Controlled Human Inhalation-Exposure Studies at EPA (2017) / Chapter Skim
Currently Skimming:
3 Value of Controlled Human Inhalation Exposure Studies
3 Value of Controlled Human Inhalation Exposure Studies
Pages 33-51
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 33... ...
In addition to informing the ISAs, CHIE studies of particles from specific sources (for example, diesel-engine exhaust particles and wood smoke particles) augment the scientific knowledge base for EPA's decision making concerning regulatory approaches that focus on source emissions (such as EPA's National Emission Standards for Hazardous Air Pollutants [NESHAP]
|
From page 34... ...
. The EPA-adapted Hill aspects provided the committee with a framework for asse d s e essing the value of CHIE study results to inform EPA's regulatory decision ma aking and for identifying t kinds of u the useful informatio CHIE stud can prov on dies vide.
|
From page 35... ...
TABLE 3-1 EPA's Reviews of Relevant Scientific Information and Revised NAAQS for O3 and PM from 1996 to 2015 Year NAAQS Review of Latest Relevant Revisions Averaging Level (Concentration) Scientific Informationa Year Finalized Completed Indicator Time for Primary Standardb Formc Air Quality Criteria for Ozone and 1996 1997 O3 8-hour 0.08 ppm Annual fourth-highest daily maximum 8-hour Related Photochemical Oxidants concentration, averaged over 3 years Air Quality Criteria for Ozone and 2006 2008 O3 8-houir 0.075 ppm Annual fourth-highest daily maximum 8-hour Related Photochemical Oxidants concentration, averaged over 3 years Integrated Science Assessment of 2013 2015 O3 8-hour 0.070 ppm Annual fourth-highest daily maximum 8-hour Ozone and Related Photochemical concentration, averaged over 3 years Oxidants Air Quality Criteria for Particulate 1996 1997 PM2.5 24-hour 65 µg/m3 98th percentile, averaged over 3 years Matter Annual 15.0 µg/m3 Annual arithmetic mean, averaged over 3 years PM10 24-hour 150 µg/m3 99th percentile, averaged over 3 years 3 Annual 50 µg/m Annual arithmetic mean, averaged over 3 years Air Quality Criteria for Particulate 2004 2006 PM2.5 24-hour 35 µg/m3 98th percentile, averaged over 3 years Matter 3 Annual 15.0 µg/m Annual arithmetic mean, averaged over 3 years 3 PM10 24-hour 150 µg/m Not to be exceeded more than once per year on average over a 3-year period Integrated Science Assessment for 2009 2012 PM2.5 24-hour 35 µg/m3 98th percentile, averaged over 3 years Particulate Matter Annual 12.0 µg/m3 Annual mean, averaged over 3 years 3 PM10 24-hour 150 µg/m Not to be exceeded more than once per year on average over 3 years a In December 2006 EPA announced a revised process for reviewing and setting NAAQS.
|
From page 36... ...
CHIE study findings might be used to generate new hypotheses or contribute to the strength of evidence regarding biomarker or physiologic responses to pollutants, when the results are consistent across CHIE studies or when they illustrate coherence with results of toxicologic ani mal studies or observational epidemiologic studies or panel studies. However humans are not as identical as inbred mice, leading to differences in interpretation of the meaning of consistency and coherence.
|
From page 37... ...
and controlled animal inhalation studies (referred to as clinically relevant animal models) provide information to help in the interpretation of the exposure–response relationships generated by panel studies and largerscale epidemiologic studies of diverse human populations.
|
From page 38... ...
Biommarkers of sh hort-term respponses detecte in CHIE s ed studies might be useful in other comple ementary studies, such as pa anel studies of human coh o horts to assess variations in biologic res s n sponses in sp pecific subpopula ations, includding potential susceptibl subpopula lly le ations, to rela atively short- -term exposur to res ambient pollutant mixt p tures. Biomar rkers detected in CHIE stu d udies also mig be useful for chronic in ght nhalation exposure studies involving ani i imals, in that seeing simila biomarker in animals and humans could ar rs provide soome validatio of the anim studies fo use in char on mal or racterizing huuman risk associated with exposure to air pollutants.
|
From page 39... ...
However, much is still to be understood about how PM composition influences toxicity. Furthermore, in ambient air, there is always simultaneous exposure of PM2.5, photochemical oxidants, sulfur oxides, and nitrogen oxides in various proportions, and the health effects associated with PM2.5 exposures can be influenced by its copollutants (Lippmann et al., 2013)
|
From page 40... ...
The discussion of PM CHIE studies also includes a consideration of the influence of particle size range and chemical composition for NAAQS decision making. CHIE OZONE STUDIES Background on the Value of CHIE Studies for the Ozone NAAQS CHIE study findings have been valuable in informing O3 NAAQS decision making.
|
From page 41... ...
The value of the contributions stem from the simplicity of the exposure, unclouded by concomitant exposures to other toxicants in the ambient air mixture, and the experimental design of CHIE studies. Subsequent epidemiologic studies have developed the knowledge base of the implications of these perturbations in sensitive subpopulations (Alexis et al., 2010; Devlin et al., 1991; Kim et al., 2011; Koren et al., 1989; Lay et al., 2007)
|
From page 42... ...
Biologic Gradient Considerations Ozone CHIE Study Contributions to the Four Basic Elements of the NAAQS This section focuses on the use of O3 CHIE studies to establish biologic gradients for O3-associated health effects in order to inform decisions about the primary photochemical oxidant standard. The most recent ISA for O3 was completed in 2013 (EPA, 2013)
|
From page 43... ...
As air pollution oxidant chemistry becomes better understood, opportunities will arise for CHIE studies to address other photochemical oxidants in ambient air, especially peroxides. Averaging time: CHIE studies provide a basis for evaluating the appropriateness of a primary NAAQS with an 8-hour averaging time, instead of using the shorter exposure duration (1 hour)
|
From page 44... ...
, providing support for a causal relationship between acute ambient O3 exposures and increased respiratory morbidity outcomes, and the 2013 ISA's conclusion that it is a causal rela tionship, providing support for lowering the O3 NAAQS; Biologic and physiologic evidence for O3 effects in human health that generated hypotheses for animal studies that looked for risk factors in complementary investigations; and An iterative process in which the results of CHIE studies inform the efforts of interdisciplinary teams working to elucidate biologic mechanisms, and those teams identifying new questions to be addressed by CHIE studies. CHIE PM STUDIES Background on the Value of CHIE Studies for the PM NAAQS CHIE study findings have been used to inform decisions about setting the NAAQS for PM2.5 and PM10.
|
From page 45... ...
The 2009 ISA showed that many CHIE studies provided evidence of biologic plausibility of outcomes observed in time-series epidemiologic studies of short-term responses conducted in the United States and elsewhere by demonstrating perturbations in pathways that are relevant to the development of clinical effects. CHIE study results also showed congruence with outcomes demonstrated in animal toxicity studies.
|
From page 46... ...
It also provides information on temporality, unequivocally connecting the pollutant exposure to biologic outcomes, excluding the possible influence of diurnal variation through the crossover design with the FA control. PM CHIE studies have examined a variety of exposures, depending on the location of the study facility, and whether the PM generation method involves the concentration of PM from the ambient air, by resuspension or instillation of source particles that are brought to the study site from different locations, or by onsite generation of PM from a specific source, such as diluted diesel-engine exhaust or wood smoke.
|
From page 47... ...
us While use eful, this para adigm is likely to be modif y fied by continnuously evolv ving understaanding of CVD etiology. FIGURE 3-4 Systemic oxidative stress and inflamm 3 o mation.
|
From page 48... ...
With some suggestion of consistency across study designs, many, but not all, animal studies, and human panel studies, as well as CHIE studies, reported altered autonomic function measured by HRV in response to PM. Some studies showed reduced HRV (increased parasympathetic activity relative to sympathetic activity)
|
From page 49... ...
That is to say, PM CHIE studies at EPA have generally used exposures within a narrow range of PM concentrations. This is likely because CHIE study investigators have often not found consistent biomarker or physiologic responses to short-term exposures at lower PM exposure concentrations, even though large epidemiologic studies have found exposure– response associations with health outcomes at lower concentrations than those used in the CHIE studies (EPA, 2009)
|
From page 50... ...
Based on prior knowledge, CHIE studies are designed such that clinical responses are expected to be absent or at least minimal. When studying sensitive groups, CHIE studies involve individuals who might exhibit risk factors to a small degree, but not those who are known through observational epidemiologic studies to be at considerable risk for clinical responses to criteria pollutants.
|
From page 51... ...
For complex mixtures of ambient air pollutants, a further challenge of CHIE studies and epidemi ologic studies is the spatial and temporal variability of the chemical compositions of the mixtures, which makes it more difficult to assess exposure–response relationships in terms of considera tions of specificity and consistency. CHIE study results combined with information from observational epidemiologic, panel, and toxicologic studies can facilitate a holistic evaluation of the evidence and thereby provide a well-considered scientific basis for establishing or revising NAAQS.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.