Neurotoxicity test validation, positive controls and proficiency: are chemicals necessary?

Area of Science:

• Toxicology
• Neuroscience
• Regulatory Science

Background:

• The U.S. Environmental Protection Agency (USEPA) neurotoxicity guidelines mandate the use of positive control data for toxicology studies.
• These guidelines emphasize the use of chemicals as positive control agents, proposing various rationales.
• The necessity and application of chemical positive controls in neurotoxicity testing warrant re-evaluation.

Purpose of the Study:

• To re-evaluate the roles of positive control data in neurotoxicity testing.
• To assess the utility of positive controls in determining what a test measures, laboratory proficiency, and the biological significance of observed effects.
• To explore alternatives to chemical positive controls in guideline neurotoxicity studies.

Main Methods:

• Review and re-evaluation of existing USEPA neurotoxicity guidelines.
• Analysis of the rationales provided for chemical positive control use.
• Consideration of non-chemical procedures as alternative positive control methods.

Main Results:

• Positive control data serve crucial roles in validating test measurements, assessing laboratory performance, and contextualizing results.
• Chemicals are the emphasized method for positive control in most guideline neurotoxicity tests.
• Non-chemical procedures, such as systematic manipulation of experimental parameters, offer a less risky alternative.

Conclusions:

• While chemical positive controls are established, their necessity should be critically assessed.
• Non-chemical procedures present a promising and safer alternative for positive control testing in neurotoxicity studies.
• Adoption of non-chemical methods could enhance the ethical and practical aspects of regulatory toxicology.