Does GLP enhance the quality of toxicological evidence for regulatory decisions?

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments.

[1]  Koji Arizono,et al.  Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A , 2008, Environmental health perspectives.

[2]  Marlene Ågerstrand,et al.  CRED: Criteria for reporting and evaluating ecotoxicity data , 2016, Environmental toxicology and chemistry.

[3]  J. McLachlan,et al.  Synergistic effect of environmental estrogens: report withdrawn. , 1997, Science.

[4]  K. Munkittrick,et al.  Statistical reporting deficiencies in environmental toxicology , 2013, Environmental toxicology and chemistry.

[5]  Marcia McNutt,et al.  Journals unite for reproducibility , 2014, Science.

[6]  M. Fortelius,et al.  Molar Tooth Diversity, Disparity, and Ecology in Cenozoic Ungulate Radiations , 1996, Science.

[7]  Journals unite for reproducibility , 2014, Nature.

[8]  K M Crofton,et al.  Evaluation of the ToxRTool's ability to rate the reliability of toxicological data for human health hazard assessments. , 2015, Regulatory toxicology and pharmacology : RTP.

[9]  Taisen Iguchi,et al.  A path forward in the debate over health impacts of endocrine disrupting chemicals , 2014, Environmental Health.

[10]  R. Tyl Basic Exploratory Research versus Guideline-Compliant Studies Used for Hazard Evaluation and Risk Assessment: Bisphenol A as a Case Study , 2009, Environmental health perspectives.

[11]  Thomas Hartung,et al.  "ToxRTool", a new tool to assess the reliability of toxicological data. , 2009, Toxicology letters.

[12]  R B Conolly,et al.  A strategy for establishing mode of action of chemical carcinogens as a guide for approaches to risk assessments. , 1995, Cancer letters.

[13]  Steven F. Arnold,et al.  Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals , 1996, Science.

[14]  P M Schlosser,et al.  Determining modes of action for biologically based risk assessments. , 1999, Regulatory toxicology and pharmacology : RTP.

[15]  A. Bayraktar,et al.  OECD (Organisation for Economic Cooperation and Development) and environment. , 2010 .

[16]  Christopher J. Borgert,et al.  Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice , 2012, Environmental health perspectives.

[17]  G. B. Gori,et al.  Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System. , 2015, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  Alan R. Boobis,et al.  IPCS Framework for Analyzing the Relevance of a Noncancer Mode of Action for Humans , 2008, Critical reviews in toxicology.

[19]  Anne M. Baldeshwiler History of FDA good laboratory practices , 2003 .

[20]  F. Prinz,et al.  Believe it or not: how much can we rely on published data on potential drug targets? , 2011, Nature Reviews Drug Discovery.

[21]  J. Corton,et al.  Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPARα) as a case study , 2014, Critical reviews in toxicology.

[22]  Laura N Vandenberg,et al.  Assessing dose–response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity , 2015, Environmental Health.

[23]  L. McCarty,et al.  Can mode of action predict mixture toxicity for risk assessment? , 2004, Toxicology and applied pharmacology.

[24]  J. Wiltse,et al.  US Environmental Protection Agency's revised guidelines for Carcinogen Risk Assessment: incorporating mode of action data. , 1998, Mutation research.

[25]  Claude Emond,et al.  Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment , 2015, Environmental Health.

[26]  Richard A. Becker,et al.  Good Laboratory Practices and Safety Assessments , 2009, Environmental health perspectives.

[27]  Richard A Becker,et al.  Hypothesis-driven weight of evidence framework for evaluating data within the US EPA's Endocrine Disruptor Screening Program. , 2011, Regulatory toxicology and pharmacology : RTP.

[28]  Seema K. Schappelle,et al.  Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[29]  Werner Kloas,et al.  Effects of Atrazine in Fish, Amphibians, and Reptiles: An Analysis Based on Quantitative Weight of Evidence , 2014, Critical reviews in toxicology.

[30]  Bruce Alberts,et al.  Making Data Maximally Available , 2011, Science.

[31]  Richard A. Becker,et al.  A survey of frameworks for best practices in weight-of-evidence analyses , 2013, Critical reviews in toxicology.

[32]  M E Meek,et al.  New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis , 2013, Journal of applied toxicology : JAT.

[33]  U. Tillmann,et al.  A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. , 1997, Regulatory toxicology and pharmacology : RTP.