The epidemiological evidence
has played a disproportionately large role in the policymaking
process. Time-series findings indicate associations of mortality
with not only PM and ozone, but with all of the criteria pollutants.
Because results of time-series studies implicate all of the criteria
pollutants, findings of mortality time-series studies do not
seem to allow one to confidently attribute observed effects specifically
to individual pollutants. This raises concern about the utility
of these types of studies in the NAAQS-setting process. Examples
of inconsistenties and inconclusive findings include the following:
- Instability of mortality
effect estimates resulting from different model specifications
of weather effects and time trends.
- Instability of effect
estimates resulting from different selections of monitoring sites
within cities.
- Increased heterogeneity
of effect estimates across cities.
- Greater diversity of findings
among studies and across study areas.
- Contradictory results
from mortality displacement studies.
- Effect lags that are inconsistent
across cities and across studies.
- Exposure-response relationships
that are inconsistent across cities and across studies.
- Inconsistencies between
short-term and long-term effect studies, such as respiratory
effects of fine particles.
- Contradictory findings
among long-term studies.
Smith et al. (2009) (Smith,
Xu, and Switzer) discussed some of the concerns about the use
of time-series data. The authors investigated intercity variability,
as well as the sensitivity of the ozone-mortality associations
to modeling assumptions and choice of daily ozone metric, based
on reanalysis of NMMAPS data. Smith et al. (2009) examined the
sensitivity of city-specific ozone-mortality estimates to adjustments
for confounders and effect modifiers, showing substantial sensitivity.
They examined ozone-mortality associations in different concentration
ranges, finding a larger incremental effect in higher ranges,
but also larger uncertainty. Alternative ozone exposure metrics
defined by maximum 8-h averages or 1-h maxima show different
ozone-mortality associations that the authors believed could
not be explained by simple scaling relationships. The authors'
view was that ozone-mortality associations, based on time-series
epidemiologic analyses of daily data from multiple cities, revealed
still-unexplained inconsistencies and showed sensitivity to modeling
choices and data selection that contribute to serious uncertainties
when epidemiological results are used to discern the nature and
magnitude of possible ozone-mortality relationships or are applied
to risk assessment.
Personal exposure is not
reflected adequately, and sometimes not at all, by concentrations
measured at central outdoor monitoring sites. Typically, personal
exposures are much lower than the ambient concentrations, and
can be dramatically lower depending on time-activity patterns,
housing characteristics, and season. In addition, and of particular
importance for the time-series studies, there can be no correlation
between personal concentrations measured over time and concentrations
measured at central outdoor sites.
Previous review comments
made by our research group were associated with spatial variability
and the statistical shortcomings associated with epidemiological
analyses. Dr. Paul Switzer's comments on some of the shortcomings
associated with the epidemiological findings can be read by clicking
here. In a slide presentation, Dr. Lefohn,
President of A.S.L. & Associates, summarized his group's
findings on some of the concerns associated with the epidemiological
methodology at an EPA
Clean Air Scientific Advisory Committee (CASAC) meeting in North Carolina. Dr. Paul Switzer,
a member of the technical team, provided written comments on
his concerns about the shortcomings of the statistical methodology
utilized in the time-series epidemiological analyses. His comments
can be viewed by clicking
here.
Professor Paul Switzer
(Stanford University) and Dr. Allen S. Lefohn (A.S.L. & Associates)
provided input to the EPA prior to the publication of the final
version of the Carbon Monoxide Criteria Document (CD). A summary
of our input is available in an Adobe
Acrobat PDF file.
The growing pattern of
inconsistent and inconclusive findings is troublesome and presents
both scientists and policymakers with a very difficult decision.
Simply stated, the science based on epidemiological results may
not be substantial enough at the moment to provide the foundation
upon which a clear path can be built that leads directly from
the science to the policymaking decision arena.
It its 2013-2015 review
by EPA of the national ambient ozone standard, the science based
on epidemiological results did not provide strong support for
reducing the current level of the Federal ozone standard in the
US (FR Vol. 80, No. 206). In November 2015, the EPA Administrator
concluded that the epidemiological risk analyses showed that
small net benefits resulted from changing the ozone standard
from its current level of 75 ppb to lower values (70, 65, or
60 ppb). EPA (2014) provided details supporting this observation
by the Administrator. The Administrator's conclusion was based
on the observation that because the short-term epidemiological
risk analyses were integrated from the maximum concentration
to zero concentration, minimum benefits occurred. As emission
reduction occurred to meet lower proposed ozone standards, the
lower concentrations began to rise (due to lack of NOx scavenging)
and the epidemiological models predicted that additional morality
and morbidity might occur due to the rising lower levels. Although
benefits occurred as the higher ozone concentrations were reduced,
this benefit was greatly neutralized by the rise in predicted
mortality and morbitidy due to the low end of the concentration
distribution rising. Many of these lower hourly average ozone
concentrations were associated with background ozone. The result
reported was associated with the model selected by the epidemiologists.
The model apparently ignored the scientific observations reported
(e.g., Hazucha and Lefohn, 2007; Lefohn et al., 2010) that higher
ozone concentrations should be provided greater weight than lower
concentrations of which many of the lower values are in the background
range (i.e., 25-55 ppb) (see Lefohn et al., 2014). The large
frequency of lower concentrations results in the lower concentrations
contributing an inappopriate weighting when benefits are calculated.
Additional discussion of the lack of NOx scavenging affecting
the movement of the lower hourly average ozone concentrations
toward the mid-levels can be found in Lefohn et al. (2017) and
Lefohn et al. (2018). As noted above, the observation by the
EPA that benefits were greatly neutralized by the rise in predicted
mortality and morbitidy due to lower concentrations rising is
an artifact of the epidemiological models. The EPA in the 2013-2015
ozone rulemaking cycle attempted to deal with this problem by
artificially applying a "threshold" to diminish the
contribution of the lower concentrations. However, no justification
was provided by the EPA for the introduction of the artificial
threshold in its calculations. Lefohn (2023) suggested that investigators
performing long-term epidemiological studies consider using an
exposure metric focused on repeated acute exposures whose effects
accumulate over time. One example of such a metric might be the
one described by Lefohn, Hazucha, Shadwick, and Adams (2010).
The authors described a sigmoidal weighting scheme for hourly
average ozone concentrations. The weighting scheme addresses
the nonlinearity of response (i.e., the greater effect of higher
ozone concentrations over the mid- and low-range values) on an
hourly basis. The Lefohn (2023) comments can be downloaded by
clicking here.
In
the October 2015 national ambient ozone standard decision, the
EPA Administrator noted that she placed the greatest weight on
controlled human exposure studies, citing significant uncertainties
with epidemiologic studies. Reasons for placing less weight on
epidemiologic-based risk estimates were key uncertainties about
(1) which co-pollutants were responsible for health effects observed,
(2) the heterogeneity in effect estimates between locations,
(3) the potential for exposure measurement errors, and (4) uncertainty
in the interpretation of the shape of concentration-response
functions for ozone concentrations in the lower portions of ambient
distributions.
As
EPA initiates a review of the ozone NAAQS
in its current 2023 review cycle, the Agency will have to deal
with the uncertainties associated with integrating epidemiological
results into the standard-setting process. Key issues identified
by the EPA in its 2015 decision were
(1) confirming which co-pollutants were responsible for the health
effects observed,
(2) explaining the heterogeneity in effect estimates between
locations,
(3) quantiying the potential for exposure measurement errors,
and
(4) the interpretation of the shape of concentration-response
functions for ozone concentrations in the lower portions of ambient
distributions.
As noted above, all of
these issues were important in the EPA's 2015 NAAQS decision
and will play a similarly important role in the EPA's 2023 ozone
NAAQS review cycle.
References
Federal Register. Vol. 80, No. 206 / Monday, October 26,
2015. National Ambient Air Quality Standards for Ozone, 40 CFR
Part 50, 51, 52, 53, and 58, pp 65292-65468.
Hazucha, M. J.; Lefohn, A. S. (2007) Nonlinearity in Human
Health Response to Ozone: Experimental Laboratory Considerations.
Atmospheric Environment. 41:4559-4570.
Lefohn, A.S. (2023). Comments on Second Draft Policy Assessment
for the Reconsideration of the Ozone National Ambient Air Quality
Standards, External Review Draft, EPA-452/P-23-002, March, 2023).
Docket ID No. EPA-HQ-OAR-2018-0279-0617.
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.
Lefohn, A.S., Emery, C., Shadwick, D., Wernli, H., Jung,
J., Oltmans, S.J. (2014). Estimates of Background Surface Ozone
Concentrations in the United States Based on Model-Derived Source
Apportionment. Atmospheric Environment, http://dx.doi.org/10.1016/j.atmosenv.2013.11.033.
84: 275-288.
Lefohn, A.S., Malley, C.S., Simon,
H., Wells. B., Xu, X., Zhang, L., Wang, T., 2017. Responses of
human health and vegetation exposure metrics to changes in ozone
concentration distributions in the European Union, United States,
and China. Atmospheric Environment 152: 123-145. doi:10.1016/j.atmosenv.2016.12.025.
Lefohn, A.S., Malley, C.S., Smith,
L., Wells, B., Hazucha, M., Simon, H., Naik, V., Mills, G., Schultz,
M.G., Paoletti, E., De Marco, A., Xu, X., Zhang, L., Wang, T.,
Neufeld, H.S., Musselman, R.C., Tarasick, T., Brauer, M., Feng,
Z., Tang, T., Kobayashi, K., Sicard, P., Solberg, S., Gerosa.
G. 2018. Tropospheric ozone assessment report: global ozone metrics
for climate change, human health, and crop/ecosystem research.
Elem Sci Anth. 2018;6(1):28. DOI:
http://doi.org/10.1525/elementa.279.
Smith, R.L., Xu, B., and Switzer,
P. (2009). Reassessing the relationship between ozone and short-term
mortality in U.S. urban communities. Inhalation Toxicology, 29(S2):
37–61.
US Environmental Protection Agency,
US EPA. (2014). Health Risk and Exposure Assessment for Ozone.
EPA/452/R-14-004a. Research Triangle Park, NC: Office of Air
Quality Planning and Standards. August.
