Paternal exposures to exogenous agents have produced various developmental defects in the offspring, including decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. Most studies assessing function of offspring following paternal exposure have utilized rats, but the NTP is validating the rabbit as an animal model for human reproductive toxicity. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. We report here a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included 7 males/group exposed for 15 weeks to lead acetate to produce 0, 50, or 110 f.1g/dL blood lead. The main study included 15 males/group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 f.1g/dL blood lead. The exposed males were mated with unexposed females. The females delivered and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were tested for exploratory activity in a standard figure8 "maze" for 30 min/day on days 15, 20, 25, and 30. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters, with a mean of 6 livebirths/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and 2 died giving birth. Significant postnatal deaths were observed in all groups, with about half of the offspring dying before day 15. There were no treatment-related effects on offspring weight gain through weaning. The data suggest that paternal lead exposure of rabbits may reduce figure-8 activity on day 25, the time of peak activity in the offspring.
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 2006, Cincinnati, Ohio