert et al, 2011b;U.S. ePA, 2011b).…”

Section: Assay Challenges Solutionmentioning

confidence: 99%

Lessons learned, challenges, and opportunities: The U.S. Endocrine Disruptor Screening Program

Juberg¹,

Borghoff

Becker

et al. 2014

ALTEX

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Evaluation of EPA’s Tier 1 Endocrine Screening Battery and recommendations for improving the interpretation of screening results

Cited by 61 publications

References 24 publications

Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice

Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice

Towards a non-animal risk assessment for anti-androgenic effects in humans

Lessons learned, challenges, and opportunities: The U.S. Endocrine Disruptor Screening Program

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