Various toxic effects have been observed in children born to mothers exposed during the Yusho and Yu-Cheng incidents, including dermal lesions, decreased birth weights, neurobehavioral deficits, and some prenatal deaths. Although no exposure-related congenital malformations have been reported in these children, oral studies in mice and rats have documented induction of hydronephrosis and/or cleft palate by 2,3,7,8-substituted tetra-, penta-, and hexaCDF congeners. Tissues other than kidney and palate were examined only in the rat studies, which provide some evidence indicating that rats are more susceptible to PCDFs than mice and that neonatal thymic toxicity is a more sensitive developmental end point than fatal mortality or cleft palate in rats.
Irregular menstrual cycles, abnormal basal body temperature patterns, and decreased urinary excretion of estrogens and pregnanediol were observed in female Yu-Cheng patients.
Some intermediate duration oral studies showed no histological alterations in the ovaries, uterus, or testes of rats treated with various PCDFs, although there is some evidence from other oral studies (intermediate duration in rats and acute duration in guinea pigs) that the testes are a target.
No information is available on reproductive effects of PCDFs in animals or humans following dermal or inhalation exposure, but limited available toxicokinetic data suggest that the potential for reproductive toxicity is likely to be qualitatively similar across routes.
Limited information is available regarding genotoxic effects of PCDFs in humans.
Examination of lymphocytes of Yu-Cheng individuals revealed an increased frequency of sister chromatid exchanges. This effect could be attributed to PCBs that were found in the serum of these subjects at a concentration level 1,000 times higher than PCDFs, because genotoxic effects of halogenated aromatic hydrocarbons are not known to be Ah receptor-mediated.
Only 2,3,7,8-tetraCDF has been tested for genotoxicity in eukaryotic organisms (S. cerevisiae yeast), and only monoCDFs, octaCDF, and 2,3,7,8-tetraCDF have been tested in prokaryotes (S. typhimurium bacteria). The results of these studies showed that 2,3,7,8-CDF was not mutagenic in S. cerevisiae and that PCDFs were generally not mutagenic in various strains of S. typhimurium, with only 2- and 3-monoCDF inducing some activity.