The effects of perinatal tebuconazole exposure on adult neurological, immunological, and reproductive function in rats

Studies are under way to address concerns of potential persistent immunotox ic, reproductive, and neurotoxic effects of perinatal exposure to several p esticides. Tebuconazole, a triazole fungicide, was evaluated as part of thi s project. Sprague-Dawley dams were administered tebuconazole (0, 6, 20, or 60 mg/kg) by oral gavage daily from gestational day 14 to postnatal day (P ND)7; the pups were then dosed daily at the same levels from PND7-42. Separ ate groups of rats were used for testing of immunological parameters, neuro behavioral testing using a screening battery of functional tests, and cogni tive evaluations. Other groups of rats were evaluated for reproductive deve lopment and function, while yet others were sacrificed at the end of the do sing period for histological analyses of major organs systems, including ne uropathological assessments. Pup viability and body weight were decreased i n the highest dose group. There were no differences in the fertility indice s in the exposed rats mated as adults. In the sheep RBC-immunized high-dose rats, spleen weights and cellularity were increased, and the ratio of cell types was altered compared to controls. There were, however, no biological ly significant changes in the immune function of these rats. At necropsy on PND46 or 152, kidney, liver, and spleen weights were altered by tebuconazo le treatment, but a dose-response relationship was not clear for most organ s; only decreased kidney and increased liver weights were consistent in bot h sexes. Histological analyses were generally unremarkable outside of the b rain. One month after the end of dosing, acquisition of learning the platfo rm location in a water tank (i.e., Morris water maze) was impaired in the h igh-dose group; there were no differences in neuromuscular ability, motor a ctivity, or swim speed to account for this finding. Furthermore, there was no effect on recall of the position during a free-swim trial. Neuropatholog ical evaluations revealed pyknotic cells across hippocampal cell fields in animals of all tebuconazole, treatment groups, with the highest incidence i n the 20 and 60 mg/kg/day dose groups, coincident with cell loss within pyr amidal cell layer of CA3-4 cell fields of the hippocampus and layer V of th e neocortex. Thus, perinatal exposure to tebuconazole produced neurobehavio ral deficits and neuropathology in rats, but did not alter immunological or reproductive function.