Skip to main content
Journal cover image

Guidelines for developmental neurotoxicity and their impact on organophosphate pesticides: a personal view from an academic perspective.

Publication ,  Journal Article
Slotkin, TA
Published in: Neurotoxicology
June 2004

The appropriate regulation of drugs, chemicals and environmental contaminants requires the establishment of clear and accepted guidelines for developmental neurotoxicity. Ideally, these guidelines should encompass the ability to assess widely disparate classes of compounds through routine tests, with high throughput and low cost. Increasingly, however, the progress in primary research from academic laboratories deviates from this goal, focusing instead on categorizing novel effects of toxicants, development of new testing paradigms, and extension of techniques into molecular biology. The differing objectives of academic science as opposed to those of regulatory agencies or industry, are driven in part, by the priorities of the agencies that fund primary research. Recent work on organophosphate pesticides (OPs) such as chlorpyrifos (CPF) illustrate this dichotomy. Originally, OPs were thought to affect brain development through their ability to elicit cholinesterase inhibition and consequent cholinergic hyperstimulation. This common mechanism allowed for parallels to be drawn between standard measures of systemic toxicity, gross morphological examinations, and exposure testing utilizing an easily-assessed surrogate endpoint, plasma cholinesterase activity. In the past decade, however, it has become increasingly evident that CPF, and probably other OPs, have direct effects on cellular processes that are unique to brain development, and that these effects are mechanistically unrelated to inhibition of cholinesterase. The identification and pursuit of these mechanisms and their consequences for brain development represent new and exciting scientific findings, while at the same obscuring the ability to sustain a uniform approach to neurotoxicity guidelines or biomarkers of exposure. In the future, a new set of test paradigms, relying on primary work in cell culture, invertebrates, or non-mammalian models, followed by more targeted examinations of specific processes in mammalian models, may unite cutting-edge academic research with the need for establishing flexible guidelines for developmental neurotoxicity.

Duke Scholars

Published In

Neurotoxicology

DOI

ISSN

0161-813X

Publication Date

June 2004

Volume

25

Issue

4

Start / End Page

631 / 640

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Practice Guidelines as Topic
  • Organophosphorus Compounds
  • Neurotoxicity Syndromes
  • Insecticides
  • Humans
  • Developmental Disabilities
  • Child
  • Brain
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Slotkin, T. A. (2004). Guidelines for developmental neurotoxicity and their impact on organophosphate pesticides: a personal view from an academic perspective. Neurotoxicology, 25(4), 631–640. https://doi.org/10.1016/S0161-813X(03)00050-0
Slotkin, Theodore A. “Guidelines for developmental neurotoxicity and their impact on organophosphate pesticides: a personal view from an academic perspective.Neurotoxicology 25, no. 4 (June 2004): 631–40. https://doi.org/10.1016/S0161-813X(03)00050-0.
Slotkin, Theodore A. “Guidelines for developmental neurotoxicity and their impact on organophosphate pesticides: a personal view from an academic perspective.Neurotoxicology, vol. 25, no. 4, June 2004, pp. 631–40. Pubmed, doi:10.1016/S0161-813X(03)00050-0.
Journal cover image

Published In

Neurotoxicology

DOI

ISSN

0161-813X

Publication Date

June 2004

Volume

25

Issue

4

Start / End Page

631 / 640

Location

Netherlands

Related Subject Headings

  • Toxicology
  • Practice Guidelines as Topic
  • Organophosphorus Compounds
  • Neurotoxicity Syndromes
  • Insecticides
  • Humans
  • Developmental Disabilities
  • Child
  • Brain
  • Animals