Test No. 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test
This screening Test Guideline describes the effects of a test chemical on male and
female reproductive performance. It has been updated with endocrine disruptor endpoints,
in particular measure of anogenital distance and male nipple retention in pups and
The test substance is administered in graduated doses to several groups of males and
females. Males should be dosed for a minimum of four weeks. Females should be dosed
throughout the study, so approximately 63 days. Matings "one male to one female" should
normally be used in this study. This Test Guideline is designed for use with the rat.
It is recommended that each group be started with at least 10 animals of each sex.
Generally, at least three test groups and a control group should be used. Dose levels
may be based on information from acute toxicity tests or on results from repeated
dose studies. The test substance is administered orally and daily. The results of
this study include clinical observations, body weight and food/water consumption,
oestrous cycle monitoring, offspring parameters observation/measurement, thyroid hormone
measurement, as well as gross necropsy and histopathology. The findings of this toxicity
study should be evaluated in terms of the observed effects, necropsy and microscopic
findings. Because of the short period of treatment of the male, the histopathology
of the testis and epididymus should be considered along with the fertility data, when
assessing male reproductive effects.
Published on July 28, 2015Also available in: French