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Acute respiratory effects of low-level ozone exposure are not well defined in older adults.MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance.The mean (95% confidence interval) FEVExposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).

In 2001, the US Environmental Protection Agency (EPA) adopted stringent new standards for on-highway heavy heavy-duty diesel engine (HHDDE) emissions of particulate matter (PM) and oxides of nitrogen (NOx) that were to become effective during the 2007–2010 time period. The Advanced Collaborative Emissions Study (ACES) was a cooperative, multiparty effort to characterize the emissions (in Phases 1 and 2) and assess the possible health impacts (in Phase 3) of the new, advanced HHDDE technologies, after introducing them to the market. Phase 1 demonstrated that the regulated emissions from four 2007-compliant engines tested were all below the 2007 standards. Both regulated and unregulated emissions were substantially reduced relative to pre-2007 technology engines, except for nitrogen dioxide (NO2) emissions that were higher compared to 2004 technology engines due to the use of diesel oxidation catalyst (DOC) and catalyzed diesel particulate filter (DPF) exhaust aftertreatment technologies. Phase 2 showed another large step in emissions reductions for 2010-compliant diesel engines. The three 2010-compliant engines tested had substantially lower regulated emissions of NOx, CO, NMHC, and PM relative to the emission standards and also relative to the 2007-compliant engines. NOx reductions were achieved using urea-based selective catalytic reduction (SCR) and an ammonia oxidation catalyst (AMOX). A wide spectrum of particle and gas phase unregulated emissions species, including NO2, were also reduced relative to 2007-compliant engines and older engines. Phase 3 consisted of an inhalation bioassay in which rats were exposed for their lifetime to the diluted exhaust from one of the 2007-compliant engines tested in Phase 1. Three exhaust dilutions were selected based on the nitrogen dioxide (NO2) concentrations to achieve three exposure levels: 4.2 ppm (high-DE exposure), 0.8 ppm (mid-DE exposure), and 0.1 ppm (low-DE exposure) NO2. The control exposure consisted of filtered air. NO2 was chosen because the particle concentrations in the exhaust were too low to set the dilution levels. Exposures were conducted 16 h/day, 5 days/week. Rats were evaluated histopathologically and for respiratory function, a large number of noncancer endpoints, and genotoxicity, at interim time points up to the final sacrifice at 28 months (males) and 30 months (females). Histopathological analyses found that exposure to exhaust from a 2007-compliant engine produced no tumors or precancerous effects in lungs and no increase in tumor incidence outside the lung, but induced mild epithelial hyperplasia in the central acinus region of the lung, interstitial fibrosis, and bronchiolization at the high exposure level. The lung histologic changes were consistent with previous findings in rats after long-term exposure to NO2—a major component of the chamber exposure atmosphere, which is substantially reduced in 2010-compliant engines. The majority of the biological endpoints were unchanged with exposure and little inflammation was observed. In summary, the ACES study shows that emissions from 2007- and 2010-compliant HHDDE have been reduced dramatically and that exhaust from a 2007-compliant engine produced no tumors or precancerous effects in rats exposed over their lifetime.

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p

Background To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality. Objectives We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction. Methods This randomized crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015. Subjects were exposed for 3 h in random order to 0 ppb (filtered air), 70 ppb ozone, and 120 ppb ozone, alternating 15 min of moderate exercise with 15 min of rest. A suite of cardiovascular endpoints was measured the day before, the day of, and up to 22 h after each exposure. Mixed effect linear and logit models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. Site and time were included in the models. Results We found no significant effects of ozone exposure on any of the primary or secondary measures of autonomic function, repolarization, ST segment change, arrhythmia, or vascular function (systolic blood pressure and flow-mediated dilation). Conclusions In this multicenter study of older healthy women and men, there was no convincing evidence for acute effects of 3-h, relatively low-level ozone exposures on cardiovascular function. However, we cannot exclude the possibility of effects with higher ozone concentrations, more prolonged exposure, or in subjects with underlying cardiovascular disease. Further, we cannot exclude the possibility that exposure to ambient ozone and other pollutants in the days before the experimental exposures obscured or blunted cardiovascular biomarker response to the controlled ozone exposures.

The use of oxygenated fuels is anticipated to increase over the next decades. This paper reviews the toxicological and exposure information for methyl tertiary-butyl ether (MTBE), a fuel additive, and methanol, a replacement fuel, and discusses the possible health consequences of exposure of the general public to these compounds. For MTBE, the health effects information available is derived almost exclusively from rodent studies, and the exposure data are limited to a few measurements at some service stations. Based on these data, it appears unlikely that the normal population is at high risk of exposure to MTBE vapor. However, in the absence of health and pharmacokinetic data in humans or in nonhuman primates, this conclusion is not strongly supported. Similarly, there are a number of uncertainties to take into consideration in estimating human risk from the use of methanol as a fuel. Although methanol may be toxic to humans at concentrations that overwhelm certain enzymes involved in methanol metabolism, the data available provide little evidence to indicate that exposure to methanol vapors from the use of methanol as a motor vehicle fuel will result in adverse health effects. The uncertainties in this conclusion are based on the lack of information on dose-response relationship at reasonable, projected exposure levels and of studies examining end points of concern in sensitive species. In developing a quantitative risk assessment, more needs to be known about health effects in primates or humans and the range of exposure expected for the general public for both compounds.