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Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use.

Publication ,  Journal Article
Aschner, M; Ceccatelli, S; Daneshian, M; Fritsche, E; Hasiwa, N; Hartung, T; Hogberg, HT; Leist, M; Li, A; Mundi, WR; Padilla, S; Piersma, AH ...
Published in: ALTEX
January 2017

There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes. The advantage of such types of assays is that they capture toxicants with multiple targets and modes-of-action. Moreover, the processes modelled by the assays can be linked to toxicity endophenotypes, i.e., alterations in neural connectivity that form the basis for neurofunctional deficits in man. The authors of this review convened in a workshop to define criteria for the selection of positive/negative controls, to prepare recommendations on their use, and to initiate the setup of a directory of reference chemicals. For initial technical optimization of tests, a set of > 50 endpoint-specific control compounds was identified. For further test development, an additional "test" set of 33 chemicals considered to act directly as bona fide DNT toxicants is proposed, and each chemical is annotated to the extent it fulfills these criteria. A tabular compilation of the original literature used to select the test set chemicals provides information on statistical procedures, and toxic/non-toxic doses (both for pups and dams). Suggestions are provided on how to use the > 100 compounds (including negative controls) compiled here to address specificity, adversity and use of alternative test systems.

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Published In

ALTEX

DOI

EISSN

1868-8551

ISSN

1868-596X

Publication Date

January 2017

Volume

34

Issue

1

Start / End Page

49 / 74

Related Subject Headings

  • Toxicology
  • Toxicity Tests
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurotoxins
  • Neurotoxicity Syndromes
  • Neurons
  • Male
  • Humans
  • Hazardous Substances
 

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Aschner, M., Ceccatelli, S., Daneshian, M., Fritsche, E., Hasiwa, N., Hartung, T., … Lein, P. J. (2017). Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use. ALTEX, 34(1), 49–74. https://doi.org/10.14573/altex.1604201
Aschner, Michael, Sandra Ceccatelli, Mardas Daneshian, Ellen Fritsche, Nina Hasiwa, Thomas Hartung, Helena T. Hogberg, et al. “Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use.ALTEX 34, no. 1 (January 2017): 49–74. https://doi.org/10.14573/altex.1604201.
Aschner M, Ceccatelli S, Daneshian M, Fritsche E, Hasiwa N, Hartung T, Hogberg HT, Leist M, Li A, Mundi WR, Padilla S, Piersma AH, Bal-Price A, Seiler A, Westerink RH, Zimmer B, Lein PJ. Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use. ALTEX. 2017 Jan;34(1):49–74.
Journal cover image

Published In

ALTEX

DOI

EISSN

1868-8551

ISSN

1868-596X

Publication Date

January 2017

Volume

34

Issue

1

Start / End Page

49 / 74

Related Subject Headings

  • Toxicology
  • Toxicity Tests
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Neurotoxins
  • Neurotoxicity Syndromes
  • Neurons
  • Male
  • Humans
  • Hazardous Substances