The mean number of nipples retained as adults were fewer than the number of areolas/ nipples noted on PCD 35 except in the highest-dosed group (Fig. 6). In all cases, inguinal areolas/nipples observed at PCD 35 were more likely to be transient, while thoracic and abdominal nipples were most likely to be retained in adults.
In the 250 mg/kg-BW per day group, 100% of males showed cleft phallus and hypospadias, 70% also had an exposed os penis (Fig. 5), and 40% had a vaginal pouch (Fig. 7).
Body weight at necropsy was reduced compared with that of controls, thus all organ weights were accordingly adjusted for body weight using the linear regression between body weight and the organ in question. Organs showing reductions in weight (adjusted) at 250 mg/kg-BW per day compared with those of controls were as follows: testes (P = 0.0052), epididymides (P = 0.0002), levator ani plus bulbocavernosus muscle (P = 0.0006), seminal vesicles (P = 0.02), and ventral prostate (P < 0.0001). Testes were typically flaccid and filled with fluid, whereas epididymides were incompletely formed and the corpus so reduced that caput and cauda were sometimes joined only by connective tissue (Fig. 8).
FIG. 5. Phallus abnormalities in adult male rats receiving a 5-day in utero exposure to PZ. Panels are arranged from left to right according to dosage group indicated by numbers to the left of the diagram. A and B) Variation within controls. C and D) Animals with a maternal dose of 125 mg/kg-BW per day. E-G) Animals with a maternal dose of 250 mg/kgBW per day. gl, glans penis; pr, prepuce; ur, urethral opening; os, os penis. Hypospadias is evident in the two highest dosage groups and (C-E) show examples of incomplete preputial separation. Severe phallus clefting and exposure of the os penis is evident in the highest dosage group (F and G).
FIG. 6. Prochloraz-induced areola/nipple retention in the male rat. Are-olas and nipples were more prominent in infant male pups at PCD 35 (PND 13) than were permanent nipples in adult male rat offspring at necropsy (PCDs 147-213). Error bars = SEM. *P < 0.05 compared with the 0 PZ dose.
FIG. 7. Prochloraz-induced vaginal morphology in adult male rats receiving a 5-day in utero exposure. A) Panoramic view of a vaginal pouch (forceps inserted) in a treated male from the 250 mg PZ/kg group. B) A close-up of a control female phallus and vaginal opening. C and D) Close-ups of vaginal pouches and phallus deformities in males from the 250 mg PZ/kg group. E-G) The most severely affected animal in the 125 mg PZ/ kg group. In one malformed male, an ejaculatory plug (F) was found embedded (E) in the vaginal opening (G).