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The Development of Ambient-Type Ozone Exposures in
Controlled Human Health Laboratory Experiments

Similar to vegetation experiments performed in the 1980s (e.g., Musselman et al., 1983; Hogsett et al., 1985), controlled human health laboratory study results have shown a difference in response to square-wave (i.e., constant concentration) O3 exposures and triangular (i.e., variable) exposures. For example, triangular exposures used by Hazucha et al. (1992) and Adams (2003; 2006a; 2006b), suggest that variable exposures can potentially lead to higher FEV1 responses than square-wave exposures at overall equivalent O3 doses. An important observation from these three experiments is that the higher hourly average concentrations elicit a greater effect than the lower hourly average values in a non-linear manner (Hazucha and Lefohn, 2007; Lefohn et al., 2010). The importance of these experiments is that long-term average concentrations are not appropriate for assessing possible human health effects for FEV1 decrements. In addition, the importance of the higher hourly average concentrations leads to the conclusion that an alternative form of the current form of the 8-h health standard may be required. Two 8-h ozone exposure regimes experiencing different hourly average concentration distributions may elicit different FEV1 decrements. In other words, the same 8-h average ozone concentration may lead to different health effects endpoints. As discussed by Lefohn et al. (2010), a possible alternative to the 8-h average form of the current U.S. ozone standard may be a cumulative exposure standard similar to the W126 vegetation exposure index currently applied by the US EPA for assessing vegetation effects.

It has become apparent that controlled human health laboratory simulations of air-pollution risk-assessment need to employ O3 concentration profiles that more accurately mimic those encountered during summer daylight ambient air pollution episodes (Adams and Ollison, 1997; Lefohn and Foley, 1993; Rombout et al., 1986). For many years, vegetation and some human health researchers have designed exposure regimes that has resulted in the application of triangular-type exposure regimes. Based on the published literature combined with findings from the EPA (2006), summarized ambient air quality data provide important evidence for those vegetation and human health clinical researchers who are applying varying hour-by-hour O3 concentrations (i.e., triangular exposure regimes) in their experiments. Findings reported by Lefohn (2006) indicated that square-wave O3 patterns of exposure occur fairly rarely under ambient conditions. The investigator found that if one defined a "square wave" profile as experiencing a variable range of 4 ppb or less over an 8-hour period, only 1.51% of all sequences (28,148) would be classified as representing a "square wave".

Over the past several years, A.S.L. & Associates has collaborated with health researchers (Adams, 2003, 2006a; Schelegle et al., 2009) in designing realistic ambient-type regimes used in experiments involving controlled laboratory exposures of human volunteers. These realistic ambient-type O3 exposures are applied to assess the influence of the exposure patterns of hourly average concentrations on specific biological endpoints. Using hourly average O3 values, A.S.L. & Associates has developed a statistical methodology for identifying "typical" sequences of 8 hourly values that are associated with actual 8-hour patterns. As part of its ongoing research to identify viable alternative forms of air pollution standards to protect human health (Lefohn et al., 2010), A.S.L. & Associates continues its collaborative research program with health researchers in assessing the effects of realistic patterns of O3 exposure on human health endpoints.



Adams, W. C. (2003) Comparison of chamber and face mask 6.6-hour exposure to 0.08 ppm ozone via square-wave and triangular profiles on pulmonary responses. Inhalation Toxicology 15: 265-281.

Adams, W. C. (2006a). Comparison of Chamber 6.6-h Exposures to 0.04 - 0.08 ppm Ozone Via Square-Wave and Triangular Profiles on Pulmonary Responses. Inhal Toxicol. Inhalation Toxicology 18, 127-136.

Adams, W.C. (2006b). Human pulmonary responses with 30-minute time intervals of exercise and rest when exposed for 8 hours to 0.12 ppm ozone via square-wave and acute triangular profiles. Inhalation Toxicology 18, 413-422.

Adams, W. C., Ollison, W. M. (1997) Effects of prolonged simulated ambient ozone dosing patterns on human pulmonary function and symptomatology. Presented at: 90th annual meeting of the Air & Waste Management Association; June; Toronto, Ontario, Canada. Pittsburgh, PA: Air & Waste Management Association; paper no. 97-MP9.02.

Hazucha, M. J.; Folinsbee, L. J.; Seal, E., Jr. (1992) Effects of steady-state and variable ozone concentration profiles on pulmonary function. Am. Rev. Respir. Dis. 146: 1487-1493.

Hazucha, M. J.; Lefohn, A. S. (2007) Nonlinearity in Human Health Response to Ozone: Experimental Laboratory Considerations. Atmospheric Environment. 41:4559-4570.

Hogsett, W. E.; Tingey, D. T.; Holman, S. R. (1985) A programmable exposure control system for determination of the effects of pollutant exposure regimes on plant growth. Atmospheric Environment 19: 1135-1145.

Lefohn, A. S.; Foley, J. K. (1993). Establishing Ozone Standards to Protect Human Health and Vegetation: Exposure/Dose-Response Considerations. J. Air Waste Manag. Assoc. 43(2):106-112.

Lefohn, A.S. (2006). Personal Communication. A.S.L. & Associates, Helena, Montana.

Lefohn, A.S., Hazucha, M.J., Shadwick, D., Adams, W.C. (2010). An Alternative Form and Level of the Human Health Ozone Standard. Inhalation Toxicology. 22: 999-1011.

Musselman, R. C.; Oshima, R. J.; Gallavan, R. E. (1983). Significance of pollutant concentration distribution in the response of `red kidney' beans to ozone. J. Am. Soc. Hortic. Sci. 108: 347-351.

Rombout, P. J. A., Lioy, P. J.; Goldstein, B. D. (1986). Rationale for an eight-hour ozone standard. J. Air Pollut. Control Assoc. Vol. 36, no. 8, 913-917.

Schelegle, E.S., Morales, C.A., Walby, W.F., Marion, S., Allen, R.P. (2009). 6.6-hour inhalation of ozone concentrations from 60 to 87 ppb in healthy humans. Am. J. Respir. Crit. Care Med., 180, 265-272.

U.S. Environmental Protection Agency (2006) Air Quality Criteria for Ozone and Related Photochemical Oxidants. Research Triangle Park, NC: Office of Research and Development; report no. EPA/600/R-05/004af.

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