The Health Effects Institute

Synopsis
Research Report Number 65
Part XII

Prolonged Ozone Exposure Leads to Structural Changes in the Rat Nose

Jack R. Harkema, Paul J. Catalano, and Jon A. Hotchkiss
Michigan State University, East Lansing, MI, and Dana-Farber Cancer Institute, Boston, MA

BACKGROUND

Ozone, a common outdoor air pollutant, is a highly reactive gas and a major component of smog. The U.S. Environmental Protection Agency (EPA) has set a one-hour National Ambient Air Quality Standard for ozone of 0.12 parts per million (ppm) that should not be exceeded more than once per year. This standard, which is based largely on data documenting the adverse effects of short-term exposure on lung function in humans, is currently being reevaluated by the EPA.

Because ozone can damage cells, prolonged or repeated exposures could increase the risk of cancer. For this reason, the National Toxicology Program (NTP) recently evaluated ozone's carcinogenicity in rodents. Another public health concern is that prolonged exposure to ozone might damage the structural components of the airways and contribute to developing noncancerous respiratory diseases. To examine this issue, the Health Effects Institute collaborated with the NTP to provide HEI-funded investigators access to animals that underwent the same rigorously controlled ozone inhalation protocol and quality assurance processes along with the NTP animals. In this NTP/HEI Collaborative Ozone Project, rats were exposed to 0, 0.12, 0.50, or 1.0 ppm ozone for six hours per day, five days per week, for 20 or 24 months.

In one of the original NTP/HEI collaborative studies, Dr. Jack Harkema and his colleagues found a number of structural and functional changes in the nasal region of the rats exposed to 0.5 or 1.0 ppm (but not 0.12 ppm) ozone. (In the rat nose, turbinates are structures that project from the walls of nasal passages and filter potentially harmful substances from the inhaled air.) One of the more provacative findings after ozone exposure was that bony areas of the nasal turbinates had atrophied. This was an intriguing finding because investigators in Mexico have reported alterations in the cells lining the nasal passages of people living in areas with high levels of mixed air pollutants, including ozone.

APPROACH

HEI funded this follow-on study to allow Dr. Harkema and his colleagues the opportunity to employ sophisticated microscopic and quantitative techniques to examine the effects of ozone exposure on the nasal passages of F344/N rats. The tissues used in this study came from the NTP/HEI animals that had been exposed to ozone for 20 months and from the NTP animals that had continued the exposure protocol for 24 months.

RESULTS AND IMPLICATIONS

The investigators confirmed and extended their original results. They found no effects in the nasal turbinates of male or female rats exposed to 0.12 ppm ozone, but the loss of turbinate bone in rats exposed to the two higher ozone concentrations (0.5 and 1.0 ppm) was a major finding. Dr. Harkema and colleagues also found that ozone exposure caused inflammation in an area adjacent to turbinate bone. The investigators proposed that ozone-induced inflammation contributed to the loss of turbinate bone.

The damage to nasal turbinate bone caused by ozone inhalation may have implications for nasal defense mechanisms. Reducing the surface area of the nasal turbinates could decrease their ability to filter potentially harmful dusts, irritant gases, bacteria, or viruses from inhaled air, a mechanism that protects the respiratory tract against infection and injury. These findings are provocative; however, they are difficult to extrapolate to humans because of marked differences between the nasal structures of rodents and humans and because rodents breathe only through the nose, whereas humans use both the nose and mouth. Nevertheless, they do point to the need for additional research on the effects of ozone on the structure and function of the human nasal passages.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies
Part XII: Atrophy of Bone in Nasal Turbinates

Table of Contents

Investigators' Report
Jack R. Harkema, Paul J. Catalano, and Jon A. Hotchkiss

Commentary
Health Review Committee

CODE: HARKEMA65XII

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