An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

Martin, Melissa M.; Baker, Nancy C.; Boyes, William K.; Carstens, Kelly E.; Culbreth, Megan E.; Gilbert, Mary E.; Harrill, Joshua A.; Nyffeler, Johanna; Padilla, Stephanie; Friedman, Katie Paul; Shafer, Timothy J.

doi:10.1016/j.ntt.2022.107117

An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

Journal Article · Fri Jul 29 00:00:00 EDT 2022 · Neurotoxicology and Teratology

DOI:https://doi.org/10.1016/j.ntt.2022.107117· OSTI ID:1981723

Martin, Melissa M. ^[1]; Baker, Nancy C. ^[2]; Boyes, William K. ^[3]; Carstens, Kelly E. ^[1]; Culbreth, Megan E. ^[1]; Gilbert, Mary E. ^[3]; Harrill, Joshua A. ^[1]; Nyffeler, Johanna ^[4]; Padilla, Stephanie ^[1]; Friedman, Katie Paul ^[1]; Shafer, Timothy J. ^[1]

US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Computational Toxicology and Exposure (CCTE)
Leidos, Inc., Research Triangle Park, NC (United States)
US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Public Health and Environmental Assessment (CPHEA)
US Environmental Protection Agency (EPA), Research Triangle Park, NC (United States). Center for Computational Toxicology and Exposure (CCTE); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

To date, approximately 200 chemicals have been tested in US Environmental Protection Agency (EPA) or Organization for Economic Co-operation and Development (OECD) developmental neurotoxicity (DNT) guideline studies, leaving thousands of chemicals without traditional animal information on DNT hazard potential. To address this data gap, a battery of in vitro DNT new approach methodologies (NAMs) has been proposed. Evaluation of the performance of this battery will increase the confidence in its use to determine DNT chemical hazards. One approach to evaluate DNT NAM performance is to use a set of chemicals to evaluate sensitivity and specificity. Since a list of chemicals with potential evidence of in vivo DNT has been established, this study aims to develop a curated list of “negative” chemicals for inclusion in a “DNT NAM evaluation set”. A workflow, including a literature search followed by an expert-driven literature review, was used to systematically screen 39 chemicals for lack of DNT effect. Expert panel members evaluated the scientific robustness of relevant studies to inform chemical categorizations. Following review, the panel discussed each chemical and made categorical determinations of “Favorable”, “Not Favorable”, or “Indeterminate” reflecting acceptance, lack of suitability, or uncertainty given specific limitations and considerations, respectively. Further, the panel determined that 10, 22, and 7 chemicals met the criteria for “Favorable”, “Not Favorable”, and “Indeterminate”, for use as negatives in a DNT NAM evaluation set. Ultimately, this approach not only supports DNT NAM performance evaluation but also highlights challenges in identifying large numbers of negative DNT chemicals.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 1981723

Alternate ID(s):: OSTI ID: 1960938

Journal Information:: Neurotoxicology and Teratology, Journal Name: Neurotoxicology and Teratology Journal Issue: C Vol. 93; ISSN 0892-0362

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (53)

Micropollutants in European rivers: A mode of action survey to support the development of effect-based tools for water monitoring Busch, Wibke; Schmidt, Susanne; Kühne, Ralph Environmental Toxicology and Chemistry, Vol. 35, Issue 8 https://doi.org/10.1002/etc.3460	journal	June 2016
Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period Philippot, Gaëtan; Gordh, Torsten; Fredriksson, Anders Journal of Applied Toxicology, Vol. 37, Issue 10 https://doi.org/10.1002/jat.3473	journal	April 2017
International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel Archives of Toxicology, Vol. 89, Issue 2 https://doi.org/10.1007/s00204-015-1464-2	journal	January 2015
pubmed.mineR: An R package with text-mining algorithms to analyse PubMed abstracts Rani, Jyoti; Shah, Ab Rauf; Ramachandran, Srinivasan Journal of Biosciences, Vol. 40, Issue 4 https://doi.org/10.1007/s12038-015-9552-2	journal	September 2015
Developmental mechanisms that generate precise patterns of neuronal connectivity Goodman, Corey S.; Shatz, Carla J. Cell, Vol. 72 https://doi.org/10.1016/S0092-8674(05)80030-3	journal	January 1993
Developmental neurotoxicity of industrial chemicals Grandjean, P.; Landrigan, Pj The Lancet, Vol. 368, Issue 9553 https://doi.org/10.1016/S0140-6736(06)69665-7	journal	December 2006
Current status of developmental neurotoxicity: an industry perspective Kaufmann, Wolfgang Toxicology Letters, Vol. 140-141 https://doi.org/10.1016/S0378-4274(02)00503-9	journal	April 2003
Neurobehavioural effects of developmental toxicity Grandjean, Philippe; Landrigan, Philip J. The Lancet Neurology, Vol. 13, Issue 3 https://doi.org/10.1016/S1474-4422(13)70278-3	journal	March 2014
Apparent activity in high-throughput screening: origins of compound-dependent assay interference Thorne, Natasha; Auld, Douglas S.; Inglese, James Current Opinion in Chemical Biology, Vol. 14, Issue 3 https://doi.org/10.1016/j.cbpa.2010.03.020	journal	June 2010
Novel application of normalized pointwise mutual information (NPMI) to mine biomedical literature for gene sets associated with disease: Use case in breast carcinogenesis Watford, Sean M.; Grashow, Rachel G.; De La Rosa, Vanessa Y. Computational Toxicology, Vol. 7 https://doi.org/10.1016/j.comtox.2018.06.003	journal	August 2018
EPA’s DSSTox database: History of development of a curated chemistry resource supporting computational toxicology research Grulke, Christopher M.; Williams, Antony J.; Thillanadarajah, Inthirany Computational Toxicology, Vol. 12 https://doi.org/10.1016/j.comtox.2019.100096	journal	November 2019
Variability in in vivo studies: Defining the upper limit of performance for predictions of systemic effect levels Pham, Ly Ly; Watford, Sean M.; Pradeep, Prachi Computational Toxicology, Vol. 15 https://doi.org/10.1016/j.comtox.2020.100126	journal	August 2020
In vitro and other alternative approaches to developmental neurotoxicity testing (DNT) Lein, Pamela; Silbergeld, Ellen; Locke, Paul Environmental Toxicology and Pharmacology, Vol. 19, Issue 3 https://doi.org/10.1016/j.etap.2004.12.035	journal	May 2005
Evaluation of multi-well microelectrode arrays for neurotoxicity screening using a chemical training set McConnell, Emma R.; McClain, Maxine A.; Ross, James NeuroToxicology, Vol. 33, Issue 5 https://doi.org/10.1016/j.neuro.2012.05.001	journal	October 2012
A qualitative retrospective analysis of positive control data in developmental neurotoxicity studies Crofton, K. Neurotoxicology and Teratology, Vol. 26, Issue 3 https://doi.org/10.1016/j.ntt.2004.02.007	journal	June 2004
Determining normal variability in a developmental neurotoxicity test A report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints Raffaele, Kathleen C.; Fisher, J. Edward; Hancock, Scott Neurotoxicology and Teratology, Vol. 30, Issue 4 https://doi.org/10.1016/j.ntt.2007.12.009	journal	July 2008
Introduction to the ILSI Research Foundation/Risk Science Institute reports from the expert working group on neurodevelopmental endpoints Fitzpatrick, Julie; Mendez, Elizabeth; Walls, Isabel Neurotoxicology and Teratology, Vol. 30, Issue 4 https://doi.org/10.1016/j.ntt.2008.03.001	journal	July 2008
The use of developmental neurotoxicity data in pesticide risk assessments Raffaele, Kathleen C.; Rowland, Jess; May, Brenda Neurotoxicology and Teratology, Vol. 32, Issue 5 https://doi.org/10.1016/j.ntt.2010.04.053	journal	September 2010
Expanding the test set: Chemicals with potential to disrupt mammalian brain development Mundy, William R.; Padilla, Stephanie; Breier, Joseph M. Neurotoxicology and Teratology, Vol. 52 https://doi.org/10.1016/j.ntt.2015.10.001	journal	November 2015
An analysis of the limitations and uncertainties of in vivo developmental neurotoxicity testing and assessment to identify the potential for alternative approaches Paparella, Martin; Bennekou, Susanne Hougaard; Bal-Price, Anna Reproductive Toxicology, Vol. 96 https://doi.org/10.1016/j.reprotox.2020.08.002	journal	September 2020
Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes Fritsche, Ellen; Grandjean, Philippe; Crofton, Kevin M. Toxicology and Applied Pharmacology, Vol. 354 https://doi.org/10.1016/j.taap.2018.02.004	journal	September 2018
Strategies to improve the regulatory assessment of developmental neurotoxicity (DNT) using in vitro methods Bal-Price, Anna; Pistollato, Francesca; Sachana, Magdalini Toxicology and Applied Pharmacology, Vol. 354 https://doi.org/10.1016/j.taap.2018.02.008	journal	September 2018
Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment Harrill, Joshua A.; Freudenrich, Theresa; Wallace, Kathleen Toxicology and Applied Pharmacology, Vol. 354 https://doi.org/10.1016/j.taap.2018.04.001	journal	September 2018
Analysis of the Local Lymph Node Assay (LLNA) variability for assessing the prediction of skin sensitisation potential and potency of chemicals with non-animal approaches Dumont, Coralie; Barroso, João; Matys, Izabela Toxicology in Vitro, Vol. 34 https://doi.org/10.1016/j.tiv.2016.04.008	journal	August 2016
Are There Other Persistent Organic Pollutants? A Challenge for Environmental Chemists Muir, Derek C. G.; Howard, Philip H. Environmental Science & Technology, Vol. 40, Issue 23 https://doi.org/10.1021/es061677a	journal	November 2006
Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15062	journal	April 2017
Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie Critical Reviews in Toxicology, Vol. 48, Issue 5 https://doi.org/10.1080/10408444.2018.1429385	journal	February 2018
Children's Environmental Health in Agricultural Settings Karr, Catherine Journal of Agromedicine, Vol. 17, Issue 2 https://doi.org/10.1080/1059924X.2012.658009	journal	April 2012
Human-relevant approaches to assess eye corrosion/irritation potential of agrochemical formulations Clippinger, Amy J.; Raabe, Hans A.; Allen, David G. Cutaneous and Ocular Toxicology, Vol. 40, Issue 2 https://doi.org/10.1080/15569527.2021.1910291	journal	April 2021
Using the ntp Database to Assess the Value of Rodent Carcinogenicity Studies for Determining Human Cancer risk Haseman, J. K. Drug Metabolism Reviews, Vol. 32, Issue 2 https://doi.org/10.1081/DMR-100100570	journal	January 2000
Evaluation of Variability Across Rat Acute Oral Systemic Toxicity Studies Karmaus, Agnes L.; Mansouri, Kamel; To, Kimberly T. Toxicological Sciences, Vol. 188, Issue 1 https://doi.org/10.1093/toxsci/kfac042	journal	April 2022
Paracetamol (Acetaminophen) Administration During Neonatal Brain Development Affects Cognitive Function and Alters Its Analgesic and Anxiolytic Response in Adult Male Mice Viberg, Henrik; Eriksson, Per; Gordh, Torsten Toxicological Sciences, Vol. 138, Issue 1 https://doi.org/10.1093/toxsci/kft329	journal	December 2013
Editor’s Highlight: Evaluation of a Microelectrode Array-Based Assay for Neural Network Ontogeny Using Training Set Chemicals Brown, Jasmine P.; Hall, Diana; Frank, Christopher L. Toxicological Sciences, Vol. 154, Issue 1 https://doi.org/10.1093/toxsci/kfw147	journal	August 2016
From the Cover: Developmental Neurotoxicants Disrupt Activity in Cortical Networks on Microelectrode Arrays: Results of Screening 86 Compounds During Neural Network Formation Frank, Christopher L.; Brown, Jasmine P.; Wallace, Kathleen Toxicological Sciences, Vol. 160, Issue 1 https://doi.org/10.1093/toxsci/kfx169	journal	August 2017
International Regulatory and Scientific Effort for Improved Developmental Neurotoxicity Testing Sachana, Magdalini; Bal-Price, Anna; Crofton, Kevin M. Toxicological Sciences, Vol. 167, Issue 1 https://doi.org/10.1093/toxsci/kfy211	journal	November 2018
Evaluation of Chemical Effects on Network Formation in Cortical Neurons Grown on Microelectrode Arrays Shafer, Timothy J.; Brown, Jasmine P.; Lynch, Brittany Toxicological Sciences, Vol. 169, Issue 2 https://doi.org/10.1093/toxsci/kfz052	journal	February 2019
The Next Generation Blueprint of Computational Toxicology at the U.S. Environmental Protection Agency Thomas, Russell S.; Bahadori, Tina; Buckley, Timothy J. Toxicological Sciences, Vol. 169, Issue 2 https://doi.org/10.1093/toxsci/kfz058	journal	March 2019
Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation*: DNT guideline study Tsuji, Ryozo; Crofton, Kevin M. Congenital Anomalies, Vol. 52, Issue 3 https://doi.org/10.1111/j.1741-4520.2012.00374.x	journal	August 2012
Synaptic Activity and the Construction of Cortical Circuits Katz, L. C.; Shatz, C. J. Science, Vol. 274, Issue 5290 https://doi.org/10.1126/science.274.5290.1133	journal	November 1996
The comparative recall of Google Scholar versus PubMed in identical searches for biomedical systematic reviews: a review of searches used in systematic reviews Bramer, Wichor M.; Giustini, Dean; Kramer, Bianca MR Systematic Reviews, Vol. 2, Issue 1 https://doi.org/10.1186/2046-4053-2-115	journal	December 2013
Comparing the coverage, recall, and precision of searches for 120 systematic reviews in Embase, MEDLINE, and Google Scholar: a prospective study Bramer, Wichor M.; Giustini, Dean; Kramer, Bianca M. R. Systematic Reviews, Vol. 5, Issue 1 https://doi.org/10.1186/s13643-016-0215-7	journal	March 2016
Brain Waves and Brain Wiring: The Role of Endogenous and Sensory-Driven Neural Activity in Development Penn, Anna A.; Shatz, Carla J. Pediatric Research, Vol. 45, Issue 4, Part 1 of 2 https://doi.org/10.1203/00006450-199904010-00001	journal	April 1999
A Curated Database of Rodent Uterotrophic Bioactivity Kleinstreuer, Nicole C.; Ceger, Patricia C.; Allen, David G. Environmental Health Perspectives, Vol. 124, Issue 5 https://doi.org/10.1289/ehp.1510183	journal	May 2016
The CHARGE Study: An Epidemiologic Investigation of Genetic and EnvironmentalFactors Contributing to Autism Hertz-Picciotto, Irva; Croen, Lisa A.; Hansen, Robin Environmental Health Perspectives, Vol. 114, Issue 7 https://doi.org/10.1289/ehp.8483	journal	July 2006
Interspecies extrapolation in carcinogenesis: prediction between rats and mice. Gold, L. S.; Bernstein, L.; Magaw, R. Environmental Health Perspectives, Vol. 81 https://doi.org/10.1289/ehp.8981211	journal	May 1989
Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder in U.S. Children Braun, Joe M.; Kahn, Robert S.; Froehlich, Tanya Environmental Health Perspectives, Vol. 114, Issue 12 https://doi.org/10.1289/ehp.9478	journal	December 2006
Meeting Report: Alternatives for Developmental Neurotoxicity Testing Lein, Pamela; Locke, Paul; Goldberg, Alan Environmental Health Perspectives, Vol. 115, Issue 5 https://doi.org/10.1289/ehp.9841	journal	May 2007
Do Pressures to Publish Increase Scientists' Bias? An Empirical Support from US States Data Fanelli, Daniele PLoS ONE, Vol. 5, Issue 4 https://doi.org/10.1371/journal.pone.0010271	journal	April 2010
OECD/EFSA workshop on developmental neurotoxicity (DNT): The use of non-animal test methods for regulatory purposes Fritsche, Ellen ALTEX https://doi.org/10.14573/altex.1701171	journal	January 2017
Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity Bal-Price, Anna ALTEX https://doi.org/10.14573/altex.1712081	journal	January 2018
Advancing the science of developmental neurotoxicity (DNT): testing for better safety evaluation Bal-Price, Anna ALTEX, Vol. 29, Issue 2 https://doi.org/10.14573/altex.2012.2.202	journal	January 2012
Publication bias: What are the challenges and can they be overcome? Joober, Ridha; Schmitz, Norbert; Annable, Lawrence Journal of Psychiatry & Neuroscience, Vol. 37, Issue 3 https://doi.org/10.1503/jpn.120065	journal	May 2012
Toward a Better Testing Paradigm for Developmental Neurotoxicity: OECD Efforts and Regulatory Considerations Sachana, Magdalini; Shafer, Timothy J.; Terron, Andrea Biology, Vol. 10, Issue 2 https://doi.org/10.3390/biology10020086	journal	January 2021

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59 BASIC BIOLOGICAL SCIENCES
Brain
Development
Developmental neurotoxicity
Neurosciences & Neurology
Reference chemicals
Toxicity testing
Toxicology

An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

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References (53)

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