Tissue levels of saccharin in the rat during two-generation feeding studies

A single oral dose of [³H]saccharin was given to female rats in late pregnancy. The concentrations of ³H in the tissues of fetal rats 6 to 12 hr after the dose were lower than those in the mother. However, the concentrations in fetal tissues, including bladder wall, decreased more slowly, so that by 48 hr they exceeded the corresponding values obtained for maternal tissues, suggesting the possibility of accumulation during chronic intake. Despite this, the steady-state concentrations of saccharin in the liver and kidneys of fetuses from mothers fed a 5% saccharin diet ad libitum were lower than the corresponding materal values, while the concentrations in the fetal bladder were similar or slightly higher. The concentrations of saccharin in the tissues of rats in utero were not markedly higher than those found in adult F₁ animals. The turnover of saccharin in the fetuses of animals maintained on 5% saccharin diet was similar to that seen after a single dose. The results showed no evidence of excessive accumulation in the bladder wall or other tissues of male rats during in utero exposure or during lactation, which could explain the reported sex and generation specificity of the tumorigenic response.