In 1958, the WHO recognized that air pollution was a threat to human health and well-being around the world. Before there was a risk to human health, the WHO began summarizing the situation and recommending preventive and remedial measures, culminating in the publication of the European AQGs in 1987. This first edition of the European air quality guidelines emphasizes the interpretation of the guidelines in terms of concentration and average time (12). Guidelines are based on the amount of ozone exposure that does not produce adverse health effects. The guidelines indicated a 1 h recommended O₃ concentration of 150–200 μg/m³ (0.076–0.1 ppm). To reduce potential acute and chronic adverse effects and provide additional protection, guidelines give 8 h concentrations of 100–120 μg/m³ (0.05–0.06 ppm). The guideline values are based on numerous scientific findings on the health effects of exposure to concentrations higher than 200 μg/m³ O₃. Changes in pulmonary function were associated with ozone exposure (235 μg/m³, 1–3 h) in healthy subjects during exercise (13, 14). Eye, nose, and throat irritation, chest discomfort, cough, and headache have been associated with hourly average oxidant levels above 200 μg/m³ (15).

Advances in epidemiological research over the 1990s showed that adverse health effects may occur at much lower levels of ozone than identified previously. Epidemiological surveys found that respiratory symptoms, lung function decrease, worsened airway responsiveness, and airway inflammation were obvious at a concentration of 160 μg/m³ for an ozone exposure of 6.6 h in healthy adults (16). Field studies in children, adolescents, and young adults indicated that pulmonary function decrements can occur as a result of short-term exposure to ozone concentrations of 120–240 μg/m³ and higher (17). In 2000, the WHO updated the European AQGs to set the guideline value for ozone at an 8 h mean concentration of 120 μg/m³ (18). Health risk assessment demonstrated that acute effects on public health would be small with 8 h of ozone exposure at 120 μg/m³.

Another important point that needs highlighting is that the guideline limit time was adjusted to 8 h. Field studies have shown that health hazards associated with reduced O₃ concentrations due to 1 h or 8 h exposure are very similar. Furthermore, a 1 h exposure to higher concentrations was comparable to an 8 h exposure at average levels to which people are usually exposed (19). Furthermore, the adverse health effects (i.e., lung function decrease and airway inflammation) would be better addressed by guidelines that limit average daily exposures, rather than a rare short-term air quality deterioration associated with abnormal weather. The 8 h guideline would protect against acute 1 h exposure in the current guideline and thus a 1 h guideline would not be necessary (18).

Since the mid-1990s there has been no major addition to the evidence from chamber studies or field studies. However, epidemiological time series studies in low- and middle-income countries in Asia, where air pollution levels are highest, show significantly increased health impacts with ozone exposure (20). The WHO’s comparative risk assessment of ozone exposure quantified not only classical health effects, such as pathological changes in the cardiopulmonary system but also new health endpoints such as disease burden (increased morbidity and mortality) (21, 22). The combined evidence from these studies suggests a compelling, albeit small, positive relationship between daily mortality and ozone levels, independent of particulate matter (23). These studies have shown effects at ozone concentrations below 120 μg/m³, without clear evidence of a threshold (23, 24). Evidence from both laboratory and field studies also indicates considerable individual variation in exposure to ozone.

Accordingly, it is necessary to reduce the guideline from the existing level of 120 μg/m³. It is recommended that the AQG for ozone be set at 100 μg/m³ for a daily maximum 8 h mean ozone concentration according to the AQGs—global update 2005 (25). This concentration will provide adequate protection to public health, though some health effects may occur below this level. There is some evidence that long-term exposure to ozone may have chronic effects but it is not sufficient to recommend an annual guideline. Besides, AQGs—global update 2005 added O₃ interim targets. These recommendations are incremental steps to gradually reduce air pollution and are intended to be used in heavily polluted areas. These targets are designed to facilitate a shift from high concentrations of air pollutants with serious health consequences to lower concentrations. The 8 h interim target value for ozone-1 (IT-1) was set at 160 μg/m³, at which transient lung function and inflammatory changes in the lungs were detected in young people undergoing intermittent exercise in the laboratory chamber (25).

Since the publication of the global update 2005, many new studies have continued to document the adverse health effects of high levels of ozone in low- and middle-income countries, and much lower levels in high-income countries with relatively clean air (26–30). Furthermore, there was a great advance in expanding the global database of air pollution and exposure measurement as well as statistical analysis techniques and conceptualization of causal modeling in epidemiology. These studies reshaped the established exposure-response function of ozone and critical health outcomes (31, 32). Combined with the systematic review of the evidence and meta-analysis of quantitative effect, as well as assessment of the level of certainty of the evidence, the WHO revised the AQG level.

In the global update 2021, recommendations on the AQG of ozone consisted of long-term and short-term guidelines (8). A peak season ozone level of 60 μg/m³ (the average of daily maximum 8 h mean ozone concentrations) was recommended as a long-term guideline (8). The peak season is defined as the six consecutive months of the year with the highest 6 months running-average ozone concentration. The average daily maximum 8 h mean ozone concentrations of 100 μg/m³ were recommended as a short-term guideline. The short-term guideline was defined as the 99th percentile of the distribution of daily values (equivalent to three exceedance days per year) (33). The form of high percentiles provides some insulation from the impacts of special conditions that are conducive to maximum O₃ formation. The reason for the high percentile rather than the maximum is that the maximum daily value for a given year is more volatile than the high percentile. The WHO has also updated the 2005 air quality interim targets to guide the implementation of the new AQGs.

For the development of long-term AQG levels, the systematic review on ozone and all non-accidental mortality reported a meta-effect estimate of relative risk =1.01 per 10 μg/m³ increase in the peak-season average of daily maximum 8 h mean ozone concentration (34). The average of the three lowest 5th percentile levels measured in these studies was the starting point for deriving an AQG level of 60 μg/m³ (35). The data obtained support a long-term, peak-season AQG level of no more than 60 μg/m³. For the development of short-term AQG levels, the systematic review on ozone for 8 h maximum concentration and all non-accidental mortality reported a meta-effect estimate of relative risk =1.0043 per 10 μg/m³ increase (36). The short-term AQG level is calculated using the ratio of 2 between the 99th percentile to the annual mean of 60 μg/m³, which gives a result of 120 μg/m³. Dividing this number by 1.24 gives a result of 97 μg/m³ (37), rounding to give a recommended short-term AQG level of 100 μg/m³. The data obtained support short-term, peak season AQG levels not exceeding 100 μg/m³.

By analyzing the WHO’s updating process of the ozone AQG, we observed a gradual improvement during the update process of the ozone guidelines. The perception of ozone health hazards changed from pathological changes in the cardiopulmonary system to increased risk of morbidity and mortality of cardiopulmonary disease, and other non-accidental diseases. In addition, the requirements for meeting guidelines have shifted from a single level to a more stable form of high percentile. In short, during the update of ozone guidelines, the improvement of ambient ozone monitoring and exposure assessment capabilities and the deepening awareness of the exposure-response relationship between ozone and adverse health effects could be possible main reasons for improvements in the guidelines.

The EPA initially established primary and secondary NAAQS for photochemical oxidants in 1971. Both primary and secondary standards were set at an hourly average of 0.08 parts per million (ppm) total photochemical oxidants, not to be exceeded for more than 1 h per year. In 1979, the EPA completed its first periodic review of the criteria and standards for O₃ and other photochemical oxidants (42). At the same time, EPA made significant revisions to the previous standard. The level of the primary and secondary NAAQS was changed to 0.12 ppm. The indicator was changed to O₃. The form of standards was changed with the expected number of days per calendar year with a maximum hourly average concentration above 0.12 ppm to be equal to or less than one.

The EPA administrator revised the existing 1 h, 0.12 ppm primary standard with a new 8 h, 0.08 ppm primary standard on September 16, 1997, after carefully considering the information presented in the Air Quality Criteria Document for O₃ and Other Photochemical Oxidants Update 1996 (43) and the Staff Paper, the advice and recommendations of CASAC, and public comments received on the proposal. The 8 h, 0.08 ppm primary standard will be met at an ambient air quality monitoring site when the 3 years average of the annual fourth-highest daily maximum 8 h average O₃ concentration is less than or equal to 0.08 ppm (44). The guideline was appropriate to provide adequate and more uniform protection of public health from both short-term (1 to 3 h) and prolonged (6 to 8 h) exposures to ambient ozone. The current 1 h secondary standard was replaced by an 8 h standard that was identical to the new primary standard.

The 8 h average time was selected for the following reasons (45): (1) In the current NAAQS, the 1 h average time was initially selected primarily based on health outcomes associated with short-term (i.e., 1 to 3 h) exposure. There was only preliminary information on potential associations between long-term exposure and health outcomes considered qualitatively. (2) The new available information indicates that long-term (i.e., 6 to 8 h) exposure levels causing various health outcomes are lower than the current 1 h NAAQS level, and lower exposures are more frequent than higher exposures. (3) At lower O₃ levels, adverse health effects were better associated with 8 h of exposure than an average time of 1 h (16, 46). (4) The quantitative risk assessment showed that the risks of short -and long-term exposure can be realized by a primary criterion with an average duration of 1 or 8 h. Therefore, there was no need to establish both 1 and 8 h standards. (5) While there was clear evidence of an association between long-term exposure and lung tissue damage in animal models, there was no corresponding evidence for human health. Therefore, it is not sufficient to select a longer time period as a criterion. Accordingly, an important public health policy consideration that an average time of 8 h results in a significantly more uniformly protective national standard than a 1 h standard supports the selection of an 8 h average time (47).

Since ozone does not have any discernible threshold, traditional paradigms of standard-setting cannot be applied in the usual way and risk assessment must play a central role in determining appropriate levels (31). The EPA administrator aimed to formulate a standard level that would sufficiently reduce risks since the CAA neither can nor requires a zero-risk standard. The existing 1 h standard set at 0.12 ppm O₃ provided little margin of safety (48). At O₃ exposure below 0.08 ppm for 8 h, the most established O₃-related effects, although considered adverse, are transient and reversible. An 8 h standard set at 0.07 ppm would be closer to the peak background levels caused by precursor substances of non-human origin and are therefore not appropriate for some regions containing these sources. After carefully reassessing quantifiable public health risks, the EPA Administrator focused on the comparison between a recommended level of 0.08 ppm and an alternative standard setting of 0.09 ppm. According to the latest EPA risk assessment, setting the 0.09 ppm standard caused approximately 40% to 65% more health effects (moderate or substantial reductions in lung function and pain in children who play outdoors) than the 0.08 ppm standard in nine urban areas (49). Exposure assessment showed that the number of children exposed to 0.09 ppm for an average of 8 h was more than three times those exposed to 0.08 ppm in nine urban areas. While recognizing the uncertainties inherent in these estimates, the EPA Administrator claimed that the public health implications described in the proposal are significant enough to warrant a 0.08 ppm standard.

When evaluating alternative forms for primary standards, the adequacy of the public health protection provided is the most important consideration. Since 1979, the current form has raised concerns due to a lack of year-to-year stability. The impact of public health exposure to ambient O₃ is related to the actual O₃ level, not just whether the concentration is higher than the specified level. The CASAC recommended that concentration-based forms, within the range considered up to the fifth-highest concentration form, are appropriate for a health-based primary O₃ standard. Concentration-based forms can minimize this instability and is protected from extreme meteorological events that contribute to O₃ formation (50). Furthermore, due to the current difference between the safety boundaries of potential health effects provided by the range of the second to fifth-highest concentration forms not being sufficiently understood, it cannot be used as a basis for selecting the most restrictive forms (i.e., the second or third highest concentration forms). The proportion of monitoring sites reaching the fifth highest concentration standard and the number of days with the fifth highest concentration above the standard level both oppose the choice of this form. Therefore, the fourth highest concentration form will be combined with the 8 h average time and 0.08 ppm level to appropriately balance these public health factors (50). Given all this, the EPA Administrator determined to establish a revised 8 h, 0.08 ppm standard with a form of the 3 years average of the annual fourth-highest daily maximum 8 h average O₃ concentrations.

After an extensive review of several scientific studies on the impact of ambient ozone on public health and the environment, the US EPA significantly strengthened NAAQS for ozone and revised the 8 h primary and secondary standards to a level of 0.075 ppm (51, 52). In addition to changing the standard level, the EPA also assigned the standard level to three decimal places. The revised standards would be met when the 3 years average of the annual fourth-highest daily maximum 8 h average is less than or equal to 0.075 ppm. These revisions were proposed to provide increased protection for children and other “at risk” populations against an array of O₃-related adverse health effects. These effects range from decreased lung function and increased respiratory symptoms to emergency department visits and hospital admissions, and possibly cardiovascular-related morbidity, as well as total non-accidental mortality (53).

We noticed that the main revision was the strengthened level of O₃ in the 2008 update. There was a strong body of clinical evidence of lung function decrements, respiratory symptoms, and other airway responses at O₃ exposure above levels of 0.080 ppm (54). Epidemiological evidence indicated the observation of a wide range of serious health effects, including emergency department visits, hospital admissions, and premature mortality, with an ozone concentration below 0.080 ppm (19). Based on the evidence and CASAC’s recommendations, the EPA Administrator recommended that a standard in the 0.070 to 0.075 ppm range be necessary to protect public health. The likelihood of obtaining benefits to public health with a standard set below 0.075 ppm O₃ decreases, so it was not suggested that a lower standard was needed to provide this degree of protection. Accordingly, a standard set at 0.075 ppm would be sufficient to protect public health with an adequate margin of safety.

We noticed that cost-benefit analysis had an important role in choosing the level of the standard. To estimate the benefits of meeting a standard, the EPA uses a sophisticated peer-reviewed approach to model the relationship between air quality and health and welfare effects and the dollar values of resulting public health improvements. The EPA estimated that the revised standards would yield health benefits valued between US$2 billion and US$17 billion (55). Those benefits include preventing cases of bronchitis, aggravated asthma, hospital and emergency room visits, non-fatal heart attacks, and premature death. To estimate the cost of meeting a standard, the EPA uses several peer-reviewed methods to model the cost of control measures needed to reduce ozone precursor. The EPA estimated that the cost of implementing a 0.075 ppm standard would range from US$7.6 billion to US$8.8 billion per year by 2020 (55).

In 2015, the US EPA further strengthened the NAAQS value for ambient ozone to 0.07 ppm based on extensive scientific evidence (56). The updated standards would improve public health protection, especially for at-risk groups, including children, older adult, people of all ages with lung diseases such as asthma, and people who are active outdoors, especially outdoor workers (57). This would also improve the health of trees, plants, and ecosystems. When determining the updated standards, the EPA Administrator considered factors such as the nature and severity of health effects, the size of the at-risk groups affected, and the degree of uncertainty on ozone-related health effects (58). The law obliges the EPA Administrator to set “necessary” standards—neither more nor less than necessary—to achieve this goal.

Based on an expanded body of scientific evidence, the 75 parts per billion (ppb) standard in 2008 was not requisite to protect public health with an adequate margin of safety, as required by law. These studies clearly showed that 72 ppb of ozone may be harmful to healthy exercising adults (59). A standard of 70 ppb is below the level shown to cause adverse health effects in clinical studies. The evidence that health effects were harmful or “adverse” in several clinical studies in which some adults were exposed to ozone at levels as low as 60 ppb was uncertain (19, 60). More importantly, the EPA Administrator focused on children’s exposure, particularly repeated exposures (61). Repeated exposures are important, because the more times children are exposed to ozone, the more likely they will experience serious health effects. Children are at increased risk from ozone exposure and are more likely to be active outdoors when ozone levels are high. A standard of 70 ppb would protect 99.5% of children from even single exposures to ozone at 70 ppb as well as more than 98%of school-age children from repeated exposures to ozone concentrations as low as 60 ppb, which would mean a 60% improvement over the current standard (58). The updated standard of 70 ppb would protect at-risk populations with an adequate margin of safety. Furthermore, the public health benefits of the updated standard would reach US$2.9 to US$5.9 billion by 2025, exceeding the estimated $1.4 billion cost (62).

By reviewing the process undertaken by the US EPA to revise ozone NAAQS, we realize that the US has a rich experience in standard development. For each NAAQS update, the EPA scientifically reviewed and demonstrated the level, form, and average time of O₃ standards, and was open to public discussion and opinion. The form and average time of the standards were established earlier and have been used ever since by the EPA. We found that the progressively tightened ozone standard levels relied not only on the perceived health hazards of ozone but also on the assessment of health and welfare benefits under current standards. These are based on surveys of relationships between ozone exposure and human health endpoints as well as accurate benefit-cost models of ozone compliance, exposure and risk assessment, and pubic opinion.