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Final Progress Reports: Michigan State University: Remediation Product Toxicity Evaluation Core

Superfund Research Program

Remediation Product Toxicity Evaluation Core

Project Leader: Stephen A. Boyd
Grant Number: P42ES004911
Funding Period: 1995 - 2006

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Final Progress Reports

Year:   2004 

The hypothesis to be tested is that the products of remediation have different biological activities compared to the starting compounds or mixtures.  One method of remediation being evaluated within the Core is ozonation. Biphenyl-2,2', 6,6'-tetracarbaldehyde is an initial byproduct formed from the ozonation of pyrene.  Subsequent to its production, biphenyl-2,2',6,6'-tetracarboxylic acid is formed.  These two ozonation byproducts were evaluated using two assays to compare the toxicity with that of the parent compound.  The first assay measured the potential for the compounds to block gap junctional intercellular communication (GJIC) using the scrape loading/dye transfer (SL/DT) technique.  In normal WB-344 rat liver epithelial cells pyrene significantly blocked intercellular communication at 40 :M, and complete inhibition of communication occurred at 50 :M.  Inhibition of GJIC in cells exposed to biphenyl-2,2´,6,6´-tetracarbaldehyde was observed at a concentration of 15 :M.  At concentrations greater than 20 :M, biphenyl-2,2´,6,6´-tetracarbaldehyde was cytotoxic, and the inhibition of GJIC was caused by cell death.  Biphenyl-2,2’,6,6’-tetracarboxylic acid was neither cytotoxic nor inhibitory to GJIC at the concentrations tested (10 – 500 :M).  Exposure to biphenyl-2,2’,6,6’-tetracarbaldehyde resulted in a concentration-dependent decrease in phorbol ester-stimulated O2- production in neutrophilic HL-60 cells.  Neither exposure to pyrene nor to biphenyl-2,2’,6,6’-tetracarboxylic acid caused a significant toxic effect on neutrophil function.  These results indicate that 2,2’,6,6’-tetracarbaldehyde is more potent than the parent compound, pyrene, in producing inhibition of GJIC and alterations in cellular function of neutrophils.

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