For this reason, administration of PZ during sexual differentiation produces severe malformations of androgen-dependent tissues in male rat offspring but is without obvious effect on the female rat. In contrast, administration of androgens to the female fetus induces malformations of the bipotential undifferentiated tissue. Androgens activate AR-dependent male-like differentiation, but treated male rats differentiate normally.
In the current study, administration of PZ from GD 14 to GD 18 delayed parturition at all dosage levels. PZ-in-duced aromatase inhibition and reductions in ovarian estrogen near term is a possible mechanism by which parturition was delayed.
Dystocia and delays in parturition are toxicities common to many conazole fungicides and, for some fungicides, these are the critical effects used to set no-observed-ad-verse-effect levels (NOAELs) in the risk assessments. For example, ketoconazole (which also targets P450 enzyme activity), like PZ, increased pup mortality and delayed parturition in dams dosed from Gd 14 to GD 18, but male offspring did not display signs of demasculinization. Similarly, the pyrimidine fungicide fenarimol also displays aromatase-inhibitory activity and delays pup delivery, but in contrast to PZ, fenarimol did not produce overt effects on F1 male development.