The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Lead Acetate Trihydrate (PbA) is used in manufacturing other lead salts, in the textile industry, and in veterinary medicine. It was tested for reproductive toxicity in Swiss mice, using the RACB protocol. From data in the literature, levels of 0.5, 1.0, and 2.0% in water were selected for the continuous breeding phase of the study.
For the first generation (Task 2), mortalities were elevated at all doses. In controls animals, 3 males and 4 females (3M/4F) died, while in low, medium, and high doses, 0M/12F, 1M/16F, and 16M17F died, respectively. This excessive mortality confounds the interpretation of the other data. In the low and middle dose groups, the death occurred late in Task 2, while the high dose deaths occurred throughout Task 2. The following number of pairs could still contribute data for Task 2: 36, 19, 10, and 4, from the control to high dose groups, respectively.
Reproductive toxicity was observable at all dose levels. The number of litters per pair was reduced by 29% and 58% in the middle and high dose groups. The number of live pups per litter was also reduced in medium and high doses (16% and 55% respectively), while adjusted live pup weight was reduced in all groups by 4% (low), 12% (medium), and 16% (high). At the high dose, cumulative days to litter increased markedly for all litters. No high-dose pair produced a fifth litter.
Despite the excessive mortality, a Task 3 crossover study was performed to attempt to identify the more affected sex, using the control and 0.5% PbA mice. Pairs with a treated female delivered nearly equal to 16% fewer pups/litter. Females in this group continued to die (3 of 9 died during this task).
After the Task 3 litters were delivered and evaluated the F0 adult control and 0.5% PbA animals were killed and necropsied. Female body weight was unaffected, but brain weight was reduced by nearly equal to 8%. The estrous cycle was unaffected in the 6 remaining femnales. Male body weight was unaffected by 0.5% PbA; organ weights did not differ between the groups, nor did sperm measures.
Task 4, the F2 generation assessment, only used offspring from the low dose group. Body weights and viability were not recorded during nursing. At the beginning of the cohabitation period for Task 4, body weights for treated mice were lower than controls by 12% (males) and 6% (females). There were sufficient mice to compose 14 control pairs and 16 treated pairs. The PbA-treated mice delivered 20% fewer live pups/litter, and those pups weighed nearly equal to 7% less than their controls. Pup viability and sex ratio were unaffected by PbA exposure.
After the F2 pups were evaluated and removed, the F1 adults were killed and necropsied. Treated females weighed nearly equal to 6% less than controls, while the pituitary weighed 35% less. Interestingly, the estrous cycle did not differ between the groups. For males, body weight was reduced by 12%, and absolute testis weight was 11% less than controls. Sperm measures did not differ between these two groups.
In conclusion, these concentrations of lead acetate trihydrate produced mortality and reproductive toxicity. A subsequent study at the other RACB laboratory used lower doses in an attempt to separate the potential reproductive/developmental toxicity of lead from the mortality induced by these concentrations.