Toxicology of Industrial Compounds

Table 20.6 OECD 422: cyclophosphamide, tabular summary
Notes:
pp=post partum.
Bold type indicates treatment effect. Female deaths at 3 and 4.5 mg kg −1 are
attributable to treatment as, at 6.7 mg kg −1 , all females died. There was a reduction
in the number of females with young, litter size, litter weight and mean pup weight.
No effects on spermatogenesis were reported but, if a dosage inducing effect on the
male had been selected, all the females would have died.
females was slow. As far as I know this has not been mentioned in the
extensive literature on EGME.
These examples and others show that the OECD tests are capable of
detecting substances with marked effects on reproduction. With such
results it would be foolhardy to consider higher level guideline tests. If the
substance is not abandoned any further testing would require case by case
designs to characterise the detected effects more completely.
Full scale testing
If pretesting prognosis suggests that a substance is unlikely to present
problems of toxicity, fast track progression to level 2 testing should be
considered (Table 20.2) to avoid unnecessary duplication of step by step
testing. Expected tests include a two generation study in rats and an
embryotoxicity study in rats and rabbits. In the harmonised guideline for
medicines this same strategy is just one of several options and the same or
greater flexibility should be made available for testing industrial
chemicals.
Tests for embryotoxicity
A.K.PALMER 289
An anomaly in this strategy is the specification for embryotoxicity studies
in two species, when only one species is required for all other aspects of