API PUBL 33-31750-1986
IMMUNOTOXICOLOGY OF BENZOPYRENES IN FISHER 344 RATS - FINAL REPORT

Standard No.
API PUBL 33-31750-1986
Release Date
1986
Published By
API - American Petroleum Institute
Latest
API PUBL 33-31750-1986
Scope
"INTRODUCTION The scope of the immunotoxicology studies set forth by Task Force PS-23 encompasses efforts to develop selected Immunological assays and validate them In host resistance studies. The first studies reported In August 1983@ entitled ""Effects of Subchronic Fourteen Day Exposure To Benzopyrene in B6C3F1 Male and Female Mice on Specific Immunological Parameters""@ showed that Immunotoxicologlcal assays could be performed In a toxicologlcal mode to demonstrate altered Immune function. Studies reported to the API In April 1985@ entitled ""Effects of Subchronic Fourteen Day Exposure To Benzopyrene In B6C3F1 Female Mice on Host Resistance""@ showed that mice exposed to B(a)P had an altered resistance to two bacteria@ one virus@ and one transplantable tumor. The next area of investigation was aimed at determining whether the rat could be used as an experimental animal for Immunotoxicology studies. The studies described In this report addressed this aim and were conducted under the auspices of Task Force PS-23j the results presented In this report were achieved through the execution of Protocol PS-23-B(a)P-14-3SC. The specific aim addressed In this study and In the report Is stated below: Develop a similar set of Immunotoxicology assays In the rat as those used to Investigate the Immunotoxicology of Benzo(a)pyrene and Benzo(e) pyrene In the mouses As part of these Investigations@ determine the effect of Benzo(a)pyrene and Benzo(e)pyrene on the Immune system of the rat. The available resources did not provide for completion of the specific aim@ and the workscope was reduced as follows: 1. One sex of experimental animal was used. 2. The high dose for benzo(e)pyrene was used. 3. One assay for humoral immunity was performed. 4. One assay for cell mediated Immunity was performed. Several preliminary studies were conducted In the Fisher 344 rat to optimize the assays. The antigenic challenge with sheep erythrocytes and keyhole limpet hemocyanin had to be established. The time course for the Immune response for each of the antigens was also optimized. These studies showed that@ in general@ exposure to benzopyrenes caused similar effects in the rat and mouse. In both@ humoral Immunity was decreased by benzo(a)pyrene@ while not affected by exposure to benzo(e)pyrene. Neither benzo(a)pyrene nor benzo(e)pyrene affected cell mediated Immunity in the two species. There was a lack of similar response in the antibody formingcell response with regard to the lowest dose of benzo(a)pyrene administered. In the mouse the low dose produced a decreased response@ while in rats it caused an enhancement. In both species@ the highest dose of benzo(a)pyrene produced a significant suppression of this response. The overall results here demonstrate that the rat can be used for general Immunotoxicology studies. The mouse remains the choice for Indepth and mechanistic studies on the effect of xenobiotlcs on the Immune system."

API PUBL 33-31750-1986 history




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