Pesticide Registration Toolkit

#626 Developmental neurotoxicity

Objective of the study

The objective of the developmental neurotoxicity study is to assess potential functional and morphological hazards to the nervous system which may arise in the offspring from repeated exposure of the mother to the pesticide during pregnancy and lactation. 
 

Circumstances under which the study is recommended to be required

An information-based approach to testing is preferred, which utilizes the best available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a standard guideline study, an enhanced guideline study, or an alternative study should be conducted to assess potential hazard to the developing animal, or in some cases to support a waiver for such testing. Applicants should submit any alternative proposed testing protocols and supporting scientific rationale to the responsible authority prior to study initiation.
The developmental neurotoxicity study is recommended after a weight-of-evidence approach indicates its relevance, considering: 
(i) The pesticide causes treatment-related neurological effects in adult animal studies (i.e. clinical signs of neurotoxicity, neuropathology, functional or behavioural effects). 
(ii) The pesticide causes treatment-related neurological effects in developing animals, following pre- and postnatal exposure (i.e. nervous system malformations or neuropathy, brain weight changes in offspring, functional or behavioural changes in the offspring).
(iii) The pesticide elicits a causative association between exposures and adverse neurological effects in human epidemiological studies. 
(iv) The pesticide evokes a mechanism that is associated with adverse effects on the development of the nervous system (e.g. SAR relationship to known neurotoxicants, altered neuroreceptor or neurotransmitter responses).
 
A combined study with the 2-generation reproduction study in rodents as the basic protocol for the addition of other endpoints or functional assessments in the immature animal is encouraged.
 

Test organism

The developmental neurotoxicity study is preferably conducted with the adult rat.
 

Test substance

Technical grade active ingredient
 

Typical endpoints of the study

Typical endpoints of the developmental neurotoxicity study include (among others):
  • no-observed-adverse effect level;
  • toxic response data, including signs of toxicity or mortality; 
  • nature, severity, duration of the detailed clinical observations; 
  • behavioural, functional, neuropathological, neurochemical, electrophysiological findings 
 

Test guidelines

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