#621 Reproductive toxicity – developmental studies (teratogenicity) (two species)
Objective of the study
The objective of the prenatal developmental toxicity study is provide general information concerning the effects of prenatal exposure on the pregnant test animal and on the developing organism. More specifically, the developmental toxicity study aims to:
- Identify direct and indirect effects on embryonic and foetal development resulting from exposure to the active substance;
- Identify any maternal toxicity;
- Establish the relationship between observed responses and dose in both dam and offspring;
- Establish NOAELs for maternal toxicity and pup development.
Circumstances under which the study is recommended to be required
The prenatal developmental toxicity study is recommended if the pesticide is intended:
- for food uses; or
- for non-food uses if use of the product is likely to result in significant human exposure over a portion of the human lifespan in terms of frequency, magnitude or duration of exposure.
If it is claimed that such testing is unnecessary, that claim shall be fully justified.
Test organism
The prenatal developmental toxicity study is normally conducted with rat and rabbit by the oral route.
The rat study may not be required if developmental toxicity has been adequately assessed as part of an extended one-generation reproductive toxicity study.
Additional testing by other routes may be recommended if the pesticide is determined to be a prenatal developmental toxicant after oral dosing.
Test substance
- Technical grade active ingredient
Typical endpoints of the study
The No Observed Adverse Effect Level (NOAEL) for maternal toxicity and pup development are reported whenever possible.
Other typical endpoints of the study include, but are not limited to: Maternal toxic response data; developmental endpoints for litters with implants; Developmental endpoints for litters with live foetuses.
Diagnostic criteria for malformations and variations should be given in the report. The glossary of terminology under development by the International Federation of Teratology Societies should be considered where possible.
Test guidelines
The following test guidelines may be used for the two-generation reproductive toxicity study:
•OECD Guidelines for the Testing of Chemicals. Test No. 414: Prenatal development toxicity study
•OECD Guidelines for the Testing of Chemicals. Test No. 426: Developmental neurotoxicity study
•US EPA Health Effects Test Guidelines. OPPTS 870.3700. Prenatal developmental toxicity study.
•EC Testing Method B.31. Prenatal developmental toxicity study. Council Regulation (EC) No 440/2008