Toxicology of Industrial Compounds

286 TESTING AND EVALUATION FOR REPRODUCTIVE TOXICITY
Figure 20.3 OECD 421 priority selection test.
Figure 20.4 Fertility and embryotoxicity.
provides the equivalent of the OECD single generation study. Conversely,
if pretesting prognosis suggests a high probability of prenatal effects,
including induction of malformation, then females could be killed just
before delivery and foetuses examined for structural defects (Figure 20.4).
This provides the equivalent of a fertility and embryotoxicity study we will
see again later.
OECD guideline 422 simply adds to OECD 421, elements for assessment
of systemic and neurotoxicity. For those who have never conducted such a
test it seems impossibly complex, but it is neither as difficult to perform,
nor to interpret, as is feared. Its rejection by EC Officialdom makes it an
even better proposition, since there need be no inhibitions about modifying
the design according to circumstances.
Some brief examples of results that may be encountered with positive
materials are illustrated by the examples of Carbendazim (metabolite of
Benomyl), DEHP, Cyclophosphamide and ethylene glycol methyl ether
(EGME, 2-methoxyethanol). With Carbendazim (Table 20.4) macroscopic
and microscopic examinations show unequivocal effects on testes and
epididymides indicating an effect on spermatogenesis. An effect on females
and offspring is indicated by an increased duration of pregnancy, reduction
in the number of females with live young and lower values for litter size,