Immunotoxicity of tributyltin oxide in rats exposed as adults or pre-weanlings

A comparison was made between adult and pre-weanling rats of the immunotoxic effects of subacute dosing with bis(tri-n-butyltin) oxide (TBTO). Adult (9 weeks old) male Fischer rats were dosed by oral gavage with TBTO for 10 consecutive days at 1.25-10 mg/kg per dose or 3 times/week for a total of 10 doses at 5-20 mg/kg per dose. Adult rats similarly dosed by oral gavage with 6 mg/kg per dose cyclophosphamide (CY) served as positive controls. Pre-weanling rats (3-24 days old) were dosed 3 times/week for a total of 10 doses at 2.5, 5 or 10 mg/kg per dose. At various times after dosing rats were evaluated for alterations in body and lymphoid organ weights, mitogen and mixed lymphocyte reaction (MLR) lymphoproliferative (LP) responses, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) responses and primary antibody plaque-forming cell (PFC) responses. In adult rats given 10 daily doses of TBTO, thymic involution was observed at a dosage of 2.5 mg/kg and mitogen responses to Con A and PHA were suppressed at 5 mg/kg. The PFC response was enhanced in adult rats dosed daily at 2.5 mg/kg. A dosage of 5 mg/kg given intermittently (3 times/week) to adults or pre-weanlings resulted in thymic involution. Reductions in mitogen responses were observed in adults dosed intermittently at 10 and 20 mg/kg and in pre-weanlings at 5 and 10 mg/kg. The MLR response was suppressed in adult rats dosed intermittently at 20 mg/kg and in pre-weanling rats at 10 mg/kg. NK cell activity was suppressed only in pups dosed intermittently at 10 mg/kg. CTL responses were not affected in either age group. Within 3 weeks following the last exposure of adult rats to TBTO all parameters returned to normal. On the other hand, LP responses to mitogens were suppressed in 10-week-old rats that were dosed with 10 mg/kg TBTO as pre-weanlings. However, this exposure regimen in reductions in body weight that persisted for up to 13 weeks of age, which suggests that TBTO may be a developmental toxicant. These data indicate that while exposure of young rats to TBTO resulted in immune alterations at doses lower than those required to suppress responses in adults, the observed effects may also be influenced by the developmental toxicity of this compound.