Sexual maturation and puberty

Assessment of fertility is included in generation studies and in the reproductive screening tests. Assessment of fertility in exposed 

Reduced fertility has been found for a number of chemicals, but often at relatively high exposure levels. However, it has to be considered that the rat is the most commonly used experimental animal and that a male rat can generally still produce normal progeny after having its sperm production reduced to 10% of the normal level (Aafjes et al., 1980). Thus, fertility data from rat studies alone can be a rather insensitive end-point. Human males may not have a similar sperm reserve capacity as rodents, and therefore the two-generation study has recently been updated to include assessment of sperm quality. It is unknown whether female rats (compared with human females) are also less sensitive to effects on fertility, but the two-generation study has recently been updated in that aspect by the inclusion of assessment of estrous cyclicity. 

The assessment of sperm quality includes measures of sperm number, anomalies, and motility, but the ability of the sperm to fertilize the ovum is not assessed. In order to increase the sensitivity for detection of fertility effects, investigation of in vitro fertilization could be considered. Another potentially more sensitive option may be the continuous breeding protocol, where the animals produce several litters instead of only one litter per pair. 

Effects manifesting during the ageing process are not included in any guideline for reproductive toxicity. For example, the reproductive span of females is limited from the time of sexual maturation to reproductive senescence. The time of sexual maturation may be assessed in the two-generation study, but reproductive senescence is not assessed. Consequently, effects on the reproductive span of females are not covered in the reproductive toxicity test guidelines. 

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