Occupational Exposure to Beryllium and Beryllium Compounds

Federal RegisterAug 7, 2015

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DEPARTMENT OF LABOR

Occupational Safety and Health Administration

29 CFR Part 1910

[Docket No. OSHA-H005C-2006-0870]

RIN 1218-AB76

Occupational Exposure to Beryllium and Beryllium Compounds

AGENCY:

Occupational Safety and Health Administration (OSHA), Department of Labor.

ACTION:

Proposed rule; request for comments.

SUMMARY:

The Occupational Safety and Health Administration (OSHA) proposes to amend its existing exposure limits for occupational exposure in general industry to beryllium and beryllium compounds and promulgate a substance-specific standard for general industry regulating occupational exposure to beryllium and beryllium compounds. This document proposes a new permissible exposure limit (PEL), as well as ancillary provisions for employee protection such as methods for controlling exposure, respiratory protection, medical surveillance, hazard communication, and recordkeeping. In addition, OSHA seeks comment on a number of alternatives, including a lower PEL, that could affect construction and maritime, as well as general industry.

DATES:

Written comments.

Written comments, including comments on the information collection determination described in Section IX of the preamble (OMB Review under the Paperwork Reduction Act of 1995), must be submitted (postmarked, sent, or received) by November 5, 2015.

Informal public hearings.

The Agency will schedule an informal public hearing on the proposed rule if requested during the comment period. The location and date of the hearing, procedures for interested parties to notify the Agency of their intention to participate, and procedures for participants to submit their testimony and documentary evidence will be announced in the

Federal Register

if a hearing is requested.

ADDRESSES:

Written comments.

You may submit comments, identified by Docket No. OSHA-H005C-2006-0870, by any of the following methods:

Electronically:

You may submit comments and attachments electronically at

http://www.regulations.gov

, which is the Federal e-Rulemaking Portal. Follow the instructions on-line for making electronic submissions. When uploading multiple attachments into Regulations.gov, please number all of your attachments because

www.Regulations.gov

will not automatically number the attachments. This will be very useful in identifying all attachments in the beryllium rule. For example, Attachment 1—title of your document, Attachment 2—title of your document, Attachment 3—title of your document, etc. Specific instructions on uploading all documents are found in the Facts, Answer, Questions portion and the commenter check list on Regulations.gov Web page.

Fax:

If your submissions, including attachments, are not longer than 10 pages, you may fax them to the OSHA Docket Office at (202) 693-1648.

Mail, hand delivery, express mail, messenger, or courier service:

You may submit your comments to the OSHA Docket Office, Docket No. OSHA-H005C-2006-0870, U.S. Department of Labor, Room N-2625, 200 Constitution Avenue NW., Washington, DC 20210, telephone (202) 693-2350 (OSHA's TTY number is (877) 889-5627). Deliveries (hand, express mail, messenger, or courier service) are accepted during the Docket Office's normal business hours, 8:15 a.m.-4:45 p.m., E.S.T.

Instructions:

All submissions must include the Agency name and the docket number for this rulemaking (Docket No. OSHA-H005C-2006-0870). All comments, including any personal information you provide, are placed in the public docket without change and may be made available online at

http://www.regulations.gov

. Therefore, OSHA cautions you about submitting personal information such as Social Security numbers and birthdates.

If you submit scientific or technical studies or other results of scientific research, OSHA requests (but is not requiring) that you also provide the following information where it is available: (1) Identification of the funding source(s) and sponsoring organization(s) of the research; (2) the extent to which the research findings were reviewed by a potentially affected party prior to publication or submission to the docket, and identification of any such parties; and (3) the nature of any financial relationships (

e.g.

, consulting agreements, expert witness support, or research funding) between investigators who conducted the research and any organization(s) or entities having an interest in the rulemaking. If you are submitting comments or testimony on the Agency's scientific or technical analyses, OSHA requests that you disclose: (1) The nature of any financial relationships you may have with any organization(s) or entities having an interest in the rulemaking; and (2) the extent to which your comments or testimony were reviewed by an interested party before you submitted them. Disclosure of such information is intended to promote transparency and scientific integrity of data and technical information submitted to the record. This request is consistent with Executive Order 13563, issued on January 18, 2011, which instructs agencies to ensure the objectivity of any scientific and technological information used to support their regulatory actions. OSHA emphasizes that all material submitted to the rulemaking record will be considered by the Agency to develop the final rule and supporting analyses.

Docket:

To read or download comments and materials submitted in response to this

Federal Register

notice, go to Docket No. OSHA-H005C-2006-0870 at

http://www.regulations.gov,

or to the OSHA Docket Office at the address above. All comments and submissions are listed in the

http://www.regulations.gov

index; however, some information (

e.g.

, copyrighted material) is not publicly available to read or download through that Web site. All comments and submissions are available for inspection at the OSHA Docket Office.

Electronic copies of this

Federal Register

document are available at

http://www.regulations.gov

. Copies also are available from the OSHA Office of Publications, Room N-3101, U.S. Department of Labor, 200 Constitution Avenue NW., Washington, DC 20210; telephone (202) 693-1888. This document, as well as news releases and other relevant information, is also available at OSHA's Web site at

http://www.osha.gov

OSHA has not provided the document ID numbers for all submissions in the record for this beryllium proposal. The proposal only contains a reference list for all submissions relied upon. The public can find all document ID numbers in an Excel spreadsheet that is posted on OSHA's rulemaking Web page (see

www.osha.gov/berylliumrulemaking

). The public will be able to locate submissions in the record in the public docked Web page:

http://www.regulations.gov

. To locate a particular submission contained in

http://www.regulations.gov

, the public should enter the full document ID number in the search bar.

FOR FURTHER INFORMATION CONTACT:

For general information and press inquiries, contact Frank Meilinger, Director, Office of Communications, Room N-3647,

OSHA, U.S. Department of Labor, 200 Constitution Avenue NW., Washington, DC 20210; telephone: (202) 693-1999; email:

meilinger.francis2@dol.gov

. For technical inquiries, contact: William Perry or Maureen Ruskin, Directorate of Standards and Guidance, Room N-3718, OSHA, U.S. Department of Labor, 200 Constitution Avenue NW., Washington, DC 20210; telephone (202) 693-1955 or fax (202) 693-1678; email:

perry.bill@dol.gov

SUPPLEMENTARY INFORMATION:

The preamble to the proposed standard on occupational exposure to beryllium and beryllium compounds follows this outline:

Executive Summary

I. Issues and Alternatives

II. Pertinent Legal Authority

III. Events Leading to the Proposed Standards

IV. Chemical Properties and Industrial Uses

V. Health Effects

VI. Preliminary Risk Assessment

VII. Response to Peer Review

VIII. Significance of Risk

IX. Summary of the Preliminary Economic Analysis and Initial Regulatory Flexibility Analysis

X. OMB Review under the Paperwork Reduction Act of 1995

XI. Federalism

XII. State-Plan States

XIII. Unfunded Mandates Reform Act

XIV. Protecting Children from Environmental Health and Safety Risks

XV. Environmental Impacts

XVI. Consultation and Coordination with Indian Tribal Governments

XVII. Public Participation

XVIII. Summary and Explanation of the Proposed Standard

(a) Scope and Application

(b) Definitions

(d) Exposure Assessment

(e) Beryllium Work Areas and Regulated Areas

(f) Methods of Compliance

(g) Respiratory Protection

(h) Personal Protective Clothing and Equipment

(i) Hygiene Areas and Practices

(j) Housekeeping

(k) Medical Surveillance

(l) Medical Removal

(m) Communication of Hazards to Employees

(n) Recordkeeping

(o) Dates

XIX. References

Executive Summary

OSHA currently enforces permissible exposure limits (PELs) for beryllium in general industry, construction, and shipyards. These PELs were adopted in 1971, shortly after the Agency was created, and have not been updated since then. The time-weighted average (TWA) PEL for beryllium is 2 micrograms per cubic meter of air (μg/m

) as an 8-hour time-weighted average. OSHA is proposing a new TWA PEL of 0.2 μg/m

in general industry. OSHA is also proposing other elements of a comprehensive health standard, including requirements for exposure assessment, preferred methods for controlling exposure, respiratory protection, personal protective clothing and equipment (PPE), medical surveillance, medical removal, hazard communication, and recordkeeping.

OSHA's proposal is based on the requirements of the Occupational Safety and Health Act (OSH Act) and court interpretations of the Act. For health standards issued under section 6(b)(5) of the OSH Act, OSHA is required to promulgate a standard that reduces significant risk to the extent that it is technologically and economically feasible to do so. See Section II of this preamble, Pertinent Legal Authority, for a full discussion of OSHA legal requirements.

OSHA has conducted an extensive review of the literature on adverse health effects associated with exposure to beryllium. The Agency has also assessed the risk of beryllium-related diseases at the current TWA PEL, the proposed TWA PEL and the alternative TWA PELs. These analyses are presented in this preamble at Section V, Health Effects, Section VI, Preliminary Risk Assessment, and Section VIII, Significance of Risk. As discussed in Section VIII of this preamble, Significance of Risk, the available evidence indicates that worker exposure to beryllium at the current PEL poses a significant risk of chronic beryllium disease (CBD) and lung cancer, and that the proposed standard will substantially reduce this risk.

Section 6(b) of the OSH Act requires OSHA to determine that its standards are technologically and economically feasible. OSHA's examination of the technological and economic feasibility of the proposed rule is presented in the Preliminary Economic Analysis and Initial Regulatory Flexibility Analysis (PEA) (OSHA, 2014), and is summarized in Section IX of this preamble, Summary of the Preliminary Economic Analysis and Initial Regulatory Flexibility Analysis. OSHA has preliminarily concluded that the proposed PEL of 0.2 μg/m

is technologically feasible for all affected industries and application groups. Thus, OSHA preliminarily concludes that engineering and work practices will be sufficient to reduce and maintain beryllium exposures to the proposed PEL of 0.2 μg/m

or below in most operations most of the time in the affected industries. For those few operations within an industry or application group where compliance with the proposed PEL cannot be achieved even when employers implement all feasible engineering and work practice controls, the proposed standard would require employers to supplement controls with respirators.

OSHA developed quantitative estimates of the compliance costs of the proposed rule for each of the affected industry sectors. The estimated compliance costs were compared with industry revenues and profits to provide a screening analysis of the economic feasibility of complying with the revised standard and an evaluation of the potential economic impacts. Industries with unusually high costs as a percentage of revenues or profits were further analyzed for possible economic feasibility issues. After performing these analyses, OSHA has preliminarily concluded that compliance with the requirements of the proposed rule would be economically feasible in every affected industry sector.

The Regulatory Flexibility Act, as amended by the Small Business Regulatory Enforcement Fairness Act (SBREFA), requires that OSHA either certify that a rule would not have a significant economic impact on a substantial number of small entities or prepare a regulatory flexibility analysis and hold a Small Business Advocacy Review (SBAR) Panel prior to proposing the rule. OSHA has determined that a regulatory flexibility analysis is needed and has provided this analysis in Chapter IX of the PEA (OSHA, 2014). A summary is provided in Section IX of this preamble, Summary of the Preliminary Economic Analysis and Initial Regulatory Flexibility Analysis. OSHA also previously held a SBAR Panel for this rule. The recommendations of the Panel and OSHA's response to them are summarized in Section IX of this preamble.

Executive Orders 13563 and 12866 direct agencies to assess all costs and benefits of available regulatory alternatives. Executive Order 13563 emphasizes the importance of quantifying both costs and benefits, of reducing costs, of harmonizing rules, and of promoting flexibility. This rule has been designated an economically significant regulatory action under section 3(f)(1) of Executive Order 12866. Accordingly, this proposed rule has been reviewed by the Office of Management and Budget. The remainder of this section summarizes the key findings of the analysis with respect to costs and benefits of the proposed standard, presents alternatives

to the proposed standard, and requests comments on a number of issues.

Table I-1, which is derived from material presented in the PEA, provides a summary of OSHA's best estimate of the costs and benefits of this proposed rule. As shown, this proposed rule is estimated to prevent 96 fatalities and 50 non-fatal beryllium-related illnesses annually once it is fully effective, and the monetized annualized benefits of the proposed rule are estimated to be $576 million using a 3-percent discount rate and $255 million using a 7-percent discount rate. Also as shown in Table I-1, the estimated annualized cost of the rule is $37.6 million using a 3-percent discount rate and $39.1 million using a 7-percent discount rate. This proposed rule is estimated to generate net benefits of $538 million annually using a 3-percent discount rate and $216 million annually using a 7-percent discount rate. These estimates are for informational purposes only and have not been used by OSHA as the basis for its decision concerning the choice of a PEL or of other ancillary requirements for this proposed beryllium rule. The courts have ruled that OSHA may not use benefit-cost analysis or a criterion of maximizing net benefits as a basis for setting OSHA health standards.

Am. Textile Mfrs. Inst., Inc.

Nat'l Cotton Council of Am.

, 452 U.S. 490, 513 (1981);

Pub. Citizen Health Research Group

U.S. Dep't of Labor

, 557 F.3d 165, 177 (3d Cir. 2009).

Table I-1—Annualized Costs, Benefits and Net Benefits of OSHA's Proposed Beryllium Standard of 0.2 μg/m

Discount rate

Annualized Costs

Engineering Controls

$9,540,189

$10,334,036

Respirators

249,684

252,281

Exposure Assessment

2,208,950

2,411,851

Regulated Areas and Beryllium Work Areas

629,031

652,823

Medical Surveillance

2,882,076

2,959,448

Medical Removal

148,826

166,054

Exposure Control Plan

1,769,506

1,828,766

Protective Clothing and Equipment

1,407,365

Hygiene Areas and Practices

389,241

389,891

Housekeeping

12,574,921

12,917,944

Training

5,797,535

5,826,975

Total Annualized Costs (Point Estimate)

37,597,325

39,147,434

Annual Benefits: Number of Cases Prevented

Fatal Lung Cancer

4.0

CBD-Related Mortality

92.0

Total Beryllium Related Mortality

96.0

572,981,864

253,743,368

Morbidity

49.5

2,844,770

1,590,927

Monetized Annual Benefits (midpoint estimate)

575,826,633

255,334,295

Net Benefits

538,229,308

216,186,861

Source:

OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.

Both the costs and benefits of Table I-1 reflect the incremental costs and benefits associated with achieving full compliance with the proposed standard. They do not include costs and benefits associated with employers' current exposure control measures or other aspects of the proposed standard they have already implemented. For example, for employers whose exposures are already below the proposed PEL, OSHA's estimated costs and benefits for the proposed standard do not include the costs of their exposure control measures or the benefits of these employers' compliance with the proposed PEL. The costs and benefits of Table I-1 also do not include costs and benefits associated with achieving compliance with existing requirements, to the extent that some employers may currently not be fully complying with applicable regulatory requirements.

I. Issues and Alternatives

In addition to the proposed standard itself, this preamble discusses more than two dozen regulatory alternatives, including various sub-alternatives, to the proposed standard and requests comments and information on a variety of topics pertinent to the proposed standard. The regulatory alternatives OSHA is considering include alternatives to the proposed scope of the standard, regulatory alternatives to the proposed TWA PEL of 0.2 μg/m

and proposed STEL of 2 μg/m

, a regulatory alternative that would modify the proposed methods of compliance, and regulatory alternatives that affect proposed ancillary provisions. The Agency solicits comment on the proposed phase-in schedule for the various provisions of the standard. Additional requests for comments and information follow the summaries of regulatory alternatives, under the “Issues” heading.

Regulatory Alternatives

OSHA believes that inclusion of regulatory alternatives serves two important functions. The first is to explore the possibility of less costly ways (than the proposed standard) to provide an adequate level of worker protection from exposure to beryllium. The second is tied to the Agency's statutory requirement, which underlies the proposed standard, to reduce significant risk to the extent feasible. Each regulatory alternative presented here is described and analyzed more fully elsewhere in this preamble or in the PEA. Where appropriate, the alternative is included in this preamble at the end of the relevant section of Section XVIII, Summary and Explanation of the Proposed Standard, to facilitate comparison of the alternative to the proposed standard. For example, alternative PELs under consideration by the Agency are presented in the discussion of paragraph (c) in Section XVIII. In addition, all

alternatives are discussed in the PEA, Chapter VIII: Regulatory Alternatives (OSHA, 2014). The costs and benefits of each regulatory alternative are presented both in Section IX of this preamble and in Chapter VIII of the PEA.

The more than two dozen regulatory alternatives, including various sub-alternatives regulatory alternatives under consideration are summarized below, and are organized into the following categories: alternatives to the proposed scope of the standard; alternatives to the proposed PELs; alternatives to the proposed methods of compliance; alternatives to the proposed ancillary provisions; and the timing of the standard.

Scope

OSHA has examined three alternatives that would alter the groups of employers and employees covered by this rulemaking. Regulatory Alternative #1a would expand the scope of the proposed standard to include all operations in general industry where beryllium exists only as a trace contaminant; that is, where the materials used contain no more than 0.1% beryllium by weight. Regulatory Alternative #1b is similar to Regulatory Alternative #1a, but exempts operations where the employer can show that employees' exposures will not meet or exceed the action level or exceed the STEL. Where the employer has objective data demonstrating that a material containing beryllium or a specific process, operation, or activity involving beryllium cannot release beryllium in concentrations at or above the proposed action level or above the proposed STEL under any expected conditions of use, that employer would be exempt from the proposed standard except for recordkeeping requirements pertaining to the objective data. Alternative #1a and Alternative #1b, like the proposed rule, would not cover employers or employees in construction or shipyards.

Regulatory Alternative #2a would expand the scope of the proposed standard to also include employers in construction and maritime. For example, this alternative would cover abrasive blasters, pot tenders, and cleanup staff working in construction and shipyards who have the potential for airborne beryllium exposure during blasting operations and during cleanup of spent media. Regulatory Alternative #2b would update §§ 1910.1000 Tables Z-1 and Z-2, 1915.1000 Table Z, and 1926.55 Appendix A so that the proposed TWA PEL and STEL would apply to all employers and employees in general industry, shipyards, and construction, including occupations where beryllium exists only as a trace contaminant. However, all other provisions of the standard would be in effect only for employers and employees that fall within the scope of the proposed rule. More detailed discussion of Regulatory Alternatives #1a, #1b, #2a, and #2b appears in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, Section XVIII of this preamble, Summary and Explanation, includes a discussion of paragraph (a) that describes the scope of the proposed rule, issues with the proposed scope, and Regulatory Alternatives #1a, #1b, #2a, and #2b.

Another regulatory alternative that would impact the scope of affected industries, extending eligibility for medical surveillance to employees in shipyards, construction, and parts of general industry excluded from the scope of the proposed standard, is discussed along with other medical surveillance alternatives later in this section (Regulatory Alternative #21) and in the discussion of paragraph (k) in this preamble at Section XVIII, Summary and Explanation of the Proposed Standard.

Permissible Exposure Limits

OSHA has examined several regulatory alternatives that would modify the TWA PEL or STEL for the proposed rule. Under Regulatory Alternative #3, OSHA would adopt a STEL of 5 times the proposed PEL. Thus, this alternative STEL would be 1.0 μg/m

if OSHA adopts a PEL of 0.2 μg/m

; it would be 0.5 μg/m

if OSHA adopts a PEL of 0.1 μg/m

; and it would be 2.5 µg/m

if OSHA adopts a PEL of 0.5 µg/m

(see Regulatory Alternatives #4 and #5). Under Regulatory Alternative #4, the proposed PEL would be lowered from 0.2 μg/m

to 0.1 μg/m

. Under Regulatory Alternative #5, the proposed PEL would be raised from 0.2 μg/m

to 0.5 μg/m

. In addition, for informational purposes, OSHA examined a regulatory alternative that would maintain the TWA PEL at 2.0 μg/m

, but all of the other proposed provisions would be required with their triggers remaining the same as in the proposed rule. This alternative is not one OSHA could legally adopt because the absence of a more protective requirement for engineering controls would not be consistent with section 6(b)(5) of the OSH Act. More detailed discussion of these alternatives to the proposed PEL appears in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, in Section XVIII of this preamble, Summary and Explanation of the Proposed Standard, the discussion of proposed paragraph (c) describes the proposed TWA PEL and STEL, issues with the proposed exposure limits, and Regulatory Alternatives #3, #4, and #5.

Methods of Compliance

The proposed standard would require employers to implement engineering and work practice controls to reduce employees' exposures to or below the TWA PEL and STEL. Where engineering and work practice controls are insufficient to reduce exposures to or below the TWA PEL and STEL, employers would still be required to implement them to reduce exposure as much as possible, and to supplement them with a respiratory protection program. In addition, for each operation where there is airborne beryllium exposure, the employer must ensure that one or more of the engineering and work practice controls listed in paragraph (f)(2) are in place, unless all of the listed controls are infeasible, or the employer can demonstrate that exposures are below the action level based on two samples taken seven days apart. Regulatory Alternative #6 would eliminate the engineering and work practice controls provision currently specified in paragraph (f)(2). This regulatory alternative does not eliminate the need for engineering controls to lower exposure levels to or below the TWA PEL and STEL; rather, it dispenses with the mandatory use of certain engineering controls that must be installed above the action level but at or below the TWA PEL.

More detailed discussion of Regulatory Alternative #6 appears in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the discussion of paragraph (f) in Section XVIII of this preamble, Summary and Explanation, provides a more detailed explanation of the proposed methods of compliance, issues with the proposed methods of compliance, and Regulatory Alternative #6.

Ancillary Provisions

The proposed rule contains several ancillary provisions, including requirements for exposure assessment, personal protective clothing and equipment (PPE), medical surveillance, medical removal, training, and regulated areas or access control. OSHA has examined a variety of regulatory alternatives involving changes to one or more of these ancillary provisions. OSHA has preliminarily determined that several of these ancillary provisions will increase the benefits of the proposed rule, for example, by helping to ensure the TWA PEL is not exceeded

or by lowering the risks to workers given the significant risk remaining at the proposed TWA PEL. However, except for Regulatory Alternative #7 (involving the elimination of all ancillary provisions), OSHA did not estimate changes in monetized benefits for the regulatory alternatives that affect ancillary provisions. Two regulatory alternatives that involve all ancillary provisions are presented below (#7 and #8), followed by regulatory alternatives for exposure monitoring (#9, #10, and #11), for regulated areas (#12), for personal protective clothing and equipment (#13), for medical surveillance (#14 through #21), and for medical removal (#22).

All Ancillary Provisions

During the Small Business Regulatory Fairness Act (SBREFA) process conducted in 2007, the SBAR Panel recommended that OSHA analyze a PEL-only standard as a regulatory alternative. The Panel also recommended that OSHA consider applying ancillary provisions of the standard so as to minimize costs for small businesses where exposure levels are low (OSHA, 2008b). In response to these recommendations, OSHA analyzed Regulatory Alternative #7, a PEL-only standard, and Regulatory Alternative #8, which would only apply ancillary provisions of the beryllium standard at exposures above the proposed PEL of 0.2 µg/m

or the proposed STEL of 2 µg/m

. Regulatory Alternative #7 would update the Z tables for § 1910.1000, so that the proposed TWA PEL and STEL would apply to all workers in general industry. All other provisions of the proposed standard would be dropped.

As indicated previously, OSHA has preliminarily determined that there is significant risk remaining at the proposed PEL of 0.2 μg/m

. However, the available evidence on feasibility suggests that 0.2 μg/m

may be the lowest feasible PEL (see Chapter IV of the PEA, OSHA 2014). Therefore, the Agency believes that it is necessary to include ancillary provisions in the proposed rule to further reduce the remaining risk. In addition, the recommended standard provided to OSHA by representatives of the primary beryllium manufacturing industry and the Steelworkers Union further supports the importance of ancillary provisions in protecting workers from the harmful effects of beryllium exposure (Materion and USW, 2012).

Under Regulatory Alternative #8, several ancillary provisions that the current proposal would require under a variety of exposure conditions (

e.g.

, dermal contact; any airborne exposure; exposure at or above the action level) would instead only apply where exposure levels exceed the TWA PEL or STEL. Regulatory Alternative #8 affects the following provisions of the proposed standard:

—Exposure monitoring. Whereas the proposed standard requires annual monitoring where exposure levels are at or above the action level and at or below the TWA PEL, Alternative #8 would require annual exposure monitoring only where exposure levels exceed the TWA PEL or STEL;

— Written exposure control plan. Whereas the proposed standard requires written exposure control plans to be maintained in any facility covered by the standard, Alternative #8 would require only facilities with exposures above the TWA PEL or STEL to maintain a plan;

—PPE. Whereas the proposed standard requires PPE for employees under a variety of conditions, such as exposure to soluble beryllium or visible contamination with beryllium, Alternative #8 would require PPE only for employees exposed above the TWA PEL or STEL;

—Housekeeping. Whereas the proposed standard's housekeeping requirements apply across a wide variety of beryllium exposure conditions, Alternative #8 would limit housekeeping requirements to areas with exposures above the TWA PEL or STEL.

—Medical Surveillance. Whereas the proposed standard's medical surveillance provisions require employers to offer medical surveillance to employees with signs or symptoms of beryllium-related health effects regardless of their exposure level, Alternative #8 would make surveillance available to such employees only if they were exposed above the TWA PEL or STEL.

More detailed discussions of Regulatory Alternatives #7 and #8, including a description of the considerations pertinent to these alternatives, appear in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014).

Exposure Monitoring

OSHA has examined three regulatory alternatives that would modify the proposed standard's provisions on exposure monitoring, which require periodic monitoring annually where exposures are at or above the action level and at or below the TWA PEL. Under Regulatory Alternative #9, employers would be required to perform periodic exposure monitoring every 180 days where exposures are at or above the action level or above the STEL, and at or below the TWA PEL. Under Regulatory Alternative #10, employers would be required to perform periodic exposure monitoring every 180 days where exposures are at or above the action level or above the STEL, including where exposures exceed the TWA PEL. Under Regulatory Alternative #11, employers would be required to perform periodic exposure monitoring every 180 days where exposures are at or above the action level or above the STEL, and every 90 days where exposures exceed the TWA PEL. More detailed discussions of Regulatory Alternatives #9, #10, and #11 appear in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the discussion of proposed paragraph (d) in Section XVIII of this preamble, Summary and Explanation of the Proposed Standard, provides a more detailed explanation of the proposed requirements for exposure monitoring, issues with exposure monitoring, and the considerations pertinent to Regulatory Alternatives #9, #10, and #11.

Regulated Areas

The proposed standard would require employers to establish and maintain two types of areas: beryllium work areas, wherever employees are, or can reasonably be expected to be, exposed to any level of airborne beryllium; and regulated areas, wherever employees are, or can reasonably be expected to be, exposed to airborne beryllium at levels above the TWA PEL or STEL. Employers are required to demarcate beryllium work areas, but are not required to restrict access to beryllium work areas or provide respiratory protection or other forms of PPE within work areas that are not also regulated areas. Employers must demarcate regulated areas, restrict access to them, post warning signs and provide respiratory protection and other PPE within regulated areas, as well as medical surveillance for employees who work in regulated areas for more than 30 days in a 12-month period. During the SBREFA process conducted in 2007, the SBAR Panel recommended that OSHA consider dropping or limiting the provision for regulated areas (OSHA, 2008b). In response to this recommendation, OSHA analyzed Regulatory Alternative #12, which would not require employers to establish regulated areas. More detailed discussion of Regulatory Alternative #12 appears in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the discussion of

paragraph (e) in Section XVIII of this preamble, Summary and Explanation, provides a more detailed explanation of the proposed requirements for regulated areas, issues with regulated areas, and considerations pertinent to Regulatory Alternative #12.

Personal Protective Clothing and Equipment (PPE)

Regulatory Alternative #13 would modify the proposed requirements for PPE, which require PPE where exposure exceeds the TWA PEL or STEL; where employees' clothing or skin may become visibly contaminated with beryllium; and where employees may have skin contact with soluble beryllium compounds. The requirement to use PPE where work clothing or skin may become “visibly contaminated” with beryllium differs from prior standards that do not require contamination to be visible in order for PPE to be required. In the case of beryllium, which OSHA has preliminarily concluded can sensitize through dermal exposure, the exposure levels capable of causing adverse health effects and the PELs in effect are so low that beryllium surface contamination is unlikely to be visible (see this preamble at section V, Health Effects). OSHA is therefore considering Regulatory Alternative #13, which would require appropriate PPE wherever there is potential for skin contact with beryllium or beryllium-contaminated surfaces. More detailed discussion of Regulatory Alternative #13 is provided in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the discussion of paragraph (h) in Section XVIII of this preamble, Summary and Explanation, provides a more detailed explanation of the proposed requirements for PPE, issues with PPE, and the considerations pertinent to Regulatory Alternative #13.

Medical Surveillance

The proposed requirements for medical surveillance include: (1) Medical examinations, including a test for beryllium sensitization, for employees who are exposed to beryllium above the proposed PEL for 30 days or more per year, who are exposed to beryllium in an emergency, or who show signs or symptoms of CBD; and (2) low-dose helical tomography (low-dose computed tomography, hereafter referred to as “CT scans”), for employees who were exposed above the proposed PEL for more than 30 days in a 12-month period for 5 years or more. This type of CT scan is a method of detecting tumors, and is commonly used to diagnose lung cancer. The proposed standard would require periodic medical exams to be provided for employees in the medical surveillance program annually, while tests for beryllium sensitization and CT scans would be provided to eligible employees biennially.

OSHA has examined eight regulatory alternatives (#14 through #21) that would modify the proposed rule's requirements for employee eligibility, the types of exam that must be offered, and the frequency of periodic exams. Medical surveillance was a subject of special concern to SERs during the SBREFA process, and the SBREFA Panel offered many comments and recommendations related to medical surveillance for OSHA's consideration. Some of the Panel's concerns have been addressed in this proposal, which was modified since the SBREFA Panel was convened (see this preamble at Section XVIII, Summary and Explanation of the Proposed Standard, for more detailed discussion). Several of the alternatives presented here (#16, #18, and #20) also respond to recommendations by the SBREFA Panel to reduce burdens on small businesses by dropping or reducing the frequency of medical surveillance requirements. OSHA also seeks to ensure that the requirements of the final standard offer workers adequate medical surveillance while limiting the costs to employers. Thus, OSHA requests feedback on several additional alternatives and on a variety of issues raised later in this section of the preamble.

Regulatory Alternatives #14, #15, and #21 would expand eligibility for medical surveillance to a broader group of employees than would be eligible in the proposed standard. Under Regulatory Alternative #14, medical surveillance would be available to employees who are exposed to beryllium above the proposed PEL, including employees exposed for fewer than 30 days per year. Regulatory Alternative #15 would expand eligibility for medical surveillance to employees who are exposed to beryllium above the proposed action level, including employees exposed for fewer than 30 days per year. Regulatory Alternative #21 would extend eligibility for medical surveillance as set forth in proposed paragraph (k) to all employees in shipyards, construction, and general industry who meet the criteria of proposed paragraph (k)(1) (or any of the alternative criteria under consideration). However, all other provisions of the standard would be in effect only for employers and employees that fall within the scope of the proposed rule.

Regulatory Alternatives #16 and #17 would modify the proposed standard's requirements to offer beryllium sensitization testing to eligible employees. Under Regulatory Alternative #16, employers would not be required to offer employees testing for beryllium sensitization. Regulatory Alternative #17 would increase the frequency of periodic sensitization testing, from the proposed standard's biennial requirement to annual testing. Regulatory Alternatives #18 and #19 would similarly modify the proposed standard's requirements to offer CT scans to eligible employees. Regulatory Alternative #18 would drop the CT scan requirement from the proposed rule, whereas Regulatory Alternative #19 would increase the frequency of periodic CT scans from biennial to annual scans. Finally, under Regulatory Alternative #20, all periodic components of the medical surveillance exams would be available biennially to eligible employees. Instead of requiring employers to offer eligible employees a medical examination every year, employers would be required to offer eligible employees a medical examination every other year. The frequency of testing for beryllium sensitization and CT scans would also be biennial for eligible employees, as in the proposed standard.

More detailed discussions of Regulatory Alternatives #14, #15, #16, #17, #18, #19, #20, and #21 appear in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, Section XVIII of this preamble, Summary and Explanation, paragraph (k) provides a more detailed explanation of the proposed requirements for medical surveillance, issues with medical surveillance, and the considerations pertinent to Regulatory Alternatives #14 through #21.

Medical Removal Protection (MRP)

The proposed requirements for medical removal protection provide an option for medical removal to an employee who is working in a job with exposure at or above the action level and is diagnosed with CBD or confirmed positive for beryllium sensitization. If the employee chooses removal, the employer must either remove the employee to comparable work in a work environment where exposure is below the action level, or if comparable work is not available, must place the employee on paid leave for 6 months or until such time as comparable work becomes available. In either case, the employer must maintain for 6 months the employee's base earnings, seniority,

and other rights and benefits that existed at the time of removal. During the SBREFA process, the Panel recommended that OSHA give careful consideration to the impacts that an MRP requirement could have on small businesses (OSHA, 2008b). In response to this recommendation, OSHA analyzed Regulatory Alternative #22, which would not require employers to offer MRP. More detailed discussion of Regulatory Alternative #22 appears in Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the discussion of paragraph (l) in section XVIII of this preamble, Summary and Explanation, provides a more detailed explanation of the proposed requirements for MRP, issues with MRP, and considerations pertinent to Regulatory Alternative #22.

Timing of the Standard

The proposed standard would become effective 60 days following publication of the final standard in the

Federal Register

. The effective date is the date on which the standard imposes compliance obligations on employers. However, the standard would not become enforceable by OSHA until 90 days following the effective date for exposure monitoring, work areas and regulated areas, written exposure control plan, respiratory protection, other personal protective clothing and equipment, hygiene areas and practices (except change rooms), housekeeping, medical surveillance, and medical removal. The proposed requirement for change rooms would not be enforceable until one year after the effective date, and the requirements for engineering controls would not be enforceable until two years after the effective date. In summary, employers will have some period of time after the standard becomes effective to come into compliance before OSHA will begin enforcing it: 90 days for most provisions, one year for change rooms, and two years for engineering controls. Beginning 90 days following the effective date, during periods necessary to install or implement feasible engineering controls where exposure exceed the TWA PEL or STEL, employers must provide employees with respiratory protection as described in the proposed standard under section (g), Respiratory Protection.

OSHA invites comment and suggestions for phasing in requirements for engineering controls, medical surveillance, and other provisions of the standard. A longer phase-in time would have several advantages, such as reducing initial costs of the standard or allowing employers to coordinate their environmental and occupational safety and health control strategies to minimize potential costs. However, a longer phase-in would also postpone and reduce the benefits of the standard. Suggestions for alternatives may apply to specific industries (

e.g.,

industries where first-year or annualized cost impacts are highest), specific size-classes of employers (

e.g.,

employers with fewer than 20 employees), combinations of these factors, or all firms covered by the rule.

OSHA requests comments on these regulatory alternatives, including the Agency's choice of regulatory alternatives (and whether there are other regulatory alternatives the Agency should consider) and the Agency's analysis of them. In addition, OSHA requests comments and information on a number of specific topics and issues pertinent to the proposed standard. These are summarized below.

Regulatory Issues

In this section, we solicit public feedback on issues associated with the proposed standard and request information that would help the Agency craft the final standard. In addition to the issues specified here, OSHA also raises issues for comment on technical questions and discussions of economic issues in the PEA (OSHA, 2014). OSHA requests comment on all relevant issues, including health effects, risk assessment, significance of risk, technological and economic feasibility, and the provisions of the proposed regulatory text. In addition, OSHA requests comments on all of the issues raised by the Small Business Advocacy Review (SBAR) Panel, as summarized in the SBAR report (OSHA, 2008b)

We present these issues and requests for information in the first chapter of the preamble to assist readers as they review the preamble and consider any comments they may want to submit. The issues are presented here in summary form. However, to fully understand the questions in this section and provide substantive input in response to them, the sections of the preamble relevant to these issues should be reviewed. These include: Section V, Health Effects; Section VI, the Preliminary Risk Assessment; Section VIII, Significance of Risk; Section IX, Summary of the Preliminary Economic Analysis and Initial Regulatory Flexibility Analysis; and Section XVIII, Summary and Explanation of the Proposed Standard.

OSHA requests that comments be organized, to the extent possible, around the following issues and numbered questions. Comment on particular provisions should contain a heading setting forth the section and the paragraph in the proposed standard that the comment addresses. Comments addressing more than one section or paragraph will have correspondingly more headings.

Submitting comments in an organized manner and with clear reference to the issue raised will enable all participants to easily see what issues the commenter addressed and how they were addressed. Many commenters, especially small businesses, are likely to confine their comments to the issues that affect them, and they will benefit from being able to quickly identify comments on these issues in others' submissions. The Agency welcomes comments concerning all aspects of this proposal. However, OSHA is especially interested in responses, supported by evidence and reasons, to the following questions:

Health Effects

1. OSHA has described a variety of studies addressing the major adverse health effects that have been associated with exposure to beryllium. Using currently available epidemiologic and experimental studies, OSHA has made a preliminary determination that beryllium presents risks of lung cancer; sensitization; CBD at 0.1 µg/m

; and at higher exposures acute beryllium disease, and hepatic, renal, cardiovascular and ocular diseases. Is this determination correct? Are there additional studies or other data OSHA should consider in evaluating any of these health outcomes?

2. Has OSHA adequately identified and documented all critical health impairments associated with occupational exposure to beryllium? If not, what other adverse health effects should be added? Are there additional studies or other data OSHA should consider in evaluating any of these health outcomes?

3. Are there any additional studies, other data, or information that would affect the information discussed or significantly change the determination of material health impairment?

Please submit any relevant information, data, or additional studies (or citations to studies), and explain your reasons for recommending any studies you suggest.

Risk Assessment and Significance of Risk

4. OSHA has developed an analysis of health risks associated with occupational beryllium exposure, including an analysis of sensitization and CBD based on a selection of recent

studies in the epidemiological literature, a data set on a population of beryllium machinists provided by the National Jewish Medical Research Center (NJMRC), and an assessment of lung cancer risk using an analysis provided by NIOSH. Did OSHA rely on the best available evidence in its risk assessment? Are there additional studies or other data OSHA should consider in evaluating risk for these health outcomes? Please provide the studies, citations to studies, or data you suggest.

5. OSHA preliminarily concluded that there is significant risk of material health impairment (lung cancer or CBD) from a working lifetime of occupational exposure to beryllium at the current TWA PEL of 2 µg/m

, which would be substantially reduced by the proposed TWA PEL of 0.2 µg/m

and the alternative TWA PEL of 0.1 µg/m

. OSHA's preliminary risk assessment also concludes that there is still significant risk of CBD and lung cancer at the proposed PEL and the alternative PELs, although substantially less than at the current PEL. Are these preliminary conclusions reasonable, based on the best available evidence? If not, please provide a detailed explanation of your position, including data to support your position and a detailed analysis of OSHA's risk assessment if appropriate.

6. Please provide comment on OSHA's analysis of risk for beryllium sensitization, CBD and lung cancer. Are there important gaps or uncertainties in the analysis, such that the Agency's preliminary conclusions regarding significance of risk at the current, proposed, and alternative PELs may be in error? If so, please provide a detailed explanation and suggestions for how OSHA's analysis should be corrected or improved.

7. OSHA has made a preliminary determination that the available data are not sufficient or suitable for risk analysis of effects other than beryllium sensitization, CBD and lung cancer. Do you have, or are you aware of, studies or data that would be suitable for a risk assessment for these adverse health effects? Please provide the studies, citations to studies, or data you suggest.

(a) Scope

8. Has OSHA defined the scope of the proposed standard appropriately? Does it currently include employers who should not be covered, or exclude employers who should be covered by a comprehensive beryllium standard? Are you aware of employees in construction or maritime, or in general industry who deal with beryllium only as a trace contaminant, who may be at significant risk from occupational beryllium exposure? Please provide the basis for your response and any applicable supporting information.

(b) Definitions

9. Has OSHA defined the Beryllium lymphocyte proliferation test appropriately? If not, please provide the definition that you believe is appropriate. Please provide rationale and citations supporting your comments.

10. Has OSHA defined CBD Diagnostic Center appropriately? In particular, should a CBD diagnostic center be required to analyze biological samples on-site, or should diagnostic centers be allowed to send samples off-site for analysis? Is the list of tests and procedures a CBD Diagnostic Center is required to be able to perform appropriate? Should any of the tests or procedures be removed from the definition? Should other tests or procedures be added to the definition? Please provide rationale and information supporting your comments.

(d) Exposure Monitoring

11. Do you currently monitor for beryllium exposures in your workplace? If so, how often? Please provide the reasoning for the frequency of your monitoring. If periodic monitoring is performed at your workplace for exposures other than beryllium, with what frequency is it repeated?

12. Is it reasonable to allow discontinuation of monitoring based on one sample below the action level? Should more than one result below the action level be required to discontinue monitoring?

(e) Work Areas and Regulated Areas

13. Does your workplace currently have regulated areas? If so, how are regulated areas demarcated?

14. Please describe work settings where establishing regulated areas could be problematic or infeasible. If establishing regulated areas is problematic, what approaches might be used to warn employees in such work settings of high risk areas?

(f) Methods of Compliance

Paragraph (f)(2) of the proposed standard would require employers to implement engineering and work practice controls to reduce employees' exposures to or below the TWA PEL and STEL. Where engineering and work practice controls are insufficient to reduce exposures to or below the TWA PEL and STEL, employers would still be required to implement them to reduce exposure as much as possible, and to supplement them with a respiratory protection program. In addition, for each operation where there is airborne beryllium exposure, the employer must ensure that at least one of the engineering and work practice controls listed in paragraph (f)(2) is in place, unless all of the listed controls are infeasible, or the employer can demonstrate that exposures are below the action level based on no fewer than two samples taken seven days apart.

15. Do you usually use engineering or work practices controls (local exhaust ventilation, isolation, substitution) to reduce beryllium exposures? If so, which controls do you use?

16. Are the controls and processes listed in paragraph (f)(2)(i)(A) appropriate for controlling beryllium exposures? Are there additional controls or processes that should be added to paragraph (f)(2)(i)(A)?

(g) Respiratory Protection

17. OSHA's asbestos standard (CFR 1910.1001) requires employers to provide each employee with a tight-fitting, powered air-purifying respirator (PAPR) instead of a negative pressure respirator when the employee chooses to use a PAPR and it provides adequate protection to the employee. Should the beryllium standard similarly require employers to provide PAPRs (instead of allowing a negative pressure respirator) when requested by the employee? Are there other circumstances where a PAPR should be specified as the appropriate respiratory protection? Please provide the basis for your response and any applicable supporting information.

(h) Personal Protective Clothing and Equipment

18. Do you currently require specific PPE or respirators when employees are working with beryllium? If so, what type?

19. The proposal requires PPE wherever work clothing or skin may become visibly contaminated with beryllium; where employees' skin can reasonably be expected to be exposed to soluble beryllium compounds; or where employee exposure exceeds or can reasonably be expected to exceed the TWA PEL or STEL. The requirement to use PPE where work clothing or skin may become “visibly contaminated” with beryllium differs from prior standards which do not require contamination to be visible in order for PPE to be required. Is “visibly contaminated” an appropriate trigger for PPE? Is there reason to require PPE where employees' skin can be exposed to insoluble beryllium compounds? Please provide the basis for your response and any applicable supporting information.

(i) Hygiene Areas and Practices

20. The proposal requires employers to provide showers in their facilities if (A) Exposure exceeds or can reasonably be expected to exceed the TWA PEL or STEL; and (B) Beryllium can reasonably be expected to contaminate employees' hair or body parts other than hands, face, and neck. Is this requirement reasonable and adequately protective of beryllium-exposed workers? Should OSHA amend the provision to require showers in facilities where exposures exceed the PEL or STEL, without regard to areas of bodily contamination?

(j) Housekeeping

21. The proposed rule prohibits dry sweeping or brushing for cleaning surfaces in beryllium work areas unless HEPA-filtered vacuuming or other methods that minimize the likelihood and level of exposure have been tried and were not effective. Please comment on this provision. What methods do you use to clean work surfaces at your facility? Are HEPA-filtered vacuuming or other methods to minimize beryllium exposure used to clean surfaces at your facility? Have they been effective? Are there any circumstances under which dry sweeping or brushing are necessary? Please explain your response.

22. The proposed rule requires that materials designated for recycling that are visibly contaminated with beryllium particulate shall be cleaned to remove visible particulate, or placed in sealed, impermeable enclosures. However, small particles (<10 μg) may not be visible to the naked eye, and there are studies suggesting that small particles may penetrate the skin, beyond which beryllium sensitization can occur (Tinkle et al., 2003). OSHA requests feedback on this provision. Should OSHA require that all material to be recycled be decontaminated regardless of perceived surface cleanliness? Should OSHA require that all material disposed or discarded be in enclosures regardless of perceived surface cleanliness? Please provide explanation or data to support your comments.

(k) Medical Surveillance

The proposed requirements for medical surveillance include: (1) Medical examinations, including a test for beryllium sensitization, for employees who are exposed to beryllium above the proposed PEL for 30 days or more per year, who are exposed to beryllium in an emergency, or who show signs or symptoms of CBD; and (2) CT scans for employees who were exposed above the proposed PEL for more than 30 days in a 12-month period for 5 years or more. The proposed standard would require periodic medical exams to be provided for employees in the medical surveillance program annually, while tests for beryllium sensitization and CT scans would be provided to eligible employees biennially.

23. Is medical surveillance being provided for beryllium-exposed employees at your worksite? If so:

a. Do you provide medical surveillance to employees under another OSHA standard or as a matter of company policy? What OSHA standard(s) does the program address?

b. How many employees are included, and how do you determine which employees receive medical surveillance (

e.g.

, by exposure level, other factors)?

c. Who administers and implements the medical surveillance (

e.g.

, company doctor, nurse practitioner, physician assistant, or nurse; or outside doctor, nurse practitioner, physician assistant, or nurse)?

d. What examinations, tests, or evaluations are included in the medical surveillance program, and with what frequency are they administered? Does your program include a surveillance program specifically for beryllium-related health effects (

e.g.

, the BeLPT or other tests for beryllium sensitization)?

e. If your facility offers the BeLPT, please provide feedback and data on your experience with the BeLPT, including the analytical or interpretive procedure you use and its role in your facility's exposure control program. Has identification of sensitized workers led to interventions to reduce exposures to sensitized individuals, or in the facility generally? If a worker is found to be sensitized, do you track worker health and possible progression of disease beyond sensitization? If so, how is this done?

f. What difficulties and benefits (

e.g.

, health, reduction in absenteeism, or financial) have you experienced with your medical surveillance program? If applicable, please discuss benefits and difficulties you have experienced with the use of the BeLPT, providing detailed information or examples if possible.

g. What are the costs of your medical surveillance program? How do your costs compare with OSHA's estimated unit costs for the physical examination and employee time involved in the medical surveillance program? Are OSHA's baseline assumptions and cost estimates for medical surveillance consistent with your experiences providing medical surveillance to your employees?

24. Please review paragraph (k) of the proposed rule, Medical Surveillance, and comment on the frequency and contents of medical surveillance in the proposed rule. Is 30 days from initial assignment a reasonable time at which to provide a medical exam? Should there be a requirement for beryllium sensitization testing at time of employment? Should there be a requirement for beryllium sensitization testing at an employee's exit exam, regardless of when the employee's most recent sensitization test was administered? Are the tests required and the testing frequencies specified appropriate? Should sensitized employees have the opportunity to be examined at a CBD Diagnostic Center more than once following a confirmed positive BeLPT? Are there additional tests or alternate testing schedules you would suggest? Should the skin be examined for signs and symptoms of beryllium exposure or other medical issues, as well as for breaks and wounds? Please explain the basis for your position and provide data or studies if applicable.

25. Please provide comments on the proposed requirements regarding referral of a sensitized employee to a CBD diagnostic center, which specify referral to a diagnostic center “mutually agreed upon” by the employer and employee. Is this requirement for mutual agreement necessary and appropriate? How should a diagnostic center be chosen if the employee and employer cannot come to agreement? Should OSHA consider alternate language, such as referral for CBD

evaluation at a diagnostic center in a reasonable location?

26. In the proposed rule, OSHA specifies that all medical examinations and procedures required by the standard must be performed by or under the direction of a licensed physician. Are physicians available in your geographic area to provide medical surveillance to workers who are covered by the proposed rule? Are other licensed health care professionals available to provide medical surveillance? Do you have access to other qualified personnel such as qualified X-ray technicians, and pulmonary specialists? Should the proposal be amended to allow examination by, or under the direction of, a physician or other licensed health care professional (PLHCP)? Please explain your position. Please note what you consider your geographic area in responding to this question.

27. The proposed standard requires the employer to obtain the Licensed Physician's Written Medical Opinion from the PLHCP within 30 days of the examination. Should OSHA revise the medical surveillance provisions of the proposed standard to allow employees to choose what, if any, medical information goes to the employer from the PLHCP? For example, the employer could instead be required to obtain a certification from the PLCHP within 30 days of the examination stating (1) when the examination took place, (2) that the examination complied with the standard, and (3) that the PLHCP provided the employee a copy of the Licensed Physician's Written Medical Opinion required by the standard. The PLHCP would need the employee's written consent to send the employer the Licensed Physician's Written Medical Opinion or any other medical information about the employee. This approach might lead to corresponding changes in proposed paragraphs (f)(1) (written exposure control program), (l) (medical removal) and (n) (recordkeeping) to reflect that employers will not automatically be receiving any medical information about employees as a result of the medical surveillance required by the proposed standard, but would instead only receive medical information the employee chooses to share with the employer. Please comment on the relative merits of the proposed standard's requirement that employers obtain the PLHCP's written opinion or an alternative that would provide employees with greater discretion over the information that goes to employers, and explain the basis for your position and the potential impact on the benefits of medical surveillance.

28. Appendix A to the proposed standard reviews procedures for conducting and interpreting the results of BeLPT testing for beryllium sensitization. Is there now, or should there be, a standard method for BeLPT laboratory procedure? If yes, please describe the existing or proposed method. Is there now, or should there be, a standard algorithm for interpreting BeLPT results to determine sensitization? Please describe the existing or proposed laboratory method or interpretation algorithm. Should OSHA require that BeLPTs performed to comply with the medical surveillance provisions of this rule adhere to the Department of Energy (DOE) analytical and interpretive specifications issued in 2001? Should interpretation of laboratory results be delegated to the employee's occupational physician or PLHCP?

29. Should OSHA require the clinical laboratories performing the BeLPT to be accredited by the College of American Pathologists or another accreditation organization approved under the Clinical Laboratory Improvement Amendments (CLIA)? What other standards, if any, should be required for clinical laboratories providing the BeLPT?

30. Are there now, or are there being developed, alternative tests to the BeLPT you would suggest? Please explain the reasons for your suggestion. How should alternative tests for beryllium sensitization be evaluated and validated? How should OSHA determine whether a test for beryllium sensitization is more reliable and accurate than the BeLPT? Please see Appendix A to the proposed standard for a discussion of the accuracy of the BeLPT.

31. The proposed rule requires employers to provide OSHA with the results of BeLPTs performed to comply with the medical surveillance provisions upon request, provided that the employer obtains a release from the tested employee. Will this requirement be unduly burdensome for employers? Are there alternative organizations that would be appropriate to send test results to?

(l) Medical Removal Protection

The proposed requirements for medical removal protection provide an option for medical removal to an employee who is working in a job with exposure at or above the action level and is diagnosed with CBD or confirmed positive for beryllium sensitization. If the employee chooses removal, the employer must remove the employee to comparable work in a work environment where exposure is below the action level, or if comparable work is not available, must place the employee on paid leave for 6 months or until such time as comparable work becomes available. In either case, the employer must maintain for 6 months the employee's base earnings, seniority, and other rights and benefits that existed at the time of removal.

32. Do you provide MRP at your facility? If so, please comment on the program's benefits, difficulties, and costs, and the extent to which eligible employees make use of MRP.

33. OSHA has included requirements for medical removal protection (MRP) in the proposed rule, which includes provisions for medical removal for employees with beryllium sensitization or CBD, and an extension of removed employees' rights and benefits for six months. Are beryllium sensitization and CBD appropriate triggers for medical removal? Are there other medical conditions or findings that should trigger medical removal? For what amount of time should a removed employee's benefits be extended?

(p) Appendices

34. Some OSHA health standards include appendices that address topics such as the hazards associated with the regulated substance, health screening considerations, occupational disease questionnaires, and PLHCP obligations. In this proposed rule, OSHA has included a non-mandatory appendix to describe and discuss the BeLPT (Appendix A), and a non-mandatory appendix presenting a non-exhaustive list of engineering controls employers may use to comply with paragraph (f) (Appendix B). What would be the advantages and disadvantages of including each appendix in the final rule? What would be the advantages and disadvantages of providing this information in guidance materials?

35. What additional information, if any, should be included in the appendices? What additional information, if any, should be provided in guidance materials?

General

36. The current beryllium proposal includes triggers that require employers to initiate certain provisions, programs, and activities to protect workers from beryllium exposure. All employers covered under an OSHA health standard are required to initiate certain activities such as initial monitoring to evaluate the potential hazard to employees. OSHA health standards typically include ancillary provisions with various triggers indicating when an

employer covered under the standard would need to comply with a provision. The most common triggers are ones based an exposure level such as the PEL or action level. These exposure level triggers are sometimes combined with a minimum duration of exposure (

e.g.,

≥ 30 days per year). Other triggers may include reasonably anticipated exposure, medical surveillance findings, certain work activities, or simply the presence of the regulated substance in the workplace.

For the current Proposal, exposures to beryllium above the TWA PEL or STEL trigger the provisions for regulated areas, additional or enhanced engineering or work practice controls to reduce airborne exposures to or below the TWA PEL and STEL, personal protective clothing and equipment, medical surveillance, showers, and respiratory protection if feasible engineering and work practice controls cannot reduce airborne exposures to or below the TWA PEL and STEL. Exposures at or above the action level in turn trigger the provisions for periodic exposure monitoring, and medical removal eligibility (along with a diagnosis of CBD or confirmed positive for beryllium sensitization). Finally, an employer covered under the scope of the proposed standard must establish a beryllium work area where employees are, or can reasonably be expected to be, exposed to airborne beryllium regardless of the level of exposure. In beryllium work areas, employers must implement a written exposure control plan, provide washing facilities and change rooms (change rooms are only necessary if employees are required to remove their personal clothing), and follow housekeeping provisions. The employers must also implement at least one of the engineering and work practice controls listed in paragraph (f)(2) of the proposed standard. An employer is exempt from this requirement if he or she can demonstrate that such controls are not feasible or that exposures are below the action level.

Certain provisions are triggered by one condition and other provisions are triggered only if multiple conditions are present. For example, medical removal is only triggered if an employee has CBD or is confirmed positive AND the employee is exposed at or above the action level.

OSHA is requesting comment on the triggers in the proposed beryllium standard. Are the triggers OSHA has proposed appropriate? OSHA is also requesting comment on these triggers relative to the regulatory alternatives affecting the scope and PELs as described in this preamble in section I, Issues and Alternatives. For example, are the triggers in the proposed standard appropriate for Alternative #1a, which would expand the scope of the proposed standard to include all operations in general industry where beryllium exists only as a trace contaminant (less than 0.1% beryllium by weight)? Are the triggers appropriate for the alternatives that change the TWA PEL, STEL, and action level? Please specify the trigger and the alternative, if applicable, and why you agree or disagree with the trigger.

Relevant Federal Rules Which May Duplicate, Overlap, or Conflict With the Proposed Rule

37. In Section IX—Preliminary Economic Analysis under the

Initial Regulatory Flexibility Analysis,

OSHA identifies, to the extent practicable, all relevant Federal rules which may duplicate, overlap, or conflict with the proposed rule. One potential area of overlap is with the U.S. Department of Energy (DOE) beryllium program. In 1999, DOE established a chronic beryllium disease prevention program (CBDPP) to reduce the number of workers (DOE employees and DOE contractors) exposed to beryllium at DOE facilities (10 CFR part 850, published at 64 FR 68854-68914 (Dec. 8, 1999)). In establishing this program, DOE has exercised its statutory authority to prescribe and enforce occupational safety and health standards. Therefore pursuant to section 4(b)(1) of the OSH Act, 29 U.S.C. 653(b)(1), the DOE facilities are exempt from OSHA jurisdiction.

Nevertheless, under 10 CFR 850.22, DOE has included in its CBDPP regulation a requirement for compliance with the current OSHA permissible exposure limit (PEL), and any lower PEL that OSHA establishes in the future. Thus, although DOE has preempted OSHA's standard from applying at DOE facilities and OSHA cannot exercise any authority at those facilities, DOE relies on OSHA's PEL in implementing its own program. However, DOE's decision to tie its own standard to OSHA's PEL has little consequence to this rulemaking because the requirements in DOE's beryllium program (controls, medical surveillance, etc.) are triggered by DOE's action level of 0.2 µg/m

, which is much lower than DOE's existing PEL and the same as OSHA's proposed PEL. DOE's action level is not tied to OSHA's standard, so 10 CFR 850.22 would not require the CBDPP's action level or any non-PEL requirements to be automatically adjusted as a result of OSHA's rulemaking. For this reason, DOE has indicated to OSHA that OSHA's proposed rule would not have any impact on DOE's CBDPP, particularly since 10 CFR 850.25(b),

Exposure reduction and minimization,

requires DOE contractors to reduce exposures to below the DOE's action level of 0.2 µg/m

, if practicable.

DOE has expressed to OSHA that DOE facilities are already in compliance with 10 CFR 850 and its action level of 0.2 µg/m

so the only potential impact on DOE's CBDPP that could flow from OSHA's rulemaking would be if OSHA ultimately adopted a PEL of 0.1 µg/m

, as discussed in alternative #4, instead of the proposed PEL of 0.2 µg/m

, and DOE did not make any additional adjustments to its standards. Even in that hypothetical scenario, the impact would still be limited because of the odd result that DOE's PEL would drop below its own action level, while the action level would continue to serve as the trigger for most of DOE's program requirements.

This would mean the prevailing beryllium exposures at DOE facilities are at or below 0.2 µg/m

DOE also has noted some potential overlap with a separate DOE provision in 10 CFR part 851, which requires its contractors to comply with DOE's CBDPP (10 CFR 851.23(a)(1)) and also with all OSHA standards under 29 CFR part 1910 except “Ionizing Radiation” (§ 1910.1096) (10 CFR 851.23(a)(3)). These requirements, which DOE established in 2006 (71 FR 6858 (February 9, 2006)), make sense in light of OSHA's current regulation because OSHA's only beryllium protection is a PEL, so compliance with 10 CFR 851.23(a)(1) and (3) merely make OSHA's current PEL the relevant level for purposes of the CBDPP. However, its function would be less clear if OSHA adopts a beryllium standard as proposed. OSHA's proposed beryllium standard would establish additional substantive protections beyond the PEL. Consequently, notwithstanding the CBDPP's preemptive effect on the OSHA beryllium standard as a result of 29 U.S.C. 653(b)(1), 10 CFR 851.23(a)(3) could be read to require DOE contractors to comply with all provisions in OSHA's proposal (if finalized), including the ancillary provisions, creating a dual regulatory scheme for beryllium protection at DOE facilities.

DOE officials have indicated that this is not their intent. Instead, their intent is that DOE contractors comply solely with the CBDPP provisions in 10 CFR part 850 for protection from beryllium.

Based on its discussions with DOE officials, OSHA anticipates that DOE will clarify that its contractors do not need to comply with any ancillary provisions in a beryllium standard that OSHA may promulgate.

OSHA can envision several potential scenarios developing from its rulemaking, ranging from OSHA retaining the proposed PEL of 0.2 µg/m

and action level of 0.1 µg/m

in the final rule to adopting the PEL of 0.1 µg/m

, as discussed in alternative #4. Because OSHA's beryllium standard does not apply directly to DOE facilities, and the only impact of its rules on those facilities is the result of DOE's regulatory choices, there is also a range of actions that DOE could take to minimize any potential impact of any change to OSHA's rules, including (1) taking no action at all, (2) simply clarifying the CBDPP, as described above, to mean that OSHA's beryllium standard (other than its PEL) does not apply to contractors, or (3) revising both parts 850 and 851 to completely disassociate DOE's regulation of beryllium at DOE facilities from OSHA's regulation of beryllium.

OSHA is aware that, in the preamble to its 1999 CBDPP rule, DOE analyzed the costs for implementing the CBDPP for action levels of 0.1 µg/m

, 0.2 µg/m

, and 0.5 µg/m

(64 FR 68875, December 8, 1999). DOE estimated costs for periodic exposure monitoring, notifying workers of the results of such monitoring, exposure reduction and minimization, regulated areas, change rooms and showers, respiratory protection, protective clothing, and disposal of protective clothing. All of these provisions are triggered by DOE's action level (64 FR 68874, December 8, 1999). Although DOE's rule is not identical to OSHA's proposed standard, OSHA believes that DOE's costs are sufficiently representative to form the basis of a preliminary estimate of the costs that could flow from OSHA's standard, if finalized.

Based on the range of potential scenarios and the prior DOE cost estimates, OSHA estimates that the annual cost impact on DOE facilities could range from $0 to $4,065,768 (2010 dollars). The upper end of the cost range would reflect the unlikely scenario in which OSHA promulgates a final PEL of 0.1 µg/m

, 10 CFR 851.23(a)(3) is found to compel DOE contractors to comply with OSHA's comprehensive beryllium standard in addition to DOE's CBDPP, and DOE takes no action to clarify that OSHA's beryllium standard does not apply to DOE contractors. The lower end of the cost range assumes OSHA promulgates its rule as proposed with a PEL of 0.2 µg/m

and action level of 0.1 µg/m

, and DOE clarifies that it intends its contractors to follow DOE's CBDPP and not OSHA's beryllium standard, so that the ancillary provisions of OSHA's beryllium standard do not apply to DOE facilities. Additionally, OSHA assumes that DOE contractors are in compliance with DOE's current rule and therefore took the difference in cost between implementation of an action level of 0.2 µg/m

and an action level of 0.1 µg/m

for the above estimates. Finally, OSHA used the GDP price deflator to present the cost estimate in 2010 dollars.

OSHA requests comment on the potential overlap of DOE's rule with OSHA's proposed rule.

II. Pertinent Legal Authority

The purpose of the Occupational Safety and Health Act, 29 U.S.C. 651

et seq.

(“the Act”), is to “. . . assure so far as possible every working man and woman in the nation safe and healthful working conditions and to preserve our human resources.” 29 U.S.C. 651(b).

To achieve this goal Congress authorized the Secretary of Labor (the Secretary) to promulgate and enforce occupational safety and health standards. 29 U.S.C. 654(b) (requiring employers to comply with OSHA standards), 655(a) (authorizing summary adoption of existing consensus and federal standards within two years of the Act's enactment), and 655(b) (authorizing promulgation, modification or revocation of standards pursuant to notice and comment).

The Act provides that in promulgating health standards dealing with toxic materials or harmful physical agents, such as this proposed standard regulating occupational exposure to beryllium, the Secretary, 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. See 29 U.S.C. 655(b)(5).

The Supreme Court has held that before the Secretary can promulgate any permanent health or safety standard, he must make a threshold finding that significant risk is present and that such risk can be eliminated or lessened by a change in practices.

Industrial Union Dept., AFL-CIO

American Petroleum Institute,

448 U.S. 607, 641-42 (1980) (plurality opinion) (“

The Benzene case”

). Thus, section 6(b)(5) of the Act requires health standards to reduce significant risk to the extent feasible.

Id.

The Court further observed that what constitutes “significant risk” is “not a mathematical straitjacket” and must be “based largely on policy considerations.”

The Benzene case,

448 U.S. at 655. The Court gave the example that if,

. . . the odds are one in a billion that a person will die from cancer . . . the risk clearly could not be considered significant. On the other hand, if the odds are one in one thousand that regular inhalation of gasoline vapors that are 2% benzene will be fatal, a reasonable person might well consider the risk significant. [

Id.

]

OSHA standards must be both technologically and economically feasible.

United Steelworkers

Marshall,

647 F.2d 1189, 1264 (D.C. Cir. 1980) (“The Lead I case”). The Supreme Court has defined feasibility as “capable of being done.”

Am. Textile Mfrs. Inst.

Donovan,

452 U.S. 490, 509-510 (1981) (“

The Cotton Dust case”

). The courts have further clarified that a standard is technologically feasible if OSHA proves a reasonable possibility,

. . . within the limits of the best available evidence . . . that the typical firm will be able to develop and install engineering and work practice controls that can meet the PEL in most of its operations. [

See The Lead I case,

647 F.2d at 1272]

With respect to economic feasibility, the courts have held that a standard is feasible if it does not threaten massive dislocation to or imperil the existence of the industry.

Id.

at 1265. A court must examine the cost of compliance with an OSHA standard,

. . . in relation to the financial health and profitability of the industry and the likely effect of such costs on unit consumer prices . . . [T]he practical question is whether the standard threatens the competitive stability of an industry, . . . or whether any intra-industry or inter-industry discrimination in the standard might wreck such stability or lead to undue concentration. [

Id.

(citing

Indus. Union Dep't, AFL-CIO

Hodgson,

499 F.2d 467 (D.C. Cir. 1974))]

The courts have further observed that granting companies reasonable time to comply with new PELs may enhance economic feasibility.

The Lead I case

at 1265. While a standard must be economically feasible, the Supreme Court has held that a cost-benefit analysis of health standards is not required by the Act because a feasibility analysis is required.

The Cotton Dust case,

453 U.S. at 509.

Finally, sections 6(b)(7) and 8(c) of the Act authorize OSHA to include among a standard's requirements labeling, monitoring, medical testing, and other information-gathering and -transmittal provisions. 29 U.S.C. 655(b)(7), 657(c).

III. Events Leading to the Proposed Standards

The first occupational exposure limit for beryllium was set in 1949 by the Atomic Energy Commission (AEC), which required that beryllium exposure in the workplaces under its jurisdiction be limited to 2 µg/m

as an 8-hour time-weighted average (TWA), and 25 µg/m

as a peak exposure never to be exceeded (Department of Energy, 1999). These exposure limits were adopted by all AEC installations handling beryllium, and were binding on all AEC contractors involved in the handling of beryllium.

In 1956, the American Industrial Hygiene Association (AIHA) published a Hygienic Guide which supported the AEC exposure limits. In 1959, the American Conference of Governmental Industrial Hygienists (ACGIH®) also adopted a Threshold Limit Value (TLV®) of 2 µg/m

as an 8-hour TWA (Borak, 2006).

In 1971, OSHA adopted, under Section 6(a) of the Occupational Safety and Health Act of 1970, and made applicable to general industry, a national consensus standard (ANSI Z37.29-1970) for beryllium and beryllium compounds. The standard set a permissible exposure limit (PEL) for beryllium and beryllium compounds at 2 µg/m

as an 8-hour TWA; 5 µg/m

as an acceptable ceiling concentration; and 25 µg/m

as an acceptable maximum peak above the acceptable ceiling concentration for a maximum duration of 30 minutes in an 8-hour shift (OSHA, 1971).

Section 6(a) stipulated that in the first two years after the effective date of the Act, OSHA was to promulgate “start-up” standards, on an expedited basis and without public hearing or comment, based on national consensus or established Federal standards that improved employee safety or health. Pursuant to that authority, in 1971, OSHA promulgated approximately 425 PELs for air contaminants, including beryllium, derived principally from Federal standards applicable to government contractors under the Walsh-Healey Public Contracts Act, 41 U.S.C. 35, and the Contract Work Hours and Safety Standards Act (commonly known as the Construction Safety Act), 40 U.S.C. 333. The Walsh-Healey Act and Construction Safety Act standards, in turn, had been adopted primarily from ACGIH®'s TLV®s.

The National Institute for Occupational Safety and Health (NIOSH) issued a document entitled

Criteria for a Recommended Standard: Occupational Exposure to Beryllium

(Criteria Document) in June 1972. OSHA reviewed the findings and recommendations contained in the Criteria Document along with the AEC control requirements for beryllium exposure. OSHA also considered existing data from animal and epidemiological studies, and studies of industrial processes of beryllium extraction, refinement, fabrication, and machining. In 1975, OSHA asked NIOSH to update the evaluation of the existing data pertaining to the carcinogenic potential of beryllium. In response to OSHA's request, the Director of NIOSH stated that, based on animal data and through all possible routes of exposure including inhalation, “beryllium in all likelihood represents a carcinogenic risk to man.”

In October 1975, OSHA proposed a new beryllium standard for all industries based on information that beryllium caused cancer in animal experiments (40 FR 48814 (October 17, 1975)). Adoption of this proposal would have lowered the 8-hour TWA exposure limit from 2 µg/m

to 1 µg/m

. In addition, the proposal included ancillary provisions for such topics as exposure monitoring, hygiene facilities, medical surveillance, and training related to the health hazards from beryllium exposure. The rulemaking was never completed.

In 1977, NIOSH recommended an exposure limit of 0.5 µg/m

and identified beryllium as a potential occupational carcinogen. In December 1998, ACGIH published a Notice of Intended Change for its beryllium exposure limit. The notice proposed a lower TLV of 0.2 µg/m

over an 8-hour TWA based on evidence of CBD and sensitization in exposed workers.

In 1999, the Department of Energy (DOE) issued a Chronic Beryllium Disease Prevention Program (CBDPP) Final Rule for employees exposed to beryllium in its facilities (DOE, 1999). The DOE rule set an action level of 0.2 μg/m

, and adopted OSHA's PEL of 2 μg/m

or any more stringent PEL OSHA might adopt in the future. The DOE action level triggers workplace precautions and control measures such as periodic monitoring, exposure reduction or minimization, regulated areas, hygiene facilities and practices, respiratory protection, protective clothing and equipment, and warning signs (DOE, 1999).

Also in 1999, OSHA was petitioned by the Paper, Allied-Industrial, Chemical and Energy Workers International Union (PACE) (OSHA, 2002) and by Dr. Lee Newman and Ms. Margaret Mroz, from the National Jewish Medical Research Center (NJMRC) (OSHA, 2002), to promulgate an Emergency Temporary Standard (ETS) for beryllium in the workplace. In 2001, OSHA was petitioned for an ETS by Public Citizen Health Research Group and again by PACE (OSHA, 2002). In order to promulgate an ETS, the Secretary of Labor must prove (1) that employees are exposed to grave danger from exposure to a hazard, and (2) that such an emergency standard is necessary to protect employees from such danger (29 U.S.C. 655(c)). The burden of proof is on the Department and because of the difficulty of meeting this burden, the Department usually proceeds when appropriate with 6(b) rulemaking rather than a 6(c) ETS. Thus, instead of granting the ETS requests, OSHA instructed staff to further collect and analyze research regarding the harmful effects of beryllium.

On November 26, 2002, OSHA published a Request for Information (RFI) for “Occupational Exposure to Beryllium” (OSHA, 2002). The RFI contained questions on employee exposure, health effects, risk assessment, exposure assessment and monitoring methods, control measures and technological feasibility, training, medical surveillance, and impact on small business entities. In the RFI, OSHA expressed concerns about health effects such as CBD, lung cancer, and beryllium sensitization. OSHA pointed to studies indicating that even short-term exposures below OSHA's PEL of 2 µg/m

could lead to CBD. The RFI also cited studies describing the relationship between beryllium sensitization and CBD (67 FR at 70708). In addition, OSHA stated that beryllium had been identified as a carcinogen by organizations such as NIOSH, the International Agency for Research on Cancer (IARC), and the Environmental Protection Agency (EPA); and cancer had been evidenced in animal studies (67 FR at 70709).

On November 15, 2007, OSHA convened a Small Business Advocacy Review Panel for a draft proposed standard for occupational exposure to beryllium. OSHA convened this panel under Section 609(b) of the Regulatory Flexibility Act (RFA), as amended by the Small Business Regulatory Enforcement Fairness Act of 1996 (SBREFA) (5 U.S.C. 601

et seq.

The Panel included representatives from OSHA, the Solicitor's Office of the Department of Labor, the Office of Advocacy within the Small Business Administration, and the Office of Information and Regulatory Affairs of the Office of Management and Budget. Small Entity Representatives (SERs) made oral and written comments on the

draft rule and submitted them to the panel.

The SBREFA Panel issued a report which included the SERs' comments on January 15, 2008. SERs expressed concerns about the impact of the ancillary requirements such as exposure monitoring and medical surveillance. Their comments addressed potential costs associated with compliance with the draft standard, and possible impacts of the standard on market conditions, among other issues. In addition, many SERs sought clarification of some of the ancillary requirements such as the meaning of “routine” contact or “contaminated surfaces.”

The SBREFA Panel issued a number of recommendations, which OSHA carefully considered. In section XVIII of this preamble, Summary and Explanation, OSHA has responded to the Panel's recommendations and clarified the requirements about which SERs expressed confusion. OSHA also examined the regulatory alternatives recommended by the SBREFA Panel. The regulatory alternatives examined by OSHA are listed in section I of this preamble, Issues and Alternatives. The alternatives are discussed in greater detail in section XVIII of this preamble, Summary and Explanation, and in the PEA (OSHA, 2014). In addition, the Agency intends to develop interpretive guidance documents following the publication of a final rule.

In 2010, OSHA hired a contractor to oversee an independent scientific peer review of a draft preliminary beryllium health effects evaluation (OSHA, 2010a) and a draft preliminary beryllium risk assessment (OSHA, 2010b). The contractor identified experts familiar with beryllium health effects research and ensured that these experts had no conflict of interest or apparent bias in performing the review. The contractor selected five experts with expertise in such areas as pulmonary and occupational medicine, CBD, beryllium sensitization, the BeLPT, beryllium toxicity and carcinogenicity, and medical surveillance. Other areas of expertise included animal modeling, occupational epidemiology, biostatistics, risk and exposure assessment, exposure-response modeling, beryllium exposure assessment, industrial hygiene, and occupational/environmental health engineering.

Regarding the health effects evaluation, the peer reviewers concluded that the health effect studies were described accurately and in sufficient detail, and OSHA's conclusions based on the studies were reasonable. The reviewers agreed that the OSHA document covered the significant health endpoints related to occupational beryllium exposure. Peer reviewers considered the preliminary conclusions regarding beryllium sensitization and CBD to be reasonable and well presented in the draft health evaluation section. All reviewers agreed that the scientific evidence supports sensitization as a necessary condition in the development of CBD. In response to reviewers' comments, OSHA made revisions to more clearly describe certain sections of the health effects evaluation. In addition, OSHA expanded its discussion regarding the BeLPT.

Regarding the preliminary risk assessment, the peer reviewers were highly supportive of the Agency's approach and major conclusions. The peer reviewers stated that the key studies were appropriate and their selection clearly explained in the document. They regarded the preliminary analysis of these studies to be reasonable and scientifically sound. The reviewers supported OSHA's conclusion that substantial risk of sensitization and CBD were observed in facilities where the highest exposure generating processes had median full-shift exposures around 0.2 µg/m

or higher, and that the greatest reduction in risk was achieved when exposures for all processes were lowered to 0.1 µg/m

or below.

In February 2012 the Agency received for consideration a draft recommended standard for beryllium (Materion and USW, 2012). This draft proposal was the product of a joint effort between two stakeholders: Materion Corporation, a leading producer of beryllium and beryllium products in the United States, and the United Steelworkers, an international labor union representing workers who manufacture beryllium alloys and beryllium-containing products in a number of industries. The United Steelworkers and Materion sought to craft an OSHA-like model beryllium standard that would have support from both labor and industry. OSHA has considered this proposal along with other information submitted during the development of the Notice of Proposed Rulemaking for beryllium.

IV. Chemical Properties and Industrial Uses

Chemical and Physical Properties

Beryllium (Be; CAS Number 7440-41-7) is a silver-grey to greyish-white, strong, lightweight, and brittle metal. It is a Group IIA element with an atomic weight of 9.01, atomic number of 4, melting point of 1,287 °C, boiling point of 2,970°C, and a density of 1.85 at 20 °C (NTP 2014). It occurs naturally in rocks, soil, coal, and volcanic dust (ATSDR, 2002). Beryllium is insoluble in water and soluble in acids and alkalis. It has two common oxidation states, Be(0) and Be(+2). There are several beryllium compounds with unique CAS numbers and chemical and physical properties. Table IV-1 describes the most common beryllium compounds.

Table IV—1, Properties of Beryllium and Beryllium Compounds

Chemical name

CAS No.

Synonyms and trade names

Molecular weight

Melting point

(°C)

Description

Density

(g/cm3)

Solubility

Beryllium metal

7440-41-7

Beryllium; beryllium-9, beryllium element; beryllium metallic

9.0122

1287

Grey, close-packed, hexagonal, brittle metal

1.85 (20 °C)

Soluble in most dilute acids and alkali; decomposes in hot water; insoluble in mercury and cold water.

Beryllium chloride

7787-47-5

Beryllium dichloride

79.92

399.2

Colorless to slightly yellow; orthorhombic, deliquescent crystal

1.899 (25 °C)

Soluble in water, ethanol, diethyl ether and pyridine; slightly soluble in benzene, carbon disulfide and chloroform; insoluble in acetone, ammonia, and toluene.

Beryllium fluoride

7787-49-7 (12323-05-6)

Beryllium difluoride

47.01

555

Colorless or white, amorphous, hygroscopic solid

1.986

Soluble in water, sulfuric acid, mixture of ethanol and diethyl ether; slightly soluble in ethanol; insoluble in hydrofluoric acid.

Beryllium hydroxide

13327-32-7 (1304-49-0)

Beryllium dihydroxide

43.3

138 (decomposes to beryllium oxide)

White, amorphous, amphoteric powder

1.92

Soluble in hot concentrated acids and alkali; slightly soluble in dilute alkali; insoluble in water.

Beryllium sulfate

13510-49-1

Sulfuric acid, beryllium salt (1:1)

105.07

550-600 °C (decomposes to beryllium oxide)

Colorless crystal

2.443

Forms soluble tetrahydrate in hot water; insoluble in cold water.

Beryllium sulfate tetrhydrate

7787-56-6

Sulfuric acid; beryllium salt (1:1), tetrahydrate

177.14

100 °C

Colorless, tetragonal crystal

1.713

Soluble in water; slightly soluble in concentrated sulfuric acid; insoluble in ethanol.

Beryllium Oxide

1304-56-9

Beryllia; beryllium monoxide thermalox TM

25.01

2508-2547 °C

Colorless to white, hexagonal crystal or amorphous, amphoteric powder

3.01 (20 °C)

Soluble in concentrated acids and alkali; insoluble in water.

Beryllium carbonate

1319-43-3

Carbonic acid, beryllium salt, mixture with beryllium hydroxide

112.05

No data

White powder

No data

Soluble in acids and alkali; insoluble in cold water; decomposes in hot water.

Beryllium nitrate trihydrate

7787-55-5

Nitric acid, beryllium salt, trihydrate

187.97

White to faintly yellowish, deliquescent mass

1.56

Very soluble in water and ethanol.

Beryllium phosphate

13598-15-7

Phosphoric acid, beryllium salt (1:1)

104.99

No data

Not reported

Slightly soluble in water.

ATSDR, 2002.

The physical and chemical properties of beryllium were realized early in the 20th century, and it has since gained commercial importance in a wide range of industries. Beryllium is lightweight, hard, spark resistant, non-magnetic, and has a high melting point. It lends strength, electrical and thermal conductivity, and fatigue resistance to alloys (NTP, 2014). Beryllium also has a high affinity for oxygen in air and water, which can cause a thin surface film of beryllium oxide to form on the bare metal, making it extremely resistant to corrosion. These properties make beryllium alloys highly suitable for defense, nuclear, and aerospace applications (IARC, 1993).

There are approximately 45 mineralized forms of beryllium. In the United States, the predominant mineral form mined commercially and refined into pure beryllium and beryllium alloys is bertrandite. Bertrandite, while containing less than 1% beryllium compared to 4% in beryl, is easily and efficiently processed into beryllium hydroxide (IARC, 1993). Imported beryl is also converted into beryllium hydroxide as the United States has very little beryl that can be economically mined (USGS, 2013a).

Industrial Uses

Materion Corporation, formerly called Brush Wellman, is the only producer of primary beryllium in the United States. Beryllium is used in a variety of industries, including aerospace, defense, telecommunications, automotive, electronic, and medical specialty industries. Pure beryllium metal is used in a range of products such as X-ray transmission windows, nuclear reactor neutron reflectors, nuclear weapons, precision instruments, rocket propellants, mirrors, and computers (NTP, 2014). Beryllium oxide is used in components such as ceramics, electrical insulators, microwave oven components, military vehicle armor, laser structural components, and automotive ignition systems (ATSDR, 2002). Beryllium oxide ceramics are used to produce sensitive electronic items such as lasers and satellite heat sinks.

Beryllium alloys, typically beryllium/copper or beryllium/aluminum, are manufactured as high beryllium content or low beryllium content alloys. High content alloys contain greater than 30% beryllium. Low content alloys are typically less than 3% beryllium. Beryllium alloys are used in automotive electronics (

e.g.,

electrical connectors and relays and audio components), computer components, home appliance parts, dental appliances (

e.g.,

crowns), bicycle frames, golf clubs, and other articles (NTP, 2014; Ballance et al., 1978; Cunningham et al., 1998; Mroz, et al., 2001). Electrical components and conductors are stamped and formed from beryllium alloys. Beryllium-copper

alloys are used to make switches in automobiles (Ballance et al., 1978, 2002; Cunningham et al., 1998) and connectors, relays, and switches in computers, radar, satellite, and telecommunications equipment (Mroz et al., 2001). Beryllium-aluminum alloys are used in the construction of aircraft, high resolution medical and industrial X-ray equipment, and mirrors to measure weather patterns (Mroz et al., 2001). High content and low content beryllium alloys are precision machined for military and aerospace applications. Some welding consumables are also manufactured using beryllium.

Beryllium is also found as a trace metal in materials such as aluminum ore, abrasive blasting grit, and coal fly ash. Abrasive blasting grits such as coal slag and copper slag contain varying concentrations of beryllium, usually less than 0.1% by weight. The burning of bituminous and sub-bituminous coal for power generation causes the naturally occurring beryllium in coal to accumulate in the coal fly ash byproduct. Scrap and waste metal for smelting and refining may also contain beryllium. A detailed discussion of the industries and job tasks using beryllium is included in the Preliminary Economic Analysis (OSHA, 2014).

Occupational exposure to beryllium can occur from inhalation of dusts, fume, and mist. Beryllium dusts are created during operations where beryllium is cut, machined, crushed, ground, or otherwise mechanically sheared. Mists can also form during operations that use machining fluids. Beryllium fume can form while welding with or on beryllium components, and from hot processes such as those found in metal foundries.

Occupational exposure to beryllium can also occur from skin, eye, and mucous membrane contact with beryllium particulate or solutions.

V. Health Effects

Beryllium-associated health effects, including acute beryllium disease (ABD), beryllium sensitization (also referred to in this preamble as “sensitization”), chronic beryllium disease (CBD), and lung cancer, can lead to a number of highly debilitating and life-altering conditions including pneumonitis, loss of lung capacity (reduction in pulmonary function leading to pulmonary dysfunction), loss of physical capacity associated with reduced lung capacity, systemic effects related to pulmonary dysfunction, and decreased life expectancy (NIOSH, 1972).

This Health Effects section presents information on beryllium and its compounds, the fate of beryllium in the body, research that relates to its toxic mechanisms of action, and the scientific literature on the adverse health effects associated with beryllium exposure, including ABD, sensitization, CBD, and lung cancer. OSHA considers CBD to be a progressive illness with a continuous spectrum of symptoms ranging from no symptomatology at its earliest stage following sensitization to mild symptoms such as a slight almost imperceptible shortness of breath, to loss of pulmonary function, debilitating lung disease, and, in many cases, death. This section also discusses the nature of these illnesses, the scientific evidence that they are causally associated with occupational exposure to beryllium, and the probable mechanisms of action with a more thorough review of the supporting studies.

A. Beryllium and Beryllium Compounds

1. Particle Physical/Chemical Properties

Beryllium (Be; CAS No. 7440-41-7) is a steel-grey, brittle metal with an atomic number of 4 and an atomic weight of 9.01 (Group IIA of the periodic table). Because of its high reactivity, beryllium is not found as a free metal in nature; however, there are approximately 45 mineralized forms of beryllium. Beryllium compounds and alloys include commercially valuable metals and gemstones.

Beryllium has two oxidative states: Be(0) and Be(2

) Agency for Toxic Substance and Disease Registry (ATSDR) 2002). It is likely that the Be(2

) state is the most biologically reactive and able to form a bond with peptides leading to it becoming antigenic (Snyder

et al.,

2003). This will be discussed in more detail in the Beryllium Sensitization section below. Beryllium has a high charge-to-radius ratio and in addition to forming various types of ionic bonds, beryllium has a strong tendency for covalent bond formation (

e.g.,

it can form organometallic compounds such as Be(CH

)

and many other complexes) (ATSDR, 2002; Greene

et al.,

1998). However, it appears that few, if any, toxicity studies exist for the organometallic compounds. Additional physical/chemical properties for beryllium compounds that may be important in their biological response are summarized in Table 1 below. This information was obtained from their International Chemical Safety Cards (ICSC) (beryllium metal (ICSC 0226), beryllium oxide (ICSC 1325), beryllium sulfate (ICSC 1351), beryllium nitrate (ICSC 1352), beryllium carbonate (ICSC 1353), beryllium chloride (ICSC 1354), beryllium fluoride (ICSC 1355)) and from the hazardous substance data bank (HSDB) for beryllium hydroxide (CASRN: 13327-32-7), and beryllium phosphate (CASRN: 13598-15-7). Additional information on chemical and physical properties as well as industrial uses for beryllium can be found in this preamble at Section IV, Chemical Properties and Industrial Uses.

Table 1—Physical/Chemical Properties of Beryllium and Compounds

Compound name

Physical

appearance

Chemical formula

Molecular mass

Acute physical hazards

Solubility in water at 20 °C

Beryllium Metal

Grey to White Powder

9.0

Combustible; Finely dispersed particles—Explosive

None.

Beryllium Oxide

White Crystals or Powder

BeO

25.0

Not combustible or explosive

Very sparingly soluble.

Beryllium Carbonate

White Powder

(OH)/Be

181.07

Not combustible or explosive

None.

Beryllium Sulfate

Colorless Crystals

BeSO

105.1

Not combustible or explosive

Slightly soluble.

Beryllium Nitrate

White to Yellow Solid

BeN

/Be(NO

)

133.0

Enhances combustion of other substances

Very soluble (1.66 × 10

mg/L).

Beryllium Hydroxide

White amorphous powder or crystalline solid

Be(OH)

43.0

Not reported

Slightly soluble 0.8 × 10

−4

mol/L

(3.44 mg/L).

Beryllium Chloride

Colorless to Yellow Crystals

BeCl

79.9

Not combustible or explosive

Soluble.

Beryllium Fluoride

Colorless Lumps

BeF

47.0

Not combustible or explosive

Very soluble.

Beryllium Phosphate

White solid

(PO

)

271.0

Not reported

Soluble.

Source:

International Chemical Safety Cards (except beryllium phosphate and hydroxide—HSDB).

Beryllium shows a high affinity for oxygen in air and water, resulting in a thin surface film of beryllium oxide on the bare metal. If the surface film is disturbed, it may become airborne or dermal exposure may occur. The solubility, particle surface area, and particle size of some beryllium compounds are examined in more detail below. These properties have been evaluated in many toxicological studies. In particular, the properties related to the calcination (firing temperatures) and differences in crystal size and solubility are important aspects in their toxicological profile.

2. Factors Affecting Potency and Effect of Beryllium Exposure

The effect and potency of beryllium and its compounds, as for any toxicant, immunogen, or immunotoxicant, may be dependent upon the physical state in which they are presented to a host. For occupational airborne materials and surface contaminants, it is especially critical to understand those physical parameters in order to determine the extent of exposure to the respiratory tract and skin since these are generally the initial target organs for either route of exposure.

For example, large particles may have less of an effect in the lung than smaller particles due to reduced potential to stay airborne to be inhaled or be deposited along the respiratory tract. In addition, once inhalation occurs particle size is critical in determining where the particle will deposit along the respiratory tract. Solubility also has an important part in determining the toxicity and bioavailability of airborne materials as well. Respiratory tract retention and skin penetration are directly influenced by the solubility and reactivity of airborne material.

These factors may be responsible, at least in part, for the process by which beryllium sensitization progresses to CBD in exposed workers. Other factors influencing beryllium-induced toxicity include the surface area of beryllium particles and their persistence in the lung. With respect to dermal exposure, the physical characteristics of the particle are important as well since they can influence skin absorption and bioavailability. This section addresses certain physical characteristics (

i.e.

, solubility, particle size, particle surface area) that are important in influencing the toxicity of beryllium materials in occupational settings.

a. Solubility

Solubility may be an important determinant of the toxicity of airborne materials, influencing the deposition and persistence of inhaled particles in the respiratory tract, their bioavailability, and the likelihood of presentation to the immune system. A number of chemical agents, including metals that contact and penetrate the skin, are able to induce an immune response, such as sensitization (Boeniger, 2003; Mandervelt

et al.

, 1997). Similar to inhaled agents, the ability of materials to penetrate the skin is also influenced by solubility since dermal absorption may occur at a greater rate for soluble materials than insoluble materials (Kimber

et al.

, 2011).

This section reviews the relevant information regarding solubility, its importance in a biological matrix and its relevance to sensitization and beryllium lung disease. The weight of evidence presented below suggests that both soluble and non-soluble forms of beryllium can induce a sensitization response and result in progression of lung disease.

Beryllium salts, including the chloride (BeCl

), fluoride (BeF

), nitrate (Be(NO

)

), phosphate (Be

(PO

)

), and sulfate (tetrahydrate) (BeSO

· 4H

O) salts, are all water soluble. However, soluble beryllium salts can be converted to less soluble forms in the lung (Reeves and Vorwald, 1967). Aqueous solutions of the soluble beryllium salts are acidic as a result of the formation of Be(OH

)

, the tetrahydrate, which will react to form insoluble hydroxides or hydrated complexes within the general physiological range of pH values (between 5 and 8) (EPA, 1998). This may be an important factor in the development of CBD since lower-solubility forms of beryllium have been shown to persist in the lung for longer periods of time and persistence in the lung may be needed in order for this disease to occur (NAS, 2008).

Beryllium oxide (BeO), hydroxide (Be(OH)

), carbonate (Be

(OH)

), and sulfate (anhydrous) (BeSO

) are either insoluble, slightly soluble, or considered to be sparingly soluble (almost insoluble or having an extremely slow rate of dissolution). The solubility of beryllium oxide, which is prepared from beryllium hydroxide by calcining (heating to a high temperature without fusing in order to drive off volatile chemicals) at temperatures between 500 and 1,750 °C, has an inverse relationship with calcination temperature. Although the solubility of the low-fired crystals can be as much as 10 times that of the high-fired crystals, low-fired beryllium oxide is still only sparingly soluble (Delic, 1992). In a study that measured the dissolution kinetics (rate to dissolve) of beryllium compounds calcined at different temperatures, Hoover

et al.

, compared beryllium metal to beryllium oxide particles and found them to have similar solubilities. This was attributed to a fine layer of beryllium oxide that coats the metal particles (Hoover

et al.

, 1989). A study conducted by Deubner

et al.

, (2011) determined ore materials to be more soluble than beryllium oxide at pH 7.2 but similar in solubility at pH 4.5. Beryllium hydroxide was more soluble than beryllium oxide at both pHs (Deubner

et al.

, 2011).

Investigators have also attempted to determine how biological fluids can dissolve beryllium materials. In two studies, insoluble beryllium, taken up by activated phagocytes, was shown to be ionized by myeloperoxidases (Leonard and Lauwerys, 1987; Lansdown, 1995). The positive charge resulting from ionization enabled the beryllium to bind to receptors on the surface of cells such as lymphocytes or antigen-presenting cells which could make it more biologically active (NAS, 2008). In a study utilizing phagolysosomal-simulating fluid (PSF) with a pH of 4.5, both beryllium metal and beryllium oxide dissolved at a greater rate than that previously reported in water or SUF (simulant fluid) (Stefaniak

et al.

, 2006), and the rate of dissolution of the multi-constituent (mixed) particles was greater than that of the single-constituent beryllium oxide powder. The authors speculated that copper in the particles rapidly dissolves, exposing the small inclusions of beryllium oxide, which have higher specific surface areas (SSA)

and therefore dissolve at a higher rate. A follow-up study by the same investigational team (Duling

et al.

, 2012) confirmed dissolution of beryllium oxide by PSF and determined the release rate was biphasic (initial rapid diffusion followed by a latter slower surface reaction-driven release). During the latter phase, dissolution half-times were 1,400 to 2,000 days. The authors speculated this indicated bertrandite was persistent in the lung (Duling

et al.

, 2012).

In a recent study investigating the dissolution and release of beryllium ions for 17 beryllium-containing materials (ore, hydroxide, metal, oxide, alloys, and processing intermediates) using artificial human airway epithelial lining fluid, Stefaniak

et al.

, (2011) found release of beryllium ions within 7 days (beryl ore melter dust). The authors calculated dissolution half-times ranging from 30 days (reduction furnace material) to 74,000 days (hydroxide). Stefaniak

et al.

, (2011) speculated that despite the rapid mechanical clearance, billions of beryllium ions could be released in the respiratory tract via dissolution in airway lining fluid (ALF). Under this scenario beryllium-containing particles depositing in the respiratory tract dissolving in ALF could provide beryllium ions for absorption in the lung and interact with immune cells in the respiratory tract (Stefaniak

et al.

, 2011).

Huang

et al.

, (2011) investigated the effect of simulated lung fluid (SLF) on dissolution and nanoparticle generation and beryllium-containing materials. Bertrandite-containing ore, beryl-containing ore, frit (a processing intermediate), beryllium hydroxide (a processing intermediate) and silica (used as a control), were equilibrated in SLF at two pH values (4.5 and 7.2) to reflect inter- and intra-cellular environments in the lung tissue. Concentrations of beryllium, aluminum, and silica ions increased linearly during the first 20 days in SLF, rose slowly thereafter, reaching equilibrium over time. The study also found nanoparticle formation (in the size range of 10-100 nm) for all materials (Huang

et al.

, 2011).

In an

in vitro

skin model, Sutton

et al.

, (2003) demonstrated the dissolution of beryllium compounds (insoluble beryllium hydroxide, soluble beryllium phosphate) in a simulated sweat fluid. This model showed beryllium can be dissolved in biological fluids and be available for cellular uptake in the skin. Duling

et al.

, (2012) confirmed dissolution and release of ions from bertrandite ore in an artificial sweat model (pH 5.3 and pH 6.5).

b. Particle Size

The toxicity of beryllium as exemplified by beryllium oxide also is dependent, in part, on the particle size, with smaller particles (<10 μm) able to penetrate beyond the larynx (Stefaniak

et al.

, 2008). Most inhalation studies and occupational exposures involve quite small (<1-2 μm) beryllium oxide particles that can penetrate to the pulmonary regions of the lung (Stefaniak

et al.

, 2008). In inhalation studies with beryllium ores, particle sizes are generally much larger, with deposition occurring in several areas throughout the respiratory tract for particles <10 μm.

The temperature at which beryllium oxide is calcined influences its particle size, surface area, solubility, and ultimately its toxicity (Delic, 1992). Low-fired (500 °C) beryllium oxide is predominantly made up of poorly crystallized small particles, while higher firing temperatures (1000—1750 °C) result in larger particle sizes (Delic, 1992).

In order to determine the extent to which particle size plays a role in the toxicity of beryllium in occupational settings, several key studies are reviewed and detailed below. The findings on particle size have been related, where possible, to work process and biologically relevant toxicity endpoints of either sensitization or CBD.

Numerous studies have been conducted evaluating the particle size generated during basic industrial and machining operations. In a study by Cohen

et al.

, (1983), a multi-cyclone sampler was utilized to measure the size mass distribution of the beryllium aerosol at a beryllium-copper alloy casting operation. Briefly, Cohen

et al.

, (1983) found variable particle size generation based on the operations being sampled with particle size ranging from 3 to 16 μm. Hoover

et al.

, (1990) also found variable particle sizes being generated based on operations. In general, Hoover

et al.

, (1990) found that milling operations generated smaller particle sizes than sawing operations. Hoover

et al.

, (1990) also found that beryllium metal generated higher concentrations than metal alloys. Martyny

et al.

, (2000) characterized generation of particle size during precision beryllium machining processes. The study found that more than 50 percent of the beryllium machining particles collected in the breathing zone of machinists were less than 10 μm in aerodynamic diameter with 30 percent of that fraction being particles of less than 0.6 μm. A study by Thorat

et al.

, (2003) found similar results with ore mixing, crushing, powder production and machining ranging from 5.0 to 9.5 μm. Kent

et al.

, (2001) measured airborne beryllium using size-selective samplers in five furnace areas at a beryllium processing facility. A statistically significant linear trend was reported between the above alveolar-deposited particle mass concentration and prevalence of CBD and sensitization in the furnace production areas. The study authors suggested that the concentration of alveolar-deposited particles (

e.g.

, <3.5 μm) may be a better predictor of sensitization and CBD than the total mass concentration of airborne beryllium.

A recent study by Virji et al. (2011) evaluated particle size distribution, chemistry and solubility in areas with historically elevated risk of sensitization and CBD at a beryllium metal powder, beryllium oxide, and alloy production facility. The investigators observed that historically, exposure-response relationships have been inconsistent when using mass concentration to identify process-related risk, possibly due to incomplete particle characterization. Two separate exposure surveys were conducted in March 1999 and June-August 1999 using multi-stage personal impactor samplers (to determine particle size distribution) and personal 37 mm closed face cassette (CFC) samplers, both located in workers' breathing zones. One hundred and ninety eight time-weighted-average (TWA) personal impactor samples were analyzed for representative jobs and processes. A total of 4,026 CFC samples were collected over the 5-month collection period and analyzed for mass concentration, particle size, chemical content and solubility and compared to process areas with high risk of sensitization and CBD. The investigators found that total beryllium concentration varied greatly between workers and among process areas. Analysis of chemical form and solubility also revealed wide variability among process areas, but high risk process areas had exposures to both soluble and insoluble forms of beryllium. Analysis of particle size revealed most process areas had particles ranging from 5-14 µm mass median aerodynamic diameter (MMAD). Rank order correlating jobs to particle size showed high overall consistency (Spearman

=0.84) but moderate correlation (Pearson

=0.43). The investigators concluded that consideration of relevant aspects of exposure such as particle size

distribution, chemical form, and solubility will likely improve exposure assessments (Virji et al., 2011)

c. Particle Surface Area.

Particle surface area has been postulated as an important metric for beryllium exposure. Several studies have demonstrated a relationship between the inflammatory and tumorigenic potential of ultrafine particles and their increased surface area (Driscoll, 1996; Miller, 1995; Oberdorster

et al.

, 1996). While the exact mechanism explaining how particle surface area influences its biological activity is not known, a greater particle surface area has been shown to increase inflammation, cytokine production, anti-oxidant defenses and apoptosis (Elder

et al.

, 2005; Carter

et al.

, 2006; Refsne

et al.

, 2006).

Finch

et al.

, (1988) found that beryllium oxide calcined at 500 °C had 3.3 times greater specific surface area (SSA) than beryllium oxide calcined at 1000 °C, although there was no difference in size or structure of the particles as a function of calcining temperature. The beryllium-metal aerosol (airborne beryllium particles), although similar to the beryllium oxide aerosols in aerodynamic size, had an SSA about 30 percent that of the beryllium oxide calcined at 1000 °C. As discussed above, a later study by Delic (1992) found calcining temperatures had an effect on SSA as well as particle size.

Several studies have investigated the lung toxicity of beryllium oxide calcined at different temperatures and generally had found that those calcined at lower temperatures have greater toxicity and effect than materials calcined at higher temperatures. This may be because beryllium oxide fired at the lower temperature has a loosely formed crystalline structure with greater specific surface area than the fused crystal structure of beryllium oxide fired at the higher temperature. For example, beryllium oxide calcined at 500 °C has been found to have stronger pathogenic effects than material calcined at 1,000 °C, as shown in several of the beagle dog, rat, mouse and guinea pig studies discussed in the section on CBD pathogenesis that follows (Finch

et al.

, 1988; Polak

et al.

, 1968; Haley

et al.

, 1989; Haley

et al.

, 1992; Hall

et al.

, 1950). Finch

et al.

have also observed higher toxicity of beryllium oxide calcined at 500 °C, an observation they attribute to the greater surface area of beryllium particles calcined at the lower temperature (Finch

et al.

, 1988). These authors found that the

in vitro

cytotoxicity to Chinese hamster ovary (CHO) cells and cultured lung epithelial cells of 500 °C beryllium oxide was greater than that of 1,000 °C beryllium oxide, which in turn was greater than that of beryllium metal. However, when toxicity was expressed in terms of particle surface area, the cytotoxicity of all three forms was similar. Similar results were observed in a study comparing the cytotoxicity of beryllium metal particles of various sizes to cultured rat alveolar macrophages, although specific surface area did not entirely predict cytotoxicity (Finch

et al.

, 1991).

Stefaniak

et al.

, (2003b) investigated the particle structure and surface area of particles (powder and process-sampled) of beryllium metal, beryllium oxide, and copper-beryllium alloy. Each of these samples was separated by aerodynamic size, and their chemical compositions and structures were determined with x-ray diffraction and transmission electron microscopy, respectively. In summary, beryllium-metal powder varied remarkably from beryllium oxide powder and alloy particles. The metal powder consisted of compact particles, in which SSA decreases with increasing surface diameter. In contrast, the alloys and oxides consisted of small primary particles in clusters, in which the SSA remains fairly constant with particle size. SSA for the metal powders varied based on production and manufacturing process with variations among samples as high as a factor of 37. Stefaniak

et al.

(2003b) found lesser variation in SSA for the alloys or oxides. This is consistent with data from other studies summarized above showing that process may affect particle size and surface area. Particle size and/or surface area may explain differences in the rate of BeS and CBD observed in some epidemiological studies. However, these properties have not been consistently characterized in most studies.

B. Kinetics and Metabolism of Beryllium

Beryllium enters the body by inhalation, ingestion, or absorption through the skin. For occupational exposure, the airways and the skin are the primary routes of uptake.

1. Exposure via the Respiratory System

The respiratory tract, especially the lung, is the primary target of inhalation exposure in workers. Inhaled beryllium particles are deposited along the respiratory tract in a size dependent manner. In general, particles larger than 10 μm tend to deposit in the upper respiratory tract or nasal region and do not appreciably penetrate lower in the tracheobronchial or pulmonary regions (Figure 1). Particles less than 10 μm increasingly penetrate and deposit in the tracheobronchial and pulmonary regions with peak deposition in the pulmonary region occurring below 5 μm in particle diameter. The CBD pathology of concern is found in the pulmonary region. For particles below 1 μm, regional deposition changes dramatically. Ultrafine particles (generally considered to be 100 nm or lower) have a higher rate of deposition along the entire respiratory system (ICRP model, 1994). Those particles depositing in the lung and along the entire respiratory tract may encounter immunologic cells or may move into the vascular system where they are free to leave the lung and can contribute to systemic beryllium concentrations.

BILLING CODE 4510-26-C

EP07AU15.000

Beryllium is removed from the respiratory tract by various clearance mechanisms. Soluble beryllium is removed from the respiratory tract via absorption. Sparingly soluble or insoluble beryllium may remain in the lungs for many years after exposure, as has been observed in workers (Schepers, 1962). Clearance mechanisms for sparingly soluble or insoluble beryllium particles include: In the nasal passage, sneezing, mucociliary transport to the throat, or dissolution; in the tracheobronchial region, mucociliary transport, coughing, phagocytosis, or dissolution; in the pulmonary or alveolar region, phagocytosis, movement through the interstitium (translocation), or dissolution (Schlesinger, 1997).

Clearance mechanisms may occur slowly in humans, which is consistent with some animal studies. For example, subjects in the Beryllium Case Registry (BCR), which identifies and tracks cases of acute and chronic beryllium diseases, had elevated concentrations of beryllium in lung tissue (

e.g.,

3.1 μg/g of dried lung tissue and 8.5 μg/g in a mediastinal node) more than 20 years after termination of short-term (generally between 2 and 5 years) occupational exposure to beryllium (Sprince

et al.,

1976).

Clearance rates may depend on the solubility, dose, and size of the beryllium particles inhaled as well as the sex and species of the animal tested. As reviewed in a WHO Report (2001), more soluble beryllium compounds generally tend to be cleared from the respiratory system and absorbed into the bloodstream more rapidly than less soluble compounds (Van Cleave and Kaylor, 1955; Hart

et al.,

1980; Finch

et al.,

1990). Animal inhalation or intratracheal instillation studies administering soluble beryllium salts demonstrated significant absorption of approximately 20 percent of the initial lung burden, while sparingly soluble compounds such as beryllium oxide demonstrated that absorption was slower and less significant (Delic, 1992). Additional animal studies have demonstrated that clearance of soluble and sparingly soluble beryllium compounds was biphasic: A more rapid initial mucociliary transport phase of particles from the tracheobronchial tree to the gastrointestinal tract, followed by a slower phase via translocation to tracheobronchial lymph nodes, alveolar macrophages uptake, and beryllium particles dissolution (Camner

et al.,

1977; Sanders

et al.,

1978; Delic, 1992; WHO, 2001). Confirmatory studies in rats have shown the half-time for the rapid phase between 1-60 days, while the slow phase ranged from 0.6-2.3 years. It was also shown that this process was influenced by the solubility of the beryllium compounds: Weeks/months for soluble compounds, months/years for sparingly soluble compounds (Reeves and Vorwald, 1967; Reeves

et al.,

1967; Zorn

et al.,

1977; Rhoads and Sanders, 1985). Studies in guinea-pigs and rats indicate that 40-50 percent of the inhaled soluble beryllium salts are retained in the respiratory tract. Similar data could not be found for the sparingly or less soluble beryllium compounds or metal administered by this exposure route. (WHO, 2001; ATSDR, 2002).

Evidence from animal studies suggests that greater amounts of beryllium deposited in the lung may result in slower clearance times. A comparative study of rats and mice using a single dose of inhaled aerosolized beryllium metal demonstrated that an acute inhalation exposure to beryllium metal can slow particle clearance and induce lung damage in rats (Haley

et al.,

1990) and mice (Finch

et al.,

1998a). In another study Finch

et al.

(1994) exposed male F344/N rats to beryllium metal at concentrations resulting in beryllium lung burdens of 1.8, 10, and 100 µg. These exposure levels resulted in an estimated clearance half-life ranging

from 250-380 days for the three concentrations. For mice (Finch

et al.,

1998a), lung clearance half-lives were 91-150 days (for 1.7- and 2.6-μg lung burden groups) or 360-400 days (for 12- and 34-μg lung burden groups). While the lower exposure groups were quite different for rats and mice, the highest groups were similar in clearance half-lives for both species.

Beryllium absorbed from the respiratory system is mainly distributed to the tracheobronchial lymph nodes via the lymph system, bloodstream, and skeleton, which is the ultimate site of beryllium storage (Stokinger

et al.,

1953; Clary

et al.,

1975; Sanders

et al.,

1975; Finch

et al.,

1990). Trace amounts are distributed throughout the body (Zorn

et al.,

1977; WHO, 2001). Studies in rats have demonstrated accumulation of beryllium chloride in the skeletal system following intraperitoneal injection (Crowley

et al.,

1949; Scott

et al.,

1950) and accumulation of beryllium phosphate and beryllium sulfate in both nonparenchymal and parenchymal cells of the liver after intravenous administration in rats (Skilleter and Price, 1978). Studies have also demonstrated intracellular accumulation of beryllium oxide in bone marrow throughout the skeletal system after intravenous administration to rabbits (Fodor, 1977; WHO, 2001).

Systemic distribution of the more soluble compounds appears to be greater than that of the insoluble compounds (Stokinger

et al.

, 1953). Distribution has also been shown to be dose dependent in research using intravenous administration of beryllium in rats; small doses were preferentially taken up in the skeleton, while higher doses were initially distributed preferentially to the liver. Beryllium was later mobilized from the liver and transferred to the skeleton (IARC, 1993). A half-life of 450 days has been estimated for beryllium in the human skeleton (ICRP, 1960). This indicates the skeleton may serve as a repository for beryllium that may later be reabsorbed by the circulatory system, making beryllium available to the immunological system.

2. Dermal Exposure

Beryllium compounds have been shown to cause skin irritation and sensitization in humans and certain animal models (Van Orstrand

et al.

, 1945; de Nardi

et al.

, 1953; Nishimura 1966; Epstein 1990; Belman, 1969; Tinkle

et al.

, 2003; Delic, 1992). The Agency for Toxic Substances and Disease Registry (ATSDR) estimated that less than 0.1 percent of beryllium compounds are absorbed through the skin (ATSDR, 2002). However, even minute contact and absorption across the skin may directly elicit an immunological sensitization response (Deubner

et al.

, 2001; Toledo

et al.

, 2011). Recent studies by Tinkle

et al.

(2003) showed that penetration of beryllium oxide particles was possible

ex vivo

for human intact skin at particle sizes of ≤ 1μm, as confirmed by scanning electron microscopy. Using confocal microscopy, Tinkle

et al.

demonstrated that surrogate fluorescent particles up to 1 μm in size could penetrate the mouse epidermis and dermis layers in a model designed to mimic the flexing and stretching of human skin in motion. Other poorly soluble particles, such as titanium dioxide, have been shown to penetrate normal human skin (Tan

et al.

, 1996) suggesting the flexing and stretching motion as a plausible mechanism for dermal penetration of beryllium as well. As earlier summarized, insoluble forms of beryllium can be solubilized in biological fluids (

e.g.

, sweat) making them available for absorption through intact skin (Sutton

et al.

, 2003; Stefaniak

et al.

, 2011; Duling

et al.

, 2012).

Although its precise role remains to be elucidated, there is evidence to indicate that dermal exposure can contribute to beryllium sensitization. As early as the 1940s it was recognized that dermatitis experienced by workers in primary beryllium production facilities was linked to exposures to the soluble beryllium salts. Except in cases of wound contamination, dermatitis was rare in workers whose exposures were restricted to exposure to poorly soluble beryllium-containing particles (Van Ordstrand

et al.

, 1945). Further investigation by McCord in 1951 indicated that direct skin contact with soluble beryllium compounds, but not beryllium hydroxide or beryllium metal, caused dermal lesions (reddened, elevated, or fluid-filled lesions on exposed body surfaces) in susceptible persons. Curtis, in 1951, demonstrated skin sensitization to beryllium with patch testing using soluble and insoluble forms of beryllium in beryllium-naïve subjects. These subjects later developed granulomatous skin lesions with the classical delayed-type contact dermatitis following repeat challenge (Curtis, 1951). These lesions appeared after a latent period of 1-2 weeks, suggesting a delayed allergic reaction. The dermal reaction occurred more rapidly and in response to smaller amounts of beryllium in those individuals previously sensitized (Van Ordstrand

et al.

, 1945). Contamination of cuts and scrapes with beryllium can result in the beryllium becoming embedded within the skin causing a granuloma to develop in the skin (Epstein, 1991). Introduction of soluble or insoluble beryllium compounds into or under the skin as a result of abrasions or cuts at work has been shown to result in chronic ulcerations with granuloma formation (Van Orstrand

et al.

, 1945; Lederer and Savage, 1954). Beryllium absorption through bruises and cuts has been demonstrated as well (Rossman

et al.

, 1991). In a study by Invannikov

et al.

, (1982), beryllium chloride was applied directly to the skin of live animals with three types of wounds: abrasions (superficial skin trauma), cuts (skin and superficial muscle trauma), and penetration wounds (deep muscle trauma). The percentage of the applied dose absorbed into the systemic circulation during a 24-hour exposure was significant, ranging from 7.8 percent to 11.4 percent for abrasions, from 18.3 percent to 22.9 percent for cuts, and from 34 percent to 38.8 percent for penetration wounds (WHO, 2001).

A study by Deubner

et al.

, (2001) concluded that exposure across damaged skin can contribute as much systemic loading of beryllium as inhalation (Deubner

et al.

, 2001). Deubner

et al.

, (2001) estimated dermal loading (amount of particles penetrating into the skin) in workers as compared to inhalation exposure. Deubner's calculations assumed a dermal loading rate for beryllium on skin of 0.43 μg/cm

, based on the studies of loading on skin after workers cleaned up (Sanderson

et al.

, 1999), multiplied by a factor of 10 to approximate the workplace concentrations and the very low absorption rate of 0.001 percent (taken from EPA estimates). It should be noted that these calculations did not take into account absorption of soluble beryllium salts that might occur across nasal mucus membranes, which may result from contact between contaminated skin and the nose (EPA, 1998).

A study conducted by Day

et al.

(2007) evaluated the effectiveness of a dermal protection program implemented in a beryllium alloy facility in 2002. The investigators evaluated levels of beryllium in air, on workplace surfaces, on cotton gloves worn over nitrile gloves, and on the necks and faces of workers over a six day period. The investigators found a good correlation between air samples and work surface contamination at this facility. The investigators also found measurable levels of beryllium on the skin of workers as a result of work processes even from workplace areas

promoted as “visually clean” by the company housekeeping policy. Importantly, the investigators found that the beryllium contamination could be transferred from body region to body region (

e.g.

, hand to face, neck to face). The investigators demonstrated multiple pathways of exposure which could lead to sensitization, increasing risk for developing CBD (Day,

et al.

, 2007).

The same group of investigators (Armstrong

et al.

, 2014) extended their work on investigating multiple exposure pathways contributing to sensitization and CBD. The investigators evaluated four different beryllium manufacturing and processing facilities to assess the contribution of various exposure pathways on worker exposure. Airborne, work surface and cotton glove beryllium concentrations were evaluated. The investigators found strong correlations between air-surface concentrations, glove-surface concentrations, and air-glove concentrations at this facility. This work confirms findings from Day et al. (2007) demonstrating the importance of airborne beryllium concentrations to surface contamination and dermal exposure even at exposures below the current OSHA PEL (Armstrong et al., 2014).

3. Oral and Gastrointestinal Exposure

According to the WHO Report (2001), gastrointestinal absorption of beryllium can occur by both the inhalation and oral routes of exposure. Through inhalation exposure, a fraction of the inhaled material is transported to the gastrointestinal tract by the mucociliary escalator or by the swallowing of the insoluble material deposited in the upper respiratory tract (WHO, 2001). Gastrointestinal absorption of beryllium can occur by both the inhalation and oral routes of exposure. In the case of inhalation, a portion of the inhaled material is transported to the gastrointestinal tract by the mucociliary escalator or by the swallowing of the insoluble material deposited in the upper respiratory tract (Schlesinger, 1997). Animal studies have shown oral administration of beryllium compounds to result in very limited absorption and storage (as reviewed by U.S. EPA, 1998). In animal ingestion studies using radio-labeled beryllium chloride in rats, mice, dogs, and monkeys, the vast majority of the ingested dose passed through the gastrointestinal tract unabsorbed and was excreted in the feces. In most studies, <1 percent of the administered radioactivity was absorbed into the bloodstream and subsequently excreted in the urine (Crowley

et al.

, 1949; Furchner

et al.

, 1973; LeFevre and Joel, 1986). Research using soluble beryllium sulfate has shown that as the compound passes into the intestine, which has a higher pH than the stomach (approximate pH of 6 to 8 for the intestine, pH of 1 or 2 for the stomach), the beryllium is precipitated as the insoluble phosphate and thus is no longer available for absorption (Reeves, 1965; WHO, 2001).

Urinary excretion of beryllium has been shown to correlate with the amount of occupational exposure (Klemperer

et al.

, 1951). Beryllium that is absorbed into the bloodstream is excreted primarily in the urine (Crowley

et al.

, 1949; Scott

et al.

, 1950; Furchner

et al.

, 1973; Stiefel

et al.

, 1980), whereas excretion of unabsorbed beryllium is primarily via the fecal route (Hart

et al.

, 1980; Finch

et al.

, 1990). A far higher percentage of the beryllium administered parenterally in various animal species was eliminated in the urine than in the feces (Crowley

et al.

, 1949; Scott

et al.

, 1950; Furchner

et al.

, 1973), confirming that beryllium found in the feces following oral exposure is primarily unabsorbed material. A study using percutaneous incorporation of soluble beryllium nitrate in rats similarly demonstrated that more than 90 percent of the beryllium in the bloodstream was eliminated via urine (Zorn

et al.

, 1977; WHO, 2001). More than 99 percent of ingested beryllium chloride was excreted in the feces (Mullen

et al.

, 1972). Elimination half-times of 890-1,770 days (2.4-4.8 years) were calculated for mice, rats, monkeys, and dogs injected intravenously with beryllium chloride (Furchner

et al.

, 1973). Mean daily excretion of beryllium metal was 4.6 × 10

−5

percent of the dose administered by intratracheal instillation in baboons and 3.1 × 10

−5

percent in rats (Andre

et al.

, 1987).

4. Metabolism

Beryllium and its compounds are not metabolized or biotransformed, but soluble beryllium salts may be converted to less soluble forms in the lung (Reeves and Vorwald, 1967). As stated earlier, solubility is an important factor for persistence of beryllium in the lung. Insoluble beryllium, engulfed by activated phagocytes, can be ionized by an acidic environment and by myeloperoxidases (Leonard and Lauwerys, 1987; Lansdown, 1995; WHO, 2001), and this positive charge could potentially make it more biologically reactive because it may allow the beryllium to bind to a peptide or protein and be presented to the T cell receptor or antigen-presenting cell (Fontenot, 2000).

5. Preliminary Conclusion for Particle Characterization and Kinetics of Beryllium

The forms and concentrations of beryllium across the workplace vary substantially based upon location, process, production and work task. Many factors influence the potency of beryllium including concentration, composition, structure, size and surface area of the particle.

Studies have demonstrated that beryllium sensitization can occur via the skin or inhalation from soluble or poorly soluble beryllium particles. Beryllium must be presented to a cell in a soluble form for activation of the immune system (NAS, 2008), and this will be discussed in more detail in the section to follow. Poorly soluble beryllium can be solubilized via intracellular fluid, lung fluid and sweat (Sutton

et al.

, 2003; Stefaniak

et al.

, 2011). For beryllium to persist in the lung it needs to be insoluble. However, soluble beryllium has been shown to precipitate in the lung to form insoluble beryllium (Reeves and Vorwald, 1967).

Some animal and epidemiological studies suggest that the form of beryllium may affect the rate of development of BeS and CBD. Beryllium in an inhalable form (either as soluble or insoluble particles or mist) can deposit in the respiratory tract and interact with immune cells located along the entire respiratory tract (Scheslinger, 1997). However, more study is needed to precisely determine the physiochemical characteristics of beryllium that influence toxicity and immunogenicity.

C. Acute Beryllium Diseases

Acute beryllium disease (ABD) is a relatively rapid onset inflammatory reaction resulting from breathing high airborne concentrations of beryllium. It was first reported in workers extracting beryllium oxide (Van Ordstrand

et al.

, 1943). Since the Atomic Energy Commission's adoption of occupational exposure limits for beryllium beginning in 1949, cases of ABD have been rare. According to the World Health Organization (2001), ABD is generally associated with exposure to beryllium levels at or above 100 μg/m

and may be fatal in 10 percent of cases. However, cases have been reported with beryllium exposures below 100 µg/m

(Cummings

et al.

, 2009). The disease involves an inflammatory reaction that may include the entire respiratory tract, involving the nasal passages, pharynx, bronchial airways and alveoli. Other tissues including skin and conjunctivae may be affected as well. The clinical features of

ABD include a nonproductive cough, chest pain, cyanosis, shortness of breath, low-grade fever and a sharp drop in functional parameters of the lungs. Pathological features of ABD include edematous distension, round cell infiltration of the septa, proteinaceous materials, and desquamated alveolar cells in the lung. Monocytes, lymphocytes and plasma cells within the alveoli are also characteristic of the acute disease process (Freiman and Hardy, 1970).

Two types of acute beryllium disease have been characterized in the literature: a rapid and severe course of acute fulminating pneumonitis generally developing within 48 to 72 hours of a massive exposure, and a second form that takes several days to develop from exposure to lower concentrations of beryllium (still above the levels set by regulatory and guidance agencies) (Hall, 1950; DeNardi

et al.

, 1953; Newman and Kreiss, 1992). Evidence of a dose-response relationship to the concentration of beryllium is limited (Eisenbud

et al.

, 1948; Stokinger, 1950; Sterner and Eisenbud, 1951). Recovery from either type of ABD is generally complete after a period of several weeks or months (DeNardi

et al.

, 1953). However, deaths have been reported in more severe cases (Freiman and Hardy, 1970). There have been documented cases of progression to CBD (ACCP, 1965; Hall, 1950) suggesting the possibility of an immune component to this disease (Cummings

et al.

, 2009) as well. According to the BCR, in the United States, approximately 17 percent of ABD patients developed CBD (BCR, 2010). The majority of ABD cases occurred between 1932 and 1970 (Eisenbud, 1983; Middleton, 1998). ABD is extremely rare in the workplace today due to more stringent exposure controls implemented following occupational and environmental standards set in 1970-1972 (OSHA, 1971; ACGIH, 1971; ANSI, 1970) and 1974 (EPA, 1974).

D. Chronic Beryllium Disease

This section provides an overview of the immunology and pathogenesis of BeS and CBD, with particular attention to the role of skin sensitization, particle size, beryllium compound solubility, and genetic variability in individuals' susceptibility to beryllium sensitization and CBD.

Chronic beryllium disease (CBD), formerly known as “berylliosis” or “chronic berylliosis,” is a granulomatous disorder primarily affecting the lungs. CBD was first described in the literature by Hardy and Tabershaw (1946) as a chronic granulomatous pneumonitis. It was proposed as early as 1951 that CBD could be a chronic disease resulting from an immune sensitization to beryllium (Sterner and Eisenbud, 1951; Curtis, 1959; Nishimura, 1966). However, for a time, there remained some controversy as to whether CBD was a delayed-onset hypersensitivity disease or a toxicant-induced disease (NAS, 2008). Wide acceptance of CBD as a hypersensitivity lung disease did not occur until bronchoscopy studies and bronchoalveolar lavage (BAL) studies were performed demonstrating that BAL cells from CBD patients responded to beryllium challenge (Epstein

et al.

, 1982; Rossman

et al.

, 1988; Saltini

et al.

, 1989).

CBD shares many clinical and histopathological features with pulmonary sarcoidosis, a granulomatous lung disease of unknown etiology. This includes such debilitating effects as airway obstruction, diminishment of physical capacity associated with reduced lung function, possible depression associated with decreased physical capacity, and decreased life expectancy. Without appropriate information, CBD may be difficult to distinguish from sarcoidosis. It is estimated that up to 6 percent of all patients diagnosed with sarcoidosis may actually have CBD (Fireman

et al.

, 2003; Rossman and Kreiber, 2003). Among patients diagnosed with sarcoidosis in which beryllium exposure can be confirmed, as many as 40 percent may actually have CBD (Muller-Quernheim

et al.

, 2006; Cherry

et al.

, 2015).

Clinical signs and symptoms of CBD may include, but are not limited to, a simple cough, shortness of breath or dypsnea, fever, weight loss or anorexia, skin lesions, clubbing of fingers, cyanosis, night sweats, cor pulmonale, tachycardia, edema, chest pain and arthralgia. Changes or loss of pulmonary function also occur with CBD such as decrease in vital capacity, reduced diffusing capacity, and restrictive breathing patterns. The signs and symptoms of CBD constitute a continuum of symptoms that are progressive in nature with no clear demarcation between any stages in the disease (Rossman, 1996; NAS, 2008). Besides these listed symptoms from CBD patients, there have been reported cases of CBD that remained asymptomatic (Muller-Querheim, 2005; NAS, 2008).

Unlike ABD, CBD can result from inhalation exposure to beryllium at levels below the current OSHA PEL, can take months to years after initial beryllium exposure before signs and symptoms of CBD occur (Newman 1996, 2005 and 2007; Henneberger, 2001; Seidler

et al.

, 2012; Schuler

et al.

, 2012), and may continue to progress following removal from beryllium exposure (Newman, 2005; Sawyer

et al.

, 2005; Seidler

et al.

, 2012). Patients with CBD can progress to a chronic obstructive lung disorder resulting in loss of quality of life and the potential for decreased life expectancy (Rossman,

et al.

, 1996; Newman

et al.

, 2005). The NAS report (2008) noted the general lack of published studies on progression of CBD from an early asymptomatic stage to functionally significant lung disease (NAS, 2008). The report emphasized that risk factors and time course for clinical disease have not been fully delineated. However, for people now under surveillance, clinical progression from immunological sensitization and early pathological lesions (

i.e.

, granulomatous inflammation) prior to onset of symptoms to symptomatic disease appears to be slow, although more follow-up is needed (NAS, 2008). A study by Newman (1996) emphasized the need for prospective studies to determine the natural history and time course from BeS and asymptomatic CBD to full-blown disease (Newman, 1996). Drawing from his own clinical experience, Newman was able to identify the sequence of events for those with symptomatic disease as follows: Initial determination of beryllium sensitization; gradual emergence of chronic inflammation of the lung; pathologic alterations with measurable physiologic changes (

e.g.

, pulmonary function and gas exchange); progression to a more severe lung disease (with extrapulmonary effects such as clubbing and cor pulmonale in some cases); and finally death in some cases (reported between 5.8 to 38 percent) (NAS, 2008; Newman, 1996).

In contrast to some occupationally related lung diseases, the early detection of chronic beryllium disease may be useful since treatment of this condition can lead not only to regression of the signs and symptoms, but also may prevent further progression of the disease in certain individuals (Marchand-Adam, 2008; NAS, 2008). The management of CBD is based on the hypothesis that suppression of the hypersensitivity reaction (

i.e.

, granulomatous process) will prevent the development of fibrosis. However, once fibrosis has developed, therapy cannot reverse the damage.

To date, there have been no controlled studies to determine the optimal treatment for CBD (Rossman, 1996; NAS 2008; Sood, 2009). Management of CBD is generally modeled after sarcoidosis treatment. Oral corticosteroid treatment can be initiated in patients with

evidence of disease (either by bronchoscopy or other diagnostic measures before progression of disease or after clinical signs of pulmonary deterioration occur). This includes treatment with other anti-inflammatory agents (NAS, 2008; Maier

et al.

, 2012; Salvator

et al.

, 2013) as well. It should be noted, however, that treatment with corticosteroids has side-effects of their own that need to be measured against the possibility of progression of disease (Gibson

et al.

, 1996; Zaki

et al.

, 1987). Alternative treatments such as azathiopurine and infliximab, while successful at treating symptoms of CBD, have been demonstrated to have side-effects as well (Pallavicino

et al.

, 2013; Freeman, 2012).

1. Development of Beryllium Sensitization

Sensitization to beryllium is an essential step for worker development of CBD. Sensitization to beryllium can result from inhalation exposure to beryllium (Newman

et al.,

2005; NAS, 2008), as well as from skin exposure to beryllium (Curtis, 1951; Newman

et al.,

1996; Tinkle

et al.,

2003). Sensitization is currently detected using a laboratory blood test described in Appendix A. Although there may be no clinical symptoms associated with BeS, a sensitized worker's immune system has been activated to react to beryllium exposures such that subsequent exposure to beryllium can progress to serious lung disease (Kreiss

et al.,

1996; Kreiss

et al.,

1997; Kelleher

et al.,

2001; and Rossman, 2001). Since the pathogenesis of CBD involves a beryllium-specific, cell-mediated immune response, CBD cannot occur in the absence of sensitization (NAS, 2008). Various factors, including genetic susceptibility, have been shown to influence risk of developing sensitization and CBD (NAS 2008) and will be discussed later in this section.

While various mechanisms or pathways may exist for beryllium sensitization, the most plausible mechanisms supported by the best available and most current science are discussed below. Sensitization occurs via the formation of a beryllium-protein complex (an antigen) that causes an immunological response. In some instances, onset of sensitization has been observed in individuals exposed to beryllium for only a few months (Kelleher

et al.,

2001; Henneberger

et al.,

2001). This suggests the possibility that relatively brief, short-term beryllium exposures may be sufficient to trigger the immune hypersensitivity reaction. Several studies (Newman et al., 2001; Henneberger et al., 2001; Rossman, 2001; Schuler et al., 2005; Donovan et al., 2007, Schuler et al., 2012) have detected a higher prevalence of sensitization among workers with less than one year of employment compared to some cross-sectional studies which, due to lack of information regarding initial exposure, cannot determine time of sensitization (Kreiss et al., 1996; Kreiss et al., 1997). While only very limited evidence has described humoral changes in certain patients with CBD (Cianciara

et al.,

1980), clear evidence exists for an immune cell-mediated response, specifically the T-cell (NAS, 2008). Figure 2 delineates the major steps required for progression from beryllium contact to sensitization to CBD.

BILLING CODE 4510-26-P

EP07AU15.001

BILLING CODE 4510-26-C

Beryllium presentation to the immune system is believed to occur either by direct present

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