Detection of immunotoxicity of benzo[a]pyrene in a subacute toxicity studyafter oral exposure in rats

In an extended OECD 407 study protocol, including immune parameters, male R iv:Tox Wistar SPF rats were treated for 35 days with benzo[a]pyrene (B[a]p) (3, 10, 30, or 90 mg/kg body weight) by gavage. Oral administration of B[a ]p in rats resulted not only in general toxicity, as indicated by the effec ts on body weight, but also in immunotoxicity, as indicated by the effects on bone marrow, thymus, spleen, and lymph nodes. Oral B[a]p induced a dose- related decrease in thymus weight (at 10, 30, and 90-mg/kg). Lymph node wei ghts (popliteal, mandibular, and mesenteric) were decreased in the 90-mg/kg rats only. Histologically, indications for cortical atrophy were noted in the thymuses of the 30- and 90-mg/kg dose groups, which was confirmed by mo rphometric analysis. Nucleated spleen and bone marrow cell counts were decr eased in the 90-mg/kg group. Both the absolute number (90 mg/kg) and relati ve number (10, 30, and 90 mg/kg) of B cells in the spleen were decreased. R ed blood cell (RBC) and white blood cell (WBC) counts were significantly de creased; for the WBC at 90 mg/kg, and for the RBC at 10, 30, and 90 mg/kg, The absolute number of lymphocytes and eosinophilic granulocytes was decrea sed in the 90-mg/kg group, while the absolute number of monocytes was incre ased, in the 10- and 30-mg/kg dose groups. Serum immunoglobulin levels show ed a decrease of IgM and IgA after treatment of the animals with 30 and 90 mg/kg, respectively. The highest dose of B[a]p treatment (90 mg/kg) resulte d in a significant decrease of natural killer (NK)-cell activity in the spl een. Most toxic effects were only observed in the highest-dose group (90 mg /kg), but compared to the general toxicity, some parameters indicating immu notoxic effects were also affected at lower doses (10 and 30 mg/kg). In con clusion, immunotoxicity of B[a]p can be detected using parameters of the im mune system such as described in the recently updated OECD 407 guideline. I n the present study thymus weight changed and spleen B-cell populations wer e affected at a dose of 10 mg/kg, a level where no overt general toxicity w as noted.