"Schwab, Margo" <Margo_Schwab@omb.eop.gov> 

06/07/2007 01:57 PM

	

To

Lydia Wegman/RTP/USEPA/US@EPA

cc

"Johansson, Robert" <Robert_C._Johansson@omb.eop.gov>, "Frey, Patrick
J." <Patrick_J._Frey@omb.eop.gov>

Subject

Suggested text from Staff Paper









Lydia: I forgot that I was going to draw your attention to pages
3-86/3-87 of Staff Paper, which I think has the type of concise
presentation of the health effects that might serve as the basis for
inserting summary text that simply refers back to the scientific
information cited earlier in the document (which in turn would cite back
to specific sections of the CD and Staff Paper) or as the basis for a
sort of executive summary before presentation of the details associated
with the studies.

 

3.7.5 Confidence in Various Health Outcomes Associated with Short-term

Exposures to Ozone

In characterizing the extent to which relationships between the various
health outcomes

discussed above and short-term exposures to ambient O3 are likely
causal, we note that several different factors have informed the
judgments made in the CD and here. These factors include the nature of
the evidence (i.e., controlled human exposure, epidemiological, and/or
toxicological studies) and the weight of evidence, including such
considerations as biological plausibility,  coherence of evidence,
strength of association, and consistency of evidence. In assessing the
health effects data base for O3, it is clear that human studies provide
the most directly applicable information because they are not limited by
the uncertainties of

dosimetry differences and species sensitivity differences, which would
need to be addressed in extrapolating animal toxicology data to human
health effects. Controlled human exposure studies provide data with the
highest level of confidence since they provide human effects data under
closely monitored conditions and can provide clear exposure-response
relationships. Epidemiological data provide evidence of associations
between ambient O3 levels and more serious acute and chronic health
effects (e.g., hospital admissions and mortality) that cannot be
assessed in

controlled human exposure studies. For these studies the degree of
uncertainty regarding

potential confounding variables (e.g., other pollutants, temperature)
and other factors affects the level of confidence that the health
effects being investigated are attributable to O3 exposures, alone and
in combination with other copollutants.

In using a weight of evidence approach to inform judgments about the
degree of

confidence that various health outcomes are likely to be caused by
exposure to O3, confidence increases as the number of studies and other
factors, such as strength, consistency, and coherence of evidence,
consistently reporting a particular health endpoint grows. For example,
there is a very high level of confidence that O3 induces lung function
decrements in healthy adults and children due in part to the dozens of
studies consistently showing that these effects were observed. As noted
above, the 2006 CD (p. 8-74) states that studies provide clear evidence
of causality for associations between short-term O3 exposures and
statistically significant declines

in lung function in children, asthmatics and adults who exercise
outdoors. An increase in

respiratory symptoms (e.g., cough, shortness of breath) has been
observed in controlled human exposure studies of short-term O3
exposures, and significant associations between ambient O3 exposures and
a wide variety of symptoms have been reported in epidemiology studies
(2006 CD, p. 8-75). Aggregate population time-series studies showing
robust associations with respiratory hospital admissions and ED visits
are strongly supported by human clinical, animal toxicologic, and
epidemiologic evidence for lung function decrements, respiratory
symptoms, 3-87 airway inflammation, and airway hyperreactivity. Taken
together, the 2006 CD (p. 8-77) concludes that the overall evidence
supports the inference of a causal relationship between acute ambient O3
exposures and increased respiratory morbidity outcomes resulting in
increased asthma ED visits and respiratory hospitalizations during the
warm season. Recent epidemiologic evidence has been characterized in the
CD (p. 8-78) as highly suggestive that O3 directly or indirectly
contributes to non-accidental and cardiopulmonary-related mortality. As
discussed above in section 3.5 and in section 8.6 of the 2006 CD,
conclusions regarding biological plausibility, consistency, and
coherence of evidence of O3-related health effects are drawn from the
integration of epidemiological studies with mechanistic information from
controlled human exposure studies and animal toxicological studies. This
type of mechanistic linkage has been firmly established for several
respiratory endpoints (e.g., lung function decrements, lung
inflammation) but remains far more equivocal for cardiovascular
endpoints (e.g., cardiovascular-related hospital admissions). Finally,
for epidemiological studies, strength of association refers to the
magnitude of the association and its statistical strength, which
includes assessment of both effects estimate size and precision (section
3.4.1). In general, when associations yield large relative risk
estimates, it is less likely that the association could be

completely accounted for by a potential confounder or some other bias.
Consistency refers to the persistent finding of an association between
exposure and outcome in multiple studies of adequate power in different
persons, places, circumstances and times (section 3.4.3). For example,
the magnitude of effect estimates is relatively consistent across recent
studies showing association between short-term, but not long-term, O3
exposure and mortality. Figure 3-5 summarizes our judgments for the
various health outcomes discussed above concerning the extent to which
relationships between various health outcomes and ambient O3 exposures
are likely causal. These judgments are informed by the conclusions and
discussion in the CD and in earlier sections of this chapter, reflecting
the nature of the evidence and overall weight of the evidence, and are
taken into consideration in our quantitative risk assessment, presented
below in Chapter 5.

 

Margo Schwab

 

Statistical and Science Policy

Office of Information and Regulatory Affairs

Office of Management and Budget

Email:  mschwab@omb.eop.gov

Phone:  202 395 5647

