Rosenman et al., 2005........  Cross-sectional   14.5 (83 cases).  5.5 (32 cases)..  Mean average      No.............  ...............  Daily weighted
                                study of 577                                          range--7.1-8.7                                      average:
                                workers.                                              [mu]g/m\3\;.                                       High exposures
                                                                                Mean peak range--                                    compared to
                                                                                53-87 [mu]g/                                        other studies.
                                                                                m\3\;.
                                                                                Mean cumulative
                                                                                range--100-209
                                                                                [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                             Beryllium Machining Operations
--------------------------------------------------------------------------------------------------------------------------------------------------------
Newman et al., 2001..........  Longitudinal      9.4 (22 cases)..  8.5 (20 cases)..  ................  No.............  ...............  Engineering and
                                study of 235                                                                                administrative
                                workers.                                                                                controls
                                                                                primarily used
                                                                                to control
                                                                                exposures.

Kelleher et al., 2001........  Case-control      11.5              11.5              0.08-0.6 [mu]g/   Yes............  ...............  Identified 20
                                study of 20       (machinists).     (machinists).     m\3\--lifetime                                      workers with
                                cases and 206    2.9 (non-         2.9 (non-          weighted                                            Sensitization
                                controls.         machinists).      machinists).      exposures.                                          or CBD.
Madl et al., 2007............  Longitudinal      ................  ................  Machining.......  Yes............  ...............  Personal
                                study of 27                                          1980-1995 median                                     sampling:
                                cases.                                                -0.33 [mu]g/                                       Required
                                                                                m\3\; 1996-1999                                     evidence of
                                                                                median--0.16                                        granulomas for
                                                                                [mu]g/m\3\;                                         CBD diagnosis.
                                                                                2000-2005
                                                                                median--0.09
                                                                                [mu]g/m\3\;.
                                                                                Non-machining
                                                                                1980-1995
                                                                                median--0.12
                                                                                [mu]g/m\3\;
                                                                                1996-1999
                                                                                median--0.08
                                                                                [mu]g/m\3\;
                                                                                2000-2005
                                                                                median--0.06
                                                                                [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                Beryllium Oxide Ceramics
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kreiss et al., 1993b.........  Cross-sectional   3.6 (18 cases)..  1.8 (9 cases)...  ................  No                                ...............
                                survey of 505
                                workers.
Kreiss et al., 1996..........  Cross-sectional   5.9 (8 cases)...  4.4 (6 cases)...  Machining         No.............  Small study      Breathing Zone
                                survey of 136                                         median--0.6                        population.      Sampling.
                                workers.                                              [mu]g/m\3\;.
                                                                                Other Areas
                                                                                median--<0.3
                                                                                [mu]g/m\3\;.
Henneberger et al., 2001.....  Cross-sectional   9.9 (15 cases)..  5.3 (8 cases)...  6.4% samples >2   Yes............  Small study      Breathing zone
                                survey of 151                                         [mu]g/m\3\;                        population.      sampling.
                                workers.                                              2.4% samples >5
                                                                                [mu]g/m\3\;.
                                                                                0.3% samples >25
                                                                                [mu]g/m\3\.
Cummings et al., 2007........  Longitudinal      0.7-5.6 (4        0.1--7.9 (3       Production......  Yes............  Small sample     Personal
                                study of 93       cases).           cases).          1994-1999                           size.            sampling was
                                workers.                                              median--0.1[mu]                                     effective in
                                                                                g/m\3\; 2000-                                       reducing rates
                                                                                2003 median--                                       of new cases
                                                                                0.04[mu]g/m\3\;.                                    of
                                                                                Administrative                                       sensitization.
                                                                                1994-1999
                                                                                median <0.2
                                                                                [mu]g/m\3\;
                                                                                2000-2003
                                                                                median--0.02
                                                                                [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                   Copper-Beryllium Alloy Processing and Distribution
--------------------------------------------------------------------------------------------------------------------------------------------------------
Schuler et al., 2005.........  Cross-sectional   7.0 (10 cases)..  4.0 (6 cases)...  Rod and Wire      ...............  Small study      Personal
                                survey of 153                                         Production                         population.      sampling.
                                workers.                                              median--0.12
                                                                                [mu]g/m\3\;
                                                                                Strip Metal
                                                                                Production
                                                                                median--0.02
                                                                                [mu]g/m\3\;.
                                                                                Production
                                                                                Support median--
                                                                                0.02 [mu]g/
                                                                                m\3\;.
                                                                                Administration
                                                                                median--0.02
                                                                                [mu]g/m\3\.

Thomas et al., 2009..........  Cross-sectional   3.8 (3 cases)...  1.9 (1 case)....  Used exposure     ...............  Authors noted    Instituted PPE
                                study of 82                                           profile from                       workers may      to reduce
                                workers.                                              Schuler study.                     have been        dermal
                                                                                sensitized       exposures.
                                                                                prior to
                                                                                available
                                                                                screening,
                                                                                underestimatin
                                                                                g
                                                                                sensitization
                                                                                rate in legacy
                                                                                workers.
Stanton et al., 2006.........  Cross-sectional   1.1 (1 case)....  1.1 (1 case)....  Bulk Products     ...............  Study did not    Personal
                                study of 88                                           Production                         report use of    sampling.
                                workers.                                              median 0.04                        PPE or
                                                                                [mu]g/m\3\;                        respirators.
                                                                                Strip Metal
                                                                                Production
                                                                                median--0.03
                                                                                [mu]g/m\3\;
                                                                                Production
                                                                                support.
                                                                                median--0.01
                                                                                [mu]g/m\3\;
                                                                                Administration
                                                                                median 0.01
                                                                                [mu]g/m\3\.
Bailey et al., 2010..........  Cross-sectional   11.0............  14.5 total......  ................  ...............  Study reported   ...............
                                study of 660                                                                             prevalence
                                total workers                                                                            rates for pre
                                (258 partial                                                                             enhanced
                                program, 290                                                                             control-
                                full program).                                                                           program,
                                                                                partial
                                                                                enhanced
                                                                                control
                                                                                program, and
                                                                                full enhanced
                                                                                control
                                                                                program.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                         Nuclear Weapons Production Facilities and Cleanup of Former Facilities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kreiss et al., 1989..........  Cross-sectional   11.8 (6 cases)..  7.8 (4 cases)...  ................  No.............  Small study      ...............
                                survey of 51                                                                             population
                                workers.
Kreiss et al., 1993a.........  Cross-sectional   1.9 (18 cases)..  1.7 (15 cases)..  ................  No.............  Study            ...............
                                survey of 895                                                                            population
                                workers.                                                                                includes some
                                                                                workers with
                                                                                no reported Be
                                                                                exposure.
Stange et al., 1996..........  Longitudinal      2.4 (76 cases)..  0.7 (29 cases)..  Annual mean       No.............  ...............  Personal
                                Study of 4,397                                        concentration.                                      sampling.
                                BHSP                                                 1970-1988 0.016
                                participants.                                         [mu]g/m\3\;
                                                                                1984-1987 1.04
                                                                                [mu]g/m\3\.
Stange et al., 2001..........  Longitudinal      4.5 (154 cases).  1.6 (81 cases)..  No quantitative   No.............  ...............  Personal
                                study of 5,173                                        information                                         sampling.
                                workers.                                              presented in
                                                                                study.
Viet et al., 2000............  Case-control....  74 workers        50 workers CBD..  Mean exposure     Yes............  Likely           Fixed airhead
                                                  sensitized.                         range: 0.083-                      underestimated   sampling away
                                                                                0.622 [mu]g/                       exposures.       from breathing
                                                                                m\3\.                                               zone:
                                                                                Maximum                                             Matched
                                                                                exposures: 0.54-                                    controls for
                                                                                36.8 [mu]g/                                         age, sex,
                                                                                m.\3\.                                              smoking.
--------------------------------------------------------------------------------------------------------------------------------------------------------
N/A = Information not available from study reports.

                                       Table A.2--Summary of Mechanistic Animal Studies for Sensitization and CBD
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Dose or exposure       Type of                              Other
           Reference                 Species               Study length            concentration        beryllium       Study results      information
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                  Intratracheal (intrabroncheal) or Nasal Instillation
--------------------------------------------------------------------------------------------------------------------------------------------------------
Barna et al., 1981............  Guinea pig.......                       3 month  10 mg-5[mu]m       beryllium oxide.  Granulomas,
                                                                                particle size.                       interstitial
                                                                                infiltrate with
                                                                                fibrosis with
                                                                                thickening of
                                                                                alveolar septae.
Barna et al., 1984............  Guinea pig.......                       3 month  5 mg.............  beryllium oxide.  Granulomatous
                                                                                lesions in
                                                                                strain 2 but
                                                                                not strain 13
                                                                                indicating a
                                                                                genetic
                                                                                component.
Benson et al., 2000...........  Mouse............  ............................  0, 12.5, 25,       beryllium copper  Acute pulmonary
                                                                                100[mu]g; 0, 2,    alloy;            toxicity
                                                                                8 [mu]g.           beryllium metal.  associated with
                                                                                beryllium/
                                                                                copper alloy
                                                                                but not
                                                                                beryllium metal.
Haley et al., 1994............  Cynomolgus monkey               14, 60, 90 days  0, 1, 50, 150      Beryllium metal,  Beryllium oxide
                                                                                [mu]g.             beryllium oxide.  particles were
                                                                                0, 2.5, 12.5,                         less toxic than
                                                                                37.5 [mu]g.                          the beryllium
                                                                                metal.
Huang et al., 1992............  Mouse............  ............................  5 [mu]g..........  Beryllium         Granulomas        ................
                                                                                1-5 [mu]g........   sulfate           produced in A/J
                                                                                immunization;     strain but not
                                                                                beryllium metal   BALB/c or C57BL/
                                                                                challenge.        6.
Votto et al., 1987............  Rat..............                       3 month  2.4 mg...........  Beryllium         Granulomas,
                                                                                8 mg/ml..........   sulfate           however, no
                                                                                immunization;     correlation
                                                                                beryllium         between T-cell
                                                                                sulfate           subsets in lung
                                                                                challenge.        and BAL fluid.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Inhalation--Single Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Haley et al., 1989a...........  Beagle dog.......             Chronic--one dose  0, 6 [mu]g/kg, 18  500 [deg]C; 1000  Positive BeLPT    Granulomas
                                                                                [mu]g/kg.          [deg]C            results--develo   resolved with
                                                                                beryllium oxide.  ped granulomas;   time, no full-
                                                                                low-calcined      blown CBD.
                                                                                beryllium oxide
                                                                                more toxic than
                                                                                high-calcined.
Haley et al., 1989b...........  Beagle dog.......      Chronic--one dose/2 year  0, 17 [mu]g/kg,    500 [deg]C; 1000  Granulomas,       Granulomas
                                                                       recovery   50 [mu]g/kg.       [deg]C            sensitization,    resolved over
                                                                                beryllium oxide.  low-fired more    time.
                                                                                toxic than high
                                                                                fired.
Robinson et al., 1968.........  Dog..............                       Chronic  0. 115mg/m\3\....  Beryllium oxide,  Foreign body
                                                                                beryllium         reaction in
                                                                                fluoride,         lung.
                                                                                beryllium
                                                                                chloride.
Sendelbach et al., 1989.......  Rat..............                        2 week  0, 4.05 [mu]g/L..  Beryllium as      Interstial
                                                                                beryllium         pneumonitis.
                                                                                sulfate.
Sendelbach and Witschi, 1987..  Rat..............                        2 week  0, 3.3, 7 [mu]g/L  Beryllium as      Enzyme changes
                                                                                beryllium         in BAL fluid.
                                                                                sulfate.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Inhalation--Repeat Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Conradi et al., 1971..........  Beagle dog.......               Chronic--2 year  0. 3300 [mu]g/     1400 [deg]C       No changes        May have been
                                                                                m\3\, 4380 [mu]g/  beryllium oxide.  detected.         due to short
                                                                                m\3\ once/month                                        exposure time
                                                                                for 3 months.                                          followed by
                                                                                long recovery.

                                Macaca irus                     Chronic--2 year  0. 3300 [mu]g/     1400 [deg]C       No changes        May have been
                                 Monkey.                                          m\3\, 4380 [mu]g/  beryllium oxide.  detected.         due to short
                                                                                m\3\ once/month                                        exposure time
                                                                                for 3 months.                                          followed by
                                                                                long recovery.
Haley et al., 1992............  Beagle dog.......     Chronic--repeat dose (2.5  17, 50 [mu]g/kg..  500 [deg]C; 1000  Granulomatous
                                                                year intervals)                      [deg]C            pneumonitis.
                                                                                beryllium oxide.
Harmsen et al., 1985..........  Beagle dog.......                       Chronic  0, 20 [mu]g/kg,    500[deg]C; 1000
                                5 dogs per group.                                 50 [mu]g/kg.       [deg]C
                                                                                beryllium oxide.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Dermal or Intradermal
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kang et al., 1977.............  Rabbit...........  ............................  10mg.............  Beryllium         Skin
                                                                                sulfate.          sensitization
                                                                                and skin
                                                                                granulomas.
Tinkle et al., 2003...........  Mouse............                       3 month  25 [mu]L.........  Beryllium         Microgranulomas
                                                                                70 [mu]g.........   sulfate.          with some
                                                                                Beryllium oxide.   resolution over
                                                                                time of study.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                      Intramuscular
--------------------------------------------------------------------------------------------------------------------------------------------------------
Eskenasy, 1979................  Rabbit...........  35 days (injections at 7 day  10mg.ml..........  Beryllium         Sensitization,
                                                                     intervals)                      sulfate.          evidence of CBD.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                Intraperitoneal Injection
--------------------------------------------------------------------------------------------------------------------------------------------------------
Marx and Burrell, 1973........  Guinea pig.......            24 weeks (biweekly  2.6 mg + 10 [mu]g  Beryllium         Sensitization...
                                                                    injections)   dermal             sulfate.
                                                                                injections.
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                           Table A-3--Summary of Beryllium Lung Cancer Epidemiological Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Confounding         Study          Additional
          Reference               Study type      Exposure range     Study number     Mortality ratio      factors        limitations        comments
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Beryllium Case Registry
--------------------------------------------------------------------------------------------------------------------------------------------------------
Infante et al., 1980.........  Cohort..........  N/D.............  421 cases from    SMR 2.12........  Not reported...  Exposure         ...............
                                                                    the BCR.         7 lung cancer                       concentration
                                                                                deaths.                            data or
                                                                                smoking habits
                                                                                not reported.
Steenland and Ward, 1991.....  Cohort..........  N/D.............  689 cases from    SMR 2.00 (95% CI  ...............  ...............  Included women:
                                                                    the BCR.          1.33-2.89).                                         93% women
                                                                                28 lung cancer                                       diagnosed with
                                                                                deaths.                                             CBD; 50% men
                                                                                diagnosed with
                                                                                CBD;
                                                                                SMR 157 for
                                                                                those with CBD
                                                                                and SMR 232
                                                                                for those with
                                                                                ABD.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                               Beryllium Manufacturing and/or Processing Plants (Extraction, Fabrication, and Processing)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Ward et al., 1992............  Retrospective     N/D.............  9,225 males.....  SMR 1.26........  ...............  Lack of job      Employment
                                Mortality                                            (95% CI 1.12-                       history and      period 1940-
                                Cohort.                                               1.42).                             air monitoring   1969.
                                                                                280 lung cancer                     data.
                                                                                deaths.

Levy et al., 2002............  Cohort..........  N/D.............  9225 males......  Statistically     Adjusted for     Lack of job      Majority of
                                                                                non-significant   smoking.         history and      workers
                                                                                elevation in                       air monitoring   studied
                                                                                lung cancer                        data.            employed for
                                                                                deaths.                                             less than one
                                                                                year
Bayliss et al., 1971.........  Nested cohort...  ................  8,000 workers...  SMR 1.06........  ...............  ...............  Employed prior
                                                                                36 lung cancer                                       to 1947 for
                                                                                deaths.                                             almost half
                                                                                lung cancer
                                                                                deaths.
Mancuso, 1970................  Cohort..........  411-43,300 [mu]g/ 1,222 workers at  SMR 1.42........  Only partial     Partial smoking  Employment
                                                  m\3\ annual       OH plant; 2,044  (95% CI 1.1-1.8)   smoking          history; No      period from
                                                  exposure          workers at PA    80 lung cancer     history.         job analysis     1937-1948.
                                                  (reported from    plant.            deaths.                            by title or
                                                  Zielinsky,                                                             exposure
                                                  1961).                                                                 category.
Mancuso, 1980................  Cohort..........  N/D.............  Same OH and PA    SMR 1.40........  No smoking       No adjustment    Employment
                                                                    plant analysis.                     adjustment.      by job title     period from
                                                                                or exposure.     1942-1948;
                                                                                Used workers
                                                                                at rayon plant
                                                                                for
                                                                                comparison.
Mancuso and El Attar, 1969...  Cohort..........  N/D.............  3,685 white       SMR 1.49........  Adjusted for     No job exposure  Employment
                                                                    males.                              age and local.   data or          history from
                                                                                smoking          1937-1944.
                                                                                adjustment.
Wagner et al., 1980..........  Cohort..........  N/D.............  3,055 white       SMR 1.25........  ...............  Inadequately     Reanalysis
                                                                    males PA plant.  (95% CI 0.9-1.7)                    adjusted for     using PA lung-
                                                                                47 lung cancer                      smoking; Used    cancer rate
                                                                                deaths.                            national lung-   revealed 19%
                                                                                cancer risk      underestimatio
                                                                                for cancer not   n of beryllium
                                                                                PA.              lung cancer
                                                                                deaths.
Sanderson et al., 2001.......  Nested case-      -- Average        3,569 males PA    SMR 1.22........  Smoking was      May not have     Found
                                control.          exposure          plant.           (95% CI 1.03-      found not to     adjusted         association
                                                  22.8[mu]g/m\3\.                     1.43).            be a             properly for     with 20 year
                                                 -- Maximum                          142 lung cancer    confounding      birth-year or    latency.
                                                  exposure                            deaths.           factor.          age at hire.
                                                  32.4[mu]g/m\3\.
Levy et al., 2007............  Nested case-      Used log          Reanalysis of     SMR 1.04........  Different        ...............  Found no
                                control.          transformed       Sanderson et     (95% CI 0.92-      methodology                       association
                                                  exposure data.    al., 2001.        1.17).            for smoking                       between
                                                                                adjustment.                       beryllium
                                                                                exposure and
                                                                                increased risk
                                                                                of lung
                                                                                cancer.
Schubauer-Berigan et al.,      Nested case-      Used exposure     Reanalysis of     Used Odds ratio:  Adjusted for     ...............  -- Controlled
 2008.                          control.          data from         Sanderson et      1.91 (95% CI      smoking, birth                    for birth-year
                                                  Sanderson et      al., 2001.        1.06-3.44)        cohort, age.                      and age at
                                                  al., 2001, Chen                     unadjusted;.                                        hire;
                                                  2001, and Couch                    1.29 (95% CI                                        -- Found
                                                  et al., 2010.                       0.61-2.71)                                          similar
                                                                                birth-year                                          results to
                                                                                adjusted;.                                          Sanderson et
                                                                                1.24 (95% CI                                         al., 2001;
                                                                                0.58-2.65) age-                                    -- Found
                                                                                hire adjusted.                                      association
                                                                                with 10 year
                                                                                latency
                                                                                -- ``0'' = used
                                                                                minuscule
                                                                                value at start
                                                                                to eliminate
                                                                                the use of 0
                                                                                in a
                                                                                logarithmic
                                                                                analysis
Schubauer-Berigan et al.,      Cohort..........  N/D.............  9199 workers      SMR 1.17 (95%CI   Adjusted for     ...............  Male workers
 2010a.                                                             from 7            1.08-1.28).       smoking.                          employed at
                                                                    processing       545 deaths......                                     least 2 days
                                                                    plants.                                                               between 1940
                                                                                and 1970.
Schubauer-Berigan et al.,      Cohort..........  Used exposure     5436 workers OH   Evaluated using   Adjusted for     ...............  -- Exposure
 2010b.                                           data from         and PA plants.    hazard ratios     age, birth                        response was
                                                  Sanderson et                        and excess        cohort,                           found between
                                                  al., 2001.                          absolute risk.    asbestos                          0-10[mu]g/m\3\
                                                                                293 deaths......   exposure,                         mean DWA;
                                                                                short-term                       -- Increased
                                                                                work status.                      with
                                                                                statistical
                                                                                significance
                                                                                at 4[mu]g/
                                                                                m\3\;
                                                                                -- 1 in 1000
                                                                                risk at
                                                                                0.033[mu]g/
                                                                                m\3\ mean DWA.
--------------------------------------------------------------------------------------------------------------------------------------------------------

                                                           Re-evaluation of Published Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
Hollins et al., 2009.........  Review..........  Re-examination    ................  ................  ...............  ...............  Found lung
                                                  of weight-of-                                                                           cancer excess
                                                  evidence from                                                                           risk was
                                                  more than 50                                                                            associated
                                                  publications.                                                                           with higher
                                                                                levels of
                                                                                exposure not
                                                                                relevant in
                                                                                today's
                                                                                industrial
                                                                                settings.
IARC, 2012...................  Multiple........  Insufficient      ................  Sufficient        IARC concluded   ...............  -- Greater lung
                                                  exposure                            evidence for      beryllium lung                    cancer risk in
                                                  concentration.                      carcinogenicity   cancer risk                       the BCR cohort
                                                 Data............                     of beryllium.     was not                          -- Correlation
                                                                                associated                        between
                                                                                with smoking.                     highest lung
                                                                                cancer rates
                                                                                and highest
                                                                                amounts of ABD
                                                                                or other non-
                                                                                malignant lung
                                                                                diseases
                                                                                -- Increased
                                                                                risk with
                                                                                longer latency
                                                                                -- Greater
                                                                                excess lung
                                                                                cancers among
                                                                                those hired
                                                                                prior to 1950.
--------------------------------------------------------------------------------------------------------------------------------------------------------
N/D = information not determined for most studies
DWA--daily weighted average

VI. Preliminary Beryllium Risk Assessment

    The Occupational Safety and Health (OSH) Act and court cases
arising under it have led OSHA to rely on risk assessment to support
the risk determinations required to set a permissible exposure limit
(PEL) for a toxic substance in standards under the OSH Act. Section
6(b)(5) of the OSH Act states that ``The Secretary [of Labor], in
promulgating standards dealing with toxic materials or harmful physical
agents under this subsection, shall set the standard which most
adequately assures, to the extent feasible, on the basis of the best
available evidence, that no employee will suffer material impairment of
health or functional capacity even if such employee has regular
exposure to the hazard dealt with by such standard for the period of
his working life'' (29 U.S.C. 655(b)(5)).
    In Industrial Union Department, AFL-CIO v. American Petroleum
Institute, 448 U.S. 607 (1980) (Benzene), the United States Supreme
Court ruled that the OSH Act requires that, prior to the issuance of a
new standard, a determination must be made that there is a significant
risk of material impairment of health at the existing PEL and that
issuance of a new standard will significantly reduce or eliminate that
risk. The Court stated that ``before [the Secretary] can promulgate any
permanent health or safety standard, the Secretary is required to make
a threshold finding that a place of employment is unsafe--in the sense
that significant risks are present and can be eliminated or lessened by
a change in practices'' (Id. at 642). The Court also stated ``that the
Act does limit the Secretary's power to requiring the elimination of
significant risks'' (488 U.S. at 644 n.49), and that ``OSHA is not
required to support its finding that a significant risk exists with
anything approaching scientific certainty'' (Id. at 656).
    OSHA's approach for the risk assessment incorporates both a review
of the recent literature on populations of workers exposed to beryllium
below the current Permissible Exposure Limit (PEL) of 2 [mu]g/m\3\ and
a statistical exposure-response analysis. OSHA evaluated risk at
several alternate PELs under consideration by the Agency: 2 [mu]g/m\3\,
1 [mu]g/m\3\, 0.5 [mu]g/m\3\, 0.2 [mu]g/m\3\, and 0.1 [mu]g/m\3\. A
number of recently published epidemiological studies evaluate the risk
of sensitization and CBD for workers exposed at and below the current
PEL and the effectiveness of exposure control programs in reducing
risk. OSHA also conducted a statistical analysis of the exposure-
response relationship for sensitization and CBD at the current PEL and
alternate PELs the Agency is considering. For this analysis, OSHA used
data provided by National Jewish Medical and Research Center (NJMRC) on
a population of workers employed at a beryllium machining plant in
Cullman, AL. The review of the epidemiological studies and OSHA's own
analysis show substantial risk of sensitization and CBD among workers
exposed at and below the current PEL of 2 [mu]g/m\3\. They also show
substantial reduction in risk where employers have implemented a
combination of controls, including stringent control of airborne
beryllium levels and additional measures such as respirators, dermal
personal protective equipment (PPE), and strict housekeeping to protect
workers against dermal and respiratory beryllium exposure. To evaluate
lung cancer risk, OSHA relied primarily on a quantitative risk
assessment published in 2011 by NIOSH. This 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) where workers were exposed to lower levels of beryllium and
worked for longer periods than at the Reading plant. The authors found
that lung cancer risk was strongly and significantly related to mean,
cumulative, and maximum measures of workers' exposure; they predicted
substantial risk of lung cancer at the current PEL, and substantial
reductions in risk at the alternate PELs OSHA considered for the
proposed rule (Schubauer-Berigan et al., 2011).

A. Review of Epidemiological Literature on Sensitization and Chronic
Beryllium Disease From Occupational Exposure

    As discussed in the Health Effects section, studies of beryllium-
exposed workers conducted using the beryllium lymphocyte proliferation
test (BeLPT) have found high rates of beryllium sensitization and CBD
among workers in many industries, including at some facilities where
exposures were primarily below OSHA's PEL of 2 [mu]g/m\3\ (Kreiss et
al., 1993; Henneberger et al., 2001; Schuler et al., 2005; Schuler et
al., 2012). In the mid-1990s, some facilities using beryllium began to
aggressively monitor and reduce workplace exposures. Four plants where
several rounds of BeLPT screening were conducted before and after
implementation of new exposure control methods provide the best
currently available evidence on the effectiveness of various exposure
control measures in reducing the risk of sensitization and CBD. The
experiences of these plants--a copper-beryllium processing facility in
Reading, PA, a beryllia ceramics facility in Tucson, AZ; a beryllium
processing facility in Elmore, OH; and a machining facility in Cullman,
AL--show that efforts to prevent sensitization and CBD by using
engineering controls to reduce workers' beryllium exposures to median
levels at or around 0.2 [mu]g/m\3\ and did not emphasize PPE and
stringent housekeeping methods, had only limited impact on risk.
However, exposure control programs implemented more recently, which
drastically reduced respiratory exposure to beryllium via a combination
of engineering controls and respiratory protection, controlled dermal
contact with beryllium using PPE, and employed stringent housekeeping
methods to keep work areas clean and prevent transfer of beryllium
between work areas, sharply curtailed new cases of sensitization among
newly-hired workers. There is additional, but more limited, information
available on the occurrence of sensitization and CBD among aluminum
smelter workers with low-level beryllium exposures (Taiwo et al., 2008;
Taiwo et al., 2010; Nilsen et al., 2010). A discussion of the
experiences at these plants follows.
    The Health Effects section also discussed the role of particle
characteristics and beryllium compound solubility in the development of
sensitization and CBD among beryllium-exposed workers. Respirable
particles small enough to reach the deep lung are responsible for CBD.
However, larger inhalable particles that deposit in the upper
respiratory tract may lead to sensitization. The weight of evidence
indicates that both soluble and insoluble forms of beryllium are able
to induce sensitization and CBD. Insoluble forms of beryllium that
persist in the lung for longer periods may pose greater risk of CBD
while soluble forms may more easily trigger immune sensitization.
Although these factors potentially influence the toxicity of beryllium,
the available data are too limited to reliably account for solubility
and particle size in the Agency estimates of risk. The qualitative
impact on conclusions and uncertainties with regard to risk are
discussed in a later section.
1. Reading, PA, Plant
    Schuler et al. conducted a study of workers at a copper-beryllium
processing facility in Reading, PA, screening 152 workers with the
BeLPT (Schuler et al., 2005). Exposures at this plant were believed to
be low throughout its history due to the low percentage of beryllium in
the metal alloys used, and the relatively low exposures found in
general area samples collected starting in 1969 (sample median <= 0.1
[mu]g/m\3\, 97% < 0.5 [mu]g/m\3\). The reported prevalences of
sensitization (6.5 percent) and CBD (3.9 percent) showed substantial
risk at this facility, even though airborne exposures were primarily
below OSHA's current PEL of 2 [mu]g/m\3\.
    Personal lapel samples were collected in production and production
support jobs between 1995 and May 2000. These samples showed primarily
very low airborne beryllium levels, with a median of 0.073 [mu]g/
m\3\.\6\ The wire annealing and pickling process had the highest
personal lapel sample values, with a median of 0.149 [mu]g/m\3\.
Despite these low exposure levels, cases of sensitization continued to
occur among workers whose first exposures to beryllium occurred in the
1990s. Five (11.5 percent) workers of 43 hired after 1992 who had no
prior beryllium exposure became sensitized, including four in
production work and one in production support (Thomas et al., 2009;
evaluation for CBD not reported). Two (13 percent) of these sensitized
workers were among 15 workers in this group who had been hired less
than a year before the screening.
---------------------------------------------------------------------------

    \6\ In their publication, Schuler et al. presented median values
for plant-wide and work-category-specific exposure levels; they did
not present arithmetic or geometric mean values for personal
samples.
---------------------------------------------------------------------------

    After the BeLPT screening was conducted in 2000, the company began
implementing new measures to further reduce workers' exposure to
beryllium. Requirements designed to minimize dermal contact with
beryllium, including long-sleeve facility uniforms and polymer gloves,
were instituted in production areas in 2000. In 2001 the company
installed local exhaust ventilation (LEV) in die grinding and
polishing. Personal lapel samples collected between June 2000 and
December 2001 show reduced exposures plant-wide. Of 2,211 exposure
samples collected during this ``pre-enclosure program'' period, 98
percent were below 0.2 [mu]g/m\3\ (Thomas et al., 2009, p. 124).
Median, arithmetic mean, and geometric mean values <= 0.03 [mu]g/m\3\
were reported in this period for all processes except the wire
annealing and pickling process. Samples for this process remained
elevated, with a median of 0.1 [mu]g/m\3\ (arithmetic mean of 0.127
[mu]g/m\3\, geometric mean of 0.083 [mu]g/m\3\). In January 2002, the
plant enclosed the wire annealing and pickling process in a restricted
access zone (RAZ), required respiratory PPE in the RAZ, and implemented
stringent measures to minimize the potential for skin contact and
beryllium transfer out of the zone. While exposure samples collected by
the facility were sparse following the enclosure, they suggest exposure
levels comparable to the 2000-01 samples in areas other than the RAZ.
Within the RAZ, required use of powered air-purifying respirators
(PAPRs) indicates that respiratory exposure was negligible. A 2009
publication on the facility reported that outside the RAZ, ``the vast
majority of employees do not wear any form of respiratory protection
due to very low airborne beryllium concentrations'' (Thomas et al.,
2009, p. 122).
    To test the efficacy of the new measures in preventing
sensitization and CBD, in June 2000 the facility began an intensive
BeLPT screening program for all new workers. The company screened
workers at the time of hire; at intervals of 3, 6, 12, 24, and 48
months; and at 3-year intervals thereafter. Among 82 workers hired
after 1999, three cases of sensitization were found (3.7 percent). Two
(5.4 percent) of 37 workers hired prior to enclosure of the wire
annealing and pickling process were found to be sensitized within 3 and
6 months of beginning work at the plant. One (2.2 percent) of 45
workers hired after the enclosure was confirmed as sensitized. Among
these early results, it appears that the greatest reduction in
sensitization risk was achieved after median exposures in all areas of
the plant were reduced to below 0.1 [mu]g/m\3\

and PPE to prevent dermal contact was instituted.
2. Tucson, AZ, Plant
    Kreiss et al. conducted a study of workers at a beryllia ceramics
plant, screening 136 workers with the BeLPT in 1992 (Kreiss et al.,
1996). Full-shift area samples collected between 1983 and 1992 showed
primarily low airborne beryllium levels at this facility. Of 774 area
samples, 76 percent were at or below 0.1 [mu]g/m\3\ and less than 1
percent exceeded 2 [mu]g/m\3\. A small set (75) of personal lapel
samples collected at the plant beginning in 1991 had a median of 0.2
[mu]g/m\3\ and ranged from 0.1 to 1.8 [mu]g/m\3\ (arithmetic and
geometric mean values not reported) (Kreiss et al., 1996, p. 19).
However, area samples and short-term breathing zone samples also showed
occasional instances of very high beryllium exposure levels, with
extreme values of several hundred [mu]g/m\3\ and 3.6 percent of short-
term breathing zone samples in excess of 5 [mu]g/m\3\.
    Kreiss et al. reported that eight (5.9 percent) of 136 workers
tested were sensitized, six (4.4 percent) of whom were diagnosed with
CBD. Seven of the eight sensitized employees had worked in machining,
where general area samples collected between October 1985 and March
1988 had a median of 0.3 [mu]g/m\3\, in contrast to a median value of
less than 0.1 [mu]g/m\3\ in other areas of the plant (Kreiss et al.,
1996, p. 20; mean values not reported). Short-term breathing zone
measurements associated with machining had a median of 0.6 [mu]g/m\3\,
double the median of 0.3 [mu]g/m\3\ for breathing zone measurements
associated with other processes (id., p. 20; mean values not reported).
One sensitized worker was one of 13 administrative workers screened,
and was among those diagnosed with CBD. Exposures of administrative
workers were not well-characterized, but were believed to be among the
lowest in the plant. Of three personal lapel samples reported for
administrative staff during the 1990s, all were below the then
detection limit of 0.2 [mu]g/m\3\ (Cummings et al., 2007, p.138).
    Following the 1992 screening, the facility reduced exposures in
machining areas by enclosing machines and installing HEPA filter
exhaust systems. Personal samples collected between 1994 and 1999 had a
median of 0.2 [mu]g/m\3\ in production jobs and 0.1 [mu]g/m\3\ in
production support (geometric means 0.21 [mu]g/m\3\ and 0.11 [mu]g/
m\3\, respectively; arithmetic means not reported. Cummings et al.,
2007, p. 138). In 1998, a second screening found that 9 percent of
tested workers hired after the 1992 screening were sensitized, of whom
one was diagnosed with CBD. All of the sensitized workers had been
employed at the plant for less than two years (Henneberger et al.,
2001).
    Following the 1998 screening, the company continued efforts to
reduce exposures and risk of sensitization and CBD by implementing
additional engineering and administrative controls and PPE. Respirator
use was required in production areas beginning in 1999, and latex
gloves were required beginning in 2000. The lapping area was enclosed
in 2000, and enclosures were installed for all mechanical presses in
2001. Between 2000 and 2003, water-resistant or water-proof garments,
shoe covers, and taped gloves were incorporated to keep beryllium-
containing fluids from wet machining processes off the skin. The new
engineering measures did not appear to substantially reduce airborne
beryllium levels in the plant. Personal lapel samples collected in
production processes between 2000 and 2003 had a median and geometric
mean of 0.18 [mu]g/m\3\, similar to the 1994-1999 samples (Cummings et
al., 2007, p. 138). However, respiratory protection requirements were
instituted in 2000 to control workers' airborne beryllium exposures.
    To test the efficacy of the new measures instituted after 1998, in
January 2000 the company began screening new workers for sensitization
at the time of hire and at 3, 6, 12, 24, and 48 months of employment
(Cummings et al., 2007). These more stringent measures appear to have
substantially reduced the risk of sensitization among new employees. Of
97 workers hired between 2000 and 2004, one case of sensitization was
identified (1 percent). This worker had experienced a rash after an
incident of dermal exposure to lapping fluid through a gap between the
glove and uniform sleeve, indicating that sensitization may have
occurred via skin exposure.
3. Elmore, OH, Plant
    Kreiss et al., Schuler et al., and Bailey et al. conducted studies
of workers at a beryllium metal, alloy, and oxide production plant.
Workers participated in BeLPT surveys in 1992 (Kreiss et al., 1997) and
in 1997 and 1999 (Schuler et al., 2012). Exposure levels at the plant
between 1984 and 1993 were characterized by a mixture of general area,
short-term breathing zone, and personal lapel samples. Kreiss et al.
reported that the median area samples for various work areas ranged
from 0.1 to 0.7 [mu]g/m\3\, with the highest values in the alloy arc
furnace and alloy melting-casting areas (other measures of central
tendency not reported). Personal lapel samples were available from
1990-1992, and showed high exposures overall (median value of 1.0
[mu]g/m\3\) with very high exposures for some processes. The authors
reported median sample values of 3.8 [mu]g/m\3\ for beryllium oxide
production, 1.75 [mu]g/m\3\ for alloy melting and casting, and 1.75
[mu]g/m\3\ for the arc furnace.
    Kreiss et al. reported that 43 (6.9 percent) of 627 workers tested
in 1992 were sensitized, six of whom were diagnosed with CBD (4.4
percent). Workers with less than one year tenure at the plant were not
tested in this survey (Bailey et al., 2010, p. 511). The work processes
that appeared to carry the highest risk for sensitization and CBD
(e.g., ceramics) were not those with the highest reported exposure
levels (e.g., arc furnace and melting-casting). The authors noted
several possible reasons for this, including factors such as
solubility, particle size/number, and particle surface area that could
not be accounted for in their analysis (Kreiss et al., 1997).
    In 1996-1999, the company took steps to reduce workers' beryllium
exposures: some high-exposure processes were enclosed, special
restricted-access zones were set up, HEPA filters were installed in air
handlers, and some ventilation systems were updated. In 1997 workers in
the pebble plant restricted access zone were required to wear half-face
air-purifying respirators, and beginning in 1999 all new employees were
required to wear loose-fitting powered air-purifying respirators (PAPR)
in manufacturing buildings (Bailey et al., 2010, p. 506). Skin
protection became part of the protection program for new employees in
2000, and glove use was required in production areas and for handling
work boots beginning in 2001. Also beginning in 2001, either half-mask
respirators or PAPRs were required in the production facility (type
determined by airborne beryllium levels), and respiratory protection
was required for roof work and during removal of work boots (Bailey et
al., 2010, p. 506). Respirator use was reported to be used on about
half or less of industrial hygiene sample records for most processes in
1990-1992 (Kreiss et al., 1996).
    Beginning in 2000, workers were offered periodic BeLPT testing to
evaluate the effectiveness of a new exposure control program
implemented by the company. Bailey et al. (2010) reported on the
results of this surveillance for 290 workers hired between February 21,
2000 and December 18, 2006. They compared the

occurrence of beryllium sensitization and disease among 258 employees
who began work at the Elmore plant between January 15, 1993 and August
9, 1999 (the `pre-program group') and among 290 employees who were
hired between February 21, 2000 and December 18, 2006 and were tested
at least once after hire (the `program group'). They found that, as of
1999, 23 (8.9 percent) of the pre-program group were sensitized to
beryllium. Six (2.1 percent) of the program group had confirmed
abnormal results on their final round of BeLPTs, which occurred in
different years for different employees. In addition, another five
employees had confirmed abnormal BeLPT results at some point during the
testing period, followed by at least one instance of a normal test
result. One of these employees had a confirmed abnormal baseline BeLPT
at hire, and had two subsequent normal BeLPT results at 6 and 12 months
after hire. Four others had confirmed abnormal BeLPT results at 3 or 6
months after hire, later followed by a normal test. Including these
four in the count of sensitized workers, there were a total of ten (3.5
percent) workers sensitized after hire in the program group. It is not
clear whether the occurrence of a normal result following an abnormal
result reflects an error in one of the test results, a change in the
presence or level of memory T-cells circulating in the worker's blood,
or other possibilities. Because most of the workers in the study had
been employed at the facility for less than two years, Bailey et al.
did not report the incidence of CBD among the sensitized workers
(Bailey et al., 2010, p. 511).
    In addition, Bailey et al. divided the program group into the
`partial program subgroup' (206 employees hired between February 21,
2000 and December 31, 2003) and the `full program subgroup' (84
employees hired between January 1, 2004 and December 18, 2006) to
account for the greater effectiveness of the exposure control program
after the first three years of implementation (Bailey et al., pp 506-
507). Four (1.9 percent) of the partial program group were found to be
sensitized on their final BeLPT (excluding one with a confirmed
abnormal BeLPT from their baseline test at hire). Two (2.4 percent) of
the full program group were found to be sensitized on their final BeLPT
(Bailey et al., 2010, p. 509). An additional three employees in the
partial program group and one in the full program group were confirmed
sensitized at 3 or 6 months after hire, then later had a single normal
BeLPT (Bailey et al., 2010, p. 509).
    Schuler et al. (2012) published a study examining beryllium
sensitization and CBD among short-term workers at the Elmore, OH plant,
using exposure estimates created by Virji et al. (2012). The study
population included 264 workers employed in 1999 with up to six years
tenure at the plant (91 percent of the 291 eligible workers). By
including only short-term workers, Virji et al. were able to construct
participants' exposures with more precision than was possible in
studies involving workers exposed for longer durations and in time
periods with less exposure sampling. Each participant completed a work
history questionnaire and was tested for beryllium sensitization. The
overall prevalence of sensitization was 9.8 percent (26/264).
Sensitized workers were offered further evaluation for CBD. Twenty-two
sensitized workers consented to clinical testing for CBD via
transbronchial biopsy. Six of those sensitized were diagnosed with CBD
(2.3 percent, 6/264).
    Exposure estimates were constructed using two exposure surveys
conducted in 1999: a survey of total mass exposures (4022 full-shift
personal samples) and a survey of size-separated impactor samples (198
samples). The 1999 exposure surveys and work histories were used to
estimate long-term lifetime weighted (LTW) average, cumulative, and
highest-job-worked exposure for total, respirable, and submicron
beryllium mass concentrations. Schuler et al. (2012) found no cases of
sensitization among workers with total mass LTW average exposures below
0.09 [mu]g/m\3\, among workers with total mass cumulative exposures
below 0.08 [mu]g/m\3\-yr, or among workers with total mass highest job
worked exposures below 0.12 [mu]g/m\3\. Twenty-four percent, 16
percent, and 25 percent of the study population were exposed below
those levels, respectively. Both total and respirable beryllium mass
concentration estimates were positively associated with sensitization
(average and highest job), and CBD (cumulative) in logistic regression
models.
4. Cullman, AL, Plant
    Newman et al. conducted a series of BeLPT screenings of workers at
a precision machining facility between 1995 and 1999 (Newman et al.,
2001). A small set of personal lapel samples collected in the early
1980s and in 1995 suggests that exposures in the plant varied widely
during this time period. In some processes, such as engineering,
lapping, and electrical discharge machining (EDM), exposures were
apparently low (<= 0.1 [mu]g/m\3\). Madl et al. reported that personal
lapel samples from all machining processes combined had a median of
0.33 [mu]g/m\3\, with a much higher arithmetic mean of 1.63 [mu]g/m\3\
(Madl et al., 2007, Table IV, p. 457). The majority of these samples
were collected in the high-exposure processes of grinding (median of
1.05 [mu]g/m\3\, mean of 8.48 [mu]g/m\3\), milling (median of 0.3
[mu]g/m\3\, mean of 0.82 [mu]g/m\3\), and lathing (median of 0.35
[mu]g/m\3\, mean of 0.88 [mu]g/m\3\) (Madl et al., 2007, Table IV, p.
457). As discussed in greater detail in the background document,\7\ the
data set of machining exposure measurements included a few extremely
high values (41-73 [mu]g/m\3\) that a NIOSH researcher identified as
probable errors, and that appear to be included in Madl et al.'s
arithmetic mean calculations. Because high single-data point exposure
errors influence the arithmetic mean far more than the median value of
a data range, OSHA believes the median values reported by Madl et al.
are more reliable than the arithmetic means they reported.
---------------------------------------------------------------------------

    \7\ When used throughout this section, ``background document''
refers to a more comprehensive, companion risk-assessment document
that can be found at www.regulations.gov in OSHA Docket No. ___.
---------------------------------------------------------------------------

    After a sentinel case of CBD was diagnosed at the plant in 1995,
the company began BeLPT screenings to identify workers at increased
risk of CBD and implemented engineering and administrative controls and
PPE designed to reduce workers' beryllium exposures in machining
operations. Newman et al. reported 22 (9.4 percent) sensitized workers
among 235 tested, 13 of whom were diagnosed with CBD within the study
period. Between 1995 and 1997, the company built enclosures and
installed or updated local exhaust ventilation (LEV) for several
machining departments, removed pressurized air hoses, and required the
use of company uniforms. Madl et al. reported that historically,
engineering and work process controls, rather than personal protective
equipment, were used to limit workers' exposure to beryllium;
respirators were used only in cases of high exposure, such as during
sandblasting (Madl et al., 2007, p. 450). In contrast to the Reading
and Tucson plants, gloves were not required at this plant.
    Personal lapel samples collected extensively between 1996 and 1999
in machining jobs have an overall median of 0.16 [mu]g/m\3\, showing
that the new controls achieved a marked reduction in machinists'
exposures during this

period. Nearly half of the samples were collected in milling (median =
0.18 [mu]g/m\3\). Exposures in other machining processes were also
reduced, including grinding (median of 0.18 [mu]g/m\3\) and lathing
(median of 0.13 [mu]g/m\3\). However, cases of sensitization and CBD
continued to occur.
    At the time that Newman et al. 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. 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). All four had been
hired in 1996. Two (one CBD case, one sensitized only) had worked only
in milling, and had worked for approximately 3-4 months (0.3-0.4 yrs)
at the time of diagnosis. One of those diagnosed with CBD worked only
in EDM, where lapel samples collected between 1996 and 1999 had a
median of 0.03 [mu]g/m\3\. This worker was diagnosed with CBD in the
same year that he began work at the plant. The last CBD case worked as
a shipper, where exposures in 1996-1999 were similarly low, with a
median of 0.09 [mu]g/m\3\.
    Beginning in 2000, exposures in all jobs at the machining facility
were reduced to extremely low levels. Personal lapel samples collected
in machining processes between 2000 and 2005 had a median of 0.09
[mu]g/m\3\, where more than a third of samples came from the milling
process (n = 765, median of 0.09 [mu]g/m\3\). A later publication on
this plant by Madl et al. reported that only one worker hired after
1999 became sensitized. This worker had been employed for 2.7 years in
chemical finishing, where exposures were roughly similar to other
machining processes (n = 153, median of 0.12 [mu]g/m\3\). Madl et al.
did not report whether this worker was evaluated for CBD.
5. Aluminum Smelting Plants
    Taiwo et al. (2008) studied a population of 734 employees at four
aluminum smelters located in Canada (2), Italy (1), and the United
States (1). In 2000, a beryllium exposure limit of 0.2 [mu]g/m\3\ 8-
hour TWA (action level 0.1 [mu]g/m\3\) and a short-term exposure limit
(STEL) of 1.0 [mu]g/m\3\ (15-minute sample) were instituted at these
plants. Sampling to determine compliance with the exposure limit began
at all smelters in 2000. Table VI-1 below, adapted from Taiwo et al.
(2008), shows summary information on samples collected from the start
of sampling through 2005.

                             Table VI-1--Exposure Sampling Data by Plant--2000-2005
----------------------------------------------------------------------------------------------------------------
                                                                                Arithmetic
                     Smelter                         Number of    Median  ([mu]g/  mean  ([mu]g/  Geometric mean
                                                      samples          m\3\)           m\3\)        ([mu]g/m\3\)
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1..............................             246            0.03            0.09            0.03
Canadian smelter 2..............................             329            0.11            0.29            0.08
Italian smelter.................................              44            0.12            0.14            0.10
U.S. smelter....................................             346            0.03            0.26            0.04
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Table 1.

    All employees potentially exposed to beryllium levels at or above
the action level for at least 12 days per year, or exposed at or above
the STEL 12 or more times per year, were offered medical surveillance
including the BeLPT (Taiwo et al., 2008, p. 158). Table VI-2 below,
adapted from Taiwo et al. (2008), shows test results for each facility
between 2001 and 2005.

                                  Table VI-2--BeLPT Results by Plant--2001-2005
----------------------------------------------------------------------------------------------------------------
                                                     Employees                    Abnormal BeLPT     Confirmed
                     Smelter                          tested          Normal       (unconfirmed)    Sensitized
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1..............................             109             107               1               1
Canadian smelter 2..............................             291             290               1               0
Italian smelter.................................              64              63               0               1
U.S. smelter....................................             270             268               2               0
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Table 2.

    The two workers with confirmed beryllium sensitization were offered
further evaluation for CBD. Both were diagnosed with CBD, based on
broncho-alveolar lavage (BAL) results in one case and pulmony function
tests, respiratory symptoms, and radiographic evidence in the other.
    In 2010, Taiwo et al. published a study of beryllium-exposed
workers from smelters at four companies, including some of the workers
from the 2008 publication. 3,185 workers were determined to be
``significantly exposed'' to beryllium and invited to participate in
BeLPT screening. Each company used different criteria to determine
``significant'' exposure, which appeared to vary considerably (p. 570).
About 60 percent of invited workers participated in the program between
2000 and 2006, of whom nine were determined to be sensitized (see Table
VI-3 below). The authors state that all nine workers were referred to a
respiratory physician for further evaluation for CBD. Two were
diagnosed with CBD, as described above (Taiwo et al., 2008). The
authors do not report the details of other sensitized workers'
evaluation for CBD.

                          Table VI-3--Medical Surveillance for BeS in ALUMINUM Smelters
----------------------------------------------------------------------------------------------------------------
                                                     Number of        At-risk        Employees
                     Company                         smelters        employees        tested            BeS
----------------------------------------------------------------------------------------------------------------
A...............................................               4            1278             734               4
B...............................................               3             423             328               0
C...............................................               1            1100             508               4
D...............................................               1             384             362               1
                                                 ---------------------------------------------------------------
    Total.......................................               9            3185            1932               9
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2011, Table 1.

    In general, there appeared to be a low level of sensitization and
CBD among employees at the aluminum smelters studied by Taiwo et al.
This is striking in light of the fact that many of the employees tested
had worked at the smelters long before the institution of exposure
limits for beryllium at some smelters in 2000. However, the authors
note that respiratory protection had long been used at these plants to
protect workers from other hazards. The results are roughly consistent
with the observed prevalence of sensitization following the institution
of respiratory protection at the Tucson beryllium ceramics plant
discussed previously. A study by Nilsen et al. (2010) also found a low
rate of sensitization among aluminum workers in Norway. Three-hundred
sixty-two workers and thirty-one control individuals received BeLPT
testing for beryllium sensitization. The authors found one sensitized
worker (0.28 percent). No borderline results were reported. The authors
reported that current exposures in this plant ranged from 0.1 [micro]g/
m\3\ to 0.31 [micro]g/m\3\ (Nilsen et al., 2010) and that respiratory
protection was in use, as is the case in the smelters studied by Taiwo
et al. (2008, 2010).

B. Preliminary Conclusions

    The published literature on beryllium sensitization and CBD shows
that risk of both can be substantial in workplaces in compliance with
OSHA's current PEL (Kreiss et al., 1993; Schuler et al., 2005). The
experiences of several facilities in developing effective industrial
hygiene programs have shown that minimizing both airborne and dermal
exposure, using a combination of engineering and administrative
controls, respiratory protection, and dermal PPE, has substantially
lowered workers' risk of beryllium sensitization. In contrast, risk-
reduction programs that relied primarily on engineering controls to
reduce workers' exposures to median levels in the range of 0.1-0.2
[micro]g/m\3\, such as those implemented in Tucson following the 1992
survey and in Cullman during 1996-1999, had only limited impact on
reducing workers' risk of sensitization. The prevalence of
sensitization among workers hired after such controls were installed at
the Cullman plant remained high (Newman et al. (6.7 percent) and
Henneberger et al. (9 percent)). A similar prevalence of sensitization
was found in the screening conducted in 2000 at the Reading plant,
where the available sampling data show median exposure levels of less
than 0.2 [micro]g/m\3\ (6.5 percent). The risk of sensitization was
found to be particularly high among newly-hired workers (<=1 year of
beryllium exposure) in the Reading 2000 screening (13 percent) and the
Tucson 1998 screening (16 percent).
    Cases of CBD have also continued to develop among workers in
facilities and jobs where exposures were below 0.2 [micro]g/m\3\. One
case of CBD was found in the Tucson 1998 screening among nine
sensitized workers hired less than two years previously (Henneberger et
al., 2001). At the Cullman plant, at least two cases of CBD were found
among four sensitized workers screened in 1995-1999 and hired less than
a year previously (Newman et al., 2001). These results suggest a
substantial risk of progression from sensitization to CBD among workers
exposed at levels well below the current PEL, especially considering
the extremely short time of exposure and follow-up for these workers.
Six of 10 sensitized workers identified at Reading in the 2000
screening were diagnosed with CBD. The four sensitized workers who did
not have CBD at their last clinical evaluation had been hired between
one and five years previously; therefore, the time may have been too
short for CBD to develop.
    In contrast, more recent exposure control programs that have used a
combination of engineering controls, PPE, and stringent housekeeping
measures to reduce workers' airborne and dermal exposures have
substantially lowered risk of sensitization among newly-hired workers.
Of 97 workers hired between 2000 and 2004 in Tucson, where respiratory
and skin protection was instituted for all workers in production areas,
only one (1 percent) worker became sensitized, and in that case the
worker's dermal protection had failed during wet-machining work (Thomas
et al., 2009). In the aluminum smelters discussed by Taiwo et al.,
where available exposure samples 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). Sensitization
was also rare among workers at a Norwegian aluminum smelter (Nilsen et
al., 2010), where estimated exposures in the plant ranged from 0.1
[mu]g/m\3\ to 0.3 [mu]g/m\3\ and respiratory protection was regularly
used. In Reading, where in 2000-2001 airborne exposures in all jobs
were reduced to a median of 0.1 [mu]g/m\3\ or below (measured as an 8-
hour TWA) and dermal protection was required for production-area
workers, two (5.4 percent) of 37 newly hired workers became sensitized
(Thomas et al., 2009). After the process with the highest exposures
(median of 0.1 [mu]g/m\3\) was enclosed in 2002 and workers in that
process were required to use respiratory protection, the remaining jobs
had very low exposures (medians ~ 0.03 [mu]g/m\3\). Among 45 workers
hired after the enclosure, one was found to be sensitized (2.2
percent). In Elmore, 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 2-3 percent (Bailey et al.,
2010). In addition, Schuler et al. (2012) found no cases of
sensitization among short-term Elmore workers employed in 1999 who had
total mass LTW average exposures below 0.09 [mu]g/m\3\, among workers
with total mass cumulative exposures below 0.08 [mu]g/m\3\-yr, or among
workers with total mass highest job worked exposures below 0.12 [mu]g/
m\3\.
    Madl et al. reported one case of sensitization among workers at the
Cullman plant hired after 2000. The median personal exposures were
about

0.1 [mu]g/m\3\ or below for all jobs during this period. Several
changes in the facility's exposure control methods were instituted in
the late 1990s that were likely to have reduced dermal as well as
respiratory exposure to beryllium. For example, the plant installed
change/locker rooms for workers entering the production facility,
instituted requirements for work uniforms and dedicated work shoes for
production workers, implemented annual beryllium hazard awareness
training that encouraged glove use, and purchased high efficiency
particulate air (HEPA) filter vacuum cleaners for workplace cleanup and
decontamination.
    The results of the Reading, Tucson, and Elmore studies show that
reducing airborne exposures to below 0.1 [mu]g/m\3\ and protecting
workers from dermal exposure, in combination, have achieved a
substantial reduction in sensitization risk among newly-hired workers.
Because respirator use, dermal protection, and engineering changes were
often implemented concurrently at these plants, it is difficult to
attribute the reduced risk to any single control measure. The reduction
is particularly evident when comparing newly-hired workers in the most
recent Reading screenings (2.2-5.4 percent), and the rate of
sensitization found among workers hired within the year before the 2000
screening (13 percent). There is a similarly striking difference
between the rate of prevalence found among newly-hired workers in the
most recent Tucson study (1 percent) and the rate found among workers
hired within the year before the 1998 screening at that plant (16
percent). These results are echoed in the Cullman facility, which
combined engineering controls to reduce airborne exposures to below 0.1
[mu]g/m\3\ with measures such as housekeeping improvements and worker
training to reduce dermal exposure.
    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 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 most recent Tucson, Reading, and
Elmore studies. 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\). 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), and workers employed only in
administration at a beryllium ceramics facility (Kreiss et al., 1996).
    Arjomandi et al. published a study of 50 sensitized workers from a
nuclear weapons research and development facility (Arjomandi et al.,
2010). Occupational and medical histories including physical
examination and chest imaging were available for the great majority
(49) of these individuals. Forty underwent testing for CBD via
bronchoscopy and transbronchial biopsies. In contrast to the studies of
low-exposure populations discussed previously, this group had much
longer follow-up time (mean time since first exposure = 32 years) and
length of employment at the facility (mean of 18 years). Quantitative
exposure estimates for the workers were not presented; however, the
authors characterized their probable exposures as ``low'' (13 workers),
``moderate'' (28 workers), or ``high'' (nine workers) based on the jobs
they performed at the facility.
    Five of the 50 sensitized workers (10 percent) were diagnosed with
CBD based on histology or high-resolution computed tomography. An
additional three (who had not undergone full clinical evaluation for
CBD) were identified as probable CBD cases, bringing the total
prevalence of CBD and probable CBD in this group to 16 percent. As
discussed in the epidemiology section of the Health Effects chapter,
the prevalence of CBD among worker populations regularly exposed at
higher levels (e.g., median > 0.1 [mu]g/m\3\) is typically much
greater, approaching 80-100% in several studies. The lower prevalence
of CBD in this group of sensitized workers, who were believed to have
primarily low exposure levels, suggests that controlling respiratory
exposure to beryllium may reduce risk of CBD among sensitized workers
as well as reducing risk of CBD via prevention of sensitization.
However, it also demonstrates that some workers in low-exposure
environments can become sensitized and go on to develop CBD. The next
section discusses an additional source of information on low-level
beryllium exposure and CBD: studies of community-acquired CBD in
residential areas surrounding beryllium production facilities.

C. Review of Community-Acquired CBD Literature

    The literature on community-acquired chronic beryllium disease (CA-
CBD) documents cases of CBD among individuals exposed to airborne
beryllium at concentrations below the proposed PEL. OSHA notes that
these case studies do not provide information on how frequently
individuals exposed to very low airborne levels develop CBD and that
reconstructed exposure estimates for CA-CBD cases are less reliable
than exposure estimates for working populations reviewed in the
previous sections. In addition, the cumulative exposure that an
occupationally exposed person would accrue at any given exposure
concentration is far less than would typically accrue from long-term
environmental exposure. The literature on CA-CBD thus has important
limitations and is not used as a basis for quantitative risk assessment
for CBD from low-level beryllium exposure. Nevertheless, these case
reports and the broader CA-CBD literature indicate that individuals
exposed to airborne beryllium below the proposed PEL can develop CBD.
    Cases of CA-CBD were first reported among residents of Lorain, OH,
and Reading, PA, who lived in the vicinity of beryllium plants. More
recently, BeLPT screening has been used to identify additional cases of
CA-CBD in Reading.
1. Lorain, OH
    In 1948, the State of Ohio Department of Public Health conducted an
X-ray program surveying more than 6,000 people who lived within 1.5
miles of a Lorain beryllium plant (Eisenbud, 1949; Eisenbud, 1982;
Eisenbud, 1998). This survey, together with a later review of all
reported cases of CBD in the area, found 13 cases of CBD. All of the
residents who developed CBD lived within 0.75 miles of the plant, and
none had occupational exposure or lived with beryllium-exposed workers.
Among the population of 500 people living within 0.25 miles of the
plant, seven residents (1.4 percent) were diagnosed with CBD. Five
cases were diagnosed among residents living between 0.25 and 0.5 miles
from the plant, one case was diagnosed among residents living between
0.5 and 0.75 miles from the plant, and no cases were found among those
living farther than 0.75 miles from the plant (total populations not
reported) (Eisenbud, 1998).
    Beginning in January 1948, air sampling was conducted using a
mobile sampling station to measure

atmospheric beryllium downwind from the plant. An approximate
concentration of 0.2 [mu]g/m\3\ was measured at 0.25 miles from the
plant's exhaust stack, and concentrations decreased with greater
distance from the plant, to 0.003 [mu]g/m\3\ at a distance of 5 miles
(Eisenbud, 1982). A 10-week sampling program was conducted using three
fixed monitoring stations within 700 feet of the plant and one station
7,000 feet from the plant. Interpolating the measurements collected at
these locations, Eisenbud and colleagues estimated an average airborne
beryllium concentration of between 0.004 and 0.02 [mu]g/m\3\ at a
distance of 0.75 miles from the plant. Accounting for the possibility
that previous exposures may have been higher due to production level
fluctuations and greater use of rooftop emissions, they concluded that
the lowest airborne beryllium level associated with CA-CBD in this
community was somewhere between 0.01 [mu]g/m\3\ and 0.1 [mu]g/m\3\
(Eisenbud, 1982).
2. Reading, PA
    Thirty-two cases of CA-CBD were reported in a series of papers
published in 1959-1969 concerning a beryllium refinery in Reading
(Lieben and Metzner, 1959; Metzner and Lieben, 1961; Dattoli et al.,
1964; Lieben and Williams, 1969). The plant, which opened in 1935,
manufactured beryllium oxide, alloys and metal, and beryllium tools and
metal products (Maier et al., 2008; Sanderson et al., 2001b). In a
follow-up study, Maier et al. presented eight additional cases of CA-
CBD who had lived within 1.5 miles of the plant (Maier et al., 2008).
Individuals with a history of occupational beryllium exposure and those
who had resided with occupationally exposed workers were not classified
as having CA-CBD.
    The Pennsylvania Department of Health conducted extensive
environmental sampling in the area of the plant beginning in 1958.
Based on samples collected in 1958, Maier et al. stated that most cases
identified in their study would typically have been exposed to airborne
beryllium at levels between 0.0155 and 0.028 [mu]g/m\3\ on average,
with the potential for some excursions over 0.35 [mu]g/m\3\ (Maier et
al 2008, p. 1015). To characterize exposures to cases identified in the
earlier publications, Lieben and Williams cited a sampling program
conducted by the Department of Health between January and July 1962,
using nine sampling stations located between 0.2 and 4.8 miles from the
plant. They reported that 72 percent of 24-hour samples collected were
below 0.01 [mu]g/m\3\. Of samples that exceeded 0.01 [mu]g/m\3\, most
were collected at close proximity to the plant (e.g., 0.2 miles from
the plant).
    In the early series of publications, cases of CA-CBD were reported
among people living both close to the plant (Maier et al., 2008; Dutra,
1948) and up to several miles away. Of new cases identified in the 1968
update, all lived between 3 and 7.5 miles from the plant. Lieben and
Williams suggested that some cases of CA-CBD found among more distant
residents might have resulted from working or visiting a graveyard
closer to the plant (Lieben and Williams, 1969). For example, a milkman
who developed CA-CBD had a route in the neighborhood of the plant.
Another resident with CA-CBD had worked as a cleaning woman in the area
of the plant, and a third worked within a half-mile of the plant.
    At the time of the final follow-up study (1968), 11 residents
diagnosed with CA-CBD were alive and 21 were deceased. Among those who
had died, berylliosis was listed as the cause of death for three,
including a 10-year-old girl and two women in their sixties. Fibrosis,
granuloma or granulomatosis, and chronic or fibrous pneumonitis were
listed as the cause of death for eight more of those deceased.
Histologic evidence of CBD was reported for nine of 12 deceased
individuals who had been evaluated for it. In addition to showing
radiologic abnormalities associated with CBD, all living cases were
dyspneic.
    Following the 1969 publication by Liebman and Williams, no
additional CA-CBD cases were reported in the Reading area until 1999,
when a new case was diagnosed. The individual was a 72-year-old woman
who had had abnormal chest x-rays for the previous six years (Maier et
al., 2008). After the diagnosis of this case, Maier et al. reviewed
medical records and/or performed medical evaluations, including BeLPT
results for 16 community residents who were referred by family members
or an attorney.
    Among those referred, eight cases of definite or probable CBD were
identified between 1999 and 2002. All eight were women who lived
between 0.1 and 1.05 miles from the plant, beginning between 1943-1953
and ending between 1956-2001. Five of the women were considered
definite cases of CA-CBD, based on an abnormal blood or lavage cell
BeLPT and granulomatous inflammation on lung biopsy. Three probable
cases of CA-CBD were identified. One had an abnormal BeLPT and
radiography consistent with CBD, but granulomatous disease was not
pathologically proven. Two met Beryllium Case Registry epidemiologic
criteria for CBD based on radiography, pathology and a clinical course
consistent with CBD, but both died before they could be tested for
beryllium sensitization. One of the probable cases, who could not be
definitively diagnosed with CBD because she died before she could be
tested, was the mother of both a definite case and the probable case
who had an abnormal BeLPT but did not show granulomatous disease.
    The individuals with CA-CBD identified in this study suffered
significant health impacts from the disease, including obstructive,
restrictive, and gas exchange pulmonary defects in the majority of
cases. All but two had abnormal pulmonary physiology. Those two were
evaluated at early stages of disease following their mother's
diagnosis. Six of the eight women required treatment with prednisone, a
step typically reserved for severe cases due to the adverse side
effects of steroid treatment. Despite treatment, three had died of
respiratory impairment from CBD as of 2002 (Maier et al., 2008). The
authors concluded that ``low levels of exposures with significant
disease latency can result in significant morbidity and mortality''
(id., p. 1017).
    OSHA notes that compared with the occupational studies discussed in
the previous section, there is comparatively sparse information on
exposure levels of Lorain and Reading residents. There remains the
possibility that some individuals with CA-CBD may have had higher
exposures than were known and reported in these studies, or have had
unreported exposure to beryllium dust via contact with beryllium-
exposed workers. Nevertheless, the studies conducted in Lorain and
Reading demonstrate that long-term exposure to the apparent low levels
of airborne beryllium, with sufficient disease latency, can lead to
serious or fatal CBD. Genetic susceptibility may play a role in cases
of CBD among individuals with very low or infrequent exposures to
beryllium. The role of genetic susceptibility in the CBD disease
process is discussed in detail in section V.D.3.

D. Exposure-Response Literature on Beryllium Sensitization and CBD

    To further examine the relationship between exposure level and risk
of both sensitization and disease, we next review exposure-response
studies in the CBD literature. Many publications have reported that
exposure levels correlate with risk, including a small number of

exposure-response analyses. Most of these studies examined the
association between job-specific beryllium air measurements and
prevalence of sensitization and CBD. This section focuses on studies at
three facilities that included a more rigorous historical
reconstruction of individual worker exposures in their exposure-
response analyses.
1. Rocky Flats, CO, Facility
    In 2000, Viet et al. published a case-control study of participants
in the Rocky Flats Beryllium Health Surveillance Program (BHSP), which
was established in 1991 to screen workers at the Department of Energy's
Rocky Flats, CO, nuclear weapons facility for beryllium sensitization
and evaluate sensitized workers for CBD (Viet et al., 2000). The
program, which at the time of publication had tested over 5,000 current
and former Rocky Flats employees, had identified a total of 127
sensitized individuals as of 1994 when Viet et al. initiated their
study.
    Workers were considered sensitized if two BeLPT results were
positive, either from two blood draws or from a single blood draw
analyzed by two different laboratories. All sensitized individuals were
offered clinical evaluation, and 51 were diagnosed with CBD based on
positive lung LPT and evidence of noncaseating granulomas upon lung
biopsy. The number of sensitized individuals who declined clinical
evaluation was not reported. Two cases, one with CBD and one who was
sensitized but not diagnosed with CBD, were excluded from the case-
control analysis due to reported or potential prior beryllium exposure
at a ceramics plant. Another sensitized individual who had not been
diagnosed with CBD was excluded because she could not be matched by the
study's criteria to a non-sensitized control within the BHSP database.
Viet et al. matched a total of 50 CBD cases to 50 controls who were
negative on the BeLPT and had the same age ( 3 years),
gender, race and smoking status, and were otherwise randomly selected
from the database. Using the same matching criteria, 74 sensitized
workers who were not diagnosed with CBD were age-, gender-, race-, and
smoking status-matched to 74 control individuals who tested negative by
the BeLPT from the BHSP database.
    Viet et al. developed exposure estimates for the cases and controls
based on daily beryllium air samples collected in one of 36 buildings
where beryllium was used at Rocky Flats, the Building 444 Beryllium
Machine Shop. Over half of the approximately 500,000 industrial hygiene
samples collected at Rocky Flats were taken from this building. Air
monitoring in other buildings was reported to be limited and
inconsistent and, thus, not utilized in the exposure assessment. The
sampling data used to develop worker exposure estimates were
exclusively Building 444 fixed airhead (FAH) area samples collected at
permanent fixtures placed around beryllium work areas and machinery.
    Exposure estimates for jobs in Building 444 were constructed for
the years 1960-1988 from this database. Viet et al. worked with Rocky
Flats industrial hygienists and staff to assign a ``building area
factor'' (BAF) to each of the other buildings, indicating the likely
level of exposure in a building relative to exposures in Building 444.
Industrial hygienists and staff similarly assigned a job factor (JF) to
all jobs, representing the likely level of beryllium exposure relative
to the levels experienced by beryllium machinists. A JF of 1 indicated
the lowest exposures, and a JF of 10 indicated the highest exposures.
For example, administrative work and vehicle operation were assigned a
JF of 1, while machining, mill operation, and metallurgical operation
were each assigned a JF of 10. Estimated FAH values for each
combination of job, building and year in the study subjects' work
histories were generated by multiplying together the job and building
factors and the mean annual FAH exposure level. Using data collected by
questionnaire from each BHSP participant, Viet et al. reconstructed
work histories for each case and control, including job title and
building location in each year of their employment at Rocky Flats.
These work histories and the estimated FAH values were used to generate
a cumulative exposure estimate (CEE) for each case and control in the
study. A long-term mean exposure estimate (MEE) was generated by
dividing each CEE by the individual's number of years employed at Rocky
Flats.
    Viet et al.'s statistical analysis of the resulting data set
included conditional logistic regression analysis, modeling the
relationship between risk of each health outcome and log-transformed
CEE and MEE. They found highly statistically significant relationships
between log-CEE and risk of CBD (coef = 0.837, p = 0.0006) and between
log-MEE (coef = 0.855, p = 0.0012) and risk of CBD, indicating that
risk of CBD increases with exposure level. These coefficients
correspond to odds ratios of 6.9 and 7.2 per 10-fold increase in
exposure, respectively. Risk of sensitization without CBD did not show
a statistically significant relationship with log-CEE (coef = 0.111, p
= 0.32), but showed a nearly-significant relationship with log-MEE
(coef = 0.230, p = 0.097).
2. Cullman, AL, Facility
    The Cullman, AL, precision machining facility discussed previously
was the subject of a case-control study published by Kelleher et al. in
2001. After the diagnosis of an index case of CBD at the plant in 1995,
NJMRC researchers worked with the plant to conduct a medical
surveillance program using the BeLPT to screen workers biennially for
beryllium sensitization and CBD. Of 235 employees screened between 1995
and 1999, 22 (9.4 percent) were found to be sensitized, including 13
diagnosed with CBD (Newman et al., 2001). Concurrently, research was
underway by Martyny et al. to characterize the particle size
distribution of beryllium exposures generated by processes at this
plant (Martyny et al., 2000). The exposure research showed that the
machining operations during this time period generated respirable
particles (10 [mu]m or less) at the worker breathing zone that made up
greater than 50 percent of the beryllium mass. Kelleher et al. used the
dataset of 100 personal lapel samples collected by Martyny et al. and
other NJMRC researchers in 1996, 1997, and 1999 to characterize
exposures for each job in the plant. Following a statistical analysis
comparing the samples collected by NJMRC with earlier samples collected
at the plant, Kelleher et al. concluded that the 1996-1999 data could
be used to represent job-specific exposures from earlier periods.
    Detailed work history information gathered from plant data and
worker interviews was used in combination with job exposure estimates
to characterize cumulative and LTW average beryllium exposures for
workers in the surveillance program. In addition to cumulative and LTW
exposure estimates based the total mass of beryllium reported in their
exposure samples, Kelleher et al. calculated cumulative and LTW
estimates based specifically on exposure to particles < 6 [mu]m and
particles < 1 [mu]m in diameter.
    To analyze the relationship between exposure level and risk of
sensitization and CBD, Kelleher et al. performed a case-control
analysis using measures of both total beryllium exposure and particle
size-fractionated exposure. The analysis included sensitization cases
identified in the 1995-1999 surveillance and 206 controls from the
group of 215 non-sensitized workers. For nine workers, the researchers
could not

reconstruct complete job histories. Logistic regression models using
categorical exposure variables showed positive associations between
risk of sensitization and the six exposure measures tested: Total CEE,
total MEE, and variations of CEE and MEE constructed based on particles
< 6 [mu]m and < 1 [mu]m in diameter. None of the associations were
statistically significant (p < 0.05); however, the authors noted that
the dataset was relatively small, with limited power to detect a
statistically significant exposure-response relationship.
    Although the Viet et al. and Kelleher et al. exposure-response
analyses provide valuable insight into exposure-response for beryllium
sensitization and CBD, both studies have limitations that affect their
suitability as a basis for quantitative risk assessment. Their
limitations primarily involve the exposure data used to estimate
workers' exposures. Viet et al.'s exposure reconstruction was based on
area samples from a single building within a large, multi-building
facility. Where possible, OSHA prefers to base risk estimates on
exposure data collected in the breathing zone of workers rather than
area samples, because data collected in the breathing zone more
accurately represent workers' exposures. Kelleher's analysis, on the
other hand, was based on personal lapel samples. However, the samples
Kelleher et al. used were collected between 1996 and 1999, after the
facility had initiated new exposure control measures in response to the
diagnosis of a case of CBD in 1995. OSHA believes that industrial
hygiene samples collected at the Cullman plant prior to 1996 better
characterize exposures prior to the new exposure controls. In addition,
since the publication of the Kelleher study, the population has
continued to be screened for sensitization and CBD. Data collected on
workers hired in 2000 and later, after most exposure controls had been
completed, can be used to characterize risk at lower levels of exposure
than have been examined in many previous studies.
    To better characterize the relationship between exposure level and
risk of sensitization and CBD, OSHA developed an independent exposure-
response analysis based on a dataset maintained by NJMRC on workers at
the Cullman, AL, machining plant. The dataset includes exposure samples
collected between 1980 and 2005, and has updated work history and
screening information for several hundred workers through 2003. OSHA's
analysis of the NJMRC data set is presented in the next section, E.
OSHA's Exposure-Response Analysis.
3. Elmore, OH, Facility
    After OSHA completed its analysis of the NJMRC data set, Schuler et
al. (2012) published a study examining beryllium sensitization and CBD
among 264 short-term workers employed at the previously described
Elmore, OH plant in 1999. The analysis used a high-quality exposure
reconstruction by Virji et al. (2012) and presented a regression
analysis of the relationship between beryllium exposure levels and
beryllium sensitization and CBD in the short-term worker population. By
including only short-term workers, Virji et al. were able to construct
participants' exposures with more precision than was possible in
studies involving workers exposed for longer durations and in time
periods with less exposure sampling. In addition, the focus on short-
term workers allowed more precise knowledge of when sensitization and
CBD occurred than had been the case for previously published cross-
sectional studies of long-term workers. Each participant completed a
work history questionnaire and was tested for beryllium sensitization,
and sensitized workers were offered further evaluation for CBD. The
overall prevalence of sensitization was 9.8 percent (26/264). Twenty-
two sensitized workers consented to clinical testing for CBD via
transbronchial biopsy. Six of those sensitized were diagnosed with CBD
(2.3 percent, 6/264).
    Schuler et al. (2012) used logistic regression to explore the
relationship between estimated beryllium exposure and sensitization and
CBD, using estimates of total, respirable, and submicron mass
concentrations. Exposure estimates were constructed using two exposure
surveys conducted in 1999: a survey of total mass exposures (4,022
full-shift personal samples) and a survey of size-separated impactor
samples (198 samples). The 1999 exposure surveys and work histories
were used to estimate long-term lifetime weighted (LTW) average,
cumulative, and highest-job-worked exposure for total, respirable, and
submicron beryllium mass concentrations.
    For beryllium sensitization, logistic models showed elevated odds
ratios for average (OR 1.48) and highest job (OR 1.37) exposure for
total mass exposure; the OR for cumulative exposure was smaller (OR
1.23) and borderline statistically significant (95 percent CI barely
included unity). Relationships between sensitization and respirable
exposure estimates were similarly elevated for average (OR 1.37) and
highest job (OR 1.32). Among the submicron exposure estimates, only
highest job (OR 1.24) had a 95 percent CI that just included unity for
sensitization. For CBD, elevated odds ratios were observed only for the
cumulative exposure estimates and were similar for total mass and
respirable exposure (total mass OR 1.66, respirable (OR 1.68).
Cumulative submicron exposure showed an elevated, borderline
significant odds ratio (OR 1.58). The odds ratios for average exposure
and highest-exposed job were not statistically significantly elevated.
Schuler et al. concluded that both total and respirable mass
concentrations of beryllium exposure were relevant predictors of risk
for beryllium sensitization and CBD.

 E. OSHA's Exposure-Response Analysis

    OSHA evaluated exposure and health outcome data on a population of
workers employed at the Cullman machining facility. NJMRC researchers,
with consent and information provided by the facility, compiled a
dataset containing employee work histories, medical diagnoses, and air
sampling results and provided it to OSHA for analysis. OSHA's
contractors from Eastern Research Group (ERG) gathered additional