In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects tooth development in rhesus monkeys

We thought to validate the current tolerable daily intake (TDI) value for dioxin (4 pg/kg) in Japan. Pregnant rhesus monkeys received an initial dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0, 30, or 300 ng/kg subcutaneously) on day 20 of gestation; the dams received additional injection of 5% of the initial dose every 30 days until day 90 after delivery. The teeth of stillborn, postnatally dead, and surviving offspring (now approximately 4 years old) were evaluated. None of the offspring in the 0 and 30 ng/kg groups (n=17 and 15, respectively) had tooth abnormalities, whereas 10 of 17 in the 300 ng/kg had them. These findings suggest the lowest-observed adverse-effect level (LOAEL) for TCDD in the rhesus monkey is between 30 and 300 ng/kg, and probably is close to that for rodents (86 ng/kg) on which the current TDI was based. It is reasonable to conclude that the current TDI needs no immediate modification.