OSHA did not rely on the results of the preliminary statistical
analysis for its findings, the Agency presented the DTPHA in order to
inform the public of its results, explain its limitations, and solicit
public comment on the Agency's approach.
    Dr. Kenny Crump and Ms. Deborah Proctor submitted comments on
OSHA's preliminary risk assessment (Document ID 1660). Crump and
Proctor agreed with OSHA's review of the epidemiological literature and
the prevalence analysis presented previously in this section. They
stated, ``we agree with OSHA's conclusion that there is a significant
risk (>1/1000 risk of CBD) at the [then] current PEL, and that risk is
reduced at the [then] proposed PEL (0.2 [mu]g/m\3\) in combination with
stringent measures (ancillary provisions) to reduce worker's exposures.
This finding is evident based on the available literature, as described
by OSHA, and the prevalence data presented for the Cullman facility''
(Document ID 1660, p. 2). They also presented a detailed evaluation of
the statistical analysis of the Cullman data presented in the NPRM,
including a critique of OSHA's modeling approach and interpretation and
suggestions for alternate analyses. However, they emphasized that the
new beryllium rule should not be altered or delayed due to their
comments regarding the statistical model (Document ID 1660, p. 2).
    After considering comments on this preliminary model, OSHA
instructed its contractor to change the statistical analysis to address
technical concerns and to incorporate suggestions from Crump and
Proctor, as well as NIOSH (Document ID 1660; 1725). OSHA reviews and
addresses these comments on the preliminary statistical analysis and
provides a presentation of the final statistical analysis in the
background document (Risk Analysis of the NJH Data Set from the
Beryllium Machining Facility in Cullman, Alabama--CBD and
Sensitization, OSHA, 2016). The results of the final statistical
analysis are summarized here.
2. OSHA's Final Statistical Analysis of the NJH Data Set
    As noted above, Dr. Roslyn Stone of University of Pittsburgh School
of Public Health reanalyzed for OSHA the Cullman data set in order to
address concerns raised by Crump and Proctor (Document ID 1660). The
reanalysis uses a Cox proportional hazards model instead of the DTPHA.
The Cox model, a regression method for survival data, provides an
estimate of the hazard ratio (HR) and its confidence interval.\17\ Like
the DTPHA, the Cox model can accommodate time-dependent data; however,
the Cox model has an advantage over the DTPHA for OSHA's purpose of
estimating risk to beryllium-exposed workers in that it does not
estimate different ``baseline'' rates of sensitization and CBD for
different years. Time-specific risk sets were constructed to
accommodate the time-dependent exposures. P-values were based on
likelihood ratio tests (LRTs), with p-values <0.05 considered to be
statistically significant.
---------------------------------------------------------------------------

    \17\ The hazard ratio is an estimate of the ratio of the hazard
rate in the exposed group to that of the control group.
---------------------------------------------------------------------------

    As in the preliminary statistical analysis, Dr. Stone used
fractional polynomials \18\ to check for possible nonlinearities in the
exposure-response models, and checked the effects of age and smoking
habits using data on birth year and smoking (current, former, never)
provided in the Cullman data set. Data on workers' estimated exposures
and health outcomes through 2005 were included in the reanalysis.\19\
The 1995 risk set (e.g., analysis of cases of sensitization and CBD
identified in 1995) was excluded from all models in the reanalysis so
as not to analyze long-standing (prevalent) cases of sensitization and
CBD together with newly arising (incident) cases of sensitization and
CBD. Finally, Dr. Stone used the testing protocols provided in the
literature on the Cullman study population to determine the years in
which each employee was scheduled to be tested, and excluded employees
from the analysis for years in which they were not scheduled to be
tested (Newman et al., 2001, Document ID 1354).
---------------------------------------------------------------------------

    \18\ Fractional polynomials are linear combinations of
polynomials that provide flexible shapes of exposure response.
    \19\ Data from 2003 to 2005 were excluded in some previous
analyses due to uncertainty in some employees' work histories. OSHA
accepted the.Crump and Proctor recommendation that these data should
be included, so as to treat uncertain exposure estimates
consistently in the reanalysis (data prior to the start of sampling
in 1980 were included in the previous analysis and most models in
the reanalysis).
---------------------------------------------------------------------------

    In the reanalysis of the NJH data set, the HR for sensitization
increased significantly with increasing LTW average exposure (HR =
2.92, 95% CI = 1.51-5.66, p = 0.001; note that HRs are rounded to the
second decimal place). Cumulative exposure was also a statistically
significant predictor for beryllium sensitization, although it was not
as strongly related to sensitization as LTW average exposure (HR =
1.04, 95% CI 1.00-1.07, p = 0.03). The HR for CBD increased
significantly with increasing cumulative exposure (HR = 1.04, 95% CI =
1.01-1.08, p = 0.02). The HR for CBD increased somewhat with increasing
LTW average exposure, but this increase was not significant at the 0.05
level (HR = 2.25, 95% CI = 0.94-5.35, p = 0.07).
    None of the analyses Dr. Stone performed to check for
nonlinearities in exposure-response or the effects of smoking or age
substantially impacted the results of the analyses for beryllium
sensitization or CBD. The sensitivity analysis recommended by Crump and
Proctor, excluding workers hired prior to 1980 (see Document ID 1660,
p. 11), did not substantially impact the results

of the analyses for beryllium sensitization, but did affect the results
for CBD. The HR for CBD using cumulative exposure dropped to slightly
below 1 and was not statistically significant following exclusion of
workers hired before 1980 (HR 0.96, 95% CI 0.81-1.13, p = 0.6). OSHA
discusses this result further in the background document, concluding
that the reduced follow-up time for CBD in the subcohort hired in 1980
or later, in combination with genetic risk factors that may attenuate
both exposure-response and disease latency in some people, may explain
the lack of significant exposure-response observed in this sensitivity
analysis.
    Because LTW average exposure was most strongly associated with
beryllium sensitization, OSHA used the final model for LTW average
exposure to estimate risk of sensitization at the preceding TWA PEL,
the final TWA PEL, and several alternate TWA PELs it considered.
Similarly, because cumulative exposure was most strongly associated
with CBD, OSHA used the final model for cumulative exposure to estimate
risk of CBD at the preceding, final, and alternate TWA PELs. In
calculating these risks, OSHA used a small, fixed estimate of
``baseline'' risk (i.e., risk of sensitization or CBD among persons
with no known exposure to beryllium), as suggested by Crump and Proctor
(Document ID 1660) and NIOSH (Document ID 1725). Table VI-6 presents
the risk estimates for sensitization and the corresponding 95 percent
confidence intervals using two different fixed ``background'' rates of
sensitization, 1 percent and 0.5 percent. Table VI-7 presents the risk
estimates for sensitization and the corresponding 95 percent confidence
intervals using a fixed ``background'' rate of CBD of 0.5 percent. The
corresponding interval is based on the uncertainty in the exposure
coefficient (i.e., the predicted values based on the 95 percent
confidence limits for the exposure coefficient). Since the Cox
proportional hazards model does not estimate a baseline risk, this 95
percent interval fully represents statistical uncertainty in the risk
estimates.

Table VI-6--Predicted Cases of Sensitization per 1,000 Workers Exposed at the Preceding and Alternate PELs Based
    on Cox Proportional Hazards Model, LTW Average Exposure Metric, With Corresponding Interval Based on the
                                    Uncertainty in the Exposure Coefficient.
                                      [1 Percent and 0.5 percent baselines]
----------------------------------------------------------------------------------------------------------------
                                                     Estimated                       Estimated
          Exposure level  ([mu]g/m\3\)              cases/1000,       95% CI        cases/1000,       95% CI
                                                   .5% baseline                     1% baseline
----------------------------------------------------------------------------------------------------------------
2.0.............................................           42.75     11.4-160.34           85.49    22.79-320.69
1.0.............................................           14.62      7.55-28.31           29.24     15.10-56.63
0.5.............................................            8.55      6.14-11.90           17.10     12.29-23.80
0.2.............................................            6.20       5.43-7.07           12.39     10.86-14.15
0.1.............................................            5.57       5.21-5.95           11.13     10.42-11.89
----------------------------------------------------------------------------------------------------------------

 Table VI-7--Predicted Cases of CBD per 1,000 Workers Exposed at the Preceding and Alternative PELs Based on Cox Proportional Hazards Model, Cumulative
                            Exposure Metric, with Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
                                                                 [0.5 percent baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Exposure Duration
                                              ----------------------------------------------------------------------------------------------------------
                                                        5 years                    10 years                   20 years                  45 years
         Exposure level ([mu]g/m\3\)          ----------------------------------------------------------------------------------------------------------
                                                Cumulative    Estimated                  Estimated                  Estimated                 Estimated
                                               ([mu]g/m\3\-  cases/1000   [mu]g/m\3\-   cases/1000   [mu]g/m\3\-   cases/1000   [mu]g/m\3\-   cases/1000
                                                   yrs)        95% CI         yrs         95% CI         yrs         95% CI         yrs         95% CI
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0..........................................         10.0         7.55          20.0        11.39          40.0        25.97          90.0       203.60
                                                             5.34-10.67                 5.70-22.78                 6.5-103.76                9.02-4595.6
                                                                                7
1.0..........................................          5.0         6.14          10.0         7.55          20.0        11.39          45.0        31.91
                                                              5.17-7.30                 5.34-10.67                 5.70-22.78                6.72-151.59
0.5..........................................          2.5         5.54           5.0         6.14          10.0         7.55          22.5        12.63
                                                              5.08-6.04                  5.17-7.30                 5.34-10.67                 5.79-27.53
0.2..........................................          1.0         5.21           2.0         5.43           4.0          5.9           9.0         7.24
                                                              5.03-5.39                  5.07-5.82                  5.13-6.77                  5.30-9.89
0.1..........................................          0.5          5.1           1.0         5.21           2.0         5.43           4.5         6.02
                                                              5.02-5.19                  5.03-5.39                  5.07-5.82                  5.15-7.03
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The Cox proportional hazards model, used with the fixed
``baseline'' rates of 0.5 percent and 1 percent, predicted risks of
sensitization totaling 43 and 86 cases per 1,000 workers, respectively,
or 4.3 and 8.6 percent, at the preceding PEL of 2 [mu]g/m\3\. The
predicted risk of CBD is 203 cases per 1,000 workers, or 20.3 percent,
at the preceding PEL of 2 [mu]g/m\3\, assuming 45 years of exposure
(cumulative exposure of 90 [mu]g/m\3\-yr).\20\ The predicted risks of
sensitization at the new PEL of 0.2 [mu]g/m\3\ are substantially lower,
at 6 and 12 cases per 1,000 for the baselines of 0.5% and 1.0%,
respectively. The predicted risk of CBD is also much lower at the new
TWA PEL of 0.2 [mu]g/m\3\ (9 [mu]g/m\3\-year), at 7 cases per 1,000
assuming 45 years of exposure.
---------------------------------------------------------------------------

    \20\ The predictions for each model represent the estimated
probability of being sensitized or having CBD at one point in time,
rather than the cumulative risk over a lifetime of exposure, which
would be higher. Lifetime risks are presented in the FEA, Benefits
Analysis.
---------------------------------------------------------------------------

    Due to limitations in the Cox analysis, including the small size of
the dataset, relatively limited exposure data from the plant's early
years, study size-related constraints on the statistical analysis of
the dataset, limited follow-

up time on many workers, and sensitivity of the results to the
``baseline'' values assumed for sensitization and CBD, OSHA must
interpret the model-based risk estimates presented in Tables VI-6 and
VI-7 with caution. Uncertainties in these risk estimates are discussed
in the background document (Risk Analysis of the NJH Data Set from the
Beryllium Machining Facility in Cullman, Alabama--CBD and
Sensitization, OSHA, 2016). However, these uncertainties do not alter
OSHA's conclusions with regard to the significance of risk at the
preceding PEL and alternate PELs that OSHA considered, which are based
primarily on the Agency's review of the literature and the prevalence
analysis presented earlier in this section (also see Section VII,
Significance of Risk).

D. Lung Cancer

    As discussed more fully in the Health Effects section of the
preamble, OSHA has determined beryllium to be a carcinogen based on an
extensive review of the scientific literature regarding beryllium and
cancer (see Section V.E). This review included an evaluation of the
human epidemiological, animal cancer, and mechanistic studies described
in the Health Effects section of this preamble. OSHA's conclusion is
supported by the findings of public health organizations such as the
International Agency for Research on Cancer (IARC), which has
determined beryllium and its compounds to be carcinogenic to humans
(Group 1 category) (IARC 2012, Document ID 0650); the National
Toxicology Program (NTP), which classifies beryllium and its compounds
as known carcinogens (NTP 2014, Document ID 0389); and the
Environmental Protection Agency (EPA), which considers beryllium to be
a probable human carcinogen (EPA 1998, Document ID 0661).
    The Sanderson et al. study previously discussed in Health Effects
evaluated the association between beryllium exposure and lung cancer
mortality based on data from a beryllium processing plant in Reading,
PA (Sanderson et al., 2001, Document ID 1419). Specifically, this case-
control study evaluated lung cancer mortality in a cohort of 3,569 male
workers employed at the plant from 1940 to 1969 and followed through
1992. For each lung cancer victim, 5 age- and race-matched controls
were selected by incidence density sampling, for a total of 142
identified lung cancer cases and 710 controls.
    A conditional logistic regression analysis showed an increased risk
of death from lung cancer in workers with higher exposures when dose
estimates were lagged by 10 and 20 years (Sanderson et al., 2001,
Document ID 1419). This lag was incorporated in order to account for
exposures that did not contribute to lung cancer because they occurred
after the induction of cancer. The authors noted that there was
considerable uncertainty in the estimation of exposure levels for the
1940s and 1950s and in the shape of the dose-response curve for lung
cancer. In a 2008 study, Schubauer-Berigan et al. reanalyzed the data,
adjusting for potential confounders of hire age and birth year
(Schubauer-Berigan et al., 2008, Document ID 1350). The study reported
a significant increasing trend (p < 0.05) in lung cancer mortality when
average (log transformed) exposure was lagged by 10 years. However, it
did not find a significant trend when cumulative (log transformed)
exposure was lagged by 0, 10, or 20 years (Schubauer-Berigan et al.,
2008, Table 3).
    In formulating the final rule, OSHA was particularly interested in
lung cancer risk estimates from a 45-year (i.e., working lifetime)
exposure to beryllium levels between 0.1 [mu]g/m\3\ and 2 [mu]g/m\3\.
The majority of case and control workers in the Sanderson et al. (2001,
Document ID 1419) case-control analysis were first hired during the
1940s and 50s when exposures were extremely high (estimated daily
weighted averages (DWAs) >20 [mu]g/m\3\ for most jobs) in comparison to
the exposure range of interest to OSHA (Sanderson et al. 2001, Document
ID 1419, Table II). About two-thirds of cases and half of controls
worked at the plant for less than a year. Thus, a risk assessment based
on this exposure-response analysis would have needed to extrapolate
from very high to low exposures, based on a working population with
extremely short tenure. While OSHA risk assessments must often make
extrapolations to estimate risk within the range of exposures of
interest, the Agency acknowledges that these issues of short tenure and
high exposures would have created substantial uncertainty in a risk
assessment based on this particular study population.
    In addition, the relatively high exposures of the least-exposed
workers in the study population might have created methodological
issues for the lung cancer case-control study design. Mortality risk is
expressed as an odds ratio that compares higher exposure quartiles to
the lowest quartile. It is preferable that excess risks attributable to
occupational beryllium be determined relative to an unexposed or
minimally exposed reference population. However, in this study
population, workers in the lowest quartile were exposed well above the
preceding OSHA TWA PEL (average exposure <11.2 [mu]g/m\3\) and may have
had a significant lung cancer risk. This issue would have introduced
further uncertainty into the lung cancer risks.
    In 2011, Schubauer-Berigan et al. published a quantitative risk
assessment that addressed several of OSHA's concerns regarding the
Sanderson et al. analysis. This new risk assessment was based on an
update of the Reading cohort analyzed by Sanderson et al., as well as
workers from two smaller plants (Schubauer-Berigan et al. 2011,
Document ID 1265). This study population was exposed, on average, to
lower levels of beryllium and had fewer short-term workers than the
previous cohort analyzed by Sanderson et al. (2001, Document ID 1250)
and Schubauer-Berigan et al. (2008, Document ID 1350). Schubauer-
Berigan et al. (2011) followed the study population through 2005 where
possible, increasing the length of follow-up time overall by an
additional 17 years of observation compared to the previous analyses.
For these reasons, OSHA considered the Schubauer-Berigan (2011)
analysis more appropriate than Sanderson et al. (2001) and Schubauer-
Berigan (2008) for its risk assessment. OSHA therefore based its
preliminary QRA for lung cancer on the results from Schubauer-Berigan
et al. (2011).
    OSHA received several comments about its choice of Schubauer-
Berigan et al. (2011) as the basis for its preliminary QRA for lung
cancer. NIOSH commented that OSHA's choice of Schubauer-Berigan et al.
for its preliminary analysis was appropriate because ``[n]o other study
is available that presents quantitative dose-response information for
lung cancer, across a range of beryllium processing facilities''
(Document ID 1725, p. 7). In supporting OSHA's use of this study, NIOSH
emphasized in particular the study's inclusion of relatively low-
exposed workers from two facilities that began operations in the 1950s
(after employer awareness of acute beryllium disease (ABD) and CBD led
to efforts to minimize worker exposures to beryllium), as well as the
presence of both soluble and poorly soluble forms of beryllium in the
facilities studied (Document ID 1725, p. 7).
    According to Dr. Paolo Boffetta, who submitted comments on this
study,

Schubauer-Berigan et al. (2011) is not the most relevant study
available to OSHA for its lung cancer risk analysis. Dr. Boffetta
argued that the most informative study of lung cancer risk in the
beryllium industry after 1965 is one that he developed in 2015
(Boffetta et al., 2015), which he described as a pooled analysis of 11
plants and 4 distribution centers (Document ID 1659, p. 1). However,
Dr. Boffetta did not provide OSHA with the manuscript of his study,
which he stated was under review for publication. Instead, he reported
some results of the study and directed OSHA to an abstract of the study
in the 2015 Annual Conference of the Society for Epidemiologic Research
(Document ID 1659; Document ID 1661, Attachment 1).
    Because only an abstract of Boffetta et al.'s 2015 study was
available to OSHA (see Document ID 1661, Attachment 1), OSHA could not
properly evaluate it or use it as the basis of a quantitative risk
assessment for lung cancer. Nevertheless, OSHA has addressed comments
Dr. Boffetta submitted based on his analyses in the relevant sections
of the final QRA for lung cancer below. Because it was not possible to
use this study for its lung cancer QRA and OSHA is not aware of other
studies appropriate for use in its lung cancer QRA (nor did commenters
besides Dr. Boffetta suggest that OSHA use any additional studies for
this purpose), OSHA finds that the body of available evidence has not
changed since the Agency conducted its preliminary QRA based on
Schubauer-Berigan et al. (2011, Document ID 1265). Therefore, OSHA
concludes that Schubauer-Berigan et al. (2011) is the most appropriate
study for its final lung cancer QRA, presented below.
1. QRA for Lung Cancer Based on Schubauer-Berigan et al. (2011)
    The cohort studied by Schubauer-Berigan et al. (2011, Document ID
1265) included 5,436 male workers who had worked for at least 2 days at
the Reading facility or at the beryllium processing plants in Hazleton,
PA and Elmore, OH prior to 1970. The authors developed job-exposure
matrices (JEMs) for the three plants based on extensive historical
exposure data, primarily short-term general area and personal breathing
zone samples, collected on a quarterly basis from a wide variety of
operations. These samples were used to create DWA estimates of workers'
full-shift exposures, using records of the nature and duration of tasks
performed by workers during a shift. Details on the JEM and DWA
construction can be found in Sanderson et al. (2001, Document ID 1250),
Chen et al. (2001, Document ID 1593), and Couch et al. (2010, Document
ID 0880).
    Workers' cumulative exposures ([mu]g/m\3\-days) were estimated by
summing daily average exposures (assuming five workdays per week)
(Schubauer-Berigan et al., 2011). To estimate mean exposure ([mu]g/
m\3\), cumulative exposure was divided by exposure time (in days),
accounting where appropriate for lag time. Maximum exposure ([mu]g/
m\3\) was calculated as the highest annual DWA on record for a worker
from the first exposure until the study cutoff date of December 31,
2005, again accounting where appropriate for lag time. Exposure
estimates were lagged by 5, 10, 15, and 20 years in order to account
for exposures that may not have contributed to lung cancer because of
the long latency required for manifestation of the disease. The authors
also fit models with no lag time.
    As shown in Table VI-8 below, estimated exposure levels for workers
from the Hazleton and Elmore plants were on average far lower than
those for workers from the Reading plant (Schubauer-Berigan et al.,
2011). Whereas the median worker from Hazleton had a mean exposure
across his tenure of less than 1.5 [mu]g/m\3\ and the median worker
from Elmore had a mean exposure of less than 1 [mu]g/m\3\, the median
worker from Reading had a mean exposure of 25 [mu]g/m\3\. The Elmore
and Hazleton worker populations also had fewer short-term workers than
the Reading population. This was particularly evident at Hazleton,
where the median value for cumulative exposure among cases was higher
than at Reading despite the much lower mean and maximum exposure
levels.

                                       Table VI-8--Cohort Description and Distribution of Cases by Exposure Level
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                All plants     Reading plant  Hazleton plant   Elmore plant
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of cases................................  .......................................             293             218              30              45
Number of non-cases............................  .......................................            5143            3337             583            1223
Median value for mean exposure.................  No lag.................................           15.42              25           1.443           0.885
([mu]g/m\3\) among cases.......................  10-year lag............................           15.15              25           1.443           0.972
Median value for cumulative exposure...........  No lag.................................            2843            2895            3968            1654
([mu]g/m\3\-days) among cases..................  10-year lag............................            2583            2832            3648            1449
Median value for maximum exposure..............  No lag.................................              25            25.1            3.15            2.17
([mu]g/m\3\) among cases.......................  10-year lag............................              25              25            3.15            2.17
Number of cases with potential asbestos          .......................................       100 (34%)        68 (31%)        16 (53%)        16 (36%)
 exposure.
Number of cases who were professional workers..  .......................................         26 (9%)        21 (10%)         3 (10%)          2 (4%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
 Table adapted from Schubauer-Berigan et al., 2011, Document ID 1265, Table 1.

    Schubauer-Berigan et al. analyzed the data set using a variety of
exposure-response modeling approaches, including categorical analyses,
continuous-variable piecewise log-linear models, and power models
(2011, Document ID 1265). All models adjusted for birth cohort and
plant. Because exposure values were log-transformed for the power model
analyses, the authors added small values to exposures of 0 in lagged
analyses (0.05 [mu]g/m\3\ for mean and maximum exposure, 0.05 [mu]g/
m\3\-days for cumulative exposure). The authors used restricted cubic
spline models to assess the shape of the exposure-response curves and
suggest appropriate parametric model forms. The Akaike Information
Criterion (AIC) value was used to evaluate the fit of different model
forms and lag times.
    Because smoking information was available for only about 25 percent
of the cohort (those employed in 1968), smoking could not be controlled
for directly in the models. Schubauer-Berigan et al. reported that
within the subset with smoking information, there was little difference
in smoking by cumulative or maximum exposure category, suggesting that
smoking was unlikely to act as a confounder in the cohort. In addition
to models based on the full cohort, Schubauer-Berigan et al. also
prepared risk estimates based on models excluding professional workers
(ten percent of cases) and workers believed to have asbestos exposure
(one-third of cases). These models were

intended to mitigate the potential impact of smoking and asbestos as
confounders.\21\
---------------------------------------------------------------------------

    \21\ The authors appeared to reason that if professional workers
had both lower beryllium exposures and lower smoking rates than
production workers, smoking could be a confounder in the cohort
comprising both production and professional workers. However,
smoking was unlikely to be correlated with beryllium exposure among
production workers, and would therefore probably not act as a
confounder in a cohort excluding professional workers.
---------------------------------------------------------------------------

    The authors found that lung cancer risk was strongly and
significantly related to mean, cumulative, and maximum measures of
workers' exposure (all models reported in Schubauer-Berigan et al.,
2011, Document ID 1265). They selected the best-fitting categorical,
power, and monotonic piecewise log-linear (PWL) models with a 10-year
lag to generate HRs for male workers with a mean exposure of 0.5 [mu]g/
m\3\ (the current NIOSH Recommended Exposure Limit for beryllium).\22\
In addition, they estimated the daily weighted average exposure that
would be associated with an excess lung cancer mortality risk of one in
one thousand (.005 [mu]g/m\3\ to .07 [mu]g/m\3\ depending on model
choice). To estimate excess risk of cancer, they multiplied these
hazard ratios by the 2004 to 2006 background lifetime lung cancer rate
among U.S. males who had survived, cancer-free, to age 30. At OSHA's
request, Dr. Schubauer-Berigan also estimated excess lung cancer risks
for workers with mean exposures at the preceding PEL of 2 [mu]g/m\3\
and at each of the other alternate PELs that were under consideration:
1 [mu]g/m\3\, 0.2 [mu]g/m\3\, and 0.1 [mu]g/m\3\ (Document ID 0521).
The resulting risk estimates are presented in Table VI-9 below.
---------------------------------------------------------------------------

    \22\ Here, ``monotonic PWL model'' means a model producing a
monotonic exposure-response curve in the 0 to 2 [mu]g/m\3\ range.

   Table VI-9--Excess Lung Cancer Risk per 1,000 [95% Confidence Interval] For Male Workers at Alternate PELs
                                    [Based on Schubauer-Berigan et al., 2011]
----------------------------------------------------------------------------------------------------------------
                                                                   Mean exposure
     Exposure-response model     -------------------------------------------------------------------------------
                                  0.1 [mu]g/m\3\  0.2 [mu]g/m\3\  0.5 [mu]g/m\3\   1 [mu]g/m\3\    2 [mu]g/m\3\
----------------------------------------------------------------------------------------------------------------
Best monotonic PWL--all workers.    7.3 [2.0-13]     15 [3.3-29]       45 [9-98]    120 [20-340]    140 [29-370]
Best monotonic PWL--excluding        3.1 [<0-11]     6.4 [<0-23]      17 [<0-74]     39 [39-230]     61 [<0-280]
 professional and asbestos
 workers........................
Best categorical--all workers...     4.4 [1.3-8]      9 [2.7-17]       25 [6-48]     59 [13-130]    170 [29-530]
Best categorical--excluding         1.4 [<0-6.0]     2.7 [<0-12]     7.1 [<0-35]      15 [<0-87]     33 [<0-290]
 professional and asbestos
 workers........................
Power model--all workers........       12 [6-19]     19 [9.3-29]      30 [15-48]      40 [19-66]      52 [23-88]
Power model--excluding               19 [8.6-31]      30 [13-50]      49 [21-87]     68 [27-130]     90 [34-180]
 professional and asbestos
 workers........................
----------------------------------------------------------------------------------------------------------------
Source: Schubauer-Berigan, Document ID 0521, pp. 6-10.

    Schubauer-Berigan et al. (2011, Document ID 1265) discuss several
strengths, weaknesses, and uncertainties of their analysis. Strengths
include a long (>30 years) follow-up time and the extensive exposure
and work history data available for the development of exposure
estimates for workers in the cohort. Weaknesses and uncertainties of
the study include the limited information available on workers' smoking
habits: As mentioned above, smoking information was available only for
workers employed in 1968, about 25 percent of the cohort. Another
potential weakness was that the JEMs used did not account for possible
respirator use among workers in the cohort. The authors note that
workers' exposures may therefore have been overestimated, and that
overestimation may have been especially severe for workers with high
estimated exposures. They suggest that overestimation of exposures for
workers in highly exposed positions may have caused attenuation of the
exposure-response curve in some models at higher exposures. This could
cause the relationship between exposure level and lung cancer risk to
appear weaker than it would in the absence of this source of error in
the estimation of workers' beryllium exposures.
    Schubauer-Berigan et al. (2011) did not discuss the reasons for
basing risk estimates on mean exposure rather than cumulative exposure,
which is more commonly used for lung cancer risk analysis. OSHA
believes the decision may involve the non-monotonic relationship the
authors observed between cancer risk and cumulative exposure level. As
discussed previously, workers from the Reading plant frequently had
very short tenures and high exposures, yielding lower cumulative
exposures compared to cohort workers from other plants with longer
employment. Despite the low estimated cumulative exposures among the
short-term Reading workers, they may have been at high risk of lung
cancer due to the tendency of beryllium to persist in the lung for long
periods. This could lead to the appearance of a non-monotonic
relationship between cumulative exposure and lung cancer risk. It is
possible that a dose-rate effect may exist for beryllium, such that the
risk from a cumulative exposure gained by long-term, low-level exposure
is not equivalent to the risk from a cumulative exposure gained by very
short-term, high-level exposure. In this case, mean exposure level may
better correlate with the risk of lung cancer than cumulative exposure
level. For these reasons, OSHA considers the authors' use of the mean
exposure metric to be appropriate and scientifically defensible for
this particular dataset.
    Dr. Boffetta's comment, mentioned above, addressed the relevance of
the Schubauer-Berigan et al. (2011) cohort to determining whether
workers currently employed in the beryllium industry experience an
increased lung cancer hazard (Document ID 1659, pp. 1-2). His comment
also analyzed the methods and findings in Schubauer-Berigan et al.
(2011) (Document ID 1659, pp. 2-3). Notably, he stated that his own
study, Boffetta et al. (2015) provides better information for risk
assessment than does Schubauer-Berigan et al. (2011) (Document ID 1659,
pp. 1-2). As discussed above, OSHA cannot rely on a study for its QRA
(Boffetta et al., 2015) that has not been submitted to the record and
is not otherwise available to OSHA. However, in the discussion below,
OSHA addresses Dr. Boffetta's study to the extent it can given the

limited information available to the Agency. OSHA also responds to Dr.
Boffetta's comments on Schubauer-Berigan et al. (2011, Document ID
1265) and Boffetta et al. (2014, Document ID 0403), which Dr. Boffetta
asserts provides evidence that poorly soluble beryllium compounds are
not associated with lung cancer (Document ID 1659, p. 1).
    Boffetta argued that the most informative study in the modern
(post-1965) beryllium industry is Boffetta et al. (2015, Document ID
1661, Attachment 1). According to Boffetta's comment, the study found
an SMR of 1.02 (95% CI 0.94-1.10, based on 672 deaths) for the overall
cohort and an SMR for lung cancer among workers exposed only to
insoluble beryllium of 0.93 (95% CI 0.79-1.08, based on 157 deaths).
Boffetta noted that his study was based on 23 percent more overall
deaths than the Schubauer-Berigan et al. cohort (Document ID 1659, pp.
1-2). As stated earlier, this study is unpublished and was not provided
to OSHA. The abstract provided by Materion (Document ID 1661,
Attachment 1) included very little information beyond the SMRs
reported; for example, it provided no information about the
manufacturing plants and distribution centers included, workers'
beryllium exposure levels, how the cohorts were defined, or how the
authors determined the solubility of the beryllium to which workers
were exposed. OSHA is therefore unable to evaluate the quality or
conclusions of this study.
    Dr. Boffetta also commented that there is a lack of evidence of
increased lung cancer risk among workers exposed only to poorly soluble
beryllium compounds (Document ID 1659, p. 1). To support this
statement, he cited a study he published in 2014 of workers at four
``insoluble facilities'' (Boffetta et al., 2014) and Schubauer-Berigan
et al.'s 2011 study, arguing that increased cancer risk in beryllium-
exposed workers in those two studies was only observed in workers
employed in Reading and Lorain prior to 1955. Workers employed at the
other plants and workers who were first employed in Reading and Lorain
after 1955, according to Dr. Boffetta, were exposed primarily to poorly
soluble forms of beryllium and did not experience an increased risk of
lung cancer. Dr. Boffetta further stated that his unpublished paper
(Boffetta et al., 2015) shows a similar result (Document ID 1659, p.
1).
    OSHA carefully considered Dr. Boffetta's argument regarding the
status of poorly soluble beryllium compounds, and did not find
persuasive evidence showing that the solubility of the beryllium to
which the workers in the studies he cited were exposed accounts for the
lack of statistically significantly elevated risk in the Boffetta et
al. (2014) cohort or the Schubauer-Berigan et al. (2011) subcohort.
While it is true that the SMR for lung cancer was not statistically
significantly elevated in the Schubauer-Berigan et al. (2011) study
when workers hired before 1955 in the Reading and Lorain plants were
excluded from the study population, or in the study of four facilities
published by Boffetta et al. in 2014, there are various possible
reasons for these results that Dr. Boffetta did not consider in his
comment. As discussed below, OSHA finds that the type of beryllium
compounds to which these workers were exposed is not likely to explain
Dr. Boffetta's observations.
    As discussed in Section V, Health Effects and in comments submitted
by NIOSH, animal toxicology evidence shows that poorly soluble
beryllium compounds can cause cancer. IARC determined that poorly
soluble forms of beryllium are carcinogenic to humans in its 2012
review of Group I carcinogens (see section V.E.5 of this preamble;
Document ID 1725, p. 9; IARC, 2012, Document ID 0650). NIOSH noted that
poorly soluble forms of beryllium remain in the lung for longer time
periods than soluble forms, and can therefore create prolonged exposure
of lung tissue to beryllium (Document ID 1725, p. 9). This prolonged
exposure may lead to the sustained tissue inflammation that causes many
forms of cancer and is believed to be one pathway for carcinogenesis
due to beryllium exposure (see Section V, Health Effects).
    The comments from NIOSH also demonstrate that the available
information cannot distinguish between the effects of soluble and
poorly soluble beryllium. NIOSH submitted information on the solubility
of beryllium in the Schubauer-Berigan et al. (2011) cohort, stating
that operations typically involving both soluble and poorly soluble
beryllium were performed at all three of the beryllium plants included
in the study (Document ID 1725, p. 9; Ward et al., 1992, Document ID
1378). Based on evaluations of the JEMs and work histories of employees
in the cohort (which were not published in the 2011 Schubauer-Berigan
et al. paper), NIOSH stated that ``the vast majority of beryllium work-
time at all three of these facilities was due to either insoluble or
mixed chemical forms. In fact, insoluble beryllium was the largest
single contributor to work-time (for beryllium exposure of known
solubility class) at the three facilities across most time periods''
(Document ID 1725, p. 9). NIOSH also provided figures showing the
contribution of insoluble beryllium to exposure over time in the
Schubauer-Berigan et al. (2011) study, as well as the relatively small
proportion of work years during which workers in the study were exposed
exclusively to either soluble or poorly soluble forms (Document ID
1725, pp. 10-11).
    Boffetta et al. (2014, Document ID 0403) examined a population of
workers allegedly exposed exclusively to poorly soluble beryllium
compounds, in which overall SMR for lung cancer was not statistically
significantly elevated (SMR 96.0, 95% CI 80.0-114.3). Boffetta et al.
concluded, ``[a]lthough a small risk for lung cancer is compatible with
our results, we can confidently exclude an excess greater than 20%'' in
the study population (Boffetta et al., 2014, p. 592). Limitations of
the study include a lack of information on many workers' job titles, a
lack of any beryllium exposure measurements, and the very short-term
employment of most cohort members at the study facilities (less than 5
years for 72 percent of the workers) (Boffetta et al., 2014).
    OSHA reviewed this study, and finds that it does not contradict the
findings of the Schubauer-Berigan et al. (2011) lung cancer risk
analysis for several reasons. First, as shown in Table VI-9 above, none
of the predictions of excess risk in the risk analysis exceed 20
percent (200 per 1,000 workers); most are well below this level, and
thus are well within the range that Boffetta et al. (2014) state they
cannot confidently exclude. Thus, the statement by Boffetta et al. that
the risk of excess lung cancer is no higher than 20 percent is actually
consistent with the risk findings from Schubauer-Berigan et al. (2011)
presented above. Second, the fact that most workers in the cohort were
employed for less than five years suggests that most workers'
cumulative exposures to beryllium were likely to be quite low, which
would explain the non-elevated SMR for lung cancer in the study
population regardless of the type of beryllium to which workers were
exposed. The SMR for workers employed in the study facilities for at
least 20 years was elevated (112.7, CI 66.8-178.1) (Boffetta et al.,
2014, Document ID 0403, Table 3),\23\ supporting OSHA's observation
that the lack of elevated SMR in the cohort overall may be due to
short-term

employment and low cumulative exposures.
---------------------------------------------------------------------------

    \23\ This SMR was not statistically significantly elevated,
probably due to the small size of this subcohort (153 total deaths,
18 lung cancer deaths).
---------------------------------------------------------------------------

    Finally, the approach of Boffetta et al. (2014), which relies on
SMR analyses, does not account for the healthy worker effect. SMRs are
calculated by comparing disease levels in the study population to
disease levels in the general population, using regional or national
reported disease rates. However, because working populations tend to
have lower disease rates than the overall population, SMRs can
underestimate excess risk of disease in those populations. The SMR in
Boffetta et al. (2014) for overall mortality in the study population
was statistically significantly reduced (94.7, 95 percent CI 89.9-
99.7), suggesting a possible healthy worker effect. The SMR for overall
mortality was even further reduced in the category of workers with at
least 20 years of employment (87.7, 95 percent CI 74.3-102.7), in which
an elevated SMR for lung cancer was observed. NIOSH commented that
``[i]n a modern industrial population, the expected SMR for lung cancer
would be approximately 0.93 [Park et al. (1991)]'' (Document ID 1725,
p. 8). This is lower than the SMR for lung cancer (96) observed in
Boffetta et al. (2014) and much lower than the SMR for lung cancer in
the category of workers employed for at least 20 years (112.7), which
is the group most likely to have had sufficient exposure and latency to
show excess lung cancer (Boffetta et al., 2014, Document ID 0403,
Tables 2 and 3). Thus, it appears that the healthy worker effect is
another factor (in addition to low cumulative exposures) that may
account for the findings of Boffetta et al.'s 2014 study.
    Taken together, OSHA finds that the animal toxicology evidence on
the carcinogenicity of poorly soluble beryllium forms, the long
residence of poorly soluble beryllium in the lung, the likelihood that
most workers in Schubauer-Berigan et al. (2011) were exposed to a
mixture of soluble and poorly soluble beryllium forms, and the points
raised above regarding Boffetta et al. (2014) rebut Boffetta's claim
that low solubility of beryllium compounds is the most likely
explanation for the lack of statistically significantly elevated SMR
results.
    Dr. Boffetta's comment also raised technical questions regarding
the Schubauer-Berigan et al. (2011, Document ID 1265) risk analysis. He
noted that risk estimates at low exposures are dependent on choice of
model in their analysis; the authors' choice of a single ``best'' model
was based on purely statistical criteria, and the results of the
statistics used (AIC) were similar between the models'' (Document ID
1659, p. 2). Therefore, according to Dr. Boffetta, ``there is ample
uncertainty about the shape of the dose-response function in the low-
dose range'' (Document ID 1659, p. 3).
    OSHA agrees that it is difficult to distinguish a single ``best''
model from the set of models presented by Schubauer-Berigan et al.
(2011), and that risk estimates at low exposure levels vary depending
on choice of model. That is one reason OSHA presented results from all
of the models (see Table VI-9). OSHA further agrees that there is
uncertainty in the lung cancer risk estimates, the estimation of which
(unlike for CBD) required extrapolation below beryllium exposure levels
experienced by workers in the Schubauer-Berigan et al. (2011) study.
However, the Schubauer-Berigan risk assessment's six best-fitting
models all support OSHA's significant risk determination, as they all
predict a significant risk of lung cancer at the preceding TWA PEL of 2
[mu]g/m\3\ (estimates ranging from 33 to 170 excess lung cancers per
1,000 workers) and a substantially reduced, though still significant,
risk of lung cancer at the new TWA PEL of 0.2 [mu]g/m\3\ (estimates
ranging from 3 to 30 excess lung cancers per 1,000 workers) (see Table
VI-9).
    Dr. Boffetta also noted that the risk estimates provided by
Schubauer-Berigan et al. (2011, Document ID 1265) for OSHA's lung
cancer risk assessment depend on the background lung cancer rate used
in excess risk calculations, and that industrial workers may have a
different background lung cancer risk than the U.S. population as a
whole (Document ID 1659, p. 2). OSHA agrees that choice of background
risk could influence the number of excess lung cancers predicted by the
models the Agency relied on for its lung cancer risk estimates.
However, choice of background risk did not influence OSHA's finding
that excess lung cancer risks would be substantially reduced by a
decrease in exposure from the preceding TWA PEL to the final TWA PEL,
because the same background risk was factored into estimates of risk at
both levels. Furthermore, the Schubauer-Berigan et al. (2011) estimates
of excess lung cancer from exposure at the preceding PEL of 2 [mu]g/
m\3\ (ranging from 33 to 170 excess lung cancers per 1,000 workers,
depending on the model) are much higher than the level of 1 per 1,000
that OSHA finds to be clearly significant. Even at the final TWA PEL of
0.2 [mu]g/m\3\, the models demonstrate a range of risks of excess lung
cancers of 3 to 30 per 1,000 workers, estimates well above the
threshold for significant risk (see Section II, Pertinent Legal
Authority). Small variations in background risk across different
populations are highly unlikely to influence excess lung cancer risk
estimates sufficiently to influence OSHA's finding of significant risk
at the preceding TWA PEL, which is the finding OSHA relies on to
support the need for a new standard.
    Finally, Dr. Boffetta noted that the models that exclude
professional and asbestos workers (the groups that Schubauer-Berigan et
al. believed could be affected by confounding from tobacco and asbestos
exposure) showed non-significant increases in lung cancer with
increasing beryllium exposure. According to Dr. Boffetta, this suggests
that confounding may contribute to the results of the models based on
the full population. He speculates that if more precise information on
confounding exposures were available, excess risk estimates might be
further reduced (Document ID 1659, p. 2).
    OSHA agrees with Dr. Boffetta that there is uncertainty in the
Schubauer-Berigan et al. (2011) lung cancer risk estimates, including
uncertainty due to limited information on possible confounding from
associations between beryllium exposure level and workers' smoking
habits or occupational co-exposures. However, in the absence of
detailed smoking and co-exposure information, the models excluding
professional and asbestos workers are a reasonable approach to
addressing the possible effects of unmeasured confounding. OSHA's
decision to include these models in its preliminary and final QRAs
therefore represents the Agency's best available means of dealing with
this uncertainty.

E. Risk Assessment Conclusions

    As described above, OSHA's risk assessment for beryllium
sensitization and CBD relied on two approaches: (1) Review of the
literature, and (2) analysis of a data set provided by NJH. OSHA has a
high level of confidence in its finding that the risks of sensitization
and CBD are above the benchmark of 1 in 1,000 at the preceding PEL, and
the Agency believes that a comprehensive standard requiring a
combination of more stringent controls on beryllium exposure will
reduce workers' risk of both sensitization and CBD. Programs that have
reduced median levels to below 0.1 [mu]g/m\3\ and tightly controlled
both respiratory exposure and dermal contact have substantially reduced
risk of sensitization within the first years of exposure. These
conclusions are supported by the results of several studies conducted
in facilities dealing

with a variety of production activities and physical forms of beryllium
that have reduced workers' exposures substantially by implementing
stringent exposure controls and PPE requirements since approximately
2000. In addition, these conclusions are supported by OSHA's analyses
of the NJH data set, which contains highly-detailed exposure and work
history information on several hundred beryllium workers.
    Furthermore, OSHA believes that more stringent control of airborne
beryllium exposures will reduce beryllium-exposed workers' significant
risk of lung cancer. The risk estimates from the lung cancer study by
Schubauer-Berigan et al. (2011, Document ID 1265; 0521), described
above, range from 33 to 170 excess lung cancers per 1,000 workers
exposed at the preceding PEL of 2 [mu]g/m\3\, based on the study's six
best-fitting models. These models each predict substantial reductions
in risk with reduced exposure, ranging from 3 to 30 excess lung cancers
per 1,000 workers exposed at the final PEL of 0.2 [mu]g/m\3\. The
evidence of lung cancer risk from the Schubauer-Berigan et al. (2011)
risk assessment provides additional support for OSHA's conclusions
regarding the significance of risk of adverse health effects for
workers exposed to beryllium levels at and below the preceding PEL.
However, the lung cancer risks required a sizable low dose
extrapolation below beryllium exposure levels experienced by workers in
the Schubauer-Berigan et al. (2011) study. As a result, there is
greater uncertainty regarding the lung cancer risk estimates than there
is for the risk estimates for beryllium sensitization and CBD. The
conclusions with regard to significance of risk are presented and
further discussed in section VII of the preamble.

VII. Significance of Risk

    In this section, OSHA discusses its findings that workers exposed
to beryllium at and below the preceding TWA PEL face a significant risk
of material impairment of health or functional capacity within the
meaning of the OSH Act, and that the new standards will substantially
reduce this risk. To make the significance of risk determination for a
new final or proposed standard, OSHA uses the best available scientific
evidence to identify material health impairments associated with
potentially hazardous occupational exposures and to evaluate exposed
workers' risk of these impairments assuming exposure over a working
lifetime. As discussed in section II, Pertinent Legal Authority, courts
have stated that OSHA should consider all forms and degrees of material
impairment--not just death or serious physical harm. To evaluate the
significance of the health risks that result from exposure to hazardous
chemical agents, OSHA relies on epidemiological, toxicological, and
experimental evidence. The Agency uses both qualitative and
quantitative methods to characterize the risk of disease resulting from
workers' exposure to a given hazard over a working lifetime (generally
45 years) at levels of exposure reflecting compliance with the
preceding standard and compliance with the new standards (see Section
II, Pertinent Legal Authority). When determining whether a significant
risk exists OSHA considers whether there is a risk of at least one-in-
a-thousand of developing a material health impairment from a working
lifetime of exposure. The Supreme Court has found that OSHA is not
required to support its finding of significant risk with scientific
certainty, but may instead rely on a body of reputable scientific
thought and may make conservative assumptions (i.e., err on the side of
protecting the worker) in its interpretation of the evidence (Section
II, Pertinent Legal Authority).
    OSHA's findings in this section follow in part from the conclusions
of the preceding sections V, Health Effects, and VI, Risk Assessment.
In this preamble at section V, Health Effects, OSHA reviewed the
scientific evidence linking occupational beryllium exposure to a
variety of adverse health effects and determined that beryllium
exposure causes sensitization, CBD, and lung cancer, and is associated
with various other adverse health effects (see section V.D, V.E, and
V.F). In this preamble at section VI, Risk Assessment, OSHA found that
the available epidemiological data are sufficient to evaluate risk for
beryllium sensitization, CBD, and lung cancer among beryllium-exposed
workers. OSHA evaluated the risk of sensitization, CBD, and lung cancer
from levels of airborne beryllium exposure that were allowed under the
previous standard, as well as the expected impact of the new standards
on risk of these conditions. In this section of the preamble, OSHA
explains its determination that the risk of material impairments of
health, particularly CBD and lung cancer, from occupational exposures
allowable under the preceding TWA PEL of 2 [mu]g/m\3\ is significant,
and is substantially reduced but still significant at the new TWA PEL
of 0.2 [mu]g/m\3\. Furthermore, evidence reviewed in section VI, Risk
Assessment, shows that significant risk of CBD and lung cancer could
remain in workplaces with exposures as low as the new action level of
0.1 [mu]g/m\3\. OSHA also explains here that the new standards will
reduce the occurrence of sensitization.
    In the NPRM, OSHA preliminarily determined that both CBD and lung
cancer are material impairments of health. OSHA also preliminarily
determined that a working lifetime (45 years) of exposure to airborne
beryllium at the preceding time-weighted average permissible exposure
limit (TWA PEL) of 2 [mu]g/m\3\ would pose a significant risk of both
CBD and lung cancer, and that this risk is substantially reduced but
still significant at the new TWA PEL of 0.2 [mu]g/m\3\. OSHA did not
make a preliminary determination as to whether beryllium sensitization
is a material impairment of health because, as the Agency explained in
the NPRM, it was not necessary to make such a determination. The
Agency's preliminary findings on CBD and lung cancer were sufficient to
support the promulgation of new beryllium standards.
    Upon consideration of the entire rulemaking record, including the
comments and information submitted to the record in response to the
preliminary Health Effects, Risk Assessment, and Significance of Risk
analyses (NPRM Sections V, VI, and VIII), OSHA reaffirms its
preliminary findings that long-term exposure at the preceding TWA PEL
of 2 [mu]g/m\3\ poses a significant risk of material impairment of
workers' health, and that adoption of the new TWA PEL of 0.2 [mu]g/m\3\
and other provisions of the final standards will substantially reduce
this risk.

Material Impairment of Health

    As discussed in Section V, Health Effects, CBD is a respiratory
disease caused by exposure to beryllium. CBD develops when the body's
immune system reacts to the presence of beryllium in the lung, causing
a progression of pathological changes including chronic inflammation
and tissue scarring. CBD can also impair other organs such as the
liver, skin, spleen, and kidneys and cause adverse health effects such
as granulomas of the skin and lymph nodes and cor pulmonale (i.e.,
enlargement of the heart) (Conradi et al., 1971 (Document ID 1319);
ACCP, 1965 (1286); Kriebel et al., 1988a (1292) and b (1473)).
    In early, asymptomatic stages of CBD, small granulomatous lesions
and mild inflammation occur in the lungs. Over time, the granulomas can
spread and lead to lung fibrosis (scarring) and

moderate to severe loss of pulmonary function, with symptoms including
a persistent dry cough and shortness of breath (Saber and Dweik, 2000,
Document ID 1421). Fatigue, night sweats, chest and joint pain,
clubbing of fingers (due to impaired oxygen exchange), loss of
appetite, and unexplained weight loss may occur as the disease
progresses (Conradi et al., 1971, Document ID 1319; ACCP, 1965 (1286);
Kriebel et al., 1988 (1292); Kriebel et al., 1988 (1473)).
    Dr. Lee Newman, speaking at the public hearing on behalf of the
American College of Occupational and Environmental Medicine (ACOEM),
testified on his experiences treating patients with CBD: ``as a
physician who has spent most of my [practicing] career seeing patients
with exposure to beryllium, with beryllium sensitization, and with
chronic beryllium disease including those who have gone on to require
treatment and to die prematurely of this disease . . . [I've seen]
hundreds and hundreds, probably over a thousand individuals during my
career who have suffered from this condition'' (Document ID 1756, Tr.
79). Dr. Newman further testified about his 30 years of experience
treating CBD in patients at various stages of the disease:

    . . . some of them will go from being sensitized to developing
subclinical disease, meaning that they have no symptoms. As I
mentioned earlier, most of those will, if we actually do the tests
of their lung function and their oxygen levels in their blood, those
people are already demonstrating physiologic abnormality. They
already have disease affecting their health. They go on to develop
symptomatic disease and progress to the point where they require
treatment. And sometimes to the extent of even requiring a [lung]
transplant (Document ID 1756, Tr. 131).

    Dr. Newman described one example of a patient who developed CBD
from his occupational beryllium exposure and ``who went on to die
prematurely with a great deal of suffering along the way due to the
condition chronic beryllium disease'' (Document ID 1756, Tr. 80).
    During her testimony at the public hearing, Dr. Lisa Maier of
National Jewish Health (NJH) provided an example from her experience
with treating CBD patients. ``This gentleman started to have a cough, a
dry cough in 2011 . . . His symptoms progressed and he developed
shortness of breath, wheezing, chills, night sweats, and fatigue. These
were so severe that he was eventually hospitalized'' (Document ID 1756,
Tr. 105). Dr. Maier noted that this patient had no beryllium exposure
prior to 2006, and that his CBD had developed from beryllium exposure
in his job melting an aluminum alloy in a foundry casting airplane
parts (Document ID 1756, Tr. 105-106). She described how her patient
could no longer work because of his condition. ``He requires oxygen and
systemic therapy . . . despite aggressive treatment [his] test findings
continue to demonstrate worsening of his disease and increased needs
for oxygen and medications as well as severe side effects from
medications. This patient may well need a lung transplant if this
disease continues to progress . . . '' (Document ID 1756, Tr. 106-107).
    The likelihood, speed, and severity of individuals' transition from
asymptomatic to symptomatic CBD is understood to vary widely, with some
individuals responding differently to exposure cessation and treatment
than others (Sood, 2009, Document ID 0456; Mroz et al., 2009 (1443)).
In the public hearing, Dr. Newman testified that the great majority of
individuals with very early stage CBD in a cross-sectional study he
published (Pappas and Newman, 1993) had physiologic impairment. Thus,
even before x-rays or CAT scans found evidence of CBD, the lung
functions of those individuals were abnormal (Document ID 1756, Tr.
112). Materion commented that the best available evidence on the
transition from asymptomatic to more severe CBD is a recent
longitudinal study by Mroz et al. (2009, Document ID 1443), which found
that 19.3 percent of individuals with CBD developed clinical
abnormalities requiring oral immunosuppressive therapy (Document ID
1661, pp. 5-6). The authors' overall conclusions in that study include
a finding that adverse physiological changes among initially
asymptomatic CBD patients progress over time, requiring many
individuals to be treated with corticosteroids, and that the patients'
levels of beryllium exposure may affect progression (Mroz et al.,
2009). Dr. Maier, a co-author of the study, testified that studies
``indicate that higher levels of exposure not only are risk factors for
[developing CBD in general] but also for more severe [CBD] (Document ID
1756, Tr. 111).\24\
---------------------------------------------------------------------------

    \24\ The study by Mroz et al. (2009, Document ID 1443) included
all individuals who were clinically evaluated at NJH between 1982
and 2002 and were found to have CBD on baseline clinical evaluation.
All cohort members were identified by abnormal BeLPTs before
identification of symptoms, physiologic abnormalities, or
radiographic changes. All members were offered evaluation for
clinical abnormalities every 2 years through 2002, including
pulmonary function testing, exercise testing, chest radiograph with
International Labor Organization (ILO) B-reading, fiberoptic
bronchoscopy with bronchoalveolar lavage (BAL), and transbronchial
lung biopsies. Of 171 CBD cases, 33 (19.3%) developed clinical
abnormalities requiring oral immunosuppressive therapy, at an
average of 1.4 years after the initial diagnosis of CBD. To examine
the effect of beryllium exposure level on the progression of CBD,
Mroz et al. compared clinical manifestations of CBD among machinists
(the group of patients likely to have had the highest beryllium
exposures) to non- machinists, including only CBD patients who had
never smoked. Longitudinal analyses showed significant declines in
some clinical indicators over time since first exposure for
machinists (p <0.01) as well as faster development of illness (p <
0.05), compared to a control group of non-machinists.
---------------------------------------------------------------------------

    Treatment of CBD using inhaled and systemic steroid therapy has
been shown to ease symptoms and slow or prevent some aspects of disease
progression. As explained below, these treatments can be most
effectively applied when CBD is diagnosed prior to development of
symptoms. In addition, the forms of treatment that can be used to
manage early-stage CBD have relatively minor side effects on patients,
while systemic steroid treatments required to treat later-stage CBD
often cause severe side effects.
    In the public hearing, Dr. Newman and Dr. Maier testified about
their experiences treating patients with CBD at various stages of the
disease. Dr. Newman stated that patients' outcomes depend greatly on
how early they are diagnosed. ``So there are those people who are
diagnosed very late in the course of disease where there's little that
we can do to intervene and they are going to die prematurely. There are
those people who may be detected with milder disease where there are
opportunities to intervene'' (Document ID 1756, Tr. 132). Both Dr.
Maier and Dr. Newman emphasized the importance of early detection and
diagnosis, stating that removing the patient from exposure and
providing treatment early in the course of the disease can slow or even
halt progression of the disease (Document ID 1756, Tr. 111, 132).
    Dr. Maier testified that inhaled steroids can be used to treat
relatively mild symptoms that may occur in early stages of the disease,
such as a cough during exercise (Document ID 1756, Tr. 139). Inhaled
steroids, she stated, are commonly used to treat other health
conditions and have fewer and milder side effects than forms of steroid
treatment that are used to treat more severe forms of CBD (Document ID
1756, Tr. 140). Early detection of CBD helps physicians to properly
treat early-onset symptoms, since appropriate forms of treatment for
early stage CBD can differ from treatments for conditions it is
commonly mistaken for, such as chronic obstructive pulmonary disease

(COPD) and asthma (Document ID 1756, Tr. 140-141).
    CBD in later stages is often managed using systemic steroid
treatments such as corticosteroids. In workers with CBD whose beryllium
exposure has ceased, corticosteroid therapy has been shown to control
inflammation, ease symptoms (e.g., difficulty breathing, fever, cough,
and weight loss), and in some cases prevent the development of fibrosis
(Marchand-Adam et al., 2008, Document ID 0370). Thus, although there is
no cure for CBD, properly-timed treatment can lead to CBD regression in
some patients (Sood, 2004, Document ID 1331). Other patients have shown
short-term improvements from corticosteroid treatment, but then
developed serious fibrotic lesions (Marchand-Adam et al., 2008). Ms.
Peggy Mroz, of NJH, discussed the results of the Marchand-Adam et al.
study in the hearing, stating that treatment of CBD using steroids has
been most successful when treatment begins prior to the development of
lung fibrosis (Document ID 1756, Tr. 113). Once fibrosis has developed
in the lungs, corticosteroid treatment cannot reverse the damage (Sood,
2009, Document ID 0456). Persons with late-stage CBD experience severe
respiratory insufficiency and may require supplemental oxygen (Rossman,
1991, Document 1332). Historically, late-stage CBD often ended in death
(NAS, 2008, Document ID 1355). While the use of steroid treatments can
help to reduce the effects of CBD, OSHA is not aware of any studies
showing the effect of these treatments on the frequency of premature
death among patients with CBD.
    Treatment with corticosteroids has severe side effects
(Trikudanathan and McMahon, 2008, Document ID 0366; Lipworth, 1999
(0371); Gibson et al., 1996 (1521); Zaki et al., 1987 (1374)). Adverse
effects associated with long-term corticosteroid use include, but are
not limited to: increased risk of opportunistic infections (Lionakis
and Kontoyiannis, 2003, Document ID 0372; Trikudanathan and McMahon,
2008 (0366)); accelerated bone loss or osteoporosis leading to
increased risk of fractures or breaks (Hamida et al., 2011, Document ID
0374; Lehouck et al., 2011 (0355); Silva et al., 2011 (0388); Sweiss et
al., 2011 (0367); Langhammer et al., 2009 (0373)); psychiatric effects
including depression, sleep disturbances, and psychosis (Warrington and
Bostwick, 2006, Document ID 0365; Brown, 2009 (0377)); adrenal
suppression (Lipworth, 1999, Document ID 0371; Frauman, 1996 (0356));
ocular effects including cataracts, ocular hypertension, and glaucoma
(Ballonzoli and Bourcier, 2010, Document ID 0391; Trikudanathan and
McMahon, 2008 (0366); Lipworth, 1999 (0371)); an increase in glucose
intolerance (Trikudanathan and McMahon, 2008, Document ID 0366);
excessive weight gain (McDonough et al., 2008, Document ID 0369; Torres
and Nowson, 2007 (0387); Dallman et al., 2007 (0357); Wolf, 2002
(0354); Cheskin et al., 1999 (0358)); increased risk of atherosclerosis
and other cardiovascular syndromes (Franchimont et al., 2002, Document
ID 0376); skin fragility (Lipworth, 1999, Document ID 0371); and poor
wound healing (de Silva and Fellows, 2010, Document ID 0390).
    Based on the above, OSHA considers late-stage CBD to be a material
impairment of health, as it involves permanent damage to the pulmonary
system, causes additional serious adverse health effects, can have
adverse occupational and social consequences, requires treatment that
can cause severe and lasting side effects, and may in some cases cause
premature death.
    Furthermore, OSHA has determined that early-stage CBD, an
asymptomatic period during which small lesions and inflammation appear
in the lungs, is also a material impairment of health. OSHA bases this
conclusion on evidence and expert testimony that early-stage CBD is a
measurable change in an individual's state of health that, with and
sometimes without continued exposure, can progress to symptomatic
disease (e.g., Mroz et al., 2009 (1443); 1756, Tr. 131). Thus,
prevention of the earliest stages of CBD will prevent development of
more serious disease. In OSHA's Lead standard, promulgated in 1978, the
Agency stated its position that a ``subclinical'' health effect may be
regarded as a material impairment of health. In the preamble to that
standard, the Agency said:

    OSHA believes that while incapacitating illness and death
represent one extreme of a spectrum of responses, other biological
effects such as metabolic or physiological changes are precursors or
sentinels of disease which should be prevented. . . . Rather than
revealing the beginnings of illness the standard must be selected to
prevent an earlier point of measurable change in the state of health
which is the first significant indicator of possibly more severe ill
health in the future. The basis for this decision is twofold--first,
pathophysiologic changes are early stages in the disease process
which would grow worse with continued exposure and which may include
early effects which even at early stages are irreversible, and
therefore represent material impairment themselves. Secondly,
prevention of pathophysiologic changes will prevent the onset of the
more serious, irreversible and debilitating manifestations of
disease (43 FR 52952, 52954).

    Since the Lead rulemaking, OSHA has also found other non-
symptomatic (or sub-clinical) health conditions to be material
impairments of health. In the Bloodborne Pathogens rulemaking, OSHA
maintained that material impairment includes not only workers with
clinically ``active'' hepatitis from the hepatitis B virus (HBV) but
also includes asymptomatic HBV ``carriers'' who remain infectious and
are able to put others at risk of serious disease through contact with
body fluids (e.g., blood, sexual contact) (56 FR 64004). OSHA stated:
``Becoming a carrier [of HBV] is a material impairment of health even
though the carrier may have no symptoms. This is because the carrier
will remain infectious, probably for the rest of his or her life, and
any person who is not immune to HBV who comes in contact with the
carrier's blood or certain other body fluids will be at risk of
becoming infected'' (56 FR 64004, 64036).
    OSHA finds that early-stage CBD is the type of asymptomatic health
effect the Agency determined to be a material impairment of health in
the Lead and Bloodborne Pathogens standards. Early stage CBD involves
lung tissue inflammation without symptoms that can worsen with--or
without--continued exposure. The lung pathology progresses over time
from a chronic inflammatory response to tissue scarring and fibrosis
accompanied by moderate to severe loss in pulmonary function. Early
stage CBD is clearly a precursor of advanced clinical disease,
prevention of which will prevent symptomatic disease. OSHA determined
in the Lead standard that such precursor effects should be considered
material health impairments in their own right, and that the Agency
should act to prevent them when it is feasible to do so. Therefore,
OSHA finds all stages of CBD to be material impairments of health
within the meaning of section 6(b)(5) of the OSH Act (29 U.S.C.
655(b)(5)).
    In reviewing OSHA's Lead standard in United Steelworkers of
America, AFL-CIO v. Marshall, 647 F.2d 1189, 1252 (D.C. Cir. 1980)
(Lead I), the D.C. Circuit affirmed that the OSH Act ``empowers OSHA to
set a PEL that prevents the subclinical effects of lead that lie on a
continuum shared with overt lead disease.'' See also AFL-CIO v.
Marshall, 617 F.2d 636, 654 n.83 (D.C. Cir. 1979) (upholding OSHA's
authority to prevent early symptoms of a disease, even if the effects
of the disease are, at that point, reversible). According to the Court,
OSHA only had to demonstrate,

on the basis of substantial evidence, that preventing the subclinical
effects would help prevent the clinical phase of disease (United
Steelworkers of America, AFL-CIO, 647 F.2d at 1252). Thus, OSHA has the
authority to regulate to prevent asymptomatic CBD whether or not it is
properly labeled as a material impairment of health.
    OSHA has also determined that exposure to beryllium can cause
beryllium sensitization. Sensitization is a precursor to development of
CBD and an essential step for development of the disease. As discussed
in Section V, Health Effects, only sensitized individuals can develop
CBD (NAS, 2008, Document ID 1355).\25\ As explained above, OSHA has the
authority to promulgate regulations designed to prevent precursors to
material impairments of health. Therefore, OSHA's new beryllium
standards aim to prevent sensitization as well as the development of
CBD and lung cancer. OSHA's risk assessment for sensitization,
presented in section VI, informs the Agency's understanding of what
exposure control measures have been successful in preventing
sensitization, which in turn prevents development of CBD. Therefore,
OSHA addresses sensitization in this section on significance of risk.
---------------------------------------------------------------------------

    \25\ In the NPRM, OSHA took no position on whether beryllium
sensitization by itself is a material impairment of health, stating
it was unnecessary to do so as part of this rulemaking. The only
comment on this issue came from Materion, which argued that ``BeS
does not constitute a material impairment of health or functional
capacity'' (document ID 1958). Because BeS is also a precursor to
CBD, OSHA finds it unnecessary to resolve this issue here.
---------------------------------------------------------------------------

Risk Assessment

    As discussed in Section VI, Risk Assessment, the risk assessment
for beryllium sensitization and CBD relied on two approaches: (1)
OSHA's review of epidemiological studies of sensitization and CBD that
contain information on exposures in the range of interest to OSHA (2
[mu]g/m\3\ and below), and (2) OSHA's analysis of a NJH data set on
sensitization and CBD in a group of beryllium-exposed machinists in
Cullman, AL.
    OSHA's review of the literature includes studies of beryllium-
exposed workers at a Tucson, AZ ceramics plant (Kreiss et al., 1996,
Document ID 1477; Henneberger et al., 2001 (1313); Cummings et al.,
2007 (1369)); a Reading, PA copper-beryllium processing plant (Schuler
et al., 2005, Document ID 0919; Thomas et al., 2009 (0590)); a Cullman,
AL beryllium machining plant (Newman et al., 2001, Document ID 1354;
Kelleher et al., 2001 (1363); Madl et al., 2007 (1056)); an Elmore, OH
metal, alloy, and oxide production plant (Kreiss et al., 1993 Document
ID 1478; Bailey et al., 2010 (0676); Schuler et al., 2012 (0473));
aluminum smelting facilities (Taiwo et al. 2008, Document ID 0621; 2010
(0583); Nilsen et al., 2010 (0460)); and nuclear facilities (Viet et
al., 2000, Document ID 1344; Arjomandi et al., 2010 (1275)).
    The published literature on beryllium sensitization and CBD
discussed in section VI shows that the risk of both can be significant
in workplaces where exposures are at or below OSHA's preceding PEL of 2
[mu]g/m\3\ (e.g., Kreiss et al., 1996, Document ID 1477; Henneberger et
al., 2001 (1313); Newman et al., 2001 (1354); Schuler et al., 2005
(0919), 2012 (0473); Madl et al., 2007 (1056)). For example, in the
Tucson ceramics plant mentioned above, Kreiss et al. (1996) reported
that eight (5.9 percent) \26\ of the 136 workers tested in 1992 were
sensitized, six (4.4 percent) of whom were diagnosed with CBD. In
addition, of 77 Tucson workers hired prior to 1992 who were tested in
1998, eight (10.4 percent) were sensitized and seven of these (9.7
percent) were diagnosed with CBD (Henneberger et al., 2001, Document ID
1313). Full-shift area samples showed most airborne beryllium levels
below the preceding PEL: 76 percent of area samples collected between
1983 and 1992 were at or below 0.1 [mu]g/m\3\ and less than 1 percent
exceeded 2 [mu]g/m\3\; short-term breathing zone measurements collected
between 1981 and 1992 had a median of 0.3 [mu]g/m\3\; and personal
lapel samples collected at the plant beginning in 1991 had a median of
0.2 [mu]g/m\3\ (Kreiss et al., 1996).
---------------------------------------------------------------------------

    \26\ Although OSHA reports percentages to indicate the risks of
sensitization and CBD in this section, the benchmark OSHA typically
uses to demonstrate significant risk, as discussed earlier, is
greater than or equal to 1 in 1,000 workers. One in 1,000 workers is
equivalent to 0.1 percent. Therefore, any value of 0.1 percent or
higher when reporting occurrence of a health effect is considered by
OSHA to indicate a significant risk.
---------------------------------------------------------------------------

    Results from the Elmore, OH beryllium metal, alloy, and oxide
production plant and the Cullman, AL machining facility also showed
significant risk of sensitization and CBD among workers with exposures
below the preceding TWA PEL. Schuler et al. (2012, Document ID 0473)
found 17 cases of sensitization (8.6 percent) among Elmore, OH workers
within the first three quartiles of LTW average exposure (198 workers
with LTW average total mass exposures lower than 1.1 [mu]g/m\3\) and 4
cases of CBD (2.2 percent) within those quartiles of LTW average
exposure (183 workers with LTW average total mass exposures lower than
1.07 [mu]g/m\3\; note that follow-up time of up to 6 years for all
study participants was very short for development of CBD). At the
Cullman, AL machining facility, Newman et al. (2001, Document ID 1354)
reported 22 (9.4 percent) sensitized workers among 235 tested in 1995-
1999, 13 of whom were diagnosed with CBD within the study period.
Personal lapel samples collected between 1980 and 1999 indicate that
median exposures were generally well below the preceding PEL (<=0.35
[mu]g/m\3\ in all job titles except maintenance (median 3.1 [mu]g/m\3\
during 1980-1995) and gas bearings (1.05 [mu]g/m\3\ during 1980-1995)).
    Although risk will be reduced by compliance with the new TWA PEL,
evidence in the epidemiological studies reviewed in section VI, Risk
Assessment, shows that significant risk of sensitization and CBD could
remain in workplaces with exposures as low as the new action level of
0.1 [mu]g/m\3\. For example, Schuler et al. (2005, Document ID 0919)
reported substantial prevalences of sensitization (6.5 percent) and CBD
(3.9 percent) among 152 workers at the Reading, PA facility screened
with the BeLPT in 2000. These results showed significant risk at this
facility, even though airborne exposures were primarily below both the
preceding and final TWA PELs due to the low percentage of beryllium in
the metal alloys used (median general area samples <=0.1 [mu]g/m\3\,
97% < 0.5 [mu]g/m\3\; 93% of personal lapel samples below the new TWA
PEL of 0.2 [mu]g/m\3\). The only group of workers with no cases of
sensitization or CBD, a group of 26 office administration workers, was
the group with exposures below the new action level of 0.1 [mu]g/m\3\
(median personal sample 0.01 [mu]g/m\3\, range <0.01-0.06 [mu]g/m\3\)
(Schuler et al., 2005). The Schuler et al. (2012, Document ID 0473)
study of short-term workers in the Elmore, OH facility found three
cases (4.6%) of sensitization among 66 workers with total mass LTW
average exposures below 0.1 [mu]g/m\3\. All three of these sensitized
workers had LTW average exposures of approximately 0.09 [mu]g/m\3\.
    Furthermore, cases of sensitization and CBD continued to arise in
the Cullman, AL machining plant after control measures implemented
beginning in 1995 brought median airborne exposures below 0.2 [mu]g/
m\3\ (personal lapel samples between 1996 and 1999 in machining jobs
had a median of 0.16 [mu]g/m\3\ and the median was 0.08 [mu]g/m\3\ in
non-machining jobs)

(Madl et al., 2007, Document ID 1056, Table IV). At the time that
Newman et al. (2001, Document ID 1354) reviewed the results of BeLPT
screenings conducted in 1995-1999, a subset of 60 workers had been
employed at the plant for less than a year and had therefore benefitted
to some extent from the exposure reductions. Four (6.7 percent) of
these workers were found to be sensitized, of whom two were diagnosed
with CBD and one with probable CBD (Newman et al., 2001). A later study
by Madl. et al. (2007, Document ID 1056) reported seven sensitized
workers who had been hired between 1995 and 1999, of whom four had
developed CBD as of 2005 (Table II; total number of workers hired
between 1995 and 1999 not reported).
    The enhanced industrial hygiene programs that have proven effective
in several facilities demonstrate the importance of minimizing both
airborne exposure and dermal contact to effectively reduce risk of
sensitization and CBD. Exposure control programs that have used a
combination of engineering controls, PPE, and stringent housekeeping
measures to reduce workers' airborne exposure and dermal contact have
substantially lowered risk of sensitization among newly-hired
workers.\27\ Of 97 workers hired between 2000 and 2004 in the Tucson,
AZ plant after the introduction of a comprehensive program which
included the use of respiratory protection (1999) and latex gloves
(2000), one case of sensitization was identified (1 percent) (Cummings
et al., 2007, Document ID 1369). In Elmore, OH, where all workers were
required to wear respirators and skin PPE in production areas beginning
in 2000-2001, the estimated prevalence of sensitization among workers
hired after these measures were put in place was around 2 percent
(Bailey et al., 2010, Document ID 0676). In the Reading, PA facility,
after workers' exposures were reduced to below 0.1 [mu]g/m\3\ and PPE
to prevent dermal contact was instituted, only one (2.2 percent) of 45
workers hired was sensitized (Thomas et al. 2009, Document ID 0590).
And, in the aluminum smelters discussed by Taiwo et al. (2008, Document
ID 0621), where available exposure samples from four plants indicated
median beryllium levels of about 0.1 [mu]g/m\3\ or below (measured as
an 8-hour TWA) and workers used respiratory and dermal protection,
confirmed cases of sensitization were rare (zero or one case per
location).
---------------------------------------------------------------------------

    \27\ As discussed in Section V, Health Effects, beryllium
sensitization can occur from dermal contact with beryllium.
---------------------------------------------------------------------------

    OSHA notes that the studies on recent programs to reduce workers'
risk of sensitization and CBD were conducted on populations with very
short exposure and follow-up time. Therefore, they could not adequately
address the question of how frequently workers who become sensitized in
environments with extremely low airborne exposures (median <0.1 [mu]g/
m\3\) develop CBD. Clinical evaluation for CBD was not reported for
sensitized workers identified in the studies examining the post-2000
worker cohorts with very low exposures in Tucson, Reading, and Elmore
(Cummings et al. 2007, Document ID 1369; Thomas et al. 2009, (0590);
Bailey et al. 2010, (0676)). In Cullman, however, two of the workers
with CBD had been employed for less than a year and worked in jobs with
very low exposures (median 8-hour personal sample values of 0.03-0.09
[mu]g/m\3\) (Madl et al., 2007, Document ID 1056, Table III). The body
of scientific literature on occupational beryllium disease also
includes case reports of workers with CBD who are known or believed to
have experienced minimal beryllium exposure, such as a worker employed
only in shipping at a copper-beryllium distribution center (Stanton et
al., 2006, Document ID 1070), and workers employed only in
administration at a beryllium ceramics facility (Kreiss et al., 1996,
Document ID 1477). Therefore, there is some evidence that cases of CBD
can occur in work environments where beryllium exposures are quite low.
    In summary, the epidemiological literature on beryllium
sensitization and CBD that OSHA's risk assessment relied on show
sufficient occurrence of sensitization and CBD to be considered
significant within the meaning of the OSH Act. These demonstrated risks
are far in excess of 1 in 1,000 among workers who had full-shift
exposures well below the preceding TWA PEL of 2 [mu]g/m\3\ and workers
who had median full-shift exposures down to the new action level of 0.1
[mu]g/m\3\. These health effects occurred among populations of workers
whose follow-up time was much less than 45 years. As stated earlier,
OSHA is interested in the risk associated with a 45-year (i.e., working
lifetime) exposure. Because CBD often develops over the course of years
following sensitization, the risk of CBD that would result from 45
years of occupational exposure to airborne beryllium is likely to be
higher than the prevalence of CBD observed among these workers.\28\ In
either case, based on these studies, the risks to workers from long-
term exposure at the preceding TWA PEL and below are clearly
significant. OSHA's review of epidemiological studies further showed
that worker protection programs that effectively reduced the risk of
beryllium sensitization and CBD incorporated engineering controls, work
practice controls, and personal protective equipment (PPE) that reduce
workers' airborne beryllium exposure and dermal contact with beryllium.
OSHA has therefore determined that an effective worker protection
program should incorporate both airborne exposure reduction and dermal
protection provisions.
---------------------------------------------------------------------------

    \28\ This point was emphasized by members of the scientific peer
review panel for OSHA's Preliminary Risk Assessment (see the NPRM
preamble at section VII).
---------------------------------------------------------------------------

    OSHA's conclusions on significance of risk at the final PEL and
action level are further supported by its analysis of the data set
provided to OSHA by NJH from which OSHA derived additional information
on sensitization and CBD at exposure levels of interest. The data set
describes a population of 319 beryllium-exposed workers at a Cullman,
AL machining facility. It includes exposure samples collected between
1980 and 2005, and has updated work history and screening information
through 2003. Seven (2.2 percent) workers in the data set were reported
as sensitized only. Sixteen (5.0 percent) workers were listed as
sensitized and diagnosed with CBD upon initial clinical evaluation.
Three (0.9 percent) workers, first shown to be sensitized only, were
later diagnosed with CBD. The data set includes workers exposed at
airborne beryllium levels near the new TWA PEL of 0.2 [mu]g/m\3\, and
extensive exposure data collected in workers' breathing zones, as is
preferred by OSHA. Unlike the Tucson, Reading, and Elmore facilities
after 2000, respirator use was not generally required for workers at
the Cullman facility. Thus, analysis of this data set shows the risk
associated with varying levels of airborne exposure rather than
estimating exposure accounting for respirators. Also unlike the Tucson,
Elmore, and Reading facilities, glove use was not reported to be
mandatory in the Cullman facility. Therefore, OSHA believes reductions
in risk at the Cullman facility to be the result of airborne exposure
control, rather than the combination of airborne and dermal exposure
controls used at other facilities.
    OSHA analyzed the prevalence of beryllium sensitization and CBD
among

workers at the Cullman facility who were exposed to airborne beryllium
levels at and below the preceding TWA PEL of 2 [mu]g/m\3\. In addition,
a statistical modeling analysis of the NJH Cullman data set was
conducted under contract with Dr. Roslyn Stone of the University of
Pittsburgh Graduate School of Public Heath, Department of
Biostatistics. OSHA summarizes these analyses briefly below, and in
more detail in section VI, Risk Assessment and in the background
document (Risk Analysis of the NJH Data Set from the Beryllium
Machining Facility in Cullman, Alabama--CBD and Sensitization, OSHA,
2016).
    Tables VII-1 and VII-2 below present the prevalence of
sensitization and CBD cases across several categories of lifetime-
weighted (LTW) average and highest-exposed job (HEJ) exposure at the
Cullman facility. The HEJ exposure is the exposure level associated
with the highest-exposure job and time period experienced by each
worker. The columns ``Total'' and ``Total percent'' refer to all
sensitized workers in the data set, including workers with and without
a diagnosis of CBD.

                            Table VII-1--Prevalence of Sensitization and CBD by LTW Average Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
            LTW average exposure ([mu]g/m\3\)               Group size         only             CBD            Total        Total  (%)       CBD  (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.080...............................................              91               1               1               2             2.2             1.0
0.081-0.18..............................................              73               2               4               6             8.2             5.5
0.19-0.51...............................................              77               0               6               6             7.8             7.8
0.51-2.15...............................................              78               4               8              12            15.4            10.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.

                        Table VII-2--Prevalence of Sensitization and CBD by Highest-Exposed Job Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
                HEJ exposure ([mu]g/m\3\)                   Group size         only             CBD            Total         Total (%)        CBD (%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.086...............................................              86               1               0               1             1.2             0.0
0.091-0.214.............................................              81               1               6               7             8.6             7.4
0.387-0.691.............................................              76               2               9              11            14.5            11.8
0.954-2.213.............................................              76               3               4               7             9.2             5.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.

    The preceding PEL of 2 [mu]g/m\3\ is close to the upper bound of
the highest quartile of LTW average (0.51-2.15 [mu]g/m\3\) and HEJ
(0.954-2.213 [mu]g/m\3\) exposure levels. In the highest quartile of
LTW average exposure, there were 12 cases of sensitization (15.4
percent), including eight (10.3 percent) diagnosed with CBD. Notably,
the Cullman workers had been exposed to beryllium dust for considerably
less than 45 years at the time of testing. A high prevalence of
sensitization (9.2 percent) and CBD (5.3 percent) is seen in the top
quartile of HEJ exposure as well, with even higher prevalences in the
third quartile (0.387-0.691 [mu]g/m\3\).\29\
---------------------------------------------------------------------------

    \29\ This exposure-response pattern, wherein higher rates of
response are seen in workers with lower exposures, is sometimes
attributed to a ``healthy worker effect'' or to exposure
misclassification, as discussed in this preamble at section VI, Risk
Assessment.
---------------------------------------------------------------------------

    The new TWA PEL of 0.2 [mu]g/m\3\ is close to the upper bound of
the second quartile of LTW average (0.81-0.18 [mu]g/m\3\) and HEJ
(0.091-0.214 [mu]g/m\3\) exposure levels and to the lower bound of the
third quartile of LTW average (0.19-0.50 [mu]g/m\3\) exposures. The
second quartile of LTW average exposure shows a high prevalence of
beryllium-related health effects, with six workers sensitized (8.2
percent), of whom four (5.5 percent) were diagnosed with CBD. The
second quartile of HEJ exposure also shows a high prevalence of
beryllium-related health effects, with seven workers sensitized (8.6
percent), of whom six (7.4 percent) were diagnosed with CBD. Among six
sensitized workers in the third quartile of LTW average exposures, all
were diagnosed with CBD (7.8 percent). The prevalence of CBD among
workers in these quartiles was approximately 5-8 percent, and overall
sensitization (including workers with and without CBD) was about 8-9
percent. OSHA considers these rates to be evidence that the risks of
developing sensitization and CBD are significant among workers exposed
at and below the preceding TWA PEL, and even below the new TWA PEL.
These risks are much higher than the benchmark for significant risk of
1 in 1,000. Much lower prevalences of sensitization and CBD were found
among workers with exposure levels less than or equal to about 0.08
[mu]g/m\3\, although these risks are still significant. Two sensitized
workers (2.2 percent), including one case of CBD (1.0 percent), were
found among workers with LTW average exposure levels less than or equal
to 0.08 [mu]g/m\3\. One case of sensitization (1.2 percent) and no
cases of CBD were found among workers with HEJ exposures of at most
0.086 [mu]g/m\3\. Strict control of airborne exposure to levels below
0.1 [mu]g/m\3\ using engineering and work practice controls can,
therefore, substantially reduce risk of sensitization and CBD. Although
OSHA recognizes that maintaining exposure levels below 0.1 [mu]g/m\3\
may not be feasible in some operations (see this preamble at section
VIII, Summary of the Economic Analysis and Regulatory Flexibility
Analysis), the Agency finds that workers in facilities that meet the
action level of 0.1 [mu]g/m\3\ will face lower risks of sensitization
and CBD than workers in facilities that cannot meet the action level.
    Table VII-3 below presents the prevalence of sensitization and CBD
cases across cumulative exposure quartiles, based on the same Cullman
data used to derive Tables 1 and 2. Cumulative exposure is the sum of a
worker's exposure across the duration of his or her employment.

                            Table VII-3--Prevalence of Sensitization and CBD by Cumulative Exposure Quartile in NJH Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
          Cumulative exposure ([mu]g/m\3\-yrs)              Group size         only             CBD            Total          Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.147...............................................              81               2               2               4             4.9             2.5
0.148-1.467.............................................              79               0               2               2             2.5             2.5
1.468-7.008.............................................              79               3               8              11            13.9             8.0
7.009-61.86.............................................              80               2               7               9            11.3             8.8
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Risk Assessment.

    A 45-year working lifetime of occupational exposure at the
preceding PEL would result in 90 [mu]g/m\3\-years of exposure, a value
far higher than the cumulative exposures of workers in this data set,
who worked for periods of time less than 45 years and whose exposure
levels were mostly well below the previous PEL. Workers with 45 years
of exposure to the new TWA PEL of 0.2 [mu]g/m\3\ would have a
cumulative exposure (9 [mu]g/m\3\-years) in the highest quartile for
this worker population. As with the average and HEJ exposures, the
greatest risk of sensitization and CBD appears at the higher exposure
levels (<1.467 [mu]g/m\3\-years). The third cumulative quartile, at
which a sharp increase in sensitization and CBD appears, is bounded by
1.468 and 7.008 [mu]g/m\3\-years. This is equivalent to 0.73-3.50 years
of exposure at the preceding PEL of 2 [mu]g/m\3\, or 7.34-35.04 years
of exposure at the new TWA PEL of 0.2 [mu]g/m\3\. Prevalence of both
sensitization and CBD is substantially lower in the second cumulative
quartile (0.148-1.467 [mu]g/m\3\-years). This is equivalent to
approximately 0.7 to 7 years at the new TWA PEL of 0.2 [mu]g/m\3\, or
1.5 to 15 years at the action level of 0.1 [mu]g/m\3\. Risks at all
levels of cumulative exposure presented in Table 3 are significant.
These findings support OSHA's determination that maintaining exposure
levels below the new TWA PEL will help to protect workers against risk
of beryllium sensitization and CBD. Moreover, while OSHA finds that
significant risk remains at the PEL, OSHA's analysis shows that further
reductions of risk will ensue if employers are able to reduce exposure
to the action level or even below.

Lung Cancer

    Lung cancer, a frequently fatal disease, is a well-recognized
material impairment of health. OSHA has determined that beryllium
causes lung cancer based on an extensive review of the scientific
literature regarding beryllium and cancer. This review included an
evaluation of the human epidemiological, animal cancer, and mechanistic
studies described in section V, Health Effects. OSHA's conclusion that
beryllium is carcinogenic is supported by the findings of expert public
health and governmental organizations such as the International Agency
for Research on Cancer (IARC), which has determined beryllium and its
compounds to be carcinogenic to humans (Group 1 category) (IARC, 2012,
Document ID 0650); the National Toxicology Program (NTP), which
classifies beryllium and its compounds as known carcinogens (NTP, 2014,
Document ID 0389); and the Environmental Protection Agency (EPA), which
considers beryllium to be a probable human carcinogen (EPA, 1998,
Document ID 0661).
    OSHA's review of epidemiological studies of lung cancer mortality
among beryllium workers found that most of them did not characterize
exposure levels sufficiently to evaluate the risk of lung cancer at the
preceding and new TWA PELs. However, as discussed in this preamble at
section V, Health Effects and section VI, Risk Assessment, Schubauer-
Berigan et al. published a quantitative risk assessment based on
beryllium exposure and lung cancer mortality among 5,436 male workers
first employed at beryllium processing plants in Reading, PA, Elmore,
OH, and Hazleton, PA, prior to 1970 (Schubauer-Berigan et al., 2011,
Document ID 1265). This risk assessment addresses important sources of
uncertainty for previous lung cancer analyses, including the sole prior
exposure-response analysis for beryllium and lung cancer, conducted by
Sanderson et al. (2001) on workers from the Reading plant alone.
Workers from the Elmore and Hazleton plants who were added to the
analysis by Schubauer-Berigan et al. were, in general, exposed to lower
levels of beryllium than those at the Reading plant. The median worker
from Hazleton had a LTW average exposure of less than 1.5 [mu]g/m\3\,
while the median worker from Elmore had a LTW average exposure of less
than 1 [mu]g/m\3\. The Elmore and Hazleton worker populations also had
fewer short-term workers than the Reading population. Finally, the
updated cohorts followed the worker populations through 2005,
increasing the length of follow-up time compared to the previous
exposure-response analysis. For these reasons, OSHA based the
preliminary risk assessment for lung cancer on the Schubauer-Berigan
risk analysis.
    Schubauer-Berigan et al. (2011, Document ID 1265) analyzed the data
set using a variety of exposure-response modeling approaches, described
in this preamble at section VI, Risk Assessment. The authors found that
lung cancer mortality risk was strongly and significantly correlated
with mean, cumulative, and maximum measures of workers' exposure to
beryllium (all of the models reported in the study). They selected the
best-fitting models to generate risk estimates for male workers with a
mean exposure of 0.5 [mu]g/m\3\ (the current NIOSH Recommended Exposure
Limit for beryllium). In addition, they estimated the daily weighted
average exposure that would be associated with an excess lung cancer
mortality risk of one in one thousand (.005 [mu]g/m\3\ to .07 [mu]g/
m\3\ depending on model choice). At OSHA's request, the authors also
estimated excess lifetime risks for workers with mean exposures at the
preceding TWA PEL of 2 [mu]g/m\3\ as well as at each of the alternate
TWA PELs that were under consideration: 1 [mu]g/m\3\, 0.2 [mu]g/m\3\,
and 0.1 [mu]g/m\3\. Table VII-4 presents the estimated excess risk of
lung cancer mortality associated with various levels of beryllium
exposure, based on the final models presented in Schubauer-Berigan et
al's risk assessment.\30\
---------------------------------------------------------------------------

    \30\ The estimates for lung cancer represent ``excess'' risks in
the sense that they reflect the risk of dying from lung cancer over
and above the risk of dying from lung cancer faced by those who are
not occupationally exposed to beryllium.

 Table VII-4--Excess Risk of Lung Cancer Mortality per 1,000 Male Workers at Alternate PELs (based on Schubauer-
                                              Berigan et al., 2011)
----------------------------------------------------------------------------------------------------------------
                                                                   Mean exposure
     Exposure-response model     -------------------------------------------------------------------------------
                                  0.1 [mu]g/m\3\  0.2 [mu]g/m\3\  0.5 [mu]g/m\3\   1 [mu]g/m\3\    2 [mu]g/m\3\
----------------------------------------------------------------------------------------------------------------
Best monotonic PWL-all workers..             7.3              15              45             120             140
Best monotonic PWL--excluding                3.1             6.4              17              39              61
 professional and asbestos
 workers........................
Best categorical--all workers...             4.4               9              25              59             170
Best categorical--excluding                  1.4             2.7             7.1              15              33
 professional and asbestos
 workers........................
Power model--all workers........              12              19              30              40              52
Power model--excluding                        19              30              49              68              90
 professional and asbestos
 workers........................
----------------------------------------------------------------------------------------------------------------
Source: Schubauer-Berigan, Document ID 0521, pp. 6-10.

    The lowest estimate of excess lung cancer deaths from the six final
models presented by Schubauer-Berigan et al. is 33 per 1,000 workers
exposed at a mean level of 2 [mu]g/m\3\, the preceding TWA PEL. Risk
estimates as high as 170 lung cancer deaths per 1,000 result from the
other five models presented. Regardless of the model chosen, the excess
risk of about 33 to 170 per 1,000 workers is clearly significant,
falling well above the level of risk the Supreme Court indicated a
reasonable person might consider acceptable (see Benzene, 448 U.S. at
655). The new PEL of 0.2 [mu]g/m\3\ is expected to reduce these risks
significantly, to somewhere between 2.7 and 30 excess lung cancer
deaths per 1,000 workers. At the new action level of 0.1 [mu]g/m\3\,
risk falls within the range of 1.4 to 19 excess lung cancer deaths.
These risk estimates still fall above the threshold of 1 in 1,000 that
OSHA considers clearly significant. However, the Agency believes the
lung cancer risks should be regarded as less certain than the risk
estimates for CBD and sensitization discussed previously. While the
risk estimates for CBD and sensitization at the preceding and new TWA
PELs were determined from exposure levels observed in occupational
studies, the lung cancer risks were extrapolated from much higher
exposure levels.

Conclusions

    As discussed throughout this section, OSHA used the best available
scientific evidence to identify adverse health effects of occupational
beryllium exposure, and to evaluate exposed workers' risk of these
impairments. The Agency reviewed extensive epidemiological and
experimental research pertaining to adverse health effects of
occupational beryllium exposure, including lung cancer, CBD, and
beryllium sensitization, and has evaluated the risk of these effects
from exposures allowed under the preceding and new TWA PELs. The Agency
has, additionally, reviewed the medical literature, as well as previous
policy determinations and case law regarding material impairment of
health, and has determined that CBD, at all stages, and lung cancer
constitute material health impairments.
    OSHA has determined that long-term exposure to beryllium at the
preceding TWA PEL would pose a risk of CBD and lung cancer greater than
the risk of 1 per 1,000 exposed workers the Agency considers clearly
significant, and that adoption of the new TWA PEL, action level, and
dermal protection requirements of the final standards will
substantially reduce this risk. OSHA believes substantial evidence
supports its determinations, including its choices of the best
available published studies on which to base its risk assessment, its
examination of the prevalence of sensitization and CBD among workers
with exposure levels comparable to the preceding TWA PEL and new TWA
PEL in the NJH data set, and its selection of the Schubauer-Berigan QRA
to form the basis for its lung cancer risk estimates. The previously-
described analyses demonstrate that workers with occupational exposure
to airborne beryllium at the preceding PEL face risks of developing CBD
and dying from lung cancer that far exceed the value of 1 in 1,000 used
by OSHA as a benchmark of clearly significant risk. Furthermore, OSHA's
risk assessment indicates that risk of CBD and lung cancer can be
significantly reduced by reduction of airborne exposure levels, and
that dermal protection measures will additionally help reduce risk of
sensitization and, therefore, of CBD.
    OSHA's risk assessment also indicates that, despite the reduction
in risk expected with the new PEL, the risks of CBD and lung cancer to
workers with average exposure levels of 0.2 [mu]g/m\3\ are still
significant and could extend down to 0.1 [mu]g/m\3\, although there is
greater uncertainty in this finding for 0.1 [mu]g/m\3\ since there is
less information available on populations exposed at and below this
level. Although significant risk remains at the new TWA PEL, OSHA is
also required to consider the technological and economic feasibility of
the standard in determining exposure limits. As explained in Section
VIII, Summary of the Final Economic Analysis and Final Regulatory
Flexibility Analysis, OSHA determined that the new TWA PEL of 0.2
[mu]g/m\3\ is both technologically and economically feasible in the
general industry, construction, and shipyard sectors. OSHA was unable
to demonstrate, however, that a lower TWA PEL of 0.1 [mu]g/m\3\ would
be technologically feasible. Therefore, OSHA concludes that, in setting
a TWA PEL of 0.2 [mu]g/m\3\, the Agency is reducing the risk to the
extent feasible, as required by the OSH Act (see section II, Pertinent
Legal Authority). In this context, the Agency finds that the action
level of 0.1 [mu]g/m\3\, dermal protection requirements, and other
ancillary provisions of the final rule are critically important in
reducing the risk of sensitization, CBD, and lung cancer among workers
exposed to beryllium. Together, these provisions, along with the new
TWA PEL of 0.2 [mu]g/m\3\, will substantially reduce workers' risk of
material impairment of health from occupational beryllium exposure.

VIII. Summary of the Final Economic Analysis and Final Regulatory
Flexibility Analysis

A. Introduction

    OSHA's Final Economic Analysis and Final Regulatory Flexibility
Analysis (FEA) addresses issues related to the costs, benefits,
technological and economic feasibility, and the economic impacts
(including impacts on small entities) of this final beryllium rule and
evaluates regulatory alternatives to the final rule. Executive Orders
13563 and

12866 direct agencies to assess all costs and benefits of available
regulatory alternatives and, if regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, and public health and safety effects;
distributive impacts; and equity). Executive Order 13563 emphasized the
importance of quantifying both costs and benefits, of reducing costs,
of harmonizing rules, and of promoting flexibility. The full FEA has
been placed in OSHA rulemaking docket OSHA-H005C-2006-0870. This rule
is an economically significant regulatory action under Sec. 3(f)(1) of
Executive Order 12866 and has been reviewed by the Office of
Information and Regulatory Affairs in the Office of Management and
Budget, as required by executive order.
    The purpose of the FEA is to:
     Identify the establishments and industries potentially
affected by the final rule;
     Estimate current exposures and the technologically
feasible methods of controlling these exposures;
     Estimate the benefits resulting from employers coming into
compliance with the final rule in terms of reductions in cases of lung
cancer, chronic beryllium disease;
     Evaluate the costs and economic impacts that
establishments in the regulated community will incur to achieve
compliance with the final rule;
     Assess the economic feasibility of the final rule for
affected industries; and
     Assess the impact of the final rule on small entities
through a Final Regulatory Flexibility Analysis (FRFA), to include an
evaluation of significant regulatory alternatives to the final rule
that OSHA has considered.
Significant Changes to the FEA Between the Proposed Standards and the
Final Standards
    OSHA made changes to the Preliminary Economic Analysis (PEA) for
several reasons:
     Changes to the rule, summarized in Section I of the
preamble and discussed in detail in the Summary and Explanation;
     Comments on the PEA;
     Updates of economic data; and
     Recognition of errors in the PEA.
    OSHA revised its technological and economic analysis in response to
these changes and to comments received on the NPRM. The FEA contains
some costs that were not included in the PEA and updates data to use
more recent data sources and, in some cases, revised methodologies.
Detailed discussions of these changes are included in the relevant
sections throughout the FEA.
    The Final Economic Analysis contains the following chapters:

Chapter I. Introduction
Chapter II. Market Failure and the Need for Regulation
Chapter III. Profile of Affected Industries
Chapter IV. Technological Feasibility
Chapter V. Costs of Compliance
Chapter VI. Economic Feasibility Analysis and Regulatory Flexibility
Determination
Chapter VII. Benefits and Net Benefits
Chapter VIII. Regulatory Alternatives
Chapter IX. Final Regulatory Flexibility Analysis

    Table VIII-1 provides a summary of OSHA's best estimate of the
costs and benefits of the final rule using a discount rate of 3
percent. As shown, the final rule is estimated to prevent 90 fatalities
and 46 beryllium-related illnesses annually once it is fully effective,
and the estimated cost of the rule is $74 million annually. Also as
shown in Table VIII-1, the discounted monetized benefits of the final
rule are estimated to be $561 million annually, and the final rule is
estimated to generate net benefits of $487 million annually. Table
VIII-1 also presents the estimated costs and benefits of the final rule
using a discount rate of 7 percent.

   Table VIII-1--Annualized Benefits, Costs and Net Benefits of OSHA's
                        Final Beryllium Standard
                 [3 Percent Discount Rate, 2015 dollars]
------------------------------------------------------------------------

------------------------------------------------------------------------
Annualized Costs:
  Control Costs.........................................     $12,269,190
  Rule Familiarization..................................         180,158
  Exposure Assessment...................................      13,748,676
  Regulated Areas.......................................         884,106
  Beryllium Work Areas..................................         129,648
  Medical Surveillance..................................       7,390,958
  Medical Removal.......................................       1,151,058
  Written Exposure Control Plan.........................       2,339,058
  Protective Work Clothing & Equipment..................       1,985,782
  Hygiene Areas and Practices...........................       2,420,584
  Housekeeping..........................................      22,763,595
  Training..............................................       8,284,531
  Respirators...........................................         320,885
                                                         ---------------
      Total Annualized Costs (Point Estimate)...........      73,868,230
Annual Benefits: Number of Cases Prevented:
  Fatal Lung Cancers (Midpoint Estimate)................               4
  Fatal Chronic Beryllium Disease.......................              86
  Beryllium-Related Mortality...........................              90
  Beryllium Morbidity...................................              46
  Monetized Annual Benefits (Midpoint Estimate).........    $560,873,424
Net Benefits:
  Net Benefits..........................................    $487,005,194
------------------------------------------------------------------------
Sources: US DOL, OSHA, Directorate of Standards and Guidance, Office of
  Regulatory Analysis

    The remainder of this section (Section VIII) of the preamble is
organized as follows:

B. Market Failure and the Need for Regulation
C. Profile of Affected Industries
D. Technological Feasibility
E. Costs of Compliance
F. Economic Feasibility Analysis and Regulatory Flexibility
Determination
G. Benefits and Net Benefits
H. Regulatory Alternatives
I. Final Regulatory Flexibility Analysis.

B. Market Failure and the Need for Regulation

    Employees in work environments addressed by the final beryllium
rule are exposed to a variety of significant hazards that can and do
cause serious injury and death. As described in Chapter II of the FEA
in support of the final rule, OSHA concludes there is a demonstrable
failure of private markets to protect workers from exposure to
unnecessarily high levels beryllium and that private markets, as well
as information dissemination programs, workers' compensation systems,
and tort liability options, each may fail to protect workers from
beryllium exposure, resulting in the need for a more protective OSHA
beryllium rule.
    After carefully weighing the various potential advantages and
disadvantages of using a regulatory approach to improve upon the
current situation, OSHA concludes that, in the case of beryllium
exposure, the final mandatory standards represent the best choice for
reducing the risks to employees.

C. Profile of Affected Industries

    Chapter III of the FEA presents profile data for industries
potentially affected by the final beryllium rule. This Chapter provides
the background data used throughout the remainder of the FEA including
estimates of what industries are affected, and their economic and
beryllium exposure characteristics. OSHA identified the following
application groups as affected by the standard:

 Beryllium Production
 Beryllium Oxide Ceramics and Composites
 Nonferrous Foundries
 Secondary Smelting, Refining, and Alloying
 Precision Turned Products
 Copper Rolling, Drawing, and Extruding
 Fabrication of Beryllium Alloy Products
 Welding
 Dental Laboratories
 Aluminum Production
 Coal-Fired Electric Power Generation

 Abrasive Blasting

    Table VIII-3 shows the affected industries by application group and
selected economic characteristics of these affected industries. Table
VIII-4 provides industry-by-industry estimates of current exposure.

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D. Technological Feasibility of the Final Standard on Occupational
Exposure to Beryllium

    The OSH Act requires OSHA to demonstrate that a proposed health
standard is technologically feasible (29 U.S.C. 655(b)(5)). As
described in the preamble to the final rule (see Section II, Pertinent
Legal Authority), technological feasibility has been interpreted
broadly to mean ``capable of being done'' (Am. Textile Mfrs. Inst. v.
Donovan, 452 U.S. 490, 509-510 (1981) (``Cotton Dust'')). A standard is
technologically feasible if the protective measures it requires already
exist, can be brought into existence with available technology, or can
be created with technology that can reasonably be expected to be
developed, i.e., technology that ``looms on today's horizon'' (United
Steelworkers of Am., AFL-CIO-CLC v. Marshall, 647 F.2d 1189, 1272 (D.C.
Cir. 1980) (``Lead I''); Amer. Iron & Steel Inst. v. OSHA, 939 F.2d
975, 980 (D.C. Cir. 1991) (``Lead II''); AFL-CIO v. Brennan, 530 F.2
109, 121 (3rd Cir. 1975)). Courts have also interpreted technological
feasibility to mean that, for health standards, a typical firm in each
affected industry will reasonably be able to implement engineering and
work practice controls that can reduce workers' exposures to meet the
permissible exposure limit in most operations most of the time, without
reliance on respiratory protection (see Lead I, 647 F.2d at 1272; Lead
II, 939 F.2d at 990).
    OSHA's technological feasibility analysis is presented in Chapter
IV of the FEA. The technological feasibility analysis identifies the
affected industries and application groups in which employees can
reasonably be expected to be exposed to beryllium, summarizes the
available air sampling data used to develop employee exposure profiles,
and provides descriptions of engineering controls and other measures
employers can take to reduce their employees' exposures to beryllium.
For each affected industry sector or application group, OSHA provides
an assessment of the technological feasibility of compliance with the
final permissible exposure limit (PEL) of 0.2 [mu]g/m\3\ as an 8-hour
TWA and a 15-minute short-term exposure limit (STEL) of 2.0 [mu]g/m\3\.