Pesticide Registration Toolkit

#625 Subchronic neurotoxicity 90-day (rat)

Objective of the study

The objective of the subchronic (90-day) neurotoxicity study is to determine potential neurotoxicity of the active substance (major neurobehavioural and neuropathological effects) after repeated exposure over a prolonged period of time.
More specifically, the subchronic neurotoxicity study, alone or in combination, provides information that can:
  • identify whether the nervous system is permanently or reversibly affected by the chemical tested;
  • contribute to the characterization of the nervous system alterations associated with exposure to the chemical, and to understanding the underlying mechanism.
  • determine dose-and time-response relationships in order to estimate a no-observed-adverse-effect level (which can be used to establish safety criteria for the chemical).
 

Circumstances under which the study is recommended to be required

The subchronic neurotoxicity study should always be conducted.
 
All 90-day subchronic studies in rats can be designed to simultaneously fulfil the requirements of the 90-day neurotoxicity study using separate groups of animals for testing. Although the subchronic guidelines include the measurement of neurological endpoints, they do not meet the requirement of the 90-day neurotoxicity study.
 

Test organism

The subchronic neurotoxicity study is conducted with the adult rat.
 

Test substance

Technical grade active ingredient
 

Typical endpoints of the study

Typical endpoints of the subchronic neurotoxicity study include (among others):
  • no-observed-adverse effect level;
  • toxic response data, including signs of toxicity or mortality;
  • neurobehavioural, neuropathological, and neurochemical or electrophysiological findings, if available.
As determined by the responsible authority, additional measurements may also be recommended, such as cholinesterase activity for certain pesticides, e.g. organophosphates and some carbamates. The route of exposure should correspond with the primary route of exposure.
 

Test guidelines

The following test guidelines may be used for the subchronic neurotoxicity study: