Toxicological Sciences, Vol 50, 214-220, Copyright © 1999 by Society of Toxicology
WH De Jong, ED Kroese, JG Vos and H Van Loveren
In an extended OECD 407 study protocol, including immune parameters, male
Riv: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
effects 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 weights (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 morphometric analysis. Nucleated spleen and bone marrow cell
counts were decreased in the 90-mg/kg group. Both the absolute number (90
mg/kg) and relative number (10, 30, and 90 mg/kg) of B cells in the spleen
were decreased. Red blood cell (RBC) and white blood cell (WBC) counts were
significantly decreased; 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 decreased in the 90-mg/kg group, while the absolute number
of monocytes was increased in the 10- and 30-mg/kg dose groups. Serum
immunoglobulin levels showed 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) resulted in a significant decrease of natural killer
(NK)-cell activity in the spleen. Most toxic effects were only observed in
the highest-dose group (90 mg/kg), but compared to the general toxicity,
some parameters indicating immunotoxic effects were also affected at lower
doses (10 and 30 mg/kg). In conclusion, immunotoxicity of B[a]p can be
detected using parameters of the immune system such as described in the
recently updated OECD 407 guideline. In the present study thymus weight
changed and spleen B-cell populations were affected at a dose of 10 mg/kg,
a level where no overt general toxicity was noted.
ARTICLES
Detection of immunotoxicity of benzo[a]pyrene in a subacute toxicity study after oral exposure in rats
Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. w.de.jong@rivm.nl
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