Evidence map›Paper›PMID 27212452›Full record

ReviewNeurotoxicology2017

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity.

Anna Bal-Price, Pamela J Lein, Kimberly P Keil, Sunjay Sethi, Timothy Shafer, Marta Barenys, Ellen Fritsche, Magdalini Sachana, M E Bette Meek

Abstract readReview
In one paragraph

Review in Neurotoxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

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  12. Effects of air pollution exposure on social behavior: a synthesis and call for research.Environmental health : a global access science source · 2021
    Review
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  15. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Anna Bal-PriceEuropean Commission Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy. Electronic address: anna.price@ec.europa.eu.
Pamela J LeinDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
Kimberly P KeilDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
Sunjay SethiDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
Timothy ShaferIntegrated Systems Toxicology Division, Office of Research and Development, U.S. Environmental Protection Agency, RTP, USA.
Marta BarenysIUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Ellen FritscheIUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Magdalini SachanaEuropean Commission Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy.
M E Bette MeekMcLaughlin Centre for Risk Science, University of Ottawa, Ottawa, Canada.

Funding

UC Davis Center for Children's Environmental Health (CCEH)P01ES011269 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI VAN DE WATER, JUDY A. · 2001 to 2018
$12.5M
Molecular and Cellular Basis of PCB Developmental Neurotoxicity: ViCTER supplementR01ES014901 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HANS-JOACHIM LEHMLER, Pamela J Lein · 2009 to 2026
$9.3M
ENVIRONMENTAL TOXICOLOGYT32ES007059 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura S Van Winkle · 1985 to 2026
$7.9M
NIEHS NIH HHS P01 ES011269NIEHS NIH HHS R01 ES014901NIEHS NIH HHS T32 ES007059
6 · The paper itself

Abstract

The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed.

Indexed as

Risk AssessmentAnimalsHumansNervous SystemNeurotoxicity SyndromesNeurotoxinsSignal TransductionStructure-Activity RelationshipNeurotoxinsAdverse outcome pathwaysMode of actionNeurotoxicityRisk assessment

Identifiers

PMID27212452
PMCPMC5114159

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.