Male and female Wistar rats were fed
bis(tri-n-butyltin)oxide (
TBTO) at 0, 5, 20, 80, or 320 mg/kg diet for 4 weeks. Clinical signs and decreases in feed and water consumption were observed in the 80 and 320 mg/kg groups. The serum
transferase activities (
alanine amino
transferase and
aspartate amino
transferase were increased at 20 (males only), 80, and 320 mg/kg. The serum
glucose and
liver glycogen concentrations were lowered in the 320 mg/kg group. At 80 and 320 mg/kg the serum
IgG level was reduced and
IgM level was increased. Compared to controls the mean relative weight of the thymus was decreased at 20 (males), 80, and 320 mg/kg. In the groups receiving 80 or 320 mg/kg microcytic
anemia was found. The white blood cell counts were decreased, due to the reduction in the number of lymphocytes in the 80 (males) and 320 mg/kg groups. The concentration of neutrophilic granulocytes was increased in the highest dose group. Histopathologic effects included a dose-related lymphocyte depletion of thymic cortex and of T lymphocytes in spleen and mesenteric lymph nodes. In the spleen also depletion of
iron stores was found, and in the medullary sinuses of mesenteric lymph nodes, rosettes of erythrocytes were found around mononuclear cells; the occurrence of rosettes increased with dose from 5 to 80 mg/kg, and appeared to be the most sensitive parameter. A low incidence of areas of liver
necrosis with inflammatory reaction and bile duct
hyperplasia was found in the 320 mg/kg group. A viral or bacterial etiology could be demonstrated for these liver lesions, but they appeared associated with
TBTO-induced ulcerative
inflammation of the common bile duct as shown in an additional study. In 6-week studies exposure of male weanlings to the 0, 20, and 80 mg/kg diets, the serum
insulin concentration in the treated groups was decreased, although the response to
glucose challenge was unaffected. The serum
thyroxin and
thyrotropin (TSH) concentrations were reduced, whereas the
luteinizing hormone (LH) concentration was increased in the 80 mg/kg group. The concentrations of
follicle-stimulating hormone (FSH) and
corticosterone were not changed. The release of LH and FSH was enhanced in the 80 mg/kg group and a tendency toward reduced release was found for TSH. Using immunocytochemistry a dose-related reduction was found in the number and staining intensity of TSH-producing cells in the pituitary, correlating with histopathologically decreased activity of the thyroid.(ABSTRACT TRUNCATED AT 400 WORDS)