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NIOSH Respiratory Diseases Research Program

Evidence Package for the National Academies' Review 2006-2007

NIOSH Programs > Respiratory Diseases > Evidence Package > 5. Respiratory Malignancies

5.2 Reduce Metal-Induced Lung Cancer (Hexavalent Chromium)

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 Risks associated with exposure to chromium were recognized five decades ago,141 and OSHA imposed a PEL of 52 μg/m3 in the 1970s. The scientific literature is definitive regarding a causal cancer link between exposure to chromium and lung cancer, but a detailed and careful exposure-response estimate has been lacking.142,143 In early 2006, Shaw Environmental Group estimated that more than 558,000 U.S. workers were exposed to hexavalent chromium (Cr[VI]) at the 52 μg/m3 PEL in 26 industrial processes across at least three industrial sectors. Most of these workers were employed in welding, painting, electroplating, and iron and steel production. Moreover, OSHA estimates that at least one million U.S. workers are exposed to chromium.144


 RDRP developed three objectives relating to Cr[VI]: conduct a risk assessment to assist OSHA, which began to reconsider proposing a Cr[VI] PEL in 2001, with rulemaking; development of a method for rapid workplace measurement of Cr[VI] that would reduce analysis costs and facilitate rapid action to reduce excessive levels of airborne Cr[VI]; and development of a portable instrument for on-site measurements of Cr[VI] that would promote more widespread monitoring of industrial sites and enable protection of workers in a greater number of industrial sectors (specifically construction).

RDRP scientists developed an improved exposure-response model for relating lung cancer to occupational airborne exposure to hexavalent chromium, and then applied this model in a risk-assessment context to estimate excess lifetime risks at various air concentrations.

There are only two known worker populations with detailed hexavalent chromium exposure history. The first, originally compiled by Mancuso145 was being updated by others and was consequently unavailable for analysis by RDRP scientists. The second, a much larger population with more intensive Cr[VI] exposure history and better smoking history, had been the focus of several published studies and was made available to RDRP scientists by Johns Hopkins University and the EPA (Drs. Peter Lees and Herman Gibbs, respectively).146 RDRP scientists analyzed this cohort for lung cancer mortality using a variety of statistical model specifications. Estimates from the two similar and best-fitting models were then used in a standard calculation for excess lifetime risk. An interesting exposure-race interaction was observed and interpretations proposed. Further analyses explored the issues of possible threshold and non-linearity in the dose-related effect.

RDRP scientists developed a sensitive, field-portable analytical method for on-site detection of trace Cr[VI] levels in workplace air samples. The method relies on a novel combination of extraction and colorimetric detection. The method allows for detection of Cr[VI] at levels well below the new OSHA PEL.

Output and Transfer

 The published RDRP risk assessment was subsequently influential and contributed to OSHA rulemaking that resulted in a revised Cr[VI] standard promulgated in early 2006. The RDRP risk assessment estimated that the excess lifetime risk from exposures to Cr[VI] at the then current OSHA permissible standard (52μg/m3 Cr[VI], measured as soluble Cr[VI]) was about 250 per thousand, thus about 250 times higher than the standard OSHA benchmark of one per thousand. The estimated exposure corresponding to one per thousand lifetime risk was 0.2μg/m3 (4, A5-9).

As in most risk assessments for carcinogens, the issues of threshold and low-dose linearity have been important in the Cr[VI] debate. The second publication from this RDRP risk assessment found no evidence to support a threshold in Cr[VI] intensity effects and no evidence to suggest saturation of defense mechanisms (such as extracellular reduction of Cr[VI] deposited on the lung epithelium) (8, A5-18).

The field-portable, rapid Cr[VI] detection method has been published in the NMAM (Method 7703). The procedure has also been patented (U.S. Patent number 6,808,931). The field technique allows for the measurement of Cr[VI] at levels well below the newly revised OSHA PEL for this chemical agent (5μg/m3). Because the method is field-portable, it can be used for on-site measurement of Cr[VI] in occupations that are not normally monitored, such as construction (9, A5-19; A5-20).

The seven RDRP publications relating to Cr[VI] are listed elsewhere (A5-21).

Intermediate Outcomes

 The new OSHA PEL has now been set at five μg/m3 Cr[VI], and OSHA’s preamble to the new Cr[VI] standard describes in detail the currently exposed population and expected benefits of the lowered PEL. Workers involved in stainless steel production and fabrication, as well as those in the production and use of chromate chemicals are the beneficiaries of this new protection. In addition, ground water Cr[VI] contamination problems may be mitigated by the successful enforcement of this limit.

The work of RDRP scientists is cited in the OSHA’s Final Rule along with the work of others.147 OSHA had originally argued against inclusion of the construction industry within the scope of the proposed rule, citing the lack of field-portable analytical capability. In formal hearings, RDRP scientists pointed out the existence of the new field method for Cr[VI], and argued that it could be used in the construction industry. OSHA later included construction within the scope of the final rule that was promulgated.

The U.S. Air Force has already started using the RDRP-developed field-portable rapid Cr[VI] detection method in aircraft painting/maintenance operations (A5-22).148 It is anticipated that applications of the field Cr[VI] method will become more widespread now that the new OSHA rule has been promulgated.

What’s Ahead

 A number of issues remain with Cr[VI] risk management, and further elucidation may permit a more nuanced regulation of Cr[VI] exposures. The relative potency of different Cr[VI] moieties cannot be estimated with current epidemiologic data, and the importance of particle size, composition, and solubility remain to be clarified. The mechanisms of carcinogenesis and role of genetic polymorphism are also areas of considerable interest. RDRP scientists have been and continue to be funded by OSHA to investigate some of these mechanistic issues.


141. Luippold RS. Mundt KA. Dell LD. Birk T [2005]. Low-level hexavalent chromium exposure and rate of mortality among U.S. chromate production employees. J Occup Environ Med. 47:381-385.

142. Park RM, Bena JF, Stayner LT, Smith RJ, Gibb HJ, Lees PSJ [2004]. Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk assessment. Risk Anal 24:1099-1108.

143. Michaels D, Monforton C, Lurie P [2006]. Selected science: an industry campaign to undermine an OSHA hexavalent chromium standard. Environ Health. 2006;5:5.

144. OSHA [2002]. 29 CFR 1910. 1847 Occupational Exposure to Hexavalent Chromium (Preventing Occupational Illness: Chromium) 29 USC 655(b); 29 USC 657.
External link: [

145. Mancuso TF [1997]. Chromium as an industrial carcinogen: Part I. Am J Indust Med. 31:129-139.

146. Lees PS [1991]. Chromium and disease: review of epidemiologic studies with particular reference to etiologic information provided by measures of exposure. Environ Health Perspect 92:93-104.

147. Federal Register [2006]. Occupational Exposure to Hexavalent Chromium, Final Rule. 71(39):10099-385.
External link:

148. England E, Grinshpun S, Carlton G, Willeke K [2000]. Metal exposure among abrasive blasting workers at four U.S. Air Force facilities. Appl Occup Environ Hyg 15:766-772.