In utero/lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure impairs molar tooth development in rats

Developmental defects caused by dioxins are causing increasing concern since they occur at low dose levels and are usually permanent. In this study we examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at low in utero/lactational exposure levels on rat tooth development in three rat lines, denoted A, B, and C, that differ in their TCDD sensitivity and aryl hydrocarbon receptor structure. These rat lines are derived from TCDD-resistant Han/Wistar (Kuopio) and TCDD-sensitive Long-Evans (Turku/AB) rats by selective breeding. The main target teeth were the third molars, since their development spans from the perinatal period to about 6 weeks after birth. Pregnant dams were exposed to 0.03-1 microg/kg TCDD on gestation day 15. Pups exposed in utero and lactationally were euthanized at the age of 5 or 10 weeks and the jaws were examined. The eruption of the third molar was observed by stereomicroscopy and the jaws were further radiographed. TCDD at 1 microg/kg completely prevented the development of the third lower molars in 60% of males and 50% of females in the most sensitive rat line, C, while only 6% or less of the pups in the more resistant lines A and B were lacking this target tooth. TCDD exposure also dose-dependently diminished the proportion of third molars erupted at the age of 5 weeks. The size of molars was dose-dependently reduced in all rat lines. The third lower molars were most severely affected, and the reduction was significant already at 0.03 microg/kg in line A and at 0.1 microg/kg in lines B and C. The results indicate that impaired tooth development is one of the most sensitive endpoints of TCDD-induced toxicity.