The Health Effects Institute

STATEMENT
Synopsis of Research Report 101

Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene

This Statement, prepared by the Health Effects Institute, summarizes a research project sponsored by HEI from September 1997 to November 1999 and conducted by Dr Per Gerde of the Lovelace Respiratory Research Institutes, Albuquerque NM. The following Research Report contains both the detailed Investigators’ Report and a Critique on the study prepared by the Institute’s Health Review Committee.
GERDE 101

INTRODUCTION

Diesel exhaust is a mixture of gases and soot. Soot consists of carbon particles with bound inorganic salts, metals, and more than 450 organic compounds. The organic compounds include genotoxic polynuclear aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), that cause cancer in laboratory animals. Soot inhalation is believed to be a possible contributor to lung cancer risk in occupationally exposed humans because it is readily inhaled and deposits in the lungs. Some researchers believe that PAHs must be released from soot and become bio-available before they exert genotoxicity. However, the fate of the PAHs and their role in the toxicity of diesel exhaust are not well understood.

For the current study, Dr Alan Dahl and colleagues of the Lovelace Respiratory Research Institute in Albuquerque, New Mexico, planned to expose dog trachea to BaP bound to model soot particles and to determine whether it became bioavailable and reacted with the tracheal epithelium. When Dr Dahl left the Lovelace Institutes, Dr Per Gerde became Principal Investigator on this project and added exposures of peripheral lung alveolar region to the study design.

APPROACH

The investigators removed most of the organic compounds from diesel exhaust particles and bound radiolabeled BaP to them as a surrogate for all PAHs. They exposed the lower respiratory tract of three dogs to the particles and measured the levels of particle-bound BaP and free BaP released from particles in the peripheral region of the lungs. After approximately six months, they exposed only the trachea to the particle-bound BaP for similar measurements and isolated peripheral lung tissue to measure the long-term stability of BaP on the particles.

RESULTS AND INTERPRETATION

Soon after lung exposure, free BaP was detected in blood but its concentration quickly dropped, indicating that most of the bioavailable BaP had been released. Metabolites of BaP later appeared in blood, and some radioactive material became bound to peripheral lung tissue. Six months later, much of the BaP remained particle-bound in peripheral lung tissue and lymph nodes and was considered unavailable for genotoxic reactions. After tracheal exposures, some BaP became bioavailable and was metabolized. Therefore, both exposures in this study indicate that some particle-bound BaP becomes bioavailable and has the potential to exert genotoxic effects.

Diesel exhaust particles may not react the same as the model particles used in this study. The model particles contain BaP as a single surrogate for a complex mixture of PAHs and other organic molecules normally found on diesel exhaust particles. Release of the other organic constituents from normal particles would likely affect the rate and extent of BaP release. Further, the binding strength between BaP and the model particles may differ from that in diesel exhaust particles. In addition, the BaP concentration on the model particles was much greater than that calculated to be present on diesel soot particles. This concentration would be expected to influence its release rate. The investigators recognize these concerns but defend their study design as critical to address their aims. The interesting and provocative results of this pilot study must be interpreted carefully. The importance of genotoxic PAHs in the diesel exhaust remains to be confirmed.

STATEMENT Synopsis of Research Report 101

Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene

INTRODUCTION

RESULTS AND INTERPRETATION

STATEMENT
Synopsis of Research Report 101