Toxicology of Industrial Compounds

284 TESTING AND EVALUATION FOR REPRODUCTIVE TOXICITY
Table 20.3 Methods for detecting effects on human reproduction
reproduction. To detect the wide range of possible effects it is necessary to
expose mammals to a substance from conception through sexual maturity.
It is necessary to look for consequences of this exposure through at least
one life cycle (Figure 20.2). This long observation period is required for
detection of latent manifestations of developmental toxicity, such as those
induced by lead, alcohol, diethylstilboestrol and other hormonally active
substances. The only means of covering all these aspects is a two generation
study or the equivalent in a combination of tests.
Restricted test systems
The use of lesser tests for industrial chemicals is a concession. Examination
for some effects is omitted because they are not perceived to be important
or because they would be difficult to detect, or because they occur very
rarely. For example, first detection of effects in offspring of second
generations is rare so such activity does not have a high priority.
With these restricted tests, emphasis should be on detecting effects and
not on manipulating a no effect level. Tests that could be considered would
include OECD 421 and 422, the OECD single generation study and the old
FDA Segment I study for medicines. The latter two are restricted tests
because they do not allow detection of latent manifestations of
developmental toxicity.
The best return for effort is afforded by OECD 422, which combines
examination for general or systemic toxicity, as well as reproductive
toxicity. However, realising its potential requires an experienced laboratory
team, the courage to modify the test and the conceptual ability to know
how to interpret the results.