[Federal Register: October 4, 2004 (Volume 69, Number 191)]
[Proposed Rules]
[Page 59305-59474]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04oc04-28]
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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, 1917, 1918, and 1926
Occupational Exposure to Hexavalent Chromium; Proposed 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: Proposed rule; request for comments and scheduling of informal
public hearings.
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SUMMARY: The Occupational Safety and Health Administration (OSHA)
proposes to amend its existing standard for employee exposure to
hexavalent chromium (Cr(VI)). The basis for issuance of this proposal
is a preliminary determination by the Assistant Secretary that
employees exposed to Cr(VI) face a significant risk to their health at
the current permissible exposure limit and that promulgating this
proposed standard will substantially reduce that risk. The information
gathered so far in this rulemaking indicates that employees exposed to
Cr(VI) well below the current permissible exposure limit are at
increased risk of developing lung cancer. Occupational exposures to
Cr(VI) may also result in asthma, and damage to the nasal epithelia and
skin.
This document proposes an 8-hour time-weighted average permissible
exposure limit of one microgram of Cr(VI) per cubic meter of air (1 mg/
m3) for all Cr(VI) compounds. OSHA also proposes other
ancillary provisions for employee protection such as preferred methods
for controlling exposure, respiratory protection, protective work
clothing and equipment, hygiene areas and practices, medical
surveillance, hazard communication, and recordkeeping. OSHA is
proposing separate regulatory texts for general industry, construction,
and shipyards in order to tailor requirements to the circumstances
found in each of these sectors.
DATES: Written comments. The Agency invites interested persons to
submit written comments regarding the proposed rule, including comments
on the information collection determination described in Section X of
the preamble (OMB Review under the Paperwork Reduction Act of 1995), by
mail, facsimile, or electronically. All comments, whether submitted by
mail, facsimile, or electronically through the Internet, must be sent
by January 3, 2005.
Informal public hearings. The Agency plans to hold an informal
public hearing in Washington, DC, beginning on February 1, 2005. OSHA
expects the hearing to last from 9:30 a.m. to 5:30 p.m.; however, the
exact daily schedule is at the discretion of the presiding
administrative law judge.
Notice of intention to appear to provide testimony at the informal
public hearing. Interested persons who intend to present testimony at
the informal public hearing in Washington, DC, must notify OSHA of
their intention to do so no later than December 3, 2004.
Hearing testimony and documentary evidence. Interested persons who
request more than 10 minutes to present their testimony, or who will be
submitting documentary evidence at the hearing, must provide the Agency
with copies of their full testimony and all documentary evidence they
plan to present by January 3, 2005. See Section XVI below for details
on the format and how to file a notice of intention to appear, submit
documentary evidence at the hearing, and request an appropriate amount
of time to present testimony.
ADDRESSES: Written comments. Interested persons may submit three copies
of written comments to the Docket Office, Docket H054A, Room N-2625,
OSHA, U.S. Department of Labor, 200 Constitution Avenue, NW.,
Washington, DC 20210; telephone (202) 693-2350. If written comments are
10 pages or fewer, they may be faxed to the OSHA Docket Office,
facsimile number (202) 693-1648. Comments may also be submitted
electronically through the Internet at http://ecomments.osha.gov.
Supplemental information such as studies and journal articles cannot be
attached to electronic submissions. Instead, three copies of each
study, article, or other supplemental document must be sent to the OSHA
Docket Office at the address above. These materials must clearly
identify the associated electronic comments to which they will be
attached in the docket by the following information: Name of person
submitting comments; date of comment submission; subject of comments;
and docket number to which comments belong.
Informal public hearings. The informal public hearing to be held in
Washington, DC, will be held in the Frances Perkins Building, U.S.
Department of Labor, 200 Constitution Avenue, NW., Washington, DC
20210.
Notice of intention to appear to provide testimony at the informal
public hearing. Interested persons who intend to present testimony at
the informal public hearing in Washington, DC, may submit three copies
of their notice of intention to appear to the Docket Office, Docket
H054A, Room N-2625, OSHA, U.S. Department of Labor, 200 Constitution
Avenue, NW., Washington, DC 20210. Notices may also be submitted
electronically through the Internet at http://ecomments.osha.gov. OSHA
Docket Office and Department of Labor hours of operation are 8:15 a.m.
to 4:45 p.m.
Hearing testimony and documentary evidence. Interested persons who
request more than 10 minutes in which to present their testimony, or
who will be submitting documentary evidence at the informal public
hearing must submit three copies of the testimony and the documentary
evidence to the Docket Office, Docket H054A, Room N-2625, OSHA, U.S.
Department of Labor, 200 Constitution Avenue, NW., Washington, DC
20210. Written testimony may also be submitted electronically through
the Internet at http://ecomments.osha.gov.
Please note that security-related problems may result in
significant delays in receiving comments and other materials by regular
mail. Telephone the OSHA Docket Office at (202) 693-2350 for
information regarding security procedures concerning delivery of
materials by express delivery, hand delivery, and messenger service.
All comments and submissions will be available for inspection and
copying in the OSHA Docket Office at the address above. Most comments
and submissions will be posted on OSHA's Web page (http://www.osha.gov
). Contact the OSHA Docket Office at (202) 693-2350 for
information about materials not available on the OSHA Web page and for
assistance in using this Web page to locate docket submissions. Because
comments sent to the docket or to OSHA's Web page are available for
public inspection, the Agency cautions interested parties against
including in these comments personal information such as social
security numbers and birth dates.
FOR FURTHER INFORMATION CONTACT: For general information and press
inquiries, contact Mr. George Shaw, Office of Communications, Room N-
3647, OSHA, U.S. Department of Labor, 200 Constitution Avenue, NW.,
Washington, DC 20210; telephone (202) 693-1999. For technical
inquiries, contact Ms. Amanda Edens, Directorate of Standards and
Guidance, Room N-3718, OSHA, U.S. Department of Labor, 200 Constitution
Avenue, NW., Washington, DC 20210; telephone (202) 693-2093 or
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fax (202) 693-1678. For hearing information contact Ms. Veneta Chatmon,
Office of Communications, Room N-3647, OSHA, U.S. Department of Labor,
200 Constitution Avenue, NW., Washington, DC 20210; telephone (202)
693-1999.
SUPPLEMENTARY INFORMATION: For additional copies of this Federal
Register document, contact the Office of Publications, Room N-3101,
OSHA, U.S. Department of Labor, 200 Constitution Avenue, NW.,
Washington, DC 20210; telephone (202) 693-1888. Electronic copies of
this Federal Register, as well as news releases and other relevant
documents, are available at OSHA's Home page at http://www.osha.gov.
I. General
The preamble to the proposed standard on occupational exposure to
chromium (VI) discusses events leading to the proposal, health effects
of exposure, the degree and significance of the risk presented, a
summary of the analysis of technological and economic feasibility,
regulatory impact, and regulatory flexibility, and the rationale behind
the specific provisions set forth in the proposed standard. The
discussion follows this outline:
I. General
II. Issues
III. Pertinent Legal Authority
IV. Events Leading to the Proposed Standards
V. Chemical Properties and Industrial Uses
VI. Health Effects
VII. Preliminary Quantitative Risk Assessment
VIII. Significance of Risk
IX. Summary of the Preliminary Economic Analysis and Initial
Regulatory Flexibility Analysis
X. OMB Review under the Paperwork Reduction Act of 1995
XI. Federalism
XII. State Plans
XIII. Unfunded Mandates
XIV. Protecting Children from Environmental Health and Safety Risks
XV. Environmental Impacts
XVI. Public Participation--Notice of Hearing
XVII. Summary and Explanation of the Standards
XVIII. Authority and Signature
XIX. Proposed Standards
II. Issues
OSHA requests comment on all relevant issues, including health
effects, risk assessment, significance of risk determination,
technological and economic feasibility, and the provisions of the
proposed regulatory text. OSHA is especially interested in responses,
supported by evidence and reasons, to the following questions:
Health Effects
1. OSHA has described a variety of studies addressing the major
adverse health effects that have been associated with exposure to
Cr(VI). Has OSHA adequately identified and documented all critical
health impairments associated with occupational exposure to Cr(VI)? Are
there any additional studies or other data that would controvert the
information discussed or significantly enhance the determination of
material health impairment or the assessment of exposure-response
relationships? Submit any relevant information, and explain your
reasoning for recommending the inclusion of any studies you suggest.
2. Using currently available epidemiologic and experimental
studies, OSHA has made a preliminary determination that all Cr(VI)
compounds (e.g., water soluble, insoluble and slightly soluble) possess
carcinogenic potential and thus present a lung cancer risk to exposed
workers. Is this determination correct? Are there additional data OSHA
should consider in evaluating the carcinogenicity or relative
carcinogenic potencies of different Cr(VI) compounds?
Risk Assessment
3. In its preliminary assessment of risk, OSHA has relied primarily
on two epidemiologic cohort studies of chromate production workers to
estimate the lung cancer risk to workers exposed to Cr(VI) (Exs. 31-22-
11; 33-10). Are there any other studies that you believe are better
suited to estimating the risk to exposed workers; if so, please provide
the studies and explain why you believe they are better.
4. OSHA is aware of two cohorts (i.e., Alexander cohort, Ex. 31-16-
3, and Pastides cohort, Ex. 35-279) in which a sizable number of
workers were probably exposed to low Cr(VI) air levels (e.g., < 10
[mu]g/m3) more consistent with concentrations found in the
workplace today. However, OSHA believes the period of follow-up
observation (median < 10 yr), the young age (< 45 yr at end of follow-up)
and the low number of observed lung cancers (< =15 lung cancers)
severely limits these cohorts as primary data sets for quantitative
risk analysis. Other limitations to the Alexander study include a lack
of data on workers who were employed between 1940 and 1974, but whose
employment ended prior to 1974, and on exposures prior to 1974. Are
there updated analyses available for the Alexander and Pastides
cohorts? How many years do these cohorts need to be followed and how
many lung cancers need to be observed in order for these data sets to
provide insight into the shape of the exposure-response curve at lower
levels of Cr(VI) exposure (e.g., 0.5 to 5 [mu]g/m3)? In the
case of the Alexander cohort, is there additional information on cohort
members' exposures prior to 1974 or workers who left prior to 1974 that
could improve the analysis? Are there other cohorts available to look
at low exposures?
5. OSHA has relied upon a linear relative risk model and cumulative
Cr(VI) exposure for estimating the lifetime occupational lung cancer
risk among Cr(VI)-exposed workers. In particular, OSHA has made a
preliminary determination that a threshold model is not appropriate for
estimating the lung cancer risk associated with Cr(VI). However, there
is some evidence that pathways (e.g., extracellular reduction, DNA
repair, cell apoptosis, etc.) may exist within the lung that protect
against Cr(VI)-induced respiratory carcinogenesis, and may potentially
introduce non-linearities into the Cr(VI) exposure-cancer response. Is
there convincing scientific evidence of a non-linear exposure-response
relationship in the range of occupational exposures of interest to
OSHA? If so, are there sufficient data to define a non-linear approach
that would provide more reliable predictions of risk than the linear
relative risk model used by OSHA?
6. OSHA's estimates of lung cancer risk are based on workers
primarily exposed to highly water-soluble sodium chromate and sodium
dichromate. OSHA has preliminarily concluded that the risk for workers
exposed to equivalent levels of other Cr(VI) compounds will be of a
similar magnitude or, in the case of some Cr(VI) compounds, possibly
greater than the risks projected in the OSHA quantitative risk
assessment. Is this determination appropriate? Are there sufficient
data to reliably quantify the risk from occupational exposure to
specific Cr(VI) compounds? If so, explain how the risk could be
estimated.
7. The preliminary quantitative risk assessment relies on two (Gibb
and Luippold) cohort studies in which most workers were exposed higher
Cr(VI) levels than the PEL proposed by OSHA, for shorter durations than
a working lifetime exposure. The risks estimated by OSHA for lifetime
exposure to the proposed PEL, therefore, carry the assumption that a
cumulative exposure achieved by short duration exposure to higher
Cr(VI) air levels (e.g., exposed 3 years to 15 [mu]g/m3)
leads to the same risk as an equivalent cumulative exposure achieved by
longer duration exposure to
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lower Cr(VI) exposure (e.g, exposed 45 years to 1 [mu]g/m3).
OSHA preliminarily finds this assumed exposure equivalency to represent
an uncertainty in the estimates of risk but does not have information
that indicates this uncertainty introduces serious error in its
predictions of risk. Does the OSHA exposure-response assessment based
on the higher Cr(VI) air levels and/or shorter durations experienced by
the Gibb and Luippold cohorts lead to a serious underprediction or
overprediction in estimated risks for the occupational exposure
scenarios of interest to OSHA? Please provide any data to support your
rationale.
8. OSHA has made a preliminary determination that suitable data are
not available for making quantitative risk estimates for the non-cancer
adverse health effects associated with exposure to Cr(VI) (e.g., nasal
septum ulcerations and perforations, asthma, irritant and allergic
contact dermatitis). Are there suitable data for a quantitative
estimation of risk for non-cancer adverse effects that OSHA should
include in its final quantitative risk assessment? If so, what models
or approaches should be used?
9. Are there other factors OSHA should take into consideration in
its final quantitative risk assessment to better characterize the risks
associated with exposure to Cr(VI)?
Technologic and Economic Feasibility
10. In its Preliminary Economic Analysis of the proposed standard,
OSHA presents a profile of the affected worker population. In that
profile are estimates of the number of affected workers by application
group and job category and the distribution of exposures by job
category. Are there additional data that will enable the Agency to
refine its profile of the worker population exposed to Cr(VI)? If so,
how should OSHA use these data in making such revisions?
11. What are the job categories in which employees are potentially
exposed to Cr(VI) in your company or industry? For each job category,
provide a brief description of the operation and describe the job
activities that may lead to Cr(VI) exposure. How many employees are
exposed, or have the potential for exposure, to Cr(VI) in each job
category in your company or industry? What are the frequency, duration
and levels of exposures to Cr(VI) at each job category in your company
or industry? Where commenters are able to provide exposure data, OSHA
requests that, where possible, exposure data be personal samples with
clear descriptions of the length of the sample and analytical method.
Exposure data that provide information concerning the controls in place
are more valuable than exposure data without such information.
12. Have there been technological changes within your industry that
have influenced the magnitude, frequency, or duration of exposure to
Cr(VI) or the means by which employers attempt to control exposures?
Describe in detail these technological changes and their effects on
Cr(VI) exposures and methods of control.
13. Has there been a trend within your industry to eliminate Cr(VI)
from production processes, products and services? If so, comments are
requested on the success of substitution efforts. Commenters should
estimate the percentage reduction in Cr(VI), and the extent to which
Cr(VI) is still necessary in their processes within product lines or
production activities. OSHA also requests that commenters describe any
technical, economic or other deterrents to substitution.
14. Does any job category or employee in your workplace have
exposures to Cr(VI) that raw air monitoring data do not adequately
portray due to the short duration, intermittent or non-routine nature,
or other unique characteristics of the exposure? Please explain your
response and indicate peak levels, duration and frequency of exposures
for employees in these job categories.
15. OSHA requests the following information regarding engineering
and work practice controls in your workplace or industry:
a. Describe the operations in which the proposed PEL is being
achieved most of the time by means of engineering and work practice
controls.
b. What engineering and work practice controls have been
implemented in these operations?
c. For all operations in facilities where Cr(VI) is used, what
engineering and work practice controls have been implemented? If you
have installed engineering controls or adopted work practices to reduce
exposure to Cr(VI), describe the exposure reduction achieved and the
cost of these controls. Where current work practices include the use of
regulated areas and hygiene facilities, provide data on the
implementation of these controls, including data on the costs of
installation, operation, and maintenance associated with these
controls.
d. Describe additional engineering and work practice controls which
could be implemented in each operation where exposure levels are
currently above the proposed PEL to further reduce exposure levels.
e. When these additional controls are implemented, to what levels
can exposure be expected to be reduced, or what per cent reduction is
expected to be achieved?
f. What are the costs and amount of time needed to develop, install
and implement these additional controls? Will the added controls affect
productivity?
g. Are there any processes or operations for which it is not
reasonably possible to implement engineering and work practice controls
within two years to achieve the proposed PEL? If so, would allowing
additional time for employers to implement engineering and work
practice controls make compliance possible? How much additional time
would be necessary?
16. OSHA requests information on whether there are any limited or
unique conditions or job tasks in Cr(VI) manufacture or use where
engineering and work practice controls are not available or are not
capable of reducing exposure levels to or below the proposed PEL most
of the time. Provide data and evidence to support your response.
17. In its Preliminary Economic Analysis, OSHA presents estimated
baseline levels of use of personal protective equipment (PPE) and the
incremental costs associated with the proposed standard. Are OSHA's
estimated compliance rates reasonable? Are OSHA's estimates of PPE
costs, and the assumptions underlying these estimates, consistent with
current industry practice? Comments are solicited on OSHA's analysis of
PPE costs.
18. In its Preliminary Economic Analysis, OSHA presents estimated
baseline levels of communication of Cr(VI)-related hazards and the
incremental costs associated with the additional requirements for
communication in the proposed standard. OSHA requests information on
hazard communication programs addressing Cr(VI) that are currently
being implemented by employers and any necessary additions to those
programs that are anticipated in response to the proposed standard. Are
OSHA's baseline estimates and unit costs for training reasonable and
consistent with current industry practice?
Effects on Small Entities
19. Will difficulties be encountered by small entities when
attempting to comply with requirements of the proposed standard? Can
any of the
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proposal's requirements be deleted or simplified for small entities,
while still protecting the health of employees? Would a longer time
allowed for compliance for small entities make a difference to their
ability to comply, and if so, why? (Information submitted in the SBREFA
process is part of the record and need not be resubmitted).
Economic Impacts and Economic Feasibility
20. OSHA, in its Preliminary Economic Analysis, has estimated, by
application group, compliance costs per affected entity and the likely
impacts on revenues and profits under alternative market scenarios.
OSHA requests that affected employers provide comment on OSHA's
estimate of revenue, profit, and the impacts of costs for their
industry or application group. Are there special circumstances--such as
unique cost factors, foreign competition, or pricing constraints--that
OSHA needs to consider when evaluating economic impacts for particular
application groups? Comments are requested on OSHA's analysis of
economic feasibility in the PEA.
Overlapping and Duplicative Regulations
21. Do any federal regulations duplicate, overlap, or conflict with
the proposed Cr(VI) standard?
22. In some facilities, adjustments in ventilation systems to
comply with the proposed PEL may require additional time and expense to
retest these systems to ensure compliance with EPA requirements or
state requirements. OSHA requests information and comment indicating
how frequently retesting would be required, and the time and costs
involved in such retesting.
Environmental Impacts
23. Submit any data, information, or comments pertaining to
possible environmental impacts of adopting this proposal, such as the
following:
a. Any positive or negative environmental effects that could
result;
b. Any irreversible commitments of natural resources which could be
involved; and
c. Estimates of the effect of the proposed standard on the levels
of Cr(VI) in the environment.
In particular, consideration should be given to the potential
direct or indirect impacts of the proposal on water and air pollution,
energy use, solid waste disposal, or land use.
d. Some small entity representatives noted that OSHA PELs are
sometimes used to set ``fence line'' standards for air pollutants. OSHA
is unable to find evidence of states formally using this procedure,
though some states may use such a procedure informally. Do any states
or other air pollution authorities base standards on OSHA PELs? What
effects might this have on the environment and on environmental
compliance?
Provisions of the Standard
24. OSHA's safety and health advisory committees for Construction
and Maritime advised the Agency to take into consideration the unique
nature of their work environments by either settings separate standards
or making accommodations for the differences in work environments in
construction and maritime. To account for differences in the workplace
environment for these different sectors OSHA has proposed separate
standards for general industry, construction, and shipyards. Is this
approach appropriate? What other approaches should the Agency consider?
Please provide a rationale for your response.
25. OSHA has not proposed to cover agriculture, because the Agency
is not aware of significant exposures to Cr(VI) in agriculture. Is this
determination correct?
26. OSHA has proposed to regulate exposures to all Cr(VI)
compounds. As discussed in the health effects section of this preamble,
the Agency has made a preliminary determination that the existing data
support coverage of all Cr(VI) compounds in the scope of the proposed
standard. Is this an appropriate determination or are there additional
data that support the exclusion of certain compounds from the scope of
the final standard? If so, describe specifically how these data would
support a decision to exclude certain compounds from the scope of the
final rule.
27. OSHA has made a preliminary determination to exclude Cr(VI)
exposures due to work with portland cement from the scope of the
construction standard. OSHA believes that guidance efforts by the
Agency may be more suitable for addressing the dermal hazards
associated with portland cement use in construction settings. OSHA's
Advisory Committee for Construction Safety and Health (ACCSH) advised
OSHA to include construction cement work under the proposed standard
because of the known hazards associated with wet cement and the large
number of workers exposed to wet cement in construction work settings.
In particular ACCSH advised OSHA that only certain provisions might be
necessary for workers exposed to wet cement (e.g., protective work
clothing, hygiene areas and practices, medical surveillance for signs
and symptoms of adverse health effects only, communication of hazards
and recordkeeping for medical surveillance and training). Other
provisions, ACCSH advised, might not be necessary (e.g., permissible
exposure levels, exposure assessment, methods of compliance and
respiratory protection). Should OSHA expand the scope of the
construction proposal to include Cr(VI) exposures from portland cement?
If so, what would be the best approach for addressing the dermal
hazards from Cr(VI) faced by these workers? If Cr(VI) exposure from
portland cement work in construction is included in the final standard,
should only certain provisions such as those outlined by ACCSH be
considered?
28. OSHA has proposed to include exposure to Cr(VI) from portland
cement in the scope of the standard for general industry. The Agency
believes that the potential for airborne exposure to Cr(VI) in general
industry due to work with portland cement, as indicated by the profile
of exposed workers presented in Table IX-2 of this preamble, is higher
than in the construction industry. OSHA acknowledges, however, that the
exposure profile indicates that no workers are exposed to Cr(VI) at
levels over the proposed action level. Given the low level of airborne
exposure among cement workers in general industry, should OSHA exclude
exposures to Cr(VI) from portland cement from the scope of the general
industry standard? OSHA seeks data to help inform this issue, and
solicits comments on particular provisions of the general industry and
construction standards that may or may not be appropriate for cement
workers.
29. OSHA has proposed to exempt from coverage Cr(VI) exposures
occurring in the application of pesticides in general industry (such as
the treatment of wood with chromium copper arsenate (CCA)) because
pesticide application is regulated by EPA, and section 4(b)(1) of the
OSH Act precludes OSHA from regulating where other Federal agencies
exercise their statutory authority to do so. OSHA has proposed to cover
exposures resulting from use of treated materials. Is this approach
appropriate? Are there any instances where EPA-regulated pesticide
application occurs in construction or shipyard workplaces?
30. Describe any additional industries, processes, or applications
that should be exempted from the Cr(VI) standard and provide detailed
reasons for any requested exemption. In
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particular, are the epidemiologic and experimental studies sufficient
to support OSHA's the inclusion of various industries or processes
under the scope of the proposed standard? Please provide the rationale
and supporting data for your response.
31. Can the proposed Cr(VI) standard for the construction industry
be modified in any way to better account for the workplace conditions
in that industry, while still providing appropriate protection to
Cr(VI)-exposed workers in that industry? Would an alternative approach
similar to that used in OSHA's asbestos standard, where the application
of specified controls in certain situations would be considered
adequate to meet the requirements of the standard, be useful? Is there
enough information available to define such technology specifications?
32. Can the proposed Cr(VI) standard for shipyards be modified in
any way to better account for the workplace conditions in that
industry, while still providing appropriate protection to Cr(VI)-
exposed workers in that industry?
33. OSHA has proposed a TWA PEL for Cr(VI) of 1.0 [mu]g/
m3. The Agency has made a preliminary determination that
this is the lowest level that is both technologically and economically
feasible and is necessary to reduce significant risks of material
health impairment from exposure to Cr(VI). Is this PEL appropriate and
is it adequately supported by the existing data? If not, what PEL would
be more appropriate or would more adequately protect employees from
Cr(VI)-associated health risks? Provide evidence to support your
response.
34. Should different PELs be established for different Cr(VI)
compounds? If so, how should they be established? Where possible,
provide specific detail about how different PELs could be established
and how the Agency should apply those PELs in instances where workers
may be exposed to more than one Cr(VI) compound.
35. OSHA has proposed an action level for Cr(VI) exposure in
general industry, but not in construction or shipyards. Is this an
appropriate approach? Should OSHA set an action level for exposure to
Cr(VI) in construction and shipyards? Should the proposed action level
in general industry be retained in the final rule?
36. If an action level is included in the final rule, is the
proposed action level for general industry (0.5 [mu]g/m3)
the appropriate level for the PEL under consideration? If not, at what
level should the action level be set?
37. If an action level is included in the final rule, which
provisions should be triggered by exposure above the action level?
Indicate the basis for your position and include any supporting
information.
38. If no action level is included in the final rule, which
provisions should apply to all Cr(VI)-exposed workers? Which provisions
should be triggered by the PEL? Are there any other appropriate
triggers for the requirements of the standard?
39. Should OSHA set a short-term exposure limit (STEL) or ceiling
for exposure to Cr(VI)? If so, please specify the appropriate air
concentration and the rationale for its selection.
40. Do you conduct initial air monitoring or do you rely on
objective data to determine Cr(VI) exposures? Describe any other
approaches you have implemented for assessing an employee's initial
exposure to Cr(VI).
41. Describe any follow-up or subsequent exposure assessments that
you conduct. How often do you conduct such follow-up or subsequent
exposure assessments? Please comment on OSHA's estimate of baseline
industry practice and the projected costs for initial and periodic
exposure assessment. Are OSHA's estimates consistent with current
industry practice?
42. Do shipyard employers presently measure their employees'
exposure to Cr(VI)? If not, do they use some alternative method of
identifying which employees may be over-exposed to Cr(VI)?
43. OSHA has proposed specific requirements for exposure assessment
in general industry, but has not proposed that these requirements apply
to construction or shipyard employers. Should requirements for exposure
assessment in construction or shipyards be included in the final Cr(VI)
standard? Are there any advantages to requiring construction or
shipyard employers to measure their employees' exposures to Cr(VI)? If
so, would the exposure assessment requirements proposed for general
industry be appropriate? Would construction or shipyard employers
encounter situations where monitoring would be infeasible if they were
required to follow the exposure assessment requirements proposed for
employers in general industry? Indicate the basis for your position and
include any supporting information. What types of exposure assessment
strategies are effective for assessing worker exposures at construction
and shipyard worksites?
44. Should requirements for exposure assessment in general industry
be included in the final Cr(VI) standard, or would the performance-
oriented requirement proposed for construction and shipyards be more
appropriate? Indicate the basis for your position and include any
supporting information.
45. OSHA has proposed that exposure monitoring in general industry
be conducted at least every six months if exposures are above the
action level but below the PEL, and at least every three months if
exposures are at or above the PEL. Are these proposed frequencies
appropriate? If not, what frequency of monitoring would be more
appropriate, and why?
46. OSHA has proposed that regulated areas be established in
general industry wherever an employee's exposure to airborne
concentrations of Cr(VI) is, or can reasonably be expected to be, in
excess of the PEL. OSHA seeks comments on this provision and in
particular:
a. Describe any work settings where establishing regulated areas
could be problematic or infeasible. If establishing regulated areas is
problematic, what approaches might be used to warn employees in such
work settings of high risk areas (i.e., areas where the airborne
concentrations of Cr(VI) exceed the PEL?).
b. Should OSHA add hazards from eye or skin contact as a trigger
for establishing regulated areas? Explain the basis for your position,
and include any supporting information. c. Describe any methods
currently used that have been found to be effective in establishing
regulated areas.
47. OSHA has not proposed requirements for establishment of
regulated areas in construction or shipyards. Should requirements for
regulated areas for construction or shipyards be included in the final
Cr(VI) standard? If so, would the requirements for regulated areas
proposed for general industry be appropriate? Are there any particular
problems in construction or shipyard settings that make regulated areas
problematic or infeasible? If requirements for regulated areas for
construction or shipyards are not included in the final Cr(VI)
standard, should OSHA include requirements for warning signs or other
measures to alert employees of the presence of Cr(VI)? If so, what
practical means could be used to determine where and when such labeling
would be required? What potential difficulties might be encountered by
using such an approach? Indicate the basis for your position and
include any supporting information.
48. Under the proposed standard, employers are required to use
engineering and work practice controls
[[Page 59311]]
to reduce and maintain employee exposure to Cr(VI) to or below the PEL
unless the employer can demonstrate that employees are not exposed
above the PEL for 30 or more days per year, or the employer can
demonstrate that such controls are not feasible. Is this approach
appropriate for Cr(VI)? Indicate the basis for your position and
include any supporting information.
49. In OSHA's Cadmium standard (29 CFR 1010.1027), the Agency
established separate engineering control air limits (SECALs) for
certain processes in selected industries. SECALs were established where
compliance with the PEL by means of engineering and work practice
controls was infeasible. For these industries, a SECAL was established
at the lowest feasible level that could be achieved by engineering and
work practice controls. The PEL was set at a lower level, and could be
achieved by any allowable combination of controls. SECALs thus allowed
OSHA to establish a lower PEL for cadmium than would otherwise have
been possible, given technological feasibility constraints. Should OSHA
establish SECALs for Cr(VI) in any industries or processes? If so, in
what industries or processes, and at what levels? Provide rationale to
support your position.
50. The proposed standard prohibits the use of job rotation for the
sole purpose of lowering employee exposures to Cr(VI). Are there any
circumstances where this practice should be allowed in order to meet
the proposed PEL?
51. OSHA is proposing that employers provide appropriate protective
clothing and equipment when a hazard is present or is likely to be
present from skin or eye contact with Cr(VI). OSHA would expect an
employer to exercise common sense and appropriate expertise to
determine if a hazard is present or likely to be present. Is this
approach appropriate? Are there other approaches that would be better
for characterizing eye and skin contact with Cr(VI)? For example, are
there methods to measure dermal exposure that could be used to
routinely monitor worker exposure to Cr(VI) that OSHA should consider
including in the final standard?
52. For employers whose employees are exposed to Cr(VI), what
approaches do you currently use to assess potential hazards from eye or
skin contact with Cr(VI)? What protective clothing and equipment do you
use to protect employees from eye or skin contact with Cr(VI)? What
does this protective clothing and equipment cost? Who pays for the
protective clothing and equipment?
53. Should OSHA require the use of protective clothing and
equipment for those employees who are exposed to airborne
concentrations of Cr(VI) in excess of the PEL? If so, what type of
protective clothing and equipment might be necessary?
54. OSHA has proposed to require that employers pay for protective
clothing and equipment provided to employees. The Agency seeks comment
on this provision, in particular:
a. Should OSHA refrain from requiring employer payment, and follow
the outcome of the rulemaking addressing employer payment for personal
protective equipment (64 FR 15401 (3/31/99))?
b. Are there circumstances where employers should not be required
to pay for clothing and equipment used to protect employees from Cr(VI)
hazards, such as situations where it is customary for employees to
provide their own protective clothing and equipment (i.e., ``tools of
the trade'')?
c. OSHA realizes that there is frequent turnover in the
construction industry, where employees frequently move from jobsite to
jobsite. This is an important factor because an employer with a high-
turnover workplace would have to buy protective clothing and equipment
for more employees if the protective clothing and equipment could only
be used by one employee. The Agency requests comment on whether this
proposal's requirement for employer payment for protective clothing and
equipment is appropriate in the construction industry. Are there any
alternative approaches that would be responsive to the turnover
situation and would also be protective of construction workers? Are
there any other issues specific to the construction industry that OSHA
should be consider in this rulemaking?
d. At some ports, employees are hired for jobs in shipyards,
longshoring, and marine terminals through a labor pool, and a single
employee may work for five different employers in the same week. How do
these factors affect who is required to pay for protective clothing and
equipment? Are there any other issues specific to shipyards,
longshoring, or marine terminals that OSHA should consider in this
rulemaking?
55. OSHA is proposing that washing facilities capable of removing
Cr(VI) from the skin be provided to affected employees, but does not
propose that showers be required. Should OSHA include requirements to
provide showers to employees exposed to Cr(VI)? If so, under what
circumstances should showers be required? Describe work situations
where showers are either unnecessary for employee protection or that
present obstacles to their implementation and describe any such
obstacles.
56. OSHA has not included housekeeping provisions in the proposed
Cr(VI) standard for construction or shipyards. The Agency has made a
preliminary determination that the housekeeping requirements proposed
for general industry are likely to be difficult to implement in the
construction and shipyard environments. Is this an appropriate
determination? If not, what practicable housekeeping measures can
construction and shipyard employers take to reduce employee exposure to
Cr(VI) at the work site? What housekeeping activities are currently
being performed?
57. Is medical surveillance being provided to Cr(VI)-exposed
employees at your worksite? If so,
a. What exposure levels or other factors trigger medical
surveillance?
b. What tests or evaluations are included in the medical
surveillance program?
c. What benefits have been achieved from the medical surveillance
program?
d. What are the costs of the medical surveillance program? How do
your current costs compare with OSHA's estimated unit costs for the
physical examination and employee time involved in the medical
surveillance program? Please comment on OSHA's baseline assumptions and
cost estimates for medical surveillance.
e. How many employees are included in your medical surveillance
program?
f. In what North American Industry Classification System (NAICS)
code does your workplace fall?
58. OSHA has proposed that medical surveillance be triggered in
general industry in the following circumstances: (1) When exposure to
Cr(VI) is above the PEL for 30 days or more per year; (2) after an
employee experiences signs or symptoms of the adverse health effects
associated with Cr(VI) exposure (e.g., dermatitis, asthma); or (3)
after exposure in an emergency. OSHA seeks comments as to whether or
not these are appropriate triggers for offering medical surveillance
and whether there are additional triggers that should be included.
Should OSHA require that medical surveillance be triggered in general
industry only upon an employee experiencing signs and symptoms of
disease or after exposure in an emergency, as in the construction and
maritime standards? OSHA also solicits comment on the optimal frequency
of medical surveillance.
[[Page 59312]]
59. OSHA has proposed that medical surveillance be triggered in
construction and shipyards in the following circumstances: (1) after an
employee experiences signs or symptoms of the adverse health effects
associated with Cr(VI) exposure (e.g., dermatitis, asthma); or (2)
after exposure in an emergency. Should medical surveillance in
construction or shipyards be triggered by exposure to Cr(VI) above the
PEL for 30 days or more per year, as proposed for general industry?
OSHA seeks comments as to whether or not the proposed triggers are
appropriate for offering medical surveillance and whether there are
additional triggers that should be included.
60. OSHA has not included certain biological tests (e.g., blood or
urine monitoring, skin patch testing for sensitization, expiratory flow
measurements for airway restriction) as a part of the medical
evaluations required to be provided to employees offered medical
surveillance under the proposed standard. OSHA has preliminarily
determined that the general application of these tests is of uncertain
value as an early indicator of potential Cr(VI)-related health effects.
However, the proposed standard does allow for the provision of any
tests (which could include urine or blood tests) that are deemed
necessary by the physician or other licensed health care professional.
Are there any tests (e.g., urine tests, blood tests, skin patch tests,
airway flow measurements, or others) that should be included under the
proposed standard's medical surveillance provisions? If there are any
that should be included, explain the rationale for their inclusion,
including the benefit to worker health they might provide, their
utility and ease of use in an occupational health surveillance program,
and associated costs.
61. OSHA has not included requirements for medical removal
protection (MRP) in the proposed standard. OSHA has made a preliminary
determination that there are few instances where temporary worker
removal and MRP will be useful. The Agency seeks comment as to whether
the final Cr(VI) standard should include provisions for the temporary
removal and extension of MRP benefits to employees with certain Cr(VI)-
related health conditions. In particular, what endpoints should be
considered for temporary removal and for what maximum amount of time
should MRP benefits be extended? OSHA also seeks information on whether
or not MRP is currently being used by employers with Cr(VI)-exposed
workers, and the costs of such programs.
62. OSHA has proposed that employers provide hazard information to
employees in accordance with the Agency's Hazard Communication standard
(29 CFR 1910.1200), and has also proposed additional requirements
regarding signs, labels, and additional training specific to work with
Cr(VI). Should OSHA include these additional requirements in the final
rule, or are the requirements of the Hazard Communication standard
sufficient?
63. OSHA has proposed that bags or containers of laundry
contaminated with Cr(VI) bear warning labels. Will this cause you to
alter your current laundry practices? Are there laundries in your area
that would accept such laundry? Would laundering costs increase? If so,
by how much?
64. OSHA requests comment on the time allowed for compliance with
the provisions of the proposed standard. Is the time proposed
sufficient, or is a longer or shorter phase-in of requirements
appropriate? Identify any industries, processes, or operations that
have special needs for additional time, the additional time required
and the reasons for the request.
65. Some other OSHA health standards have included appendices that
address topics such as the hazards associated with the regulated
substance, health screening considerations, occupational disease
questionnaires, and PLHCP obligations. OSHA has not proposed to include
any appendices with the Cr(VI) rule because the Agency has made a
preliminary determination that such topics would be best addressed with
guidance materials. What would be the advantage of including such
appendices in the final rule? If you believe they should be included,
what information should be included? What would be the disadvantage of
including these appendices in the final rule?
III. 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 to
promulgate and enforce occupational safety and health standards. 29
U.S.C. 655(a)(authorizing summary adoption of existing consensus and
federal standards within two years of Act's enactment),
655(b)(authorizing promulgation of standards pursuant to notice and
comment), 654(b)(requiring employers to comply with OSHA standards).
A safety or health standard is a standard ``which requires
conditions or the adoption of or use of one or more practices, means,
methods, operations or processes, reasonably necessary or appropriate
to provide safe or healthful employment or places of employment 29
U.S.C. 652(8).
A standard is reasonably necessary or appropriate within the
meaning of Section 652(8) if it substantially reduces or eliminates
significant risk, and is economically feasible, technologically
feasible, cost effective, consistent with prior Agency action or
supported by a reasoned justification for departing from prior Agency
actions, supported by substantial evidence, and is better able to
effectuate the Act's purpose than any national consensus standard it
supersedes. See 58 Fed. Reg. 16612-16616 (March 30, 1993).
OSHA has generally considered, at minimum, fatality risk of 1/1000
over a 45-year working lifetime to be a significant health risk. See
the Benzene standard, Industrial Union Dep't v. American Petroleum
Institute, 448 U.S. 607, 646 ((1980); the Asbestos standard,
International Union, UAW v. Pendergrass, 878 F.2d 389, 393 (D.C. Cir.
1989).
A standard is technologically feasible if the protective measures
it requires already exist, can be brought into existence with available
technology, or can be created with technology that can reasonably be
expected to be developed. American Textile Mfrs. Institute v. OSHA, 452
U.S. 490, 513 (1981)(``ATMI'') American Iron and Steel Institute v.
OSHA, 939 F.2d 975, 980 (D.C. Cir. 1991)(``AISI'').
A standard is economically feasible if industry can absorb or pass
on the costs of compliance without threatening its long-term
profitability or competitive structure. See ATMI, 452 U.S. at 530 n.
55; AISI, 939 F. 2d at 980.
A standard is cost effective if the protective measures it requires
are the least costly of the available alternatives that achieve the
same level of protection. ATMI, 453, U.S, at 514 n. 32; International
Union, UAW v. OSHA, 37 F.3d 665, 668 (D.C., Cir 1994)(``LOTO III'').
All standards must be highly protective. See 58 FR 16614-16615;
LOTO III, 37 F. 3d at 669. However, health standards must also meet the
``feasibility mandate'' of Section 6(b)(7) of the Act, 29 U.S.C.
655(b)(5). Section 6(b)(5) requires OSHA to select ``The most
protective standard consistent with feasibility'' that is needed to
reduce significant risk when regulating health standards. ATMI, 452
U.S. at 509.
[[Page 59313]]
Section 6(b)(5) also directs OSHA to base health standard on ``the
best available evidence,'' including research, demonstrations, and
experiments. 29 U.S.C. 655(b)(5). OSHA shall consider ``in addition to
the attainment of the highest degree of health and safety protection *
* * feasibility and experience gained under this and other health and
safety laws.'' Id.
Section 6(b)(7) authorizes OSHA to include among a standard's
requirements labeling, monitoring, medical testing and other
information gathering and transmittal provisions. 29 U.S.C. 655(b)(7).
Finally, whenever practical, standards shall ``be expressed in
terms of objective criteria and of the performance desired.'' Id.
IV. Events Leading to the Proposed Standards
OSHA's present standards for workplace exposure to Cr(VI) were
adopted in 1971, pursuant to section 6(a) of the OSH Act, from a 1943
American National Standards Institute (ANSI) recommendation originally
established to control irritation and damage to nasal tissues (Ex. 20-
3). OSHA's general industry standard set a permissible exposure limit
(PEL) of 1 mg chromium trioxide per 10 m3 air in the
workplace (1 mg/10 m3 CrO3) as a ceiling
concentration, which corresponds to a concentration of 52 [mu]g/
m3 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/
m3 Cr(VI), adopted from the American Conference of
Governmental Industrial Hygienists (ACGIH) 1970 Threshold Limit Value
(TLV) (36 FR 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/m3 for
chromic acid and chromates as Cr2O3 (Ex. 5-37),
and 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/m3, 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 ``There 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, p. 8). 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 (HRG), 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, OSHA was sued by HRG for unreasonable delay in issuing a
Cr(VI) standard. The U.S. Court of Appeals for the Third Court ruled in
OSHA's favor and the Agency continued its data collection and analytic
efforts on Cr(VI) (Ex. 35-208, p. 3). OSHA was sued again in 2002 by
HRG for continued unreasonable delay in issuing a Cr(VI) standard (Ex.
31-24-1). In August 2002, OSHA published a Request for Information on
Cr(VI) to solicit additional information on key issues related to
controlling exposures to Cr(VI)(67 FR 54389 (8/22/02)), and on December
4, 2002 announced its intent to proceed with developing a proposed
standard (Ex. 307). The Court ruled in favor of HRG on December 24,
2002, ordering the Agency to proceed expeditiously with a Cr(VI)
standard (Ex. 35-208). On April 2, 2003 the Court set deadlines of
October 4, 2004 for publication of a proposed standard and January 18,
2006 for publication of a final standard (Ex. 35-306).
OSHA initiated Small Business Regulatory Enforcement Act (SBREFA)
proceedings in 2003, 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).
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 in early 2004. OSHA representatives met with ACCSH in February
2004 and May 2004 to discuss the rulemaking and receive their comments
and recommendations. On February 13, ACCSH recommended that portland
cement should be included
[[Page 59314]]
within the scope of the proposed standard (Ex. 35-308, pp. 288-293) and
that identical PELs should be set for the construction, maritime, and
general industries (Ex. 35-308, pp. 293-297). The Committee recommended
on May 18 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, MACOSH decided to collect and forward additional exposure
monitoring data to OSHA to help the Agency better evaluate exposures to
Cr(VI) in shipyards (Ex. 310, 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. 310, p.
227).
V. 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. They range from very
soluble to insoluble in water. 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 potassium chromate
(lemon yellow crystals), sodium chromate (yellow crystals), and sodium
dichromate (reddish to bright orange crystals). Nickel chromate, lead
chromate oxide, and zinc chromate are completely insoluble in water.
The nickel chromate (black crystals) dissolves in nitric acid and
hydrogen peroxide. Lead chromate oxide is a red crystalline powder. The
zinc chromate (lemon yellow crystals) decomposes in hot water and is
soluble in acids and liquid ammonia. Examples of slightly soluble
Cr(VI) compounds are barium (light yellow), calcium (yellow), lead
(yellow to orange-yellow), and strontium (yellow) chromates, and zinc
chromate hydroxide (yellow). They all exist in solid form as crystals
or powder. Potassium zinc chromate hydroxide (greenish-yellow crystals)
is also slightly soluble in water.
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 (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 IX of this preamble.
VI. Health Effects
The studies of adverse health effects resulting from exposure to
hexavalent chromium (Cr(VI)) in humans and experimental animals are
summarized in the section below. Section VI includes 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. This chapter on health effects will not attempt to
describe every study ever conducted on Cr(VI) toxicity. Instead, only
the most important articles and reviews of studies will be evaluated.
A. Absorption, Distribution, Metabolic Reduction and Elimination
Chromium can exist in a number of valence states from -2 to +6
valence. The most common forms are the elemental metal Cr(0), trivalent
Cr(III), and hexavalent Cr(VI). Chromium exists naturally in the
environment in
[[Page 59315]]
chromite ore as Cr(III). Cr(0) and Cr(VI), as well as Cr(III) are
produced during industrial processes. Cr(VI) is the form considered to
be the greatest health risk. A small amount of Cr(III) is needed for
optimal insulin receptor function in human tissues but much larger
amounts may be harmful. Much less is known about the toxicity of Cr(0),
but it is believed to be converted to Cr(III) in the body and is not
considered to be a serious 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.
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. Schlesinger and
Lippman have shown a high degree of correlation between sites of
greatest particle deposition in the tracheobronchial airways and
increased incidence of bronchial tumors (Ex. 35-102). It is possible to
have a buildup of chromium at certain sites in the bronchial tree that
could create areas of very high chromium concentration. This would
especially be true for occupational environments that are particularly
dusty or contain other irritating aerosols.
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 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 anion
(CrO4)2-enter cells via facilitated diffusion
through non-specific anion channels (similar to phosphate and sulfate
anions). Suzuki et al. have demonstrated that Cr(VI) is rapidly and
extensively transported to the bloodstream in rats (Ex. 35-97). They
exposed rats to 7.3-15.9 mg Cr(VI)/m3 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. Bragt and van Dura
demonstrated that more soluble chromates are absorbed faster than less
soluble chromates (Ex. 35-56). Insoluble chromates are poorly absorbed
and therefore have longer resident time in the lungs. They studied the
kinetics of three Cr(VI) compounds: Sodium chromate, zinc chromate and
lead chromate. They instilled 51chromium-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 51chromium 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 due to irritative properties of the zinc chromate used, as it
caused hemorrhages in the lungs which were macroscopically visible as
early as 24 hours after intratracheal administration.
The studies by Langard et al. and Adachi et al. provide further
evidence of absorption of chromates from the lungs (Exs. 35-93; 189).
Rats exposed to 2.1 mg Cr(VI)/m3 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)/m3
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 that are encapsulated in a
paint matrix may be released in the lungs (Ex. 31-15, p. 2). LaPuma et
al. measured the mass of Cr(VI) released from particles into water
originating from three types of paint particles: solvent-borne expoxy
(25% strontium chromate (SrCrO4)), water-borne expoxy (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 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.
A number of questions remain unanswered regarding encapsulated
Cr(VI) and bioavailability from the lung. There is a lack of detailed
information on the encapsulation process. The efficiency of
encapsulation and whether all of the chromate molecules are
[[Page 59316]]
encapsulated is not known. The stability of the encapsulated product in
physiological and environmental conditions has not been demonstrated.
It would be useful to know if any processes can break the encapsulation
during its use. Finally, the fate of inhaled encapsulated and
unencapsulated Cr(VI) in the respiratory tract as well as the systemic
tissues needs to be more 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. 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)/cm2/hour for a 0.01 molar
solution, 6.4 [mu]g Cr(VI)/cm2/hour for a 0.1 molar
solution, and 10 [mu]g Cr(VI)/cm2/hour for a 0.2 molar
solution.
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 exposed to 51
chromium labeled Cr(VI) compounds (Ex. 35-81). In this study
radiolabeled sodium chromate solution was dermally applied to guinea
pigs and 51Cr was monitored by scintillation counting in
tissues. These studies demonstrate that the absorption of Cr(VI)
compounds can take place through the dermal route. Also, the absorption
of Cr(VI) can be facilitated by organic solvents.
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. 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 51chromium
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). The mechanism by which Cr(VI) is carried
across the intestinal wall and the site of absorption are not known and
may well depend upon the efficiency of defense mechanisms (Mertz, 1969
as cited in Ex. 19-1).
Kuykendall et al. studied the absorption of Cr(VI) in human
volunteers after oral administration of potassium dichromate (Ex. 35-
77). They reported the bioavailability based on 14-day urinary
excretion to be 6.9% (range 1.2-18%) for Cr(VI). Other investigators
have also reported absorption of Cr(VI) compounds after oral
administration (Exs. 35-76; 31-22-13; 35-91).
Studies with 51chromium in animals also indicate that
chromium and its compounds are poorly absorbed from the
gastrointestinal tract after oral exposure. When radioactive sodium
chromate (Cr(VI)) was given orally to rats, the amount of chromium in
the feces was greater than that found when sodium chromate was injected
directly into the small intestine. These results are consistent with
evidence that the gastric environment has a capacity to reduce Cr(VI)
to Cr(III) and therefore decrease the amount of Cr(VI) absorbed from
the GI tract.
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. The binding of chromium
compounds by proteins in the blood has been studied in some detail
(Exs. 5-24; 35-41; 35-52). It was found that intravenously injected
anionic Cr(VI) passes through the membrane of red blood cells and binds
to the globin fraction of hemoglobin. It has been hypothesized that
before Cr(VI) is bound by hemoglobin, it is reduced to Cr(III) by an
enzymatic reaction within red blood cells. Once inside the blood cell,
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). According to Aaseth et
al., the intracellular Cr(VI) reduction 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
[[Page 59317]]
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.
The highest lung level reported was 456 mg/10 g tissue in the first
worker, 178 in the second worker, and 1,920 for the third worker. There
were significant chromium levels in the tissue of the second worker
even though he had not been exposed to chromium for 18 years. 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. The distribution of Cr(VI) compared with Cr(III)
was investigated in guinea pigs after intratracheal instillation of
potassium dichromate or chromium trichloride (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. After chromium trichloride instillation, 69%
of the dose remained in the lungs at 20 minutes, while only 4% was
found in the blood and other tissues, with the remaining 27% cleared
from the lungs and swallowed. The only tissue that contained a
significant amount of chromium two days after instillation of chromium
trichloride was the spleen. After 30 and 60 days, 30 and 12%,
respectively, of the Cr(III) was retained in the lungs, while only 2.6
and 1.6%, respectively, of the Cr(VI) dose was retained in the lungs.
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 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.
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). As
discussed earlier, Cr(VI) is also reduced to Cr(III) in the gastric
environment by the gastric juice (Ex. 35-85) and ascorbate after oral
exposure (Ex. 35-82).
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 0.05-
1.7 mg Cr(III)/m \3\ as chromium sulfate and 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) and 92 days for Cr(III) (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 less 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 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
O'Flaherty developed physiologically-based pharmacokinetic (PBPK)
models 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-
[[Page 59318]]
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. Soluble Cr(VI) compounds enter
the bloodstream more readily than highly insoluble Cr(VI) compounds.
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, Maryland and one in Painesville,
Ohio 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, Ohio 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 consistently elevated lung
cancer mortality reported in these cohorts and the significant upward
trends with duration of employment and cumulative exposure provide some
of the strongest evidence that Cr(VI) be regarded as carcinogenic to
workers. A summary of selected human epidemiologic studies in chromate
production workers is presented in Table VI-1.
[[Page 59319]]
Table VI-1.--Summary of Selected Epidemiologic Studies of Lung Cancer in Workers Exposed to Hexavalent Chromium--
Chromate Production
----------------------------------------------------------------------------------------------------------------
Reference Chromium (VI)
Reference/exhibit number Study population population exposure Lung Cancer Risk
----------------------------------------------------------------------------------------------------------------
Hayes et al. (1979, Ex. 7-14)... 1803 male workers Baltimore City Primarily sodium --O/E of 2.0
Braver et al. (1985, Ex. 7-17).. initially mortality. chromate and (p< 0.01) based on
employed 3 or dichromate 59 lung cancer
more months 1945- production. Avg deaths.
1974 at old and Cr(VI) of 21 to --Increased risk
new Baltimore MD 413 [mu]g/m\3\ with duration of
production and avg duration employment.
facility; follow- 1.6 yr to 13 yr
up through 1977. depending on
subcohort, plant,
and year employed.
Gibb et al. (2000, Ex. 31-22-11) 2357 male workers U.S. mortality.... Primarily sodium --O/E of 1.86
initially chromate and (p< 0.01) based on
employed 1950- dichromate. Mean 71 lung cancer
1974 only at new cumulative Cr(VI) deaths.
Baltimore MD of 0.070 mg/m\3\ - --Significant
production yr and work upward mortality
facility; follow- duration of 3.1 trend with
up through 1992. yr. cumulative Cr(VI)
exposure.
Mancuso (1997, Ex. 23).......... 332 male workers Mortality rate Primarily sodium O/E not calculated
Mancuso (1975, Ex. 7-11)........ employed at directly chromate and but significant
Mancuso and Heuper (1951, Ex. 7- Painesville OH calculated using dichromate increase in age-
13).. facility 1931- the distribution production with adjusted lung
Bourne and Yee (1950, Ex. 7-98). 1937; follow-up of person years some calcium cancer death rate
through 1993. by age group for chromate as a with cumulative
the entire result of using chromium exposure
exposed high lime based on 66
population as the process. Most deaths.
standard. cumulative
soluble Cr(VI)
between 0.25 and
4.0 mg/m\3\ - yr
based on 1949
survey.
Luippold et al. (2003, Ex. 31-18- 492 male workers U.S. and Ohio Primarily sodium --O/E of
4). employed one year Mortality Rates. chromate and 2.41(p< 0.01)
between 1940 and dichromate based on Ohio
1972 at production with rates and 51
Painesville OH minor calcium deaths.
facility; follow- chromate. Mean --Significant
up through 1997. cumulative upward mortality
soluble Cr(VI) of trend with
1.58 mg/m\3\ - yr. cumulative Cr(VI)
exposure
Davies et al. (1991, Ex. 7-99).. 2298 male chromate Cancer mortality Principally sodium --O/E of 1.97
Alderson et al. (1981, Ex. 7- production of England, Wales chromate and (p< 0.01) pre-
22).. workers employed and Scotland and dichromate process change
Bistrup and Case (1956, Ex. 7- for one year unexposed local production with based on 175
20).. between 1950 and workers. some calcium deaths.
1976 at three chromate before --SMR of 1.02 (NS)
different UK switch from high post-process
plants; follow-up lime to no lime change based on
through 1989. process. Avg 14 deaths.
soluble Cr(VI) in --Increased risk
early 1950s from for high exposed
2 to 880 [mu]g/ compared with
m\3\ depending on less exposed.
job.
Korallus et al. (1993, Ex. 7- 1417 chromate Mortality rates Principally sodium --O/E of 2.27
91).. production for North Rhine- chromate and (p< 0.01) pre-
Korallus et al. (1982, Ex. 7- workers employed Westphalia region dichromate process change
26).. for one year of Germany where production with based on 66
between 1948 and plants located. some calcium deaths.
1987 at two chromate before --O/E of 1.25 (NS)
different German switch from high post-process
plants; follow-up lime to no lime change based on 9
through 1988. process. Annual deaths.
mean Cr(VI)
between 6.2 and
38 [mu]g/m\3\
after 1977.
Cr(VI) exposure
not reported
before 1977.
----------------------------------------------------------------------------------------------------------------
Observed/Expected (O/E)
Relative Risk (RR)
Not Statistically Significant (NS)
Odds Ratio (OR)
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-
[[Page 59320]]
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 was abstracted from plant records, but was not
utilized in any analyses since the investigators thought it ``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
[[Page 59321]]
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/m\3\.
The usual exposure to Cr(VI) was estimated to be 218 [mu]g/m\3\ 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 x
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/m\3\ and 7.3 years at an exposure of 218
[mu]g/m\3\. For the long-term workers hired 1950-1959, 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 [mu]g/m\3\-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.
In an attempt 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.
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.
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). 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. SMRs were not adjusted for smoking.
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 mgCrO3/m3-yr; 0.0015-0.0089
mgCrO3/m3-yr; 0.009-0.0769 mgCrO3/
m3-yr; and 0.077-5.25 mgCrO3/m3-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
[[Page 59322]]
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 asking 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 are 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 suggests that Gibb's use of U.S. and Maryland mortality
rates for developing expectations for the SMR analysis was
inappropriate and 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 employee's
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 < 1 year and
for those who worked one year or more. Exponent defined short-term
workers as those who work