Toxicology of Industrial Compounds

Figure 20.5 Manifestations of developmental toxicity
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the high sperm production capacity of animals compared with humans.
Interim results from an ongoing survey show that, where data are
available, direct methods are effective and that a combination of direct
methods with a premating dosing time of 2 weeks or less is even more
effective (Table 20.10). The combination compares favourably with
prolonged premating treatment and mating. Why have agencies and
industry failed to conduct or sponsor such surveys?
For non-medicines, use of a prolonged premating treatment period for the
parent generation is an unnecessary duplication as treatment is continued
into the F1 generation; this cannot be mated until animals have reached
sexual maturity. Using science facts, a more efficient design for a two
generation study (Figure 20.6) would include the following features:
– One control and 2–4 test groups with dosages set at 2–5 fold descending
intervals from a high dosage.
– The high dosage should be a limit dose (1000 mg kg −1 ) or one inducing
a minimal systemic effect on adults.
– A short 2–4 week premating treatment period for both sexes of the
parent (F0) generation.
– A greater group size for the F0 generation to allow balanced selection of
the F1 generation.