a given pollutant there were few, if any, controlled
human exposure studies. The data from laboratory
animal studies with specific pollutants had frequently been acquired in studies with exposure
concentrations much higher than ambient concentrations of the pollutants. The results of these
studies raised questions about extrapolation both
from laboratory animals to humans and high to
low exposure concentrations. The general
approach taken was to identify the lowest levels
where effects were statistically significant and
assume this was the inflection point in the
concentration-response relationship. It could be
argued that setting the Standard at a lower concentration satisfied the requirement for “an adequate margin of safety.”
In contrast, the most recent reviews have
involved thousands of papers with observations
ranging from human population level to studies
of intact laboratory animals to studies of effects
of air pollutants on cells and molecules. Despite
the huge number of published studies, attention has
ultimately focused on the results of a few studies
where attention turns to the critical issue of how
they inform the setting of the level and statistical
form of the standard. In the epidemiological studies, the debate often focuses on whether relative
risks of less than 1.1 for excess morbidity and
mortality are significant. Of course, the specific
relative number is dependent on the denominator
being used, for example, per 10 ppb of ozone (24-h
average). For controlled exposure clinical studies,
attention has focused on the lowest levels with
statistically significant changes, which in turn, triggers debate over whether the changes are adverse.
A news report [63] in Science that I view as a
classic report highlighted the issues involved in the
search for subtle links between diet, lifestyle, or
environmental factors and disease, especially using
retrospective observational studies. I especially
liked the quote at the end attributed to Sander
Greenland, a well-known epidemiologist, in offering advice to his “most sensible, level-headed,
estimatable colleagues.” Remember, he says –
“there is nothing sinful about going out and getting
evidence, like asking people how much do you
drink and checking breast cancer records. There’s
nothing sinful about seeing if that evidence
correlates. There’s nothing sinful about checking
for confounding variables. The sin comes in believing a casual hypothesis is true because your study
came up with a positive result, or believing the
opposite because your study was negative.”
It is interesting to note that CASAC discussions of criteria pollutant effects have frequently
focused initially on the level of the standard sometimes devoid of any consideration of the statistical
form of the level. This approach was in keeping
with traditional practice in the setting of standards
such as Threshold Limit Values for occupational
exposures to chemicals based on scientific judgments [34–36, 40]. That approach has involved a
review of the available human data on a toxic
chemical to determine a no-observed effect level,
or the lowest observed effect level, and then using
safety factors to arrive at an acceptable exposure
level set at a lower level. In the absence of adequate human data, laboratory animal data are used
and an additional safety factor used to account for
the potential that the animal observations might
not adequately predict human effects. This
approach was routinely used for a wide range of
health responses that were assumed to have an
exposure-response relationship that exhibited
either a true or practical threshold, an excess of
effects above some level and an absence of effects
below that level. A review of the earliest Criteria
Documents and, indeed, also the Staff Papers,
documents that a similar line of reasoning was
used in the setting of the NAAQS.
The implementation of standards set with this
approach soon revealed that if the standard was to
be rigorously enforced, that is, no exceedances of
the specific level of the standard, the practical
effect would be to cause average levels of the
pollutant to be reduced to levels far below the
standard so as to avoid the occasional high value
exceeding the standard. Fortunately, common
sense prevailed and the EPA, over time, moved
to the practice of routinely linking the specific
level of the standard with a statistical form such
as the 98th percentile 24-h concentration averaged
over 3 years or the fourth highest 8-h average
concentration during a 3-year period. In my opinion, most of the attention of the CASAC in the
NAAQS setting process has focused on the level
Air Quality Guidelines and Standards
23
human exposure studies. The data from laboratory
animal studies with specific pollutants had frequently been acquired in studies with exposure
concentrations much higher than ambient concentrations of the pollutants. The results of these
studies raised questions about extrapolation both
from laboratory animals to humans and high to
low exposure concentrations. The general
approach taken was to identify the lowest levels
where effects were statistically significant and
assume this was the inflection point in the
concentration-response relationship. It could be
argued that setting the Standard at a lower concentration satisfied the requirement for “an adequate margin of safety.”
In contrast, the most recent reviews have
involved thousands of papers with observations
ranging from human population level to studies
of intact laboratory animals to studies of effects
of air pollutants on cells and molecules. Despite
the huge number of published studies, attention has
ultimately focused on the results of a few studies
where attention turns to the critical issue of how
they inform the setting of the level and statistical
form of the standard. In the epidemiological studies, the debate often focuses on whether relative
risks of less than 1.1 for excess morbidity and
mortality are significant. Of course, the specific
relative number is dependent on the denominator
being used, for example, per 10 ppb of ozone (24-h
average). For controlled exposure clinical studies,
attention has focused on the lowest levels with
statistically significant changes, which in turn, triggers debate over whether the changes are adverse.
A news report [63] in Science that I view as a
classic report highlighted the issues involved in the
search for subtle links between diet, lifestyle, or
environmental factors and disease, especially using
retrospective observational studies. I especially
liked the quote at the end attributed to Sander
Greenland, a well-known epidemiologist, in offering advice to his “most sensible, level-headed,
estimatable colleagues.” Remember, he says –
“there is nothing sinful about going out and getting
evidence, like asking people how much do you
drink and checking breast cancer records. There’s
nothing sinful about seeing if that evidence
correlates. There’s nothing sinful about checking
for confounding variables. The sin comes in believing a casual hypothesis is true because your study
came up with a positive result, or believing the
opposite because your study was negative.”
It is interesting to note that CASAC discussions of criteria pollutant effects have frequently
focused initially on the level of the standard sometimes devoid of any consideration of the statistical
form of the level. This approach was in keeping
with traditional practice in the setting of standards
such as Threshold Limit Values for occupational
exposures to chemicals based on scientific judgments [34–36, 40]. That approach has involved a
review of the available human data on a toxic
chemical to determine a no-observed effect level,
or the lowest observed effect level, and then using
safety factors to arrive at an acceptable exposure
level set at a lower level. In the absence of adequate human data, laboratory animal data are used
and an additional safety factor used to account for
the potential that the animal observations might
not adequately predict human effects. This
approach was routinely used for a wide range of
health responses that were assumed to have an
exposure-response relationship that exhibited
either a true or practical threshold, an excess of
effects above some level and an absence of effects
below that level. A review of the earliest Criteria
Documents and, indeed, also the Staff Papers,
documents that a similar line of reasoning was
used in the setting of the NAAQS.
The implementation of standards set with this
approach soon revealed that if the standard was to
be rigorously enforced, that is, no exceedances of
the specific level of the standard, the practical
effect would be to cause average levels of the
pollutant to be reduced to levels far below the
standard so as to avoid the occasional high value
exceeding the standard. Fortunately, common
sense prevailed and the EPA, over time, moved
to the practice of routinely linking the specific
level of the standard with a statistical form such
as the 98th percentile 24-h concentration averaged
over 3 years or the fourth highest 8-h average
concentration during a 3-year period. In my opinion, most of the attention of the CASAC in the
NAAQS setting process has focused on the level
Air Quality Guidelines and Standards
23