[Federal Register: February 28, 2006 (Volume 71, Number 39)]
[Rules and Regulations]
[Page 10099-10385]
[DOCID:fr28fe06-25]

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Part II

Department of Labor

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Occupational Safety and Health Administration

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29 CFR Parts 1910, 1915, et al.

Occupational Exposure to Hexavalent Chromium; Final Rule

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DEPARTMENT OF LABOR

Occupational Safety and Health Administration

29 CFR Parts 1910, 1915, 1917, 1918, and 1926

[Docket No. H054A]
RIN 1218-AB45

Occupational Exposure to Hexavalent Chromium

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

ACTION: Final rule.

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SUMMARY: The Occupational Safety and Health Administration (OSHA) is
amending the existing standard which limits occupational exposure to
hexavalent chromium (Cr(VI)). OSHA has determined based upon the best
evidence currently available that at the current permissible exposure
limit (PEL) for Cr(VI), workers face a significant risk to material
impairment of their health. The evidence in the record for this
rulemaking indicates that workers exposed to Cr(VI) are at an increased
risk of developing lung cancer. The record also indicates that
occupational exposure to Cr(VI) may result in asthma, and damage to the
nasal epithelia and skin.
    The final rule establishes an 8-hour time-weighted average (TWA)
exposure limit of 5 micrograms of Cr(VI) per cubic meter of air (5
[mu]g/m\3\). This is a considerable reduction from the previous PEL of
1 milligram per 10 cubic meters of air (1 mg/10 m\3\, or 100 [mu]g/
m\3\) reported as CrO3, which is equivalent to a limit of 52
[mu]g/m\3\ as Cr(VI). The final rule also contains ancillary provisions
for worker protection such as requirements for exposure determination,
preferred exposure control methods, including a compliance alternative
for a small sector for which the new PEL is infeasible, respiratory
protection, protective clothing and equipment, hygiene areas and
practices, medical surveillance, recordkeeping, and start-up dates that
include four years for the implementation of engineering controls to
meet the PEL.
    The final standard separately regulates general industry,
construction, and shipyards in order to tailor requirements to the
unique circumstances found in each of these sectors.
    The PEL established by this rule reduces the significant risk posed
to workers by occupational exposure to Cr(VI) to the maximum extent
that is technologically and economically feasible.

DATES: This final rule becomes effective on May 30, 2006. Start-up
dates for specific provisions are set in Sec.  1910.1026(n) for general
industry; Sec.  1915.1026(l) for shipyards; and Sec.  1926.1126(l) for
construction. However, affected parties do not have to comply with the
information collection requirements in the final rule until the
Department of Labor publishes in the Federal Register the control
numbers assigned by the Office of Management and Budget (OMB).
Publication of the control numbers notifies the public that OMB has
approved these information collection requirements under the Paperwork
Reduction Act of 1995.

ADDRESSES: In compliance with 28 U.S.C. 2112(a), the Agency designates
the Associate Solicitor for Occupational Safety and Health, Office of
the Solicitor, Room S-4004, U.S. Department of Labor, 200 Constitution
Avenue, NW., Washington, DC 20210, as the recipient of petitions for
review of these standards.

FOR FURTHER INFORMATION CONTACT: Mr. Kevin Ropp, Director, OSHA Office
of Communications, Room N-3647, U.S. Department of Labor, 200
Constitution Avenue, NW., Washington, DC 20210; telephone (202) 693-
1999.

SUPPLEMENTARY INFORMATION: The following table of contents lays out the
structure of the preamble to the final standards. This preamble
contains a detailed description of OSHA's legal obligations, the
analyses and rationale supporting the Agency's determination, including
a summary of and response to comments and data submitted during the
rulemaking.

I. General
II. Pertinent Legal Authority
III. Events Leading to the Final Standard
IV. Chemical Properties and Industrial Uses
V. Health Effects
    A. Absorption, Distribution, Metabolic Reduction and Elimination
    1. Deposition and Clearance of Inhaled Cr(VI) From the
Respiratory Tract
    2. Absorption of Inhaled Cr(VI) Into the Bloodstream
    3. Dermal Absorption of Cr(VI)
    4. Absorption of Cr(VI) by the Oral Route
    5. Distribution of Cr(VI) in the Body
    6. Metabolic Reduction of Cr(VI)
    7. Elimination of Cr(VI) From the Body
    8. Physiologically-Based Pharmacokinetic Modeling
    9. Summary
    B. Carcinogenic Effects
    1. Evidence From Chromate Production Workers
    2. Evidence From Chromate Pigment Production Workers
    3. Evidence From Workers in Chromium Plating
    4. Evidence From Stainless Steel Welders
    5. Evidence From Ferrochromium Workers
    6. Evidence From Workers in Other Industry Sectors
    7. Evidence From Experimental Animal Studies
    8. Mechanistic Considerations
    C. Non-Cancer Respiratory Effects
    1. Nasal Irritation, Nasal Tissue Ulcerations and Nasal Septum
Perforations
    2. Occupational Asthma
    3. Bronchitis
    4. Summary
    D. Dermal Effects
    E. Other Health Effects
VI. Quantitative Risk Assessment
    A. Introduction
    B. Study Selection
    1. Gibb Cohort
    2. Luippold Cohort
    3. Mancuso Cohort
    4. Hayes Cohort
    5. Gerin Cohort
    6. Alexander Cohort
    7. Studies Selected for the Quantitative Risk Assessment
    C. Quantitative Risk Assessments Based on the Gibb Cohort
    1. Environ Risk Assessments
    2. National Institute for Occupational Safety and Health (NIOSH)
Risk Assessment
    3. Exponent Risk Assessment
    4. Summary of Risk Assessments Based on the Gibb Cohort
    D. Quantitative Risk Assessments Based on the Luippold Cohort
    E. Quantitative Risk Assessments Based on the Mancuso, Hayes,
Gerin, and Alexander Cohorts
    1. Mancuso Cohort
    2. Hayes Cohort
    3. Gerin Cohort
    4. Alexander Cohort
    F. Summary of Risk Estimates Based on Gibb, Luippold, and
Additional Cohorts
    G. Issues and Uncertainties
    1. Uncertainty With Regard to Worker Exposure to Cr(VI)
    2. Model Uncertainty, Exposure Threshold, and Dose Rate Effects
    3. Influence of Smoking, Race, and the Healthy Worker Survivor
Effect
    4. Suitability of Risk Estimates for Cr(VI) Exposures in Other
Industries
    H. Conclusions
VII. Significance of Risk
    A. Material Impairment of Health
    1. Lung Cancer
    2. Non-Cancer Impairments
    B. Risk Assessment
    1. Lung Cancer Risk Based on the Gibb Cohort
    2. Lung Cancer Risk Based on the Luippold Cohort
    3. Risk of Non-Cancer Impairments
    C. Significance of Risk and Risk Reduction
VIII. Summary of the Final Economic Analysis and Regulatory
Flexibility Analysis
IX. OMB Review Under the Paperwork Reduction Act of 1995
X. Federalism
XI. State Plans

XII. Unfunded Mandates
XIII. Protecting Children from Environmental Health and Safety Risks
XIV. Environmental Impacts
XV. Summary and Explanation of the Standards
    (a) Scope
    (b) Definitions
    (c) Permissible Exposure Limit (PEL)
    (d) Exposure Determination
    (e) Regulated Areas
    (f) Methods of Compliance
    (g) Respiratory Protection
    (h) Protective Work Clothing and Equipment
    (i) Hygiene Areas and Practices
    (j) Housekeeping
    (k) Medical Surveillance
    (l) Communication of Chromium (VI) Hazards to Employees
    (m) Recordkeeping
    (n) Dates
XVI. Authority and Signature
XVII. Final Standards

I. General

    This final rule establishes a permissible exposure limit (PEL) of 5
micrograms of Cr(VI) per cubic meter of air (5 [mu]g/m\3\) as an 8-hour
time-weighted average for all Cr(VI) compounds. After consideration of
all comments and evidence submitted during this rulemaking, OSHA has
made a final determination that a PEL of 5 [mu]g/m\3\ is necessary to
reduce the significant health risks posed by occupational exposures to
Cr(VI); it is the lowest level that is technologically and economically
feasible for industries impacted by this rule. A full explanation of
OSHA's rationale for establishing this PEL is presented in the
following preamble sections: V (Health Effects), VI (Quantitative Risk
Assessment), VII (Significance of Risk), VIII (Summary of the Final
Economic Analysis and Regulatory Flexibility Analysis), and XV (Summary
and Explanation of the Standard, paragraph (c), Permissible Exposure
Limit).
    OSHA is establishing three separate standards covering occupational
exposures to Cr(VI) for: general industry (29 CFR 1910.1026); shipyards
(29 CFR 1915.1026), and construction (29 CFR 1926.1126). In addition to
the PEL, these three standards include ancillary provisions for
exposure determination, methods of compliance, respiratory protection,
protective work clothing and equipment, hygiene areas and practices,
medical surveillance, communication of Cr(VI) hazards to employees,
recordkeeping, and compliance dates. The general industry standard has
additional provisions for regulated areas and housekeeping. The Summary
and Explanation section of this preamble (Section XV, paragraphs (d)
through (n)) includes a full discussion of the basis for including
these provisions in the final standards.
    Several major changes were made to the October 4, 2004 proposed
rule as a result of OSHA's analysis of comments and data received
during the comment periods and public hearings. The major changes are
summarized below and are fully discussed in the Summary and Explanation
section of this preamble (Section XV)
    Scope. As proposed, the standards apply to occupational exposures
to Cr(VI) in all forms and compounds with limited exceptions. OSHA has
made a final determination to exclude from coverage of these final
standards exposures that occur in the application of pesticides
containing Cr(VI) (e.g., the treatment of wood with preservatives).
These exposures are already covered by the Environmental Protection
Agency. OSHA is also excluding exposures to portland cement and
exposures in work settings where the employer has objective data
demonstrating that a material containing chromium or a specific
process, operation, or activity involving chromium cannot release
dusts, fumes, or mists of Cr(VI) in concentrations at or above 0.5
[mu]g/m\3\ under any expected conditions of use. OSHA believes that the
weight of evidence in this rulemaking demonstrates that the primary
risk in these two exposure scenarios can be effectively addressed
through existing OSHA standards for personal protective equipment,
hygiene, hazard communication and the PELs for portland cement or
particulates not otherwise regulated (PNOR).
    Permissible Exposure Limit. OSHA proposed a PEL of 1 [mu]g/m\3\ but
has now determined that a PEL 5 [mu]g/m\3\ is the lowest level that is
technologically and economically feasible.
    Exposure Determination. OSHA did not include a provision for
exposure determination in the proposed shipyard and construction
standards, reasoning that the obligation to meet the proposed PEL would
implicitly necessitate performance-based monitoring by the employer to
ensure compliance with the PEL. However, OSHA was convinced by
arguments presented during the rulemaking that an explicit requirement
for exposure determination is necessary to ensure that employee
exposures are adequately characterized. Therefore OSHA has included a
provision for exposure determination for general industry, shipyards
and construction in the final rule. In order to provide additional
flexibility in characterizing employee exposures, OSHA is allowing
employers to choose between a scheduled monitoring option and a
performance-based option for making exposure determinations.
    Methods of Compliance. Under the proposed rule employers were to
use engineering and work practice controls to achieve the proposed PEL
unless the employer could demonstrate such controls are not feasible.
In the final rule, OSHA has retained this exception but has added a
provision that only requires employers to use engineering and work
practice controls to reduce or maintain employee exposures to 25 [mu]g/
m\3\ when painting aircraft or large aircraft parts in the aerospace
industry to the extent such controls are feasible. The employer must
then supplement those engineering controls with respiratory protection
to achieve the PEL. As discussed more fully in the Summary of the Final
Economic Analysis and Regulatory Flexibility Analysis (Section VIII)
and the Summary and Explanation (Section XV) OSHA has determined that
this is the lowest level achievable through the use of engineering and
work practice controls alone for these limited operations.
    Housekeeping. In the proposed rule, cleaning methods such as
shoveling, sweeping, and brushing were prohibited unless they were the
only effective means available to clean surfaces contaminated with
Cr(VI). The final standard has modified this prohibition to make clear
only dry shoveling, sweeping and brushing are prohibited so that
effective wet shoveling, sweeping, and brushing would be allowed. OSHA
is also adding a provision that allows the use of compressed air to
remove Cr(VI) when no alternative method is feasible.
    Medical Surveillance. As proposed and continued in these final
standards, medical surveillance is required to be provided to employees
experiencing signs or symptoms of the adverse health effects associated
with Cr(VI) exposure or exposed in an emergency. In addition, for
general industry, employees exposed above the PEL for 30 or more days a
year were to be provided medical surveillance. In the final standard,
OSHA has changed the trigger for medical surveillance to exposure above
the action level (instead of the PEL) for 30 days a year to take into
account the existing risks at the new PEL. This provision has also been
extended to the standards for shipyards and construction since those
employers now will be required to perform an exposure determination and
thus will be able to determine which employees are exposed above the
action level 30 or more days a year.

    Communication of Hazards. In the proposed standard, OSHA specified
the sign for the demarcation of regulated areas in general industry and
the label for contaminated work clothing or equipment and Cr(VI)
contaminated waste and debris. The proposed standard also listed the
various elements to be covered for employee training. In order to
simplify requirements under this section of the final standard and
reduce confusion between this standard and the Hazard Communication
Standard, OSHA has removed the requirement for special signs and labels
and the specification of employee training elements. Instead, the final
standard requires that signs, labels and training be in accordance with
the Hazard Communication Standard (29 CFR 1910.1200). The only
additional training elements required in the final rule are those
related specifically to the contents of the final Cr(VI) standards.
While the final standards have removed language in the communication of
hazards provisions to make them more consistent with OSHA's existing
Hazard Communication Standard, the employers obligation to mark
regulated areas (where regulated areas are required), to label Cr(VI)
contaminated clothing and wastes, and to train on the hazards of Cr(VI)
have not changed.
    Recordkeeping. In the proposed standards for shipyards and
construction there were no recordkeeping requirements for exposure
records since there was not a requirement for exposure determination.
The final standard now requires exposure determination for shipyards
and construction and therefore, OSHA has also added provisions for
exposure records to be maintained in these final standards. In keeping
with its intent to be consistent with the Hazard Communication
Standard, OSHA has removed the requirement for training records in the
final standards.
    Dates. In the proposed standard, the effective date of the standard
was 60 days after the publication date; the start-up date for all
provisions except engineering controls was 90 days after the effective
date; and the start-up date for engineering controls was two years
after the effective date. OSHA believes that it is appropriate to allow
additional time for employers, particularly small employers, to meet
the requirements of the final rule. The effective and start-up dates
have been extended as follows: the effective date for the final rule is
changed to 90 days after the publication date; the start-up date for
all provisions except engineering controls is changed to 180 days after
the effective date for employers with 20 or more employees; the start-
up date for all provisions except engineering controls is changed to
one year after the effective date for employers with 19 or fewer
employees; and the start-up date for engineering controls is changed to
four years after the effective date for all employers.

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 standard
regulating occupational exposure to Cr(VI), 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. 29
U.S.C. Sec.  655(b)(5).

    The Supreme Court has held that before the Secretary can promulgate
any permanent health or safety standard, she 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 v. American Petroleum Institute, 448 U.S. 607, 641-42
(1980) (plurality opinion) (``The Benzene case''). 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 v. 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.'' American Textile Mfrs. Inst.
v. Donovan, 425 U.S. 490, 509 (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. See The Lead case, 647 F.2d 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.'' Id.

    [The] 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
Industrial Union Dept., AFL-CIO v. Hodgson, 499 F.2d 467 (D.C. Cir.
1974)).

    The courts have further observed that granting companies reasonable
time to comply with new PEL's may enhance economic feasibility. Id.
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. The Cotton dust case, 453
U.S. at 509. Finally, unlike safety standards, health standards must
eliminate risk or reduce it to the maximum extent that is
technologically and economically feasible. See International Union,
United Automobile, Aerospace & Agricultural Implement Workers of
America, UAW v. OSHA, 938 F.2d 1310, 1313 (D.C. Cir. 1991); Control of
Hazardous Energy Sources (Lockout/Tagout), Final rule; supplemental
statement of reasons, (58 FR 16612, March 30, 1993).

III. Events Leading to the Final Standard

    OSHA's previous standards for workplace exposure to Cr(VI) were
adopted in 1971, pursuant to section 6(a) of the Act, from a 1943
American National Standards Institute (ANSI) recommendation originally
established to control irritation and damage to nasal

tissues (36 FR at 10466, 5/29/71; Ex. 20-3). OSHA's general industry
standard set a permissible exposure limit (PEL) of 1 mg chromium
trioxide per 10 m\3\ air in the workplace (1 mg/10 m\3\
CrO3) as a ceiling concentration, which corresponds to a
concentration of 52 [mu]g/m\3\ Cr(VI). A separate rule promulgated for
the construction industry set an eight-hour time-weighted-average PEL
of 1 mg/10 m3 CrO3, also equivalent to 52 [mu]g/
m\3\ Cr(VI), adopted from the American Conference of Governmental
Industrial Hygienists (ACGIH) 1970 Threshold Limit Value (TLV) (36 FR
at 7340, 4/17/71).
    Following the ANSI standard of 1943, other occupational and public
health organizations evaluated Cr(VI) as a workplace and environmental
hazard and formulated recommendations to control exposure. The ACGIH
first recommended control of workplace exposures to chromium in 1946,
recommending a time-weighted average Maximum Allowable Concentration
(later called a Threshold Limit Value) of 100 [mu]g/m\3\ for chromic
acid and chromates as Cr2O3 (Ex. 5-37), and later
classified certain Cr(VI) compounds as class A1 (confirmed human)
carcinogens in 1974. In 1975, the NIOSH Criteria for a Recommended
Standard recommended that occupational exposure to Cr(VI) compounds
should be limited to a 10-hour TWA of 1 [mu]g/m\3\, except for some
forms of Cr(VI) then believed to be noncarcinogenic (Ex. 3-92). The
National Toxicology Program's First Annual Report on Carcinogens
identified calcium chromate, chromium chromate, strontium chromate, and
zinc chromate as carcinogens in 1980 (Ex. 35-157).
    During the 1980s, regulatory and standards organizations came to
recognize Cr(VI) compounds in general as carcinogens. The Environmental
Protection Agency (EPA) Health Assessment Document of 1984 stated that,

* * * using the IARC [International Agency for Research on Cancer]
classification scheme, the level of evidence available for the
combined animal and human data would place hexavalent chromium (Cr
VI) compounds into Group 1, meaning that there is decisive evidence
for the carcinogenicity of those compounds in humans (Ex. 19-1, p.
7-107).

    In 1988 IARC evaluated the available evidence regarding Cr(VI)
carcinogenicity, concluding in 1990 that

* * * [t]here is sufficient evidence in humans for the
carcinogenicity of chromium[VI] compounds as encountered in the
chromate production, chromate pigment production and chromium
plating industries, [and] sufficient evidence in experimental
animals for the carcinogenicity of calcium chromate, zinc chromates,
strontium chromate and lead chromates (Ex. 18-3, p. 213).

    In September 1988, NIOSH advised OSHA to consider all Cr(VI)
compounds as potential occupational carcinogens (Ex. 31-22-22). ACGIH
now classifies water-insoluble and water-soluble Cr(IV) compounds as
class A1 carcinogens (Ex. 35-207). Current ACGIH standards include
specific 8-hour time-weighted average TLVs for calcium chromate (1
[mu]g/m3), lead chromate (12 [mu]g/m3), strontium
chromate (0.5 [mu]g/m3), and zinc chromates (10 [mu]g/
m3), and generic TLVs for water soluble (50 [mu]g/
m3) and insoluble (10 [mu]g/m3) forms of
hexavalent chromium not otherwise classified, all measured as chromium
(Ex. 35-207).
    In July 1993, OSHA was petitioned for an emergency temporary
standard to reduce occupational exposures to Cr(VI) compounds (Ex. 1).
The Oil, Chemical, and Atomic Workers International Union (OCAW) and
Public Citizen's Health Research Group (Public Citizen), citing
evidence that occupational exposure to Cr(VI) increases workers' risk
of lung cancer, petitioned OSHA to promulgate an emergency temporary
standard to lower the PEL for Cr(VI) compounds to 0.5 [mu]g/
m3 as an eight-hour time-weighted average (TWA). Upon review
of the petition, OSHA agreed that there was evidence of increased
cancer risk from exposure to Cr(VI) at the existing PEL, but found that
the available data did not show the ``grave danger'' required to
support an emergency temporary standard (Ex. 1-C). The Agency therefore
denied the request for an emergency temporary standard, but initiated
Section 6(b)(5) rulemaking and began performing preliminary analyses
relevant to the rule.
    In 1997, Public Citizen petitioned the United States Court of
Appeals for the Third Circuit to compel OSHA to complete rulemaking
lowering the standard for occupational exposure to Cr(VI). The Court
denied Public Citizen's request, concluding that there was no
unreasonable delay and dismissed the suit. Oil, Chemical and Atomic
Workers Union and Public Citizen Health Research Group v. OSHA, 145
F.3d 120 (3rd Cir. 1998). Afterwards, the Agency continued its data
collection and analytic efforts on Cr(VI) (Ex. 35-208, p. 3). In 2002,
Public Citizen again petitioned the Court to compel OSHA to commence
rulemaking to lower the Cr(VI) standard (Ex. 31-24-1). Meanwhile on
August 22, 2002, OSHA published a Request for Information on Cr(VI) to
solicit additional information on key issues related to controlling
exposures to Cr(VI) (FR 67 at 54389), and on December 4, 2002 announced
its intent to proceed with developing a proposed standard (Ex. 35-306).
On December 24, 2002, the Court granted Public Citizen's petition, and
ordered the Agency to proceed expeditiously with a Cr(VI) standard. See
Public Citizen Health Research Group v. Chao, 314 F.3d 143 (3rd Cir.
2002)). In a subsequent order, the Court established a compressed
schedule for completion of the rulemaking, with deadlines of October 4,
2004 for publication of a proposed standard and January 18, 2006 for
publication of a final standard (Ex. 35-304).
    In 2003, as required by the Small Business Regulatory Enforcement
Act (SBREFA), OSHA initiated SBREFA proceedings, seeking the advice of
small business representatives on the proposed rule. The SBREFA panel,
including representatives from OSHA, the Small Business Administration
(SBA), and the Office of Management and Budget (OMB), was convened on
December 23, 2003. The panel conferred with representatives from small
entities in chemical, alloy, and pigment manufacturing, electroplating,
welding, aerospace, concrete, shipbuilding, masonry, and construction
on March 16-17, 2004, and delivered its final report to OSHA on April
20, 2004. The Panel's report, including comments from the small entity
representatives (SERS) and recommendations to OSHA for the proposed
rule, is available in the Cr(VI) rulemaking docket (Ex. 34). The SBREFA
Panel made recommendations on a variety of subjects. The most important
recommendations with respect to alternatives that OSHA should consider
included: A higher PEL than the PEL of 1; excluding cement from the
scope of the standard; the use of SECALs for some industries; different
PELS for different Hexavalent chromium compounds; a multi-year phase-in
to the standards; and further consideration to approaches suited to the
special conditions of the maritime and construction industries. OSHA
has adapted many of these recommendations: The PEL is now 5; cement has
been excluded from the scope of the standard; a compliance alternative,
similar to a SECAL, has been used in aerospace industry; the standard
allows four years to phase in engineering controls; and a new
performance based monitoring approach for all industries, among other
changes, all of which should make it easier for all

industries with changing work place conditions to meet the standard in
a cost effective way. A full discussion of all of the recommendations,
and OSHA's responses to them, is provided in Section VIII of this
Preamble.
    In addition to undertaking SBREFA proceedings, in early 2004, OSHA
provided the Advisory Committee on Construction Safety and Health
(ACCSH) and the Maritime Advisory Committee on Occupational Safety and
Health (MACOSH) with copies of the draft proposed rule for review. OSHA
representatives met with ACCSH in February 2004 and May 2004 to discuss
the rulemaking and receive their comments and recommendations. On
February 13, 2004, ACCSH recommended that portland cement should be
included within the scope of the proposed standard (Ex. 35-307, pp.
288-293) and that identical PELs should be set for construction,
maritime, and general industry (Ex. 35-307, pp. 293-297). On May 18,
2004, ACCSH recommended that the construction industry should be
included in the current rulemaking, and affirmed its earlier
recommendation regarding portland cement. OSHA representatives met with
MACOSH in March 2004. On March 3, 2004, MACOSH collected and forwarded
additional exposure monitoring data to OSHA to help the Agency better
evaluate exposures to Cr(VI) in shipyards (Ex. 35-309, p. 208). MACOSH
also recommended a separate Cr(VI) standard for the maritime industry,
arguing that maritime involves different exposures and requires
different means of exposure control than general industry and
construction (Ex. 35-309, p. 227).
    In accordance with the Court's rulemaking schedule, OSHA published
the proposed standard for hexavalent chromium on October 4, 2004 (69 FR
at 59306). The proposal included a notice of public hearing in
Washington, DC (69 FR at 59306, 59445-59446). The notice also invited
interested persons to submit comments on the proposal until January 3,
2005. In the proposal, OSHA solicited public input on 65 issues
regarding the human health risks of Cr(VI) exposure, the impact of the
proposed rule on Cr(VI) users, and other issues of particular interest
to the Agency (69 FR at 59306-59312).
    OSHA convened the public hearing on February 1, 2005, with
Administrative Law Judges John M. Vittone and Thomas M. Burke
presiding. At the conclusion of the hearing on February 15, 2005, Judge
Burke set a deadline of March 21, 2005, for the submission of post
hearing comments, additional information and data relevant to the
rulemaking, and a deadline of April 20, 2005, for the submission of
additional written comments, arguments, summations, and briefs. A wide
range of employees, employers, union representatives, trade
associations, government agencies and other interested parties
participated in the public hearing or contributed written comments.
Issues raised in their comments and testimony are addressed in the
relevant sections of this preamble (e.g., comments on the risk
assessment are discussed in section VI; comments on the benefits
analysis in section VIII). On December 22, 2005, OSHA filed a motion
with the U.S. Court of Appeals for the Third Circuit requesting an
extension of the court-mandated deadline for the publication of the
final rule by six weeks, to February 28, 2006 (Ex. 48-13). The Court
granted the request on January 17, 2006 (Ex. 48-15).
    As mandated by the Act, the final standard on occupational exposure
to hexavalent chromium is based on careful consideration of the entire
record of this proceeding, including materials discussed or relied upon
in the proposal, the record of the hearing, and all written comments
and exhibits received.
    OSHA has developed separate final standards for general industry,
shipyards, and the construction industry. The Agency has concluded that
excess exposure to Cr(VI) in any form poses a significant risk of
material impairment to the health of workers, by causing or
contributing to adverse health effects including lung cancer, non-
cancer respiratory effects, and dermal effects. OSHA determined that
the TWA PEL should not be set above 5 [mu]g/m3 based on the
evidence in the record and its own quantitative risk assessment. The
TWA PEL of 5 [mu]g/m3 reduces the significant risk posed to
workers by occupational exposure to Cr(VI) to the maximum extent that
is technologically and economically feasible. (See discussion of the
PEL in Section XV below.)

IV. Chemical Properties and Industrial Uses

    Chromium is a metal that exists in several oxidation or valence
states, ranging from chromium (-II) to chromium (+VI). The elemental
valence state, chromium (0), does not occur in nature. Chromium
compounds are very stable in the trivalent state and occur naturally in
this state in ores such as ferrochromite, or chromite ore
(FeCr2O4). The hexavalent, Cr(VI) or chromate, is
the second most stable state. It rarely occurs naturally; most Cr(VI)
compounds are man made.
    Chromium compounds in higher valence states are able to undergo
``reduction'' to lower valence states; chromium compounds in lower
valence states are able to undergo ``oxidation'' to higher valence
states. Thus, Cr(VI) compounds can be reduced to Cr(III) in the
presence of oxidizable organic matter. Chromium can also be reduced in
the presence of inorganic chemicals such as iron.
    Chromium does exist in less stable oxidation (valence) states such
as Cr(II), Cr(IV), and Cr(V). Anhydrous Cr(II) salts are relatively
stable, but the divalent state (II, or chromous) is generally
relatively unstable and is readily oxidized to the trivalent (III or
chromic) state. Compounds in valence states such as (IV) and (V)
usually require special handling procedures as a result of their
instability. Cr(IV) oxide (CrO2) is used in magnetic
recording and storage devices, but very few other Cr(IV) compounds have
industrial use. Evidence exists that both Cr(IV) and Cr(V) are formed
as transient intermediates in the reduction of Cr(VI) to Cr(III) in the
body.
    Chromium (III) is also an essential nutrient that plays a role in
glucose, fat, and protein metabolism by causing the action of insulin
to be more effective. Chromium picolinate, a trivalent form of chromium
combined with picolinic acid, is used as a dietary supplement, because
it is claimed to speed metabolism.
    Elemental chromium and the chromium compounds in their different
valence states have various physical and chemical properties, including
differing solubilities. Most chromium species are solid. Elemental
chromium is a steel gray solid, with high melting and boiling points
(1857 [deg]C and 2672 [deg]C, respectively), and is insoluble in water
and common organic solvents. Chromium (III) chloride is a violet or
purple solid, with high melting and sublimation points (1150 [deg]C and
1300 [deg]C, respectively), and is slightly soluble in hot water and
insoluble in common organic solvents. Ferrochromite is a brown-black
solid; chromium (III) oxide is a green solid; and chromium (III)
sulfate is a violet or red solid, insoluble in water and slightly
soluble in ethanol. Chromium (III) picolinate is a ruby red crystal
soluble in water (1 part per million at 25 [deg]C). Chromium (IV) oxide
is a brown-black solid that decomposes at 300 [deg]C and is insoluble
in water.
    Cr(VI) compounds have mostly lemon yellow to orange to dark red
hues. They are typically crystalline, granular, or powdery although one
compound (chromyl chloride) exists in liquid form. For example, chromyl
chloride is a dark

red liquid that decomposes into chromate ion and hydrochloric acid in
water. Chromic acids are dark red crystals that are very soluble in
water. Other examples of soluble chromates are sodium chromate (yellow
crystals) and sodium dichromate (reddish to bright orange crystals).
Lead chromate oxide is typically a red crystalline powder. Zinc
chromate is typically seen as lemon yellow crystals which decompose in
hot water and are soluble in acids and liquid ammonia. Other chromates
such as barium, calcium, lead, strontium, and zinc chromates vary in
color from light yellow to greenish yellow to orange-yellow and exist
in solid form as crystals or powder.
    The Color Pigments Manufacturers Association (CPMA) provided
additional information on lead chromate and some other chromates used
in their pigments (Ex. 38-205, pp. 12-13). CPMA describes two main lead
chromate color groups: the chrome yellow pigments and the orange to red
varieties known as molybdate orange pigments. The chrome yellow
pigments are solid solution crystal compositions of lead chromate and
lead sulfate. Molybdate orange pigments are solid solution crystal
compositions of lead chromate, lead sulfate, and lead molybdate (Ex.
38-205, p. 12). CPMA also describes a basic lead chromate called
``chrome orange,'' and a lead chromate precipitated ``onto a core'' of
silica (Ex. 38-205, p. 13).
    OSHA re-examined available information on solubility values in
light of comments from the CPMA and Dominion Color Corporation (DCC) on
qualitative solubility designations and CPMA's claim of low
bioavailability of lead chromate due to its extremely low solubility
(Exs. 38-201-1, p. 4; 38-205, p. 95). There was not always agreement or
consistency with the qualitative assignments of solubilities.
Quantitative values for the same compound also differ depending on the
source of information.
    The Table IV-1 is the result of OSHA's re-examination of
quantitative water solubility values and qualitative designations.
Qualitative designations as well as quantitative values are listed as
they were provided by the source. As can be seen by the Table IV-1,
qualitative descriptions vary by the descriptive terminology chosen by
the source.
BILLING CODE 4510-26-P

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BILLING CODE 4510-26-C
    OSHA has made some generalizations to describe the water
solubilities of chromates in subsequent sections of this Federal
Register notice. OSHA has divided Cr(VI) compounds and mixtures into
three categories based on solubility values. Compounds and mixtures
with water solubilities less than 0.01 g/l are referred to as water
insoluble. Compounds and mixtures between 0.01 g/l and 500 g/l are
referred to as slightly

soluble. Compounds and mixtures with water solubility values of 500 g/l
or greater are referred to as highly water soluble. It should be noted
that these boundaries for insoluble, slightly soluble, and highly
soluble are arbitrary designations for the sake of further description
elsewhere in this document. Quantitative values take precedence over
qualitative designations. For example, zinc chromates would be slightly
soluble where their solubility values exceed 0.01 g/l.
    Some major users of chromium are the metallurgical, refractory, and
chemical industries. Chromium is used by the metallurgical industry to
produce stainless steel, alloy steel, and nonferrous alloys. Chromium
is alloyed with other metals and plated on metal and plastic substrates
to improve corrosion resistance and provide protective coatings for
automotive and equipment accessories. Welders use stainless steel
welding rods when joining metal parts.
    Cr(VI) compounds are widely used in the chemical industry in
pigments, metal plating, and chemical synthesis as ingredients and
catalysts. Chromates are used as high quality pigments for textile
dyes, paints, inks, glass, and plastics. Cr(VI) can be produced during
welding operations even if the chromium was originally present in
another valence state. While Cr(VI) is not intentionally added to
portland cement, it is often present as an impurity.
    Occupational exposures to Cr(VI) can occur from inhalation of mists
(e.g., chrome plating, painting), dusts (e.g., inorganic pigments), or
fumes (e.g., stainless steel welding), and from dermal contact (e.g.,
cement workers).
    There are about thirty major industries and processes where Cr(VI)
is used. These include producers of chromates and related chemicals
from chromite ore, electroplating, welding, painting, chromate pigment
production and use, steel mills, and iron and steel foundries. A
detailed discussion of the uses of Cr(VI) in industry is found in
Section VIII of this preamble.

V. Health Effects

    This section summarizes key studies of adverse health effects
resulting from exposure to hexavalent chromium (Cr(VI)) in humans and
experimental animals, as well as information on the fate of Cr(VI) in
the body and laboratory research that relates to its toxic mode of
action. The primary health impairments from workplace exposure to
Cr(VI) are lung cancer, asthma, and damage to the nasal epithelia and
skin. While this chapter on health effects does not describe all of the
many studies that have been conducted on Cr(VI) toxicity, it includes a
selection of those that are relevant to the rulemaking and
representative of the scientific literature on Cr(VI) health effects.

A. Absorption, Distribution, Metabolic Reduction and Elimination

    Although chromium can exist in a number of different valence
states, Cr(VI) is the form considered to be the greatest health risk.
Cr(VI) enters the body by inhalation, ingestion, or absorption through
the skin. For occupational exposure, the airways and skin are the
primary routes of uptake. The following discussion summarizes key
aspects of Cr(VI) uptake, distribution, metabolism, and elimination.

1. Deposition and Clearance of Inhaled Cr(VI) From the Respiratory
Tract

    Various anatomical, physical and physiological factors determine
both the fractional and regional deposition of inhaled particulate
matter. Due to the airflow patterns in the lung, more particles tend to
deposit at certain preferred regions in the lung. It is therefore
possible to have a buildup of chromium at certain sites in the
bronchial tree that could create areas of very high chromium
concentration. A high degree of correspondence between the efficiency
of particle deposition and the frequency of bronchial tumors at sites
in the upper bronchial tree was reported in research by Schlesinger and
Lippman that compared the distribution of cancer sites in published
reports of primary bronchogenic tumors with experimentally determined
particle deposition patterns (Ex. 35-102).
    Large inhaled particles (>5 [mu]m) are efficiently removed from the
air-stream in the extrathoracic region (Ex. 35-175). Particles greater
than 2.5 [mu]m are generally deposited in the tracheobronchial regions,
whereas particles less than 2.5 [mu]m are generally deposited in the
pulmonary region. Some larger particles (>2.5 [mu]m) can reach the
pulmonary region. The mucociliary escalator predominantly clears
particles that deposit in the extrathoracic and the tracheobronchial
region of the lung. Individuals exposed to high particulate levels of
Cr(VI) may also have altered respiratory mucociliary clearance.
Particulates that reach the alveoli can be absorbed into the
bloodstream or cleared by phagocytosis.
2. Absorption of Inhaled Cr(VI) Into the Bloodstream
    The absorption of inhaled chromium compounds depends on a number of
factors, including physical and chemical properties of the particles
(oxidation state, size, solubility) and the activity of alveolar
macrophages (Ex. 35-41). The hexavalent chromate anions
(CrO4)2- enter cells via facilitated diffusion
through non-specific anion channels (similar to phosphate and sulfate
anions). As demonstrated in research by Suzuki et al., a portion of
water soluble Cr(VI) is rapidly transported to the bloodstream in rats
(Ex. 35-97). Rats were exposed to 7.3-15.9 mg Cr(VI)/m\3\ as potassium
dichromate for 2-6 hours. Following exposure to Cr(VI), the ratio of
blood chromium/lung chromium was 1.440.30 at 0.5 hours,
0.810.10 at 18 hours, 0.850.20 at 48 hours, and
0.960.22 at 168 hours after exposure.
    Once the Cr(VI) particles reach the alveoli, absorption into the
bloodstream is greatly dependent on solubility. More soluble chromates
are absorbed faster than water insoluble chromates, while insoluble
chromates are poorly absorbed and therefore have longer resident time
in the lungs. This effect has been demonstrated in research by Bragt
and van Dura on the kinetics of three Cr(VI) compounds: highly soluble
sodium chromate, slightly soluble zinc chromate and water insoluble
lead chromate (Ex. 35-56). They instilled \51\chromium-labeled
compounds (0.38 mg Cr(VI)/kg as sodium chromate, 0.36 mg Cr(VI)/kg as
zinc chromate, or 0.21 mg Cr(VI)/kg as lead chromate) intratracheally
in rats. Peak blood levels of \51\chromium were reached after 30
minutes for sodium chromate (0.35 [mu]g chromium/ml), and after 24
hours for zinc chromate (0.60 [mu]g chromium/ml) and lead chromate
(0.007 [mu]g chromium/ml). At 30 minutes after administration, the
lungs contained 36, 25, and 81% of the respective dose of the sodium,
zinc, and lead chromate. On day six, >80% of the dose of all three
compounds had been cleared from the lungs, during which time the
disappearance from lungs followed linear first-order kinetics. The
residual amount left in the lungs on day 50 or 51 was 3.0, 3.9, and
13.9%, respectively. From these results authors concluded that zinc
chromate, which is less soluble than sodium chromate, is more slowly
absorbed from the lungs. Lead chromate was more poorly and slowly
absorbed, as indicated by very low levels in blood and greater
retention in the lungs. The authors also noted that the kinetics of
sodium and zinc chromates were very similar. Zinc chromate, which is
less soluble than sodium chromate, was slowly absorbed from the lung,
but the maximal blood levels were higher than those resulting from an
equivalent dose of sodium chromate. The authors

believe that this was probably the result of hemorrhages
macroscopically visible in the lungs of zinc chromate-treated rats 24
hours following intratracheal administration. Boeing Corporation
commented that this study does not show that the highly water soluble
sodium chromate is cleared more rapidly or retained in the lung for
shorter periods than the less soluble zinc chromate (Ex. 38-106-2, p.
18-19). This comment is addressed in the Carcinogenic Effects
Conclusion Section V.B.9 dealing with the carcinogenicity of slightly
soluble Cr(VI) compounds.
    Studies by Langard et al. and Adachi et al. provide further
evidence of absorption of chromates from the lungs (Exs. 35-93; 189).
In Langard et al., rats exposed to 2.1 mg Cr(VI)/m\3\ as zinc chromate
for 6 hours/day achieved steady state concentrations in the blood after
4 days of exposure (Ex. 35-93). Adachi et al. studied rats that were
subject to a single inhalation exposure to chromic acid mist generated
from electroplating at a concentration of 3.18 mg Cr(VI)/m\3\ for 30
minutes which was then rapidly absorbed from the lungs (Ex. 189). The
amount of chromium in the lungs of these rats declined from 13.0 mg
immediately after exposure to 1.1 mg after 4 weeks, with an overall
half-life of five days.
    Several other studies have reported absorption of chromium from the
lungs after intratracheal instillation (Exs. 7-9; 9-81; Visek et al.
1953 as cited in Ex. 35-41). These studies indicated that 53-85% of
Cr(VI) compounds (particle size < 5 [mu]m) were cleared from the lungs
by absorption into the bloodstream or by mucociliary clearance in the
pharynx; the rest remained in the lungs. Absorption of Cr(VI) from the
respiratory tract of workers has been shown in several studies that
identified chromium in the urine, serum and red blood cells following
occupational exposure (Exs. 5-12; 35-294; 35-84).
    Evidence indicates that even chromates encapsulated in a paint
matrix may be released in the lungs (Ex. 31-15, p. 2). In a study of
chromates in aircraft spray paint, LaPuma et al. measured the mass of
Cr(VI) released from particles into water originating from three types
of paint particles: solvent-borne epoxy (25% strontium chromate
(SrCrO4)), water-borne epoxy (30% SrCrO4) and
polyurethane (20% SrCrO4) (Ex. 31-2-1). The mean fraction of
Cr(VI) released into the water after one and 24 hours for each primer
averaged: 70% and 85% (solvent epoxy), 74% and 84% (water epoxy), and
94% and 95% (polyurethane). Correlations between particle size and the
fraction of Cr(VI) released indicated that smaller particles (< 5 [mu]m)
release a larger fraction of Cr(VI) versus larger particles (>5 [mu]m).
This study demonstrates that the paint matrix only modestly hinders
Cr(VI) release into a fluid, especially with smaller particles. Larger
particles, which contain the majority of Cr(VI) due to their size,
appear to release proportionally less Cr(VI) (as a percent of total
Cr(VI)) than smaller particles. Some commenters suggested that the
above research shows that the slightly soluble Cr(VI) from aircraft
spray paint is less likely to reach and be absorbed in the
bronchoalveolar region of the lung than a highly soluble Cr(VI) form,
such as chromic acid aerosol (Exs. 38-106-2; 39-43, 44-33). This issue
is further discussed in the Carcinogenic Effects Conclusion Section
V.B.9.a and in the Quantitative Risk Assessment Section VI.G.4.a.
    A number of questions remain unanswered regarding encapsulated
Cr(VI) and bioavailability from the lung. There is a lack of detailed
information on the efficiency of encapsulation and whether all of the
chromate molecules are encapsulated. The stability of the encapsulated
product in physiological and environmental conditions over time has not
been demonstrated. Finally, the fate of inhaled encapsulated Cr(VI) in
the respiratory tract and the extent of distribution in systemic
tissues has not been thoroughly studied.
3. Dermal Absorption of Cr(VI)
    Both human and animal studies demonstrate that Cr(VI) compounds are
absorbed after dermal exposure. Dermal absorption depends on the
oxidation state of chromium, the vehicle and the integrity of the skin.
Cr(VI) readily traverses the epidermis to the dermis (Exs. 9-49; 309).
The histological distribution of Cr(VI) within intact human skin was
studied by Liden and Lundberg (Ex. 35-80). They applied test solutions
of potassium dichromate in petrolatum or in water as occluded circular
patches of filter paper to the skin. Results with potassium dichromate
in water revealed that Cr(VI) penetrated beyond the dermis and
penetration reached steady state with resorption by the lymph and blood
vessels by 5 hours. About 10 times more chromium penetrated when
potassium dichromate was applied in petrolatum than when applied in
water, indicating that organic solvents facilitate the absorption of
Cr(VI) from the skin. Research by Baranowska-Dutkiewicz also
demonstrated that the absorption rates of sodium chromate solutions
from the occluded forearm skin of volunteers increase with increasing
concentration (Ex. 35-75). The rates were 1.1 [mu]g Cr(VI)/cm\2\/hour
for a 0.01 molar solution, 6.4 [mu]g Cr(VI)/cm\2\/hour for a 0.1 molar
solution, and 10 [mu]g Cr(VI)/cm\2\/hour for a 0.2 molar solution.
    Additional studies have demonstrated that the absorption of Cr(VI)
compounds can take place through the dermal route. Using volunteers,
Mali found that potassium dichromate penetrates the intact epidermis
(Exs. 9-49; 35-41). Wahlberg and Skog demonstrated the presence of
chromium in the blood, spleen, bone marrow, lymph glands, urine and
kidneys of guinea pigs dermally exposed to \51\chromium labeled Cr(VI)
compounds (Ex. 35-81).
4. Absorption of Cr(VI) by the Oral Route
    Inhaled Cr(VI) can enter the digestive tract as a result of
mucocilliary clearance and swallowing. Studies indicate Cr(VI) is
absorbed from the gastrointestinal tract. For example, in a study by
Donaldson and Barreras, the six-day fecal and 24-hour urinary excretion
patterns of radioactivity in groups of six volunteers given Cr(VI) as
sodium chromate labeled with \51\chromium indicated that at least 2.1%
of the Cr(VI) was absorbed. After intraduodenal administration at least
10% of the Cr(VI) compound was absorbed. These studies also
demonstrated that Cr(VI) compounds are reduced to Cr(III) compounds in
the stomach, thereby accounting for the relatively poor
gastrointestinal absorption of orally administered Cr(VI) compounds
(Exs. 35-96; 35-41). In the gastrointestinal tract, Cr(VI) can be
reduced to Cr(III) by gastric juices, which is then poorly absorbed
(Underwood, 1971 as cited in Ex. 19-1; Ex. 35-85).
    In a study conducted by Clapp et al., treatment of rats by gavage
with an unencapsulated lead chromate pigment or with a silica-
encapsulated lead chromate pigment resulted in no measurable blood
levels of chromium (measured as Cr(III), detection limit = 10 [mu]g/L)
after two or four weeks of treatment or after a two-week recovery
period. However, kidney levels of chromium (measured as Cr(III)) were
significantly higher in the rats that received the unencapsulated
pigment when compared to the rats that received the encapsulated
pigment, indicating that silica encapsulation may reduce the
gastrointestinal bioavailability of chromium from lead chromate
pigments (Ex. 11-5). This study does not address the bioavailability of
encapsulated chromate pigments from the lung where residence time could
be different.

5. Distribution of Cr(VI) in the Body
    Once in the bloodstream, Cr(VI) is taken up into erythrocytes,
where it is reduced to lower oxidation states and forms chromium
protein complexes during reduction (Ex. 35-41). Once complexed with
protein, chromium cannot leave the cell and chromium ions are unable to
repenetrate the membrane and move back into the plasma (Exs. 7-6; 7-7;
19-1; 35-41; 35-52). Once inside the blood cell, the intracellular
Cr(VI) reduction to Cr(III) depletes Cr(VI) concentration in the red
blood cell (Ex. 35-89). This serves to enhance diffusion of Cr(VI) from
the plasma into the erythrocyte resulting in very low plasma levels of
Cr(VI). It is also believed that the rate of uptake of Cr(VI) by red
blood cells may not exceed the rate at which they reduce Cr(VI) to
Cr(III) (Ex. 35-99). The higher tissue levels of chromium after
administration of Cr(VI) than after administration of Cr(III) reflect
the greater tendency of Cr(VI) to traverse plasma membranes and bind to
intracellular proteins in the various tissues, which may explain the
greater degree of toxicity associated with Cr(VI) (MacKenzie et al.
1958 as cited in 35-52; Maruyama 1982 as cited in 35-41; Ex. 35-71).
    Examination of autopsy tissues from chromate workers who were
occupationally exposed to Cr(VI) showed that the highest chromium
levels were in the lungs. The liver, bladder, and bone also had
chromium levels above background. Mancuso examined tissues from three
individuals with lung cancer who were exposed to chromium in the
workplace (Ex. 124). One was employed for 15 years as a welder, the
second and third worked for 10.2 years and 31.8 years, respectively, in
ore milling and preparations and boiler operations. The cumulative
chromium exposures for the three workers were estimated to be 3.45,
4.59, and 11.38 mg/m\3\-years, respectively. Tissues from the first
worker were analyzed 3.5 years after last exposure, the second worker
18 years after last exposure, and the third worker 0.6 years after last
exposure. All tissues from the three workers had elevated levels of
chromium, with the possible exception of neural tissues. Levels were
orders of magnitude higher in the lungs when compared to other tissues.
Similar results were also reported in autopsy studies of people who may
have been exposed to chromium in the workplace as well as chrome
platers and chromate refining workers (Exs. 35-92; 21-1; 35-74; 35-88).
    Animal studies have shown similar distribution patterns after
inhalation exposure. For example, a study by Baetjer et al.
investigated the distribution of Cr(VI) in guinea pigs after
intratracheal instillation of slightly soluble potassium dichromate
(Ex. 7-8). At 24 hours after instillation, 11% of the original dose of
chromium from potassium dichromate remained in the lungs, 8% in the
erythrocytes, 1% in plasma, 3% in the kidney, and 4% in the liver. The
muscle, skin, and adrenal glands contained only a trace. All tissue
concentrations of chromium declined to low or nondetectable levels in
140 days, with the exception of the lungs and spleen.
6. Metabolic Reduction of Cr(VI)
    Cr(VI) is reduced to Cr(III) in the lungs by a variety of reducing
agents. This serves to limit uptake into lung cells and absorption into
the bloodstream. Cr(V) and Cr(IV) are transient intermediates in this
process. The genotoxic effects produced by the Cr(VI) are related to
the reduction process and are further discussed in the section V.B.8 on
Mechanistic Considerations.
    In vivo and in vitro experiments in rats indicated that, in the
lungs, Cr(VI) can be reduced to Cr(III) by ascorbate and glutathione. A
study by Suzuki and Fukuda showed that the reduction of Cr(VI) by
glutathione is slower than the reduction by ascorbate (Ex. 35-65).
Other studies have reported the reduction of Cr(VI) to Cr(III) by
epithelial lining fluid (ELF) obtained from the lungs of 15 individuals
by bronchial lavage. The average overall reduction capacity was 0.6
[mu]g Cr(VI)/mg of ELF protein. In addition, cell extracts made from
pulmonary alveolar macrophages derived from five healthy male
volunteers were able to reduce an average of 4.8 [mu]g Cr(VI)/10\6\
cells or 14.4 [mu]g Cr(VI)/mg protein (Ex. 35-83). Postmitochondrial
(S12) preparations of human lung cells (peripheral lung parenchyma and
bronchial preparations) were also able to reduce Cr(VI) to Cr(III) (De
Flora et al. 1984 as cited in Ex. 35-41).
7. Elimination of Cr(VI) From the Body
    Excretion of chromium from Cr(VI) compounds is predominantly in the
urine, although there is some biliary excretion into the feces. In both
urine and feces, the chromium is present as low molecular weight
Cr(III) complexes. Absorbed chromium is excreted from the body in a
rapid phase representing clearance from the blood and at least two
slower phases representing clearance from tissues. Urinary excretion
accounts for over 50% of eliminated chromium (Ex. 35-41). Although
chromium is excreted in urine and feces, the intestine plays only a
minor part in chromium elimination, representing only about 5% of
elimination from the blood (Ex. 19-1). Normal urinary levels of
chromium in humans have been reported to range from 0.24-1.8 [mu]g/L
with a median level of 0.4 [mu]g/L (Ex. 35-79). Humans exposed to 0.01-
0.1 mg Cr(VI)/m\3\ as potassium dichromate (8-hour time-weighted
average) had urinary excretion levels from 0.0247 to 0.037 mg Cr(III)/
L. Workers exposed mainly to Cr(VI) compounds had higher urinary
chromium levels than workers exposed primarily to Cr(III) compounds. An
analysis of the urine did not detect Cr(VI), indicating that Cr(VI) was
rapidly reduced before excretion (Exs. 35-294; 5-48).
    A half-life of 15-41 hours has been estimated for chromium in urine
for four welders using a linear one-compartment kinetic model (Exs. 35-
73; 5-52; 5-53). Limited work on modeling the absorption and deposition
of chromium indicates that adipose and muscle tissue retain chromium at
a moderate level for about two weeks, while the liver and spleen store
chromium for up to 12 months. The estimated half-life for whole body
chromium retention is 22 days for Cr(VI) (Ex. 19-1). The half-life of
chromium in the human lung is 616 days, which is similar to the half-
life in rats (Ex. 7-5).
    Elimination of chromium was shown to be very slow in rats exposed
to 2.1 mg Cr(VI)/m\3\ as zinc chromate six hours/day for four days.
Urinary levels of chromium remained almost constant for four days after
exposure and then decreased (Ex. 35-93). After intratracheal
administration of sodium dichromate to rats, peak urinary chromium
concentrations were observed at six hours, after which the urinary
concentrations declined rapidly (Ex. 35-94). The more prolonged
elimination of the moderately soluble zinc chromate as compared to the
more soluble sodium dichromate is consistent with the influence of
Cr(VI) solubility on absorption from the respiratory tract discussed
earlier.
    Information regarding the excretion of chromium in humans after
dermal exposure to chromium or its compounds is limited. Fourteen days
after application of a salve containing water soluble potassium
chromate, which resulted in skin necrosis and sloughing at the
application site, chromium was found at 8 mg/L in the urine and 0.61
mg/100 g in the feces of one individual (Brieger 1920 as cited in Ex.
19-1). A slight increase over background levels of urinary chromium was
observed in four

subjects submersed in a tub of chlorinated water containing 22 mg
Cr(VI)/L as potassium dichromate for three hours (Ex. 31-22-6). For
three of the four subjects, the increase in urinary chromium excretion
was less than 1 [mu]g/day over the five-day collection period. Chromium
was detected in the urine of guinea pigs after radiolabeled sodium
chromate solution was applied to the skin (Ex. 35-81).
8. Physiologically-Based Pharmacokinetic Modeling
    Physiologically-based pharmacokinetic (PBPK) models have been
developed that simulate absorption, distribution, metabolism, and
excretion of Cr(VI) and Cr(III) compounds in humans (Ex. 35-95) and
rats (Exs. 35-86; 35-70). The original model (Ex. 35-86) evolved from a
similar model for lead, and contained compartments for the lung, GI
tract, skin, blood, liver, kidney, bone, well-perfused tissues, and
slowly perfused tissues. The model was refined to include two lung
subcompartments for chromium, one of which allowed inhaled chromium to
enter the blood and GI tract and the other only allowed chromium to
enter the GI tract (Ex. 35-70). Reduction of Cr(VI) to Cr(III) was
considered to occur in every tissue compartment except bone.
    The model was developed from several data sets in which rats were
dosed with Cr(VI) or Cr(III) intravenously, orally or by intratracheal
instillation, because different distribution and excretion patterns
occur depending on the route of administration. In most cases, the
model parameters (e.g., tissue partitioning, absorption, reduction
rates) were estimated by fitting model simulations to experimental
data. The optimized rat model was validated against the 1978 Langard
inhalation study (Ex. 35-93). Chromium blood levels were overpredicted
during the four-day inhalation exposure period, but blood levels during
the post-exposure period were well predicted by the model. The model-
predicted levels of liver chromium were high, but other tissue levels
were closely estimated.
    A human PBPK model recently developed by O'Flaherty et al. is able
to predict tissue levels from ingestion of Cr(VI) (Ex. 35-95). The
model incorporates differential oral absorption of Cr(VI) and Cr(III),
rapid reduction of Cr(VI) to Cr(III) in major body fluids and tissues,
and concentration-dependent urinary clearance. The model does not
include a physiologic lung compartment, but can be used to estimate an
upper limit on pulmonary absorption of inhaled chromium. The model was
calibrated against blood and urine chromium concentration data from a
group of controlled studies in which adult human volunteers drank
solutions of soluble Cr(III) or Cr(VI).
    PBPK models are increasingly used in risk assessments, primarily to
predict the concentration of a potentially toxic chemical that will be
delivered to any given target tissue following various combinations of
route, dose level, and test species. Further development of the
respiratory tract portion of the model, specific Cr(VI) rate data on
extracellular reduction and uptake into lung cells, and more precise
understanding of critical pathways inside target cells would improve
the model value for risk assessment purposes.
9. Summary
    Based on the studies presented above, evidence exists in the
literature that shows Cr(VI) can be systemically absorbed by the
respiratory tract. The absorption of inhaled chromium compounds depends
on a number of factors, including physical and chemical properties of
the particles (oxidation state, size, and solubility), the reduction
capacity of the ELF and alveolar macrophages and clearance by the
mucocliary escalator and phagocytosis. Highly water soluble Cr(VI)
compounds (e.g. sodium chromate) enter the bloodstream more readily
than highly insoluble Cr(VI) compounds (e.g. lead chromate). However,
insoluble compounds may have longer residence time in lung. Absorption
of Cr(VI) can also take place after oral and dermal exposure,
particularly if the exposures are high.
    The chromate (CrO4) 2- enters cells via
facilitated diffusion through non-specific anion channels (similar to
phosphate and sulfate anions). Following absorption of Cr(VI) compounds
from various exposure routes, chromium is taken up by the blood cells
and is widely distributed in tissues as Cr(VI). Inside blood cells and
tissues, Cr(VI) is rapidly reduced to lower oxidation states and bound
to macromolecules which may result in genotoxic or cytotoxic effects.
However, in the blood a substantial proportion of Cr(VI) is taken up
into erythrocytes, where it is reduced to Cr(III) and becomes bound to
hemoglobin and other proteins.
    Inhaled Cr(VI) is reduced to Cr(III) in vivo by a variety of
reducing agents. Ascorbate and glutathione in the ELF and macrophages
have been shown to reduce Cr(VI) to Cr(III) in the lungs. After oral
exposure, gastric juices are also responsible for reducing Cr(VI) to
Cr(III). This serves to limit the amount of Cr(VI) systemically
absorbed.
    Absorbed chromium is excreted from the body in a rapid phase
representing clearance from the blood and at least two slower phases
representing clearance from tissues. Urinary excretion is the primary
route of elimination, accounting for over 50% of eliminated chromium.
Although chromium is excreted in urine and feces, the intestine plays
only a minor part in chromium elimination representing only about 5% of
elimination from the blood.

B. Carcinogenic Effects

    There has been extensive study on the potential for Cr(VI) to cause
carcinogenic effects, particularly cancer of the lung. OSHA reviewed
epidemiologic data from several industry sectors including chromate
production, chromate pigment production, chromium plating, stainless
steel welding, and ferrochromium production. Supporting evidence from
animal studies and mechanistic considerations are also evaluated in
this section.
1. Evidence from Chromate Production Workers
    The epidemiologic literature of workers in the chromate production
industry represents the earliest and best-documented relationship
between exposure to chromium and lung cancer. The earliest study of
chromate production workers in the United States was reported by Machle
and Gregorius in 1948 (Ex. 7-2). In the United States, two chromate
production plants, one in Baltimore, MD, and one in Painesville, OH,
have been the subject of multiple studies. Both plants were included in
the 1948 Machle and Gregorius study and again in the study conducted by
the Public Health Service and published in 1953 (Ex. 7-3). Both of
these studies reported the results in aggregate. The Baltimore chromate
production plant was studied by Hayes et al. (Ex. 7-14) and more
recently by Gibb et al. (Ex. 31-22-11). The chromate production plant
in Painesville, OH, has been followed since the 1950s by Mancuso with
his most recent follow-up published in 1997. The most recent study of
the Painesville plant was published by Luippold et al. (Ex. 31-18-4).
The studies by Gibb and Luippold present historical exposure data for
the time periods covered by their respective studies. The Gibb exposure
data are especially interesting since the industrial hygiene data were
collected on a routine basis and not for compliance purposes. These
routine air

measurements may be more representative of those typically encountered
by the exposed workers. In Great Britain, three plants have been
studied repeatedly, with reports published between 1952 and 1991. Other
studies of cohorts in the United States, Germany, Italy and Japan are
also reported. The elevated lung cancer mortality reported in the great
majority of these cohorts and the significant upward trends with
duration of employment and cumulative exposure provide some of the
strongest evidence that Cr(VI) is carcinogenic to workers. A summary of
selected human epidemiologic studies in chromate production workers is
presented in Table V-1.

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BILLING CODE 4510-26-C
    The basic hexavalent chromate production process involves milling
and mixing trivalent chromite ore with soda ash, sometimes in the
presence of lime (Exs. 7-103; 35-61). The mixture is `roasted' at a
high temperature, which oxidizes much of the chromite to hexavalent
sodium chromate. Depending on the lime content used in the process, the
roast also contains other chromate species, especially calcium

chromate under high lime conditions. The highly water-soluble sodium
chromate is water-extracted from the water-insoluble trivalent chromite
and the less water-soluble chromates (e.g., calcium chromate) in the
`leaching' process. The sodium chromate leachate is reacted with
sulfuric acid and sodium bisulfate to form sodium dichromate. The
sodium dichromate is prepared and packaged as a crystalline powder to
be sold as final product or sometimes used as the starting material to
make other chromates such as chromic acid and potassium dichromate.

a. Cohort Studies of the Baltimore Facility. The Hayes et al. study of
the Baltimore, Maryland chromate production plant was designed to
determine whether changes in the industrial process at one chromium
chemical production facility were associated with a decreased risk of
cancer, particularly cancer of the respiratory system (Ex. 7-14). Four
thousand two hundred and seventeen (4,217) employees were identified as
newly employed between January 1, 1945 and December 31, 1974. Excluded
from this initial enumeration were employees who: (1) were working as
of 1945, but had been hired prior to 1945 and (2) had been hired since
1945 but who had previously been employed at the plant. Excluded from
the final cohort were those employed less than 90 days; women; those
with unknown length of employment; those with no work history; and
those of unknown age. The final cohort included 2,101 employees (1,803
hourly and 298 salaried).
    Hayes divided the production process into three departments: (1)
The mill and roast or ``dry end'' department which consists of
grinding, roasting and leaching processes; (2) the bichromate
department which consists of the acidification and crystallization
processes; and (3) the special products department which produces
secondary products including chromic acid. The bichromate and special
products departments are referred to as the ``wet end''.
    The construction of a new mill and roast and bichromate plant that
opened during 1950 and 1951 and a new chromic acid and special products
plant that opened in 1960 were cited by Hayes as ``notable production
changes'' (Ex. 7-14). The new facilities were designed to ``obtain
improvements in process technique and in environmental control of
exposure to chromium bearing dusts * * *'' (Ex. 7-14).
    Plant-related work and health histories were abstracted for each
employee from plant records. Each job on the employee's work history
was characterized according to whether the job exposure occurred in (1)
a newly constructed facility, (2) an old facility, or (3) could not be
classified as having occurred in the new or the old facility. Those who
ever worked in an old facility or whose work location(s) could not be
distinguished based upon job title were considered as having a high or
questionable exposure. Only those who worked exclusively in the new
facility were defined for study purposes as ``low exposure''. Data on
cigarette smoking were abstracted from plant records, but were not
utilized in any analyses since the investigators thought them ``not to
be of sufficient quality to allow analysis.''
    One thousand one hundred and sixty nine (1,169) cohort members were
identified as alive, 494 not individually identified as alive and 438
as deceased. Death certificates could not be located for 35 reported
decedents. Deaths were coded to the 8th revision of the International
Classification of Diseases.
    Mortality analysis was limited to the 1,803 hourly employees
calculating the standardized mortality ratios (SMRs) for specific
causes of death. The SMR is a ratio of the number of deaths observed in
the study population to the number that would be expected if that study
population had the same specific mortality rate as a standard reference
population (e.g., age-, gender-, calendar year adjusted U.S.
population). The SMR is typically multiplied by 100, so a SMR greater
than 100 represents an elevated mortality in the study cohort relative
to the reference group. In the Hayes study, the expected number of
deaths was based upon Baltimore, Maryland male mortality rates
standardized for age, race and time period. For those where race was
unknown, the expected numbers were derived from mortality rates for
whites. Cancer of the trachea, bronchus and lung accounted for 69% of
the 86 cancer deaths identified and was statistically significantly
elevated (O=59; E=29.16; SMR=202; 95% CI: 155-263).
    Analysis of lung cancer deaths among hourly workers by year of
initial employment (1945-1949; 1950-1959 and 1960-1974), exposure
category (low exposure or questionable/high exposure) and duration of
employment (short term defined as 90 days-2 years; long term defined as
3 years +) was also conducted. For those workers characterized as
having questionable/high exposure, the SMRs were significantly elevated
for the 1945-1949 and the 1950-1959 hire periods and for both short-
and long-term workers (not statistically significant for the short-term
workers initially hired 1945-1949). For those characterized as low
exposure, there was an elevated SMR for the long-term workers hired
between 1950 and 1959, but based only on three deaths (not
statistically significant). No lung cancer cases were observed for
workers hired 1960-1974.
    Case-control analyses of (1) a history of ever having been employed
in selected jobs or combinations of jobs or (2) a history of specified
morbid conditions and combinations of conditions reported on plant
medical records were conducted. Cases were defined as decedents (both
hourly and salaried were included in the analyses) whose underlying or
contributing cause of death was lung cancer. Controls were defined as
deaths from causes other than malignant or benign tumors. Cases and
controls were matched on race (white/non-white), year of initial
employment (+/-3 years), age at time of initial employment (+/-5 years)
and total duration of employment (90 days-2 years; 3-4 years and 5
years +). An odds ratio (OR) was determined where the ratio is the odds
of employment in a job involving Cr(VI) exposure for the cases relative
to the controls.
    Based upon matched pairs, analysis by job position showed
significantly elevated odds ratios for special products (OR=2.6) and
bichromate and special products (OR=3.3). The relative risk for
bichromate alone was also elevated (OR=2.1, not statistically
significant).
    The possible association of lung cancer and three health conditions
(skin ulcers, nasal perforation and dermatitis) as recorded in the
plant medical records was also assessed. Of the three medical
conditions, only the odds ratio for dermatitis was statistically
significant (OR=3.0). When various combinations of the three conditions
were examined, the odds ratio for having all three conditions was
statistically significantly elevated (OR=6.0).
    Braver et al. used data from the Hayes study discussed above and
the results of 555 air samples taken during the period 1945-1950 by the
Baltimore City Health Department, the U.S. Public Health Service, and
the companies that owned the plant, in an attempt to examine the
relationship between exposure to Cr(VI) and the occurrence of lung
cancer (Ex. 7-17). According to the authors, methods for determining
the air concentrations of Cr(VI) have changed since the industrial
hygiene data were collected at the Baltimore plant between 1945 and
1959. The authors asked the National Institute for Occupational Safety
and Health (NIOSH) and the Occupational Safety and Health

Administration (OSHA) to review the available documents on the methods
of collecting air samples, stability of Cr(VI) in the sampling media
after collection and the methods of analyzing Cr(VI) that were used to
collect the samples during that period.
    Air samples were collected by both midget impingers and high volume
samplers. According to the NIOSH/OSHA review, high volume samplers
could have led to a ``significant'' loss of Cr(VI) due to the reduction
of Cr(VI) to Cr(III) by glass or cellulose ester filters, acid
extraction of the chromate from the filter, or improper storage of
samples. The midget impinger was ``less subject'' to loss of Cr(VI)
according to the panel since neither filters nor acid extraction from
filters was employed. However, if iron was present or if the samples
were stored for too long, conversion from Cr(VI) to Cr(III) may have
occurred. The midget impinger can only detect water soluble Cr(VI). The
authors noted that, according to a 1949 industrial hygiene survey by
the U.S. Public Health Service, very little water insoluble Cr(VI) was
found at the Baltimore plant. One NIOSH/OSHA panel member characterized
midget impinger results as ``reproducible'' and ``accuracy * * * fairly
solid unless substantial reducing agents (e.g., iron) are present''
(Ex. 7-17, p. 370). Based upon the panel's recommendations, the authors
used the midget impinger results to develop their exposure estimates
even though the panel concluded that the midget impinger methods ``tend
toward underestimation'' of Cr(VI).
    The authors also cite other factors related to the industrial
hygiene data that could have potentially influenced the accuracy of
their exposure estimates (either overestimating or underestimating the
exposure). These include: Measurements may have been taken primarily in
``problem'' areas of the plant; the plants may have been cleaned or
certain processes shut down prior to industrial hygiene monitoring by
outside groups; respirator use; and periodic high exposures (due to
infrequent maintenance operations or failure of exposure control
equipment) which were not measured and therefore not reflected in the
available data.
    The authors estimated exposure indices for cohorts rather than for
specific individuals using hire period (1945-1949 or 1950-1959) and
duration of exposure, defined as short (at least 90 days but less than
three years) and long (three years or more). The usual exposure to
Cr(VI) for both the short- and long-term workers hired 1945-1949 was
calculated as the average of the mean annual air concentration for
1945-1947 and 1949 (data were missing for 1948). This was estimated to
be 413 [mu]g/m3. The usual exposure to Cr(VI) was estimated
to be 218 [mu]g/m3 for the short and long employees hired
between 1950 and 1959 based on air measurements in the older facility
in the early 1950s.
    Cumulative exposure was calculated as the usual exposure level
times average duration. Short-term workers, regardless of length of
employment, were assumed to have received 1.6 years of exposure
regardless of hire period. For long-term workers, the average length of
exposure was 12.3 years. Those hired 1945-1949 were assigned five years
at an exposure of 413 [mu]g/m3 and 7.3 years at an exposure
of 218 [mu]g/m3. For the long-term workers hired between
1950 and 1959, the average length of exposure was estimated to be 13.4
years. The authors estimated that the cumulative exposures at which
``significant increases in lung cancer mortality'' were observed in the
Hayes study were 0.35, 0.67, 2.93 and 3.65 mg/m3--years. The
association seen by the authors appears more likely to be the result of
duration of employment rather than the magnitude of exposure since the
variation in the latter was small.
    Gibb et al. relied upon the Hayes study to investigate mortality in
a second cohort of the Baltimore plant (Ex. 31-22-11). The Hayes cohort
was composed of 1,803 hourly and 298 salaried workers newly employed
between January 1, 1945 and December 31, 1974. Gibb excluded 734
workers who began work prior to August 1, 1950 and included 990 workers
employed after August 1, 1950 who worked less than 90 days, resulting
in a cohort of 2,357 males followed for the period August 1, 1950
through December 31, 1992. Fifty-one percent (1,205) of the cohort was
white; 36% (848) nonwhite. Race was unknown for 13% (304) of the
cohort. The plant closed in 1985.
    Deaths were coded according to the 8th revision of the
International Classification of Diseases. Person years of observation
were calculated from the beginning of employment until death or
December 31, 1992, whichever came earlier. Smoking data (yes/no) were
available for 2,137 (93.3%) of the cohort from company records.
    Between 1950 and 1985, approximately 70,000 measurements of
airborne Cr(VI) were collected utilizing several different sampling
methods. The program of routine air sampling for Cr(VI) was initiated
to ``characterize `typical/usual exposures' of workers'' (Ex. 31-22-11,
p. 117). Area samples were collected during the earlier time periods,
while both area and personal samples were collected starting in 1977.
Exposure estimates were derived from the area sampling systems and were
adjusted to ``an equivalent personal exposure estimate using job-
specific ratios of the mean area and personal sampling exposure
estimates for the period 1978-1985 * * *'' (Ex. 31-22-11, p. 117).
According to the author, comparison of the area and personal samples
showed ``no significant differences'' for about two-thirds of the job
titles. For several job titles with a ``significant point source of
contamination'' the area sampling methods ``significantly
underestimated'' personal exposure estimates and were adjusted ``by the
ratio of the two'' (Ex. 31-22-11, p. 118).
    A job exposure matrix (JEM) was constructed, where air sampling
data were available, containing annual average exposure for each job
title. Data could not be located for the periods 1950-1956 and 1960-
1961. Exposures were modeled for the missing data using the ratio of
the measured exposure for a job title to the average of all measured
job titles in the same department. For the time periods where
``extensive'' data were missing, a simple straight line interpolation
between years with known exposures was employed.
    To estimate airborne Cr(III) concentrations, 72 composite dust
samples were collected at or near the fixed site air monitoring
stations about three years after the facility closed. The dust samples
were analyzed for Cr(VI) content using ion chromatography. Cr(III)
content was determined through inductively coupled plasma spectroscopic
analysis of the residue. The Cr(III):Cr(VI) ratio was calculated for
each area corresponding to the air sampling zones and the measured
Cr(VI) air concentration adjusted based on this ratio. Worker exposures
were calculated for each job title and weighted by the fraction of time
spent in each air-monitoring zone. The Cr(III):Cr(VI) ratio was derived
in this manner for each job title based on the distribution of time
spent in exposure zones in 1978. Cr(VI) exposures in the JEM were
multiplied by this ratio to estimate Cr(III) exposures.
    Information on smoking was collected at the time of hire for
approximately 90% of the cohort. Of the 122 lung cancer cases, 116 were
smokers and four were non smokers at the time of hire. Smoking status
was unknown for two lung cancer cases. As discussed below, these data
were used by the study authors to adjust for smoking in their
proportional hazards regression models used to determine whether lung
cancer mortality in the worker cohort increased

with increasing cumulative Cr(VI) exposure.
    A total of 855 observed deaths (472 white; 323 nonwhite and 60 race
unknown) were reported. SMRs were calculated using U.S. rates for
overall mortality. Maryland rates (the state in which the plant was
located) were used to analyze lung cancer mortality in order to better
account for regional differences in disease fatality. SMRs were not
adjusted for smoking. In the public hearing, Dr. Gibb explained that it
was more appropriate to adjust for smoking in the proportional hazards
models than in the SMRs, because the analyst must make more assumptions
to adjust the SMRs for smoking than to adjust the regression model (Tr.
124).
    A statistically significant lung cancer SMR, based on the national
rate, was found for whites (O=71; SMR=186; 95% CI: 145-234); nonwhites
(O=47; SMR=188; 95% CI: 138-251) and the total cohort (O=122; SMR=180;
95% CI: 149-214). The ratio of observed to expected lung cancer deaths
(O/E) for the entire cohort stratified by race and cumulative exposure
quartile were computed. Cumulative exposure was lagged five years (only
exposure occurring five years before a given age was counted). The cut
point for the quartiles divided the cohort into four equal groups based
upon their cumulative exposure at the end of their working history (0-
0.00149 mgCrO\3\/m3-yr; 0.0015-0.0089 mgCrO3/m\3\-yr; 0.009-
0.0769 mgCrO3/m\3\-yr; and 0.077-5.25 mgCrO3/
m\3\-yr). For whites, the relative risk of lung cancer was
significantly elevated for the second through fourth exposure quartiles
with O/E values of 0.8, 2.1, 2.1 and 1.7 for the four quartiles,
respectively. For nonwhites, the O/E values by exposure quartiles were
1.1, 0.9, 1.2 and 2.9, respectively. Only the highest exposure quartile
was significantly elevated. For the total cohort, a significant
exposure-response trend was observed such that lung cancer mortality
increased with increasing cumulative Cr(VI) exposure.
    Proportional hazards models were used to assess the relationship
between chromium exposure and the risk of lung cancer. The lowest
exposure quartile was used as the reference group. The median exposure
in each quartile was used as the measure of cumulative Cr(VI) exposure.
When smoking status was included in the model, relative lung cancer
risks of 1.83, 2.48 and 3.32 for the second, third and fourth exposure
quartiles respectively were estimated. Smoking, Cr(III) exposure, and
work duration were also significant predictors of lung cancer risk in
the model.
    The analysis attempted to separate the effects into two
multivariate proportionate hazards models (one model incorporated the
log of cumulative Cr(VI) exposure, the log of cumulative Cr(III)
exposure and smoking; the second incorporated the log of cumulative
Cr(VI), work duration and smoking). In either regression model, lung
cancer mortality remained significantly associated (p <  .05) with
cumulative Cr(VI) exposure even after controlling for the combination
of smoking and Cr(III) exposure or the combination of smoking and work
duration. On the other hand, lung cancer mortality was not
significantly associated with cumulative Cr(III) or work duration in
the multivariate analysis indicating lung cancer risk was more strongly
correlated with cumulative Cr(VI) exposure than the other variables.
    Exponent, as part of a larger submission from the Chrome Coalition,
submitted comments on the Gibb paper prior to the publication of the
proposed rule. These comments asked that OSHA review methodological
issues believed by Exponent to impact upon the usefulness of the Gibb
data in a risk assessment analysis. While Exponent states that the Gibb
study offers data that ``are substantially better for cancer risk than
the Mancuso study * * * they believe that further scrutiny of some of
the methods and analytical procedures is necessary (Ex. 31-18-15-1, p.
5).
    The issues raised by Exponent and the Chrome Coalition (Ex. 31-18-
14) concerning the Gibb paper are: selection of the appropriate
reference population for compilation of expected numbers for use in the
SMR analysis; inclusion of short term workers (<  1 year); expansion of
the number of exposure groupings to evaluate dose response trends;
analyzing dose response by peak JEM exposure levels; analyzing dose-
response at exposures above and below the current PEL and calculating
smoking-adjusted SMRs for use in dose-response assessments. Exponent
obtained the original data from the Gibb study. The data were
reanalyzed to address the issues cited above. Exponent's findings are
presented in Exhibit 31-18-15-1 and are discussed below.
    Exponent suggested that Gibb's use of U.S. and Maryland mortality
rates for developing expectations for the SMR analysis was
inappropriate. It suggested that Baltimore city mortality rates would
have been the appropriate standard to select since those mortality
rates would more accurately reflect the mortality experience of those
who worked at the plant. Exponent reran the SMR analysis to compare the
SMR values reported by Gibb (U.S. mortality rates for SMR analysis)
with the results of an SMR analysis using Maryland mortality rates and
Baltimore mortality rates. Gibb reported a lung cancer SMR of 1.86 (95%
CI: 1.45-2.34) for white males based upon 71 lung cancer deaths using
U.S. mortality rates. Reanalysis of the data produced a lung cancer SMR
of 1.85 (95% CI: 1.44-2.33) for white males based on U.S. mortality
rates, roughly the same value obtained by Gibb. When Maryland and
Baltimore rates are used, the SMR drops to 1.70 and 1.25 respectively.
    Exponent suggested conducting sensitivity analysis that excludes
short-term workers (defined as those with one year of employment) since
the epidemiologic literature suggests that the mortality of short-term
workers is different than long-term workers. Short-term workers in the
Gibb study comprise 65% of the cohort and 54% of the lung cancers. The
Coalition also suggested that data pertaining to short-term employees'
information are of ``questionable usefulness for assessing the
increased cancer risk from chronic occupational exposure to Cr(VI)''
(Ex. 31-18-15-1, p. 5).
    Lung cancer SMRs were calculated for those who worked for less than
one year and for those who worked one year or more. Exponent defined
short-term workers as those who worked less than one year ``because it
is consistent with the inclusion criteria used by others studying
chromate chemical production worker cohorts'' (Ex. 31-18-15-1, p. 12).
Exponent also suggested that Gibb's breakdown of exposure by quartile
was not the most ``appropriate'' way of assessing dose-response since
cumulative Cr(VI) exposures remained near zero until the 50th to 60th
percentile, ``so there was no real distinction between the first two
quartiles * * * (Ex. 31-18-15-1, p. 24). They also suggested that
combining ``all workers together at the 75th quartile * * * does not
properly account for the heterogeneity of exposure in this group'' (Ex.
31-18-15-1, p. 24). The Exponent reanalysis used six cumulative
exposure levels of Cr(VI) compared with the four cumulative exposure
levels of Cr(VI) in the Gibb analysis. The lower levels of exposure
were combined and ``more homogeneous'' categories were developed for
the higher exposure levels.
    Using these re-groupings and excluding workers with less than one
year of employment, Exponent reported that the highest SMRs are seen in
the highest exposure group (1.5-< 5.25 mg

CrO3/m\3\-years) for both white and nonwhite, based on
either the Maryland or the Baltimore mortality rates. The authors did
not find ``that the inclusion of short-term workers had a significant
impact on the results, especially if Baltimore rates are used in the
SMR calculations' (Ex. 31-18-15-1, p. 28).
    Analysis of length of employment and ``peak'' (i.e., highest
recorded mean annual) exposure level to Cr(VI) was conducted. Exponent
reported that approximately 50% of the cohort had ``only very low''
peak exposure levels (<7.2 [mu]g CrO3/m\3\ or approximately
3.6 [mu]g/m\3\ of Cr(VI)). The majority of the short-term workers had
peak exposures of <100 [mu]g CrO3/m\3\. There were five peak
Cr(VI) exposure levels (<7.2 [mu]g CrO3/m\3\; 7.2-<19.3
[mu]g CrO3/m\3\; 19.3-<48.0 [mu]g CrO3/m\3\;
48.0-<105 [mu]g CrO3/m\3\; 105-<182 [mu]g CrO3/
m\3\; and 182-<806 [mu]g CrO3/m\3\) included in the
analyses. Overall, the lung cancer SMRs for the entire cohort grouped
according to the six peak exposure categories were slightly higher
using Maryland reference rates compared to Baltimore reference rates.
    The Exponent analysis of workers who were ever exposed above the
current PEL versus those never exposed above the current PEL produced
slightly higher SMRs for those ever exposed, with the SMRs higher using
the Maryland standard rather than the Baltimore standard. The only
statistically significant result was for all lung cancer deaths
combined.
    Assessment was made of the potential impact of smoking on the lung
cancer SMRs since Gibb did not adjust the SMRs for smoking. Exponent
stated that the smoking-adjusted SMRs are more appropriate for use in
the risk assessment than the unadjusted SMRs. It should be noted that
smoking adjusted SMRs could not be calculated using Baltimore reference
rates. As noted by the authors, the smoking adjusted SMRs produced
using Maryland reference rates are, by exposure, ``reasonably
consistent with the Baltimore-referenced SMRs'' (Ex. 31-18-15-1, p.
41).
    Gibb et al. included workers regardless of duration of employment,
and the cohort was heavily weighted by those individuals who worked
less than 90 days. In an attempt to clarify this issue, Exponent
produced analyses of short-term workers, particularly with respect to
exposures. Exponent redefined short-term workers as those who worked
less than one year, to be consistent with the definition used in other
studies of chromate producers. OSHA finds this reanalysis excluding
short-term workers to be useful. It suggests that including cohort
workers employed less than one year did not substantively alter the
conclusions of Gibb et al. with regard to the association between
Cr(VI) exposure and lung cancer mortality. It should be noted that in
the Hayes study of the Baltimore plant, the cohort is defined as anyone
who worked 90 days or more.
    Hayes et al. used Baltimore mortality rates while Gibb et al. used
U.S. mortality rates to calculate expectations for overall SMRs. To
calculate expectations for the analysis of lung cancer mortality and
exposure, Gibb et al. used Maryland state mortality rates. The SMR
analyses provided by Exponent using both Maryland and Baltimore rates
are useful. The data showed that using Baltimore rates raised the
expected number of lung cancer deaths and, thus, lowered the SMRs.
However, there remained a statistically significant increase in lung
cancer risk among the exposed workers and a significant upward trend
with cumulative Cr(VI) exposure. The comparison group should be as
similar as possible with respect to all other factors that may be
related to the disease except the determinant under study. Since the
largest portion of the cohort (45%) died in the city of Baltimore, and
even those whose deaths occurred outside of Baltimore (16%) most likely
lived in proximity to the city, the use of Baltimore mortality rates as
an external reference population is preferable.
    Gibb's selection of the cut points for the exposure quartiles was
accomplished by dividing the workers in the cohort into four equal
groups based on their cumulative exposure at the end of their working
history. Using the same method but excluding the short-term workers
would have resulted in slightly different cumulative exposure
quartiles. Exponent expressed a preference for a six-tiered exposure
grouping. The impact of using different exposure groupings is further
discussed in section VI.C of the quantitative risk assessment.
    The exposure matrix of Gibb et al. utilizes an unusually high-
quality set of industrial hygiene data. Over 70,000 samples taken to
characterize the ``typical/usual'' working environment is more
extensive industrial hygiene data then is commonly available for most
exposure assessments. However, there are several unresolved issues
regarding the exposure assessment, including the impact of the
different industrial hygiene sampling techniques used over the sampling
time frame, how the use of different sampling techniques was taken into
account in developing the exposure assessment and the use of area vs.
personal samples.
    Exponent and the Chrome Coalition also suggested that the SMRs
should have been adjusted for smoking. According to Exponent, smoking
adjusted SMRs based upon the Maryland mortality rates produced SMRs
similar to the SMRs obtained using Baltimore mortality rates (Ex. 31-
18-15-1). The accuracy of the smoking data is questionable since it
represents information obtained at the time of hire. Hayes abstracted
the smoking data from the plant medical records, but ``found it not to
be of sufficient quality to allow analysis.'' One advantage to using
the Baltimore mortality data may be to better control for the potential
confounding of smoking.
    The Gibb study is one of the better cohort mortality studies of
workers in the chromium production industry. The quality of the
available industrial hygiene data and its characterization as
``typical/usual'' makes the Gibb study particularly useful for risk
assessment.

b. Cohort Studies of the Painesville Facility. The Ohio Department of
Health conducted epidemiological and environmental studies at a plant
in Painesville that manufactured sodium bichromate from chromite ore.
Mancuso and Hueper (Ex. 7-12) reported an excess of respiratory cancer
among chromate workers when compared to the county in which the plant
was located. Among the 33 deaths in males who had worked at the plant
for a minimum of one year, 18.2% were from respiratory cancer. In
contrast, the expected frequency of respiratory cancer among males in
the county in which the plant was located was 1.2%. Although the
authors did not include a formal statistical comparison, the lung
cancer mortality rate among the exposed workers would be significantly
greater than the county rate.
    Mancuso (Ex. 7-11) updated his 1951 study of 332 chromate
production workers employed during the period 1931-1937. Age adjusted
mortality rates were calculated by the direct method using the
distribution of person years by age group for the total chromate
population as the standard. Vital status follow-up through 1974 found
173 deaths. Of the 66 cancer deaths, 41 (62.1%) were lung cancers. A
cluster of lung cancer deaths was observed in workers with 27-36 years
since first employment.
    Mancuso used industrial hygiene data collected in 1949 to calculate
weighted average exposures to water-soluble (presumed to be Cr(VI)),
insoluble (presumed to be principally Cr(III)) and

total chromium (Ex. 7-98). The age-adjusted lung cancer death rate
increased from 144.6 (based upon two deaths) to 649.6 (based upon 14
deaths) per 100,000 in five exposure categories ranging from a low of
0.25-0.49 to a high of 4.0+ mg/m\3\-years for the insoluble Cr(III)
exposures. For exposure to soluble Cr(VI), the age adjusted lung cancer
rates ranged from 80.2 (based upon three deaths) to 998.7 (based upon
12 deaths) in five exposure categories ranging from < 0.25 to 2.0+ mg/
m\3\-years. For total chromium, the age-adjusted death rates ranged
from 225.7 (based upon three deaths) to 741.5 (based upon 16 deaths)
for exposures ranging from 0.50-0.99 mg/m\3\-years to 6.0+ mg/m\3\-
years.
    Age-adjusted lung cancer death rates also were calculated by
classifying workers by the levels of insoluble Cr(III) and total
chromium exposure. From the data presented, it appears that for a fixed
level of insoluble Cr(III), the lung cancer risk appears to increase as
the total chromium increases (Ex. 7-11).
    Mancuso (Ex. 23) updated the 1975 study. As of December 31, 1993,
283 (85%) cohort members had died and 49 could not be found. Of the 102
cancer deaths, 66 were lung cancers. The age-adjusted lung cancer death
rate per 100,000 ranged from 187.9 (based upon four deaths) to 1,254.1
(based upon 15 deaths) for insoluble Cr(III) exposure categories
ranging from 0.25-0.49 to 4.00-5.00 mg/m\3\ years. For the highest
exposure to insoluble Cr(III) (6.00+ mg/m\3\ years) the age-adjusted
lung cancer death rate per 100,000 fell slightly to 1,045.5 based upon
seven deaths.
    The age-adjusted lung cancer death rate per 100,000 ranged from
99.7 (based upon five deaths) to 2,848.3 (based upon two deaths) for
soluble Cr(VI) exposure categories ranging from < 0.25 to 4.00+ mg/m\3\
years. For total chromium, the age-adjusted lung cancer death rate per
100,000 ranged from 64.7 (based upon two deaths) to 1,106.7 (based upon
21 deaths) for exposure categories ranging from < 0.50 to 6.00+ mg/m\3\
years.
    To investigate whether the increase in the lung cancer death rate
was due to one form of chromium compound (presumed insoluble Cr(III) or
soluble Cr(VI)), age-adjusted lung cancer mortality rates were
calculated by classifying workers by the levels of exposure to
insoluble Cr(III) and total chromium. For a fixed level of insoluble
Cr(III), the lung cancer rate appears to increase as the total chromium
increases for each of the six total chromium exposure categories,
except for the 1.00-1.99 mg/m\3\-years category. For the fixed exposure
categories for total chromium, increasing exposures to levels of
insoluble Cr(III) showed an increased age-adjusted death rate from lung
cancer in three of the six total chromium exposure categories.
    For a fixed level of soluble Cr(VI), the lung cancer death rate
increased as total chromium categories of exposure increased for three
of the six gradients of soluble Cr(VI). For the fixed exposure
categories of total chromium, the increasing exposure to specific
levels of soluble Cr(VI) led to an increase in two of the six total
chromium exposure categories. Mancuso concluded that the relationship
of lung cancer is not confined solely to either soluble or insoluble
chromium. Unfortunately, it is difficult to attribute these findings
specifically to Cr(III) [as insoluble chromium] and Cr(VI) [as soluble
chromium] since it is likely that some slightly soluble and insoluble
Cr(VI) as well as Cr(III) contributed to the insoluble chromium
measurement.
    Luippold et al. conducted a retrospective cohort study of 493
former employees of the chromate production plant in Painesville, Ohio
(Ex. 31-18-4). This Painesville cohort does not overlap with the
Mancuso cohort and is defined as employees hired beginning in 1940 who
worked for a minimum of one year at Painesville and did not work at any
other facility owned by the same company that used or produced Cr(VI).
An exception to the last criterion was the inclusion of workers who
subsequently were employed at a company plant in North Carolina (number
not provided). Four cohort members were identified as female. The
cohort was followed for the period January 1, 1941 through December 31,
1997. Thirty-two percent of the cohort worked for 10 or more years.
    Information on potential confounders was limited. Smoking status
(yes/no) was available for only 35% of the cohort from surveys
administered between 1960 and 1965 or from employee medical files. For
those employees where smoking data were available, 78% were smokers
(responded yes on at least one survey or were identified as smokers
from the medical file). Information on race also was limited, the death
certificate being the primary source of information.
    Results of the vital status follow-up were: 303 deaths; 132
presumed alive and 47 vital status unknown. Deaths were coded to the
9th revision of the International Classification of Diseases. Cause of
death could not be located for two decedents. For five decedents the
cause of death was only available from data collected by Mancuso and
was recoded from the 7th to the 9th revision of the ICD. There were no
lung cancer deaths among the five recoded deaths.
    SMRs were calculated based upon two reference populations: The U.S.
(white males) and the state of Ohio (white males). Lung cancer SMRs
stratified by year of hire, duration of exposure, time since first
employment and cumulative exposure group also were calculated.
    Proctor et al. analyzed airborne Cr(VI) levels throughout the
facility for the years 1943 to 1971 (the plant closed April 1972) from
800 area air sampling measurements from 21 industrial hygiene surveys
(Ex. 35-61). A job exposure matrix (JEM) was constructed for 22
exposure areas for each month of plant operation. Gaps in the matrix
were completed by computing the arithmetic mean concentration from area
sampling data, averaged by exposure area over three time periods (1940-
1949; 1950-1959 and 1960-1971) which coincided with process changes at
the plant (Ex. 31-18-1)
    The production of water-soluble sodium chromate was the primary
operation at the Painesville plant. It involved a high lime roasting
process that produced a water insoluble Cr(VI) residue (calcium
chromate) as byproduct that was transported in open conveyors and
likely contributed to worker exposure until the conveyors were covered
during plant renovations in 1949. The average airborne soluble Cr(VI)
from industrial hygiene surveys in 1943 and 1948 was 0.72 mg/m\3\ with
considerable variability among departments. During these surveys, the
authors believe the reported levels may have underestimated total
Cr(VI) exposure by 20 percent or less for some workers due to the
presence of insoluble Cr(VI) dust.
    Reductions in Cr(VI) levels over time coincided with improvements
in the chromate production process. Industrial hygiene surveys over the
period from 1957 to 1964 revealed average Cr(VI) levels of 270 [mu]g/
m\3\. Another series of plant renovations in the early 1960s lowered
average Cr(VI) levels to 39 [mu]g/m\3\ over the period from 1965 to
1972. The highest Cr(VI) concentrations generally occurred in the
shipping, lime and ash, and filtering operations while the locker
rooms, laboratory, maintenance shop and outdoor raw liquor storage
areas had the lowest Cr(VI) levels.
    The average cumulative Cr(VI) exposure (mg/m\3\-yrs) for the cohort
was 1.58 mg/m\3\-yrs and ranged from 0.006 to 27.8 mg/m\3\-yrs. For
those who died from lung cancer, the average Cr(VI) exposure was 3.28
mg/m\3\-yrs and ranged from 0.06 to 27.8 mg/m\3\-yrs.

According to the authors, 60% of the cohort accumulated an estimated
Cr(VI) exposure of 1.00 mg/m\3\-yrs or less.
    Sixty-three per cent of the study cohort was reported as deceased
at the end of the follow-up period (December 31, 1997). There was a
statistically significant increase for the all causes of death category
based on both the national and Ohio state standard mortality rates
(national: O=303; E=225.6; SMR=134; 95% CI: 120-150; state: O=303;
E=235; SMR=129; 95% CI: 115-144). Fifty-three of the 90 cancer deaths
were cancers of the respiratory system with 51 coded as lung cancer.
The SMR for lung cancer is statistically significant using both
reference populations (national O= 51; E=19; SMR 268; 95% CI: 200-352;
state O=51; E=21.2; SMR 241; 95% CI: 180-317).
    SMRs also were calculated by year of hire, duration of employment,
time since first employment and cumulative Cr(VI) exposure, mg/m\3\-
years. The highest lung cancer SMRs were for those hired during the
earliest time periods. For the period 1940-1949, the lung cancer SMR
was 326 (O=30; E=9.2; 95% CI: 220-465); for 1950-1959, the lung cancer
SMR was 275 (O=15; E=5.5; 95% CI: 154-454). For the period 1960-1971,
the lung cancer SMR was just under 100 based upon six deaths with 6.5
expected.
    Lung cancer SMRs based upon duration of employment (years)
increased as duration of employment increased. For those with one to
four years of employment, the lung cancer SMR was 137 based upon nine
deaths (E=6.6; 95% CI: 62-260); for five to nine years of employment,
the lung cancer SMR was 160 (O=8; E=5.0; 95% CI: 69-314). For those
with 10-19 years of employment, the lung cancer SMR was 169 (O=7;
E=4.1; 95% CI: 68-349), and for those with 20 or more years of
employment, the lung cancer SMR was 497 (O=27; E=5.4; 95% CI: 328-723).
    Analyses of cumulative Cr(VI) exposure found the lung cancer SMR
(based upon the Ohio standard) in the highest exposure group (2.70-
27.80 mg/m\3\-yrs) was 463 (O=20; E=4.3; 95% CI: 183-398). In the 1.05-
2.69 mg/m\3\-yrs cumulative exposure group, the lung cancer SMR was 365
based upon 16 deaths (E=4.4; 95% CI: 208-592). For the cumulative
exposure groups 0.49-1.04, 0.20-0.48 and 0.00-0.19, the lung cancer
SMRs were 91 (O=4; E=4.4; 95% CI: 25-234; 184 (O=8; E=4.4; 95% CI: 79-
362) and 67 (O=3; E=4.5; 95% CI: 14-196). A test for trend showed a
strong relationship between lung cancer mortality and cumulative Cr(VI)
exposure (p=0.00002). The authors claim that the SMRs are also
consistent with a threshold effect since there was no statistically
significant trend for excess lung cancer mortality with cumulative
Cr(VI) exposures less than about 1 mg/m\3\-yrs. The issue of whether
the cumulative Cr(VI) exposure-lung cancer response is best represented
by a threshold effect is discussed further in preamble section VI on
the quantitative risk assessment.
    The Painesville cohort is small (482 employees). Excluded from the
cohort were six employees who worked at other chromate plants after
Painesville closed. However, exceptions were made for employees who
subsequently worked at the company's North Carolina plant (number not
provided) because exposure data were available from the North Carolina
plant. Subsequent exposure to Cr(VI) by other terminated employees is
unknown and not taken into account by the investigators. Therefore, the
extent of the bias introduced is unknown.
    The 10% lost to follow-up (47 employees) in a cohort of this size
is striking. Four of the forty-seven had ``substantial'' follow-up that
ended in 1997 just before the end date of the study. For the remaining
43, most were lost in the 1950s and 1960s (most is not defined). Since
person-years are truncated at the time individuals are lost to follow
up, the potential implication of lost person years could impact the
width of the confidence intervals.
    The authors used U.S. and Ohio mortality rates for the standards to
compute the expectations for the SMRs, stating that the use of Ohio
rates minimizes bias that could occur from regional differences in
mortality. It is unclear why county rates were not used to address the
differences in regional mortality.
c. Other Cohort Studies. The first study of cancer of the respiratory
system in the U.S. chromate producing industry was reported by Machle
and Gregorius (Ex. 7-2). The study involved a total of 11,000 person-
years of observation between 1933 and 1947. There were 193 deaths; 42
were due to cancer of the respiratory system. The proportion of
respiratory cancer deaths among chromate workers was compared with
proportions of respiratory cancer deaths among Metropolitan Life
Insurance industrial policyholders. A non-significant excess
respiratory cancer among chromate production workers was found. No
attempt was made to control for confounding factors (e.g., age). While
some exposure data are presented, the authors state that one cannot
associate tumor rates with tasks (and hence specific exposures) because
of ``shifting of personnel'' and the lack of work history records.
    Baetjer reported the results of a case-control study based upon
records of two Baltimore hospitals (Ex. 7-7). A history of working with
chromates was determined from these hospital records and the proportion
of lung cancer cases determined to have been exposed to chromates was
compared with the proportion of controls exposed. Of the lung cancer
cases, 3.4% had worked in a chromate manufacturing plant, while none of
the controls had such a history recorded in the medical record. The
results were statistically significant and Baetjer concluded that the
data confirmed the conclusions reached by Machle and Gregorius that
``the number of deaths due to cancer of the lung and bronchi is greater
in the chromate-producing industry than would normally be expected''
(Ex. 7-7, p. 516).
    As a part of a larger study carried out by the U.S. Public Health
Service, the morbidity and mortality of male workers in seven U.S.
chromate manufacturing plants during the period 1940-1950 was reported
(Exs. 7-1; 7-3). Nearly 29 times as many deaths from respiratory cancer
(excluding larynx) were found among workers in the chromate industry
when compared to mortality rates for the total U.S. for the period
1940-1948. The lung cancer risk was higher at the younger ages (a 40-
fold risk at ages 15-45; a 30-fold risk at ages 45-54 and a 20-fold
risk at ages 55-74). Analysis of respiratory cancer deaths (excluding
larynx) by race showed an observed to expected ratio of 14.29 for white
males and 80 for nonwhite males.
    Taylor conducted a mortality study in a cohort of 1,212 chromate
workers followed over a 24 year (1937-1960) period (Ex. 7-5). The
workers were from three chromate plants that included approximately 70%
of the total population of U.S. chromate workers in 1937. In addition,
the plants had been in continuous operation for the study period
(January 1, 1937 to December 31, 1960). The cohort was followed
utilizing records of Old Age and Survivors Disability Insurance
(OASDI). Results were reported both in terms of SMRs and conditional
probabilities of survival to various ages comparing the mortality
experience of chromate workers to the U.S. civilian male population. No
measures of chromate exposure were reported although results are
provided in terms of duration of employment. Taylor concluded that not
only was there an excess in mortality from respiratory cancer, but from
other causes as well, especially as duration of employment increased.

    In a reanalysis of Taylor's data, Enterline excluded those workers
born prior to 1889 and analyzed the data by follow-up period using U.S.
rates (Ex. 7-4). The SMR for respiratory cancer for all time periods
showed a nine-fold excess (O=69 deaths; E=7.3). Respiratory cancer
deaths comprised 28% of all deaths. Two of the respiratory cancer
deaths were malignant neoplasms of the maxillary sinuses, a number
according to Enterline, ``greatly in excess of that expected based on
the experience of the U.S. male population.'' Also slightly elevated
were cancers of the digestive organs (O=16; E=10.4) and non-malignant
respiratory disease (O=13; E=8.9).
    Pastides et al. conducted a cohort study of workers at a North
Carolina chromium chemical production facility (Ex. 7-93). Opened in
1971, this facility is the largest chromium chemical production
facility in the United States. A low-lime process was used since the
plant began operation. Three hundred and ninety eight workers employed
for a minimum of one year between September 4, 1971 and December 31,
1989 comprised the study cohort. A self-administered employee
questionnaire was used to collect data concerning medical history,
smoking, plant work history, previous employment and exposure to other
potential chemical hazards. Personal air monitoring results for Cr(VI)
were available from company records for the period February 1974
through April 1989 for 352 of the 398 cohort members. A job matrix
utilizing exposure area and calendar year was devised. The exposure
means from the matrix were linked to each employee's work history to
produce the individual exposure estimates by multiplying the mean
Cr(VI) value from the matrix by the duration (time) in a particular
exposure area (job). Annual values were summed to estimate total
cumulative exposure.
    Personal air monitoring indicated that TWA Cr(VI) air
concentrations were generally very low. Roughly half the samples were
less than 1 [mu]g/m3, about 75 percent were below 3 [mu]g/
m3, and 96 percent were below 25 [mu]g/m3. The
average worker's age was 42 years and mean duration of employment was
9.5 years. Two thirds of the workers had accumulated less than 0.01
[mu]g/m3-yr cumulative Cr(VI) exposure. SMRs were computed
using National, State (not reported) and county mortality rates (eight
adjoining North Carolina counties, including the county in which the
plant is located). Two of the 17 recorded deaths in the cohort were
from lung cancers. The SMRs for lung cancer were 127 (95% CI: 22-398)
and 97 (95% CI: 17-306) based on U.S. and North Carolina county
mortality rates, respectively. The North Carolina cohort is still
relatively young and not enough time has elapsed to reach any
conclusions regarding lung cancer risk and Cr(VI) exposure.
    In 2005, Luippold et al. published a study of mortality among two
cohorts of chromate production workers with low exposures (Ex. 47-24-
2). Luippold et al. studied a total of 617 workers with at least one
year of employment, including 430 at the North Carolina plant studied
by Pastides et al. (1994) (``Plant 1'') and 187 hired after the 1980
institution of exposure-reducing process and work practice changes at a
second U.S. plant (``Plant 2''). A high-lime process was never used at
Plant 1, and workers drawn from Plant 2 were hired after the
institution of a low lime process, so that exposures to calcium
chromate in both cohorts were likely minimal. Personal air-monitoring
measures available from 1974 to 1988 for the first plant and from 1981
to 1998 for the second plant indicated that exposure levels at both
plants were low, with overall geometric mean concentrations below 1.5
[mu]g/m3 and area-specific average personal air sampling
values not exceeding 10 [mu]g/m3 for most years (Ex. 47-24-
2, p. 383).
    Workers were followed through 1998. By the end of follow-up, which
lasted an average of 20.1 years for workers at Plant 1 and 10.1 years
at Plant 2, 27 cohort members (4%) were deceased. There was a 41%
deficit in all-cause mortality when compared to all-cause mortality
from age-specific state reference rates, suggesting a strong healthy
worker effect. Lung cancer was 16% lower than expected based on three
observed vs. 3.59 expected cases, also using age-specific state
reference rates (Ex. 47-24-2, p. 383). The authors stated that ``[t]he
absence of an elevated lung cancer risk may be a favorable reflection
of the postchange environment'', but cautioned that longer follow-up
allowing an appropriate latency for the entire cohort would be required
to confirm this conclusion (Ex. 47-24-2, p. 381). OSHA received several
written testimony regarding this cohort during the post-hearing comment
period. These are discussed in section VI.B.7 on the quantitative risk
assessment.
    A study of four chromate producing facilities in New Jersey was
reported by Rosenman (Ex. 35-104). A total of 3,408 individuals were
identified from the four facilities over different time periods (plant
A from 1951-1954; plant B from 1951-1971; plant C from 1937-1964 and
plant D 1937-1954). No Cr(VI) exposure data was collected for this
study. Proportionate mortality ratios (PMRs) and proportionate cancer
mortality ratios (PCMRs), adjusted by race, age, and calendar year,
were calculated for the three companies (plants A and B are owned by
one company). Unlike SMRs, PMRs are not based on the expected mortality
rates in a standardized population but, instead, merely represent the
proportional distribution of deaths in the cohort relative to the
general U.S. population. Analyses were done evaluating duration of work
and latency from first employment.
    Significantly elevated PMRs were seen for lung cancer among white
males (170 deaths, PMR=1.95; 95% CI: 1.67-2.27) and black males (54
deaths, PMR=1.88; 95% CI: 1.41-2.45). PMRs were also significantly
elevated (regardless of race) for those who worked 1-10, 11-20 and >20
years and consistently higher for white and black workers 11-20 years
and >20 years since first hire. The results were less consistent for
those with 10 or fewer years since first hire.
    Bidstrup and Case reported the mortality experience of 723 workers
at three chromate producing factories in Great Britain (Ex. 7-20). Lung
cancer mortality was 3.6 times that expected (O=12; E=3.3) for England
and Wales. Alderson et al. conducted a follow-up of workers from the
three plants in the U.K. (Bolton, Rutherglen and Eaglescliffe)
originally studied by Bidstrup (Ex. 7-22). Until the late 1950s, all
three plants operated a ``high-lime'' process. This process potentially
produced significant quantities of calcium chromate as a by-product as
well as the intended sodium dichromate. Process changes occurred during
the 1940s and 1950s. The major change, according to the author, was the
introduction of the ``no-lime'' process, which eliminated unwanted
production of calcium chromate. The no-lime process was introduced at
Eaglescliffe 1957-1959 and by 1961 all production at the plant was by
this process. Rutherglen operated a low-lime process from 1957/1959
until it closed in 1967. Bolton never changed to the low lime process.
The plant closed in 1966. Subjects were eligible for entry into the
study if they had received an X-ray examination at work and had been
employed for a minimum of one year between 1948 and 1977. Of the 3,898
workers enumerated at the three plants, 2,715 met the cohort entrance
criteria, (alive: 1,999; deceased: 602; emigrated: 35; and lost to
follow-up: 79). Those lost to follow-up were not included in the
analyses. Eaglescliffe contributed the greatest number of subjects to
the study (1,418). Rutherglen contributed the

largest number of total deaths (369, or 61%). Lung cancer comprised the
majority of cancer deaths and was statistically significantly elevated
for the entire cohort (O=116; E=47.96; SMR= 240; p < 0.001). Two deaths
from nasal cancer were observed, both from Rutherglen.
    SMRs were computed for Eaglescliffe by duration of employment,
which was defined based upon plant process updates (those who only
worked before the plant modification, those who worked both before and
after the modifications, or those who worked only after the
modifications were completed). Of the 179 deaths at the Eaglescliffe
plant, 40 are in the pre-change group; 129 in the pre-/post-change and
10 in the post-change. A total of 36 lung cancer deaths occurred at the
plant, in the pre-change group O=7; E=2.3; SMR=303; in the pre-/post-
change group O=27; E=13; SMR=2.03 and in the post-change group O=2;
E=1.07; SMR=187.
    In an attempt to address several potential confounders, regression
analysis examined the contributions of various risk factors to lung
cancer. Duration of employment, duration of follow-up and working
before or after plant modification appear to be greater risk factors
for lung cancer, while age at entry or estimated degree of chromate
exposure had less influence.
    Davies updated the work of Alderson, et al. concerning lung cancer
in the U.K. chromate producing industry (Ex. 7-99). The study cohort
included payroll employees who worked a minimum of one year during the
period January 1, 1950 and June 30, 1976 at any of the three facilities
(Bolton, Eaglescliffe or Rutherglen). Contract employees were excluded
unless they later joined the workforce, in which case their contract
work was taken into account.
    Based upon the date of hire, the workers were assigned to one of
three groups. The first, or ``early'' group, consists of workers hired
prior to January 1945 who are considered long term workers, but do not
comprise a cohort since those who left or died prior to 1950 are
excluded. The second group, ``pre-change'' workers, were hired between
January 1, 1945 to December 31, 1958 at Rutherglen or to December 31,
1960 at Eaglescliffe. Bolton employees starting from 1945 are also
termed pre-change. The cohort of pre-change workers is considered
incomplete since those leaving 1946-1949 could not be included and