Exposure to the Widely Used Fungicide Mancozeb Causes Thyroid Hormone Disruption in Rat Dams but No Behavioral Effects in the Offspring

The widely used fungicide mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100, or 150 mg mancozeb/kg body weight (bw)/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T(4)) levels were measured in dams during gestation. On PND 16, hormone levels and several organ weights were measured in the offspring, whereas motor activity, startle response, and cognitive function were assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams and was therefore reduced to 100 mg/kg bw/day in mid study. T(4) levels showed a dose-dependent and significant decrease in dams from all three dose groups on GD 15, whereas offspring T(4) levels, thyroid weights, and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did, however, reduce T(4) levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affects the developing brain.