al. (2001a) and Mannetje et al. (2002b) to conduct comprehensive
exposure-response analyses of the risk of lung cancer and silicosis
mortality associated with exposure to crystalline silica. These
studies, referred to as the IARC multi-center studies of lung cancer
and silicosis mortality, relied on all available cohort data from
previously published epidemiological studies for which there were
adequate quantitative data on worker exposures to crystalline silica to
derive pooled estimates of disease risk. In addition, OSHA identified
four single-cohort studies of lung cancer mortality that it judged
suitable for quantitative risk assessment; two of these cohorts
(Attfield and Costello, 2004; Rice et al., 2001) were included among
the 10 used in the IARC multi-center study and studies of two other
cohorts appeared later (Hughes et al., 2001; McDonald et al., 2001,
2005; Miller and MacCalman, 2009). For non-malignant respiratory
disease mortality, in addition to the silicosis mortality study by
Mannetje et al. (2002b), Park et al. (2002) conducted an exposure-
response analysis of non-malignant respiratory disease mortality
(including silicosis and other chronic obstructive pulmonary diseases)
among diatomaceous earth workers. Exposure-response analyses for
silicosis morbidity have been published in several single-cohort
studies (Chen et al., 2005; Hnizdo and Sluis-Cremer, 1993; Steenland
and Brown, 1995b; Miller et al., 1998; Buchanan et al., 2003). Finally,
a quantitative assessment of end-stage renal disease mortality based on
data from three worker cohorts was developed by Steenland et al.
(2002a).
    In addition to these published studies, OSHA's contractor,
Toxichemica, Inc., commissioned Drs. Kyle Steenland and Scott Bartell
of Emory University to perform an uncertainty analysis to examine the
effect on lung cancer and silicosis mortality risk estimates of
uncertainties that exist in the exposure assessments underlying the two
IARC multi-center analyses (Toxichemica, Inc., 2004).
    OSHA's Preliminary QRA presents estimates of the risk of silica-
related diseases assuming exposure over a working life (45 years) to
the proposed 8-hour time-weighted average (TWA) PEL and action level of
0.05 and 0.025 mg/m\3\, respectively, of respirable crystalline silica,
as well as to OSHA's current PELs. OSHA's current general industry PEL
for respirable quartz is expressed both in terms of a particle count
formula and a gravimetric concentration formula, while the current
construction and shipyard employment PELs for respirable quartz are
only expressed in terms of a particle count formula. The current PELs
limit exposure to respirable dust; the specific limit in any given
instance depends on the concentration of crystalline silica in the
dust. For quartz, the gravimetric general industry PEL approaches a
limit of 0.1 mg/m\3\ as respirable quartz as the quartz content
increases (see discussion in Section XVI of this preamble, Summary and
Explanation for paragraph (c)). OSHA's Preliminary QRA presents risk
estimates for

exposure over a working lifetime to 0.1 mg/m\3\ to represent the risk
associated with exposure to the current general industry PEL. OSHA's
current PEL for construction and shipyard employment is a formula PEL
that limits exposure to respirable dust expressed as a respirable
particle count concentration. As with the gravimetric general industry
PEL, the limit varies depending on quartz content of the dust. There is
no single mass concentration equivalent for the construction and
shipyard PELs; OSHA's Preliminary QRA reviews several studies that
suggest that the current construction/shipyard PEL likely lies in the
range between 0.25 and 0.5 mg/m\3\ respirable quartz, and OSHA presents
risk estimates for this range of exposure to represent the risks
associated with exposure to the current construction/shipyard PEL. In
general industry, for both the gravimetric and particle count PELs,
OSHA's current PEL for cristobalite and tridymite are half the value
for quartz. Thus, OSHA's Preliminary QRA presents risk estimates
associated with exposure over a working lifetime to 0.025, 0.05, 0.1,
0.25, and 0.5 mg/m\3\ respirable silica (corresponding to cumulative
exposures over 45 years to 1.125, 2.25, 4.5, 11.25, and 22.5 mg/m\3\-
years).
    Risk estimates for lung cancer mortality, silicosis and non-
malignant respiratory disease mortality, and renal disease mortality
are presented in terms of lifetime (up to age 85) excess risk per 1,000
workers for exposure over an 8-hour working day, 250 days per year, and
a 45-year working life. For silicosis morbidity, OSHA based its risk
estimates on cumulative risk models used by the various investigators
to develop quantitative exposure-response relationships. These models
characterized the risk of developing silicosis (as detected by chest
radiography) up to the time that cohort members (including both active
and retired workers) were last examined. Thus, risk estimates derived
from these studies represent less-than-lifetime risks of developing
radiographic silicosis. OSHA did not attempt to estimate lifetime risk
(i.e., up to age 85) for silicosis morbidity because the relationships
between age, time, and disease onset post-exposure have not been well
characterized.
    A draft preliminary quantitative risk assessment document was
submitted for external scientific peer review in accordance with the
Office of Management and Budget's ``Final Information Quality Bulletin
for Peer Review'' (OMB, 2004). A summary of OSHA's responses to the
peer reviewers' comments appears in Section III of the background
document.
    In the sections below, OSHA describes the studies and the published
risk assessments it uses to estimate the occupational risk of
crystalline silica-related disease. (The Preliminary QRA itself also
discusses several other available studies that OSHA does not include
and OSHA's reasons for not including these studies.)

B. Lung Cancer Mortality

1. Summary of Studies
    In its Preliminary QRA, OSHA discusses risk assessments from six
published studies that quantitatively analyzed exposure-response
relationships for crystalline silica and lung cancer; some of these
also provided estimates of risks associated with exposure to OSHA's
current PEL or NIOSH's Recommended Exposure Limit (REL) of 0.05 mg/
m\3\. These studies include: (1) A quantitative analysis by Steenland
et al. (2001a) of worker cohort data pooled from ten studies; (2) an
exposure-response analysis by Rice et al. (2001) of a cohort of
diatomaceous earth workers primarily exposed to cristobalite; (3) an
analysis by Attfield and Costello (2004) of U.S. granite workers; (4) a
risk assessment by Kuempel et al. (2001), who employed a kinetic rat
lung model to describe the relationship between quartz lung burden and
cancer risk, then calibrated and validated that model using the
diatomaceous earth worker and granite worker cohort mortality data; (5)
an exposure-response analysis by Hughes et al., (2001) of U.S.
industrial sand workers; and (6) a risk analysis by Miller et al.
(2007) and Miller and MacCalman (2009) of British coal miners. These
six studies are described briefly below and are followed by a summary
of the lung cancer risk estimates derived from these studies.
a. Steenland et al. (2001a) Pooled Cohort Analysis
    OSHA considers the lung cancer analysis conducted by Steenland et
al. (2001a) to be of prime importance for risk estimation because of
its size, incorporation of data from multiple cohorts, and availability
of detailed exposure and job history data. Subsequent to its
publication, Steenland and Bartell (Toxichemica, Inc., 2004) conducted
a quantitative uncertainty analysis on the pooled data set to evaluate
the potential impact on the risk estimates of random and systematic
exposure misclassification, and Steenland (personal communication,
2010) conducted additional exposure-response modeling.
    The original study consisted of a pooled exposure-response analysis
and risk assessment based on raw data obtained from ten cohorts of
silica-exposed workers (65,980 workers, 1,072 lung cancer deaths).
Steenland et al. (2001a) initially identified 13 cohort studies as
containing exposure information sufficient to develop a quantitative
exposure assessment; the 10 studies included in the pooled analysis
were those for which data on exposure and health outcome could be
obtained for individual workers. The cohorts in the pooled analysis
included U.S. gold miners (Steenland and Brown, 1995a), U.S.
diatomaceous earth workers (Checkoway et al., 1997), Australian gold
miners (de Klerk and Musk, 1998), Finnish granite workers (Koskela et
al., 1994), U.S. industrial sand employees (Steenland and Sanderson,
2001), Vermont granite workers (Costello and Graham, 1988), South
African gold miners (Hnizdo and Sluis-Cremer, 1991; Hnizdo et al.,
1997), and Chinese pottery workers, tin miners, and tungsten miners
(Chen et al., 1992).
    The exposure assessments developed for the pooled analysis are
described by Mannetje et al. (2002a). The exposure information and
measurement methods used to assess exposure from each of the 10 cohort
studies varied by cohort and by time and included dust measurements
representing particle counts, mass of total dust, and respirable dust
mass. All exposure information was converted to units of mg/m\3\
respirable crystalline silica by generating cohort-specific conversion
factors based on the silica content of the dust to which workers were
exposed.
    A case-control study design was employed for which cases and
controls were matched for race, sex, age (within 5 years) and study;
100 controls were matched to each case. To test the reasonableness of
the cumulative exposure estimates for cohort members, Mannetje et al.
(2002a) examined exposure-response relationships for silicosis
mortality by performing a nested case-control analysis for silicosis or
unspecified pneumoconiosis using conditional logistic regression. Each
cohort was stratified into quartiles by cumulative exposure, and
standardized rate ratios (SRR) for silicosis were calculated using the
lowest-exposure quartile as the baseline. Odds ratios (OR) for
silicosis were also calculated for the pooled data set overall, which
was stratified into quintiles based on cumulative exposure.

    For the pooled data set, the relationship between odds ratio for
silicosis mortality and increasing cumulative exposure was ``positive
and reasonably monotonic'', ranging from 3.1 for the lowest quartile of
exposure to 4.8 for the highest. In addition, in seven of the ten
individual cohorts, there were statistically significant trends between
silicosis mortality rate ratios (SRR) and cumulative exposure. For two
of the cohorts (U.S. granite workers and U.S. gold miners), the trend
test was not statistically significant (p=0.10). A trend analysis could
not be performed on the South African gold miner cohort since silicosis
was not coded as an underlying cause of death in that country. A more
rigorous analysis of silicosis mortality on pooled data from six of
these cohorts also showed a strong, statistically significant
increasing trend with increasing decile of cumulative exposure
(Mannetje et al., 2002b), providing additional evidence for the
reasonableness of the exposure assessment used for the Steenland et al
(2001a) lung cancer analysis.
    For the pooled lung cancer mortality analysis, Steenland et al.
(2001a) conducted a nested case-control analysis via Cox regression, in
which there were 100 controls chosen for each case randomly selected
from among cohort members who survived past the age at which the case
died, and matched on age (the time variable in Cox regression), study,
race/ethnicity, sex, and date of birth within 5 years (which, in
effect, matched on calendar time given the matching on age). Using
alternative continuous exposure variables in a log-linear relative risk
model (log RR=[beta]x, where x represents the exposure variable and
[beta] the coefficient to be estimated), Steenland et al. (2001a) found
that the use of either 1) cumulative exposure with a 15-year lag, 2)
the log of cumulative exposure with a 15-year lag, or 3) average
exposure resulted in positive statistically significant (p<=0.05)
exposure-response coefficients. The models that provided the best fit
to the data were those that used cumulative exposure and log-
transformed cumulative exposure. The fit of the log-linear model with
average exposure was clearly inferior to those using cumulative and
log-cumulative exposure metrics.
    There was significant heterogeneity among studies (cohorts) using
either cumulative exposure or average exposure. The authors suggested a
number of possible reasons for such heterogeneity, including errors in
measurement of high exposures (which tends to have strong influence on
the exposure-response curve when untransformed exposure measures are
used), the differential toxicity of silica depending on the crystalline
polymorph, the presence of coatings or trace minerals that alter the
reactivity of the crystal surfaces, and the age of the fractured
surfaces. Models that used the log transform of cumulative exposure
showed no statistically significant heterogeneity among cohorts
(p=0.36), possibly because they are less influenced by very high
exposures than models using untransformed cumulative exposure. For this
reason, as well as the good fit of the model using log-cumulative
exposure, Steenland et al. (2001a) conducted much of their analysis
using log-transformed cumulative exposure. The sensitivity analysis by
Toxichemica, Inc. (2004) repeated this analysis after correcting some
errors in the original coding of the data set. At OSHA's request,
Steenland (2010) also conducted a categorical analysis of the pooled
data set and additional analyses using linear relative risk models
(with and without log-transformation of cumulative exposure) as well as
a 2-piece spline model.
    The cohort studies included in the pooled analysis relied in part
on particle count data and the use of conversion factors to estimate
exposures of workers to mass respirable quartz. A few studies were able
to include at least some respirable mass sampling data. OSHA believes
that uncertainty in the exposure assessments that underlie each of the
10 studies included in the pooled analysis is likely to represent one
of the most important sources of uncertainty in the risk estimates. To
evaluate the potential impact of uncertainties in the underlying
exposure assessments on estimates of the risk, OSHA's contractor,
Toxichemica, Inc. (2004), commissioned Drs. Kyle Steenland and Scott
Bartell of Emory University to conduct an uncertainty analysis using
the raw data from the pooled cancer risk assessment. The uncertainty
analysis employed a Monte Carlo technique in which two kinds of random
exposure measurement error were considered; these were (1) random
variation in respirable dust measurements and (2) random error in
estimating respirable quartz exposures from historical data on particle
count concentration, total dust mass concentration, and respirable dust
mass concentration measurements. Based on the results of this
uncertainty analysis, OSHA does not have reason to believe that random
error in the underlying exposure estimates in the Steenland et al.
(2001a) pooled cohort study of lung cancer is likely to have
substantially influenced the original findings, although a few
individual cohorts (particularly the South African and Australian gold
miner cohorts) appeared to be sensitive to measurement errors.
    The sensitivity analysis also examined the potential effect of
systematic bias in the use of conversion factors to estimate respirable
crystalline silica exposures from historical data. Absent a priori
reasons to suspect bias in a specific direction (with the possible
exception of the South African cohort), Toxichemica, Inc. (2004)
considered possible biases in either direction by assuming that
exposure was under-estimated by 100% (i.e., the true exposure was twice
the estimated) or over-estimated by 100% (i.e., the true exposure was
half the estimated) for any given cohort in the original pooled
dataset. For the conditional logistic regression model using log
cumulative exposure with a 15-year lag, doubling or halving the
exposure for a specific study resulted in virtually no change in the
exposure-response coefficient for that study or for the pooled analysis
overall. Therefore, based on the results of the uncertainty analysis,
OSHA believes that misclassification errors of a reasonable magnitude
in the estimation of historical exposures for the 10 cohort studies
were not likely to have substantially biased risk estimates derived
from the exposure-response model used by Steenland et al. (2001a).
b. Rice et al. (2001) Analysis of Diatomaceous Earth Workers
    Rice et al. (2001) applied a variety of exposure-response models to
the same California diatomaceous earth cohort data originally reported
on by Checkoway et al. (1993, 1996, 1997) and included in the pooled
analysis conducted by Steenland et al. (2001a) described above. The
cohort consisted of 2,342 white males employed for at least one year
between 1942 and 1987 in a California diatomaceous earth mining and
processing plant. The cohort was followed until 1994, and included 77
lung cancer deaths. Rice et al. (2001) relied on the dust exposure
assessment developed by Seixas et al. (1997) from company records of
over 6,000 samples collected from 1948 to 1988; cristobalite was the
predominate form of crystalline silica to which the cohort was exposed.
Analysis was based on both Poisson regression models Cox's proportional
hazards models with various functions of cumulative silica exposure in
mg/m\3\-years to estimate the relationship between silica exposure and
lung cancer mortality rate. Rice et al. (2001) reported that exposure
to crystalline silica was a significant predictor of lung cancer

mortality for nearly all of the models employed, with the linear
relative risk model providing the best fit to the data in the Poisson
regression analysis.
c. Attfield and Costello (2004) Analysis of Granite Workers
    Attfield and Costello (2004) analyzed the same U.S. granite cohort
originally studied by Costello and Graham (1988) and Davis et al.
(1983) and included in the Steenland et al. (2001a) pooled analysis,
consisting of 5,414 male granite workers who were employed in the
Vermont granite industry between 1950 and 1982 and who had received at
least one chest x-ray from the surveillance program of the Vermont
Department of Industrial Hygiene. Their 2004 report extended follow-up
from 1982 to 1994, and found 201 deaths. Workers' cumulative exposures
were estimated by Davis et al. (1983) based on historical exposure data
collected in six environmental surveys conducted between 1924 and 1977,
plus work history information.
    Using Poisson regression models and seven cumulative exposure
categories, the authors reported that the results of the categorical
analysis showed a generally increasing trend of lung cancer rate ratios
with increasing cumulative exposure, with seven lung cancer death rate
ratios ranging from 1.18 to 2.6. A complication of this analysis was
that the rate ratio for the highest exposure group in the analysis
(cumulative exposures of 6.0 mg/m\3\-years or higher) was substantially
lower than those for other exposure groups. Attfield and Costello
(2004) reported that the best-fitting model was based on a 15-year lag,
use of untransformed cumulative exposure, and omission of the highest
exposure group.
    The authors argued that it was appropriate to base their risk
estimates on a model that was fitted without the highest exposure group
for several reasons. They believed the underlying exposure data for the
high-exposure group was weaker than for the others, and that there was
a greater likelihood that competing causes of death and misdiagnoses of
causes of death attenuated the lung cancer death rate. Second, all of
the remaining groups comprised 85 percent of the deaths in the cohort
and showed a strong linear increase in lung cancer mortality with
increasing exposure. Third, Attfield and Costello (2004) believed that
the exposure-response relationship seen in the lower exposure groups
was more relevant given that the exposures of these groups were within
the range of current occupational standards. Finally, the authors
stated that risk estimates derived from the model after excluding the
highest exposure group were more consistent with other published risk
estimates than was the case for estimates derived from the model using
all exposure groups. Because of these reasons, OSHA believes it is
appropriate to rely on the model employed by Attfield and Costello
(2004) after omitting the highest exposure group.
d. Kuempel et al. (2001) Rat-Based Model for Human Lung Cancer
    Kuempel et al. (2001) published a rat-based toxicokinetic/
toxicodynamic model for silica exposure for predicting human lung
cancer, based on lung burden concentrations necessary to cause the
precursor events that can lead to adverse physiological effects in the
lung. These adverse physiological effects can then lead to lung
fibrosis and an indirect genotoxic cause of lung cancer. The
hypothesized first step, or earliest expected response, in these
disease processes is chronic lung inflammation, which the authors
consider as a disease limiting step. Since the NOAEL of lung burden
associated with this inflammation, based on the authors' rat-to-human
lung model conversion, is the equivalent of exposure to 0.036 mg/m\3\
(Mcrit) for 45 years, exposures below this level would
presumably not lead to (based on an indirect genotoxic mechanism) lung
cancer, at least in the ``average individual.'' Since silicosis also is
inflammation mediated, this exposure could also be considered to be an
average threshold level for that disease as well.
    Kuempel et al. (2001) have used their rat-based lung cancer model
with human data, both to validate their model and to estimate the lung
cancer risk as a function of quartz lung burden. First they
``calibrated'' human lung burdens from those in rats based on exposure
estimates and lung autopsy reports of U.S. coal miners. Then they
validated these lung burden estimates using quartz exposure data from
U.K. coal miners. Using these human lung burden/exposure concentration
equivalence relationships, they then converted the cumulative exposure-
lung cancer response slope estimates from both the California
diatomaceous earth workers (Rice et al., 2001) and Vermont granite
workers (Attfield and Costello, 2001) to lung burden-lung cancer
response slope estimates. Finally, they used these latter slope
estimates in a life table program to estimate lung cancer risk
associated with their ``threshold'' exposure of 0.036 mg/m\3\ and to
the OSHA PEL and NIOSH REL. Comparing the estimates from the two
epidemiology studies with those based on a male rat chronic silica
exposure study the authors found that, '' the lung cancer excess risk
estimates based on male rat data are approximately three times higher
than those based on the male human data.'' Based on this modeling and
validation exercise, Keumpel et al. concluded, ``the rat-based
estimates of excess lung cancer risk in humans exposed to crystalline
silica are reasonably similar to those based on two human occupational
epidemiology studies.''
    Toxichemica, Inc. (2004) investigated whether use of the dosimetry
model would substantially affect the results of the pooled lung cancer
data analysis initially conducted by Steenland et al. (2001a). They
replicated the lung dosimetry model using Kuempel et al.'s (2001)
reported median fit parameter values, and compared the relationship
between log cumulative exposure and 15-year lagged lung burden at the
age of death in case subjects selected for the pooled case-control
analysis. The two dose metrics were found to be highly correlated
(r=0.99), and models based on either log silica lung burden or log
cumulative exposure were similarly good predictors of lung cancer risk
in the pooled analysis (nearly identical log-likelihoods of -4843.96
and--4843.996, respectively). OSHA believes that the Kuempel et al.
(2001) analysis is a credible attempt to quantitatively describe the
retention and accumulation of quartz in the lung, and to relate the
external exposure and its associated lung burden to the inflammatory
process. However, using the lung burden model to convert the cumulative
exposure coefficients to a different exposure metric appears to add
little additional information or insight to the risk assessments
conducted on the diatomaceous earth and granite cohort studies.
Therefore, for the purpose of quantitatively evaluating lung cancer
risk in exposed workers, OSHA has chosen to rely on the epidemiology
studies themselves and the cumulative exposure metrics used in those
studies.
e. Hughes et al. (2001), McDonald et al. (2001), and McDonald et al.
(2005) Study of North American Industrial Sand Workers
    McDonald et al. (2001), Hughes et al. (2001) and McDonald et al.
(2005) followed up on a cohort study of North American industrial sand
workers that overlapped with the industrial sand cohort (18 plants,
4,626 workers) studied by Steenland and Sanderson (2001) and included
in Steenland et al.'s (2001a) pooled cohort analysis. The McDonald et
al. (2001) follow-up cohort

included 2,670 men employed before 1980 for three years or more in one
of nine North American (8 U.S. and 1 Canadian) sand-producing plants,
including 1 large associated office complex. Information on cause of
death was obtained, from 1960 through 1994, for 99 percent of the
deceased workers for a total 1,025 deaths representing 38 percent of
the cohort. A nested case-control study and analysis based on 90 lung
cancer deaths from this cohort was also conducted by Hughes et al.
(2001). A later update through 2000, of both the cohort and nested
case-control studies by McDonald et al. (2005), eliminated the Canadian
plant, following 2,452 men from the eight U.S. plants. For the lung
cancer case-control part of the study the update included 105 lung
cancer deaths. Both the initial and updated case control studies used
up to two controls per case.
    Although the cohort studies provided evidence of increased risk of
lung cancer (SMR = 150, p = 0.001, based on U.S. rates) for deaths
occurring 20 or more years from hire, the nested case-control studies,
Hughes et al. (2001) and McDonald et al. (2005), allowed for individual
job, exposure, and smoking histories to be taken into account in the
exposure-response analysis for lung cancer. Both of these case-control
analyses relied on an analysis of exposure information reported by
Sanderson et al. (2000) and by Rando et al. (2001) to provide
individual estimates of average and cumulative exposure. Statistically
significant positive exposure-response trends for lung cancer were
found for both cumulative exposure (lagged 15 years) and average
exposure concentration, but not for duration of employment, after
controlling for smoking. A monotonic increase was seen for both lagged
and unlagged cumulative exposure when the four upper exposure
categories were collapsed into two. With exposure lagged 15 years and
after adjusting for smoking, increasing quartiles of cumulative silica
exposure were associated with lung cancer mortality (odds ratios of
1.00, 0.84, 2.02 and 2.07, p-value for trend=0.04). There was no
indication of an interaction effect of smoking and cumulative silica
exposure (Hughes et al., 2001).
    OSHA considers this Hughes et al. (2001) study and analysis to be
of high enough quality to provide risk estimates for excess lung cancer
for silica exposure to industrial sand workers. Using the median
cumulative exposure levels of 0, 0.758, 2.229 and 6.183 mg/m\3\-years,
Hughes et al. estimated lung cancer odds ratios, ORs (no. of deaths),
for these categories of 1.00 (14), 0.84 (15), 2.02 (31), and 2.07 (30),
respectively, on a 15-year lag basis (p-value for trend=0.04.) For the
updated nested case control analysis, McDonald et al. (2005) found very
similar results, with exposure lagged 15 years and, after adjusting for
smoking, increasing quartiles of cumulative silica exposure were
associated with lung cancer ORs (no. of deaths) of 1.00 (13), 0.94
(17), 2.24 (38), and 2.66 (37) (p-value for trend=0.006). Because the
Hughes et al. (2001) report contained information that allowed OSHA to
better calculate exposure-response estimates and because of otherwise
very similar results in the two papers, OSHA has chosen to base its
lifetime excess lung cancer risk estimate for these industrial sand
workers on the Hughes et al. (2001) case-control study. Using the
median exposure levels of 0, 0.758, 2.229 and 6.183 mg-years/m\3\,
respectively, for each of the four categories described above, and
using the model: ln OR = [alpha] + [beta] x Cumulative Exposure, the
coefficient for the exposure estimate was [beta] = 0.13 per (mg/m\3\-
years), with a standard error of [beta] = 0.074 (calculated from the
trend test p-value in the same paper). In this model, with background
lung cancer risks of about 5 percent, the OR provides a suitable
estimate of the relative risk.
f. Miller et al. (2007) and Miller and MacCalman (2009) Study of
British Coal Workers Exposed to Respirable Quartz
    Miller et al. (2007) and Miller and MacCalman (2009) continued a
follow-up mortality study, begun in 1970, of 18,166 coalminers from 10
British coalmines initially followed through the end of 1992 (Miller et
al., 1997). The two recent reports on mortality analyzed the cohort of
17,800 miners and extended the analysis through the end of 2005. By
that time there were 516,431 person years of observation, an average of
29 years per miner, with 10,698 deaths from all causes. Causes of
deaths of interest included pneumoconiosis, other non-malignant
respiratory diseases (NMRD), lung cancer, stomach cancer, and
tuberculosis. Three of the strengths of this study are its use of
detailed time-exposure measurements of both quartz and total mine dust,
detailed individual work histories, and individual smoking histories.
However, the authors noted that no additional exposure measurements
were included in the updated analysis, since all the mines had closed
by the mid 1980's.
    For this cohort mortality study there were analyses using both
external (regional age-time and cause specific mortality rates)
internal controls. For the analysis from external mortality rates, the
all-cause mortality SMR from 1959 through 2005 was 100.9 (95% C.I.,
99.0-102.8), based on all 10,698 deaths. However, these death ratios
were not uniform over time. For the period from 1990 to 2005, the all-
cause SMR was 109.6 (95% C.I., 106.5-112.8), while the ratios for
previous periods were less than 100. This pattern of recent increasing
SMRs was also seen in the recent cause-specific death rate for lung
cancer, SMR=115.7 (95% C.I., 104.8-127.7). For the analysis based on
internal rates and using Cox regression methods, the relative risk for
lung cancer risk based on a cumulative quartz exposure equivalent to
approximately 0.055 mg/m\3\ for 45 years was RR = 1.14 (95% C.I., 1.04
to 1.25). This risk is adjusted for concurrent coal dust exposure and
smoking status, and incorporated a 15-year lag in quartz exposures. The
analysis showed a strong effect for smoking (independent of quartz
exposure) on lung cancer. For lung cancer, OSHA believes that the
analyses based on the Cox regression method provides strong evidence
that for these coal miners' quartz exposures were associated with
increased lung cancer risk, but that simultaneous exposures to coal
dust did not cause increased lung cancer risk. To estimate lung cancer
risk from this study, OSHA estimated the regression slope for a log-
linear relative risk model based on the Miller and MacCalman's (2009)
finding of a relative risk of 1.14 for a cumulative exposure of 0.055
mg/m\3\-years.
2. Summary of OSHA's Estimates of Lung Cancer Mortality Risk
    Tables VI-1 and VI-2 summarize the excess lung cancer risk
estimates from occupational exposure to crystalline silica, based on
five of the six lung cancer risk assessments discussed above. OSHA's
estimates of lifetime excess lung cancer risk associated with 45 years
of exposure to crystalline silica at 0.1 mg/m\3\ (approximately the
current general industry PEL) range from 13 to 60 deaths per 1,000
workers. For exposure to the proposed PEL of 0.05 mg/m\3\, the lifetime
risk estimates calculated by OSHA are in the range of 6 to 26 deaths
per 1,000 workers. For a 45-year exposure at the proposed action level
of 0.025 mg/m\3\, OSHA estimates the risk to range from 3 to 23 deaths
per 1,000 workers. The results from these assessments are reasonably
consistent despite the use of data from different cohorts and the
reliance on different analytical techniques for evaluating dose-
response relationships. Furthermore, OSHA notes that in this range of
exposure, 0.025--0.1 mg/m\3\, there is statistical consistency between

the risk estimates, as evidenced by the considerable overlap in the 95-
percent confidence intervals of the risk estimates presented in Table
VI-1.
    OSHA also estimates the lung cancer risk associated with 45 years
of exposure to the current construction/shipyard PEL (in the range of
0.25 to 0.5 mg/m\3\) to range from 37 to 653 deaths per 1,000 workers.
Exposure to 0.25 or 0.5 mg/m\3\ over 45 years represents cumulative
exposures of 11.25 and 22.5 mg-years/m\3\, respectively. This range of
cumulative exposure is well above the median cumulative exposure for
most of the cohorts used in the risk assessment, primarily because most
of the individuals in these cohorts had not been exposed for as long as
45 years. Thus, estimating lung cancer excess risks over this higher
range of cumulative exposures of interest to OSHA required some degree
of extrapolation and adds uncertainty to the estimates.

C. Silicosis and Non-Malignant Respiratory Disease Mortality

    There are two published quantitative risk assessment studies of
silicosis and non-malignant respiratory disease (NMRD) mortality; a
pooled analysis of silicosis mortality by Mannetje et al. (2002b) of
data from six epidemiological studies, and an exposure-response
analysis of NMRD mortality among diatomaceous earth workers (Park et
al., 2002).
1. Mannetje et al. (2002b) Six Cohort Pooled Analysis
    The Mannetje et al. (2002b) silicosis analysis was part of the IARC
ten cohort pooled study included in the Steenland et al. (2001a) lung
cancer mortality analysis above. These studies included 18,634 subjects
and 170 silicosis deaths (n = 150 for silicosis, and n = 20 unspecified
pneumoconiosis). The silicosis deaths had a median duration of exposure
of 28 years, a median cumulative exposure of 7.2 mg/m\3\-years, and a
median average exposure of 0.26 mg/m\3\, while the respective values of
the whole cohort were 10 years, 0.62 mg/m\3\-years, and 0.07 mg/m\3\.
Rates for silicosis adjusted for age, calendar time, and study were
estimated by Poisson regression; rates increased nearly monotonically
with deciles of cumulative exposure, from a mortality rate of 5/100,000
person-years in the lowest exposure category (0-0.99 mg/m\3\-years) to
299/100,000 person-years in the highest category (>28.10 mg/m\3\-
years). Quantitative estimates of exposure to respirable silica (mg/
m\3\) were available for all six cohorts (Mannetje et al. 2002a).
Lifetime risk of silicosis mortality was estimated by accumulating
mortality rates over time using the formula
    Risk = 1 - exp(-[sum]time * rate).
    To estimate the risk of silicosis mortality at the current and
proposed PELs, OSHA used the model described by Mannetje et al. (2002b)
to estimate risk to age 85 but used rate ratios that were estimated
from a nested case-control design that was part of a sensitivity
analysis conducted by Toxichemica, Inc. (2004), rather than the Poisson
regression originally conducted by Mannetje et al. (2002b). The case-
control design was selected because it was expected to better control
for age; in addition, the rate ratios derived from the case-control
study reflect exposure measurement uncertainty via conduct of a Monte
Carlo analysis (Toxichemica, Inc., 2004).
2. Park et al. (2002) Study of Diatomaceous Earth Workers
    Park et al. (2002) analyzed the California diatomaceous earth
cohort data originally studied by Checkoway et al. (1997), consisting
of 2,570 diatomaceous earth workers employed for 12 months or more from
1942 to 1994, to quantify the relationship between exposure to
cristobalite and mortality from chronic lung disease other than cancer
(LDOC). Diseases in this category included pneumoconiosis (which
included silicosis), chronic bronchitis, and emphysema, but excluded
pneumonia and other infectious diseases. Industrial hygiene data for
the cohort were available from the employer for total dust, silica
(mostly cristobalite), and asbestos. Park et al. (2002) used the
exposure assessment previously reported by Seixas et al. (1997) and
used by Rice et al. (2001) to estimate cumulative crystalline silica
exposures for each worker in the cohort based on detailed work history
files. The mean silica concentration for the cohort overall was 0.29
mg/m\3\ over the period of employment (Seixas et al., 1997). The mean
cumulative exposure values for total respirable dust and respirable
crystalline silica were 7.31 and 2.16 mg/m\3\-year, respectively.
Similar cumulative exposure estimates were made for asbestos. Smoking
information was available for about 50 percent of the cohort and for 22
of the 67 LDOC deaths available for analysis, permitting Park et al.
(2002) to at least partially adjust for smoking. Estimates of LDOC
mortality risks were derived via Poisson and Cox's proportional hazards
models; a variety of relative rate model forms were fit to the data,
with a linear relative rate model being selected for risk estimation.
3. Summary Risk Estimates for Silicosis and NMRD Mortality
    Table VI-2 presents OSHA's risk estimates for silicosis and NMRD
mortality derived from the Mannetje et al. (2002b) and Park et al.
(2002) studies, respectively. For 45 years of exposure to the current
general industry PEL (approximately 0.1 mg/m\3\ respirable crystalline
silica), OSHA's estimates of excess lifetime risk are 11 deaths per
1,000 workers for the pooled analysis and 83 deaths per 1,000 workers
based on Park et al.'s (2002) estimates. At the proposed PEL, estimates
of silicosis and NMRD mortality are 7 and 43 deaths per 1,000,
respectively. For exposures up to 0.25 mg/m\3\, the estimates based on
Park et al. are about 5 to 11 times as great as those calculated for
the pooled analysis of silicosis mortality (Mannetje et al., 2002b).
However, these two sets of risk estimates are not directly comparable.
First, the Park et al. analysis used untransformed cumulative exposure
as the exposure metric, whereas the Mannertje et al. analysis used log
cumulative exposure, which causes the exposure-response to flatten out
in the higher exposure ranges. Second, the mortality endpoint for the
Park et al. (2002) analysis is death from all non-cancer lung diseases,
including pneumoconiosis, emphysema, and chronic bronchitis, whereas
the pooled analysis by Mannetje et al. (2002b) included only deaths
coded as silicosis or other pneumoconiosis. Less than 25 percent of the
LDOC deaths in the Park et al. (2002) analysis were coded as silicosis
or other pneumoconiosis (15 of 67). As noted by Park et al. (2002), it
is likely that silicosis as a cause of death is often misclassified as
emphysema or chronic bronchitis; thus, Mannetje et al.'s (2002b)
selection of deaths may tend to underestimate the true risk of
silicosis mortality, and Park et al.'s (2002) analysis would more
fairly capture the total respiratory mortality risk from all non-
malignant causes, including silicosis and chronic obstructive pulmonary
disease.

D. Renal Disease Mortality

    Steenland et al. (2002a) examined renal disease mortality in three
cohorts and evaluated exposure-response relationships from the pooled
cohort data. The three cohorts included U.S. gold miners (Steenland and
Brown, 1995a), U.S. industrial sand workers (Steenland et al., 2001b),
and Vermont granite workers (Costello and Graham, 1988), all three of
which are included in both the lung cancer mortality and silicosis
mortality pooled analyses reported above. Follow up for the U.S.

gold miners study was extended six years from that in the other pooled
analyses. Steenland et al. (2002a) reported that these cohorts were
chosen because data were available for both underlying cause mortality
and multiple cause mortality; this was believed important because renal
disease is often listed on death certificates without being identified
as an underlying cause of death. In the three cohorts, there were 51
total renal disease deaths using underlying cause, and 204 total renal
deaths using multiple cause mortality.
    The combined cohort for the pooled analysis (Steenland et al.,
2002a) consisted of 13,382 workers with exposure information available
for 12,783 (95 percent). Exposure matrices for the three cohorts had
been used in previous studies (Steenland and Brown, 1995a; Attfield and
Costello, 2001; Steenland et al., 2001b). The mean duration of
exposure, the mean cumulative exposure, and the mean concentration of
respirable silica for the pooled cohort were 13.6 years, 1.2 mg/m\3\-
years, and 0.07 mg/m\3\, respectively. SMRs (compared to the U.S.
population) for renal disease (acute and chronic glomerulonephritis,
nephrotic syndrome, acute and chronic renal failure, renal sclerosis,
and nephritis/nephropathy) were statistically significantly elevated
using multiple cause data (SMR 1.29, 95% CI 1.10-1.47, 193 deaths) and
underlying cause data (SMR 1.41, 95% CI 1.05-1.85, 51 observed deaths).
    OSHA's estimates of renal disease mortality appear in Table VI-2.
Based on the life table analysis, OSHA estimates that exposure to the
current (0.10 mg/m\3\) and proposed general industry PEL (0.0.05 mg/
m\3\) over a working life would result in a lifetime excess renal
disease risk of 39 (95% CI 2-200) and 32 (95% CI 1.7-147) deaths per
1,000, respectively. For exposure to the current construction/shipyard
PEL, OSHA estimates the excess lifetime risk to range from 52 (95% CI
2.2-289) to 63 (95% CI 2.5-368) deaths per 1,000 workers.

E. Silicosis Morbidity

    OSHA's Preliminary QRA summarizes the principal cross-sectional and
cohort studies that have quantitatively characterized relationships
between exposure to crystalline silica and development of radiographic
evidence of silicosis. Each of these studies relied on estimates of
cumulative exposure to evaluate the relationship between exposure and
silicosis prevalence in the worker populations examined. The health
endpoint of interest in these studies is the appearance of opacities on
chest roentgenograms indicative of pulmonary fibrosis.
    The International Labour Organization's (ILO) 1980 International
Classification of Radiographs of the Pneumoconioses is accepted as the
standard against which chest radiographs are measured in epidemiologic
studies, for medical surveillance and for clinical evaluation.
According to this standard, if radiographic findings are or may be
consistent with pneumoconiosis, then the size, shape, and extent of
profusion of opacities are characterized by comparing the radiograph to
standard films. Classification by shape (rounded vs. irregular) and
size involves identifying primary and secondary types of small
opacities on the radiograph and classifying them into one of six size/
shape categories. The extent of profusion is judged from the
concentrations of opacities as compared with that on the standard
radiographs and is graded on a 12-point scale of four major categories
(0-3, with Category 0 representing absence of opacities), each with
three subcategories. Most of the studies reviewed by OSHA considered a
finding consistent with an ILO classification of 1/1 to be a positive
diagnosis of silicosis, although some also considered an x-ray
classification of 1/0 or 0/1 to be positive.
    Chest radiography is not the most sensitive tool used to diagnose
or detect silicosis. In 1993, Hnizdo et al. reported the results of a
study that compared autopsy and radiological findings of silicosis in a
cohort of 557 white South African gold miners. The average period from
last x-ray to autopsy was 2.7 years. Silicosis was not diagnosed
radiographically for over 60 percent of the miners for whom
pathological examination of lung tissue showed slight to marked
silicosis. The likelihood of false negatives (negative by x-ray, but
silicosis is actually present) increased with years of mining and
average dust exposure of the miners. The low sensitivity seen for
radiographic evaluation suggests that risk estimates derived from
radiographic evidence likely understate the true risk of developing
fibrotic lesions as a result of exposure to crystalline silica.
    OSHA's Preliminary QRA examines multiple studies from which
silicosis occupational morbidity risks can be estimated. The studies
evaluated fall into three major types. Some are cross-sectional studies
in which radiographs taken at a point in time were examined to
ascertain cases (Kreiss and Zhen, 1996; Love et al., 1999; Ng and Chan,
1994; Rosenman et al., 1996; Churchyard et al., 2003, 2004); these
radiographs may have been taken as part of a health survey conducted by
the investigators or represent the most recent chest x-ray available
for study subjects. Other studies were designed to examine radiographs
over time in an effort to determine onset of disease. Some of these
studies examined primarily active, or current, workers (Hughes et al.,
1998; Muir et al., 1989a, 1989b; Park et al., 2002), while others
included both active and retired workers (Chen et al., 2001, 2005;
Hnizdo and Sluis-Cremer, 1993; Miller et al., 1998; Buchanan et al.,
2003; Steenland and Brown, 1995b).
    Even though OSHA has presented silicosis risk estimates for all of
the studies identified, the Agency is relying primarily on those
studies that examined radiographs over time and included both active
and retired workers. It has been pointed out by others (Chen et al.,
2001; Finkelstein, 2000; NIOSH, 2002) that lack of follow-up of retired
workers consistently resulted in lower risk estimates compared to
studies that included retired workers. OSHA believes that the most
reliable estimates of silicosis morbidity, as detected by chest
radiographs, come from the studies that evaluated radiographs over
time, included radiographic evaluation of workers after they left
employment, and derived cumulative or lifetime estimates of silicosis
disease risk. Brief descriptions of these cumulative risk studies used
to estimate silicosis morbidity risks are presented below.
1. Hnizdo and Sluis Cremer (1993) Study of South African White Gold
Miners
    Hnizdo and Sluis-Cremer (1993) described the results of a
retrospective cohort study of 2,235 white gold miners in South Africa.
These workers had received annual examinations and chest x-rays while
employed; most returned for occasional examinations after employment. A
case was defined as one with an x-ray classification of ILO 1/1 or
greater. A total of 313 miners had developed silicosis and had been
exposed for an average of 27 years at the time of diagnosis. Forty-
three percent of the cases were diagnosed while employed and the
remaining 57 percent were diagnosed an average of 7.4 years after
leaving the mines. The average latency for the cohort was 35 years
(range of 18-50 years) from start of exposure to diagnosis.
    The average respirable dust exposure for the cohort overall was
0.29 mg/m\3\ (range 0.11-0.47), corresponding to an estimated average
respirable silica concentration of 0.09 mg/m\3\ (range

0.033-0.14). The average cumulative dust exposure for the overall
cohort was 6.6 mg/m\3\-years (range 1.2-18.7), or an average cumulative
silica exposure of 1.98 mg/m\3\-years (range 0.36-5.61). OSHA believes
that the exposure estimates for the cohort are uncertain given the need
to rely on particle count data generated over a fairly narrow
production period.
    Silicosis risk increased exponentially with cumulative exposure to
respirable dust and was modeled using log-logistic regression. Using
the exposure-response relationship developed by Hnizdo and Sluis-Cremer
(1993), and assuming a quartz content of 30 percent in respirable dust,
Rice and Stayner (1995) and NIOSH (2002) estimated the risk of
silicosis to be 70 percent and 13 percent for a 45-year exposure to 0.1
and 0.05 mg/m\3\ respirable crystalline silica, respectively.
2. Steenland and Brown (1995b) Study of South Dakota Gold Miners
    Three thousand three hundred thirty South Dakota gold miners who
had worked at least a year underground between 1940 and 1965 were
studied by Steenland and Brown (1995b). Workers were followed though
1990 with 1,551 having died; loss to follow up was low (2 percent).
Chest x-rays taken in cross-sectional surveys in 1960 and 1976 and
death certificates were used to ascertain cases of silicosis. One
hundred twenty eight cases were found via death certificate, 29 by x-
ray (defined as ILO 1/1 or greater), and 13 by both. Nine percent of
deaths had silicosis mentioned on the death certificate. Inclusion of
death certificate diagnoses probably increases the risk estimates from
this study compared to those that rely exclusively on radiographic
findings to evaluate silicosis morbidity risk (see discussion of Hnizdo
et al. (1993) above).
    Exposure was estimated by conversion of impinger (particle count)
data and was based on measurements indicating an average of 13 percent
silica in the dust. Based on these data, the authors estimated the mean
exposure concentration to be 0.05 mg/m\3\ for the overall cohort, with
those hired before 1930 exposed to an average of 0.15 mg/m\3\. The
average duration of exposure for cases was 20 years (s.d = 8.7)
compared to 8.2 years (s.d = 7.9) for the rest of the cohort. This
study found that cumulative exposure was the best disease predictor,
followed by duration of exposure and average exposure. Lifetime risks
were estimated from Poisson regression models using standard life table
techniques. The authors estimated a risk of 47 percent associated with
45 years of exposure to 0.09 mg/m\3\ respirable crystalline silica,
which reduced to 35 percent after adjustment for age and calendar time.
3. Miller et al. (1995, 1998) and Buchanan et al. (2003) Study of
Scottish Coal Miners
    Miller et al. (1995, 1998) and Buchanan et al. (2003) reported on a
1990/1991 follow-up study of 547 survivors of a 1,416 member cohort of
Scottish coal workers from a single mine. These men had all worked in
the mine during a period between early 1971 and mid 1976, during which
they had experienced ``unusually high concentrations of freshly cut
quartz in mixed coalmine dust. The population's exposures to both coal
and quartz dust had been measured in unique detail, for a substantial
proportion of the men's working lives.'' Thus, this cohort allowed for
the study of the effects of both higher and lower silica
concentrations, and exposure-rate effects on the development of
silicosis. The 1,416 men had all had previous radiographs dating from
before, during, or just after this high concentration period, and the
547 participating survivors received their follow-up chest x-rays
between November 1990 and April 1991. Follow-up interviews consisted of
questions on current and past smoking habits, and occupational history
since leaving the coal mine, which closed in 1981.
    Silicosis cases were identified as such if the median
classification of the three readers indicated an ILO (1980)
classification of 1/0 or greater, plus a progression from the earlier
reading. Of the 547 men, 203 (38 percent) showed progression of at
least one ILO category from the 1970's surveys to the 1990-91 survey;
in 128 of these (24 percent) there was progression of two or more
steps. In the 1970's survey 504 men had a profusion score of 0; of
these, 120 (24 percent) progressed to an ILO classification of 1/0 or
greater. Of the 36 men who had shown earlier profusions of 1/0 or
greater, 27 (75 percent) showed further progression at the 1990/1991
follow-up. Only one subject showed a regression from any earlier
reading, and that was slight, from ILO 1/0 to 0/1.
    To study the effects of exposure to high concentrations of quartz
dust, the Buchanan et al. (2003) analysis presented the results of
logistic regression modeling that incorporated two independent terms
for cumulative exposure, one arising from exposure to concentrations
less than 2 mg/m\3\ respirable quartz and the other from exposure to
concentrations greater than or equal to 2 mg/m\3\. Both of the
cumulative quartz exposure concentration variables were ``highly
statistically significant in the presence of the other,'' and
independent of the presence of coal dust. Since these quartz variables
were in the same units, g-hr/m\3\, the authors noted that coefficient
for exposure concentrations equal to or above 2.0 mg/m\3\ was 3 times
that of the coefficient for concentrations less than 2.0 mg/m\3\. From
this, the authors concluded that their analysis showed that ``the risk
of silicosis over a working lifetime can rise dramatically with
exposure to such high concentrations over a timescale of merely a few
months.''
    Buchanan et al., (2003) provided analysis and risk estimates only
for silicosis cases defined as having an x-ray classified as ILO 2/1+,
after adjusting for the disproportionately severe effect of exposure to
high concentrations on silicosis risk. Estimating the risk of acquiring
a chest x-ray classified as ILO 1/0+ from the Buchanan (2003) or the
earlier Miller et al. (1995, 1998) publications can only be roughly
approximated because of the limited summary information included; this
information suggests that the risk of silicosis defined as an ILO
classification of 1/0+ could be about three times higher than the risk
of silicosis defined as an ILO 2/1+ x-ray. OSHA has a high degree of
confidence in the estimates of progression to stages 2/1+ from this
Scotland coal mine study, mainly because of the highly detailed and
extensive exposure measurements, the radiographic records, and the
detailed analyses of high exposure-rate effects.
4. Chen et al. (2001) Study of Tin Miners
    Chen et al. (2001) reported the results of a retrospective study of
a Chinese cohort of 3,010 underground miners who had worked in tin
mines at least one year between 1960 and 1965. They were followed
through 1994, by which time 2,426 (80.6%) workers had either retired or
died, and only 400 (13.3%) remained employed at the mines.
    The study incorporated occupational histories, dust measurements
and medical examination records. Exposure data consisted of high-flow,
short-term gravimetric total dust measurements made routinely since
1950; the authors used data from 1950 to represent earlier exposures
since dust control measures were not implemented until 1958. Results
from a 1998-1999 survey indicated that respirable silica measurements
were 3.6 percent (s.d = 2.5 percent) of total dust measurements. Annual
radiographs were taken since 1963 and all cohort members continued

to have chest x-rays taken every 2 or 3 years after leaving work.
Silicosis was diagnosed when at least 2 of 3 radiologists classified a
radiograph as being a ``suspected case'' or at Stage I, II, or III
under the 1986 Chinese pneumoconiosis roentgen diagnostic criteria.
According to Chen et al. (2001), these four categories under the
Chinese system were found to agree closely with ILO categories 0/1,
Category 1, Category 2, and Category 3, respectively, based on studies
comparing the Chinese and ILO classification systems. Silicosis was
observed in 33.7 percent of the group; 67.4 percent of the cases
developed after exposure ended.
5. Chen et al. (2005) Study of Chinese Pottery Workers, Tin Miners, and
Tungsten Miners
    In a later study, Chen et al. (2005) investigated silicosis
morbidity risks among three cohorts to determine if the risk varied
among workers exposed to silica dust having different characteristics.
The cohorts consisted of 4,547 pottery workers, 4,028 tin miners, and
14,427 tungsten miners selected from a total of 20 workplaces. Cohort
members included all males employed after January 1, 1950 and who
worked for at least one year between 1960 and 1974. Radiological
follow-up was through December 31, 1994 and x-rays were scored
according to the Chinese classification system as described above by
Chen et al. (2001) for the tin miner study. Exposure estimates of
cohort members to respirable crystalline silica were based on the same
data as described by Chen et al. (2001). In addition, the investigators
measured the extent of surface occlusion of crystalline silica
particles by alumino-silicate from 47 dust samples taken at 13
worksites using multiple-voltage scanning electron microscopy and
energy dispersive X-ray spectroscopy (Harrison et al., 2005); this
method yielded estimates of the percent of particle surface that is
occluded.
    Compared to tin and tungsten miners, pottery workers were exposed
to significantly higher mean total dust concentrations (8.2 mg/m\3\,
compared to 3.9 mg/m\3\ for tin miners and 4.0 mg/m\3\ for tungsten
miners), worked more net years in dusty occupations (mean of 24.9 years
compared to 16.4 years for tin miners and 16.5 years for tungsten
miners), and had higher mean cumulative dust exposures (205.6 mg/m\3\-
years compared to 62.3 mg/m\3\-years for tin miners and 64.9 mg/m\3\-
years for tungsten miners) (Chen et al., 2005). Applying the authors'
conversion factors to estimate respirable crystalline silica from
Chinese total dust measurements, the approximate mean cumulative
exposures to respirable silica for pottery, tin, and tungsten workers
are 6.4 mg/m\3\-years, 2.4 mg/m\3\-years, and 3.2 mg/m\3\-years,
respectively. Measurement of particle surface occlusion indicated that,
on average, 45 percent of the surface area of respirable particles
collected from pottery factory samples was occluded, compared to 18
percent of the particle surface area for tin mine samples and 13
percent of particle surface area for tungsten mines.
    Based on Chen et al. (2005), OSHA estimated the cumulative
silicosis risk associated with 45 years of exposure to 0.1 mg/m\3\
respirable crystalline silica (a cumulative exposure of 4.5 mg/m\3\-
years) to be 6 percent for pottery workers, 12 percent for tungsten
miners, and 40 percent for tin miners. For a cumulative exposure of
2.25 mg/m\3\-years (i.e., 45 years of exposure to 0.05 mg/m\3\),
cumulative silicosis morbidity risks were estimated to be 2, 2, and 10
percent for pottery workers, tungsten miners, and tin miners,
respectively. When cumulative silica exposure was adjusted to reflect
exposure to surface-active quartz particles (i.e., not occluded), the
estimated cumulative risk among pottery workers more closely
approximated those of the tin and tungsten miners, suggesting to the
authors that alumino-silicate occlusion of the crystalline particles in
pottery factories at least partially explained the lower risk seen
among workers, despite their having been more heavily exposed.
6. Summary of Silicosis Morbidity Risk Estimates.
    Table VI-2 presents OSHA's risk estimates for silicosis morbidity
that are derived from each of the studies described above. Estimates of
silicosis morbidity derived from the seven cohorts in cumulative risk
studies with post-employment follow-up range from 60 to 773 per 1,000
workers for 45-year exposures to the current general industry PEL of
0.10 mg/m\3\, and from 20 to 170 per 1,000 workers for a 45-year
exposure to the proposed PEL of 0.05 mg/m\3\. The study results provide
substantial evidence that the disease can progress for years after
exposure ends. Results from an autopsy study (Hnizdo et al., 1993),
which found pathological evidence of silicosis absent radiological
signs, suggest that silicosis cases based on radiographic diagnosis
alone tend to underestimate risk since pathological evidence of
silicosis. Other results (Chen et al., 2005) suggest that surface
properties among various types of silica dusts can have different
silicosis potencies. Results from the Buchanan et al. (2003) study of
Scottish coal miners suggest that short-term exposures to >2 mg/m\3\
silica can cause a disproportionately higher risk of silicosis than
would be predicted by cumulative exposure alone, suggesting a dose-rate
effect for exposures to concentrations above this level. OSHA believes
that, given the consistent finding of a monotonic exposure-response
relationship for silicosis morbidity with cumulative exposure in the
studies reviewed, that cumulative exposure is a reasonable exposure
metric upon which to base risk estimates in the exposure range of
interest to OSHA (i.e., between 0.025 and 0.5 mg/m\3\ respirable
crystalline silica).

F. Other Considerations in OSHA's Risk Analysis

    Uncertainties are inherent to any risk modeling process and
analysis; assessing risk and associated complexities of silica exposure
among workers is no different. However, the Agency has a high level of
confidence that the preliminary risk assessment results reasonably
reflect the range of risks experienced by workers exposed to silica in
all occupational settings. First, the preliminary assessment is based
on an analysis of a wide range of studies, conducted in multiple
industries across a wide range of exposure distributions, which
included cumulative exposures equivalent to 45 years of exposure to and
below the current PEL.
    Second, risk models employed in this assessment are based on a
cumulative exposure metric, which is the product of average daily
silica concentration and duration of worker exposure for a specific
job. Consequently, these models predict the same risk for a given
cumulative exposure regardless of the pattern of exposure. For example,
a manufacturing plant worker exposed to silica at 0.05 mg/m\3\ for
eight hours per day will have the same cumulative exposure over a given
period of time as a construction worker who is exposed each day to
silica at 0.1 mg/m\3\ for one hour, at 0.075 mg/m\3\ for four hours and
not exposed to silica for three hours. The cumulative exposure metric
thus reflects a worker's long-term average exposure without regard to
the pattern of exposure experienced by the worker, and is therefore
generally applicable to all workers who are exposed to silica in the
various industries. For example, at construction sites, conditions may
change often since the nature of work can be intermittent and involve
working with a variety of materials that contain different
concentrations of quartz. Additionally, workers may perform

construction operations for relatively short periods of time where they
are exposed to concentrations of silica that may be significantly
higher than many continuous operations in general industry. However,
these differences are taken into account by the use of the cumulative
exposure metric that relates exposure to disease risk. OSHA believes
that use of cumulative exposure is the most appropriate dose-metric
because each of the studies that provide the basis for the risk
assessment demonstrated strong exposure-response relationships between
cumulative exposure and disease risk. This metric is especially
important in terms of progression of silica-related disease, as
discussed in Section VII of the preamble, Significance of Risk, in
section B.1.a.
    OSHA's risk assessment relied upon many studies that utilized
cumulative exposures of cohort members. Table VI-3 summarizes these
lung cancer studies, including worker exposure quartile data across a
number of industry sectors. The cumulative exposures exhibited in these
studies are equivalent to the cumulative exposure that would result
from 45 years of exposure to the current and proposed PELs (i.e., 4.5
and 2,25 mg/m\3\, respectively). For this reason, OSHA has a high
degree of confidence in the risk estimates associated with exposure to
the current and proposed PELs; additionally, the risk assessment does
not require significant low-dose extrapolation of the model beyond the
observed range of exposures. OSHA acknowledges there is greater
uncertainty in the risk estimates for the proposed action level of
0.025 mg/m\3\, particularly given some evidence of a threshold for
silicosis between the proposed PEL and action level. Given the Agency's
findings that controlling exposures below the proposed PEL would not be
technologically feasible for employers, OSHA believes that estimating
risk for exposures below the proposed action level, which becomes
increasingly more uncertain, is not necessary to further inform the
Agency's regulatory action.
    Although the Agency believes that the results of its risk
assessment are broadly relevant to all occupational exposure situations
involving crystalline silica, OSHA acknowledges that differences exist
in the relative toxicity of crystalline silica particles present in
different work settings due to factors such as the presence of mineral
or metal impurities on quartz particle surfaces, whether the particles
have been freshly fractured or are aged, and size distribution of
particles. At this time, however, OSHA preliminarily concludes that it
is not yet possible to use available information on factors that
mediate the potency of silica to refine available quantitative
estimates of the lung cancer and silicosis mortality risks, and that
the estimates from the studies and analyses relied upon are fairly
representative of a wide range of workplaces reflecting differences in
silica polymorphism, surface properties, and impurities.

                                   Table VI-1--Estimates of Lifetime \a\ Lung Cancer Mortality Risk Resulting from 45-Years of Exposure to Crystalline Silica
                                                                      [Deaths per 1,000 workers (95% confidence interval)]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Exposure level (mg/m\3\)
                  Cohort                              Model               Exposure    Model parameters (standard -------------------------------------------------------------------------------
                                                                        lag (years)             error)                 0.025           0.05            0.10            0.25            0.50
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Ten pooled cohorts (see Table II-1)......  Log-linear \b\.............           15  [beta] = 0.60 (0.015)......      22 (11-36)      26 (12-41)      29 (13-48)      34 (15-56)      38 (17-63)
                                           Linear \b\.................           15  [beta] = 0.074950                 23 (9-38)      26 (10-43)      29 (11-47)      33 (12-53)      36 (14-58)
                                                                                (0.024121).
                                           Linear.....................           15  [beta]1 = 0.16498 (0.0653)         9 (2-16)       18 (4-31)       22 (6-38)      27 (12-43)      36 (20-51)
                                                                                and.
                                           SplineSec.  \c\ \d\........  ...........  [beta]2 = -0.1493 (0.0657).  ..............  ..............  ..............  ..............  ..............
Range from 10 cohorts....................  ...........................           15  Various....................         0.21-13         0.41-28         0.83-69         2.1-298         4.2-687
                                           Log-linear \c\.............  ...........                               ..............  ..............  ..............  ..............  ..............
Diatomaceous earth workers...............  Linear \c\.................           10  [beta] = 0.1441 \e\........        9 (2-21)       17 (5-41)      34 (10-79)     81 (24-180)    152 (46-312)
U.S.Granite workers......................  Log-linear \c\.............           15  [beta] = 0.19 \e\..........       11 (4-18)       25 (9-42)     60 (19-111)    250 (59-502)   653 (167-760)
North American industrial sand workers...  Log-linear \c\.............           15  [beta] = 0.13 (0.074) \f\..        7 (0-16)       15 (0-37)       34 (0-93)     120 (0-425)     387 (0-750)
British coal miners......................  Log-linear \c\.............           15  [Bgr] = 0.0524 (0.0188)....         3 (1-5)        6 (2-11)       13 (4-23)       37 (9-75)     95 (20-224)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\a\ Risk to age 85 and based on 2006 background mortality rates for all males (see Appendix for life table method).
\b\ Model with log cumulative exposure (mg/m\3\-days + 1).
\c\ Model with cumulative exposure (mg/m\3\-years).
\d\ 95% confidence interval calculated as follows (where CE = cumulative exposure in mg/m\3\-years and SE is standard error of the parameter estimate):
For CE <= 2.19: 1 + [([beta]1  (1.96*SE1)) * CE].
For CE > 2.19: 1 + [([beta]1 * CE) + ([beta]2 * (CE-2.19))]  1.96 * SQRT[ (CE\2\ * SE1\2\) + ((CE-2.19)\2\* SE2\2\) + (2*CE*(CE-3.29)*-0.00429)].
\e\ Standard error not reported, upper and lower confidence limit on beta estimated from confidence interval of risk estimate reported in original article.
\f\ Standard error of the coefficient was estimated from the p-value for trend.

               Table VI-2--Summary of Lifetime or Cumulative Risk Estimates for Crystalline Silica
----------------------------------------------------------------------------------------------------------------
                                    Risk associated with 45 years of occupational exposure (per 1,000 workers)
                                 -------------------------------------------------------------------------------
    Health endpoint (source)                  Respirable crystalline silica exposure level (mg/m\3\)
                                 -------------------------------------------------------------------------------
                                       0.025           0.05            0.100           0.250           0.500
----------------------------------------------------------------------------------------------------------------
Lung Cancer Mortality (Lifetime
 Risk):
    Pooled Analysis,                        9-23           18-26           22-29           27-34           36-38
     Toxichemica, Inc (2004) \a\
     \b\........................

    Diatomaceous Earth Worker                  9              17              34              81             152
     study (Rice et al., 2001)
     \a\ \c\....................
    U.S. Granite Worker study                 11              25              60             250             653
     (Attfield and Costello,
     2004) \a\ \d\..............
    North American Industrial                  7              15              34             120             387
     Sand Worker study (Hughes
     et al., 2001) \a\ \e\......
    British Coal Miner study                   3               6              13              37              95
     (Miller and MacCalman,
     2009) \a\ \f\..............
Silicosis and Non-Malignant Lung
 Disease Mortality (Lifetime
 Risk):
    Pooled Analysis                            4               7              11              17              22
     (Toxichemica, Inc., 2004)
     (silicosis) \g\............
    Diatomaceous Earth Worker                 22              43              83             188             321
     study (Park et al., 2002)
     (NMRD) \h\.................
Renal Disease Mortality
 (Lifetime Risk):
    Pooled Cohort study                       25              32              39              52              63
     (Steenland et al., 2002a)..
Silicosis Morbidity (Cumulative
 Risk):
    Chest x-ray category of 2/1               21              55             301             994            1000
     or greater (Buchanan et
     al., 2003) \j\.............
    Silicosis mortality and/or x-             31              74             431             593             626
     ray of 1/1 or greater
     (Steenland and Brown,
     1995b) \k\.................
    Chest x-ray category of 1/1                6             127             773             995            1000
     or greater (Hnizdo and
     Sluis-Cremer, 1993) \l\....
    Chest x-ray category of 1 or              40             170             590            1000            1000
     greater (Chen et al., 2001)
     \m\........................
    Chest x-ray category of 1 or  ..............  ..............  ..............  ..............  ..............
     greater (Chen et al., 2005)
     \n\
        Tin miners..............              40             100             400             950            1000
        Tungsten miners.........               5              20             120             750            1000
        Pottery workers.........               5              20              60             300             700
----------------------------------------------------------------------------------------------------------------
From Table II-12, ``Respirable Crystalline Silica--Health Effects Literature Review and Preliminary Quantitative
  Risk Assessment'' (Docket OSHA-2010-0034).

                                                                    Table VI-3--Exposure Distribution in Lung Cancer Studies
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Cum(exp) (mg/m\3\-y)                 Average* exposure (mg/m\3\)        Mean respirable
                                                                                No. of   --------------------------------------------------------------------------------    crystalline
                                                         Primary  exposure (as       deaths                                                                                silica exposure
                  Study                        n          described  in study)      from lung             median                         25th     median     75th               over employment
                                                                                cancer      q\1\     (q\2\)     q\3\       max     (q\1\)    (q\2\)    (q\3\)      max       period (mg/
                                                                                m[caret]3)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. diatomaceous earth workers \1\            2,342  cristobalite...............          77      0.37      1.05      2.48     62.52      0.11      0.18      0.46      2.43                n/a
 (Checkoway et al., 1997).
S. African gold miners \1\ (Hnizdo and         2,260  quartz and other silicates.          77       n/a      4.23       n/a       n/a      0.15      0.19      0.22      0.31                n/a
 Sluis-cremer, 1991 & Hnizdo et al.,
 1997).
U.S. gold miners \1\ (Steenland and            3,328  silica dust................         156       0.1      0.23      0.74       6.2      0.02      0.05       0.1      0.24                n/a
 Brown, 1995a).
Australian gold miners \1\ (de Klerk and       2,297  silica dust................         135      6.52     11.37     17.31     50.22      0.25      0.43      0.65      1.55                n/a
 Musk, 1998).
U.S. granite workers (Costello and             5,414  silica dust from granite...         124      0.14      0.71      2.19        50      0.02      0.05      0.08      1.01                n/a
 Graham, 1988).
Finnish granite workers (Koskela et al.,       1,026  quartz dust................          38      0.84      4.63     15.42    100.98      0.39      0.59      1.29       3.6                n/a
 1994).

U.S. industrial sand workers \1\               4,626  silica dust................          85      0.03      0.13       5.2     8.265      0.02      0.04      0.06       0.4                n/a
 (Steenland et al., 2001b).
North American industrial sand workers            90  crystalline silica.........          95      1.11      2.73      5.20       n/a     0.069      0.15     0.025       n/a                n/a
 \1\ (Hughes et al., 2001).
Ch. Tungsten (Chen et al., 1992).........     28,442  silica dust................         174      3.49      8.56     29.79    232.26      0.15      0.32      1.28      4.98                6.1
Ch. Pottery (Chen et al., 1992)..........     13,719  silica dust................          81      3.89      6.07      9.44     63.15      0.18      0.22      0.34       2.1               11.4
Ch. Tin (Chen et al., 1992)..............      7,849  silica dust................         119      2.79      5.27      5.29     83.09      0.12      0.19      0.49      1.95                7.7
British coal workers \1\ (Miller and          17,820  quartz.....................         973       n/a       n/a       n/a       n/a       n/a       n/a       n/a       n/a                n/a
 MacCalman, 2009).
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Study adjusted for effects smoking.
* Average exposure is cumulative exposure averaged over the entire exposure period.
n/a Data not available.

VII. Significance of Risk

A. Legal Requirements

    To promulgate a standard that regulates workplace exposure to toxic
materials or harmful physical agents, OSHA must first determine that
the standard reduces a ``significant risk'' of ``material impairment.''
The first part of this requirement, ``significant risk,'' refers to the
likelihood of harm, whereas the second part, ``material impairment,''
refers to the severity of the consequences of exposure.
    The Agency's burden to establish significant risk derives from the
OSH Act, 29 U.S.C. 651 et seq. Section 3(8) of the Act requires that
workplace safety and health standards be ``reasonably necessary and
appropriate to provide safe or healthful employment.'' 29 U.S.C.
652(8). The Supreme Court, in the ``benzene'' decision, stated that
section 3(8) ``implies that, before promulgating any standard, the
Secretary must make a finding that the workplaces in question are not
safe.'' Indus. Union Dep't, AFL-CIO v. Am. Petroleum Inst., 448 U.S.
607, 642 (1980). Examining section 3(8) more closely, the Court
described OSHA's obligation to demonstrate significant risk:

``[S]afe'' is not the equivalent of ``risk-free.'' A workplace can
hardly be considered ``unsafe'' unless it threatens the workers with
a significant risk of harm. Therefore, before the Secretary can
promulgate any permanent health or safety standard, he must make a
threshold finding that the place of employment is unsafe in the
sense that significant risks are present and can be eliminated or
lessened by a change in practices.

    Id. While clarifying OSHA's responsibilities, the Court emphasized
the Agency's discretion in determining what constitutes significant
risk, stating, ``[the Agency's] determination that a particular level
of risk is `significant' will be based largely on policy
considerations.'' Benzene, 448 U.S. at 655, n. 62. The Court explained
that significant risk is not a ``mathematical straitjacket,'' and
maintained that OSHA could meet its burden without ``wait[ing] for
deaths to occur before taking any action.'' Benzene, 448 U.S. at 655.
    Because section 6(b)(5) of the Act requires that the Agency base
its findings on the ``best available evidence,'' a reviewing court must
``give OSHA some leeway where its findings must be made on the
frontiers of scientific knowledge.'' Benzene, 448 U.S. at 656. Thus,
while OSHA's significant risk determination must be supported by
substantial evidence, the Agency ``is not required to support the
finding that a significant risk exists with anything approaching
scientific certainty.'' Id. Furthermore, ``the Agency is free to use
conservative assumptions in interpreting the data with respect to
carcinogens, risking error on the side of over protection rather than
under protection,'' so long as such assumptions are based in ``a body
of reputable scientific thought.'' Id.
    The Act also requires that the Agency make a finding that the toxic
material or harmful physical agent at issue causes material impairment
to workers' health. Section 6(b)(5) of the Act directs the Secretary of
Labor to ``set the standard which most adequately assures, to the
extent feasible, on the basis of the best available evidence, that no
employee will suffer material impairment of health or functional
capacity even if such employee has regular exposure to the hazard . . .
for the period of his working life.'' 29 U.S.C. 655(b)(5). As with
significant risk, what constitutes material impairment in any given
case is a policy determination for which OSHA is given substantial
leeway. ``OSHA is not required to state with scientific certainty or
precision the exact point at which each type of [harm] becomes a
material impairment.'' AFL-CIO v. OSHA, 965 F.2d 962, 975 (11th Cir.
1992). Courts have also noted that OSHA should consider all forms and
degrees of material impairment--not just death or serious physical
harm--and that OSHA may act with a ``pronounced bias towards worker
safety.'' Id; Bldg & Constr. Trades Dep't v. Brock, 838 F.2d 1258, 1266
(D.C. Cir. 1988).
    It is the Agency's practice to estimate risk to workers by using
quantitative

risk assessment and determining the significance of that risk based on
judicial guidance, the language of the OSH Act, and Agency policy
considerations. Thus, using the best available evidence, OSHA
identifies material health impairments associated with potentially
hazardous occupational exposures, and, when possible, provides a
quantitative assessment of exposed workers' risk of these impairments.
The Agency then evaluates whether these risks are severe enough to
warrant regulatory action and determines whether a new or revised rule
will substantially reduce these risks.
    In this case, OSHA has reviewed extensive toxicological,
epidemiological, and experimental research pertaining to adverse health
effects of occupational exposure to respirable crystalline silica,
including silicosis, other non-malignant respiratory disease, lung
cancer, and autoimmune and renal diseases. As a result of this review,
the Agency has developed preliminary quantitative estimates of the
excess risk of mortality and morbidity that is attributable to
currently allowable respirable crystalline silica exposure
concentrations. The Agency is proposing a new PEL of 0.05 mg/m\3\
because exposures at and above this level present a significant risk to
workers' health. Even though OSHA's preliminary risk assessment
indicates that a significant risk exists at the proposed action level
of 0.025 mg/m\3\, the Agency is not proposing a PEL below the proposed
0.05 mg/m\3\ limit because OSHA must also consider technological and
economic feasibility in determining exposure limits. As explained in
the Summary and Explanation for paragraph (c), Permissible Exposure
Limit (PEL), OSHA has preliminary determined that the proposed PEL of
0.05 mg/m\3\ is technologically and economically feasible, but that a
lower PEL of 0.025 mg/m\3\ is not technologically feasible. OSHA has
preliminarily determined that long-term exposure at the current PEL
presents a significant risk of material harm to workers' health, and
that adoption of the proposed PEL will substantially reduce this risk
to the extent feasible.
    As discussed in Section V of this preamble (Health Effects
Summary), inhalation exposure to respirable crystalline silica
increases the risk of a variety of adverse health effects, including
silicosis, chronic obstructive pulmonary disease (COPD), lung cancer,
immunological effects, kidney disease, and infectious tuberculosis
(TB). OSHA considers each of these conditions to be a material
impairment of health. These diseases result in significant discomfort,
permanent functional limitations including permanent disability or
reduced ability to work, reduced quality of life, and decreased life
expectancy. When these diseases coexist, as is common, the effects are
particularly debilitating (Rice and Stayner, 1995; Rosenman et al.,
1999). Based on these findings and on the scientific evidence that
respirable crystalline silica substantially increases the risk of each
of these conditions, OSHA preliminarily concludes that workers who are
exposed to respirable crystalline silica at the current PEL are at
significant risk of material impairment of health or functional
capacity.

B. OSHA's Preliminary Findings

1. Material Impairments of Health
    Section I of OSHA's Health Effects Literature Review and
Preliminary Quantitative Risk Assessment (available in Docket OSHA-
2010-0034) describes in detail the adverse health conditions that
workers who are exposed to respirable crystalline silica are at risk of
developing. The Agency's findings are summarized in Section V of this
preamble (Health Effects Summary). The adverse health effects discussed
include lung cancer, silicosis, other non-malignant respiratory disease
(NMRD), and immunological and renal effects.
a. Silicosis
    Silicosis refers to a spectrum of lung diseases attributable to the
inhalation of respirable crystalline silica. As described in Section V
(Health Effects Summary), the three types of silicosis are acute,
accelerated, and chronic. Acute silicosis can occur within a few weeks
to months after inhalation exposure to extremely high levels of
respirable crystalline silica. Death from acute silicosis can occur
within months to a few years of disease onset, with the exposed person
drowning in their own lung fluid (NIOSH, 1996). Accelerated silicosis
results from exposure to high levels of airborne respirable crystalline
silica, and disease usually occurs within 5 to 10 years of initial
exposure (NIOSH, 1996). Both acute and accelerated silicosis are
associated with exposures that are substantially above the current
general industry PEL, although precise information on the relationships
between exposure and occurrence of disease are not available.
    Chronic silicosis is the most common form of silicosis seen today,
and is a progressive and irreversible condition characterized as a
diffuse nodular pulmonary fibrosis (NIOSH, 1996). Chronic silicosis
generally occurs after 10 years or more of inhalation exposure to
respirable crystalline silica at levels below those associated with
acute and accelerated silicosis. Affected workers may have a dry
chronic cough, sputum production, shortness of breath, and reduced
pulmonary function. These symptoms result from airway restriction
caused by the development of fibrotic scarring in the alveolar sacs and
the ends of the lung tissue. The scarring can be detected in chest x-
ray films when the lesions become large enough to appear as visible
opacities. The result is restriction of lung volumes and decreased
pulmonary compliance with concomitant reduced gas transfer (Balaan and
Banks, 1992). Chronic silicosis is characterized by small, rounded
opacities that are symmetrically distributed in the upper lung zones on
chest radiograph.
    The diagnosis of silicosis is based on a history of exposure to
respirable crystalline silica, chest radiograph findings, and the
exclusion of other conditions, including tuberculosis (TB). Because
workers affected by early stages of chronic silicosis are often
asymptomatic, the finding of opacities in the lung is key to detecting
silicosis and characterizing its severity. The International Labour
Organization (ILO) International Classification of Radiographs of
Pneumoconioses (ILO, 1980, 2002, 2011) is the currently accepted
standard against which chest radiographs are evaluated in epidemiologic
studies, for medical surveillance, and for clinical evaluation. The ILO
system standardizes the description of chest x-rays, and is based on a
12-step scale of severity and extent of silicosis as evidenced by the
size, shape, and density of opacities seen on the x-ray film. Profusion
(frequency) of small opacities is classified on a 4-point major
category scale (0-3), with each major category divided into three,
giving a 12-point scale between 0/- and 3/+. Large opacities are
defined as any opacity greater than 1 cm that is present in a film.
    The small rounded opacities seen in early stage chronic silicosis
(i.e., ILO major category 1 profusion) may progress (through ILO major
categories 2 and/or 3) and develop into large fibrotic masses that
destroy the lung architecture, resulting in progressive massive
fibrosis (PMF). This stage of advanced silicosis is usually
characterized by impaired pulmonary function, disability, and premature
death. In cases involving PMF, death is commonly attributable to
progressive respiratory insufficiency (Balaan and Banks, 1992).

    The appearance of ILO category 2 or 3 background profusion of small
opacities has been shown to increase the risk of developing large
opacities characteristic of PMF. In one study of silicosis patients in
Hong Kong, Ng and Chan (1991) found the risk of PMF increased by 42 and
64 percent among patients whose chest x-ray films were classified as
ILO major category 2 or 3, respectively. Research has shown that people
with silicosis advanced beyond ILO major category 1 have reduced median
survival times compared to the general population (Infante-Rivard et
al., 1991; Ng et al., 1992a; Westerholm, 1980).
    Silicosis is the oldest known occupational lung disease and is
still today the cause of significant premature mortality. In 2005,
there were 161 deaths in the U.S. where silicosis was recorded as an
underlying or contributing cause of death on a death certificate
(NIOSH, 2008c). Between 1996 and 2005, deaths attributed to silicosis
resulted in an average of 11.6 years of life lost by affected workers
(NIOSH, 2007). In addition, exposure to respirable crystalline silica
remains an important cause of morbidity and hospitalizations. State-
based hospital discharge data show that in the year 2000, 1,128
silicosis-related hospitalizations occurred, indicating that silicosis
continues to be a significant health issue in the U.S. (CSTE, 2005).
Although there is no national silicosis disease surveillance system in
the U.S., a published analysis of state-based surveillance data from
the time period 1987-1996 estimated that between 3,600-7,000 new cases
of silicosis occurred in the U.S. each year (Rosenman et al., 2003). It
has been widely reported that available statistics on silicosis-related
mortality and morbidity are likely to be understated due to
misclassification of causes of death (for example, as tuberculosis,
chronic bronchitis, emphysema, or cor pulmonale), errors in recording
occupation on death certificates, or misdiagnosis of disease by health
care providers (Goodwin, 2003; Windau et al., 1991; Rosenman et al.,
2003). Furthermore, reliance on chest x-ray findings may miss cases of
silicosis because fibrotic changes in the lung may not be visible on
chest radiograph; thus, silicosis may be present absent x-ray signs or
may be more severe than indicated by x-ray (Hnizdo et al., 1993;
Craighead and Vallyathan, 1980; Rosenman et al., 1997).
    Although most workers with early-stage silicosis (ILO categories 0/
1 or 1/0) typically do not experience respiratory symptoms, the primary
risk to the affected worker is progression of disease with progressive
decline of lung function. Several studies of workers exposed to
crystalline silica have shown that, once silicosis is detected by x-
ray, a substantial proportion of affected workers can progress beyond
ILO category 1 silicosis, even after exposure has ceased (for example,
Hughes et al., 1982; Hessel et al., 1988; Miller et al., 1998; Ng et
al., 1987a; Yang et al., 2006). In a population of coal miners whose
last chest x-ray while employed was classified as major category 0, and
who were examined again 10 years after the mine had closed, 20 percent
had developed opacities consistent with a classification of at least 1/
0, and 4 percent progressed further to at least 2/1 (Miller et al.,
1998). Although there were periods of extremely high exposure to
respirable quartz in the mine (greater than 2 mg/m\3\ in some jobs
between 1972 and 1976, and more than 10 percent of exposures between
1969 and 1977 were greater than 1 mg/m\3\), the mean cumulative
exposure for the cohort over the period 1964-1978 was 1.8 mg/m\3\-
years, corresponding to an average silica concentration of 0.12 mg/
m\3\. In a population of granite quarry workers exposed to an average
respirable silica concentration of 0.48 mg/m\3\ (mean length of
employment was 23.4 years), 45 percent of those diagnosed with simple
silicosis showed radiological progression of disease after 2 to 10
years of follow up (Ng et al., 1987a). Among a population of gold
miners, 92 percent progressed in 14 years; exposures of high-, medium-,
and low-exposure groups were 0.97, 0.45, and 0.24 mg/m\3\, respectively
(Hessel et al., 1988). Chinese mine and factory workers categorized
under the Chinese system of x-ray classification as ``suspected''
silicosis cases (analogous to ILO 0/1) had a progression rate to stage
I (analogous to ILO major category 1) of 48.7 percent and the average
interval was about 5.1 years (Yang et al., 2006). These and other
studies discussed in the Health Effects section are of populations of
workers exposed to average concentrations of respirable crystalline
silica above those permitted by OSHA's current general industry PEL.
The studies, however, are of interest to OSHA because the Agency's
current enforcement data indicate that exposures in this range are
still common in some industry sectors. Furthermore, the Agency's
preliminary risk assessment is based on use of an exposure metric that
is less influenced by exposure pattern and, instead, characterizes the
accumulated exposure of workers over time. Further, the use of a
cumulative exposure metric reflects the progression of silica-related
diseases: While it is not known that silicosis is a precursor to lung
cancer, continued exposure to respirable crystalline silica among
workers with silicosis has been shown to be associated with malignant
respiratory disease (Chen et al., 1992). The Chinese pottery workers
study offers an example of silicosis-associated lung cancer among
workers in the clay industry, reflecting the variety of health outcomes
associated with diverse silica exposures across industrial settings.
    The risk of silicosis, and particularly its progression, carries
with it an increased risk of reduced lung function. There is strong
evidence in the literature for the finding that lung function
deteriorates more rapidly in workers exposed to silica, especially
those with silicosis, than what is expected from a normal aging process
(Cowie 1998; Hughes et al., 1982; Malmberg et al., 1993; Ng and Chan,
1992). The rates of decline in lung function are greater in those whose
disease showed evidence of radiologic progression (B[eacute]gin et al.,
1987a; Cowie 1998; Ng and Chan, 1992; Ng et al., 1987a). Additionally,
the average deterioration of lung function exceeds that in smokers
(Hughes et al., 1982).
    Several studies have reported no decrease in pulmonary function
with an ILO category 1 level of profusion of small opacities but found
declines in pulmonary function with categories 2 and 3 (Ng et al.,
1987a; Begin et al., 1988; Moore et al., 1988). A study by Cowie
(1998), however, found a statistically significantly greater annual
loss in FVC and FEV1 among those with category 1 profusion
compared to category 0. In another study, Cowie and Mabena (1991) found
that the degree of profusion of opacities was associated with
reductions in several pulmonary function metrics. Still, other studies
have reported no associations between radiographic silicosis and
decreases in pulmonary function (Ng et al., 1987a; Wiles et al., 1992;
Hnizdo, 1992), with some studies (Ng et al., 1987a; Wang et al., 1997)
finding that measurable changes in pulmonary function are evident well
before the changes seen on chest x-ray. This may reflect the general
insensitivity of chest radiography in detecting lung fibrosis, and/or
may reflect that exposure to respirable silica has also been shown to
increase the risk of chronic obstructive pulmonary disease (COPD) (see
Section V, Health Effects Summary).
    Finally, silicosis, and exposure to respirable crystalline silica
in and of itself, increases the risk that latent

tuberculosis infection can convert to active disease. Early
descriptions of dust diseases of the lung did not distinguish between
TB and silicosis, and most fatal cases described in the first half of
this century were a combination of silicosis and TB (Castranova et al.,
1996). More recent findings demonstrate that exposure to silica, even
without silicosis, increases the risk of infectious (i.e., active)
pulmonary TB (Sherson et al., 1990; Cowie, 1994; Hnizdo and Murray,
1998; WaterNaude et al., 2006). Both conditions together can hasten the
development of respiratory impairment and increase mortality risk even
beyond that experienced by unexposed persons with active TB (Banks,
2005).
    Based on the information presented above and in its review of the
health literature, OSHA preliminarily concludes that silicosis remains
a significant cause of early mortality and of serious morbidity,
despite the existence of an enforceable exposure limit over the past 40
years. Silicosis in its later stages of progression (i.e., with chest
x-ray findings of ILO category 2 or 3 profusion of small opacities, or
the presence of large opacities) is characterized by the likely
appearance of respiratory symptoms and decreased pulmonary function, as
well as increased risk of progression to PMF, disability, and early
mortality. Early-stage silicosis, although without symptoms among many
who are affected, nevertheless reflects the formation of fibrotic
lesions in the lung and increases the risk of progression to later
stages, even after exposure to respirable crystalline silica ceases. In
addition, the presence of silicosis increases the risk of pulmonary
infections, including conversion of latent TB infection to active TB.
Silicosis is not a reversible condition and there is no specific
treatment for the disease, other than administration of drugs to
alleviate inflammation and maintain open airways, or administration of
oxygen therapy in severe cases. Based on these considerations, OSHA
preliminarily finds that silicosis of any form, and at any stage, is a
material impairment of health and that fibrotic scarring of the lungs
represents loss of functional respiratory capacity.
b. Lung Cancer
    OSHA considers lung cancer, an irreversible and usually fatal
disease, to be a clear material impairment of health. According to the
National Cancer Institute (Horner et al., 2009), the five-year survival
rate for all forms of lung cancer is only 15.6 percent, a rate that has
not improved in nearly two decades. OSHA's preliminary finding that
respirable crystalline silica exposure substantially increases the risk
of lung cancer mortality is based on the best available toxicological
and epidemiological data, reflects substantial supportive evidence from
animal and mechanistic research, and is consistent with the conclusions
of other government and public health organizations, including the
International Agency for Research on Cancer (IARC, 1997), the National
Toxicology Program (NTP, 2000), the National Institute for Occupational
Safety and Health (NIOSH, 2002), the American Thoracic Society (1997),
and the American Conference of Governmental Industrial Hygienists
(ACGIH, 2001). The Agency's primary evidence comes from evaluation of
more than 50 studies of occupational cohorts from many different
industry sectors in which exposure to respirable crystalline silica
occurs, including granite and stone quarrying; the refractory brick
industry; gold, tin, and tungsten mining; the diatomaceous earth
industry; the industrial sand industry; and construction. Studies key
to OSHA's risk assessment are outlined in Table VII-1, which summarizes
exposure characterization and related lung cancer risk across several
different industries. In addition, the association between exposure to
respirable crystalline silica and lung cancer risk was reported in a
national mortality surveillance study (Calvert et al., 2003) and in two
community-based studies (Pukkala et al., 2005; Cassidy et al., 2007),
as well as in a pooled analysis of 10 occupational cohort studies
(Steenland et al., 2001a).

                                                    Table VII-1-- Summary of Key Lung Cancer Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                  Type of study and
   Industry sector/population      description of          Exposure       No. of lung cancer   Risk ratios (95%       Additional            Source
                                     population        characterization      deaths/cases             CI)             information
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Diatomaceous earth workers  Cohort study. Same  Assessment based on  77................  SMR 129 (CI 101-    Smoking history     Checkoway et al.,
                                  as Checkoway et     almost 6,400                             161) based on       available for       1997.
                                  al., 1993,          samples taken from                       national rates,     half cohort.
                                  excluding 317       1948-1988; about                         and SMR 144 (CI     Under worst-case
                                  workers whose       57 percent of                            114-180) based on   assumptions, the
                                  exposures could     samples                                  local rates. Risk   risk ratio for
                                  not be              represented                              ratios by           the high-exposure
                                  characterized,      particle counts,                         exposure quintile   group would be
                                  and including 89    17 percent were                          were 1.00, 0.96,    reduced to 1.67
                                  workers with        personal                                 0.77, 1.26, and     after accounting
                                  asbestos exposure   respirable dust                          2.15, with the      for smoking.
                                  who were            samples. JEM                             latter being
                                  previously          included 135 jobs                        stat. sig. RR=
                                  excluded from the   over 4 time                              2.15 and 1.67.
                                  1993 study.         periods (Seixas et
                                  Follow up through   al., 1997).
                                  1994.
South African gold miners......  Cohort study.       Particle count data  77................  RR 1.023 (CI 1.005- Model adjusted for  Hnizdo and Sluis-
                                  N=2,209 white       from Beadle (1971).                      1.042) per 1,000    smoking and year    Cremer, 1991.
                                  male miners                                                  particle-years of   of birth. Lung
                                  employed between                                             exposure based on   cancer was
                                  1936 and 1943.                                               Cox proportional    associated with
                                  Followed from                                                hazards model.      silicosis of the
                                  1968-1986.                                                                       hilar glands not
                                                                                silicosis of lung
                                                                                or pleura.
                                                                                Possible
                                                                                confounding by
                                                                                radon exposure
                                                                                among miners with
                                                                                20 or more years
                                                                                experience.

South African gold miners......  Nested case-        Particle count data  78................  RR 2.45 (CI 1.2-    Lung cancer         Hnizdo et al.,
                                  control study       converted to                             5.2) when           mortality           1997.
                                  from population     respirable dust                          silicosis was       associated with
                                  study by Hnizdo     mass (Beadle and                         included in model.  smoking,
                                  and Sluis-          Bradley, 1970, and                                           cumulative dust
                                  Cremer,1991. N=78   Page-Shipp and                                               exposure, and
                                  cases, 386          Harris, 1972).                                               duration of
                                  controls.                                                                        underground work.
                                                                                Latter two
                                                                                factors were most
                                                                                significantly
                                                                                associated with
                                                                                lung cancer with
                                                                                exposure lagged
                                                                                20 years.
US gold miners.................  Cohort and nested   Particle count       115...............  SMR 113 (CI 94-     Smoking data        Steenland and
                                  case-control        data, conversion                         136) overall.       available for       Brown, 1995a,
                                  study, same         to mass                                  SMRs increased      part of cohort,     1995b
                                  population as       concentration                            for workers with    habits comparable
                                  Brown et al.        based on Vt.                             30 or more years    to general US
                                  (1986); workers     Granite study,                           of latency, and     population;
                                  with at least 1     construction of                          when local cancer   attributable
                                  year underground    JEM. Median quartz                       rates used as       smoking-related
                                  work between 1940   exposures were                           referents. Case-    cancer risk
                                  and 1965. Follow    0.15, 0.07, and                          control study       estimated to be
                                  up through 1990.    0.02 mg/m\3\ prior                       showed no           1.07.
                                                      to 1930, from 1930-                      relationship of
                                                      1950, and after                          risk to
                                                      1950 respectively.                       cumulative
                                                                                exposure to dust.
Australian gold miners.........  Cohort and nested   Expert ranking of    Nested case         SMR 126 (CI 107-    Association         de Klerk and Musk,
                                  case-control        dustiness by job.    control of 138      159) lower bound;   between exposure    1998
                                  study. N=2,297,                          lung cancer         SMR 149 (CI 126-    and lung cancer
                                  follow up of                             deaths.             176) upper bound.   mortality not
                                  Armstrong et al.                                             From case-          stat. sig. after
                                  (1979). Follow up                                            control, RR 1.31    adjusting for
                                  through 1993.                                                (CI 1.10-1.7) per   smoking,
                                                                                unit exposure       bronchitis, and
                                                                                score.              silicosis.
                                                                                Authors concluded
                                                                                lung cancer
                                                                                restricted to
                                                                                miners who
                                                                                received
                                                                                compensation for
                                                                                silicosis..
U.S. (Vermont) granite shed and  Cohort study.       Exposure data not    53 deaths among     SMR 129 for pre-    Dust controls       Costello and
 quarry workers -.                N=5,414 employed    used in analysis.    those hired         1930 hires (not     employed between    Graham, 1988.
                                  at least 1 year                          before 1930; 43     stat. sig.); SMR    1938 and 1940
                                  between 1950 and                         deaths among        95 for post-1940    with continuing
                                  1982.                                    those hired after   hires (not stat.    improvement
                                                                           1940.               sig). SMR 181       afterwards.
                                                                                (stat. sig) for
                                                                                shed workers
                                                                                hired before 1930
                                                                                and with long
                                                                                tenure and
                                                                                latency.
Finnish granite workers........  Cohort and nested   Personal sampling    31 through 1989...  Through 1989, SMR   Smoking habits      Koskela et al.,
                                  case-control        data collected                           140 (CI 98-193).    similar to other    1987, 1990, 1994.
                                  studies. N=1,026,   from 1970-1972                           For workers in      Finnish
                                  follow up from      included total and                       two regions where   occupational
                                  1972-1981,          respirable dust                          silica content of   groups. Minimal
                                  extended to 1985    and respirable                           rock was highest,   work-related
                                  (Koskella et al.,   silica sampling.                         SMRs were 126 (CI   exposures to
                                  1990) and 1989      Average silica                           71-208) and 211     other carcinogens.
                                  (Koskella et al.,   concentrations                           (CI 120-342),
                                  1994).              ranged form 0.3-                         respectively.
                                                      4.9 mg/m\3\.
North American industrial sand   Case-control study  Assessment based on  95 cases, two       OR 1.00, 0.84,      Adjusted for        Hughes et al.,
 workers.                         from McDonald et    14,249 respirable    controls per case.  2.02 and 2.07 for   smoking. Positive   2001.
                                  al. (2001) cohort.  dust and silica                          increasing          association
                                                      samples taken from                       quartiles of        between silica
                                                      1974 to 1998.                            exposure p for      exposure and lung
                                                      Exposures prior to                       trend=0.04).        cancer. Median
                                                      this based on                                                exposure for
                                                      particle count                                               cases and
                                                      data. Adjustments                                            controls were
                                                      made for                                                     0.148 and 0.110
                                                      respirator use                                               mg/m\3\
                                                      (Rando et al.,                                               respirable
                                                      2001).                                                       silica,
                                                                                respectively.

U.S. industrial sand workers...  Cohort and nested   Exposure assessment  109 deaths overall  SMR 160 (CI 131-    Smoking data from   Steenland and
                                  case-control        based on 4,269                           193) overall.       358 workers         Sanderson, 2001.
                                  study. N=4,626      compliance dust                          Positive trends     suggested that
                                  workers. Follow     samples taken from                       seen with           smoking could not
                                  up from 1960-1996.  1974-1996 and                            cumulative silica   explain the
                                                      analyzed for                             exposure (p=0.04    observed increase
                                                      respirable quartz.                       for unlagged,       in lung cancer
                                                      Exposures prior to                       p=0.08 for          mortality rates.
                                                      1974 based on                            lagged).
                                                      particle count
                                                      data and quartz
                                                      analysis of
                                                      settled dust and
                                                      dust collected by
                                                      high-volume air
                                                      samplers, and use
                                                      of a conversion
                                                      factor (1
                                                      mppcf=0.1 mg/m\3\).
Chinese Tin, Tungsten, and       Cohort study.       Measurements for     ..................  SMRs 198 for tin    Non-statistically   Chen et al., 1992.
 Copper miners.                   N=54,522 workers    total dust, quartz                       workers (no CI      significantly
                                  employed 1 yr. or   content, and                             reported but        increased risk
                                  more between 1972   particle size                            stat. sig.). No     ratio for lung
                                  and 1974. Follow    taken from 1950's-                       stat. sig.          cancer among
                                  up through 1989.    1980's. Exposures                        increased SMR for   silicotics. No
                                                      categorized as                           tungsten or         increased
                                                      high, medium, low,                       copper miners.      gradient in risk
                                                      or non-exposed.                                              observed with
                                                                                exposure.
Chinese Pottery workers........  Cohort study.       Measurements of job- ..................  SMR 58 (p<0.05)     No reported         Chen et al., 1992.
                                  N=13,719 workers    specific total                           overall. RR 1.63    increase in lung
                                  employed in 1972-   dust and quartz                          (CI 0.8-3.4)        cancer with
                                  1974. Follow up     content of settled                       among silicotics    increasing
                                  through 1989.       dust used to                             compared to non-    exposure.
                                                      classify workers                         silicotics.
                                                      into one of four
                                                      total dust
                                                      exposure groups.
British Coal workers...........  Cohort study.       Quartz exposure      973...............  Significant         Adjusted for        Miller et al,
                                  N=17,820 miners     assessed from                            relationship        smoking.            2007; Miller and
                                  from 10             personal                                 between                                 MacCalman, 2009
                                  collieries..        respirable dust                          cumulative silica
                                                      samples.                                 exposure (lagged
                                                                                15 years) and
                                                                                lung cancer
                                                                                mortality VIA Cox
                                                                                regression.
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Toxicity studies provide additional evidence of the carcinogenic
potential of crystalline silica (Health Effects Summary, Section V).
Acellular studies using DNA exposed directly to freshly fractured
crystalline silica demonstrate the direct effect silica has on DNA
breakage. Cell culture research has investigated the processes by which
crystalline silica disrupts normal gene expression and replication
(Section V). Studies demonstrate that chronic inflammatory and fibrotic
processes resulting in oxidative and cellular damage set up another
possible mechanism that leads to neoplastic changes in the lung
(Goldsmith, 1997; see also Health Effects discussion in Section V). In
addition, the biologically damaging physical characteristics of
crystalline silica, and the direct and indirect genotoxicity of
crystalline silica (Schins, 2002; Borm and Driscoll, 1996), support the
Agency's preliminary position that respirable crystalline silica should
be considered as an occupational carcinogen that causes lung cancer, a
clear material impairment of health.
c. Non-Malignant Respiratory Disease (Other Than Silicosis)
    Exposure to respirable crystalline silica increases the risk of
developing chronic obstructive pulmonary disease (COPD), in particular
chronic bronchitis and emphysema. COPD results in loss of pulmonary
function that restricts normal activity in individuals afflicted with
these conditions (ATS, 2003). Both chronic bronchitis and emphysema can
occur in conjunction with development of silicosis. Several studies
have documented increased prevalence of chronic bronchitis and
emphysema among silica-exposed workers even absent evidence of
silicosis (see Section I of the Health Effects Literature Review and
Preliminary Quantitative Risk Assessment; NIOSH, 2002; ATS, 1997).
There is evidence that smoking may have an additive or synergistic
effect on silica-related COPD morbidity or mortality (Hnizdo, 1990;
Hnizdo et al., 1990; Wyndham et al., 1986; NIOSH, 2002). In a study of
diatomaceous earth workers, Park et al. (2002) found a positive
exposure-response relationship between exposure to respirable
cristobalite and increased mortality from non-malignant respiratory
disease.
    Decrements in pulmonary function have often been found among
workers exposed to respirable crystalline silica absent radiologic
evidence of silicosis. Several cross-sectional studies have reported
such findings among granite workers (Theriault, 1974a, 1974b; Ng et
al., 1992b; Montes et al., 2004b), South African gold miners (Irwig and
Rocks, 1978; Hnizdo et al., 1990; Cowie and Mabena, 1991), gemstone
cutters (Ng et al., 1987b), concrete workers (Meijer et al., 2001),
refractory brick workers (Wang et al., 1997), hard rock miners
(Manfreda et al., 1982; Kreiss et al., 1989), pottery workers (Neukirch
et al., 1994), slate workers (Suhr et al., 2003), and potato sorters
(Jorna et al., 1994).
    OSHA also evaluated several longitudinal studies where exposed
workers were examined over a period of time to track changes in
pulmonary function. Among both active and retired Vermont granite
workers exposed to an average of 60 [mu]g/m\3\, Graham did not find
exposure-related decrements in pulmonary function (Graham et al., 1981,
1994). However, Eisen et al.