Circadian variation in ozone tolerance.

Circadian variation in ozone tolerance

Most ozone studies involving rodents are done during theday, when the human experimenters are most alert, notes toxicologist Leendert van Bree. But this is not the most active period for nocturnal animals such as rats. Even if rats are awake during a daytime study period, their bodies may not have adjusted--it may still feel like their rest period.

Because the body's production of various chemicals--including those involved in an animal's antioxidant defense system--can undergo large circadian variation, van Bree and his colleagues at the Dutch National Institute of Public Health's Laboratory of Toxicology in Bilthoven decided to compare health effects of ozone exposures delivered at different times. They now report that, in rats, a 12-hour nocturnal exposure to 0.4 parts per million ozone yields twice the respiratory damage as a 12-hour daytime exposure.

"The toxic process that was taking place is an inflammatoryone,' van Bree notes. "It damages the blood-air barrier in the lungs,' causing, among other problems, an increase of blood-serum infiltration into the small lung airways. "So if you lavage [wash out] the lung and analyze for serum ingredients and inflammatory cells, you can detect evidence of inflammation.' Related studies by the Bilthoven researchers indicate that this time-of-day effect is a more important factor in the amount of damage that will occur than the number of consecutive days of exposure. Another unexpected finding: 24-hour exposures were not measurably worse than 12-hour nocturnal ones.

There's a potentially important message here for air-qualityregulators, van Bree believes: Extrapolations from rat data based on daytime (sleep period) exposures "may seriously underestimate human effects' from daytime exposures.