The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may or may not have been peer reviewed and were not evaluated in accordance with the Explanation of Levels of Evidence for Reproductive Toxicity criteria (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09_3566_NTP_ReproTOX_R1.pdf or with the Explanation of Levels of Evidence for Developmental Toxicity criteria (see http://ntp.niehs.nih.gov/ntp/Test_info/NTP_DevTox20090507.pdf) established by the NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Lead Acetate Trihydrate (PbA) was evaluated in this follow-up study as a possible reproductive toxicant using the RACB protocol. A previous study at the other RACB laboratory found significant toxicity at concentrations in the drinking water equal to or greater than 0.5%. Thus, levels for this study were set at 0.125, 0.25, and 0.5% w/v in drinking water. The highest level of PbA caused a slight (nearly equal to 10%) reduction in water consumption, though body weight was unaffected during Task 2. Based on measures of water consumption and body weights, these concentrations of PbA produced consumption estimates of nearly equal to 200, 375, and 700 mg PbA/kg/d.
In the first generation (Task 2), 1 control female, 1 low dose female, 4 middle dose females, and 7 females and 1 male at the high dose died during Task 2. These deaths were considered treatment-related, but the cause of death was not determined. F0 body weights were not affected by PbA consumption. There was a 7% decrease in adjusted live pup weight at the high dose, though PbA did not alter the number of litters/pair or the number of pups/litter.
Task 3 (the crossover study) was not conducted since there were no changes in pup number, and only small changes in pup weight which were expected to be difficult to replicate in the single-mating trial of Task 3.
Thus, Task 4 was conducted with offspring from the control and 0.5% groups. Body weights to weaning were not collected during nursing of the second generation, though mortality in these mice was increased at 4 wks. of age by 15% and 30% for males and females, respectively.
At F1 mating, mating and fertility indices were equal between the two groups. F2 pup body weight was reduced by nearly equal to 16%, though litter size and pup viability were unaffected.
After the F2 litters were evaluated, the F1 adults were killed and necropsied. Females consuming 0.5% PbA weighed nearly equal to 12% less than controls, and brain weight was nearly equal to 7% less than controls, while adjusted spleen weight was 2.2 times greater than controls. Ante-mortem estrous cycle evaluations were not performed. For treated males, body weight was reduced by nearly equal to 11%, while absolute testis weight was nearly equal to 9% less than controls. Absolute brain and relative kidney weights were reduced by nearly equal to 5% and 13%, respectively, while relative spleen weight was increased 1.7-fold. Sperm measures were unaffected by PbA consumption.
Thus, this study replicated the Task 2 mortality and pup body weight effects seen in the first study, while showing that lead acetate trihydrate caused reproductive toxicity only in the presence of adult mortality or systemic changes (spleen weight, brain weight changes).
Report Date: May 29, 1984