DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

Criteria for a Recommended Standard

Occupational Exposure

to Hexavalent Chromium
On the cover left to right, top to bottom: (1) Spray painting aircraft with chromate 

paint, (2) Electroplating tank, (3) Welder, and (4) Working with Portland cement. 

Images courtesy of U.S. Navy, NIOSH Division of Applied Research and Technology, 

and Thinkstock. Used with permission.
Criteria for a Recommended Standard

Occupational Exposure

to Hexavalent Chromium

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
ii Hexavalent Chromium

This document is in the public domain and may be freely copied or reprinted

Disclaimer

Mention of any company or product does not constitute endorsement by the National Institute for 

Occupational Safety and Health (NIOSH). In addition, citations to Web sites external to NIOSH do 

not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. 

Furthermore, NIOSH is not responsible for the content of these Web sites.

Ordering Information

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documents or other information about occupational safety and health topics, contact NIOSH at

Telephone: 1–800–CDC–INFO (1–800–232–4636)

TTY: 1–888–232–6348

E-mail: cdcinfo@cdc.gov

or visit the NIOSH Web site at www.cdc.gov/niosh.

DHHS (NIOSH) Publication No. 2013–128

(Revised with minor technical changes)

September 2013

Safer • Healthier • PeopleTM
Hexavalent Chromium iii

Foreword

When the U.S. Congress passed the Occupational Safety and Health Act of 1970 (Public Law 91-

596), it established the National Institute for Occupational Safety and Health (NIOSH). Through 

the Act, Congress charged NIOSH with recommending occupational safety and health standards 

and describing exposure levels that are safe for various periods of employment, including but not 

limited to the exposures at which no worker will suffer diminished health, functional capacity, or 

life expectancy because of his or her work experience. 

Criteria documents contain a critical review of the scientific and technical information about the 

prevalence of hazards, the existence of safety and health risks, and the adequacy of control methods. By means of criteria documents, NIOSH communicates these recommended standards to 

regulatory agencies, including the Occupational Safety and Health Administration (OSHA), health 

professionals in academic institutions, industry, organized labor, public interest groups, and others 

in the occupational safety and health community.

This criteria document is derived from the NIOSH evaluation of critical health effects studies of 

occupational exposure to hexavalent chromium (Cr[VI]) compounds. It provides recommendations for controlling workplace exposures including a revised recommended exposure limit (REL) 

derived using current quantitative risk assessment methodology on human health effects data. This 

document supersedes the 1975 Criteria for a Recommended Standard: Occupational Exposure to 

Chromium(VI) and NIOSH Testimony to OSHA on the Proposed Rule on Occupational Exposure to 

Hexavalent Chromium [NIOSH 1975a, 2005a]. 

Cr(VI) compounds include a large group of chemicals with varying chemical properties, uses, and 

workplace exposures. Their properties include corrosion-resistance, durability, and hardness. Sodium dichromate is the most common chromium chemical from which other Cr(VI) compounds 

may be produced. Materials containing Cr(VI) include various paint and primer pigments, graphic 

art supplies, fungicides, corrosion inhibitors, and wood preservatives. Some of the industries in 

which the largest numbers of workers are exposed to high concentrations of Cr(VI) compounds 

include electroplating, welding, and painting. An estimated 558,000 U.S. workers are exposed to 

airborne Cr(VI) compounds in the workplace.

Cr(VI) is a well-established occupational carcinogen associated with lung cancer and nasal and 

sinus cancer. NIOSH considers all Cr(VI) compounds to be occupational carcinogens. NIOSH recommends that airborne exposure to all Cr(VI) compounds be limited to a concentration of 0.2 μg 

Cr(VI)/m3 for an 8-hr time-weighted average (TWA) exposure, during a 40-hr workweek. The REL 

is intended to reduce workers’ risk of lung cancer associated with occupational exposure to Cr(VI) 

compounds over a 45-year working lifetime. It is expected that reducing airborne workplace exposures to Cr(VI) will also reduce the nonmalignant respiratory effects of Cr(VI) compounds, including irritated, ulcerated, or perforated nasal septa and other potential adverse health effects. Because 
iv Hexavalent Chromium

Foreword

of the residual risk of lung cancer at the REL, NIOSH further recommends that continued efforts 

be made to reduce Cr(VI) exposures to below the REL. A hierarchy of controls, including elimination, substitution, engineering controls, administrative controls, and the use of personal protective 

equipment, should be followed to control workplace exposures. 

In addition to limiting airborne concentrations of Cr(VI) compounds, NIOSH recommends that 

dermal exposure to Cr(VI) be prevented in the workplace to reduce the risk of adverse dermal 

effects, including irritation, corrosion, ulcers, skin sensitization, and allergic contact dermatitis. 

An estimated 1,045,500 U.S. workers have dermal exposure to Cr(VI) in cement, primarily in the 

construction industry.

NIOSH urges employers to disseminate this information to workers and customers. NIOSH also 

requests that professional and trade associations and labor organizations inform their members 

about the hazards of occupational exposure to Cr(VI) compounds.

NIOSH appreciates the time and effort taken by the expert peer, stakeholder, and public reviewers 

to provide comments on this document. Their input strengthened this document.

John Howard, MD

Director, National Institute for 

 Occupational Safety and Health

Centers for Disease Control and Prevention
Hexavalent Chromium v

Executive Summary

In this criteria document, the National Institute for Occupational Safety and Health (NIOSH) reviews the critical health effects studies of hexavalent chromium (Cr[VI]) compounds in order to 

update its assessment of the potential health effects of occupational exposure to Cr(VI) compounds 

and its recommendations to prevent and control these workplace exposures. NIOSH reviews the 

following aspects of workplace exposure to Cr(VI) compounds: the potential for exposures (Chapter 2), analytical methods and considerations (Chapter 3), human health effects (Chapter 4), experimental studies (Chapter 5), and quantitative risk assessments (Chapter 6). Based on evaluation of this information, NIOSH provides recommendations for a revised recommended exposure 

limit (REL) for Cr(VI) compounds (Chapter 7) and other recommendations for risk management 

(Chapter 8).

This criteria document supersedes previous NIOSH Cr(VI) policy statements, including the 1975 

NIOSH Criteria for a Recommended Standard: Occupational Exposure to Chromium(VI) and NIOSH 

Testimony to OSHA on the Proposed Rule on Occupational Exposure to Hexavalent Chromium 

[NIOSH 1975a, 2005a]. Key information in this document, including the NIOSH site visits and 

the NIOSH quantitative risk assessment, were previously submitted to the Occupational Safety and 

Health Administration (OSHA) and were publicly available during the OSHA Cr(VI) rule-making 

process. OSHA published its final standard for Cr(VI) compounds in 2006 [71 Fed. Reg. 10099 

(2006)].

Cr(VI) compounds include a large group of chemicals with varying chemical properties, uses, 

and workplace exposures. Their properties include corrosion-resistance, durability, and hardness. 

Workers may be exposed to airborne Cr(VI) when these compounds are manufactured from other forms of Cr (e.g., the production of chromates from chromite ore); when products containing 

Cr(VI) are used to manufacture other products (e.g., chromate-containing paints, electroplating); 

or when products containing other forms of Cr are used in processes that result in the formation of 

Cr(VI) as a by-product (e.g., welding). In the marketplace, the most prevalent materials that contain chromium are chromite ore, chromium chemicals, ferroalloys, and metal. Sodium dichromate 

is the most common chromium chemical from which other Cr(VI) compounds may be produced. 

Cr(VI) compounds commonly manufactured include sodium dichromate, sodium chromate, potassium dichromate, potassium chromate, ammonium dichromate, and Cr(VI) oxide. Other manufactured materials containing Cr(VI) include various paint and primer pigments, graphic arts 

supplies, fungicides, and corrosion inhibitors.

An estimated 558,000 U.S. workers are exposed to airborne Cr(VI) compounds in the workplace. 

Some of the industries in which the largest numbers of workers are exposed to high concentrations of airborne Cr(VI) compounds include electroplating, welding, and painting. An estimated 

1,045,500 U.S. workers have dermal exposure to Cr(VI) in cement, primarily in the construction 

industry.
vi Hexavalent Chromium

Executive Summary

Cr(VI) is a well-established occupational carcinogen associated with lung cancer and nasal and 

sinus cancer. NIOSH considers all Cr(VI) compounds to be occupational carcinogens [NIOSH 

1988b, 2002, 2005a]. In 1989, the International Agency for Research on Cancer (IARC) critically 

evaluated the published epidemiologic studies of chromium compounds. IARC concluded 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” (i.e., IARC category “Group 1” carcinogen) [IARC 1990]. Cr(VI) compounds were reaffirmed as an IARC Group 1 carcinogen (lung) in 2009 [Straif et al. 2009; IARC 2012]. The National 

Toxicology Program (NTP) identified Cr(VI) compounds as carcinogens in its first annual report 

on carcinogens in 1980 [NTP 2011]. Nonmalignant respiratory effects of Cr(VI) compounds include irritated, ulcerated, or perforated nasal septa. Other adverse health effects, including reproductive and developmental effects, have been reviewed by other government agencies [71 Fed. Reg. 

10099 (2006); ATSDR 2012; EPA 1998; Health Council of the Netherlands 2001; OEHHA 2009].

Studies of the Baltimore and Painesville cohorts of chromate production workers [Gibb et al. 2000b; 

Luippold et al. 2003] provide the best information for predicting Cr(VI) cancer risks because of the 

quality of the exposure estimation, large amount of worker data available for analysis, extent of exposure, and years of follow-up [NIOSH 2005a]. NIOSH selected the Baltimore cohort [Gibb et al. 

2000b] for analysis because it has a greater number of lung cancer deaths, better smoking histories, 

and a more comprehensive retrospective exposure archive. The NIOSH risk assessment estimates 

an excess lifetime risk of lung cancer death of 6 per 1,000 workers at 1 μg Cr(VI)/m3 (the previous REL) and approximately 1 per 1,000 workers at 0.2 μg Cr(VI)/m3

 (the revised REL) [Park et 

al. 2004]. The basis for the previous REL for carcinogenic Cr(VI) compounds was the quantitative 

limitation of the analytical method available in 1975.

Based on the results of the NIOSH quantitative risk assessment [Park et al. 2004], NIOSH recommends that airborne exposure to all Cr(VI) compounds be limited to a concentration of 0.2 μg 

Cr(VI)/m3 for an 8-hr TWA exposure, during a 40-hr workweek. The REL is intended to reduce 

workers’ risk of lung cancer associated with occupational exposure to Cr(VI) compounds over a 

45-year working lifetime. It is expected that reducing airborne workplace exposures to Cr(VI) will 

also reduce the nonmalignant respiratory effects of Cr(VI) compounds, including irritated, ulcerated, or perforated nasal septa and other potential adverse health effects. Because of the residual 

risk of lung cancer at the REL, NIOSH recommends that continued efforts be made to reduce exposures to Cr(VI) compounds below the REL. 

The available scientific evidence supports the inclusion of all Cr(VI) compounds into this recommendation. Cr(VI) compounds studied have demonstrated their carcinogenic potential in animal, 

in vitro, or human studies [NIOSH 1988b; 2002; 2005a,b]. Molecular toxicology studies provide 

additional support for classifying Cr(VI) compounds as occupational carcinogens. 

The NIOSH REL is a health-based recommendation derived from the results of the NIOSH quantitative risk assessment conducted on human health effects data. Additional considerations include 

analytical feasibility and the achievability of engineering controls. NIOSH Method 7605, OSHA 

Method ID-215, and international consensus standard analytical methods can quantitatively assess 

worker exposure to Cr(VI) at the REL. Based on a qualitative assessment of workplace exposure 
Hexavalent Chromium vii

Executive Summary

data, NIOSH acknowledges that Cr(VI) exposures below the REL can be achieved in some workplaces using existing technologies but are more difficult to control in others [Blade et al. 2007]. 

Some operations, including hard chromium electroplating, chromate-paint spray application, atomized-alloy spray-coating, and welding may have difficulty in consistently achieving exposures 

at or below the REL by means of engineering controls and work practices [Blade et al. 2007]. The 

extensive analysis of workplace exposures conducted for the OSHA rule-making process supports 

the NIOSH assessment that the REL is achievable in some workplaces but difficult to achieve in 

others [71 Fed. Reg. 10099 (2006)]. 

A hierarchy of controls, including elimination, substitution, engineering controls, administrative 

controls, and the use of personal protective equipment, should be followed to control workplace 

exposures. The REL is intended to promote the proper use of existing control technologies and to 

encourage the research and development of new control technologies where needed, in order to 

control workplace Cr(VI) exposures. 

At this time, there are insufficient data to conduct a quantitative risk assessment for workers exposed to Cr(VI), other than chromate production workers or specific Cr(VI) compounds other 

than sodium dichromate. However, epidemiologic studies demonstrate that the health effects of 

airborne exposure to Cr(VI) are similar across workplaces and industries (see Chapter 4). Therefore, the results of the NIOSH quantitative risk assessment conducted on chromate production 

workers [Park et al. 2004] are used as the basis of the REL for all workplace exposures to Cr(VI) 

compounds.

The primary focus of this document is preventing workplace airborne exposure to Cr(VI) compounds to reduce workers’ risk of lung cancer. However, NIOSH also recommends that dermal 

exposure to Cr(VI) compounds be prevented in the workplace to reduce adverse dermal effects 

including skin irritation, skin ulcers, skin sensitization, and allergic contact dermatitis. 

NIOSH recommends that employers implement measures to protect the health of workers exposed 

to Cr(VI) compounds under a comprehensive safety and health program, including hazard communication, respiratory protection programs, smoking cessation, and medical monitoring. These 

elements, in combination with efforts to maintain airborne Cr(VI) concentrations below the REL 

and prevent dermal contact with Cr(VI) compounds, will further protect the health of workers.

Hexavalent Chromium ix

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .v

Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xvii

1 Introduction 1

1.1 Purpose and Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

1.2 History of NIOSH Cr(VI) Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

1.3 The REL for Cr(VI) Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2

2 Properties, Production, and Potential for Exposure 5

2.1 Physical and Chemical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

2.2 Production and Use in the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.3 Potential Sources of Occupational Exposure . . . . . . . . . . . . . . . . . . . . . . . . .7

2.3.1 Airborne Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7

2.3.2 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

2.4 Industries with Potential Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.4.1 Airborne Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

2.4.2 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

2.5 Number of U.S. Workers Potentially Exposed . . . . . . . . . . . . . . . . . . . . . . . . 8

2.6 Measured Exposure in the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

2.6.1 NIOSH Multi-Industry Field Study [Blade et al. 2007] . . . . . . . . . . . . . . . .9

2.6.2 Shaw Environmental Report [2006] . . . . . . . . . . . . . . . . . . . . . . . . . . 11

2.6.3 Welding and Thermal Cutting of Metals . . . . . . . . . . . . . . . . . . . . . . . .21

2.7 Occupational Exposure Limits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

2.8 IDLH Value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

2.9 Future Trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

3 Measurement of Exposure 25

3.1 Air-Sampling Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

3.1.1 Air Sample Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

3.1.2 Air-Sampling Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26

3.2 Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26

3.2.1 Cr(VI) Detection in Workplace Air . . . . . . . . . . . . . . . . . . . . . . . . . . 26

3.2.2 Wipe Sampling Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27

3.3 Biological Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29

3.3.1 Biological Markers of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29
x Hexavalent Chromium

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3.3.2 Biological Markers of Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

4 Human Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

4.1 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

4.1.1 Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

4.1.2 Nasal and Sinus Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

4.1.3 Nonrespiratory Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

4.1.4 Cancer Meta-Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

4.1.5 Summary of Cancer and Cr(VI) Exposure . . . . . . . . . . . . . . . . . . . . . . 40

4.2 Nonmalignant Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41

4.2.1 Respiratory Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41

4.2.2 Dermatologic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

4.2.3 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

4.2.4 Other Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47

5 Experimental Studies 59

5.1 Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .59

5.2 Mechanisms of Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .59

5.3 Health Effects in Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62

5.3.1 Subchronic Inhalation Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

5.3.2 Chronic Inhalation Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

5.3.3 Intratracheal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65

5.3.4 Intrabronchial Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65

5.3.5 Chronic Oral Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65

5.3.6 Reproductive Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67

5.4 Dermal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67

5.4.1 Human Dermal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

5.4.2 Animal Dermal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .68

5.4.3 In Vitro Dermal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .68

5.5 Summary of Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69

6 Quantitative Assessment of Risk . . . . . . . . . . . . . . . . . . . . . . . . .71

6.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71

6.2 Baltimore Chromate Production Risk Assessments . . . . . . . . . . . . . . . . . . . . .72

6.3 Painesville Chromate Production Risk Assessments . . . . . . . . . . . . . . . . . . . . .75

6.4 Other Cancer Risk Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76

6.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .77

7 Recommendations for an Exposure Limit 79

7.1 The NIOSH REL for Cr(VI) Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . .79

7.2 Basis for NIOSH Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79

7.3 Evidence for the Carcinogenicity of Cr(VI) Compounds . . . . . . . . . . . . . . . . . .81

7.3.1 Epidemiologic Lung Cancer Studies . . . . . . . . . . . . . . . . . . . . . . . . . .81
Hexavalent Chromium xi

Contents

7.3.2 Lung Cancer Meta-Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

7.3.3 Animal Experimental Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .83

7.4 Basis for the NIOSH REL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .83

7.4.1 Park et al. [2004]Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

7.4.2 Crump et al. [2003] Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . .85

7.4.3 Risk Assessment Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

7.5 Applicability of the REL to All Cr(VI) Compounds . . . . . . . . . . . . . . . . . . . . .86

7.6 Analytical Feasibility of the REL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86

7.7 Controlling Workplace Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

7.8 Preventing Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

7.9 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87

8 Risk Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

8.1 NIOSH Recommended Exposure Limit . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

8.1.1 The NIOSH REL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

8.1.2 Sampling and Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

8.2 Informing Workers about the Hazard . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90

8.2.1 Safety and Health Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

8.2.2 Labeling and Posting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90

8.3 Exposure Control Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

8.3.1 Elimination and Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

8.3.2 Engineering Controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

8.3.3 Administrative Controls and Work Practices . . . . . . . . . . . . . . . . . . . . .97

8.3.4 Protective Clothing and Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . 97

8.4 Emergency Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100

8.5 Exposure Monitoring Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100

8.6 Medical Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102

8.6.1 Worker Participation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102

8.6.2 Medical Monitoring Program Director . . . . . . . . . . . . . . . . . . . . . . . . 103

8.6.3 Medical Monitoring Program Elements . . . . . . . . . . . . . . . . . . . . . . . .103

8.6.4 Medical Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105

8.6.5 Employer Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105

8.7 Smoking Cessation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

8.8 Record Keeping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109

Appendix A: Hexavalent Chromium and Lung Cancer in the

Chromate Industry: A Quantitative Risk Assessment . . . . . . . .127

Hexavalent Chromium xiii

Abbreviations

ACD allergic contact dermatitis

ACGIH American Conference of Governmental Industrial Hygienists

AIHA American Industrial Hygiene Association

ACS American Cancer Society

AlM alveolar macrophage

AL action level

APF assigned protection factor

ASTM American Society for Testing and Materials

ATSDR Agency for Toxic Substances and Disease Registry

BAL bronchoalveolar lavage

BEI Biological Exposure Index

CCA chromated copper arsenate

CI confidence interval

CPC chemical protective clothing

Cr chromium

Cr(0) metallic or elemental chromium

Cr(III) trivalent chromium

Cr(VI) hexavalent chromium

CrO3 chromic acid or chromium trioxide

d day

DECOS Dutch Expert Committee on Occupational Standards

DNA deoxyribonucleic acid

DPC diphenylcarbazide/diphenylcarbazone

EID Education and Information Division of the National Institute for Occupational

 Safety and Health

EPA U.S. Environmental Protection Agency

EPRI Electric Power Research Institute

FCAW flux cored arc welding

Fed. Reg. Federal Register

FEV1 forced expiratory volume in one second
xiv Hexavalent Chromium

Abbreviations

FEV1/FVC ratio of forced expiratory volume in one second (FEV1) to forced vital

 capacity (FVC)

FVC forced vital capacity

G2/M gap 2/mitosis

GHS Globally Harmonized System of Classification and Labelling of Chemicals 

GM geometric mean

GMAW gas-metal arc welding

GTAW gas-tungsten arc welding

GSD geometric standard deviation 

HCS (OSHA) Hazard Communication Standard

HEPA high-efficiency particulate air

hr hour

H2O2 hydrogen peroxide

HIF-1 hypoxia-induced factor 1

HHE Health Hazard Evaluation

IARC International Agency for Research on Cancer

ICDA International Chromium Development Association

IDLH Immediately Dangerous to Life and Health

Ig immunoglobulin

ILO International Labour Organization

IMIS Integrated Management Information System

ISO International Organization for Standardization

IU International Unit

l liter

LDH lactate dehydrogenase

LD50 lethal dose resulting in 50% mortality

LEV local exhaust ventilation

LH luteinizing hormone

LOD limit of detection

InL log-likelihood

M molar

MCE mixed cellulose ester

mg/m3 milligrams per cubic meter of air

MIG metal inert gas (welding)
Hexavalent Chromium xv

Abbreviations

mM millimolar

MMA manual metal arc (welding)

MMD mass median diameter

MMAD mass median aerodynamic diameter

MRL minimum risk level

MSDS Material Safety Data Sheet

n number (sample size)

NAG N-acetyl-β-D-glucosaminidase

nd not detectable

ng nanogram

nmol nanomoles

Ni nickel

NADPH nicotinamide adenine dinucleotide phosphate

NIOSH National Institute for Occupational Safety and Health

NOAEL no observed adverse effect level

NOES National Occupational Exposure Survey

NTP National Toxicology Program

OEL occupational exposure limit

 ̇OH hydroxyl radical

OR odds ratio

OSHA Occupational Safety and Health Administration

P probability

PAPR powered air-purifying respirator

PBZ personal breathing zone

PCMR proportionate cancer mortality ratio

PEL Permissible Exposure Limit

PPE personal protective equipment

ppm parts per million

PVC polyvinyl chloride

redox reduction-oxidation

REL Recommended Exposure Limit

ROS reactive oxygen species

SD standard deviation
xvi Hexavalent Chromium

Abbreviations

SDS Safety Data Sheet

SIC Standard Industrial Classification

SMAW shielded-metal arc welding

SMR standardized mortality ratio

SOD superoxide dismutase

T tons

TIG tungsten inert gas (welding)

TLV Threshold Limit Value

TWA time-weighted average

μg microgram(s)

μg/l microgram(s) per liter

μg/m3 microgram(s) per cubic meter of air

μM micromolar

U.K. United Kingdom

U.S. United States

UV-Vis ultraviolet-visible

VEGF vascular endothelial growth factor

WHO World Health Organization

wk week

yr year(s)
Hexavalent Chromium xvii

Acknowledgments

This document was prepared by the Education and Information Division (EID), Paul Schulte, Director; Document Development Branch, T.J. Lentz, Chief; Risk Evaluation Branch, Christine 

Sofge, Chief. Kathleen MacMahon was the Project Officer. Faye Rice; Robert Park; Henryka Nagy 

(NIOSH retired); Leo Michael Blade (NIOSH retired); Kevin Ashley (NIOSH/DART); G. Kent 

Hatfield (NIOSH retired); and Thurman Wenzl (NIOSH retired) were major contributors. 

For contributions to the technical content and review of this document, the authors gratefully acknowledge the following NIOSH personnel:

Division of Applied Research

 and Technology

James Bennett

Michael Gressel

Division of Respiratory Disease Studies

Lee Petsonk

Division of Surveillance, Hazard 

 Evaluations, and Field Studies

Steven Ahrenholz

Douglas Trout

Education and Information Division

David Dankovic

Charles Geraci 

Leslie Stayner

David Votaw

Ralph Zumwalde

Health Effects Laboratory Division

Vincent Castranova

Xianglin Shi

Stephen Leonard

Office of the Director

John Decker

Matthew Gillen

Paul Middendorf

Anita Schill

Pittsburgh Research Laboratory

Heinz Ahlers

Roland Berry Ann

Pengfei Gao

Bill Hoffman

Bob Stein

Doris Walter
xviii Hexavalent Chromium

Acknowledgments

The authors wish to thank Vanessa Williams for the document design and layout. Editorial and 

document assistance was provided by John Lechliter, Norma Helton, and Daniel Echt.

Special appreciation is expressed to the following individuals for serving as independent, external 

peer reviewers and providing comments that contributed to the development of this document: 

Harvey J. Clewell, Ph.D., D.A.B.T.

Director, Center for Human Health Assessment

The Hamner Institutes for Health Sciences

Research Triangle Park, NC

Richard Danchik, Ph.D.

President, PittCon

Pittsburgh, PA 

Herman J. Gibb, Ph.D., MPH

President, Tetra Tech Sciences

Arlington, VA

Edwin van Wijngaarden, Ph.D.

Associate Professor of Community and Preventive Medicine,

Environmental Medicine, and Dentistry

Chief, Division of Epidemiology

University of Rochester School of Medicine and Dentistry

John Wise, Ph.D.

Professor, Toxicology and Molecular Epidemiology

Department of Applied Medical Sciences

Director, Maine Center for Toxicology and Environmental Health

University of Southern Maine
Hexavalent Chromium 1

1 Introduction

1.1 Purpose and Scope

This criteria document describes the most recent 

NIOSH scientific evaluation of occupational exposure to hexavalent chromium (Cr[VI]) compounds, including the justification for a revised 

recommended exposure limit (REL) derived using current quantitative risk assessment methodology on human health effects data. This criteria document focuses on the relevant critical 

literature published since the 1975 Criteria for a 

Recommended Standard: Occupational Exposure 

to Chromium(VI) [NIOSH 1975a]. The policies 

and recommendations in this document provide updates to the NIOSH Testimony on the 

OSHA Proposed Rule on Occupational Exposure 

to Hexavalent Chromium and the corresponding NIOSH Post-Hearing Comments [NIOSH 

2005a,b]. This final document incorporates the 

NIOSH response to peer, stakeholder, and public review comments received during the external review process.

1.2 History of NIOSH

Cr(VI) Policy

In the 1973 Criteria for a Recommended Standard: Occupational Exposure to Chromic Acid, 

NIOSH recommended that the federal standard 

for chromic acid, 0.1 mg chromium trioxide/

m3, as a 15-minute ceiling concentration, be 

retained because of reports of nasal ulceration 

occurring at concentrations only slightly above 

this concentration [NIOSH 1973a]. In addition, 

NIOSH recommended 0.05 mg chromium 

trioxide/m3 time-weighted average (TWA) for 

an 8-hour workday, 40-hour work week, to 

protect against possible chronic effects, including lung cancer and liver damage. 

In the 1975 Criteria for a Recommended Standard: Occupational Exposure to Chromium(VI), 

NIOSH supported two distinct recommended 

standards for Cr(VI) compounds [NIOSH 

1975a]. Some Cr(VI) compounds were considered noncarcinogenic at that time, including 

the chromates and bichromates of hydrogen, 

lithium, sodium, potassium, rubidium, cesium, and ammonium, and chromic acid anhydride. These Cr(VI) compounds are relatively 

soluble in water. It was recommended that 

a 10-hr TWA limit of 25 μg Cr(VI)/m3 and a 

15-minute ceiling limit of 50 μg Cr(VI)/m3 be 

applied to these Cr(VI) compounds.

All other Cr(VI) compounds were considered 

carcinogenic [NIOSH 1975a]. These Cr(VI) 

compounds are relatively insoluble in water. 

At that time, NIOSH subscribed to a carcinogen policy that called for “no detectable exposure levels for proven carcinogenic substances” 

[Fairchild 1976]. The basis for the REL for carcinogenic Cr(VI) compounds, 1 μg Cr(VI)/m3

TWA, was the quantitative limitation of the analytical method available at that time for measuring workplace exposures to Cr(VI). 

NIOSH revised its policy on Cr(VI) compounds in the NIOSH Testimony on the OSHA 

Proposed Rule on Air Contaminants [NIOSH 

1988b]. NIOSH testified that although insoluble Cr(VI) compounds had previously been 
2 Hexavalent Chromium

1 ■ Introduction

demonstrated to be carcinogenic, there was now 

sufficient evidence that soluble Cr(VI) compounds were also carcinogenic. NIOSH recommended that all Cr(VI) compounds, whether 

soluble or insoluble in water, be classified as potential occupational carcinogens based on the 

OSHA carcinogen policy. NIOSH also recommended the adoption of the most protective of 

the available standards, the NIOSH RELs. Consequently the REL of 1 μg Cr(VI)/m3

 TWA was 

adopted by NIOSH for all Cr(VI) compounds.

NIOSH reaffirmed its policy that all Cr(VI) 

compounds be classified as occupational carcinogens in the NIOSH Comments on the 

OSHA Request for Information on Occupational Exposure to Hexavalent Chromium and the 

NIOSH Testimony on the OSHA Proposed Rule 

on Occupational Exposure to Hexavalent Chromium [NIOSH 2002, 2005a]. Other NIOSH 

Cr(VI) policies were reaffirmed or updated at 

that time [NIOSH 2002, 2005a]. This criteria 

document updates the NIOSH Cr(VI) policies, 

including the revised REL, based on its most 

recent scientific evaluation. 

1.3 The REL for Cr(VI)

Compounds

NIOSH recommends that airborne exposure 

to all Cr(VI) compounds be limited to a concentration of 0.2 μg Cr(VI)/m3

 for an 8-hr 

TWA exposure during a 40-hr workweek. 

The use of NIOSH Method 7605 (or validated 

equivalents) is recommended for Cr(VI) determination. The REL represents the upper 

limit of exposure for each worker during each 

work shift. Because of the residual risk of lung 

cancer at the REL, NIOSH further recommends that all reasonable efforts be made to 

reduce exposures to Cr(VI) compounds below 

the REL. The available scientific evidence supports the inclusion of all Cr(VI) compounds 

into this recommendation. The REL is intended 

to reduce workers’ risk of lung cancer associated with occupational exposure to Cr(VI) 

compounds over a 45-year working lifetime. 

Although the quantitative analysis is based on 

lung cancer mortality data, it is expected that 

reducing airborne workplace exposures will 

also reduce the nonmalignant respiratory effects of Cr(VI) compounds, which include irritated, ulcerated, or perforated nasal septa. 

Workers are exposed to various Cr(VI) compounds in many different industries and workplaces. Currently there are inadequate exposure 

assessment and health effects data to quantitatively assess the occupational risk of exposure 

to each Cr(VI) compound in every workplace. 

NIOSH used the quantitative risk assessment 

of chromate production workers conducted by 

Park et al. [2004] as the basis for the derivation of the revised REL for Cr(VI) compounds. 

This assessment analyzes the data of Gibb et al. 

[2000b], the most extensive database of workplace Cr(VI) exposure measurements available, 

including smoking data on most workers. These 

chromate production workers were exposed primarily to sodium dichromate, a soluble Cr(VI) 

compound. Although the risk of worker exposure to insoluble Cr(VI) compounds cannot be 

quantified, the results of animal studies indicate that this risk is likely as great, if not greater 

than, exposure to soluble Cr(VI) compounds 

[Levy et al. 1986]. The carcinogenicity of insoluble Cr(VI) compounds has been demonstrated in animal and human studies [NIOSH 

1988b]. Animal studies have demonstrated the 

carcinogenic potential of soluble and insoluble Cr(VI) compounds [NIOSH 1988b, 2002, 

2005a; ATSDR 2012]. Recent molecular toxicology studies provide further support for classifying Cr(VI) compounds as occupational carcinogens without providing sufficient data to 

quantify different RELs for specific compounds 

[NIOSH 2005a]. Based on its evaluation of the 

data currently available, NIOSH recommends 
Hexavalent Chromium 3

1 ■ Introduction

that the REL apply to all Cr(VI) compounds. 

There are inadequate data to exclude any single 

Cr(VI) compound from this recommendation. 

In addition to limiting airborne concentrations 

of Cr(VI) compounds, NIOSH recommends 

that dermal exposure to Cr(VI) be prevented 

in the workplace to reduce the risk of adverse 

dermal health effects, including irritation, ulcers, skin sensitization, and allergic contact 

dermatitis.

Hexavalent Chromium 5

2 Properties, Production,and Potential for Exposure

2.1 Physical and Chemical

Properties

Chromium (Cr) is a metallic element that occurs in several valence states, including Cr−4

and Cr−2 through Cr+6. In nature, chromium exists almost exclusively in the trivalent (Cr[III]) 

and hexavalent (Cr[VI]) oxidation states. In 

industry, the oxidation states most commonly 

found are Cr(0)  (metallic or elemental chromium), Cr(III), and Cr(VI). 

Chemical and physical properties of select 

Cr(VI) compounds are listed in Table 2–1. The 

chemical and physical properties of Cr(VI) 

compounds relevant to workplace sampling 

and analysis are discussed further in Chapter 3, 

“Measurement of Exposure.”

2.2 Production and Use in

the United States

In the marketplace, the most prevalent materials that contain chromium are chromite ore, 

chromium chemicals, ferroalloys, and metal. 

In 2010, the United States consumed about 2% 

of world chromite ore production in imported materials such as chromite ore, chromium 

chemicals, chromium ferroalloys, chromium 

metal, and stainless steel [USGS 2011]. One 

U.S. company mined chromite ore and one 

U.S. chemical firm used imported chromite to 

produce chromium chemicals. Stainless- and 

heat-resisting-steel producers were the leading consumers of ferrochromium. The United 

States is a major world producer of chromium 

metal, chromium chemicals, and stainless steel 

[USGS 2009]. Table 2–2 lists select statistics 

of chromium use in the United States [USGS 

2011].

Sodium dichromate is the primary chemical 

from which other Cr(VI) compounds are produced. Currently the United States has only 

one sodium dichromate production facility. 

Although production processes may vary, the 

following is a general description of Cr(VI) 

compound production. The process begins 

by roasting chromite ore with soda ash and 

varying amounts of lime at very high temperatures to form sodium chromate. Impurities 

are removed through a series of pH adjustments and filtrations. The sodium chromate 

is acidified with sulfuric acid to form sodium 

dichromate. Chromic acid can be produced 

by reacting concentrated sodium dichromate 

liquor with sulfuric acid. Other Cr(VI) compounds can be produced from sodium dichromate by adjusting the pH and adding other 

compounds. Solutions of Cr(VI) compounds 

thus formed can then be crystallized, purified, packaged, and sold. Cr(VI) compounds 

commonly manufactured include sodium 

dichromate, sodium chromate, potassium dichromate, potassium chromate, ammonium 

dichromate, and Cr(VI) oxide. Other materials containing Cr(VI) commonly manufactured include various paint and primer pigments, graphic art supplies, fungicides, and 

corrosion inhibitors.
6 Hexavalent Chromium

2 ■ Properties, Production, and Potential for Exposure

Table 2–1. Chemical and physical properties of select hexavalent chromium compounds 

Solubility

Cold water Other

Compound

Molecular 

weight

Boiling 

point (°C)

Melting point 

(°C) g/100 cc °C

Ammonium

chromate

152.07 — Decomposes

at 180

 40.5 30 Insoluble in alcohol; 

slightly soluble in 

NH3, acetone

Ammonium 

dichromate

252.06 — Decomposes

at 170

 30.8 15 Soluble in alcohol; 

insoluble in acetone

Barium chromate 253.32 — — 0.00034 160 Soluble in mineral 

acid

Calcium chromate 

(dehydrate)

156.07 — −2H2O, 200 16.3 20 Soluble in acid, 

alcohol

Chromium (VI) 

oxide (chromic 

acid)

 99.99 Decomposes 196 67.45 100 Soluble in alcohol, 

ether, sulfuric acid, 

nitric acid

Lead chromate 323.19 Decomposes 844 0.0000058 25 Soluble in acid, 

alkali; insoluble in 

acetic acid

Lead chromate 

oxide

546.39 — — Insoluble — Soluble in acid, 

alkali

Potassium

chromate

194.19 — 968.3

975

62.9 

 36

20

20

Insoluble in alcohol

Potassium

dichromate

294.18 Decomposes 

at 500

Triclinic becomes 

monoclinic at 

241.6; Melting 

point is 398

4.9 

102

0

100

Insoluble in alcohol

Silver chromate 331.73 — Decomposes 0.0014 — Soluble in NH4OH, 

KCN

Sodium chromate 161.97 — 19.92 87.3 30 Slightly soluble in 

alcohol; soluble in 

MeOH

Sodium

dichromate 

261.97 Decomposes 

at 400

(anhydrous)

— 238

(anhydrous)

180

0

20

Insoluble in alcohol

Strontium

chromate

203.61 — — 0.12 15 Soluble in HCl, 

HNO3, acetic acid, 

NH4 salts

Zinc chromate 181.36 — — Insoluble Insoluble Soluble in acid, liquid NH3

; insoluble 

in acetone

Source: The Merck Index [2006].
Hexavalent Chromium 7

2 ■ Properties, Production, and Potential for Exposure

2.3 Potential Sources of

Occupational Exposure

2.3.1 Airborne Exposure

Workers are potentially exposed to airborne 

Cr(VI) compounds in three different workplace 

scenarios: (1) when Cr(VI) compounds are 

manufactured from other forms of Cr such as 

in the production of chromates from chromite 

ore; (2) when products or substances containing Cr(VI) are used to manufacture other products such as chromate-containing paints; or (3) 

when products containing other forms of Cr are 

used in processes and operations that result in 

the formation of Cr(VI) as a by-product, such 

as in welding. 

Many of the processes and operations with 

worker exposure to Cr(VI) are those in which 

products or substances that contain Cr(VI) are 

used to manufacture other products. Cr(VI) 

compounds impart critical chemical and physical properties such as hardness and corrosion 

resistance to manufactured products. Chromate compounds used in the manufacture of 

paints result in products with superior corrosion resistance. Chromic acid used in electroplating operations results in the deposition of a 

durable layer of chromium metal onto a basemetal part. Anti-corrosion pigments, paints, 

and coatings provide durability to materials 

and products exposed to the weather and other 

extreme conditions.

Operations and processes in which Cr(VI) is 

formed as a by-product include those utilizing 

metals containing metallic chromium, including welding and the thermal cutting of metals; 

steel mills; and iron and steel foundries. Ferrous metal alloys contain chromium metal in 

varying compositions, lower concentrations 

in mild steel and carbon steel, and higher 

concentrations in stainless steels and other 

high-chromium alloys. The extremely high 

temperatures used in these operations and 

processes result in the oxidation of the metallic forms of chromium to Cr(VI). In welding 

operations both the base metal of the parts being joined and the consumable metal  (welding rod or wire) added to create the joint have 

varying compositions of chromium. During the 

welding process, both are heated to the melting 

point, and a fraction of the melted metal vaporizes. Any vaporized metal that escapes the 

welding-arc area quickly condenses and oxidizes 

into welding fume, and an appreciable fraction 

of the chromium in this fume is in the form 

of Cr(VI)  [EPRI  2009; Fiore  2006; Heung et 

al. 2007]. The Cr(VI) content of the fume and the 

resultant potential for Cr(VI) exposures are dependent on several process factors, most importantly the welding process and shield-gas type, 

and the Cr content of both the consumable material and the base metal [Keane et al. 2009; Heung 

et al. 2007; EPRI 2009; Meeker et al. 2010]. 

The bioaccessibility of inhaled Cr(VI) from 

welding fume may vary depending on the 

Table 2–2. Selected chromium statistics, United States, 2007–2010

(In thousands of metric tons, gross weight)

Statistic 2007 2008 2009 2010

Production, recycling 162 146 141 144

Imports for consumption 485 559 273 499

Exports 291 287 280 274

Source: USGS [2012].
8 Hexavalent Chromium

2 ■ Properties, Production, and Potential for Exposure

fume-generation source. Characterizations of 

bioaccessibility and biological indices of Cr(VI) 

exposure have been reported [Berlinger et al. 2008; 

Scheepers et al. 2008; Brand et al. 2010].

2.3.2 Dermal Exposure 

Dermal exposure to Cr(VI) may occur with 

any task or process in which there is the potential for splashing, spilling, or other skin 

contact with material that contains Cr(VI). If 

not adequately protected, workers’ skin may 

be directly exposed to liquid forms of Cr(VI) 

as in electroplating baths or solid forms, as in 

Portland cement. Dermal exposure may also 

occur because of the contamination of workplace surfaces or equipment. Sanitation and 

hygiene practices and the use of adequate PPE 

are important to preventing dermal exposures, 

contamination of workplace surfaces, and 

take-home exposures.

2.4 Industries with

Potential Exposure

2.4.1 Airborne Exposure

Workers have potential exposures to airborne 

Cr(VI) compounds in many industries, including chromium metal and chromium metal alloy production and use, electroplating, welding, and the production and use of compounds 

containing Cr(VI). Primary industries with the 

majority of occupational exposures to airborne 

Cr(VI) compounds include welding, painting, 

electroplating, steel mills, iron and steel foundries, wood preserving, paint and coatings production, chromium catalyst production, plastic colorant producers and users, production 

of chromates and related chemicals from chromite ore, plating mixture production, printing 

ink producers, chromium metal production, 

chromate pigment production, and chromated copper arsenate (CCA) producers [Shaw 

Environmental 2006]. Industries with limited 

potential for occupational exposure to Cr(VI) 

compounds include chromium dioxide, chromium dye, and chromium sulfate production; 

chemical distribution; textile dyeing; glass 

production; printing; leather tanning; chromium catalyst use; refractory brick production; 

woodworking; solid waste incineration; oil and 

gas well drilling; Portland cement production; 

non-ferrous superalloy production and use; 

construction; and makers of concrete products 

[Shaw Environmental 2006]. 

2.4.2 Dermal Exposure

The construction industry has the greatest 

number of workers at risk of dermal exposure 

to Cr(VI) due to working with Portland cement. 

Exposures can occur from contact with a variety of construction materials containing Portland cement, including cement, mortar, stucco, 

and terrazzo. Examples of construction workers 

with potential exposure to wet cement include 

bricklayers, cement masons, concrete finishers, 

construction craft laborers, hod carriers, plasterers, terrazzo workers, and tile setters [CPWR 

1999a; NIOSH 2005a; OSHA 2008]. 

Workers in many other industries are at risk of 

dermal exposure if there is any splashing, spilling, or other skin contact with material containing Cr(VI). Other industries with reported 

dermal exposure include chromate production 

[Gibb et al. 2000a]; electroplating [Makinen 

and Linnainmaa 2004a]; and grinding of stainless and acid-proof steel [Makinen and Linnainmaa 2004b]. 

2.5 Number of U.S. Workers

Potentially Exposed

The National Occupational Hazard Survey, 

conducted by NIOSH from 1972 through 1974, 

estimated that 2.5 million workers were potentially exposed to chromium and its compounds 

[NIOSH 1974]. It was estimated that 175,000 
Hexavalent Chromium 9

2 ■ Properties, Production, and Potential for Exposure

workers were potentially exposed to Cr(VI) 

compounds. The National Occupational Exposure Survey (NOES), conducted from 1981 

through 1983, estimated that 196,725 workers 

were potentially exposed to Cr(VI) compounds 

[NIOSH 1983a]. These estimates are obsolete. 

They are provided for historical purposes only.

In 1981, Centaur Research, Inc. estimated that 

391,400 workers were exposed to Cr(VI) in U.S. 

workplaces, with 243,700 workers exposed to 

Cr(VI) only and an additional 147,700 workers exposed to a mixture of Cr(VI) and other 

forms of chromium [Centaur 1981].

In 1994, Meridian Research, Inc. estimated 

that the number of production workers in U.S. 

industries with potential exposure to Cr(VI) 

was 808,177 [Meridian 1994]. Industries included in the analysis included electroplating, welding, painting, chromate producers, 

chromate pigment producers, CCA producers, 

chromium catalyst producers, paint and coatings producers, printing ink producers, plastic 

colorant producers, plating mixture producers, 

wood preserving, ferrochromium producers, 

iron and steel producers, and iron and steel 

foundries. More than 98 percent of the potentially exposed workforce was found in six 

industries: electroplating, welding, painting, 

paint and coatings production, iron and steel 

production, and iron and steel foundries.

In 2006, OSHA estimated that more than 

558,000 U.S. workers were exposed to Cr(VI) 

compounds [71 Fed. Reg.* 10099 (2006); Shaw 

Environmental 2006]. The largest number of 

workers potentially exposed to Cr(VI) were in 

the following application groups: carbon steel 

welding (>  141,000), stainless steel welding 

(> 127,000), painting (>  82,000), electroplating (> 66,000), steel mills (> 39,000), iron and 

steel foundries (>  30,000), and textile dyeing 

(>  25,000) [71 Fed. Reg. 10099 (2006); Shaw 

*

Federal Register. See Fed. Reg. in references.

Environmental 2006]. Within the welding 

application group (stainless steel and carbon steel combined), the largest numbers of 

exposed workers were reported in the construction (>  140,000) and general industries 

(>  105,000). Within the painting application 

group, the largest number of exposed workers was reported in the general (> 37,000) and 

construction industries (>  33,000). Table 2–3 

summarizes the estimated number of workers exposed by application group [71 Fed. Reg. 

10099 (2006)].

In addition to those workers exposed to airborne 

Cr(VI) compounds, an estimated 1,045,500 U.S. 

workers are potentially exposed to Cr(VI) in 

cement [Shaw Environmental 2006]. Most of 

these workers are exposed to wet cement.

2.6 Measured Exposure in

the Workplace

2.6.1 NIOSH Multi-Industry Field

Study [Blade et al. 2007]

From 1999 through 2001, NIOSH conducted a 

Cr(VI) field research study consisting of industrial hygiene and engineering surveys at 21 selected sites representing a variety of industrial 

sectors, operations, and processes [Blade et 

al. 2007]. This study characterized workers’ 

exposures to airborne particulate containing 

Cr(VI) and evaluated existing technologies for 

controlling these exposures. Evaluation methods included the collection of full work shift, 

personal breathing-zone (PBZ) air samples for 

Cr(VI), measurement of ventilation system 

parameters, and documentation of processes 

and work practices. Operations and facilities 

evaluated included chromium electroplating; 

painting and coating; welding in construction; 

metal-cutting operations on materials containing chromium in ship breaking; chromatepaint removal with abrasive blasting; atomized 

alloy-spray coating; foundry operations; printing; 
10 Hexavalent Chromium

2 ■ Properties, Production, and Potential for Exposure

and the manufacture of refractory brick, colored glass, prefabricated concrete products, 

and treated wood products. The field surveys 

represent a series of case studies rather than a 

statistically representative characterization of 

U.S. occupational exposures to Cr(VI). A limitation of this study is that for some operations 

only one or two samples were collected.

The industrial processes and operations were 

classified into four categories, using the exposure and exposure-control information collected at each site. Each category was determined 

based on a qualitative assessment of the relative 

difficulty of controlling Cr(VI) exposures to 

the existing REL of 1 μg/m3. The measured exposures were compared with the existing REL. 

Table 2–3. Estimated number of workers exposed to Cr(VI) by application group 

Application group Number of exposed workers

Welding (stainless steel and carbon steel) 269,379

Painting 82,253

Electroplating 66,859

Steel mills 39,720

Iron and steel foundries 30,222

Textile dyeing 25,341

Woodworking 14,780

Printing 6,600

Glass producers 5,384

Construction, other* 4,069

Chemical distributors 3,572

Paint and coatings producers 2,569

Solid waste incineration 2,391

Non-ferrous metallurgical uses 2,164

Chromium catalyst users 949

Plastic colorant producers and users 492

Chromium catalyst producers 313

Chromate production 150

Plating mixture producers 118

Printing ink producers 112

Chromium dye producers 104

Refractory brick producers 90

Ferrochromium producers 63

Chromate pigment producers 52

Chromated copper arsenate producers 27

Chromium sulfate producers 11

Total 558,431

Adapted from 71 Fed. Reg. 10099, Table VIII-3 [2006].

*Does not include welding, painting, and woodworking; does include government construction.
Hexavalent Chromium 11

2 ■ Properties, Production, and Potential for Exposure

For exposures exceeding the existing REL, the 

extent to which the REL was exceeded was 

considered, and a qualitative assessment of the 

effectiveness of the existing controls was made. 

An assessment based on professional judgment 

determined the relative difficulty of improving 

control effectiveness to achieve the REL. The 

four categories into which the processes or operations were categorized are as follows: 

1. Those with minimal worker exposures to 

Cr(VI) in air (Table 2–4). 

2. Those with workers’ exposures to Cr(VI) in 

air easier to control to existing NIOSH REL 

than categories (3) and (4) (Table 2–5). 

3. Those with workers’ exposures to Cr(VI) in 

air moderately difficult to control to the existing NIOSH REL (Table 2–6). 

4. Those with workers’ exposures to Cr(VI) in 

air most difficult to control to the existing 

NIOSH REL (Table 2–7).

The results of the field surveys are summarized 

in Tables 2–4 through 2–7. The results characterize the potential exposures as affected by 

engineering controls and other environmental 

factors, but not by the use or disuse of PPE. The 

PBZ air samples were collected outside any respiratory protection or other PPE  (such as 

welding helmets) worn by the workers. A wide 

variety of processes and operations were classified as those with minimal worker exposures 

to Cr(VI) in air (Table 2–4) or where workers’ 

Cr(VI) exposures were determined to be easier 

to control to the existing REL (Table 2–5). Most 

of the processes and operations where controlling workers’ Cr(VI) exposures to the existing 

REL were determined to be moderately difficult to control involved joining and cutting 

metals, when the chromium content of the materials involved was relatively high (Table 2–6). 

In the category where it was determined to 

be most difficult to control workers’ airborne 

Cr(VI) exposures to the existing REL, all of 

the processes and operations involved the application of coatings and finishes (Table 2–7). 

The classification of these processes, based on 

the potential relative difficulty of controlling 

occupational exposures to Cr(VI) in air without reliance on respiratory protection devices, 

represents qualitative assessments based on 

the professional judgment of the researchers. 

Recommendations for reducing workers’ exposures to Cr(VI) at these sites are discussed 

in Chapter 8 and in Blade et al. [2007].

2.6.2 Shaw Environmental

Report [2006]

The full-shift exposure data from OSHA and 

NIOSH site visits, NIOSH industrial hygiene 

surveys, NIOSH health hazard evaluations 

(HHEs), OSHA Integrated Management Information System (IMIS) data, U.S. Navy and 

other government and private sources were 

compiled to demonstrate the distribution of 

full-shift personal exposures to Cr(VI) compounds in various industries [Shaw Environmental 2006]. Industry sectors identified as 

having the majority of occupational exposures 

include electroplating, welding, painting, production of chromates and related chemicals 

from chromite ore, chromate pigment production, CCA production, chromium catalyst production, paint and coatings production, printing ink producers, plastic colorant producers 

and users, plating mixture production, wood 

preserving, chromium metal production, steel 

mills, and iron and steel foundries. An estimate 

of the number of workers exposed to various 

Cr(VI) exposure levels in each primary industry sector is summarized in Table 2–8 [adapted from Shaw Environmental 2006]. Industry 

sectors with the greatest number of workers 

exposed above the revised REL include welding, painting, electroplating, steel mills, and 

iron and steel foundries. These industries also 

have the greatest number of workers exposed 

to Cr(VI) compounds. 
12 Hexavalent Chromium

2 

■ Properties, Production, and Potential for Exposure

Table 2–4. Cr(VI) sampling, category 1 operations (Minimal Cr[VI] exposures).

Operation(s)

SIC‡

code

NIOSH

site no. and 

description

Key job(s) exposed

Other jobs

exposed, full-shift 

PBZ Cr(VI)

exposures in air†

(μg/m3)

Process details,

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI)

exposures in air†

Tasks,

comments

Range, μg/m3

(n =  no.

of values)

Geometric

mean, μg/m3

(GSD)

Bright chromium electroplating (mfg)

3471 (1) Chromium electroplating and coating processes (mfg) Production worker ~0.09–0.28 (n = 6) 0.15 (1.6) Place and remove parts to be plated, 

tend tanks.

None No LEV.

Chromium coating processes (nonelectroplating) (mfg)

3471 (1) Chromium electroplating and coating processes (mfg) Production worker 0.27 (n = 1) 0.25 (n = 1) N/A Place and remove parts to be coated, 

tend tanks.

Strip line operator 0.25 μg/m3 (n = 1)Dye line operator ~0.10 μg/m3 (n = 1)

No LEV. One tank on cad line covered with tarp.

TIG, fusion, dualshield welding; submerged-arc plasma cutting

3494 (14) Welding and 

cutting on stainless and mild steels (mfg)

TIG welder < 0.06–< 0.08

(n = 6, all ND)

N/A TIG welding 

on stainless steel

Fusion, dual-shield weld, submergedarc plasma cut (all on mild steel); all not detected, < 0.2 (n = 15)

Welding fume extractor LEV on welding stations, but contaminant capture poor; none on plasma cutting.

Foundry—casting operations—stainless steel, other ferrous alloys (mfg)

3324 (19) Foundry— 

stainless steel and other ferrous alloys (mfg)

All casting operations workers

0.008–0.19(n = 13)

0.032 (2.4) Melt alloy, 

pour. Alloy Cr content < 0.25%–26%

None Good LEV in old 

facility (n = 3 exposure measurements, all ≤ 0.02), but none yet in new facility.

Stick, MIG welding on steel, galvanized piping and sheet metal (construction)

1711 (20) Welding on piping and sheet metal 

(construction)

Welder < 0.04–0.42

(n = 7)(n = 4 ND)

N/A Welding 

(mainly stick) and grinding, indoors

Welding outdoors, < 0.04–0.053(n = 8)(n = 6 ND)

One indoor area had effective LEV. Other work areas in the open, partially enclosed, or passive ventilation.

See footnotes at end of table. (Continued)
Hexavalent Chromium 13

2 

■ Properties, Production, and Potential for Exposure

Operation(s)

SIC‡

code

NIOSH

site no. and 

description

Key job(s) exposed

Other jobs

exposed, full-shift 

PBZ Cr(VI)

exposures in air†

(μg/m3)

Process details,

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI)

exposures in air†

Tasks,

comments

Range, μg/m3

(n =  no.

of values)

Geometric

mean, μg/m3

(GSD)

Manufacturing of precast concrete products 3272 (10) Manufacture of pre-cast concrete 

products

Mixer operator

0.22, 0.36(n = 2)

N/A Mixes 

batches

All other jobs,< 0.02–0.25(n = 32)(n = 9 ND)

Cr(VI) is natural constituent of Portland cement. Minimal exposure-control measures, no engineering exposure controls.

Foundry—ductile iron(mfg)

3321 (15) Foundry— ductile iron (mfg) All jobs < 0.04–0.04 (n = 27)

(n = 26 ND)

N/A All foundry 

tasks

None Little to no exposure. 

LEV in furnace area, but ineffective capture. Elsewhere, general ventilation.

Crushing and recycling of concrete from demolition

1795 (12) Crushing and 

recycling of concrete from demolition

All jobs < 0.02–0.03

(n = 4)(n = 3 ND)

N/A All tasks None Cr(VI) is natural 

constituent of Portland cement. Little to no exposure. Outdoor operations, water-spray dust suppression.

Manufacturing of colored glass products, using chromate pigments

3229 (6) Manufacture of 

colored glass products

All jobs < 0.02–0.02

(n = 9)(n = 8 ND)

N/A All tasks None LEV at pigment weighing, and batch weighing and mixing; spraymist dust suppression 

at cullet station.

Table 2–4 (Continued). Cr(VI) sampling, category 1 operations (Minimal Cr[VI] exposures).

See footnotes at end of table. (Continued)
14 Hexavalent Chromium

2 

■ Properties, Production, and Potential for Exposure

Operation(s)

SIC‡

code

NIOSH

site no. and 

description

Key job(s) exposed

Other jobs

exposed, full-shift 

PBZ Cr(VI)

exposures in air†

(μg/m3)

Process details,

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI)

exposures in air†

Tasks,

comments

Range, μg/m3

(n =  no.

of values)

Geometric

mean, μg/m3

(GSD)

Screen printing (mfg) with inks containing chromate pigments

2759 (8) Screen printing 

(mfg), electronic component mfg

All jobs < 0.02

(n = 4 ND)

N/A Ink mixing, 

screen printing

None No detectable exposure. 

LEV for ink-mixing, general ventilation with HEPA-filtered supply for screenprinting.

Chromate-conversion treatment process (mfg) for electroniccomponent boards

3679 (8) Screen printing 

(mfg), electronic component mfg

All jobs < 0.02

(n = 2 ND)

N/A Operate 

chromic-acid tank (chromate conversion)

None No detectable exposure. LEV for chromic 

acid tanks, general ventilation for adjacent shipping dept.

Source: Blade et al. [2007].*Abbreviations: GSD = geometric standard deviation; n = number of samples; LEV = local exhaust ventilation; mfg=manufacturing; MIG = metal inert gas; n = number of samples; 

ND = not detected; PBZ = personal breathing zone; SIC = Standard Industrial Classification; TIG = tungsten inert gas.

†Concentration value preceded by a “less-than” symbol (<) indicates that the Cr(VI) level in the sampled air was less than the minimum detectable concentration (i.e., the mass of 

Cr[VI] collected in the sample was less than the analytical limit of detection [LOD]). A concentration value preceded by an “approximately” symbol (~) indicates that Cr(VI) was detectable in the sampled air, but at a level less than the minimum quantifiable concentration (i.e., the mass of Cr[VI] collected in the sample was between the analytical LOD and limit of quantification [LOQ]). These concentration values are less precise than fully quantifiable values.

‡SIC codes were in use when these surveys were conducted. See the SIC Manual at www.osha.gov/pls/imis/sic_manual.html.

Table 2–4 (Continued). Cr(VI) sampling, category 1 operations (Minimal Cr[VI] exposures).
Hexavalent Chromium 15

2 

■ Properties, Production, and Potential for Exposure

Table 2–5. Cr(VI) sampling, category 2 operations (Exposures easier to control to 1 μg Cr[VI]/m3 than category 3 or 4).

Operation(s)

SIC‡

code

NIOSH

site no. and

description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ 

Cr(VI) exposures in 

air† (μg/m3)

Process details, 

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

Alodyne/anodize chromium-coating processes (mfg)

3471 (2) Painting

and coating processes (mfg)

Chem line operator

0.55, 1.1(n = 2)

N/A Tending 

chromic-acid dip tanks (nonelectroplating)

Chemist (lab and waste treatment)0.82 and 1.2 μg/m3

No LEV.Dip tanks covered with tarps.

TIG weldingon stainless steelin sheet-metal fabrication (mfg)

3444 (9) Welding and 

cutting in sheetmetal fabrication(mfg)

TIGwelder

0.65(n = 1)

N/A TIG welding on 

stainless steel

None (welder’s exposure inside welding helmet = 0.67 μg/m3)

LEV for welding, but poor capture.

Manufacturing of refractory brick using chromic oxide

3297 (5) Manufacture 

of refractory brick (non-clay)

Salvage operator

0.04, 1.8(n = 2)

N/A Exposure higher 

when cleaned yellow chromate matl.

All other jobs:

0.012–0.74 (n = 20), GM = 0.052,GSD = 3.4

No LEV on the salvagematerial cleaning operation. Local ventilation, and other controls, in other areas.

Manufacturing of chromium sulfate from sodium dichromate

2819 (4) Manufacture 

of chromium sulfate

Reactor operator

0.22, 1.4(n = 2)

N/A Transfer materials, collect 

process QC samples

Railcar operator. Transfers sodium dichromate solution. 0.12, 0.22 (n = 2)

Reactors equipped with LEV, and anti-frothing surfactant. Railcar unloading is closed process.

Remove chromatecontaining paint by abrasive blasting (construction)

1721 (17) Remove paint 

(by abrasive blast) and reapply (construction)

Painter 0.10–1.3

(n = 8)

0.43 (2.3) Spot abrasive 

blasting on steel bridge

Exposures during blowdown and nonchromate repainting tasks, 0.077–0.29 (n = 7)

Work inside containment area for environmental contaminants. Natural ventilation only. Low production job, spot blasting only.

See footnotes at end of table. (Continued)
16 Hexavalent Chromium

2 

■ Properties, Production, and Potential for Exposure

Operation(s)

SIC‡

code

NIOSH

site no. and

description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ 

Cr(VI) exposures in 

air† (μg/m3)

Process details, 

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

SMAW, FCAW, dual-shield, TIG, MIG welding on stainless, other steels (shipyd)

3731 (16) Welding in 

shipyard operations

Welder 0.19–0.96

(n = 3)

0.36 (2.4) SMAW, TIG 

welding in tight below-deck spaces

TIG, MIG, stick welding in relatively open areas,< 0.04–0.22 (n = 15)

LEV was provided to varying degrees in the tight below-deck spaces by moving flex ducts to work space.

Manufacturing of products from wood treated with CrCopper-Arsenate

2452 (11) Manufacture 

of products from treated wood

Fabricator Limited 

evaluation, no full-shift measurements

N/A Sawing, drilling None (two shortterm samples collected outdoors; no 

Cr(VI) detected.)

No engineering exposure-control measures used, even indoors. Thus, indoor operations may result in detectable exposures.

Source: Blade et al. [2007].*Abbreviations: FCAW = flux cored arc welding; GM = geometric mean; GSD = geometric standard deviation; n = number of samples; LEV = local exhaust ventilation; mfg = manufacturing; MIG = metal inert gas; n = number of samples; ND = not detected; PBZ = personal breathing zone; SIC = Standard Industrial Classification; SMAW = shield-metal arc 

welding; TIG = tungsten inert gas.

†Concentration value preceded by a “less-than” symbol (<) indicates that the Cr(VI) level in the sampled air was less than the minimum detectable concentration (i.e., the mass of 

Cr[VI] collected in the sample was less than the analytical limit of detection [LOD]).

‡SIC codes were in use when these surveys were conducted. See the SIC Manual at www.osha.gov/pls/imis/sic_manual.html.

Table 2–5. Cr(VI) sampling, category 2 operations (Exposures easier to control to 1 μg Cr[VI]/m3 than category 3 or 4).
Hexavalent Chromium 17

2 

■ Properties, Production, and Potential for Exposure

Table 2–6. Cr(VI) sampling, category 3 operations (Exposures moderately difficult to control to 1 μg Cr[VI]/m3)

Operation(s)

SIC‡

code

NIOSH site no.

and description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ 

Cr(VI) exposures in 

air† (μg/m3)

Process details, 

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

Manufacturing of screen-printing inks containing chromate pigments

2893 (3) Manufacture 

of screen-printing inks

Ink-batch weigher

< 0.08–3.0(n = 4)(n = 1 ND)

0.9 (6.2) Add pigment 

(powder), other ingredients, thenmix ink batch

Other jobs in process:< 0.08–0.4 μg/m3

(n = 6)(n = 4 ND)

LEV (fair) for batch weighing/mixing, and certain other operations. Others only general ventilation.

MIG weldingon stainless steelin sheet-metal fabrication (mfg)

3444 (9) Welding and 

cutting in sheetmetal fabrication(mfg)

MIGWelder

2.8, 5.2(n = 2)

N/A MIG welding on 

stainless steel

None (welder’s exposures inside welding helmet = 2.6, 1.0, respectively)

LEV for welding, but poor capture.

MIG, TIG welding, plasma-arc cutting, on stainless-steel sheet metal (mfg)

3444 (9) Welding and 

cutting in sheetmetal fabrication(mfg)

Weldingsupervisor

2.0, 3.7(n = 2)

N/A MIG, TIG weld, 

plasma-arc cut, grind, metal forming

None.(Supervisor’s exposures inside welding helmet = 8.5, 3.2, respectively)

LEV for welding, but poor capture. Only general ventilation for plasma-arc cutting, no local ventilation.

MIG weldingon stainless steel (mfg)

3494 (14) Welding 

and cutting on stainless and mild steels (mfg)

MIGWelder

0.20–5.5(n = 4)(n = 1, > 1.0)

0.84 (4.0) MIG welding

(non-automated)on stainless steel

Automated MIGwelder operator (stainless steel)< 0.07, < 0.08 μg/m3(n = 2)

Welding fume extractor LEV on welding stations, but contaminant capture poor. Also general ventilation.

See footnotes at end of table. (Continued)
18 Hexavalent Chromium

2 

■ Properties, Production, and Potential for Exposure

Operation(s)

SIC‡

code

NIOSH site no.

and description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ 

Cr(VI) exposures in 

air† (μg/m3)

Process details, 

engineering exposurecontrol measures,

other comments Job title

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

Metal cutting (torch and carbon-arc)in ship demolition (shipyard)

4499 (13) Metal cutting 

in ship demolition (shipyard)

Burner < 0.07–27

(n = 14)(n = 2, > 1.0)

0.35 (5.4) Carbon-arc and 

torch cutting on steel (some with chromate paint)

Firewatch (assist burner) < 0.04–1.0 (n = 10)Supervisor< 0.07 (n = 2)

Most work performed outdoors, including a partly enclosed area. Some work indoors, only general ventilation provided there.

Repair welding and cutting on alloy and stainless-steel castings (mfg)

3324 (19) Foundry— 

stainless steel and other ferrous alloys (mfg)

Welder 0.37–22

(n = 4)(n = 1, < 12)

6.6 (7.0) MIG, TIG, 

SMAW weld, carbon-arc gouge

None Welding workload 

2- to 3-times normal, on various Cr-content steels and alloys. Cutting on 25% Cr alloy. No local ventilation.

Source: Blade et al. [2007].*Abbreviations: GM = geometric mean; GSD = geometric standard deviation; n = number of samples; LEV = local exhaust ventilation; mfg = manufacturing; MIG = metal inert gas; 

n = number of samples; ND = not detected; PBZ = personal breathing zone; SIC = Standard Industrial Classification; TIG = tungsten inert gas. 

†Concentration value preceded by a “less-than” symbol (<) indicates that the Cr(VI) level in the sampled air was less than the minimum detectable concentration (i.e., the mass of 

Cr[VI] collected in the sample was less than the analytical limit of detection [LOD]). For some other samples in these sets, Cr(VI) was detectable in the sampled air but at a level less than the minimum quantifiable concentration (i.e., the mass of Cr[VI] collected in the sample was between the analytical LOD and limit of quantification [LOQ]). These concentration values are less precise than fully quantifiable values.

‡SIC codes were in use when these surveys were conducted. See the SIC Manual at www.osha.gov/pls/imis/sic_manual.html.

Table 2–6 (Continued). Cr(VI) sampling, category 3 operations (Exposures moderately difficult to control to 1 μg Cr[VI]/m3)
Hexavalent Chromium 19

2 

■ Properties, Production, and Potential for Exposure

Table 2–7. Cr(VI) Sampling, Category 4 Operations (Exposures Most Difficult to Control to 1 μg Cr[VI]/m3).

Operation(s)

SIC‡

code

NIOSH

site no. and 

description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ Cr(VI) 

exposures in air†

(μg/m3)

Process details,

engineering exposurecontrol measures,

other comments Job title(s)

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

Spray application and re-sanding of chromate-containing paints (mfg)

3479 (2) Painting

and coating processes (mfg)

Painter 3.8–55

(n = 5)

16 (3.4) Spray/

sand/clean up. Paints: 1–30% chromates

Painter’s helpers (same work areas)2.4–22 (n = 4)

Painting in fully and partially enclosed paint booths—effectiveness judged as fair.

Spray application and re-sanding of chromate-containing paints (mfg)

3728 (7) Painting

and associatedre-sanding (mfg)

Painter < 0.02–4.3

(n = 13)

0.23 (6.3) Spraying paint,

some sanding.Paints: 1–30% chromates

Assemblers using rotarydisc sanders0.27–2.1 (n = 4)

Fully enclosed paint booths.Vacuum-attached disc sanders.Both judged as fair. Other workers’ exposures were lower.

Hard chromium electroplating (mfg)

3471 (1) Chromium 

electroplating and coating processes (mfg)

Plater 3.0–16

(n = 4)

7.9 (2.0) Place and 

remove parts to be plated, tend tanks.

Lab tech 9.0 μg/m3when adding CrO3 flake. Otherwise, lab workers 0.22, 0.27 (n = 3)

Mist suppressant, pushpull LEV, tarps used on tanks. Lab workers work at tanks along with lab duties.

Hard and bright chromium electroplating (mfg)

3471 (18) Chromium 

electroplating (mfg)

Plater 0.22–8.3

(n = 12)

2.5 (2.6) Place and 

remove parts to be plated, tend tanks.

None Platers work throughout plant, various 

plating tanks. LEV on all tanks, new mist suppressant on one.

See footnotes at end of table. (Continued)
20 Hexavalent Chromium

2 

■ Properties, Production, and Potential for Exposure

Operation(s)

SIC‡

code

NIOSH

site no. and 

description

Key job(s) exposed

Other jobs exposed, 

full-shift PBZ Cr(VI) 

exposures in air†

(μg/m3)

Process details,

engineering exposurecontrol measures,

other comments Job title(s)

Full-shift PBZ* Cr(VI) 

exposures in air†

Tasks,

comments

Range,

μg/m3

(n = no.

of values)

Geometric

mean, μg/m3

(GSD)

Atomized Cr-alloy spray-coating operation (industrial maintenance)

1799 (21) Cr-alloy 

metalization coating operation (industrial maintenance)

Production worker

≥ 820, ≥ 1900(n = 2)

N/A Prep surfaces 

by abrasive blasting. Then spray coating.

Supervisor, entered enclosed work area: 330Other supervisors: 44, 47Abrasive-pot tender: 7.0

Work area inside large boiler, resurfacing heat-exchange tubes. Electric arc melts alloy, then compressed air propels to surface.

Source: Blade et al. [2007].*Abbreviations: GM = geometric mean; GSD = geometric standard deviation; n = number of samples; LEV = local exhaust ventilation; mfg = manufacturing; n = number of 

samples; ND = not detected; PBZ = personal breathing zone; SIC = Standard Industrial Classification.

†Concentration value preceded by a “less-than” symbol (<) indicates that the Cr(VI) concentration in the sampled air was less than the minimum detectable concentration (i.e., the 

mass of Cr[VI] collected in the sample was less than the analytical limit of detection [LOD]). For some other samples in these sets, Cr(VI) was detectable in the sampled air, but at a level less than the minimum quantifiable concentration (i.e., the mass of Cr[VI] collected in the sample was between the analytical LOD and limit of quantification [LOQ]). These concentration values are less precise than fully quantifiable values. Additionally, a concentration value preceded by a “greater-than-or-equal-to” symbol (≥) indicates that the reported value is an estimate, and the “true” concentration likely is greater, because of air-sampling pump failure before the end of the intended sampling period.

‡SIC codes were in use when these surveys were conducted. See the SIC Manual at www.osha.gov/pls/imis/sic_manual.html.

Table 2–7 (Continued). Cr(VI) Sampling, Category 4 Operations (Exposures Most Difficult to Control to 1 μg Cr[VI]/m3).
Hexavalent Chromium 21

2 ■ Properties, Production, and Potential for Exposure

Industry sectors that were identified with a 

lesser potential for airborne Cr(VI) exposure 

include chromium dioxide, chromium dye, 

and chromium sulfate production; chemical 

distribution; textile dyeing; glass production; 

printing; leather tanning; chromium catalyst 

use; refractory brick production; woodworking; solid waste incineration; oil and gas well 

drilling; Portland cement production; non-ferrous superalloy production and use; construction; and makers of concrete products [Shaw 

Environmental 2006].

Table 2–8. Full-shift 8-Hour TWA personal Cr(VI) exposures in primary industry sectors

Industry

Total no.

exposed 

workers

Below

LOD

LOD to 

0.25 μg/m3

0.25 to 0.5 

μg/m3

0.5 to 1 

μg/m3

≥ 1

μg/m3

Welding 247,269 47,361 12,588 50,709 75,722 77,307

Painting 82,254 11,283 20,120 17,766 12,876 20,209

Electroplating 66,857 0 21,410 27,470 2,028 16,149

Steel mills 39,720 10,038 9,390 6,417 8,456 5,419

Iron and steel foundries 30,222 4,184 11,875 3,481 4,578 6,104

Paint and coating production 2569 400 1443 38 38 650

Plastic colorant producers; users 492 37 15 15 0 425

Chromium catalyst production 313 0 127 25 31 130

Chromate chemical production 150 1 89 24 24 12

Plating mixture producers 118 0 16 80 0 22

Printing ink production 112 27 4 3 17 61

Chromium metal producers 63 16 8 9 17 13

Chromate pigment production 52 0 0 0 1 51

CCA production 27 0 12 0 5 10

Source: Shaw Environmental [2006]. 

Abbreviations: CCA = chromated copper arsenate; LOD = limit of detection; TWA = time-weighted average.

More detailed, extensive exposure data by industry sector, process type, and job or operation description are available in the Shaw Environmental Report [2006] and the OSHA Final 

Rule on Hexavalent Chromium [71 Fed. Reg. 

10099 (2006)]. 

2.6.3 Welding and Thermal Cutting

of Metals

Welders are the largest group of workers potentially exposed to Cr(VI) compounds. Cr(VI) 
22 Hexavalent Chromium

2 ■ Properties, Production, and Potential for Exposure

level depends on how strong the wind is, what 

direction the wind is moving, where the worker is standing in relation to the welding plume, 

and where the LEV is positioned [NIOSH 1997]. 

2.7 Occupational Exposure

Limits

The NIOSH REL for all Cr(VI) compounds is 

0.2 μg Cr(VI)/m3 8-hr TWA. Values for other 

U.S. occupational exposure limits (OELs) are 

also listed in Table 2–9. Values for OELs from 

other countries are presented in Table 2–10.

2.8 IDLH Value

An immediately dangerous to life or health 

(IDLH) condition is one that poses a threat of 

exposure to airborne contaminants when that 

exposure is likely to cause death or immediate 

or delayed permanent adverse health effects 

or prevent escape from such an environment 

[NIOSH 2004]. The purpose of establishing an 

IDLH value is (1) to ensure that the worker can 

escape from a given contaminated environment in the event of failure of the respiratory 

protection equipment and (2) is considered a 

maximum level above which only a highly reliable breathing apparatus providing maximum 

worker protection is permitted [NIOSH 2004]. 

The IDLH for chromic acid and chromates is 

15 mg Cr(VI)/m3 [NIOSH 1994a].

2.9 Future Trends

Industry sectors with the greatest number of 

workers exposed to Cr(VI) compounds, and the 

largest number of workers exposed to Cr(VI) 

compounds above the revised REL, include 

welding, painting, electroplating, steel mills, 

and iron and steel foundries [Shaw Environmental 2006; 71 Fed. Reg. 10099 (2006)]. Recent national and international regulations on 

workplace and environmental Cr(VI) exposures 

have stimulated the research and development 

exposures to welders are dependent on several 

process factors, most importantly the welding 

process and shield-gas type, and the Cr content 

of both the consumable material and the base 

metal  [Keane et al.  2009; Heung et al.  2007; 

EPRI 2009; Meeker et al. 2010]. The exposure 

data associated with different welding processes has been reported [Shaw Environmental 

2006; 71 Fed. Reg. 10099 (2006)].

The Electric Power Research Institute (EPRI) 

analyzed Cr(VI) exposures during welding and 

thermal cutting activities conducted at electric 

utility operations [EPRI 2009]. EPRI reported 

Cr(VI) exposures associated with shielded-metal arc welding (SMAW) and gas-metal arc welding (GMAW), with geometric means (GMs) of 

1.4 μg/m3 for SMAW and 1.3 μg/m3 for GMAW. 

This was higher than gas-tungsten arc welding (GTAW), with a GM exposure of 0.14 μg/m3

. 

All exposure values represent full work shift 

TWA personal-breathing-zone exposures to 

particulate-borne Cr(VI) in air. Metal cutting 

with arc gouging resulted in GM exposures of 

12 μg/m3. All exposures were below the OSHA 

PEL when GTAW was used. During the use 

of SMAW, exposures were below the PEL only 

when both the consumable metal contained less 

than 3% Cr and adequate ventilation was provided [EPRI 2009].

Others have found similar associations between Cr(VI) exposures and welding processes, 

materials, and ventilation. Meeker et al. [2010] 

reported GM exposures of about 5 μg/m3 for 

SMAW and 0.7–0.8  μg/m3 for GTAW, versus 

a maximum exposure of 0.4 μg/m3 for GTAW, 

with many exposures below detection limits. 

In addition to welding process type, other predictors of Cr(VI) inhalation exposures included the base metal Cr content and whether local 

exhaust ventilation (LEV) was used. 

The environmental conditions of the work site 

also affect worker Cr(VI) exposures. For example, 

when welding outdoors the worker’s exposure 
Hexavalent Chromium 23

2 ■ Properties, Production, and Potential for Exposure

Table 2–9. U.S. occupational exposure limits for Cr(VI) compounds*

Agency OEL Cr(VI) compound(s)

8-hr TWA

μg Cr(VI)/m3

NIOSH REL All 0.2

OSHA PEL 5

ACGIH TLV Water-soluble 50

Insoluble 10

Source: ACGIH [2011a]; OSHA [2007].

*Specific Cr(VI) compounds such as calcium, lead, and strontium chromate may have distinct OELs.

Table 2–10. Occupational exposure limits for Cr(VI) compounds in various countries*

Country

Insoluble Cr(VI)

TWA (μg/m3)

 Soluble Cr(VI)

 TWA (μg/m3)

Australia 50 50

Canada

Alberta

British Columbia

Quebec

10

10

10

50

20

50

Hong Kong 10 50

Ireland 50 50

Japan 10 10

Mexico 10 50

Netherlands 10 25

Poland 100 100

Sweden 20 20

United Kingdom 50 50

Source: ACGIH [2011b]. 

*Specific Cr(VI) compounds such as calcium, lead, strontium, and zinc chromate may have distinct OELs.
24 Hexavalent Chromium

2 ■ Properties, Production, and Potential for Exposure

of substitutes for Cr(VI). Some defense-related 

industries are eliminating or limiting Cr(VI) 

use where proven substitutes are available [76 

Fed. Reg. 25569 (2011)]. However, it is expected that worker exposure to Cr(VI) compounds will continue in many operations until acceptable substitutes have been developed 

and adopted. It is expected that some existing 

exposures, such as Cr(VI) exposure during the 

removal of lead chromate paints, will continue 

to be a risk of Cr(VI) exposure to workers for 

many years [71 Fed. Reg. 10099 (2006)]. 

Some industries, such as woodworking, printing ink manufacturing, and printing have decreased their use of Cr(VI) compounds [71 

Fed. Reg. 10099 (2006)]. However, many of 

these workplaces have only a small number of 

employees or low exposure levels.
Hexavalent Chromium 25

3 Measurement of Exposure

Recently developed analytical methods provide 

an improved ability to determine hexavalent 

chromium (Cr[VI]) concentrations in workplace air. These methods and sampling considerations for Cr(VI) compounds have been 

reviewed [Ashley et al. 2003]. NIOSH Method 

7605 for Cr(VI) determination in the laboratory 

and NIOSH Method 7703 for Cr(VI) determination in the field are published in the NIOSH 

Manual of Analytical Methods [http://www.

cdc.gov/niosh/nmam] [NIOSH 1994b]. These 

methods provide improved Cr(VI) measurement 

by allowing for the detection of Cr(VI) (versus 

total chromium), quantification of Cr(VI) at 

trace levels, and measurement of Cr(VI) in 

soluble and insoluble chromate compounds. 

NIOSH Method 7605, OSHA Method ID-215, 

and international consensus standard analytical methods can accurately quantify workplaces 

exposures at the recommended exposure limit 

(REL) of 0.2 μg Cr(VI)/m3 8-hr TWA [NIOSH 

2003b; OSHA 2006; ASTM 2002; ISO 2005].

3.1 Air-Sampling Methods

3.1.1 Air Sample Collection

There are several methods developed by 

NIOSH and others to quantify Cr(VI) levels 

in workplace air. Specific air-sampling procedures such as sampling airflow rates and recommended sample-air volumes are specified 

in each of the methods, but they share similar 

sample-collection principles. All are suitable 

for the collection of long-term, time-integrated 

samples to characterize time-weighted average (TWA), personal breathing zone (PBZ) 

exposures across full work shifts.

Each PBZ sample is collected using a batterypowered air-sampling pump to draw air at 

a measured rate through a plastic cassette 

containing a filter selected in accordance with 

the specific sampling method and the considerations described above. The airflow rate of 

each air-sampling pump should be calibrated 

before and after each work shift it is used, and 

the flow rate adjusted as needed according to 

the nominal rate specified in the method. Usually when measuring a PBZ exposure, the air 

inlet of the filter cassette is held in the worker’s 

breathing zone by clipping the cassette to the 

worker’s shirt collar, and the pump is clipped 

to the worker’s belt, with flexible plastic tubing 

connecting the filter cassette and pump. The 

air inlet should be located so that the exposure 

is measured outside a respirator or any other 

personal protective equipment (PPE) being 

worn by the worker. 

When sampling for welding fumes, the filter 

cassette should be placed inside the welding 

helmet to obtain an accurate measurement 

of the worker’s exposure [OSHA 1999b; ISO 

2001]. The practice of placing the sampling 

device inside PPE applies only to PPE that is 

not intended to provide respiratory protection, 

such as welding helmets or face shields. If the 

PPE has supplied air, such as a welding hood 

or an abrasive blasting hood, then the sample is 

taken outside the PPE [OSHA 1999b].
26 Hexavalent Chromium

3 ■ Measurement of Exposure

For the collection of an area air sample, an entire sampling apparatus  (pump, tubing, filter 

cassette) can be placed in a stationary location. This method can also be used to collect 

short-term task samples (e.g., 15 minutes), if 

high enough concentrations are expected, so 

that the much smaller air volume collected 

during the short sample duration contains 

enough Cr(VI) to exceed the detection limits.

The procedures specified in each method for 

handling the samples and preparing them for 

on-site analysis or shipment to an analytical laboratory should be carefully followed, including 

providing the proper numbers of field-blank and 

media-blank samples specified in the method.

3.1.2 Air Sampling Considerations

Important sampling considerations when determining Cr(VI) levels in workplace air have been 

reviewed [Ashley et al. 2003]. One of the most important considerations is the reduction of Cr(VI) 

to Cr(III) during sampling and sample preparation. Another concern is the possibility of oxidation of Cr(III) to Cr(VI) during sample preparation. Factors that affect the reduction of Cr(VI) 

or oxidation of Cr(III) include the presence of 

other compounds in the sampled workplace 

air, which may affect reduction or oxidation (notably iron, especially Fe[II]), the ratio of Cr(VI) to 

Cr(III) concentrations in the sample, and solution 

pH [Ashley et al. 2003]. The pH of a solution is 

an important factor, because in acidic conditions 

the reduction of Cr(VI) is favorable, while in basic 

conditions Cr(VI) is stabilized. The sampling and 

analytical methods developed for the determination of Cr(VI) in the workplace attempt to 

minimize the influence of these redox reactions 

in order to obtain accurate Cr(VI) measurements. 

Using NIOSH Method 7703 in the field is one 

option to minimize the reduction of Cr(VI) that 

may occur during sample transport and storage [Marlow et al. 2000; Wang et al. 1999].

It is important to select a filter material that 

does not react with Cr(VI). All filter types to 

be used for sampling should be tested before 

use, but ordinarily polyvinyl chloride (PVC) filters are recommended (NIOSH Method 7605; 

OSHA Method ID-215). Other suitable filter 

materials that are generally acceptable for airborne Cr(VI) sampling include polyvinyl fluoride (PVF), polytetrafluoroethylene (PTFE), 

PVC- and PVF-acrylic copolymers, and quartz 

fiber filters [Ashley et al. 2003].

3.2 Analytical Methods

3.2.1 Cr(VI) Detection in Workplace Air

There are several methods developed by NIOSH 

and others to quantify Cr(VI) levels in workplace air. NIOSH Method 7605 describes the 

determination of Cr(VI) levels in workplace air 

by ion chromatography [NIOSH 2003b]. This 

method is a modification of previous NIOSH 

Methods 7604 and 7600, employing the hot 

plate extraction and ion chromatographic separation method of the former and the spectrophotometric detection technique of the latter. 

NIOSH Method 7605 also includes ultrasonic 

extraction as an optional sample preparation 

method for Cr(VI) [Wang et al. 1999]. The 

limits of detection (LOD) per sample is 0.02 

μg for NIOSH Method 7605. OSHA Method 

ID-215 also uses ion chromatography to separate Cr(VI) [OSHA 1998, 2006]. The OSHA 

method employs a precipitation reagent to prevent Cr(III) oxidation to Cr(VI) during sample 

preparation, while NIOSH Method 7605 relies 

on sonication and/or a nitrogen atmosphere to 

achieve the same end.

NIOSH Method 7703 measures Cr(VI) levels 

by field-portable spectrophotometry [NIOSH 

2003a]. This method is designed to be used in 

the field with portable laboratory equipment but 

can also be used in the fixed-site laboratory. It is a 
Hexavalent Chromium 27

3 ■ Measurement of Exposure

relatively simple, fast, and sensitive method for 

Cr(VI) determination [Wang et al. 1999; Marlow et al. 2000]. The method uses ultrasonic 

extraction instead of hotplate extraction, and 

solid-phase extraction instead of ion chromatography to isolate Cr(VI). Its estimated LOD 

is 0.08  μg per sample. The method has been 

modified to enable the determination of insoluble Cr(VI) compounds [Hazelwood et al. 

2004]. Sequential extraction of soluble and insoluble Cr(VI) compounds in air filter samples, 

as described in ISO 16740, has been evaluated 

[Ashley et al. 2009]. 

Boiano et al. [2000] conducted a field study to 

compare results of airborne Cr(VI) determination obtained using NIOSH Methods 7605 

and 7703 and OSHA Method ID-215 (Table 

3–1). All three of these methods use extraction of the PVC filter in alkaline buffer solution, 

chemical isolation of Cr(VI), complexation of 

Cr(VI) with 1,5-diphenylcarbazide, and spectrometric measurement. However, there are 

specific differences regarding sample handling 

in each method. Three sets of 20 side-by-side 

air samples (10 at each facility on each of three 

sampling media) were collected at a chromic 

acid electroplating operation and a spray paint 

operation, and analyzed using the three methods. No statistically significant differences were 

found between the mean Cr(VI) values obtained 

using the three methods (P < 0.05). Overall results obtained using NIOSH Method 7703 were 

slightly higher (statistically significant) than 

those obtained using OSHA ID-215.

International standards for the determination 

of Cr(VI) in workplace air are available that 

can accurately quantify Cr(VI) exposures at 

the REL. American Society for Testing and 

Materials (ASTM) Method D6832-02, “Standard Test Method for the Determination of 

Hexavalent Chromium in Workplace Air by 

Ion Chromatography and Spectrophotometric 

Measurement Using 1,5-Diphenylcarbazide,” 

allows for the determination of airborne 

Cr(VI) [ASTM 2002]. International Organization for Standardization (ISO) 16740, “Workplace Air—Determination of Hexavalent Chromium in Airborne Particulate Matter—Method 

by Ion Chromatography and Spectrophotometric 

Measurement using Diphenylcarbazide,” provides a method to extract Cr(VI) compounds 

of different solubilities [ISO 2005]. Sulfate buffers are suitable for extraction of Cr(VI) from 

soluble and sparingly soluble compounds, 

while carbonate buffers are required for the 

dissolution of Cr(VI) from insoluble chromate 

compounds [Hazelwood et al. 2004]. Several 

other validated procedures for the sampling 

and analysis of Cr(VI) in occupational settings 

have been published in the United Kingdom, 

France, and Germany [Ashley et al. 2003].

3.2.2 Wipe Sampling Methods

NIOSH, OSHA, and ASTM have developed 

methods that can be used to detect Cr(VI) by 

using wipe samples. Information about surface and dermal sampling is available [ASTM 

2011]. However, there currently are no consensus criteria for interpreting wipe sampling data 

for chromium. Analytical results from wipe sampling and analysis should be viewed as qualitative 

or semi-quantitative. OSHA Method W-4001 

is a wipe method specific for Cr(VI) sampling 

[OSHA 2001]. NIOSH Method 9102, “Elements 

on Wipes,” is a simultaneous elemental analysis 

that is not compound specific [NIOSH 2003d]. 

ASTM D6966, “Standard Practice for the Collection of Dust Samples Using Wipe Sampling 

Methods for Subsequent Determination of Metals” [ASTM 2003] applies to metals determination, so the same sampling procedure can be applicable to the collection of Cr(VI) in surface dust. 

Sample preparation and analysis procedures using this method for Cr(VI) determination would 
28 Hexavalent Chromium

3 ■ Measurement of Exposure

be similar to those for the airborne Cr(VI) 

methods in Section 3.2.1. However, media and 

matrix effects could be problematic for the reasons already discussed (i.e., biases in Cr(VI) 

measurement due to redox reactions with the 

sampling media and/or the co-sampled matrix).

NIOSH Method 9101, “Hexavalent Chromium 

in Settled Dust Samples,” allows for screening of 

soluble Cr(VI) in settled dust [NIOSH 1996a]. 

Estimation of Cr(VI) in dust can be obtained 

by laboratory analysis for Cr(VI) using NIOSH 

Method 7605 or equivalent methods.

Table 3–1. Comparison of NIOSH and OSHA analytical methods for airborne hexavalent 

chromium determination

Parameter NIOSH 7605 OSHA ID-215 NIOSH 7703

Sample collection, handling and storage:

Media PVC

37 mm; 5.0 μm

Cellulose backup pad

PVC

37 mm; 5.0 μm

Cellulose backup pad

PVE, MCE, or PTFE

37 mm; 5.0, 0.8, 1.0 μm

Cellulose backup pad

Equipment Personal sampling pump Personal sampling pump Personal sampling pump

Flow rate 1–4 L min ̄1 2 L min ̄1 1–4 L min ̄1

Sample preparation for 

shipment to laboratory

Using Teflon®-coated

tweezers, transfer filter 

to 20 mL glass vial with 

Teflon cap liner

Using Teflon-coated 

tweezers, transfer filter to 

20 mL glass vial with Teflon 

cap liner

Not applicable if analyzed

on-site. Same sample handling 

as NIOSH 7605 and OSHA 

ID-215 if analyzed off-site.

Sample refrigeration Optional 4 oC None required

Sample preparation and analysis:

Extraction solution 2% NaOH/3% Na2CO3 or 

0.05 M (NH4)2SO4/0.05 M 

NH4OH (pH 8)

10% Na2CO3/2% NaHCO3/

phosphate buffer/Mg II (as 

MgSO4) (pH 8)

0.05 M (NH4)2SO4/0.05 M 

NH40H (pH 8)

Extraction equipment Hot plate Hot plate Ultrasonic bath

Cr(VI) isolation Ion chromatography Ion chromatography Strong anion exchange solid 

phase extraction

Eluent 0.25 M (NH4)2SO4/

0.1M NH4OH

0.25 M (NH4)2SO4/

0.1M NH4OH

0.5M (NH4)2SO4/ 

0.1M NH4OH

Post-column reagent 

(derivatization)

2 mM 1,5 diphenylcarbazide/10% methanol/1 M H2

SO4

2 mM 1,5 diphenyl-carbazide/ 

10% methanol/1 M H2SO4

1,5 diphenylcarbazide/acetonitrile solution added to eluent acidified with 1 M HCl

Analyte Cr-DPC complex Cr-DPC complex Cr-DPC complex

Detection UV-Vis: 540 nm UV-Vis: 540 nm UV-Vis: 540 nm

LOD/LOQ/μg 0.02/0.06 0.01/0.03 0.09/0.27

Accuracy ±16.5% ±12.9% ±16.8%

Source: Boiano et al. [2000].

Abbreviations: DPC = diphenylcarbazide/diphenylcarbazone; LOD/LOQ = limit of detection/limit of quantitation; MCE = mixed 

cellulose ester; PTFE = polytetrafluoroethylene; PVC = polyvinylchloride; UV-Vis = ultraviolet-visible. 
Hexavalent Chromium 29

3 ■ Measurement of Exposure

3.3 Biological Markers

Biological markers, or biomarkers, can serve 

several purposes where there is epidemiological evidence that exposure causes a particular disease: answering questions of intensity 

and timing of exposure; testing the effectiveness of controls; assessing subgroups within a 

worker population; and functioning as an indicator of early disease [Schulte 1995]. Research is 

ongoing to identify reliable quantifiable biomarkers of Cr(VI) occupational exposure 

that can indicate exposure levels, effects of 

exposure, or early disease conditions. The biological markers of Cr(VI) exposure and effect 

have been reviewed [ATSDR 2012]. Biomarkers should be evaluated carefully as variables, 

including diet, capacity to reduce Cr(VI), type 

of occupational exposure, sensitivity of the analytical method used, and other factors affect 

results. Biomarkers for Cr(VI) compounds are 

currently of uncertain value as early indicators 

of potential health effects related to Cr(VI) 

exposure [NIOSH 2005a]. 

An important consideration in biological testing for Cr(VI) is the reduction of Cr(VI) to 

Cr(III) throughout the body. Some biological 

markers distinguish Cr(VI) levels while others 

assess only total chromium levels because of 

the varying distribution of Cr(III) and Cr(VI) 

within body compartments. Inhalation is the 

primary route of concern for occupational 

Cr(VI) exposure. Inhaled Cr(VI) enters the respiratory system, where it may remain, be reduced, or enter the bloodstream. Cr(VI) may 

be reduced to Cr(III) in the lungs or plasma 

and excreted as Cr(III) in the urine. Cr(VI) 

that is not reduced in the plasma may enter 

erythrocytes and lymphocytes. This distribution of absorbed Cr(VI) permits the biological monitoring of Cr in urine, whole blood, 

plasma, and blood cells in workers exposed to 

Cr(VI) [Miksche and Lewalter 1997]. 

Urinary chromium levels have been extensively studied. They are a measure of total chromium exposure as Cr(VI) is reduced within the 

body to Cr(III). Blood Cr levels are lower than 

urinary levels. Biological monitoring of blood 

chromium requires careful techniques and 

equipment to avoid contamination of the samples, and such monitoring requires a sensitive 

method of analytical detection. Measurement 

of erythrocyte Cr levels is a measure of Cr(VI) 

exposure, because Cr(VI) passes through the 

cell membranes, but Cr(III) does not [Gray 

and Sterling 1950]. 

3.3.1 Biological Markers of Exposure

3.3.1.1 Measurement of chromium

in urine

Urinary chromium levels are a measure of total chromium exposure as Cr(VI) is reduced 

within the body to Cr(III). The ACGIH 

has Biological Exposure Indices (BEIs) for 

Cr(VI) compounds as a water-soluble fume 

[ACGIH 2011a]. The BEI for total chromium in urine measured at the end of the shift 

at the end of the workweek is 25 μg/L. The 

BEI for the increase in total chromium during a shift is 10 μg/L. 

Gylseth et al. [1977] reported a significant correlation (P  <  0.001) between workplace Cr 

exposure and urinary Cr concentration after work in five alloyed steel welders. It was 

assumed that most of their exposure was to 

soluble Cr(VI). A urinary Cr concentration 

of 40–50 μg Cr per liter of urine corresponded to an approximate workplace exposure of 

50 μg Cr/m3. 

Lindberg and Vesterberg [1983] measured with 

personal air samplers the Cr(VI) exposures 

of eight chrome platers and monitored their 

urinary Cr concentrations. The urinary Cr 

levels increased from Monday morning until 
30 Hexavalent Chromium

3 ■ Measurement of Exposure

Tuesday afternoon and then remained constant throughout the workweek. The Monday 

and Thursday preshift and postshift urinary Cr 

level and exposure were also monitored on a 

larger group of 90 chrome platers. Exposure 

correlated with Thursday postshift urinary Cr 

levels with exposures of approximately 2  μg/

m3, correlating with ≤ 100 nmol Cr/l urine.

Angerer et al. [1987] measured Cr concentrations in the erythrocytes, plasma, and urine 

of 103 MMA welding and/or metal inert gas 

(MIG) welders. Personal air monitoring was 

also conducted; chromium trioxide exposures 

ranged from < 1 to 50 μg/m3. The urinary Cr 

concentrations ranged from 5.40 to 229.4 μg/l; 

approximately 5 and 200 times higher than the 

level of non-exposed people. Erythrocyte, plasma, and urine Cr levels were highly correlated 

(P < 0.0001). The authors reported that plasma 

chromium levels of approximately 10 μg/l and 

urine Cr levels of 40 μg/l corresponded to an 

external exposure of 100  μg CrO3/m3, while 

erythrocyte chromium concentrations greater 

than 0.60 μg/l indicated exposures greater than 

100 μg CrO3/m3. 

Minoia and Cavalleri [1988] measured urinary 

Cr levels in dichromate production workers 

exposed predominantly to Cr(VI) or Cr(III). 

A correlation was found between Cr(VI) exposure as measured by personal air sampling 

and postshift urinary levels. Cr(VI) was not 

detected in the urine samples, indicating the in 

vivo reduction of Cr(VI) to Cr(III).

Liu et al. [1998] reported a correlation between 

air and urinary chromium concentrations in 

hard-chrome platers, nickel-chrome electroplaters, and aluminum anode-oxidation plant 

workers. Hard-chrome plating workers had the 

highest air and urinary chromium concentrations, with geometric means of 4.2  μg Cr/m3 

TWA for air and 2.44 μg/g creatinine for urine. 

Chen et al. [2008] reported an association of 

skin disease and/or smoking habit with elevated urinary Cr levels in cement workers. Smoking increased urinary Cr levels an average of 

25  μg/L; hand eczema increased urinary Cr 

levels more than 30  μg/L. Workers with skin 

disease who were also smokers had higher urinary Cr levels than those with only skin disease 

or smoking habits. Workers who did not regularly wear PPE had higher average urinary Cr 

levels, with the difference between glove users 

and non-users being the greatest (P < 0.001).

Individual differences in the ability to reduce 

Cr(VI) have been demonstrated [Miksche and 

Lewalter 1997]. Individuals with a weaker capacity to reduce Cr(VI) have lower urine Cr 

levels compared with individuals who have a 

stronger capacity to reduce Cr(VI). Therefore, 

analyzing only urinary Cr levels may not provide an accurate analysis of occupational exposure and health hazard. 

3.3.1.2 Measurement of chromium in 

blood, plasma, and blood cells

Plasma or whole blood chromium levels are 

indicative of total chromium exposure because 

Cr(VI) may be reduced to Cr(III) in the plasma. Intracellular chromium levels are indicative of Cr(VI) exposure because Cr(VI) passes 

through cell membranes, while Cr(III) does 

not [Gray and Sterling 1950]. The chromium 

concentration inside erythrocytes indicates exposure to Cr(VI) sometime during the approximate 120-day lifespan of the cells. There are 

two advantages to the monitoring of chromium 

levels in erythrocytes (red blood cells) versus 

urine: (1) the sampling time may be relatively 

independent of the time of exposure, and (2) 

it permits the determination of Cr(VI), rather 

than only total chromium, absorption [Wiegand et al. 1988]. 
Hexavalent Chromium 31

3 ■ Measurement of Exposure

Wiegand et al. [1985] investigated the kinetics 

of 51Cr(VI) uptake into human erythrocytes in 

vitro. Two different first-order processes, with 

half-life times of 22.7 seconds and 10.4 minutes, were observed when erythrocytes were 

incubated with sodium dichromate concentrations ranging from 10 μM to 50 mM. Approximately 15 percent of the administered dose of 

Cr(VI) remained in the plasma after a 2-hour 

incubation. The maximal capacity for Cr(VI) 

uptake into erythrocytes was 3.1 ×  108 chromate ions per cell, per minute. 

Many variables can affect chromium levels in 

the blood, including diet, individual capacity 

to reduce Cr(VI), and type of occupational exposure. Corbett et al. [1998] reported an enhanced in vitro ability to reduce Cr(VI) in the 

plasma from an individual who had recently 

eaten, in comparison with a fasted individual. 

A concentration-dependent distribution of Cr 

between the erythrocytes (RBCs) and plasma 

was reported. A higher Cr(VI) concentration 

was associated with a higher Cr(VI) concentration in erythrocytes, resulting in a lower 

plasma to erythrocyte ratio of total chromium. 

Individual differences in the ability to reduce 

Cr(VI) have been demonstrated [Miksche 

and Lewalter 1997]. Individuals with a weaker 

plasma capacity to reduce Cr(VI) have elevated 

plasma Cr(VI) levels in comparison with individuals who have a stronger capacity to reduce 

Cr(VI). Therefore, elevated blood plasma levels 

may be indicative of high chromium exposures 

and/or a low plasma ability to reduce Cr(VI). 

Cr(VI) uptake into erythrocytes may also be 

dependent on the Cr(VI) particle size [Miksche and Lewalter 1997]. Smaller particles, as 

in welding fume exposure (<  0.5 μm), may 

be more efficiently reduced in the lungs than 

larger particles, such as those of chromate dust 

exposure (> 10 μm). 

Minoai and Cavalleri [1988] measured serum and erythrocyte Cr levels in dichromate 

production workers exposed predominantly 

to Cr(VI) compounds (chromic trioxide or 

potassium dichromate) or Cr(III) (basic chromium sulphate) compounds. Workers exposed 

predominantly to Cr(VI) compounds had 

lower serum and higher erythrocyte Cr levels 

compared with predominantly Cr(III)-exposed 

workers, providing evidence of an enhanced 

ability of Cr(VI) to enter erythrocytes compared 

with Cr(III). 

Angerer et al. [1987] measured Cr concentrations in the erythrocytes, plasma, and urine 

of 103 MMA and/or MIG welders. Personal 

air monitoring was also conducted. Airborne 

chromium trioxide concentrations for MMA 

welders ranged from < 1 to 50 μg/m3, with 50% 

< 4 μg/m3. Airborne chromium trioxide concentrations for MIG welders ranged from < 1 

to 80 μg/m3 with a median of 10 μg/m3. More 

than half (54%) of measured erythrocyte Cr 

levels were below the limit of detection (LOD) 

of 0.6 μg/l. Erythrocyte Cr concentration was 

recommended for its specificity but limited by 

its low sensitivity. Chromium was detected in 

the plasma of all welders, ranging from 2.2 to 

68.5 μg/l; approximately 2 to 50 times higher 

than the level in non-exposed people. Plasma 

Cr concentration was recommended as a sensitive parameter, limited by its lack of specificity. Erythrocyte, plasma, and urine chromium 

levels were highly correlated with each other 

(P < 0.0001). 

3.3.2 Biological Markers of Effect

3.3.2.1 Renal biomarkers

The concentration levels of certain proteins and 

enzymes in the urine of workers may indicate 

early effects of Cr(VI) exposure. Liu et al. [1998] 

measured urinary N-acetyl-ß-glucosaminidase 

(NAG), ß2-microglobulin (ß2M), total protein, 
32 Hexavalent Chromium

3 ■ Measurement of Exposure

and microalbumin levels in 34 hard-chrome plating workers, 98 nickel-chrome electroplating 

workers, and 46 aluminum anode-oxidation 

workers who had no metal exposure and served 

as the reference group. Hard-chrome platers 

were exposed to the highest airborne chromium concentrations (geometric mean 4.20  μg 

Cr/m3 TWA) and had the highest urinary 

NAG concentrations (geometric mean of 4.9 

IU/g creatinine). NAG levels were significantly 

higher among hard-chrome plating workers, 

while the other biological markers measured 

were not. NAG levels were significantly associated with age (P < 0.05) and gender (P < 0.01) 

and not associated with employment duration.

3.3.2.2 Genotoxic biomarkers

Genotoxic biomarkers may indicate exposure 

to mutagenic carcinogens. More information 

about the genotoxic effects of Cr(VI) compounds is presented in Chapter 5, Section 5.2.

Gao et al. [1992] detected DNA strand breaks 

in human lymphocytes in vitro 3 hours after sodium dichromate incubation, and in male Wistar rat lymphocytes 24 hours after intratracheal 

instillation. The DNA damage resulting from 

Cr(VI) exposure is dependent on the reactive 

intermediates generated [Aiyar et al. 1991]. 

Gao et al. [1994] investigated DNA damage in 

the lymphocytes of workers exposed to Cr(VI). 

No significant increases in DNA strand breaks 

or 8-OHdG levels were found in the lymphocytes of exposed workers in comparison with 

the lyphocytes of controls. The exposure level 

for the exposed group was reported to be approximately 0.01 mg Cr(VI)/m3

.

Gambelunghe et al. [2003] evaluated DNA 

strand breaks and apoptosis in the peripheral 

lymphocytes of chrome-plating workers. Previous air monitoring at this plant indicated 

total chromium levels from 0.4 to 4.5  μg/m3. 

Workers exposed to Cr(VI) had higher levels 

of chromium in their urine, erythrocytes, and 

lymphocytes than unexposed controls. The 

comet assay demonstrated an increase in DNA 

strand breaks in workers exposed to Cr(VI). 

The percentage of apoptotic nuclei did not 

differ between exposed workers and controls. 

Urinary chromium concentrations correlated 

with erythrocyte chromium concentrations 

while lymphocyte chromium concentrations 

correlated with comet tail moment, an indicator 

of DNA damage.

Kuo et al. [2003] reported positive correlations 

between urinary 8-OHdG concentrations and 

both urinary Cr concentration (P < 0.01) and 

airborne Cr concentration (P < 0.1) in a study 

of 50 electroplating workers. 

3.3.2.3 Other biomarkers of effect

Li et al. [2001] reported that sperm count 

and sperm motility were significantly lower 

(P  <  0.05) in the semen of workers exposed 

to Cr(VI) in comparison with the semen of 

unexposed control workers. The seminal volume and liquefaction time of the semen from 

the two groups was not significantly different. 

Workers exposed to Cr(VI) had significantly 

(P < 0.05) increased serum follicle stimulating 

hormone levels compared with controls; LH 

and Cr levels were not significantly different 

between groups. The seminal fluid of exposed 

workers contained significantly (P  <  0.05) 

lower levels of lactate dehydrogenase (LDH), 

lactate dehydrogenase C4 isoenzyme (LDH-x), 

and zinc; Cr levels were not different.
Hexavalent Chromium 33

4 Human Health Effects

Most of the health effects associated with occupational hexavalent chromium (Cr[VI]) exposure are well known and have been widely 

reviewed (see Section 4.1.1, Lung Cancer). The 

following discussion focuses on quantitative 

exposure-response studies of those effects and 

new information not previously reviewed by 

NIOSH [1975, 1980]. Comprehensive reviews 

of welding studies are available from ATSDR 

[2012]; IARC [1990]; and OSHA [71 Fed. Reg. 

10099 (2006)]. Analyses of epidemiologic studies with the most robust data for quantitative 

risk assessment are described in Chapter 6, 

“Assessment of Risk.”

4.1 Cancer

4.1.1 Lung Cancer

Hexavalent chromium is a well-established occupational carcinogen associated with lung 

cancer and nasal and sinus cancer. In 1989, the 

International Agency for Research on Cancer 

(IARC) critically evaluated the published epidemiologic studies of chromium compounds 

including Cr(VI) and concluded 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” (i.e., IARC category “Group 1” 

carcinogen) [IARC 1990]. The IARC-reviewed 

studies of workers in those industries and the 

ferrochromium industry are presented in Tables 

4–1 through 4–4. (Cr[VI] compounds were 

reaffirmed as an IARC Group 1 carcinogen 

[lung] in 2009 [Straif et al. 2009; IARC 2012].) 

Additional details and reviews of those studies are available in the IARC monograph and 

elsewhere [IARC 1990; NIOSH 1975a, 1980; 

WHO 1988; ATSDR 2012; EPA 1998; Dutch 

Expert Committee on Occupational Standards 

(DECOS) 1998; Government of Canada et al. 

1994; Hughes et al. 1994; Cross et al. 1997; Cohen et al. 1993; Lees 1991; Langård 1983, 1990, 

1993; Hayes 1980, 1988, 1997; Gibb et al. 1986; 

Committee on Biologic Effects of Atmospheric 

Pollutants 1974]. Although these studies established an association between occupational 

exposure to chromium and lung cancer, the 

specific form of chromium responsible for the 

excess risk of cancer was usually not identified, 

nor were the effects of tobacco smoking always 

taken into account. However, the observed 

excesses of respiratory cancer (i.e., 2-fold to 

more than 50-fold in chromium production 

workers) were likely too high to be solely due 

to smoking.

4.1.1.1 Epidemiologic exposureresponse analyses of lung cancer

Sections 4.1.1.1.1 through 4.1.1.1.6 include 

several epidemiologic studies published after the IARC [1990] review that investigated 

exposure-response relationships for Cr(VI) 

and lung cancer using cumulative quantitative Cr(VI) exposure data. Exposure-response 

models based on cumulative exposure data can 

predict disease risk for a particular Cr(VI) exposure over a period of time. Epidemiologic 

studies that provided evidence of an exposureresponse relationship based on other kinds of 
34 Hexavalent Chromium

4 ■ Human Health Effects

exposure data (e.g., duration of exposure) 

have been reviewed by the authors cited above 

and others [CRIOS 2003; K.S. Crump Division 1995]. Reanalyses of data from published 

epidemiologic studies (i.e., quantitative risk assessments) are described in Chapter 6, “Assessment of Risk,” and Chapter 7, “Recommendations for an Exposure Limit.” 

4.1.1.1.1 U.S. chromate production workers,

North Carolina (Pastides et al. [1994a])

A retrospective cohort study of 398 current 

and former workers employed for at least 

1 year from 1971 through 1989 was conducted 

in a large chromate production facility in Castle Hayne, North Carolina. The plant opened 

in 1971 and was designed to reduce the high 

level of chromium exposure found at the company’s former production facilities in Ohio 

and New Jersey. The study was performed to 

determine if there was early evidence for an 

increased risk of cancer incidence or mortality and to determine whether any increase was 

related to the level or duration of exposure to 

Cr(VI). More than 5,000 personal breathing zone 

(PBZ) samples collected from 1974 through 

1989 were available from company records for 

352 of the 398 employees. Concentrations of 

Cr(VI) ranged from below the limit of detection (LOD) to 289 μg/m3

 (8-hour TWA), with 

> 99% of the samples less than 50 μg/m3. Area 

samples were used to estimate personal monitoring concentrations for 1971–1972. (Further 

description of the exposure data is available 

in Pastides et al. [1994b].) Forty-two of the 45 

workers with previous occupational exposure 

to chromium had transferred from the older 

Painesville, Ohio plant to Castle Hayne. Estimated airborne chromium concentrations 

at the Ohio plant ranged from 0.05 mg/m3 to 

1.45  mg/m3 of total chromium for production workers to a maximum of 5.67 mg/m3

 for 

maintenance workers (mean not reported). 

Mortality of the 311 white male Castle Hayne 

workers from all causes of death (n = 16), 

cancer (all sites) (n = 6), or lung cancer (n = 2) 

did not differ significantly from the mortality 

experience of eight surrounding North Carolina counties or the United States white male 

population. Internal comparisons were used 

to address an apparent “healthy worker” effect 

in the cohort. Workers with “high” cumulative Cr(VI) exposure (i.e., ≥  10 “μg-years” of 

Cr[VI]) were compared with workers who had 

“low” exposure (i.e., < 10 “μg-years” Cr[VI]). 

No significant differences in cancer risk were 

found between the two groups after considering the effects of age, previous chromium exposure, and smoking. There was a significantly increased risk of mortality and cancer, including 

lung cancer, among a subgroup of employees 

(11% of the cohort) that transferred from older 

facilities (odds ratio [OR] for mortality = 1.27 

for each 3  years of previous exposure; 90% 

CI = 1.07–1.51; OR for cancer = 1.22 for each 

3 years of previous exposure; 90% CI = 1.03–

1.45, controlling for age, years of previous exposure, and smoking status and including malignances among living and deceased subjects). 

(The authors reported 90% confidence intervals, rather than 95%. Regression analyses that 

excluded transferred employees were not reported.) The results of this study are limited by 

a small number of deaths and cases and a short 

follow-up period, and the authors stated “only 

a large and early-acting cancer risk would have 

been identifiable” [Pastides et al. 1994a]. The 

average total years between first employment 

in any chromate production facility and death 

was 15.2 years; the maximum was 35.3 years 

[Pastides et al. 1994a]. 

4.1.1.1.2 U.S. chromate production workers,

Maryland (Hayes et al. [1979];

Gibb et al. [2000b])

Gibb et al. [2000b] conducted a retrospective 

analysis of lung cancer mortality in a cohort of 
Hexavalent Chromium 35

4 ■ Human Health Effects

Maryland chromate production workers first 

studied by Hayes et al. [1979]. The cohort studied 

by Hayes et al. [1979] consisted of 2,101 male 

salaried and hourly workers (restricted to 1,803 

hourly workers) employed for at least 90 days 

between January 1, 1945, and December 31, 

1974, who had worked in new and/or old production sites (Table 4–1). Gibb et al. [2000b] 

identified a study cohort of 2,357 male workers 

first employed between 1950 and 1974. Workers who started employment before August 1, 

1950, were excluded because a new plant was 

completed on that date and extensive exposure 

information began to be collected. Workers 

starting after that date, but with short-term 

employment (i.e., < 90 days) were included in 

the study group to increase the size of the low 

exposure group. The Hayes et al. [1979] study 

identified deaths through July 1977. Gibb et al. 

[2000b] extended the follow-up period until 

the end of 1992, and included a detailed retrospective assessment of Cr(VI) exposure and 

information about most workers’ smoking 

habits (see Chapter 6, “Assessment of Risk,” for 

further description of the exposure and smoking data.) The mean length of employment 

was 3.3 years for white workers (n  =  1,205), 

3.7 years for nonwhite workers (n = 848), 0.6 

years for workers of unknown race (n = 304), 

and 3.1 years for the total cohort (n = 2,357). 

The mean follow-up time ranged from 26 years 

to 32 years; there were 70,736 person-years of 

observation. The mean cumulative exposures 

to Cr(VI) were 0.18 mg/m3-years for nonwhite 

employees (n = 848) and 0.13 mg/m3-years for 

white employees (n = 1,205). The mean exposure concentration was 43  μg/m3

 [Park and 

Stayner 2006; NIOSH 2005b]. 

Lung cancer mortality ratios increased with increasing cumulative exposure (i.e., mg CrO3

/

m3-years)—from 0.96 in the lowest quartile to 

1.57 (95%  CI 1.07–2.20; 5-year exposure lag) 

and 2.24 (95% CI 1.60–3.03; 5-year exposure 

lag) in the two highest quartiles. The number 

of expected lung cancer deaths was based on 

age-, race-, and calendar year-specific rates for 

Maryland. Proportional hazards models that 

controlled for the effects of smoking predicted increasing lung cancer risk with increasing 

Cr(VI) cumulative exposure (relative risks: 

1.83 for second exposure quartile, 2.48 for 

third exposure quartile, and 3.32 for fourth 

exposure quartile, compared with first quartile 

of cumulative exposure; confidence intervals 

not reported; 5-year exposure lag) [Gibb et al. 

2000b]. For further exploration of time and exposure variables and lung cancer mortality see 

Gibb et al. [2011]. 

In an analysis by industry consultants of simulated cohort data, lung cancer mortality ratios 

remained statistically significant for white 

workers and the total cohort regardless of 

whether city, county, or state reference populations were used [Exponent 2002]. The simulated data were based on descriptive statistics 

for the entire cohort provided in Gibb et al. 

[2000b], mainly Table 2.

4.1.1.1.3 U.S. chromate production workers,

Ohio (Luippold et al. [2003])

Luippold et al. [2003] conducted a retrospective cohort study of lung cancer mortality in 

482 chromate production workers (four female workers) employed ≥  1 year from 1940 

through 1972 in a Painesville, Ohio plant 

studied earlier by Mancuso [1975, 1997]. The 

current study identified a more recent cohort 

that did not overlap with the Mancuso cohorts. These workers had not been employed 

in any of the company’s other facilities that 

used or produced Cr(VI). However, workers who later worked at the North Carolina 

plant that had available quantitative estimates 

of Cr(VI) were included in this study. The 

number included was not reported in Luippold et al. [2003]; Proctor et al. [2004] stated 

that 17 workers who transferred to the North 
36 Hexavalent Chromium

4 ■ Human Health Effects

Carolina plant had their exposure profiles incorporated. Their mortality was followed from 

1941 through 1997 and compared with United 

States and Ohio rates. Nearly half (i.e., 45%) of 

the cohort worked in exposed jobs for 1 to 4 

years; 16% worked in them > 20 years. Followup length averaged 30 years, ranging from 1 

to 58 years. However, of the workers who died 

from lung cancer (n = 51), 43% worked 20 or 

more years and 82% began plant employment 

before 1955. Their follow-up length averaged 

31.6 years, ranging from 7 to 52 years and totaling 14,048 person-years. More than 800 area 

samples of airborne Cr(VI) from 21 industrial 

hygiene surveys were available for formation 

of a job-exposure matrix. The surveys were 

conducted in 1943, 1945, 1948, and every year 

from 1955 through 1971. Samples were collected in impingers and analyzed colorimetrically 

for Cr(VI). Concentrations tended to decrease 

over time. The average airborne concentration of Cr(VI) in the indoor operating areas of 

the plant in the 1940s was 0.72 mg/m3, 0.27 mg/

m3 from 1957 through 1964, and 0.039  mg/

m3 from 1965 through 1972 [Proctor et al. 

2003]. Further details about the exposure data 

are in Proctor et al. [2003]. For the lung cancer deaths, mean cumulative Cr(VI) exposure 

was 1.58  mg/m3-years (range: 0.003–23  mg/

m3-years) for the cohort and 3.28 mg/m3-years 

(range: 0.06–23 mg/m3-years). The effects of 

smoking could not be assessed because of insufficient data. 

Cumulative Cr(VI) exposure was divided into 

five categories to allow for nearly equal numbers of expected deaths from cancer of the 

trachea, bronchus, or lung in each category: 

0.00–0.19, 0.20–0.48, 0.49–1.04, 1.05–2.69, 

and 2.70–23.0 mg/m3-years [Luippold et al. 

2003]. Person-years in each category ranged 

from 2,369 to 3,220, and the number of deaths 

from trachea, bronchus, or lung cancer ranged 

from 3 in the lowest exposure category to 20 

in the highest (n = 51). The standardized mortality ratios (SMRs) were statistically significant in the two highest cumulative exposure 

categories (3.65 [95% CI 2.08–5.92] and 4.63 

[2.83–7.16], respectively). SMRs were also 

significantly increased for year of hire before 

1960, ≥ 20 years of employment, and ≥ 20 years 

since first exposure. The tests for trend across 

increasing categories of cumulative Cr(VI) exposure, year of hire, and duration of employment were statistically significant (P ≤ 0.005). 

A test for departure of the data from linearity 

was not statistically significant (χ2 goodness of 

fit of linear model; P = 0.23). Van Wijngaarden 

et al. [2004] reported further examination and 

discussion of cumulative Cr(VI) exposure and 

lung cancer mortality in this study and Gibb et 

al. [2000b]. 

4.1.1.1.4 U.S. chromate production workers

(Luippold et al. [2005])

Luippold et al. [2005] conducted a retrospective cohort mortality study of 617 male and female chromate production workers employed 

at least 1  year at one of two U.S. plants: 430 

workers from the North Carolina plant studied 

by Pastides et al. [1994a] (i.e., “Plant 1”) and 

187 workers hired after the 1980 implementation of exposure-reducing process changes at 

“Plant 2”. The study’s primary goal was to investigate possible cancer mortality risks associated with Cr(VI) exposure after production process changes and enhanced industrial hygiene 

controls (i.e., the “postchange environment”). 

Employees who had worked less than 1 year in 

a postchange plant or in a facility using a highlime process were excluded from the cohort. 

Personal air-monitoring measurements available from 1974 to 1988 for Plant 1 and from 

1981 through 1998 for Plant 2 indicated that, 

for most years, overall geometric mean Cr(VI) 

concentrations for both plants were less than 

1.5  μg/m3 and area-specific average personal 

air-sampling values were generally less than 

10 μg/m3.
Hexavalent Chromium 37

4 ■ Human Health Effects

Cohort mortality was followed through 1998. 

The mean time since first exposure was 20.1 

years for Plant 1 workers and 10.1 years for 

Plant 2. Only 27 cohort members (4%) were 

deceased, and stratified analyses with individual exposure estimates and available smoking 

history data could not be conducted because 

of the small number of deaths. Mortality from 

all causes was lower than the expected number of deaths based on state-specific referent 

rates, suggesting a strong healthy worker effect 

(SMR 0.59; 95% CI 0.39–0.85; 27 deaths). Lung 

cancer mortality was also lower than expected 

compared with state reference rates (SMR 0.84; 

95% CI 0.17–2.44; 3 deaths). However, the 

study results are limited by a small number of 

deaths and short follow-up period. The authors 

stated that the “absence of an elevated lung 

cancer risk may be a favorable reflection of the 

postchange environment,” but longer followup allowing an appropriate latency period for 

the entire cohort is needed to confirm this preliminary conclusion [Luippold et al. 2005].

4.1.1.1.5 Chromate production workers,

Germany (Birk et al. [2006])

Birk et al. [2006] conducted a retrospective cohort study of lung cancer mortality using Cr 

levels in urine as a biomarker of occupational 

exposure to Cr(VI). Cohort members were 

males employed in two German chromate production plants after each plant converted to a 

no-lime production process, a process believed 

to result in dusts containing less Cr(VI) [Birk 

et al. 2006]. The average duration of Cr(VI) 

exposure was 9–11 years and mean time since 

first exposure was 16–19 years, depending on 

the plant (i.e., Plant A or Plant B). Smoking 

status from medical examinations/medical records was available for > 90% of the cohort as 

were >  12,000 urinary chromium results collected during routine employee medical examinations of workers from both plants.

Mortality was followed through 1998; 130 deaths 

(22 deaths from cancer of the trachea, bronchus, 

or lung) were identified among 901  workers 

employed at least 1 year in the plant with no 

history of work in a plant before conversion to 

the no-lime process. The number of personyears was 14,684. Although mortality from all 

causes was significantly less than the expected 

number compared with mortality rates for 

Germany, the number of deaths from cancer of 

the trachea, bronchus, or lung was greater than 

expected (SMR  =  1.48; 22 deaths observed; 

14.83 expected; 95% CI 0.93–2.25). When regional mortality rates were used (i.e., North 

Rhine-Westphalia), the SMRs were somewhat 

lower (SMR for all respiratory cancers including trachea, bronchus, and lung = 1.22; 95% CI 

0.76–1.85). 

Geometric mean values of Cr in urine varied 

by work location, plant, and time period, and 

tended to decrease over the years of plant operation (both plants are now closed). Results of 

statistical analysis found lung cancer mortality 

SMRs > 2.00 in the highest cumulative Crin-urine exposure category, for no exposure 

lag, 10-year lag, and 20-year lag (e.g., a statistically significant highest SMR was reported in 

the highest exposure category of ≥ 200 μg/Lyears Cr in urine: SMR 2.09; 12 lung cancer 

deaths observed; 95% CI 1.08–3.65; regional 

rates; no exposure lag). However, few study 

subjects accrued high cumulative exposures 

of 20 years or more before the end of the study. 

Cumulative urinary Cr concentrations of ≥ 200 

μg/L-years compared with concentrations < 200 

μg/L-years were associated with a significantly 

increased risk of lung cancer mortality (OR = 6.9; 

95% CI 2.6–18.2), and the risk was unchanged 

after controlling for smoking [Birk et al. 2006]. 

The use of urinary Cr measurements as a marker 

for Cr(VI) exposure has limitations, primarily 

that it may reflect exposure to Cr(VI), Cr(III), 

or both. In addition, urinary Cr levels may reflect beer consumption or smoking; however, 
38 Hexavalent Chromium

4 ■ Human Health Effects

the study authors stated that “. . . workplace exposures to hexavalent chromium are expected 

to have a much greater impact on overall urinary chromium levels than normal variability 

across individuals due to dietary and metabolic differences” [Birk et al. 2006].

4.1.1.1.6 European welders

(Simonato et al. [1991]) 

IARC researchers conducted a large study of 

lung cancer in 11,092 male welders (164,077 

person-years) from 135  companies in nine 

European countries. Stainless steel welders are 

exposed to welding fumes that can contain 

Cr(VI) and other carcinogens such as nickel. 

Mortality and incidence were analyzed by cause, 

time since first exposure, duration of employment, and estimated cumulative exposure to 

total fumes, chromium (Cr), Cr(VI), and nickel (Ni). The observation period and criteria for 

inclusion of welders varied from country to 

country. Data about subjects’ smoking habits 

were not available for the entire cohort, so no 

adjustment could be made. While mortality 

from all causes of death was significantly lower 

than national rates, the number of deaths from 

lung cancer (116 observed; 86.81 expected; 

SMR 1.34 [95% CI 1.10–1.60]), and malignant neoplasms of the bladder (15  observed; 

7.86 expected; SMR 1.91 [95% CI 1.07–3.15]) 

were significantly higher. Lung cancer SMRs 

tended to increase with years since first exposure for stainless steel welders and mild steel 

welders; the trend was statistically significant 

for the stainless steel welders (P  <  0.05). The 

SMRs for subgroups of stainless steel welders with at least 5  years of employment and 

20 years since first exposure and high cumulative exposure to either Cr(VI) or Ni (i.e., ≥ 0.5 

mg-years/m3) were not significantly higher than 

SMRs for the low cumulative exposure subgroup 

(i.e., < 0.5 mg-years/m3) [Simonato et al. 1991].

IARC classifies welding fumes and gases as 

Group 2B carcinogens—limited evidence of 

carcinogenicity in humans [IARC 1990]. During a 2009 review, IARC found sufficient evidence for ocular melanoma in welders [El 

Ghissassi et al. 2009]. NIOSH recommends 

that “exposures to all welding emissions be reduced to the lowest feasible concentrations using state-of-the-art engineering controls and 

work practices” [NIOSH 1988a]. 

4.1.2 Nasal and Sinus Cancer

Cases or deaths from sinonasal cancers were 

reported in five IARC-reviewed studies of 

chromium production workers in the United 

States, United Kingdom, and Japan, chromate 

pigment production workers in Norway, and 

chromium platers in the United Kingdom (see 

Tables 4–1 through 4–3). IARC concluded that 

the findings represented a “pattern of excess 

risk” for these rare cancers [IARC 1990] and 

in 2009 concluded there is limited evidence 

for human cancers of the nasal cavity and paranasal sinuses from exposure to Cr(VI) compounds [Straif et al. 2009; IARC 2012]. 

Subsequent mortality studies of chromium or 

chromate production workers employed in New 

Jersey from 1937 through 1971 and in the United Kingdom from 1950 through 1976 reported 

significant excesses of deaths from nasal and sinus cancer (proportionate cancer mortality ratio (PCMR) = 5.18 for white males, P < 0.05, six 

deaths observed and no deaths observed in black 

males [Rosenman and Stanbury 1996]; SMR adjusted for social class and area = 1,538, P < 0.05, 

four deaths observed [Davies et al. 1991]). Cr(VI) 

exposure concentrations were not reported. 

However, an earlier survey of three chromate 

production facilities in the U.K. found that average air concentrations of Cr(VI) in various phases of the process ranged from 0.002 to 0.88 mg/

m3 [Buckell and Harvey 1951; ATSDR 2012]. 

Four cases of carcinoma of the nasal region 

were described in male workers with 19 to 32 
Hexavalent Chromium 39

4 ■ Human Health Effects

years of employment in a Japanese chromate 

factory [Satoh et al. 1994]. No exposure concentrations were reported. 

Although increased or statistically significant 

numbers of cases of nasal or sinonasal cancer 

have been reported in case-control or incidence studies of leather workers (e.g., boot and 

shoe production) or leather tanning workers in 

Sweden and Italy [Comba et al. 1992; Battista 

et al. 1995; Mikoczy and Hagmar 2005], a U.S. 

mortality study did not find an excess number 

of deaths from cancer of the nasal cavity [Stern 

et al. 2003]. The studies did not report quantitative exposure concentrations of Cr(VI), and 

a causative agent could not be determined. 

Leather tanning workers may be exposed to 

several other potential occupational carcinogens, including formaldehyde.

4.1.3 Nonrespiratory Cancers

Statistically significant excesses of cancer of 

the oral region, liver, esophagus, and all cancer 

sites combined were reported in a few studies 

reviewed by IARC (Tables 4–1  through  4–4). 

IARC [1990] concluded that “for cancers other 

than of the lung and sinonasal cavity, no consistent pattern of cancer risk has been shown 

among workers exposed to chromium compounds.” More recent reviews by other groups 

also did not find a consistent pattern of nonrespiratory cancer risk in workers exposed to inhaled Cr(VI) [ATSDR 2012; Proctor et al. 2002; 

Chromate Toxicity Review 2001; EPA 1998; 

Government of Canada 1994; Cross et al. 1997; 

CRIOS 2003; Criteria Group for Occupational 

Standards 2000]. IARC [2012] concluded that 

“there is little evidence that exposure to chromium (VI) causes stomach or other cancers.”

4.1.4 Cancer Meta-Analyses

Meta-analysis and other systematic literature review methods are useful tools for summarizing 

exposure risk estimates from multiple studies. 

Meta-analyses or summary reviews of epidemiologic studies have been conducted to investigate cancer risk in chromium-exposed 

workers.

Steenland et al. [1996] reported overall relative 

risks for specific occupational lung carcinogens, including chromium. Ten epidemiologic studies were selected by the authors as the 

largest and best-designed studies of chromium 

production workers, chromate pigment production workers, and chromium platers (i.e., 

Enterline 1974; Hayes et al. 1979; Alderson et 

al. 1981; Satoh et al. 1981; Korallus et al. 1982; 

Frentzel-Beyme 1983; Davies 1984; Sorahan 

et al. 1987; Hayes et al. 1989; Takahashi and 

Okubo 1990). 

The summary relative risk for the 10 studies 

was 2.78 (95% CI 2.47–3.52; random effects 

model), which was the second-highest relative 

risk among eight carcinogens summarized.

Cole and Rodu [2005] conducted meta-analyses 

of epidemiologic studies published in 1950 or 

later to test for an association of chromium 

exposure with all causes of death, and death 

from malignant diseases (i.e., all cancers combined, lung cancer, stomach cancer, cancer 

of the central nervous system [CNS], kidney 

cancer, prostate gland cancer, leukemia, Hodgkin’s disease, and other lymphatohematopoietic cancers). Available papers (n = 114) were 

evaluated independently by both authors on 

eight criteria that addressed study quality. In 

addition, papers with data on lung cancer were 

assessed for control of cigarette smoking, and 

papers with data on stomach cancer were assessed for economic status. Lung or stomach 

cancer papers that were negative or “essentially negative” regarding chrome exposure 

were included with papers that controlled for 

smoking or economic status. Forty-nine epidemiologic studies, based on 84 papers published 

since 1950, were used in the meta-analyses. 
40 Hexavalent Chromium

4 ■ Human Health Effects

The number of studies in each meta-analysis 

ranged from 9 for Hodgkin’s disease to 47 for 

lung cancer. Most studies investigated occupational exposure to chromium. Association was 

measured by an author-defined “SMR,” which 

included odds ratios, proportionate mortality 

ratios and, most often, standardized mortality ratios. Confidence intervals (i.e., 95%) were 

calculated by the authors. Mortality risks were 

not significantly increased for most causes of 

death (i.e., all causes, prostate gland cancer, 

kidney cancer, CNS cancer, leukemia, Hodgkin’s disease, or other lymphatohematopoietic 

cancers). However, SMRs were significantly 

increased in all lung cancer meta-analyses 

(smoking controlled: 26 studies; 1,325 deaths; 

SMR  =  118; 95% CI 112–125) (smoking not 

controlled: 21 studies; 1,129 deaths; SMR = 181; 

95% CI 171–192) (lung cancer—all: 47 studies; 

2,454 deaths; SMR  =  141; 95% CI 135–147). 

Stomach cancer mortality risk was significantly increased only in meta-analyses of studies 

that did not control for effects of economic status (economic status not controlled: 18 studies; 324 deaths; SMR  =  137; 95% 123–153). 

The authors stated that statistically significant 

SMRs for “all cancer” mortality were mainly 

due to lung cancer (all cancer: 40 studies; 6,011 

deaths; SMR = 112; 95% CI 109–115). Many of 

the studies contributing to the meta-analyses 

did not address bias from the healthy worker 

effect, and thus the results are likely underestimates of the cancer mortality risks. Other 

limitations of these meta-analyses include lack 

of (1) exposure characterization of populations 

such as  the route of exposure (i.e., airborne 

versus ingestion) and (2) detail of criteria used 

to exclude studies based on “no or little chrome 

exposure” or “no usable data.” 

Paddle [1997] conducted a meta-analysis of 

four studies of chromate production workers in plants in the United States (Hayes et al. 

[1979]; Pastides et al. [1994a]), United Kingdom (i.e., Davies et al. [1991]), and Germany 

(i.e., Korallus et al. [1993]) that had undergone 

modifications to reduce chromium exposure. 

Most of the modifications occurred around 

1960. This meta-analysis of lung cancer “postmodification” did not find a statistically significant excess of lung cancer (30 deaths observed; 

27.2 expected; risk measure and confidence 

interval not reported). The author surmised 

that none of the individual studies in the meta-analysis or the meta-analysis itself had sufficient statistical power to detect a lung cancer 

risk of moderate size because of the need to 

exclude employees who worked before plant 

modifications and the need to incorporate a 

latency period, thus leading to very small observed and expected numbers. Meta-analyses 

of gastrointestinal cancer, laryngeal cancer, or 

any other nonlung cancer were considered inappropriate by the author because of reporting 

bias and inconsistent descriptions of the cancer sites [Paddle 1997]. 

Sjögren et al. [1994] authored a brief report of 

their meta-analysis of five lung cancer studies 

of Canadian and European welders exposed to 

stainless steel welding fumes. The meta-analysis found an estimated relative risk of 1.94 (95% 

CI 1.28–2.93) and accounted for the effects of 

smoking and asbestos exposure [Sjögren et al. 

1994]. (Details of each study’s exposure assessment and concentrations were not included.)

4.1.5 Summary of Cancer

and Cr(VI) Exposure

Occupational exposure to Cr(VI) has long 

been associated with nasal and sinus cancer 

and cancers of the lung, trachea, and bronchus. 

No consistent pattern of nonrespiratory cancer 

risk has been identified. 

Few studies of Cr(VI) workers had sufficient 

data to determine the quantitative relationship 

between cumulative Cr(VI) exposure and lung 

cancer risk while controlling for the effects of 
Hexavalent Chromium 41

4 ■ Human Health Effects

other lung carcinogens, such as tobacco smoke. 

One such study found a significant relationship between cumulative Cr(VI) exposure 

(measured as CrO3) and lung cancer mortality 

[Gibb et al. 2000b]; the data were reanalyzed 

by NIOSH to further investigate the exposureresponse relationship (see Chapter 6, “Assessment of Risk”).

The three meta-analyses and summary reviews 

of epidemiologic studies with sufficient statistical power found significantly increased lung 

cancer risks with chromium exposure. 

4.2 Nonmalignant Effects

Cr(VI) exposure is associated with contact dermatitis, skin ulcers, irritation and ulceration of 

the nasal mucosa, and perforation of the nasal septum [NIOSH 1975a]. Reports of kidney 

damage, liver damage, pulmonary congestion 

and edema, epigastric pain, erosion and discoloration of teeth, and perforated ear drums were 

found in the literature, and NIOSH concluded 

that “sufficient contact with any chromium(VI) 

material could cause these effects” [NIOSH 

1975a]. Later studies that provided quantitative 

Cr(VI) information about the occurrence of 

those effects is discussed here. (Studies of nonmalignant health effects and total chromium 

concentrations [i.e., non-speciated] are included in reviews by the Criteria Group for Occupational Standards [2000] and ATSDR [2012].)

4.2.1 Respiratory Effects

The ATSDR [2012] review found many reports and studies published from 1939 to 1991 

of workers exposed to Cr(VI) compounds for 

intermediate (i.e., 15–364 days) to chronic 

durations that noted these respiratory effects: 

epistaxis, chronic rhinorrhea, nasal itching and 

soreness, nasal mucosal atrophy, perforations 

and ulcerations of the nasal septum, bronchitis, pneumoconiosis, decreased pulmonary 

function, and pneumonia. 

Five recent epidemiologic studies of three cohorts analyzed quantitative information about 

occupational exposures to Cr(VI) and respiratory effects. The three worksite surveys 

described below provide information about 

workplace Cr(VI) concentrations and health 

effects at a particular point in time only and do 

not include statistical analysis of the quantitative relationship between specific work exposures and reported health symptoms; thus they 

contribute little to evaluation of the exposureresponse association. (Studies and surveys previously reviewed by NIOSH [1975, 1980] are 

not included.)

4.2.1.1 Work site surveys

A NIOSH HHE of 11 male employees in an 

Ohio electroplating facility reported that most 

men had worked in the “hard-chrome” area 

for the majority of their employment (average 

duration: 7.5 years; range: 3–16 years). Four of 

the 11 workers had a perforated nasal septum. 

Nine of the 11 men had hand scars resulting 

from past chrome ulcerations. Other effects 

found during the investigation included nose 

bleeds, “runny nose,” and nasal ulcerations. 

A total of 17 air samples were collected for 

Cr(VI) with a vacuum pump in 2 days during 

periods of 2–4 hours (14 personal; 3 area). The 

mean Cr(VI) concentration was 0.004 mg/m3

(range: < 0.001 mg/m3–0.02 mg/m3) [NIOSH 

1975c]. This survey focused on chromic acid 

exposure; other potential exposures were not 

noted in the report. Possible limitations of this 

study include (1) lack of a comparison or unexposed “control” group, (2) inclusion of only 

current workers, and (3) a small and possibly 

unrepresentative study group. Other NIOSH 

HHEs that noted nasal sores or other respiratory effects in workers exposed to chromium 

had similar limitations and are not discussed 

here. In addition, some surveys were conducted 

in workplaces with air concentrations of chromium and other metals, dusts, and chemicals 
42 Hexavalent Chromium

4 ■ Human Health Effects

(e.g., nickel, copper, zinc, particulates, ammonia [NIOSH 1985a,b], sulfur dioxide, welding 

fume, aluminum, carbon monoxide, nitrogen 

dioxide [Burkhart and Knutti 1994]) that could 

have contributed to observed and reported effects. 

An HHE at a small chrome plating shop with 

six workers (including four platers) found 

among the workers no nasal ulcerations, nasal 

septal perforations, or lesions on the hands. 

However, information was obtained by interview, observation, and questionnaire, and no 

medical examinations were performed. Four 

PBZ samples with durations of 491 to 505 minutes were analyzed and found to contain low air 

concentrations of Cr(VI) (0.003–0.006 mg/m3) 

and total chromium (0.009–0.011 mg/m3). The 

HHE was requested because of reported overexposure to chemicals used in chrome plating, 

poor ventilation, and cardiovascular disorders 

among employees. NIOSH determined that 

(1) overexposures to plating chemicals did not 

exist, (2) local exhaust systems were operating 

“below recommended levels,” and (3) no occupational factors contributing to heart disease 

were identified. Recommendations were made 

for ventilation, housekeeping, and personal 

protective equipment (PPE) [Ahrenholz and 

Anderson 1981].

Eleven cases of nasal septum perforation were 

found in 2,869 shipyard welders in Korea [Lee 

et al. 2002]. The affected workers had no history 

of trauma, surgery, diseases, or medication use 

that could account for the perforations. Blood 

and urine chrome concentrations of the affected workers were below the LOD. The affected 

workers ranged in age from 37 to 51 years and 

had welded 12–25 years. Personal air samples 

for Cr(VI) were collected from 31 workers in a 

stainless steel welding shop (shop F) and the 

five work locations (i.e., CO2 welding shops 

A–E), where the 11 workers who had septum 

perforation were last employed. (“Most” of 

the workers had not recently worked in shop F.) 

Mean, maximum, and minimum Cr(VI) concentrations, and number of affected workers 

were reported for each shop (shops A, B, D, and 

E had two affected workers; shop C had three). 

The number of unaffected workers (non-cases) 

per shop was not reported. The mean concentrations of Cr(VI) in the welding fume ranged 

from 0.0012  mg/m3 (shop B) to 0.22  mg/m3

(8-hour TWA) in shop F. The highest maximum (0.34 mg/m3

) and minimum (0.044 mg/

m3) Cr(VI) concentrations were also measured 

in shop F. The mean Cr(VI) concentrations in 

shops A, C, D and E ranged from 0.0014 (shop 

C) to 0.0028 mg/m3 (shop E) (maximums for 

A–E: 0.0013 mg/m3–0.0050 mg/m3). Annual 

industrial hygiene surveys for air concentrations of metals conducted from 1991 through 

2000 found that mean total “chrome” (i.e., Cr) 

concentrations ranged from 0.002  to 0.025 

mg/m3, and the maximum concentrations 

were 0.010–0.509 mg/m3. The authors judged 

that pre-1990 concentrations were higher. The 

authors could not obtain annual total Cr or 

Cr(VI) concentrations for the stainless steel 

welding workplace. Use of a comparison group 

was not reported. The authors assumed that the 

nasal septal perforations were caused by “longterm exposure to the low levels of hexavalent 

chromium during welding” [Lee et al. 2002] 

(mean concentrations exceeded the existing 

and revised Cr(VI) RELs).

4.2.1.2 Epidemiologic studies

4.2.1.2.1 Lindberg and Hedenstierna [1983]

A cross-sectional study of respiratory symptoms, changes in nasal mucosa, and lung function was conducted in chrome-plating workers 

in Swedish factories (n = 43: 16 male nonsmokers; 21 male smokers; 3 female nonsmokers; 3 

female smokers) [Lindberg and Hedenstierna 

1983]. Five chrome baths in three factories were 

studied for a total of 19 work days. Office employees (n = 19: 13 males; 14 nonsmokers) and 
Hexavalent Chromium 43

4 ■ Human Health Effects

auto mechanics (n = 119 males; 52 nonsmokers) were used as comparison groups for nose 

and throat effects, and lung function, respectively. For analysis of subjective symptoms and 

nasal conditions, the 43 exposed workers were 

divided into two groups: “low” exposure (8-

hour mean ≤ 1.9 μg/m3 chromic acid; 19 workers) and “high” mean exposure (2–20 μg/m3

chromic acid; 24 workers). Mean daily Cr(VI) 

exposures ranged from ≤ 1.9 to 20 μg/m3. Their 

median duration of employment was 2.5 years 

(range: 0.2–23.6 years). Exposure concentrations were measured with personal air samplers and stationary equipment placed near the 

chromic acid baths. A statistically significant 

difference was found in the low exposure group 

when compared with controls for the effect 

of “smeary and crusty septal mucosa” (11/19 

workers versus 5/19 controls; P < 0.05). There 

were no perforations or ulcerations in the low 

exposure group. Frequency of nasal atrophy was 

significantly greater in the high exposure group 

compared with the controls (8/24 workers versus 0/19 controls; P < 0.05). The high exposure 

group also had higher frequency of nasal mucosal ulcerations and/or septal perforations (8 

workers with ulcerations—2 of those also had 

perforations; 5 workers with perforations—2 of 

those also had ulcerations; P < 0.01; number of 

controls not reported). Fourteen workers were 

temporarily exposed to peak concentrations 

of 20–46 μg/m3 when working near the baths; 

10 of those workers had nasal mucosal ulcerations with or without perforation, or perforation only. Workers with low exposure had no 

significant changes in lung function during the 

survey. Workers in the high exposure group 

had slight transient decreases in forced vital 

capacity (FVC), forced expired volume in one 

second (FEV1) and forced mid-expiratory flow 

during the work week.

The results of that study were used by ATSDR 

to determine an inhalation minimum risk 

level (MRL) of 0.000005 mg/m3 (0.005 μg/m3) 

for intermediate-duration exposure (15–364 

days) to Cr(VI) as chromium trioxide mist 

and other dissolved Cr(VI) aerosols and mists. 

(An intermediate-duration inhalation MRL of 

0.0003 mg Cr(VI)/m3 for exposure to chromium (VI) particulates was derived from a study 

in rats, Glaser et al. [1990].) 

4.2.1.2.2 Huvinen et al. [1996; 2002a,b]

No increased prevalences of respiratory symptoms, lung function deficits, or signs of pneumoconiosis (i.e., small radiographic opacities) 

were found in a 1993 cross-sectional study of 

stainless steel production workers [Huvinen 

et al. 1996]. The median personal Cr(VI) concentration measured in the steel smelting shop 

in 1987 was 0.5  μg/m3 (i.e., 0.0005  mg/m3). 

(Duration of sample collection and median 

Cr(VI) concentrations for other work areas 

were not reported.) The study group consisted 

of 221 production workers with at least 8 years 

of employment in the same department and a 

control group of 95 workers from the cold rolling mill and other areas where chromium or 

dust exposure was minimal or non-existent. 

The chromium-exposed workers were divided 

into three groups: Cr(VI)-exposed (n = 109), 

Cr(III)-exposed (n = 76), and chromite-exposed 

(n = 36). Questionnaires regarding health symptoms were completed by 37  former workers; 

none of those workers reported leaving the 

company because of a disease. One person reported having chronic bronchitis, two reported 

having bronchial asthma, and no former workers reported other pulmonary diseases, allergic rhinitis, or cancer. Controls and workers 

exposed to Cr(VI) had similar mean durations 

of employment (exposed: 16.0 years; controls: 

14.4 years), smoking habits, and other characteristics. Logistic regression analyses adjusted 

for effects of confounding factors and found no 

significant differences between Cr(VI)-exposed 

workers and controls in reported symptom 

prevalences, prevalence of impaired lung function (with the exception of impaired peak 
44 Hexavalent Chromium

4 ■ Human Health Effects

expiratory flow which was significantly more 

prevalent in the control group [P < 0.05]), or 

occurrence of small opacities.

A similar cross-sectional study of the same 

cohort 5  years later yielded similar results 

[Huvinen et al. 2002a]. The median Cr(VI) 

personal concentration (duration of sample 

collection time not reported) measured in the 

steel smelting shop in 1999 had decreased to 

0.0003  mg/m3 (maximum: 0.0007  mg/m3), 

which the authors attributed to technological 

improvements in production processes. (Exposure concentrations reported in the text and 

tables differed; table values are reported here.) 

Cr(VI)-exposed workers (n = 104; mean duration of employment: 21.0 years) and controls 

(n = 81; mean employment: 19.4 years) did not 

differ significantly in prevalence of respiratory 

symptoms or lung function deficits. The profusion of small opacities had progressed in three 

workers (ILO category ≥  1/0), including one 

exposed to Cr(VI). Based on the findings in 

both studies, the authors concluded that exposure to chromium compounds at the measured 

concentrations does not produce pulmonary 

fibrosis. Clinical examinations of 29 workers 

exposed to Cr(VI) from the steel smelting shop 

found no nasal tumors, chronic ulcerations, or 

septal perforations (mean duration of employment: 21.4 years) [Huvinen et al. 2002b].

4.2.1.2.3 Gibb et al. [2000a]

A retrospective study of 2,357 males first employed from 1950 through 1974 at a chromate 

production plant included a review of clinic 

and first aid records for physician findings of 

nasal irritation, ulceration, perforation; and 

bleeding, skin irritation and ulceration, dermatitis, burns, conjunctivitis, and perforated 

eardrum [Gibb et al. 2000a]. The mean and 

median annual airborne Cr(VI) concentrations (measured as CrO3

) for the job title where 

the clinical finding first occurred and cohort 

percentages with various clinical findings, 

from start of employment to occurrence of the 

first finding, were determined. (See Chapter 6 

for further description of the exposure data.) 

About 40% of the cohort (n  =  990) worked 

fewer than 90 days. These short-term workers were included to increase the low exposure 

group. Medical records were available for 2,307 

men (97.9% of total cohort). The record review 

found that more than 60% of the cohort had 

irritated nasal septum (68.1%) or ulcerated nasal septum (62.9%). Median Cr(VI) exposure 

(measured as CrO3) at the time of first diagnosis of these findings and all others (i.e., perforated nasal septum, bleeding nasal septum, 

irritated skin, ulcerated skin, dermatitis, burn, 

conjunctivitis, and perforated eardrum) was 

0.020–0.028 mg/m3 (20–28 μg/m3). The median time from date first employed to date of first 

diagnosis was less than 1 month for three conditions: irritated nasal septum (20 days), ulcerated nasal septum (22 days), and perforated 

eardrum (10 days). The mean time from date 

first employed to date of first diagnosis for each 

of these conditions was 89 days for irritated 

nasal septum, 86 days for ulcerated nasal septum, and 235 days for perforated eardrum. The 

relationship between Cr(VI) exposure and first 

occurrence of each clinical finding was evaluated with a proportional hazards model. The 

model predicted that ambient Cr(VI) exposure 

was significantly associated with occurrence 

of ulcerated nasal septum (P = 0.0001), ulcerated skin (P = 0.004), and perforated eardrum 

(P = 0.03). Relative risks per 0.1 mg/m3 increase 

in CrO3 were 1.20 for ulcerated nasal septum, 

1.11 for ulcerated skin, and 1.35 for “perforated ear.” Calendar year of hire was associated 

with each finding except conjunctivitis and irritated skin; the risk decreased as year of hire 

became more recent. The authors suggested 

that the reduction could possibly be because 

of decreases in ambient Cr(VI) exposure from 

1950 to 1985 or changes in plant conditions, 

such as use of respirators and personal hygiene 
Hexavalent Chromium 45

4 ■ Human Health Effects

measures [Gibb et al. 2000a]. The authors also 

suggested that the proportional hazards model 

did not find significant associations with all 

symptoms because the Cr(VI) concentrations 

were based on annual averages rather than on 

shorter, more recent average exposures, which 

may have been a more relevant choice.

4.2.1.3 Summary of respiratory effects

studies and surveys

A few workplace surveys measured Cr(VI) air 

concentrations and conducted medical evaluations of workers. These short-term surveys did 

not include comparison groups or exposureresponse analyses. Two surveys found U.S. 

electroplaters and Korean welders with nasal perforations or other respiratory effects; 

the lowest mean Cr(VI) concentrations at the 

worksites were 0.004  mg/m3 for U.S. electroplaters and 0.0012 mg/m3

 for Korean welders 

[NIOSH 1975c; Lee et al. 2002].

Cross-sectional epidemiologic studies of chromeplating workers [Lindberg and Hedenstierna 

1983] and stainless steel production workers 

[Huvinen et al. 1996; 2002a,b] found no nasal 

perforations at average chromic acid concentrations < 2 μg/m3

. The platers experienced nasal 

ulcerations and/or septal perforations and transient reductions in lung function at mean concentrations ranging from 2 μg/m3

 to 20 μg/m3. 

Nasal mucosal ulcerations and/or septal perforations occurred in plating workers exposed to 

peak concentrations of 20–46 μg/m3. 

The best exposure-response information to 

date is from the only epidemiologic study with 

sufficient health and exposure data to estimate 

the risks of ulcerated nasal septum, ulcerated 

skin, perforated nasal septum, and perforated 

eardrum over time [i.e., Gibb et al. 2000a]. This 

retrospective study reviewed medical records 

of more than 2,000 male workers and analyzed 

thousands of airborne Cr(VI) measurements 

collected from 1950 through 1985. More than 

60% of the cohort had experienced an irritated 

nasal septum (68.1%) or ulcerated nasal septum (62.9%) at some time during their employment. The median Cr(VI) exposure (measured 

as CrO3) at the time of first diagnosis of these 

findings and all others (i.e., perforated nasal 

septum, bleeding nasal septum, irritated skin, 

ulcerated skin, dermatitis, burn, conjunctivitis, 

perforated eardrum) was 0.020  mg/m3–0.028 

mg/m3 (20  μg/m3–28  μg/m3). Of particular 

concern is the finding of nasal and ear effects 

occurring in less than 1 month: the median 

time from date first employed to date of first 

diagnosis was less than 1 month for irritated 

nasal septum (20 days), ulcerated nasal septum 

(22 days), and perforated eardrum (10 days). A 

proportional hazards model predicted relative 

risks of 1.20 for ulcerated nasal septum, 1.11 

for ulcerated skin, and 1.35 for “perforated ear” 

for each 0.1 mg/m3 increase in ambient CrO3. 

The authors noted that the chrome platers 

studied by Lindberg and Hedenstierna [1983] 

were exposed to chromic acid, which may be 

more irritative than the chromate chemicals 

occurring with chromate production [Gibb et 

al. 2000a].

4.2.1.4 Asthma

Occupational asthma caused by chromium exposure occurs infrequently compared with allergic contact dermatitis [Leroyer et al. 1998]. 

The exposure concentration below which no 

cases of occupational asthma would occur, 

including cases induced by chromium compounds, is not known [Chan-Yeung 1995]. 

Furthermore, that concentration is likely to be 

lower than the concentration that initially led 

to the employee’s sensitization [Chan-Yeung 

1995]. Case series of asthma have been reported in U.K. electroplaters [Bright et al. 1997], 

Finnish stainless steel welders [Keskinen et al. 

1980], Russian alumina industry workers [Budanova 1980]; Korean metal plating, construction, and cement manufacturing workers, [Park 
46 Hexavalent Chromium

4 ■ Human Health Effects

et al. 1994]; and a cross-sectional study of U.K. 

electroplaters [Burges et al. 1994]. However, 

there are no quantitative exposure-response assessments of asthma related to Cr(VI) in occupational cohorts, and further research is needed.

4.2.2 Dermatologic Effects

Cr(VI) compounds can cause skin irritation, skin ulcers, skin sensitization, and allergic contact dermatitis. In 1975, NIOSH 

recommended protective clothing and other 

measures to prevent occupational exposure 

[NIOSH 1975a]. Because of those health hazards, potential eye contact, or other nonrespiratory hazards, protective measures and 

appropriate work practices are recommended 

“regardless of the airborne concentration of 

chromium(VI)” [NIOSH 1975a]. Current recommendations for prevention of dermal exposure to Cr(VI) compounds are presented in 

Chapter 8, “Risk Management.”

There are many occupational sources of chromium compounds. Dermatologic effects (i.e., 

mainly allergic contact dermatitis [ACD]) 

have been reported from exposure to cement 

and cement-hardening agents, cleaning, washing, and bleaching materials, textiles and furs, 

leather and artificial leather tanned with chromium, chrome baths, chromium ore, chrome 

colors and dyes, pigments in soaps, primer 

paints, anti-corrosion agents, cutting fluids, 

machine oils, lubricating oils and greases, 

glues, resin hardeners, wood preservatives, 

boiler linings, foundry sand, matches, welding 

fumes, and other sources [Burrows et al. 1999; 

Burrows 1983, 1987; Handley and Burrows 

1994; Haines and Nieboer 1988; Polak 1983]. 

No occupational studies have examined the 

quantitative exposure-response relationship between Cr(VI) exposure and a specific dermatologic 

effect, such as ACD; thus, an exposure-response 

relationship has not been clearly established. 

Gibb et al. [2000a] evaluated mean Cr(VI) exposure and mean and median time from first 

employment to the diagnosis of several skin or 

membrane irritations: irritated skin, ulcerated 

skin, dermatitis, burn, and conjunctivitis (see 

Sections 4.2.1.2 and 4.2.1.3). Ulcerated skin 

and burns were reported in more than 30% of 

the cohort. The mean Cr(VI) concentration 

(measured as CrO3) ranged from 0.049 mg/m3

to 0.058 mg/m3 at the time of first diagnosis of 

those five effects. The mean days on the job until first diagnosis ranged from 373 to 719 days 

(median 110–221 days).

Other assessments evaluated the occurrence 

of ACD from contact with Cr(VI) in soil (e.g., 

Proctor et al. [1998]; Paustenbach et al. [1992]; 

Bagdon and Hazen [1991]; Stern et al. [1993]; 

Nethercott et al. [1994, 1995]).

4.2.3 Reproductive Effects

The six available studies of pregnancy occurrence, course, or outcome reported little or no 

information about total Cr or Cr(VI) concentrations at the workplaces of female chromium 

production workers [Shmitova 1978, 1980] or 

male welders that were also spouses [Bonde et 

al. 1992; Hjollund et al. 1995, 1998, 2000]. The 

lack of consistent findings and exposureresponse analysis precludes formation of conclusions about occupational Cr(VI) exposure 

and adverse effects on pregnancy and childbirth. Further research is needed.

4.2.4 Other Health Effects

4.2.4.1 Mortality studies

More than 30 studies examined numerous noncancer causes of death in jobs with potential 

chromium exposure, such as chromate production, chromate pigment production, chromium 

plating, ferrochromium production, leather 

tanning, welding, metal polishing, cement 
Hexavalent Chromium 47

4 ■ Human Health Effects

finishing, stainless steel grinding or production, gas generation utility work, and paint 

production or spraying. (Studies previously 

cited by NIOSH [1975, 1980] are not included.) 

Most studies found no statistically significant 

increases (i.e., P  <  0.05) in deaths from nonmalignant respiratory diseases, cardiovascular 

diseases, circulatory diseases, accidents, or any 

other noncancer cause of death that was included [Hayes et al. 1979, 1989; Korallus et al. 

1993; Satoh et al. 1981; Sheffet et al. 1982; Royle 1975a; Franchini et al. 1983; Sorahan and 

Harrington 2000; Axelsson et al. 1980; Becker 

et al. 1985; Becker 1999; Blair 1980; Dalager et 

al. 1980; Järvholm et al. 1982; Silverstein et al. 

1981; Sjögren et al. 1987; Svensson et al. 1989; 

Bertazzi et al. 1981; Blot et al. 2000; Montanaro 

et al. 1997; Milatou-Smith et al. 1997; Moulin 

et al. 2000; Pastides et al. 1994a; Simonato et 

al. 1991; Takahashi and Okubo 1990; Luippold 

et al. 2005]. However, these studies did not include further investigation of the nonsignificant outcomes and therefore do not confirm 

the absence of an association. 

Some studies did identify significant increases 

in deaths from various causes [Davies et al. 

1991; Alderson et al. 1981; Sorahan et al. 1987; 

Deschamps et al. 1995; Itoh et al. 1996; Rafnsson and Jóhannesdóttir 1986; Gibb et al. 2000b; 

Kano et al. 1993; Luippold 2003; Moulin et al. 

1993; Rosenman and Stanbury 1996; Stern et 

al. 1987; Stern 2003]. However, the findings 

were not consistent: no noncancer cause of 

death was found to be significantly increased 

in at least five studies. Furthermore, exposureresponse relationships were not examined for 

those outcomes. Therefore, the results of these 

studies do not support a causal association 

between occupational Cr(VI) exposure and a 

nonmalignant cause of death.

4.2.4.2 Other health effects

NIOSH [1975a] concluded that Cr(VI) exposure could cause other health effects such 

as kidney damage, liver damage, pulmonary 

congestion and edema, epigastric pain, and 

erosion and discoloration of the teeth. Other 

effects of exposure to chromic acid and chromates not discussed elsewhere in this section 

include eye injury, leukocytosis, leukopenia, 

and eosinophilia [NIOSH 2003c; Johansen et 

al. 1994]. Acute renal failure and acute chromium intoxication occurred in a male worker following a burn with concentrated chromic acid 

solution to 1% of his body [Stoner et al. 1988]. 

There has been little post-1975 research of those 

effects in occupational cohorts. Furthermore, 

there is insufficient evidence to conclude that 

occupational exposure to respirable Cr(VI) 

is related to other health effects infrequently 

reported in the literature after the NIOSH 

[1975a] review. These effects included cerebral 

arachnoiditis in 47 chromium industry workers [Slyusar and Yakovlev 1981] and cases of 

gastric disturbances (e.g., chronic gastritis, 

polyps, ulcers, and mucous membrane erosion) in chromium salt workers [Sterekhova et 

al. 1978]. Neither study analyzed the relationship of air Cr(VI) concentrations and health 

effects, and one had no comparison group 

[Sterekhova et al. 1978]. 
48 Hexavalent Chromium

4 

■ Human Health Effects

Table 4–1. IARC [1990]-reviewed epidemiologic studies of cancer in workers in chromate-producing industries.

Reference

and country

Study population 

and follow-up

Reference

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and 

Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Alderson et al. [1981], United Kingdom

Same U.K.chromate producing factories as Bidstrup and Case [1956]; employed ≥ 1 yr 1948–1977; 2,715 males.

Cancer mortality— England, Wales, Scotland

Lung 116 deaths 2.4* Other sites

Nasal cancer

80

 2

1.2

7.1*

No No

Baetjer [1950], United States

290 male lung cancer patients admitted to two hospitals near U.S. chromate plant 1925–1948.

Random sample of hospital admissions

Lung or bronchi

11 reported exposure to chromium

Reported as statistically significant

— — — No No

Bidstrup and Case [1956], UnitedKingdom

Three U.K. chromate factories; mortality follow-up of 723 men employed 1949–1955.

Cancer mortality— England and Wales

Lung 12 3.6* Other sites 9 1.1 No No

Brinton et al. [1952], United States

Male workers in seven chromate plants; active employees 1940–1950.

U.S. male mortality, white, nonwhite

Respiratory system, except larynx

10 white; 16 nonwhite

14.3*80.0*

Other sites 5 white; 

 1 nonwhite

1.0 No No

See footnotes at end of table. (Continued)
Hexavalent Chromium 49

4 

■ Human Health Effects

Reference

and country

Study population 

and follow-up

Reference

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and 

Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

De Marco et al. [1988], Italy

540 Italian chromate producers employed 1948–1985 with ≥ 1 year cumulative exposure entered into study ≥ 10 years after starting work.

Italian causespecific death rates

LungHighly exposed (qualitative estimate of Cr[VI] exposure) 

14

 6

2.2*4.2*

LarynxPleura

33

2.9

30.0*

No No

Federal Security Agency [1953], United States

Health survey of 897 chromate workers in six chromateproducing plants.

Boston chest X-ray survey

Bronchogenic/Lung

7 white; 3 nonwhite

53.6

(prevalence ratio)

— — — No Yes

Hayes et al. [1979], United States

2,101 male workers (restricted to 1,803 workers) employed in a U.S. chromate plant ≥ 90 days 1945–1974, working in new and/or old production sites.

Baltimore city mortality

Trachea, bronchus, lung

59 2.0* Digestive 

systemOther

1314

0.600.40

No No

Korallus et al. [1982], Germany

1,140 male workers employed > 1 year 1934–1979 at two German chromate plants.

North-Rhine Westphalia mortality

Respiratory organs

51 2.1* Stomach 12 0.94 No No

See footnotes at end of table. (Continued)

Table 4–1 (Continued). IARC [1990]-reviewed epidemiologic studies of cancer in workers in chromate-producing industries.
50 Hexavalent Chromium

4 

■ Human Health Effects

Reference

and country

Study population 

and follow-up

Reference

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and 

Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Machle and Gregorius [1948], United States

Male workers in seven chromate plants; active employees 1930–1947; 193 deaths.

Male oil refinery workers 1933–1938

Respiratory system

42 20.7 Digestive

 tractOral region (also included in respiratory system)

13

 3

 2.0

5.4*

No Reported as 

“chromates” (see NIOSH [1975a])

Mancuso and Hueper [1951]; Mancuso [1975], United States

332 U.S. chromate plant workers employed ≥ 1 year 1931–1937; all jobs related to exposure to soluble and insoluble chromium; mortality followed through 1974. 

No independent comparison group

Lung 41 — — — — No Soluble 

chromium described as “chiefly hexavalent”

See footnotes at end of table. (Continued)

Table 4–1 (Continued). IARC [1990]-reviewed epidemiologic studies of cancer in workers in chromate-producing industries.
Hexavalent Chromium 51

4 

■ Human Health Effects

Reference

and country

Study population 

and follow-up

Reference

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and 

Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Satoh et al. [1981], Japan

896 male workers in chromium manufacturing plant in Japan employed ≥ 1 year between 1918 and 1975; mortality followed until 1978, or death. 84% of chromium compounds manufactured 1934–1975 were hexavalent compounds.

Age-, causespecific mortality, Japanese males

Respiratory cancerYears worked:

1–1011–20≥ 21

31

(includes six sinonasal)

 5 9

17

9.2*4.2*7.5*

17.5*

Stomach 11 1.0 No No

Taylor [1966]; Enterline [1974], United States

1,200 males [Enterline 1974] from three U.S. chromate plants, employed 1937–1940 and surveyed 1941–1960. 

Cancer mortality; U.S. males 1950, 1953, 1958

Respiratory cancer

69

(2 maxillary sinus)

9.4* Digestive 

system

16 1.5 No No

Watanabe and Fukuchi [1984], Japan

273 chromate production workers employed ≥ 5 years 1947–1973 and followed for mortality 1960–1982.

Age-, year-, cause-specific mortality, Japanese males

Lung 25

(plus one maxillary sinus)

18.3* Digestive 

system

6 0.9 No No

Source: Adapted from IARC [1990].Dash in “Estimated relative risk” indicates not reported.*Significant at 95% level.

Table 4–1 (Continued). IARC [1990]-reviewed epidemiologic studies of cancer in workers in chromate-producing industries.
52 Hexavalent Chromium

4 

■ Human Health Effects

Table 4–2. IARC [1990]-reviewed epidemiologic studies of cancer in workers in chromate-pigment industries.

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Davies [1978, 1979, 1984], United Kingdom

1,002 male workers in three chromate pigment factories: A, lead and zinc chromate; B, lead and zinc chromate; C, lead chromate; followed up to 1981.

Mortality, England and Wales

Lung: ≥ 1 year worked, “high” or “medium” exposure to chromatecontaining dust:A (entered 1932–1954)B (1948–1967)“high,” “medium,” or “low” exposure: C (1946–1960)

2111

7

2.2* 4.4*

1.1

Nasal sinuses Larynx

12

5

2.15

No (smoking habits of lung cancer cases reported only)

No

FrentzelBeyme [1983], Germany, Netherlands

978 male workers from five factories employed > 6 months in three German or Dutch factories manufacturing zinc and lead chromates and followed for 15,076 person-years.

Local death rates for Federal Republic of Germany and the Netherlands

Lung 19 2.0* — — — No No

Haguenoer et al. [1981], France

251 male workers in a lead and zinc chromate pigment factory employed> 6 months between 1958 and 1977.

Standard death rates, northern France 1958–1977

Lung 11 4.6* — — — No (Smoking 

habits of cancer cases reported only)

No

See footnotes at end of table. (Continued)
Hexavalent Chromium 53

4 

■ Human Health Effects

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

identified Site

Number of 

deaths or 

cases

Estimated 

relative 

risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Langård and Norseth [1975, 1979]; Langård and Vigander [1983], Norway

133 Norwegian workers producing zinc chromate pigments employed between 1948 and December 1972. Twenty-four workers had more than 3 years of employment to 1972. Cohort was observed to the end of 1980.

Cancer incidence, Norway 1955–1976

Lung 6 (excluding 

one case with < 3 years’ employment)

44 Gastrointestinal

Nasal cavity

31

6.4

—

No (Smoking habits of cancer cases reported only)

No and Yes: Exposure reported as μg/m3 or mg/m3 of chromium by Langård and Norseth [1975] and Langård and Vigander [1983]; later reported as mg/m3of Cr (VI) in a review by Langård [1993].

Sheffet et al. [1982]; Hayes et al. [1989], United States

1,181 white and 698 nonwhite males employed in a lead and zinc chromate pigment factory for ≥ 1 month between 1940 and 1969; followed to end of 1982.

Mortality, U.S. whiteand nonwhite males

Lung ≥ 30 years after initial employment and:

< 1 year employment 1–9 years’ employment> 10 years’ employment

24

336

1.4

1.4†2.0†3.2†

Stomach 6 1.8 No No

Source: Adapted from IARC [1990].Dash in “Estimated relative risk” indicates not reported.*Significant at 95% level.†P for trend < 0.01.

Table 4–2 (Continued). IARC-reviewed epidemiologic studies of cancer in workers in chromate-pigment industries.
54 Hexavalent Chromium

4 

■ Human Health Effects

Table 4-3. IARC [1990]-reviewed studies of workers in chromium plating industries.

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

Identified Site

Number 

of deaths 

or cases

Estimated 

relative 

risk Site

Number 

of deaths

or cases

Estimated 

relative 

risk

Franchini et al. [1983], Italy

178 male workers from nine chrome plating plants (116 in “thick” plating; 62 in “thin”) employed ≥ 1 year between 1951 and 1981.

Italy, male mortality

Lung 3 3.3

(4.3* for “thick” platers”)

All sitesStomachPancreas

222

1.94

18*

No Yes; Chromium 

trioxide CrO3) 1980 averages: 7 μg/m3 near plating baths; 3 μg/m3 in middle of the room.

Okubo and Tsuchiya [1977, 1979, 1987], Japan

Japanese chromium platers; 952 male and female workers with > 6 months’ experience. Average follow-up period was 5.2 years for the chromium workers and 5.1 years for controls.

Platers not exposed to chromium; clerical and unskilled workers

Lung 0 — All sites 5 0.5 No No

Royle [1975a,b], United Kingdom

Mortality study of 1,056 past and current male platers in 54 chromiumplating plants, employed ≥ 3 months; 130 men had died by May 31, 1974 (Female workers were also studied.)

1,099 nonexposed males in the plants and in two nonplating industries.

Lung and pleura

24 1.4 All sites 

(including lung) Gastrointestinal Other sites (excluding lung, gastrointestinal)

44

8

12

1.7*

1.51.9

Yes. Information available; smoking habits of platers were compared with controls—“no important differences.”

Yes, at 42 plants. Reported “chromic acid air content” at breathing zone height was generally < 0.03 mg/m3.

See footnotes at end of table. (Continued)
Hexavalent Chromium 55

4 

■ Human Health Effects

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

Identified Site

Number 

of deaths 

or cases

Estimated 

relative 

risk Site

Number 

of deaths

or cases

Estimated 

relative 

risk

Silverstein et al. [1981], United States

Workers with ≥ 10 years of service in a die-casting and nickel and chrome electroplating plant; 238 deaths (white and nonwhite) between 1974 and 1978.

U.S. national mortality statistics

Lung: White menWhite women 

2810

1.9*3.7*

All sites (men) Larynx (men) Stomach (men) Lymphosarcoma, reticulosarcoma (men)

53

242

1.4*

3.32.52.9 

No Limited to only 

a few samples of airborne chromic acid.

Sorahan et al. [1987], United Kingdom

2,689 nickel and chromium platers (1,288 men; 1,401 women). First employed 1946–1975 for ≥ 6 months and observed 1946–1983.

Mortality, England and Wales

Lung, bronchus:MenWomenLarynx:MenWomenNose, nasal cavities (men and women)

63

9303

1.6*

1.13.0

—

10*

Stomach (men and women)LiverMenWomen All sites (men and women)

25

40

213

1.5

6.7*

—

1.3*

No Yes, as chromic 

acid. Median value of 60 “measurements” before 1973 was “not detectable or trace.” After 1973, majority of measurements were recorded in factory records as “less than 0.05 mg/m3.”

Source: Adapted from IARC [1990].Dash in “Estimated relative risk” indicates not reported.*Significant at 95% level.

Table 4–3 (Continued). IARC [1990]-reviewed studies of workers in chromium plating industries.
56 Hexavalent Chromium

4 

■ Human Health Effects

See footnotes at end of table. (Continued)

Table 4-4. IARC [1990]-reviewed epidemiologic studies of cancer in workers in ferrochromium industries.

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

identified Site

Number 

of deaths 

or cases

Estimated 

relative risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Axelsson et al. [1980], Sweden

1,876 male workers employed ≥ 1 year 1930–1975 in a ferrochromium plant; traced by parish lists and cancer registry.

County deaths, male or national statistics (incidence) 

Lung, trachea, bronchus, pleura:All workers Maintenance workersArc furnace workers

7

4 (2 mesotheliomas) 2 (1 mesothelioma)

1.2

4.0*

1.0

Prostate (all workers)

23 1.2 No Yes (Cr6+ and 

Cr3+). Cr6+exposures ranged 0–0.25 mg/m3. Sampling method not described. 

Langård et al. [1980, 1990]; Norway

1,235 male ferrochromium and ferrosilicon workers employed > 1 year 1928–1965 and observed 1953– 1985.

General population and internal comparison group

Lung (ferrochromium workers)

10 1.5 All sites (all 

workers) Ferrochromium workers:Kidney Prostate Stomach

132 

5

12

7

0.82.81.51.4

No Yes, in 1975 

survey, mean atmospheric concentration of chromium ranged from 0.01 mg/m3 to 0.29 mg/m3with a watersoluble content of 11%–33%. Authors stated “Water soluble chromium compounds are considered to be in the hexavalent state.”
Hexavalent Chromium 57

4 

■ Human Health Effects

Reference 

and country

Study population 

and follow-up

Reference 

population

Cancer of respiratory organs Cancer at other sites Cohort 

smoking 

information 

available and 

analyzed

Sampling 

conducted 

and Cr(VI) 

identified Site

Number 

of deaths 

or cases

Estimated 

relative risk Site

Number 

of deaths 

or cases

Estimated 

relative 

risk

Pokrovskaya and Shabynina [1973], USSR

Male and female chromium ferroalloy production workers employed between 1955 and 1969.

Mortality, general population of municipality

Lung (men) Not 

reported

4.4

(age 30–39)

6.6*

(age 50–59)

All sites (men)Esophagus (men)

Not reported Not reported

3.3*

(age 50–59)

2.0*

(age 50–59)

11.3*

(age 60–69)

No Yes, specific 

concentrations and sampling methods not reported—average hexavalent concentrations were 2–7 times greater than allowed.

Source: Adapted from IARC [1990].Dash in “Estimated relative risk” indicates not reported.*Significant at 95% level.

Table 4-4 (Continued). IARC [1990]-reviewed epidemiologic studies of cancer in workers in ferrochromium industries.

Hexavalent Chromium 59

5 Experimental Studies

Experimental studies provide important information about the pharmacokinetics, mechanisms of toxicity, and potential health effects 

of hexavalent chromium (Cr[VI]) compounds. 

Studies using cell culture and in vitro techniques, animal models, and human volunteers 

provide data about these compounds. The 

results of these experimental studies, when 

considered with the results of other health effects studies, provide a more comprehensive 

database for the evaluation of the mechanisms 

and health effects of occupational exposure to 

Cr(VI) compounds.

5.1 Pharmacokinetics

The absorption of inhaled Cr(VI) depends on 

the oxidation state, particle size, and solubility 

of the compound [ATSDR 2012]. Large particles (> 10 μm) of inhaled Cr(VI) compounds 

are deposited in the upper respiratory tract; 

smaller particles can reach the lower respiratory tract. Some of the inhaled Cr(VI) is reduced to trivalent chromium (Cr[III]) in the 

epithelial or interstitial lining fluids within the 

bronchial tree. The extracellular reduction of 

Cr(VI) to Cr(III) reduces the cellular uptake 

of chromium because Cr(III) compounds cannot enter cells as readily as Cr(VI) compounds. 

At physiological pH most Cr(VI) compounds 

are tetrahedral oxyanions that can cross cell 

membranes. Cr(III) compounds are predominantly octahedral structures to which the cell 

membrane is practically impermeable. Cr(III) 

can enter the cell only via pinocytosis [Jennette 

1979]. The Cr(VI) ions that cross the cell membrane become a target of intracellular reductants. The Cr(VI) concentration decreases with 

increasing distance from the point of entry as 

Cr(VI) is reduced to Cr(III). The Cr(III) ions 

are transported to the kidneys and excreted.

Inhaled Cr(VI) that is not absorbed in the 

lungs may enter the gastrointestinal tract following mucociliary clearance. Much of this 

Cr(VI) is rapidly reduced to Cr(III) by reductants in the saliva and gastric juice and excreted in the feces. The remaining 3% to 10% of 

the Cr(VI) is absorbed from the intestines into 

the blood stream, distributed throughout the 

body, transported to the kidneys, and excreted 

in the urine [Costa 1997; Weber 1983]. 

5.2 Mechanisms of Toxicity

The possible mechanisms of the genotoxicity 

and carcinogenicity of Cr(VI) compounds have 

been reviewed [Holmes et al. 2010; Nickens et 

al. 2010]. However, the exact mechanisms of 

Cr(VI) toxicity and carcinogenicity are not 

yet fully understood. A significant body of 

research suggests that Cr(VI) carcinogenicity 

may result from damage mediated by the bioreactive products of Cr(VI) reduction, which 

include the Cr(VI) intermediates (Cr[V] and 

Cr[IV]), and reactive oxygen species (ROS). 

Factors that may affect the toxicity of a chromium compound include its bioavailability, 

oxidative properties, and solubility [Långard 

1993; Katz and Salem 1993; De Flora et al. 

1990; Luo et al. 1996; Klein et al. 1991]. 
60 Hexavalent Chromium

5 ■ Experimental Studies

Intracellular Cr(VI) undergoes metabolic reduction to Cr(III) in microsomes, in mitochondria, and by cellular reductants such as 

ascorbic acid, lipoic acid, glutathione, cysteine, 

reduced nicotinamide adenine dinucleotide 

phosphate (NADPH), ribose, fructose, arabinose and diol- and thiol-containing molecules, 

as well as NADPH/flavoenzymes. Although the 

extracellular reduction of Cr(VI) to Cr(III) is a 

mechanism of detoxification as it decreases the 

number of bioavailable Cr(VI) ions, intracellular reduction may be an essential element in 

the mechanism of intracellular Cr(VI) toxicity.

The intracellular Cr(VI) reduction process 

generates products including Cr(V), Cr(IV), 

Cr(III) molecular oxygen radicals, and other 

free radicals. The molecular oxygen is reduced 

to superoxide radical, which is further reduced 

to hydrogen peroxide (H2O2) by superoxide 

dismutase (SOD). H2O2 reacts with Cr(V), 

Cr(IV) or Cr(III) to generate hydroxyl radicals ( ̇OH) via the Fenton-like reaction, and it 

undergoes reduction-oxidation cycling [Ding 

and Shi 2002]. The high concentration of oxygen radicals and other free radical species generated in the process of Cr(VI) reduction may 

result in a variety of lesions on nuclear chromatin, leading to mutation and possible neoplastic transformation [Kasprzak 1991].

In the presence of cellular reducing systems 

that generate chromium intermediates and 

hydroxyl radicals, Cr(VI) salts induce various 

types of DNA damage, resulting either from 

the breakage of existing covalent bonds or 

the formation of new covalent bonds among 

molecules, such as DNA interstrand crosslinks, DNA-protein crosslinking, DNA double 

strand breaks, and depurination. Such lesions 

could lead to mutagenesis and ultimately to 

carcinogenicity [Shi et al. 1994; Tsapakos and 

Wetterhahn 1983; Tsapakos et al. 1983; Sterns 

et al. 1995; Sugiyama et al. 1986; Singh et al. 

1998; Ding and Shi 2002; Fornace et al. 1981]. 

The oxidative damage may result from a direct 

binding of the reactive Cr(VI) intermediates to 

the DNA or may be due to the indirect effect 

of ROS interactions with nuclear chromatin, 

depending on their intracellular location and 

proximity to DNA [Ding and Shi 2002; Shi 

and Dalal 1990a,b,c; Singh et al. 1998; Liu et al. 

1997b]. Cr(VI) does not bind irreversibly to native DNA and does not produce DNA lesions 

in the absence of the microsomal reducing systems in vitro [Tsapakos and Wetterhahn 1983]. 

In addition to their oxidative properties, the 

solubility of Cr(VI) compounds is another important factor in the mechanism of their carcinogenicity. Animal studies indicate that insoluble and sparingly soluble Cr(VI) compounds 

may be more carcinogenic than soluble chromium compounds [Levy et al. 1986]. 

Particles of lead chromate, a relatively insoluble 

Cr(VI) compound, when added directly to the 

media of mammalian cell culture, induced cell 

transformation [Douglas et al. 1980]. When 

injected into whole animals, the particles produced tumors at the site of injection [Furst et 

al. 1976]. Several hypotheses have been proposed to explain the effects of insoluble Cr(VI) 

compounds. One hypothesis proposes that 

particles dissolve extracellularly, resulting in 

chronic, localized exposure to ionic chromate. 

This hypothesis is consistent with studies demonstrating that extracellular dissolution is required for lead chromate-induced clastogenesis [Wise et al. 1993, 1994; Xie et al. 2004]. Xie 

et al. [2004] demonstrated that lead chromate 

clastogenesis in human bronchial cells is mediated by the extracellular dissolution of the particles but not their internalization.

Another hypothesis suggests that a high Cr(VI) 

concentration is created locally inside the cell 

during internalization of Cr(VI) salt particles 

by phagocytosis [Leonard et al. 2004]. 
Hexavalent Chromium 61

5 ■ Experimental Studies

High intracellular local Cr(VI) concentrations 

can generate high concentration of ROS inside 

the cell, which may overwhelm the local ROS 

scavenging system and result in cytotoxicity and genotoxicity [Kasprzak 1991]. Highly 

soluble compounds do not generate such high 

local concentrations of Cr(VI). However, once 

inside the cell, both soluble (sodium chromate) 

and insoluble (lead chromate) Cr(VI) compounds induce similar amounts and types of 

concentration-dependent chromosomal damage in exposed cultured mammalian cells [Wise 

et al. 1993, 2002, 2003]. Pretreatment of these 

cells with ROS scavengers such as vitamin E or 

C prevented the toxic effects of both sodium 

chromate and lead chromate. 

Numerous studies report a broad spectrum of 

cellular responses induced by exposure to various Cr(VI) compounds. These cytotoxic and 

genotoxic responses are consistent with mechanistic events associated with carcinogenesis. 

Studies in human lung cells provide data regarding the genotoxicity of many Cr(VI) compounds 

[Wise et al. 2006a; Holmes et al. 2006b; Xie et al. 

2009]. Cr(VI) compounds induce transformation of human cells, including bronchial epithelial cells [Xie et al. 2007; Xie et al. 2008]. 

Barium chromate induced concentrationdependent chromosomal damage, including 

chromatid and chromosomal lesions, in human lung cells after 24 hours of exposure 

[Wise et al. 2003]. Lead chromate and soluble 

sodium chromate induced concentrationdependent chromosomal aberration in human bronchial fibroblasts after 24 hours of 

exposure [Wise et al. 2002; Xie et al. 2004]. 

Cotreatment of cells with vitamin C blocked 

the chromate induced toxicity. Calcium chromate induced DNA single-strand breaks and 

DNA protein cross-links in a dose-dependent 

manner in three cell lines. Exposing human 

lung cell cultures to lead chromate induced 

chromosome instability including centrosome amplification and aneuploidy [Holmes 

et al. 2006a] and spindle assembly checkpoint 

bypass [Wise et al. 2006b]. Sodium dichromate 

generated ROS that increased the level and activity of the protein p53 in human lung epithelial cells. In normal cells the protein p53 is usually inactive. It is usually activated to protect 

cells from tumorigenic alterations in response 

to oxidative stress and other stimuli such as 

ultraviolet or gamma radiation. An increased 

 ̇OH concentration activated p53; elimination 

of  ̇OH by H2O2 scavengers inhibited p53 activation [Ye et al. 1999; Wang et al. 2000; Wang 

and Shi 2001]. 

The ROS (mainly H2O2) formed during potassium chromate reduction induced the expression of vascular endothelial growth factor 

(VEGF) and hypoxia-induced factor 1 (HIF–1) 

in DU145 human prostate carcinoma cells. 

VEGF is the essential protein for tumor angiogenesis. HIF–1, a transcription factor, regulates 

the expression of many genes including VEGF. 

The level of HIF–1 activity in cells correlates 

with the tumorigenic response and angiogenesis in nude mice, is induced by the expression 

of various oncogenes, and is overexpressed in 

many human cancers [Gao et al. 2002; Ding 

and Shi 2002].

Early stages of apoptosis have been induced in 

human lung epithelial cells in vitro following 

exposure to potassium dichromate. Scavengers 

of ROS, such as catalase, aspirin, and N-acetylL-cysteine, decreased apoptosis induced by 

Cr(VI); reductants such as NADPH and glutathione enhanced it. Apoptosis can be triggered 

by oxidative stress. Agents that promote or 

suppress apoptosis may change the rates of cell 

division and lead to the neoplastic transformation of cells [Singh et al. 1998; Ye et al. 1999; 

Chen et al. 1999].
62 Hexavalent Chromium

5 ■ Experimental Studies

The treatment of mouse macrophage cells in 

vitro with sodium chromate induced a dosedependent activation of the transcription enhancement factors NF-кB and AP–1 [Chen 

et al. 1999, 2000]. Activation of these factors 

represents a primary cellular oxidative stress 

response. These factors enhance the transcription of many genes and the enhanced expression of oncogenes [Ji et al. 1994]. 

Sodium dichromate increased tyrosine phosphorylation in human epithelial cells. The 

phosphorylation could be inhibited by antioxidants [Wang and Shi 2001]. Tyrosine phosphorylation is essential in the regulation of 

many cellular functions, including cancer development [Qian et al. 2001]. 

Human lung epithelial A549 cells exposed to 

potassium dichromate in vitro generated ROSinduced cell arrest at the G2/M phase of the 

cell proliferation cycle at relatively low concentrations and apoptosis at high concentrations. Interruption of the proliferation process 

is usually induced in response to cell damage, 

particularly DNA damage. The cell remains 

arrested in a specific cell cycle phase until the 

damage is repaired. If damage is not repaired, 

mutations and cell death or cancer may result 

[Zhang et al. 2001].

Gene expression profiles indicate that exposing human lung epithelial cells to potassium 

dichromate in vitro resulted in up regulation 

of the expression of 150 genes, and down regulation of 70 genes. The analysis of gene expression profiles indicated that exposure to Cr(VI) 

may be associated with cellular oxidative stress, 

protein synthesis, cell cycle regulation, and oncogenesis [Ye and Shi 2001].

These in vitro studies have limitations of models of human exposure because they cannot 

account for the detoxification mechanisms 

that take place in intact physiological systems. 

However, these studies represent a body of 

data on cellular responses to Cr(VI) that provide important information regarding the potential genotoxic mechanisms of Cr(VI) compounds. The cellular damage induced by these 

compounds is consistent with the mechanisms 

of carcinogenesis.

5.3 Health Effects in Animals

Chronic inhalation studies provide the best 

data for extrapolation to airborne occupational 

exposure. Only a few of these chronic inhalation studies have been conducted using Cr(VI) 

compounds. Glaser et al. [1985, 1990] conducted subchronic inhalation studies of sodium dichromate exposure in rats. Adachi et al. [1986, 

1987] conducted chronic inhalation studies of 

chromic acid mist exposure in mice. Glaser et 

al. [1986] conducted chronic inhalation studies 

of sodium dichromate exposure in rats. Steinhoff et al. [1986] conducted an intratracheal 

study of sodium dichromate exposure in rats. 

Levy et al. [1986] conducted an intrabronchial 

implantation study of various Cr(VI) materials 

in rats. The results of these animal studies support the classification of Cr(VI) compounds as 

occupational carcinogens. 

5.3.1 Subchronic Inhalation Studies

Glaser et al. [1985] exposed male Wistar rats 

to whole body aerosol exposures of sodium dichromate at 0, 25, 50, 100, or 200 μg Cr(VI)/m3

 for 

22 hr/day, 7 days/wk for 28 or 90 days. Twenty 

rats were exposed at each dose level. An additional 10 rats were exposed at 50 μg for 90 days 

followed by 2  months of nonexposure before 

sacrifice. The average mass median diameter 

(MMD) of the aerosol particles was 0.2  μm. 

Significant increases (P < 0.05) occurred in the 

serum triglyceride, phospholipid contents, and 
Hexavalent Chromium 63

5 ■ Experimental Studies

mitogen-stimulated splenic mean T-lymphocyte 

count of rats exposed at the 200 μg/m3 level for 

90  days. Serum total immunoglobulins were 

statistically increased (P < 0.01) for the 50 and 

100 μg exposure groups. 

To further study the humoral immune effects, 

half of the rats in each group were immunized 

with sheep red blood cells 4  days before sacrifice [Glaser et al. 1985]. The primary antibody responses for IgM B-lymphocytes were 

statistically increased (P < 0.05) for the groups 

exposed to 25  μg Cr(VI)/m3 and higher. The 

mitogen-stimulated T-lymphocyte response of 

spleen cells to Concanavalin A was significantly increased (P < 0.05) for the 90-day, 200 μg/

m3 group compared with the control group. 

The mean macrophage cell counts were significantly lower (P < 0.05) than control values 

for only the 50 and 200 μg Cr(VI)/m3, 90-day 

groups. Alveolar macrophage phagocytosis 

was statistically increased in the 50 μg level of 

the 28-day study, and the 25 and 50 μg mg/m3

Cr(VI) levels of the 90-day study (P < 0.001). 

A significant depression of phagocytosis occurred in the 200  μg/m3

 group of the 90-day 

study versus controls. 

A group of rats exposed to 200  μg Cr(VI)/m3 

for 42 days and controls received an acute 

iron oxide particulate challenge to study lung 

clearance rates during a 49-day nonexposure 

post-challenge period [Glaser et al. 1985]. Iron 

oxide clearance was dramatically and increasingly decreased in a bi-exponential manner for 

the group exposed to Cr(VI) compared with 

the controls. 

Glaser et al. [1990] studied lung toxicity in animals exposed to sodium dichromate aerosols. 

Groups of 30 male Wistar rats were exposed to 

0, 50, 100, 200, or 400 μg Cr(VI)/m3 for 22 hr/

day, 7  days/week for 30 or 90 days, followed 

by a 30-day nonexposure recovery period. 

Aerosol mass median aerodynamic diameter 

(MMAD) ranged from 0.28 to 0.39  μm. Sacrifices of 10 rats occurred after experimental 

days 30, 90, and 120. The only sign or symptom induced was an obstructive dyspnea present at the 200 and 400 μg/m3

 levels. Statistically 

significant reductions in body weight gains 

were present at 30  days for the 200  μg level, 

with similar reductions for the 400  μg level 

rats at the 30, 90, and 120-day intervals. White 

blood cell counts were statistically increased 

(P  <  0.05) for all four dichromate exposure 

groups for the 30- and 90-day intervals, but 

the white blood cell counts returned to control 

levels after 30 days of nonexposure. The lung 

parameters studied had statistically significant dose-related increases after either 30  or 

90 days of inhalation exposure to dichromate; 

some remained elevated despite the nonexposure recovery period. A No Observed Adverse 

Effect Level (NOAEL) was not achieved. 

Bronchoalveolar lavage (BAL) provided information about pulmonary irritation induced by 

sodium dichromate exposure in these rats [Glaser et al. 1990]. Total protein levels present on 

day 30 progressively decreased at days 90 and 

120 but remained above control values. Alveolar vascular integrity was compromised as BAL 

albumin levels were increased for all treatment 

groups, with only the 200 and 400 μg/m3 levels 

remaining above those of the controls at the end 

of the recovery period. Lung cell cytotoxicity as 

measured by cytosolic lactate dehydrogenase, 

and lysosomal ß-glucuronidase was increased 

by dichromate exposure but normalized during the post-exposure period. Mononuclear 

macrophages comprised 90% of recovered total BAL cells. The two highest exposure groups 

had equal increases throughout the treatment 

period, but they returned to normal during the 

recovery period. These macrophages had higher cell division rates, sometimes were multinuclear, and were bigger when compared with 

control cells. Sodium dichromate exposure 
64 Hexavalent Chromium

5 ■ Experimental Studies

induced statistically significant increased lung 

weights for the 100, 200, and 400 μg/m3 groups 

throughout the study, including the nonexposure period. Histopathology of lung tissue revealed an initial bronchoalveolar hyperplasia 

for all exposure groups at day  30, while only 

the 200 and 400  μg/m3 levels retained some 

lower levels of hyperplasia at study day 120. 

There was also an initial lung fibrosis observed 

in some animals at the levels above 50 μg/m3

on day 30, which was not present during the 

remainder of the study. Lung histiocytosis remained elevated throughout the entire study 

for all treatment groups. 

5.3.2 Chronic Inhalation Studies

Adachi et al. [1986] exposed 50 female ICR/JcI 

mice to 3.63 mg Cr(VI)/m3 chromic acid mist 

(85% of mist measuring < 5 μm) for 30 min/

day, 2 days/week for 12 months, followed by a 

6-month nonexposure recovery period. Proliferative changes were observed within the respiratory tract after 26 weeks of chromate exposure. 

Pin-hole-sized perforations of the nasal septum 

occurred after 39 weeks at this exposure level. 

When the incidence rates for histopathological 

findings (listed below) for chromate-exposed 

animals were compared for successive study periods, the treatment group data were generally 

similar for weeks 40–61 when compared with 

weeks 62–78, with the exception of the induction 

of two adenocarcinomas of the lungs present in 

two  females at the terminal 78-week sacrifice. 

The total study pathology incidence rates for the 

48 chromate-exposed females were the following: 

perforated nasal septum (n = 6), tracheal (n = 43)/

bronchial (n  =  19) epithelial proliferation, and 

emphysema (n  =  11), adenomatous metaplasia 

(n = 3), adenoma (n = 5), and adenocarcinoma 

(n = 2) of the lungs. Total control incidence rates 

for the 20 females examined were confined to the 

lung: emphysema (n = 1), adenomatous metaplasia (n = 1), and adenoma (n = 2). 

Adachi [1987] exposed 43 female C57BL mice 

to 1.81 mg Cr(VI)/m3 chromic acid mist (with 

85% of mist measuring ~5  μm) for 120  min/

day, 2 days/week for 12 months, followed by a 

6-month nonexposure recovery period. Twenty-three animals were sacrificed at 12 months, 

with the following nontumorigenic histological changes observed: nasal cavity perforation 

(n = 3); tracheal hyperplasia (n = 1); and emphysema (n = 9) and adenomatous metaplasia 

(n = 4) of the lungs. A terminal sacrifice of the 

20 remaining females occurred at 18 months, 

which demonstrated perforated nasal septa (n  =  3) and papillomas (n  =  6); laryngeal/

tracheal hyperplasia (n = 4); and emphysema 

(n = 11), adenomatous metaplasia (n = 5), and 

adenoma (n = 1) of the lungs. Only emphysema (n = 2) and lung metaplasia (n = 1) were 

observed in control females sacrificed after 

week 78. 

Glaser et al. [1986] exposed groups of 20 male 

Wistar rats to aerosols of 25, 50, or 102 μg/m3

sodium dichromate for 22 to 23 hr/day, 7 days/

week for 18 months, followed by a 12-month 

nonexposure recovery period. Mass median 

diameter of the sodium dichromate aerosol 

was 0.36 μm. No clinical sign of irritation induced by Cr(VI) was observed in any treated 

animal. Statistically increased liver weights 

(+26%) were observed at 30  months for the 

102  μg/m3 dichromate males. Weak accumulations of pigment-loaded macrophages were 

present in the lungs of rats exposed to 25 μg/m3 

sodium dichromate; moderate accumulations 

were present in rats exposed to 50 and 102 μg/

m3 sodium dichromate. Three primary lung tumors occurred in the 102 μg Cr(VI)/m3

 group: 

two adenomas and one adenocarcinoma. The 

authors concluded that the 102 μg Cr(VI)/m3

level of sodium dichromate induced a weak 

lung carcinogenic effect in rats exposed under 

these conditions.
Hexavalent Chromium 65

5 ■ Experimental Studies

5.3.3 Intratracheal Studies

Steinhoff et al. [1986] dosed Sprague-Dawley 

rats via intratracheal instillation with equal total weekly doses of sodium dichromate for 30 

months: either five consecutive daily doses of 

0.01, 0.05, or 0.25 mg/kg or one weekly dose of 

0.05, 0.25, or 1.25 mg/kg. Each group consisted 

of 40 male and 40 female rats. Groups left untreated or given saline were negative controls. 

Body weight gains were suppressed in males 

treated with single instillations of 1.25  mg/

kg of sodium dichromate. Chromate-induced 

nonneoplastic and neoplastic lesions were detected only in the lungs. The nonneoplastic 

pulmonary lesions were primarily found at the 

maximum tolerated irritant concentration level for the high dose sodium dichromate group 

rather than having been dependent upon the 

total dose administered. The nonneoplastic 

pulmonary lesions occurred predominantly 

in the highest dose group and were characterized by fibrotic regions that contained residual 

distorted bronchiolar lumen or cellular inflammatory foci containing alveolar macrophages, 

proliferated epithelium, and chronic inflammatory thickening of the alveolar septa plus atelectasis. The neoplastic lesions were non-fatal 

lung tumors found in these chromate-treated 

animals. Fourteen rats given single weekly instillations of 1.25  mg sodium dichromate/kg 

developed a significant (P < 0.01) number of 

tumors: 12 benign bronchioalveolar adenomas and 8 malignant tumors including 2 bronchioalveolar adenocarcinomas and 6 squamous 

cell carcinomas. Only one additional tumor, a 

bronchioalveolar adenocarcinoma, was found 

in a rat that had received single weekly instillations of 0.25 mg/kg sodium dichromate. 

5.3.4 Intrabronchial Studies

Levy et al. [1986] conducted a 2-year intrabronchial implantation study of 20 chromiumcontaining materials in Porton-Wistar rats. 

Test groups consisted of 100 animals with equal 

numbers of male and female rats. A small, 

hook-equipped stainless steel wire mesh basket 

containing 2 mg of cholesterol and test material was inserted into the left bronchus of each 

animal. Two positive control groups received 

pellets loaded with 20-methylcholanthrene or 

calcium chromate. The negative control group 

received a blank pellet loaded with cholesterol. 

Pulmonary histopathology was the primary 

parameter studied. There were inflammatory 

and metaplastic changes present in the lungs 

and bronchus, with a high level of bronchial 

irritation induced by the presence of the basket alone. A total of 172 tumors were obtained 

throughout the study, with only 18 found at the 

terminal sacrifice. Nearly all tumors were large 

bronchial keratinizing squamous cell carcinomas that affected a major part of the left lung 

and were the cause of death for most affected 

animals. The authors noted that no squamous 

cell carcinomas had been found in 500 of their 

historical laboratory controls. 

In Table 5–1, study data from Levi et al. [1986] 

were transformed by NIOSH to present the 

rank order of tumor induction potential for 

the test compounds through calculation of 

the mean μg of Cr(VI) required to induce a 

single bronchiolar squamous cell carcinoma. 

The rank order of tumor induction potential for the positive Cr(VI) compounds using 

these data was the following: strontium > calcium > zinc > lead, chromic acid > sodium dichromate > barium. The role solubility played 

in tumor production for these test materials 

was inconsistent and not able to be determined. 

5.3.5 Chronic Oral Studies

The National Toxicology Program (NTP) conducted 2-year drinking water studies of sodium 

dichromate dehydrate (SDD) in rodents [NTP 

2008; Stout et al. 2009]. Male and female F344/N 
66 Hexavalent Chromium

5 ■ Experimental Studies

Table 5–1. Single intrabronchiolar pellet implantation of Cr(VI) or Cr(III) materials and 

their potential to induce lung carcinomas during a 2-year period in rats

Test compound

Water solubility,

mg Cr(VI)/L

Cr(VI)

(%)

Pellet Cr(VI) 

content

(μg)

Number of 

carcinomas

μg Cr(VI)

to induce

carcinoma*

Strontium chromate 207,000 8.7 174 43 4

Strontium chromate 63,000 24.3 486 62 8

Hi Lime Residue

(2.7% calcium chromate)

 1,820 1.2 24 1 24

Calcium chromate

Positive control 

181,000 32.5 649 25 26

Zinc chromate 420 8.7 173 5 35

Zinc chromate 64,000 9.2 184 3 61

Kiln frit† 84,600 9.3 186 2 93

LD chrome yellow supra‡ < 1 5.7 114 1 114

Lead chromate 17 5.7 115 1 115

Vanadium solids/leach† 54,000 7.3 146 1 146

Zinc tetroxychromate 230 8.8 176 1 176

Chromic acid 400,000 21.2 424 2 212

Primrose chrome yellow‡ 5 12.6 252 1 252

Med chrome yellow‡ 2 16.3 326 1 326 

Sodium dichromate

 dehydrate

328,000 34.8 696 1 696

Molybdate chrome orange‡ < 1 12.9 258 0 —

Light chrome yellow‡ 1 12.5 250 — —

Med chrome yellow‡ 17 10.5 210 — —

Barium chromate 11 6.8 135 0 —

Recycled residue 6,000 0.7 14 0 —

High silica Cr(III) ore 5 13.7 750 0 —

Cholesterol

Negative control§

Not reported NA NA 0 NA

3-Methylcholanthrene

Positive control

Not reported NA NA 22¶ NA

Data source: Levy et al. [1986]; calculations by NIOSH.

Abbreviations: NA = Not applicable.

*μg Cr(VI) to induce carcinomas = capsule Cr(VI) content / number of carcinomas

†

This process material contained unstated amounts of calcium chromate.

‡

Identified also as being a lead chromate containing group.

§

No lung tumors were previously found in 500 negative historical control rats that had basket implants.

¶

21 squamous cell carcinomas and one anaplastic carcinoma of the lung.
Hexavalent Chromium 67

5 ■ Experimental Studies

rats and female B6C3F1 mice were exposed to 

0, 14.3, 57.3, 172, or 516 mg/L SDD, and male 

mice to 0, 14.3, 28.6, 85.7, or 257.4 mg/L SDD. 

Statistically significant concentration-related 

increased incidences of neoplasms of the oral 

cavity in male and female rats, and of the small 

intestine in male and female mice, were reported. The NTP concluded that these results provide clear evidence of the carcinogenic activity of SDD in rats and mice [Stout et al. 2009]. 

This conclusion was reinforced by the similar 

results reported between the sexes in both rats 

and mice.

5.3.6 Reproductive Studies

Reviews and analyses of the animal studies of 

the reproductive effects of Cr(VI) compounds 

are available [EPA 1998; ATSDR 2012; Health 

Council of the Netherlands 2001; 71 Fed. Reg. 

10099 (2006); OEHHA 2009]. Animal studies conducted using the oral route of exposure 

have reported adverse effects on reproductive 

organs, sperm, fertility, reproductive outcomes, 

and other adverse reproductive and developmental effects [OEHHA 2009]. Negative studies have also been reported; potassium dichromate administered in the diet to mice and rats 

did not result in adverse reproductive effects or 

outcomes in rats or mice [NTP 1996a,b; 1997]. 

Inhalation studies in male and female rats did 

not result in adverse reproductive effects [Glaser et al. 1985, 1986, 1988; ATSDR 2012].

The California Environmental Protection Agency (EPA) Office of Environmental Health Hazard Assessment (OEHHA) determined that 

Cr(VI) compounds “have been clearly shown 

through scientifically valid testing according 

to generally accepted principles to cause developmental, male reproductive toxicity, and 

female reproductive toxicity” [OEHHA 2009]. 

The Health Council of the Netherlands’ Committee for Compounds Toxic to Reproduction 

recommended that Cr(VI) compounds be classified as “substances which cause concern for 

human fertility” (category 3) and “substances 

which should be regarded as if they impair fertility in humans” (category 2) [Health Council 

of the Netherlands 2001]. OSHA concluded 

in its evaluation of reproductive studies that 

there is insufficient evidence to classify Cr(VI) 

compounds as a reproductive toxin in normal 

working situations [71 Fed. Reg. 10099 (2006)]. 

5.4 Dermal Studies

Dermal exposure is another important route of 

exposure to Cr(VI) compounds in the workplace. Experimental studies have been conducted using human volunteers, animal models, and 

in vitro systems to investigate the dermal effects 

of Cr(VI) compounds.

5.4.1 Human Dermal Studies

Mali et al. [1963] reported the permeation of 

intact epidermis by potassium dichromate in 

human volunteers in vivo. Sensitization was reported in humans exposed to this Cr(VI) compound but not Cr(III) sulfate. 

Baranowska-Dutkiewicz [1981] conducted 

27 Cr(VI) absorption experiments on seven 

human volunteers. The forearm skin absorption rate for 0.01 molar solution of sodium 

chromate was 1.1 μg/cm2/hr, for 0.1 molar solution it was 6.5 μg/cm2

/hr, and for 0.2 molar 

solution it was 10.0 μg/cm2/hr. The amount of 

Cr(VI) absorbed as a percent of the applied 

dose decreased with increasing concentration. 

The absorption rate increased as the Cr(VI) 

concentration applied increased, and it decreased as the exposure time increased. 

Corbett et al. [1997] immersed four human 

volunteers below the shoulders in water containing 22  mg/L potassium dichromate for 
68 Hexavalent Chromium

5 ■ Experimental Studies

3 hours to assess their uptake and elimination 

of chromium. The concentration of Cr in the 

urine was used as the measure of systemic uptake. The total Cr excretion above historical 

background ranged from 1.4 to 17.5  μg. The 

dermal uptake rates ranged from approximately 3.3 × 10-5 to 4.1 × 10-4 μg/cm2

/hr, with an 

average of 1.5 × 10-4. One subject had a dermal 

uptake rate approximately seven times higher 

than the average for the other three subjects.

5.4.2 Animal Dermal Studies 

Mali et al. [1963] demonstrated the experimental sensitization of 13 of 15 guinea pigs by 

injecting them with 0.5 mg potassium dichromate in Freund adjuvant subdermally twice at 

1-week intervals.

Gad et al. [1986] conducted standard dermal 

LD50 tests to evaluate the acute toxicity of sodium chromate, sodium dichromate, potassium 

dichromate, and ammonium dichromate salts 

in New Zealand white rabbits. All salts were 

tested at 1.0, 1.5, and 2.0 g/kg dosage, with the 

exception of sodium chromate, which was tested at the two higher doses only. In males, the 

dermal LD50 ranged from a mean of 0.96 g/kg 

(SD = 0.19) for sodium dichromate to 1.86 g/

kg (SD = 0.35) for ammonium dichromate. In 

females the dermal LD50 ranged from a mean 

of 1.03 g/kg (SD = 0.15) for sodium dichromate 

to 1.73 g/kg (SD = 0.28) for sodium chromate. 

Each of the four salts, when moistened with 

saline and occluded to the skin for 4  hours, 

caused marked irritation. Occlusion of each 

salt on the skin of the rabbit’s back for 24 hours 

caused irreversible cutaneous damage.

Liu et al. [1997a] demonstrated the reduction 

of an aqueous solution of sodium dichromate 

to Cr(V) on the skin of Wistar rats using in vivo 

electron paramagnetic resonance spectroscopy. 

Removal of the stratum corneum by stripping 

the skin with surgical tape 10 times before the 

application of the dichromate solution increased 

the rates of formation and decay of Cr(V). 

5.4.3 In Vitro Dermal Studies

Gammelgaard et al. [1992] conducted chromium permeation studies on full thickness human skin in an in vitro diffusion cell system. 

Application of 0.034 M potassium chromate to 

the skin resulted in significantly higher levels of 

chromium in the epidermis and dermis, compared with Cr(III) nitrate and Cr(III) chloride. 

Chromium levels in the epidermis and dermis 

increased with the application of increasing 

concentrations of potassium chromate up to 

0.034  M Cr. Chromium skin levels increased 

with the application of potassium chromate 

solutions with increasing pH. The percentage 

of Cr(VI) converted to Cr(III) in the skin was 

largest at low total chromium concentrations 

and decreased with increasing total concentrations, indicating a limited ability of the skin to 

reduce Cr(VI).

Van Lierde et al. [2006] conducted chromium 

permeation studies on human and porcine skin 

using a Franz static diffusion cell. Potassium 

dichromate was determined to permeate human and pig skin after 168 hours of exposure, 

while the Cr(III) compounds tested did not. 

Exposure of the skin to 5% potassium dichromate resulted in an increased, but not proportionally increased, amount of total Cr concentration in the skin, compared with exposure to 

0.25% potassium dichromate. Exposure to 5% 

potassium dichromate compared with 2.5% 

potassium did not result in much more of an 

increased Cr skin concentration dichromate, 

indicating a possible limited binding capacity 

of the skin. A smaller amount of Cr was bound 

to the skin when the salts were incubated in 
Hexavalent Chromium 69

5 ■ Experimental Studies

simulated sweat before application onto the 

skin. A larger accumulation of Cr was found 

in the skin after exposure to potassium dichromate compared with Cr(III) compounds.

Rudolf et al. [2005] reported a pronounced effect of potassium chromate on the morphology and motile activity of human dermal fibroblasts at concentrations ranging from 1.5 

to 45 μM in tissue culture studies. A time and 

concentration-dependent effect on cell shrinkage, reorganization of the cytoskeleton, and 

inhibition of fibroblast motile activity was reported. The inhibitory effect on fibroblast migration was seen at all concentrations 8 hours 

after treatment; effects at higher doses were 

seen by 4 hours after treatment. Cr(VI) exposure also resulted in oxidative stress, alteration 

of mitochondrial function, and mitochondriadependent apoptosis in dermal fibroblasts.

5.5 Summary of

Animal Studies

Cr(VI) compounds have been tested in animals 

using many different experimental conditions 

and exposure routes. Although experimental 

conditions are often different from occupational exposures, these studies provide data to assess the carcinogenicity of the test compounds. 

Chronic inhalation studies provide the best data 

for extrapolation to occupational exposure; few 

have been conducted using Cr(VI) compounds. 

However, the body of animal studies supports 

the classification of Cr(VI) compounds as occupational carcinogens. 

The few chronic inhalation studies available 

demonstrate the carcinogenic effects of Cr(VI) 

compounds in mice and rats [Adachi et al. 

1986, 1987; Glaser et al. 1986]. Animal studies conducted using other respiratory routes 

of administration have also produced positive 

results with some Cr(VI) compounds. Zinc 

chromate and calcium chromate produced a 

statistically significant (P  <  0.05) number of 

bronchial carcinomas when administered via 

an intrabronchial pellet implantation system 

[Levy et al. 1986]. Cr(VI) compounds with 

a range of solubilities were tested using this 

system. Although soluble Cr(VI) compounds 

did produce tumors, these results were not 

statistically significant. Some lead chromate 

compounds produced squamous carcinomas, 

which although not statistically significant 

may be biologically significant because of the 

historical absence of this cancer in control rats.

Steinhoff et al. [1986] administered the same 

total dose of sodium dichromate either once 

per week or five times per week to rats via intratracheal instillation. No increased incidence of 

lung tumors was observed in animals dosed five 

times weekly. However, in animals dosed once 

per week, a statistically significant (P  <  0.01) 

tumor incidence was reported in the 1.25 mg/

kg exposure group. This study demonstrates a 

dose-rate effect within the constraints of the experimental design. It suggests that limiting exposure to high Cr(VI) levels may be important 

in reducing carcinogenicity. However, quantitative extrapolation of these animal data to the 

human exposure scenario is difficult. 

Animal studies conducted using nonrespiratory routes of administration have also produced 

positive results with some Cr(VI) compounds 

[Hueper 1961; Furst 1976]. These studies provide another data set for hazard identification.

IARC [2012] concluded "there is sufficient evidence in experimental animals for the carcinogenicity of chromium (VI) compounds".

Molecular toxicology studies provide support 

for classifying Cr(VI) compounds as occupational carcinogens. They demonstrate the cytotoxic and genotoxic effects associated with 

carcinogenesis of Cr(VI) compounds.
70 Hexavalent Chromium

5 ■ Experimental Studies

Animal studies using the oral route of exposure demonstrate the carcinogenicity and 

potential adverse reproductive and developmental toxicity of Cr(VI) compounds. These 

studies and the nonmalignant health effects 

of Cr(VI) have been reviewed and evaluated 

by other government agencies [71 Fed. Reg. 

10099 (2006); ATSDR 2012; EPA 1998; Health 

Council of the Netherlands 2001; NTP 2011; 

OEHHA 2009].
Hexavalent Chromium 71

6 Quantitative Assessment of Risk 

populations are described in the human health 

effects chapter (see Chapter 4). Goldbohm et 

al. [2006] discusses the framework necessary 

to conduct quantitative risk assessments based 

on epidemiological studies in a structured, 

transparent, and reproducible manner.

The Baltimore and Painesville cohorts [Gibb 

et al. 2000b; Luippold et al. 2003] are the best 

studies for predicting Cr(VI) cancer risks because of the quality of the exposure estimation, 

large amount of worker data available for analysis, extent of exposure, and years of follow-up 

[NIOSH 2005a]. NIOSH selected the Baltimore 

cohort [Gibb et al. 2000b] for analysis because it had the greater number of lung cancer 

deaths, better smoking histories, and a more 

comprehensive retrospective exposure archive. 

The results of these occupational quantitative 

risk assessments demonstrated an elevated 

risk of lung cancer death to workers exposed 

to Cr(VI) at the previous NIOSH REL (1  μg 

Cr(VI)/m3) over a working lifetime. A risk assessment conducted on the Painesville data 

reports an excess lifetime risk estimate of lung 

cancer death of 2 per 1,000 workers at the previous NIOSH REL [Crump et al. 2003]. The 

NIOSH risk assessment conducted on the Baltimore data indicates an excess lifetime risk estimate of lung cancer death of 6 per 1,000 workers at 1 μg/m3

 and approximately 1 per 1,000 

workers at 0.2 μg/m3 [Park et al. 2004]. These 

estimates of increased lung cancer risk vary depending on the data set used, the assumptions 

made, and the models tested. 

6.1 Overview

This chapter uses standard epidemiological and 

risk assessment methods to present numerical 

estimates of the excess lifetime risk of lung cancer due to occupational exposure to hexavalent 

chromium (Cr[VI]) compounds. The excess 

lifetime risk is the increase in risk over a lifetime above the background level. These estimates are based on mathematical models that 

describe the relationship between exposure to 

Cr(VI) and lung cancer deaths in known populations of exposed workers. Exposure-response 

modeling requires making assumptions about 

workers’ exposures over the course of their 

working lifetime, and the mathematical form 

of the exposure-response relationship. A range 

of excess working lifetime risk estimates is provided that are associated with various levels of 

Cr(VI) workplace exposure.

Exposure-response data are needed to quantify the risk of occupational exposure to Cr(VI) 

compounds. The exposure and health data 

from two chromate production facilities provide the bases for the quantitative risk assessments of lung cancer due to occupational 

Cr(VI) exposure. Dose-response data from the 

Painesville, Ohio chromate production facility were analyzed by Crump et al. [2003], K.S. 

Crump [1995], Gibb et al. [1986], and EPA 

[1984]. Dose-response data from the Baltimore, Maryland chromium chemical production facility were analyzed by Park et al. [2004], 

K.S. Crump [1995], and Gibb et al. [1986]. 

The epidemiologic studies of these worker 
72 Hexavalent Chromium

6 ■ Quantitative Assessment of Risk

Environmental risk assessments of Cr(VI) 

exposure have also been conducted [ATSDR 

2012; EPA 1998, 1999]. These analyses assess 

the risks of nonoccupational Cr(VI) exposure. 

6.2 Baltimore Chromate

Production Risk

Assessments

NIOSH calculated estimates of excess lifetime 

risk of lung cancer death resulting from occupational exposure to chromium-containing 

mists and dusts [Park et al. 2004] using data 

from a cohort of chromate chemical production workers [Gibb et al. 2000b]. NIOSH determined that Gibb et al. [2000b] was the best 

data set available for quantitative risk assessment because of its extensive exposure assessment and smoking information, strong statistical power, and its relative lack of potentially 

confounding exposures. Several aspects of the 

exposure-response relationship were examined. Different model specifications were used 

permitting nonlinear dependence on cumulative exposure to be considered, and the possibility of a nonlinear dose-rate effect was also 

investigated. All models evaluated fit the data 

comparably well. The linear (additive) relative 

rate model was selected as the basis for the risk 

assessment. It was among the better-fitting 

models and was also preferred on biological 

grounds because linear low-dose extrapolation 

is the default assumption for carcinogenesis. 

There was some suggestion of a negative doserate effect, (greater than proportional excess 

risk at low exposures and less than proportional risk at high exposures but still a monotic relationship) but the effect was small. Although 

lacking statistical power, the analyses examining thresholds were consistent with no threshold on exposure intensity. Some misclassification on exposure in relation to race appeared 

to be present, but models with and without the 

exposure-race interaction produced a clear exposure response. Taken together, the analyses 

constitute a robust assessment of the risk of 

chromium carcinogenicity.

The excess lifetime (45  years) risk for lung 

cancer mortality from exposure to Cr(VI) was 

estimated to be 255 per thousand workers at 

the previous OSHA PEL of 52 μg/m3 based on 

the exposure-response estimate for all men in 

the Baltimore cohort. At the previous NIOSH 

REL of 1  μg/m3 for Cr(VI) compounds, the 

excess lifetime risk was estimated to be 6 lung 

cancer deaths per 1,000 workers and at the REL 

of 0.2 μg/m3 the excess lifetime risk is approximately 1 lung cancer death per 1,000 workers.

The data analyzed were from the Baltimore, 

Maryland cohort previously studied by Hayes 

et al. [1979] and Gibb et al. [2000b]. The cohort 

comprised 2,357 men first hired from 1950 

through 1974 whose vital status was followed 

through 1992. The racial makeup of the study 

population was 1,205 white (51%), 848 nonwhite (40%) and 304 of unknown race (13%). 

This cohort had a detailed retrospective exposure assessment that was used to estimate individual worker current and cumulative Cr(VI) 

exposures across time. Approximately 70,000 

both area and personal airborne Cr(VI) measurements of typical exposures were collected 

and analyzed by the employer from 1950 to 

1985, when the plant closed. These samples 

were used to assign, in successive annual periods, average exposure levels to exposure zones 

that had been defined by the employer. These 

job title estimated exposures were combined 

with individual work histories to calculate the 

Cr(VI) exposure of each member of the cohort.

Smoking information at hire was available from 

medical records for 91 percent of the population, including packs per day for 70 percent of 

the cohort. The cohort was largely free of other 

potentially confounding exposures. The mean 
Hexavalent Chromium 73

6 ■ Quantitative Assessment of Risk

duration of employment of workers in the cohort was 3.1 years, while the median duration 

was only 0.39 of a year. 

In this study population of 2,357 workers, 122 

lung cancer deaths were documented. This 

mortality experience was analyzed using Poisson regression methods. Diverse models of 

exposure-response for Cr(VI) were evaluated 

by comparing deviances and inspecting cubic 

splines. The models using cumulative smoking (as a linear spline) fit significantly better 

in comparison with models using a simple 

categorical classification (smoking at hire: yes, 

no, unknown). For this reason, smoking cumulative exposure imputed from cigarette use 

at hire was included as a predictor in the final 

models despite absence of detailed smoking 

histories. Lifetime risks of lung cancer death 

from exposure to Cr(VI) were estimated using an actuarial calculation that accounted for 

competing causes of death. 

An additive relative rate model was selected 

which fit the data well and which was readily interpretable for excess lifetime risk calculations:

relative rate = exp(â0+ â1 Smk1+ â2 Smk2 ) × (1 + â3X)

where Smk1 and Smk2 are the smoking terms 

(Smk1, number of pack-years up to 30; and 

Smk2, above 30) and X is the cumulative chromium exposure (lagged 5 years). The model 

adjusted for age, race, and calendar time by 

incorporating national U.S. mortality rates 

into the model. In the final model, the estimated rate ratio (RR) for 1 mg/m3

-yr cumulative exposure to Cr(VI) was 2.44 with a 95% 

confidence interval of 1.54–3.83 (Δ[–2 lnL] = 

15.1). Addition of a race-chromium interaction term in the preferred linear relative rate 

model resulted in a further reduction in deviance of 10.6, a highly statistically significant 

result (P = 0.001), and the observed chromium 

effect for nonwhite workers (RR  =  5.31, 95% 

CI = 2.78–10.1) was larger than for all workers combined. White workers showed only an 

overall excess, weakly related to measured cumulative exposure. All the well-fitting models 

examined had strong race-exposure interactions. This interaction was observed whether 

age, race, and calendar time were adjusted by 

stratification (internal adjustment) or by using 

external population rates. No other important 

interactions were detected.

A working lifetime of 45 years of exposure to 

Cr(VI) at the previous OSHA PEL of 100 μg/m3

as CrO3 corresponds to a cumulative exposure 

of 4.5 mg/m3-yr. The excess lifetime risk for 

lung cancer mortality from exposure to Cr(VI) 

at this exposure level was estimated to be 255 

per thousand workers (95% CI: 109–416). At 

the previous NIOSH REL, 45 years of occupational exposure corresponded to a lifetime 

excess risk of six (95% CI: 3–12) lung cancer 

deaths per thousand workers. 

Based on a categorical analysis, the exposurerace interaction was found to be largely due 

to an inverse trend in lung cancer mortality 

among whites: an excess in the range 0.03–0.09 

mg/m3-yr of chromium cumulative exposure 

and a deficit in the range 0.37–1.1 mg/m3-yr. 

Park et al. [2004] concluded that a biological 

basis for the chromium-race interaction was 

unlikely and that more plausible explanations 

include, but are not limited to, misclassification 

of smoking status, misclassification of chromium exposures, or chance. It is doubtful that 

confounding factors play an important role, because it is unlikely that another causal risk factor 

is strongly and jointly associated with exposure 

and race. The asbestos exposure that was present 

was reported to be typical of industry generally 

at that time. Some asbestos exposure may have 

been associated with certain chromium process 

areas wherein workers were not representative 

of the entire workforce on race. For this to ex-
74 Hexavalent Chromium

6 ■ Quantitative Assessment of Risk

plain a significant amount of the observed lung 

cancer excess would require relatively high asbestos exposures correlated with Cr(VI) levels 

for non-white workers. It would not explain the 

relative deficit of lung cancer observed among 

white workers with high cumulative Cr(VI) exposures. Furthermore, no mesothelioma deaths 

were observed, and the observed lung cancer 

excess would correspond to asbestos exposures 

at levels seen only in asbestos manufacturing or 

processing environments. 

Exposure misclassification, on the other hand, 

is plausible given the well-known disparities 

in exposure by race often observed in occupational settings. In this study, average exposure 

levels were assigned to exposure zones within 

which there may have been substantial racerelated differences in work assignments and 

resulting individual exposures. Race-exposure 

interactions would inevitably follow. If the racial disparity was the result of exposure misclassification, then models without the racechromium interaction term would provide an 

unbiased estimate of the exposure-response, 

although less precisely than if race had been 

taken into account in the processing of airsampling results and in the specification of exposure zone averages.

Park and Stayner [2006] examined the possibility of an exposure threshold in the Baltimore cohort by calculating different measures 

of cumulative exposure in which only concentrations exceeding some specified threshold 

value were summed over time. The best–fitting 

models, evaluated with the profile likelihood 

method, were those with a threshold lower 

than 1.0 μg/m3, the lowest threshold tested. The 

test was limited by statistical power but established upper confidence limits for a threshold 

consistent with the observed data of 16  μg/

m3 Cr(VI) for models with the exposure-race 

interaction or 29  μg/m3 Cr(VI), for models 

without the exposure-race interaction. Other 

models using a cumulative exposure metric 

in which concentration raised to some power, 

Xa, is summed over time, found that the best 

fit corresponded to a  =  0.8. If saturation of 

some protective process were taking place, 

one would expect a > 1.0. However, statistical 

power limited interpretation as a = 1.0 could 

not be ruled out. Analyses in which a cumulative exposure threshold was tested found the 

best-fitting models with thresholds of 0.02 

mg/m3-yr (with exposure-race interaction) or 

0.3  mg/m3-yr Cr(VI)(without exposure-race 

interaction) but could not rule out no threshold. The retrospective exposure assessment for 

the Baltimore cohort, although the best available for a chromium-exposed population, has 

limitations that reduce the certainty of negative findings regarding thresholds. Nevertheless, the best estimate at this time is that there 

is no concentration threshold for the Cr(VI)-

lung cancer effect.

Crump KS [1995] conducted an analysis of a 

cohort from the older Baltimore plant reported 

by Hayes et al. [1979]. The cumulative exposure 

estimates of Braver et al. [1985] were also used 

in the risk assessment. From a Poisson regression model, the maximum likelihood estimate 

of ß, the potency parameter (i.e., unit risk), was 

7.5 × 10-4 per μg/m3-yr. Occupational exposure 

to Cr(VI) for 45 years was estimated to result 

in 88 excess lung cancer deaths per 1,000 workers exposed at the previous OSHA PEL and 1.8 

excess lung cancer deaths per 1,000 workers 

exposed at the previous NIOSH REL.

Gibb et al. [1986] conducted a quantitative assessment of the Baltimore production workers 

reported by Hayes et al. [1979], whose exposure 

was reconstructed by Braver et al. [1985]. This 

cohort was divided into six subcohorts based on 

their period of hire and length of employment 

[Braver et al. 1985]. Gibb et al. [1986] calculated 
Hexavalent Chromium 75

6 ■ Quantitative Assessment of Risk

the lifetime respiratory cancer mortality risk 

estimates for the four subcohorts who were 

hired before 1960 and had worked in the old 

facility. The slopes for these subcohorts ranged 

from 5.1 × 10-3/μg/m3 to 2.0 × 10-2/μg/m3 with a 

geometric mean of 9.4 × 10-3/μg/m3. 

6.3 Painesville Chromate

Production Risk

Assessments

Crump et al. [2003] calculated estimates of excess lifetime risk of lung cancer death resulting 

from occupational and environmental exposure to Cr(VI) in a cohort of chromate chemical production workers. The excess lifetime 

(45 years) risk for lung cancer mortality from 

occupational exposure to Cr(VI) at 1  μg/m3 

(the previous NIOSH REL) was estimated to 

be approximately 2 per 1,000 workers for both 

the relative and additive risk models.

The cohort analyzed was a Painesville, Ohio 

worker population described by Luippold et 

al. [2003]. The cohort comprised 493 workers 

who met the following criteria: first hired from 

1940 through 1972, worked for at least 1 year, 

and did not work in any of the other Cr(VI) 

facilities owned by the same company, other 

than the North Carolina plant. The vital status 

of the cohort was followed through 1997. 

All but four members of the cohort were male. 

Little information was available on the racial 

makeup of the study population other than 

that available from death certificates. Information on potential confounders such as smoking histories and other occupational exposures 

was limited, so this information was not included in the mortality analysis. There were 

303 deaths, including 51 lung cancer deaths, 

reported in the cohort. SMRs were significantly increased for the following: all causes 

combined, all cancers combined, lung cancer, 

year of hire before 1960, 20 or more years of exposed employment, and latency of 20 or more 

years. A trend test showed a strong relationship 

between lung cancer mortality and cumulative 

Cr(VI) exposure. Lung cancer mortality was 

statistically significantly increased for observation groups with cumulative exposures greater 

than or equal to 1.05 mg/m3-years. 

The exposure assessment of the cohort was 

reported by Proctor et al. [2003]. More than 

800  Cr(VI) air-sampling measurements from 

21 industrial hygiene surveys were identified. These data were airborne area samples. 

Airborne Cr(VI) concentration profiles were 

constructed for 22 areas of the plant for each 

month from January 1940 through April 1972. 

Cr(VI) exposure estimates for each worker 

were reconstructed by correlating their job 

titles and work areas with the corresponding 

area exposure levels for each month of their 

employment. The cumulative exposure and 

highest average monthly exposure levels were 

determined for each worker. 

K.S. Crump [1995] calculated the risk of 

Cr(VI) occupational exposure in its analysis of 

the Mancuso [1975] data. Cr(III) and Cr(VI) 

data from the Painesville, Ohio plant [Bourne 

and Yee 1950] were used to justify a conversion 

factor of 0.4 to calculate Cr(VI) concentrations 

from the total chromium concentrations presented by Mancuso [1975]. The cumulative 

exposure of workers to Cr(VI) (μg/m3-yr) was 

used in the analysis. All of the original exposure categories presented by Mancuso [1975] 

were used in the analysis, including those that 

had the greatest cumulative exposure. A sensitivity analysis using different average values 

was applied to these exposure categories. U.S. 

vital statistics data from 1956, 1967, and 1971 

were used to calculate the expected numbers 

of lung cancer deaths. Estimates of excess lung 
76 Hexavalent Chromium

6 ■ Quantitative Assessment of Risk

cancer deaths at the previous NIOSH REL 

ranged from 5.8 to 8.9 per 1,000 workers. Estimates of excess lung cancer deaths at the previous OSHA PEL ranged from 246 to 342 per 

1,000 workers. 

DECOS [1998] used the EPA [1984] environmental risk assessment that was based on the 

Mancuso [1975] data to calculate the additional 

lung cancer mortality risk due to occupational 

Cr(VI) exposure. The EPA estimate that occupational exposure to 8 μg/m3

 total dust resulted in an additional lung cancer mortality 

risk of 1.4 × 10-2 was used to calculate occupational risk. It was assumed that total dust concentrations were similar to inhalable dust concentrations because of the small aerodynamic 

diameters of the particulates. Additional cancer mortality risks for 40-year occupational 

exposure to inhalable dust were calculated as 

4 × 10-3 for 2 μg/m3 Cr(VI).

The EPA used the data of Mancuso [1975] to 

calculate a unit risk estimate for Cr(VI). A unit 

risk estimate is the incremental lifetime cancer 

risk over the background cancer risk occurring 

in a hypothetical population in which all individuals are exposed continuously throughout 

life to a concentration of 1 μg/m3 of the agent 

in the air that they breathe [EPA 1984]. This 

unit risk quantifies the risk resulting from environmental exposure to Cr(VI) as an air pollutant. The U.S. EPA calculated, based on the 

Mancuso [1975] data, a unit risk estimate for 

Cr(VI) of 1.2 ×  10-2 for environmental exposures. If this lifetime unit risk estimate is adjusted to a hypothetical working lifetime of 

Cr(VI) exposure (8-hour work day, 250  days 

per year for 45 years), there would be 92.5 predicted additional deaths from lung cancer per 

1,000 workers at the previous OSHA PEL of 

52 μg/m3 and 1.8 predicted additional deaths 

from lung cancer per 1,000 workers at the previous NIOSH REL of 1 μg/m3

 [Crump 1995].

6.4 Other Cancer Risk

Assessments

The International Chromium Development 

Association (ICDA) [1997] used the overall 

SMR for lung cancer from 10  Cr(VI) studies 

to assess the risk of occupational exposure to 

various levels of Cr(VI) exposure. The 10 studies evaluated were those selected by Steenland 

et al. [1996] as the largest and best-designed 

studies of workers in the chromium production, chromate paint production, and chromate plating industries. It was assumed that 

the mean length of employment of all workers 

was 15 years. Although this assumption may be 

appropriate for some of the cohorts, for others 

it is not: the mean duration of employment for 

the Painesville cohort was less than 10  years, 

and for the Baltimore cohort it was less than 

4 years. Occupational exposures to Cr(VI) were 

assumed to be 500 μg/m3, 1,000 μg/m3, or 2,000 

μg/m3 TWA. These are very unlikely Cr(VI) exposure levels. The mean exposure concentrations in the Painesville cohort were less than 

100  μg/m3 after 1942, and in the Baltimore 

cohort the mean exposure concentration was 

45  μg/m3. For these different exposure levels, 

three different assumptions were tested: (1) the 

excess SMR was due to only Cr(VI) exposure, 

(2) Cr(VI) exposure was confounded by smoking or other occupational exposures so that the 

baseline SMR should be 130, or (3) confounders set the baseline SMR to 160. The investigators did not adjust for the likely presence of 

a healthy worker effect in these SMR analyses. 

A baseline SMR of 80 or 90 would have been 

appropriate based on other industrial cohorts 

and would have addressed smoking differences between industrial worker populations 

and national reference populations [Park et al. 

1991]. The reference used for expected deaths 

was the 1981 life-table for males in England 

and Wales. The lung cancer mortality risk estimates ranged from 5 to 28 per 1,000 at exposure 
Hexavalent Chromium 77

6 ■ Quantitative Assessment of Risk

to 50 μg/m3 Cr(VI), to 0.1 to 0.6 per 1,000 at 

exposure to 1 μg/m3 Cr(VI). The assumptions 

made and methods used in this risk assessment 

make it a weaker analysis than those in which 

worker exposure data at a particular plant are 

correlated with their incidence of lung cancer. 

The excess lung cancer deaths may have been 

underestimated by at least a factor of 10, given 

the assumptions used on duration (factor of 

1.5–2.0), exposure level (factor of 10–20), and 

healthy worker bias (factor of 1.1–1.2).

6.5 Summary

The data sets of the Painesville, Ohio and Baltimore, Maryland chromate production workers 

provide the bases for the quantitative risk assessments of excess lung cancer deaths due to 

occupational Cr(VI) exposure. In 1975, Mancuso presented the first data set of the Painesville, Ohio workers, which was used for quantitative risk analysis. Its deficiencies included 

very limited exposure data, information on 

total chromium only, and no reporting of the 

expected number of deaths from lung cancer. Proctor et al. [2003] presented more than 

800 airborne Cr(VI) measurements from 23 

newly identified surveys conducted from 1943 

through 1971 at the Painesville plant. These data 

and the mortality study of Luippold et al. [2003] 

provided the basis for an improved lung cancer 

risk assessment of the Painesville workers. 

In 1979, Hayes presented the first data of the 

Baltimore, Maryland production facility workers, which were later used for quantitative 

risk assessment. In 2000, Gibb and coworkers 

provided additional exposure data for an improved cancer risk assessment of the Baltimore 

workers [Gibb et al. 2000b]. NIOSH selected 

the Gibb et al. [2000b] cohort for quantitative 

risk analysis [Park et al. 2004] rather than the 

Painesville cohort because of its greater number of lung cancer deaths, better smoking histories, and a more comprehensive retrospective 

exposure archive [NIOSH 2005a]. 

In spite of the different data sets analyzed and 

the use of different assumptions, models, and 

calculations, these risk assessments have estimates of excess risk that are within an order of 

magnitude of each other (see Tables 6–1, 6–2). 

All of these risk assessments indicate considerable excess risk of lung cancer death to workers exposed to Cr(VI) at the previous OSHA 

PEL and previous NIOSH REL. The risk assessments of Crump et al. [2003] and Park et 

al. [2004] analyzed the most complete data sets 

available on occupational exposure to Cr(VI). 

These risk assessments estimated excess risks 

of lung cancer death of 2 per 1,000 workers 

[Crump et al. 2003] and 6 per 1,000 workers 

[Park et al. 2004], at a working lifetime exposure to 1  μg/m3

. Park et al. [2004] estimated 

an excess risk of lung cancer death of approximately 1 per 1,000 workers at a steady 45-year 

workplace exposure to 0.2 μg/m3 Cr(VI).

Park and Stayner [2006] evaluated the possibility of a threshold concentration for lung cancer 

in the Baltimore cohort. Although a threshold 

could not be ruled out because of the limitations of the analysis, the best estimate at this 

time is that there is no concentration threshold 

for the Cr(VI)-lung cancer effect.
78 Hexavalent Chromium

6 ■ Quantitative Assessment of Risk

Table 6–1. Risk Assessments of the Painesville Cohort

Estimated additional deaths from lung cancer per 1,000 workers

Cr(VI) exposure

μg/m3* EPA [1984] Crump [1995]§ Crump et al. [2003]

0.25 0.44 1.4–2.2

0.5 2.9–4.4

1.0† 1.8 5.8–8.9 2.1 (1.3–2.9); 2.2 (1.4–3.0)¶

2.5 4.4 14.0–22.0

5.0‡ 8.8 28.0–43.0

52.0 91.5 246–342

*Assumes steady working lifetime exposure

†

Previous NIOSH REL

‡

OSHA PEL

§

Range results from different treatments of high-exposure groups

¶

Result (95% confidence interval) for relative risk and additive risk models, respectively.

Table 6–2. Risk Assessments of the Baltimore Cohorts

Estimated additional deaths from lung cancer per 1,000 workers

Cr(VI) exposure

μg/m3* Gibb et al. [1986] KS Crump [1995]

Park et al. [2004]

linear model

Park et al. [2004]

log-linear model

0.25 0.34 0.45 1.5 —

0.5 — 0.90 3 (1–6)§ 3 (1–4)

1.0† 1.4 1.8 6 (3–12) 5 (3–8)

2.5 3.4 4.5 16 (6–30) 14 (7–20)

 5.0‡ 6.8 9.0 31 (12–59) 28 (13–43)

52.0 70.2 88.0 255 (109–416) 281 (96–516)

*Assumes steady working lifetime exposure

†

Previous NIOSH REL

‡

OSHA PEL

§

95% confidence interval
Hexavalent Chromium 79

Recommendations for an 

Exposure Limit

available scientific evidence supports the inclusion of all Cr(VI) compounds into this recommendation. The REL is intended to reduce 

workers’ risk of lung cancer associated with 

occupational exposure to Cr(VI) compounds 

over a working lifetime. It is expected that reducing airborne workplace exposures will also 

reduce the nonmalignant respiratory effects of 

Cr(VI) compounds, including irritated, ulcerated, or perforated nasal septa and other potential adverse health effects. Additional controls 

are needed or administrative actions should be 

taken to reduce 8-hr TWA exposure to Cr(VI) 

compounds when the results of the exposure 

monitoring plan do not produce a high degree 

of confidence that a high percentage of daily 

8-hr TWA exposures are below the REL.

In addition to limiting airborne concentrations 

of Cr(VI) compounds, NIOSH recommends 

that dermal exposure to Cr(VI) be prevented 

in the workplace to reduce the risk of adverse 

dermal health effects, including irritation, ulcers, skin sensitization, and allergic contact 

dermatitis. 

7.2 Basis for NIOSH

Standards

In the 1973 Criteria for a Recommended Standard: Occupational Exposure to Chromic Acid, 

NIOSH recommended that the federal standard for chromic acid, 0.1 mg/m3

 as a 15- minute 

ceiling concentration, be retained because 

of reports of nasal ulceration occurring at 

NIOSH is mandated under the authority of 

the Occupational Safety and Health Act of 

1970 (Public Law 91-596) to develop and 

recommend criteria for identifying and controlling workplace hazards that may result in 

occupational illness or injury. NIOSH evaluated the available literature on hexavalent 

chromium (Cr[VI]) compounds, including 

quantitative risk assessment, epidemiologic, 

toxicologic, and industrial hygiene studies to 

develop recommendations for occupational 

exposure to Cr(VI) compounds. This chapter summarizes the information relevant to 

the NIOSH recommended exposure limit 

(REL) for Cr(VI) compounds and the scientific data used to derive and support the revised REL. More detailed information about 

the studies summarized here is available in 

the respective document chapters. 

7.1 The NIOSH REL for

Cr(VI) Compounds

NIOSH recommends that airborne exposure to 

all Cr(VI) compounds be limited to a concentration of 0.2 μg Cr(VI)/m3

 for an 8-hr TWA 

exposure during a 40-hr workweek. The use 

of NIOSH Method 7605 (or validated equivalents) is recommended for Cr(VI) determination. The REL represents the upper limit of exposure for each worker during each work shift. 

Because of the residual risk of lung cancer at 

the REL, NIOSH further recommends that all 

reasonable efforts be made to reduce exposures 

to Cr(VI) compounds below the REL. The 

7
80 Hexavalent Chromium

7 ■ Recommendations for an Exposure Limit

concentrations only slightly above this concentration [NIOSH 1973a]. In addition, NIOSH 

recommended supplementing the ceiling 

concentration with a TWA of 0.05 mg/m3 for 

an 8-hour workday to protect against possible 

chronic effects, including lung cancer and liver damage. The association of these chronic 

effects with chromic acid exposure was not 

proven at that time, but the possibility of a 

correlation could not be rejected [NIOSH 

1973a].

In the 1975 Criteria for a Recommended Standard: Occupational Exposure to Chromium(VI), 

NIOSH supported two distinct recommended 

standards for Cr(VI) compounds [NIOSH 

1975a]. Some Cr(VI) compounds were considered noncarcinogenic at that time, including 

the chromates and bichromates of hydrogen, 

lithium, sodium, potassium, rubidium, cesium, 

and ammonium, and chromic acid anhydride. 

These Cr(VI) compounds were relatively soluble in water. It was recommended that a 10-hr 

TWA limit of 25 μg Cr(VI)/m3 and a 15-minute 

ceiling limit of 50 μg Cr(VI)/m3 be applied to 

these Cr(VI) compounds.

All other Cr(VI) compounds were considered 

carcinogenic [NIOSH 1975a]. These Cr(VI) 

compounds were relatively insoluble in water. 

At that time, NIOSH had a carcinogen policy 

that called for “no detectable exposure levels 

for proven carcinogenic substances” [Fairchild 

1976]. Thus the basis for the REL for carcinogenic Cr(VI) compounds, 1  μg Cr(VI)/m3

TWA, was the quantitative limitation of the 

analytical method available for measuring 

workplace exposures to Cr(VI) at that time. 

NIOSH revised its policy on Cr(VI) compounds in its 1988 Testimony to OSHA on the 

Proposed Rule on Air Contaminants [NIOSH 

1988b]. NIOSH testified that while insoluble 

Cr(VI) compounds had previously been demonstrated to be carcinogenic, there was now 

sufficient evidence that soluble Cr(VI) compounds were also carcinogenic. Human studies 

cited in support of this position included Blair 

and Mason [1980], Franchini et al. [1983], Royle [1975a,b], Silverstein et al. [1981], Sorahan 

et al. [1987], and Waterhouse [1975]. In addition, the animal studies of Glaser et al. [1986] 

and Steinhoff et al. [1986] were cited as demonstrating that lifespan exposure of rats to soluble 

chromates could induce statistically significant 

excess cancer rates. NIOSH recommended 

that all Cr(VI) compounds, whether soluble 

or insoluble, be classified as potential occupational carcinogens. NIOSH recommended 

that OSHA adopt the most protective of the 

available standards, the NIOSH RELs. Subsequently, based on this testimony to OSHA, the 

REL of 1 μg Cr(VI)/m3 TWA was adopted by 

NIOSH for all Cr(VI) compounds.

NIOSH reaffirmed its policy that all Cr(VI) 

compounds be classified as occupational carcinogens in the NIOSH Comments on the OSHA 

Request for Information on Occupational Exposure to Hexavalent Chromium and the NIOSH 

Testimony on the OSHA Proposed Rule on Occupational Exposure to Hexavalent Chromium

[NIOSH 2002; 2005a].

This criteria document describes the most recent NIOSH scientific evaluation of occupational exposure to Cr(VI) compounds, including the justification for a revised REL derived 

using current quantitative risk assessment 

methodology on human health effects data. 

Derivation of the REL follows the criteria established by NIOSH in 1995 in which RELs, 

including those for carcinogens, would be 

based on risk evaluations using human or animal health effects data, and on an assessment 

of what levels can be feasibly achieved by engineering controls and measured by analytical 

techniques [NIOSH 1995b].
Hexavalent Chromium 81

7 ■ Recommendations for an Exposure Limit

7.3 Evidence for the

Carcinogenicity of

Cr(VI) Compounds

Hexavalent chromium is a well-established 

occupational carcinogen associated with lung 

cancer and nasal and sinus cancer [ATSDR 

2012; EPA 1998; IARC 1990, 2012; Straif et al. 

2009]. NTP identified Cr(VI) compounds as 

carcinogens in its first report on carcinogens in 

1980 [NTP 2011]. Toxicologic studies, epidemiologic studies, and lung cancer meta-analyses provide evidence for the carcinogenicity of Cr(VI) 

compounds. 

7.3.1 Epidemiologic Lung

Cancer Studies

In 1989, the IARC critically evaluated the published epidemiologic studies of chromium 

compounds including Cr(VI) and concluded 

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” (i.e., IARC category “Group 1” carcinogen) [IARC 1990]. 

Results from two recent lung cancer mortality 

studies of chromate production workers support this evaluation [Gibb et al. 2000b; Luippold et al. 2003]. In 2009, an IARC Working 

Group reviewed and reaffirmed Cr(VI) compounds as Group 1 carcinogens (lung) [Straif 

et al. 2009; IARC 2012].

Gibb et al. [2000b] conducted a retrospective 

analysis of lung cancer mortality in a cohort of 

Maryland chromate production workers. The 

cohort of 2,357 male workers first employed 

from 1950 through 1974 was followed until 

1992. Workers with short-term employment 

(i.e., <  90 days) were included in the study 

group to increase the size of the low exposure 

group. The mean length of employment was 

3.1 years. A detailed retrospective assessment 

of Cr(VI) exposure based on more than 70,000 

personal and area samples (short-term and 

full-shift) and information about most workers’ smoking habits at hire was available. 

Lung cancer standardized mortality ratios increased with increasing cumulative exposure 

(i.e., mg CrO3/m3-years, with 5-year exposure 

lag)—from 0.96 in the lowest quartile to 1.57 

(95% CI 1.07—2.20) and 2.24 (95% CI 1.60—

3.03) in the two highest quartiles. The number 

of expected lung cancer deaths was based on 

age-, race-, and calendar year-specific rates for 

Maryland. Proportional hazards models that 

controlled for the effects of smoking predicted increasing lung cancer risk with increasing 

Cr(VI) cumulative exposure (relative risks: 

1.83 for second exposure quartile, 2.48 for 

third, and 3.32 for fourth, compared with first 

quartile of cumulative exposure; confidence 

intervals not reported; 5-year exposure lag).

Luippold et al. [2003] conducted a retrospective cohort study of lung cancer mortality in 

493 chromate production workers employed 

for at least 1 year from 1940 through 1972 in 

a Painesville, Ohio plant. Their mortality was 

followed from 1941 to the end of 1997 and 

compared with United States and Ohio rates. 

The effects of smoking could not be assessed 

because of insufficient data. More than 800 area 

samples of airborne Cr(VI) from 21 industrial 

hygiene surveys were available for formation 

of a job-exposure matrix [Proctor et al. 2003]. 

Cumulative Cr(VI) exposure was divided into 

five categories: 0.00–0.19, 0.20–0.48, 0.49–1.04, 

1.05–2.69, and 2.70–23.0 mg/m3-years [Luippold et al. 2003]. Person-years in each category 

ranged from 2,369 to 3,220, and the number of 

deaths from trachea, bronchus, or lung cancer 

ranged from 3 in the lowest exposure category 

to 20 in the highest (n = 51). The SMRs were statistically significant in the two highest cumulative 

exposure categories (3.65 [95% CI 2.08–5.92] 
82 Hexavalent Chromium

7 ■ Recommendations for an Exposure Limit

and 4.63 [2.83–7.16], respectively). SMRs were 

also significantly increased for year of hire before 1960, ≥ 20 years of employment, and ≥ 20 

years since first exposure. The tests for trend 

across increasing categories of cumulative exposure, year of hire, and duration of employment were statistically significant (P ≤ 0.005). 

A test for departure of the data from linearity 

was not statistically significant (χ2 goodness of 

fit of linear model; P = 0.23).

7.3.2 Lung Cancer Meta-Analyses

Meta-analyses of epidemiologic studies have 

been conducted to investigate cancer risk in 

chromium-exposed workers. Most of these 

studies also provide support for the classification of Cr(VI) compounds as occupational 

lung carcinogens.

Sjögren et al. [1994] reported a meta-analysis 

of five lung cancer studies of Canadian and 

European welders exposed to stainless steel 

welding fumes. The meta-analysis found an estimated relative risk of 1.94 (95% CI 1.28–2.93) 

and accounted for the effects of smoking and 

asbestos exposure. 

Steenland et al. [1996] reported overall relative 

risks for specific occupational lung carcinogens identified by IARC, including chromium. 

Ten epidemiologic studies were selected by the 

authors as the largest and best-designed studies of chromium production workers, chromate pigment production workers, and chromium platers. The summary relative risk for 

the 10 studies was 2.78 (95% confidence interval 2.47–3.52; random effects model), which 

was the second-highest relative risk among the 

eight carcinogens summarized.

Cole and Rodu [2005] conducted meta-analyses 

of epidemiologic studies published in 1950 or 

later to test for an association of chromium 

exposure with all causes of death, and death 

from malignant diseases (i.e., all cancers combined, lung cancer, stomach cancer, cancer 

of the central nervous system [CNS], kidney cancer, prostate gland cancer, leukemia, 

Hodgkin’s disease, and other lymphatohematopoietic cancers). Available papers (n = 114) 

were evaluated independently by both authors 

on eight criteria that addressed study quality. 

In addition, papers with data on lung cancer 

were assessed for control of cigarette smoking 

effects, and papers with data on stomach cancer were assessed for economic status. Fortynine epidemiologic studies based on 84 papers 

published were used in the meta-analyses. 

The number of studies in each meta-analysis 

ranged from 9 for Hodgkin’s disease to 47 for 

lung cancer. Association was measured by an 

author-defined “SMR” that included odds ratios, proportionate mortality ratios, and most 

often, standardized mortality ratios. Mortality risks were not significantly increased for 

most causes of death. However, SMRs were 

significantly increased in all lung cancer 

meta-analyses (smoking controlled: 26 studies; 1,325 deaths; SMR  =  118; 95% CI 112–

125) (smoking not controlled: 21 studies; 

1,129 deaths; SMR = 181; 95% CI 171–192) 

(lung cancer—all: 47 studies; 2,454 deaths; 

SMR = 141; 95% CI 135–147). Stomach cancer mortality risk was significantly increased 

only in meta-analyses of studies that did not 

control for effects of economic status (economic status not controlled: 18 studies; 324 

deaths; SMR = 137; 95% 123–153). The authors stated that statistically significant SMRs 

for “all cancer” mortality were mainly due 

to lung cancer (all cancer: 40 studies; 6,011 

deaths; SMR = 112; 95% CI 109–115). Many 

of the studies contributing to the meta-analyses did not address bias from the healthy 

worker effect, and thus the results are likely 

underestimates of the cancer mortality risks. 

Other limitations of these meta-analyses include lack of (1) exposure characterization of 
Hexavalent Chromium 83

7 ■ Recommendations for an Exposure Limit

populations, such as the route of exposure (i.e., 

airborne versus ingestion); and (2) detail  of 

criteria  used to exclude studies based on “no 

or little chrome exposure” or “no usable data.” 

7.3.3 Animal Experimental Studies

Cr(VI) compounds have been tested in animals using many different experimental conditions and exposure routes. Although experimental conditions are often different from 

occupational exposures, these studies provide 

additional data to assess the carcinogenicity of 

the test compounds. Chronic inhalation studies 

provide the best data for extrapolation to occupational exposure; few have been conducted 

using Cr(VI) compounds. However, the body 

of animal studies support the classification of 

Cr(VI) compounds as occupational carcinogens. 

The few chronic inhalation studies available 

demonstrate the carcinogenic effects of Cr(VI) 

compounds in mice and rats [Adachi et al. 

1986, 1987; Glaser et al. 1986]. Female mice exposed to 1.8 mg/m3

 chromic acid mist (2 hours 

per day, 2 days per week for up to 12 months) 

developed a significant number of nasal papillomas compared with control animals [Adachi 

1987]. Female mice exposed to a higher dose 

of chromic acid mist, 3.6 mg/m3 (30 minutes 

per day, 2 days per week for up to 12 months) 

developed an increased, but not statistically 

significant, number of lung adenomas [Adachi 

et al. 1986]. Glaser et al. [1986] reported a statistically significant number of lung tumors in 

male rats exposed for 18 months to 100 μg/m3

sodium dichromate; no tumors were reported 

at lower dose levels.

Animal studies conducted using other routes 

of administration have also produced adverse 

health effects with some Cr(VI) compounds. 

Zinc chromate and calcium chromate produced 

a statistically significant (P < 0.05) number of 

bronchial carcinomas when administered to 

rats via an intrabronchial pellet implantation 

system [Levy et al. 1986]. Cr(VI) compounds 

with a range of solubilities were tested using 

this system. Although some soluble Cr(VI) 

compounds did produce bronchial carcinomas, these results were not statistically significant. Some lead chromate compounds produced bronchial squamous carcinomas that, 

although not statistically significant, may be 

biologically significant because of the absence 

of this cancer in control rats.

Steinhoff et al. [1986] administered the same 

total dose of sodium dichromate either once 

per week or five times per week to male and 

female rats via intratracheal instillation. No increased incidence of lung tumors was observed 

in animals dosed five times weekly. However, 

in animals dosed once per week, a statistically significant tumor incidence was reported 

in the 1.25 mg/kg exposure group. This study 

demonstrates a dose-rate effect within the constraints of the experimental design. It suggests 

that limiting exposure to high Cr(VI) concentrations may be important in reducing carcinogenicity. However, quantitative extrapolation 

of these animal data to the human exposure 

scenario is difficult. 

Animal studies conducted using nonrespiratory routes of administration have also produced injection-site tumors with some Cr(VI) 

compounds [Hueper 1961; Furst 1976]. These 

studies provide another data set for hazard 

identification.

IARC [2012] concluded “there is sufficient evidence in experimental animals for the carcinogenicity of chromium (VI) compounds”.

7.4 Basis for the NIOSH REL

The primary basis for the NIOSH REL is the results of the Park et al. [2004] quantitative risk 
84 Hexavalent Chromium

7 ■ Recommendations for an Exposure Limit

assessment of lung cancer deaths of Maryland 

chromate production workers conducted on the 

data of Gibb et al. [2000b]. NIOSH determined 

that this was the best Cr(VI) data set available 

for analysis because of its extensive exposure assessment and smoking information, strong statistical power, and its relative lack of potentially 

confounding exposures [NIOSH 2005a]. The 

results of the NIOSH risk assessment are supported by other quantitative Cr(VI) risk assessments (see Chapter 6).

NIOSH selected the revised REL at an excess 

risk of lung cancer of approximately 1 per 

1,000 workers based on the results of Park et 

al. [2004]. Table 7–1 presents the range of risk 

levels of lung cancer from 1 per 500 to 1 per 

100,000 for workers exposed to Cr(VI). Cancer risks greater than 1 per 1,000 are considered significant and worthy of intervention 

by OSHA. This level of risk is consistent with 

those for other carcinogens in recent OSHA 

rules [71 Fed. Reg. 10099 (2006)]. NIOSH 

has used this risk level in a variety of circumstances, including citing this level as appropriate for developing authoritative recommendations in criteria documents and peer-reviewed 

risk assessments [NIOSH 1995a, 2006; Rice et 

al. 2001; Park et al. 2002; Stayner et al. 2000; 

Dankovic et al. 2007]. 

Additional considerations in the derivation of 

the REL include analytical feasibility and the 

ability to control exposure concentrations to 

the REL in the workplace. The REL for Cr(VI) 

compounds is intended to reduce workers’ risk 

of lung cancer over a 45-year working lifetime. 

Although the quantitative analysis is based on 

lung cancer mortality data, it is expected that 

reducing airborne workplace exposures will 

also reduce the nonmalignant respiratory effects of Cr(VI) compounds, including irritated, 

ulcerated, or perforated nasal septa, and other 

potential adverse health effects.

The available scientific evidence supports the 

inclusion of workers exposed to all Cr(VI) 

compounds into this recommendation. All 

Cr(VI) compounds studied have demonstrated their carcinogenic potential in animal, in 

vitro, or human studies [NIOSH 1988b; 2002; 

2005a,b]. Molecular toxicology studies provide 

additional support for classifying Cr(VI) compounds as occupational carcinogens. 

At this time, there is insufficient data to quantify a different REL for each specific Cr(VI) 

compound [NIOSH 2005a,b]. Although there 

are inadequate epidemiologic data to quantify the risk of human exposure to insoluble 

Cr(VI) compounds, the results of animal studies indicate that this risk is likely as great as, 

if not greater than, exposure to soluble Cr(VI) 

compounds [Levy et al. 1986]. Because of the 

similar mechanisms of action of soluble and 

insoluble Cr(VI) compounds, and the quantitative risk assessments demonstrating significant risk of lung cancer death resulting 

from occupational lifetime exposure to soluble 

Cr(VI) compounds, NIOSH recommends that 

the REL apply to all Cr(VI) compounds.

Table 7–1. Cr(VI) exposure associated with 

various levels of excess risk of lung cancer 

after a 45-year working lifetime 

Lifetime added risk* 

for a 45-year working 

lifetime exposure

Cr(VI)

exposure

μg/m3 Cr

Cr(VI)

exposure

μg/m3 CrO3

1 in 500 0.32 0.64

1 in 1,000 0.16 0.32

1 in 2,000 0.08 0.16

1 in 5,000 0.032 0.064

1 in 10,000 0.016 0.032

1 in 100,000 0.0016 0.0032

*Risk estimates from Park et al. [2004]
Hexavalent Chromium 85

7 ■ Recommendations for an Exposure Limit

At this time, there are inadequate data to conduct a quantitative risk assessment for workers exposed to Cr(VI), other than chromate 

production workers. However, epidemiologic 

studies demonstrate that the health effects of 

airborne exposure to Cr(VI) are similar across 

workplaces and industries (see Chapter 4). 

Therefore, the results of the NIOSH quantitative risk assessment conducted on chromate 

production workers [Park et al. 2004] are being used as the basis of the REL for workplace 

exposures to all Cr(VI) compounds.

7.4.1 Park et al. [2004]

Risk Assessment

NIOSH calculated estimates of excess lifetime 

risk of lung cancer death resulting from occupational exposure to water-soluble chromium-containing mists and dusts in a cohort of 

Baltimore, MD chromate chemical production 

workers [Park et al. 2004]. This cohort, originally studied by Gibb et al. [2000b], comprised 

2,357 men first hired from 1950 through 1974, 

whose vital status was followed through 1992. 

The mean duration of employment of workers 

in the cohort was 3.1 years, and the median 

duration was 0.39 year.

This cohort had a detailed retrospective exposure assessment of approximately 70,000 measurements, which was used to estimate individual worker current and cumulative Cr(VI) 

exposures across time. Smoking information 

at hire was available from medical records for 

91% of the population, including packs per 

day for 70 percent of the cohort. In this study 

population of 2,357 workers, 122 lung cancer 

deaths were documented. 

The excess working lifetime (45 years) risk estimates of lung cancer death associated with 

occupational exposure to water-soluble Cr(VI) 

compounds using the linear risk model are 255 

(95% CI: 109–416) per 1,000 workers at 52 μg 

Cr(VI)/m3, 6 (95% CI: 3–12) per 1,000 workers at 1 μg Cr(VI)/m3

, and approximately 1 per 

1,000 workers at 0.2 μg Cr(VI)/m3.

7.4.2 Crump et al. [2003]

Risk Assessment

Crump et al. [2003] analyzed data from the 

Painesville, Ohio chromate production worker cohort described by Luippold et al. [2003]. 

The cohort comprised 493 workers who met 

the following criteria: first hired from 1940 

through 1972, worked for at least 1 year, and 

did not work in any of the other Cr(VI) facilities owned by the same company other than 

the North Carolina plant. The vital status of the 

cohort was followed through 1997. 

Information on potential confounders (e.g., 

smoking) and other occupational exposures 

was limited and not included in the mortality 

analysis. There were 303 deaths reported, including 51 lung cancer deaths. SMRs were significantly increased for the following: all causes 

combined, all cancers combined, lung cancer, 

year of hire before 1960, 20 or more years of 

exposed employment, and latency of 20 or more 

years. A trend test showed a strong relationship 

between lung cancer mortality and cumulative 

Cr(VI) exposure. Lung cancer mortality was increased for cumulative exposures greater than 

or equal to 1.05 mg/m3-years. 

The estimated lifetime additional risk of lung 

cancer mortality associated with 45  years of 

occupational exposure to water-soluble Cr(VI) 

compounds at 1 μg/m3 was approximately 2 per 

1,000 (0.00205 [90% CI: 0.00134, 0.00291] for 

the relative risk model and 0.00216 [90% CI: 

0.00143, 0.00302] for the additive risk model), 

assuming a linear dose response for cumulative exposure with a 5-year lag.
86 Hexavalent Chromium

7 ■ Recommendations for an Exposure Limit

7.4.3 Risk Assessment Summary

Quantitative risk assessments of the Baltimore, 

Maryland and Painesville, Ohio chromate production workers consistently demonstrate significant risk of lung cancer mortality to workers exposed to Cr(VI) at the previous NIOSH 

REL of 1  μg Cr(VI)/m3. These results justify 

lowering the NIOSH REL to decrease the risk 

of lung cancer in workers exposed to Cr(VI). 

NIOSH used the results of the risk assessment of Park et al. [2004] as the basis of the 

current REL because this assessment analyzes 

the most extensive database of workplace exposure measurements, including smoking data 

on most workers.

7.5 Applicability of the REL

to All Cr(VI) Compounds

NIOSH recommends that the REL of 0.2  μg 

Cr(VI)/m3 be applied to all Cr(VI) compounds. 

Currently, there are inadequate data to exclude 

any single Cr(VI) compound from this recommendation. IARC [2012] concluded that “there 

is sufficient evidence in humans for the carcinogenicity of chromium (VI) compounds”.

Epidemiologic studies were often unable to identify the specific Cr(VI) compound responsible for 

the excess risk of cancer. However, these studies have documented the carcinogenic risk of 

occupational exposure to soluble Cr(VI). Gibb 

et al. [2000b] and Luippold et al. [2003] reported the health effects of chromate production 

workers with sodium dichromate being their 

primary Cr(VI) exposure. These studies, and 

the risk assessments conducted on their data, 

demonstrate the carcinogenic effects of this 

soluble Cr(VI) compound. The NIOSH risk 

assessment on which the REL is based evaluated the risk of exposure to sodium dichromate 

[Park et al. 2004]. 

Although there are inadequate epidemiologic 

data to quantify the cancer risk of human exposure to insoluble Cr(VI) compounds, the results of animal studies indicate that this risk is 

likely as great, if not greater than, exposure to 

soluble Cr(VI) compounds [Levy et al. 1986]. 

The carcinogenicity of insoluble Cr(VI) compounds has been demonstrated in animal and 

human studies [NIOSH 1988b]. Animal studies have demonstrated the carcinogenic potential of soluble and insoluble Cr(VI) compounds 

[NIOSH 1988b, 2002, 2005a; ATSDR 2012]. 

IARC [2012] concluded that “there is sufficient evidence in experimental animals for the 

carcinogencity of chromium (VI) compounds”. 

Based on the current scientific evidence, NIOSH 

recommends including all Cr(VI) compounds 

in the revised REL. There are inadequate data to 

exclude any single Cr(VI) compound from this 

recommendation. 

7.6 Analytical Feasibility

of the REL

Several validated methods can quantify airborne exposures to Cr(VI) in workplace air. 

NIOSH Method 7605, OSHA Method ID-215, 

and international consensus standard analytical methods can quantitatively assess worker exposure to Cr(VI) at the REL of 0.2  μg 

Cr(VI)/m3. The LOD for NIOSH Method 7605 

is 0.02  μg per sample [NIOSH 2003b]. Sampling considerations to ensure accurate workplace Cr(VI) measurements are discussed in 

Chapter 3. 

7.7 Controlling Workplace

Exposures 

Elimination of and substitution for Cr(VI) 

compounds, and the use of good work practices and engineering controls, should be the 
Hexavalent Chromium 87

7 ■ Recommendations for an Exposure Limit

highest priorities for controlling Cr(VI) exposures. Control techniques such as source 

enclosure (i.e., isolating the generation source 

from the worker) and LEV systems are the 

preferred methods for preventing worker exposure to airborne hazards. OSHA determined 

that the primary engineering control measures 

most likely to be effective in reducing worker 

exposure to airborne Cr(VI) are LEV, process 

enclosure, process modification, and improving general dilution ventilation  [71 Fed. Reg. 

10099 (2006)]. Section 8.3 provides additional 

information and recommendations for exposure control measures.

The NIOSH REL is a health-based recommendation. Additional considerations include 

analytical feasibility and the achievability of 

engineering controls. Based on a qualitative assessment of workplace exposure data, NIOSH 

acknowledges Cr(VI) exposures below the REL 

can be achieved in some workplaces using existing technologies, but exposures are more difficult to control in other workplaces. Some operations, including hard chromium electroplating, 

chromate-paint spray application, atomizedalloy spray-coating, and welding may have difficulty in consistently achieving exposures at 

or below the REL by means of work practices 

and engineering controls (see Table 2–7) [Blade 

et al. 2007]. The extensive industry analysis of 

workplace exposures conducted for the OSHA 

rule-making process supports the NIOSH assessment that the REL is achievable in some 

workplaces but difficult to achieve in others 

(see Table 2–8) [71 Fed. Reg. 10099 (2006)]. The 

Cr(VI) REL is intended to promote the proper 

use of existing control technologies and encourage the development of new control technologies where needed to control workplace Cr(VI) 

exposures. The consistent and proper use of 

control technologies will continue to reduce 

workplace Cr(VI) exposures. 

NIOSH acknowledges that the frequent use of 

PPE, including respirators, may be required 

by some workers in environments where airborne Cr(VI) concentrations cannot be controlled below the REL in spite of implementing 

all other possible measures in the hierarchy of 

controls. The frequent use of PPE may be required during job tasks for which (1) routinely 

high airborne concentrations of Cr(VI) exist, 

(2) the airborne concentration of Cr(VI) is unknown or unpredictable, and (3) job tasks are associated with highly variable airborne concentrations because of environmental conditions or the 

manner in which the job task is performed. 

7.8 Preventing Dermal

Exposure 

NIOSH recommends that dermal exposure to 

Cr(VI) be prevented by elimination or substitution of Cr(VI) compounds. When this is not 

possible, appropriate sanitation and hygiene 

procedures and appropriate PPE should be 

used (see Chapter 8). Preventing dermal exposure is important to reduce the risk of adverse 

dermal health effects, including dermal irritation, ulcers, skin sensitization, and allergic 

contact dermatitis. The prevention of dermal 

exposure to Cr(VI) compounds is critical in 

preventing skin disorders related to Cr(VI).

7.9 Summary

NIOSH determined that the data of Gibb et 

al. [2000b] is the most comprehensive data set 

available for assessing the health risk of occupational exposure to Cr(VI), including an 

extensive exposure assessment database and 

smoking information on workers. The revised 

REL is a health-based recommendation derived 

from the results of the NIOSH quantitative risk 

assessment conducted on these human health 

effects data [Park et al. 2004]. Other considerations include analytical feasibility and the 

achievability of engineering controls.
88 Hexavalent Chromium

7 ■ Recommendations for an Exposure Limit

NIOSH recommends a REL of 0.2 μg Cr(VI)/

m3 for an 8-hr TWA exposure within a 40-hr 

workweek, for all airborne Cr(VI) compounds. 

The REL is intended to reduce workers’ risk 

of lung cancer over a 45-year working lifetime. The excess risk of lung cancer death at 

the revised REL is approximately 1 per 1,000 

workers. NIOSH has used this risk level in 

other authoritative recommendations in criteria documents and peer-reviewed risk assessments. Results from epidemiologic and toxicologic studies provide the scientific evidence to 

classify all Cr(VI) compounds as occupational 

carcinogens and support the recommendation 

of having one REL for all Cr(VI) compounds 

[NIOSH 1988b, 2002, 2005a,b].

Exposure to Cr(VI) compounds should be 

eliminated from the workplace where possible because of the carcinogenic potential of 

these compounds. Where possible, less-toxic 

compounds should be substituted for Cr(VI) 

compounds. Where elimination or substitution 

of Cr(VI) compounds is not possible, attempts 

should be made to control workplace exposures 

below the REL. Compliance with the REL for 

Cr(VI) compounds is currently achievable in 

some industries and for some job tasks. It may 

be difficult to achieve the REL during certain 

job tasks including welding, electroplating, 

spray painting, and atomized-alloy spray-coating operations. Where airborne exposures to 

Cr(VI) cannot be reduced to the REL through 

using state-of-the-art engineering controls and 

work practices, the use of respiratory protection will be needed. 

The REL may not be sufficiently protective 

to prevent all occurrences of lung cancer and 

other adverse health effects among workers 

exposed for a working lifetime. NIOSH therefore recommends that worker exposures be 

maintained as far below the REL as achievable 

during each work shift. NIOSH also recommends that a comprehensive safety and health 

program be implemented that includes worker 

education and training, exposure monitoring, 

and medical monitoring.

In addition to controlling airborne exposures 

at the REL, NIOSH recommends that dermal 

exposures to Cr(VI) compounds be prevented 

to reduce the risk of adverse dermal health effects, including dermal irritation, ulcers, skin 

sensitization, and allergic contact dermatitis. 
Hexavalent Chromium 89

8 Risk Management

NIOSH recommends the following guidelines 

to minimize worker exposure to hexavalent 

chromium (Cr[VI]) compounds. Adherence 

to these recommendations should decrease 

the risk of lung cancer in workers exposed to 

Cr(VI) compounds. It is expected that reducing airborne workplace exposures will also reduce the nonmalignant respiratory effects of 

Cr(VI) compounds, including irritated, ulcerated, or perforated nasal septa and other potential adverse health effects. Although workplaces in which workers are exposed to Cr(VI) 

levels above the recommended exposure limit 

(REL) warrant particular concern and attention, all workplaces should attempt to decrease 

worker exposures to Cr(VI) compounds to the 

lowest level that is reasonably achievable in order to minimize adverse health effects, including lung cancer, in workers. The following recommendations should be incorporated into a 

comprehensive safety and health plan in each 

workplace in which workers manufacture, use, 

handle, or dispose of Cr(VI) compounds, or 

perform any other activity that involves exposure to Cr(VI) compounds. 

In 2006, OSHA amended its standard for occupational exposure to Cr(VI) compounds [71 

Fed. Reg. 10099 (2006)]. The final standard 

separately regulates general industry, construction, and shipyards in order to tailor requirements to the unique circumstances found 

in each of these industry sectors. For a full list 

and explanation of relevant OSHA standards, 

see the OSHA hexavalent chromium topic 

page (http://www.osha.gov/SLTC/hexavalentchromium/index.html).

8.1 NIOSH Recommended 

Exposure Limit

8.1.1 The NIOSH REL 

NIOSH recommends that airborne exposure to 

all Cr(VI) compounds be limited to a concentration of 0.2 μg Cr(VI)/m3

 for an 8-hr TWA 

exposure during a 40-hr workweek. The use 

of NIOSH Method 7605 (or validated equivalents) is recommended for Cr(VI) determination. The REL represents the upper limit of exposure for each worker during each work shift. 

Because of the residual risk of lung cancer at 

the REL, NIOSH further recommends that all 

reasonable efforts be made to reduce exposures 

to Cr(VI) compounds below the REL. The 

available scientific evidence supports the inclusion of all Cr(VI) compounds into this recommendation. The REL is intended to reduce 

workers’ risk of lung cancer associated with 

occupational exposure to Cr(VI) compounds 

over a 45-year working lifetime. It is expected 

that reducing airborne workplace exposures 

will also reduce the nonmalignant respiratory 

effects of Cr(VI) compounds, including irritated, ulcerated, or perforated nasal septa and 

other potential adverse health effects.

In addition to limiting airborne concentrations of Cr(VI) compounds, NIOSH recommends that dermal exposure to Cr(VI) be 

prevented in the workplace to reduce the risk 

of adverse dermal health effects, including 

irritation, ulcers, allergic contact dermatitis, 

and skin sensitization. 
90 Hexavalent Chromium

8 ■ Risk Management

8.1.2 Sampling and Analytical Methods

The sampling and analysis of Cr(VI) in workplace air should be performed using precise, accurate, sensitive, and validated methods. The use 

of NIOSH Method 7605 (or validated equivalents) is recommended for Cr(VI) determination in the laboratory. Other standardized methods for Cr(VI) analysis include OSHA Method 

ID-215 [OSHA 1998, 2006], ASTM Method 

D6832-02 [ASTM 2002], and ISO Method 16740 

[ISO 2005]. More detailed discussion of sampling 

and analytical methods for Cr(VI) is provided 

in Chapter 3, “Measurement of Exposure.” 

8.2 Informing Workers

about the Hazard

8.2.1 Safety and Health Programs 

Employers should establish a comprehensive 

safety and health training program for all 

workers who manufacture, use, handle, or 

dispose of Cr(VI) compounds, or perform 

any other activity that involves exposure to 

Cr(VI) compounds. This program should include training on workplace hazards, monitoring of airborne Cr(VI) levels, and medical 

surveillance of employees exposed to Cr(VI). 

Workers should receive training as mandated 

by the revised OSHA Hazard Communication 

Standard (HCS, 29 CFR 1910.1200). OSHA 

revised the HCS to align with the United Nations’ Globally Harmonized System of Classification and Labeling of Chemicals (GHS). 

Employers should be aware of the changes, 

requirements, phase-in dates, and compliance effective dates of the revised HCS. 

Workers should be trained on the new label 

elements (pictograms, signal words, hazard 

statements, and precautionary statements) 

and Safety Data Sheet (SDS) format. 

Worker training should include information 

about the following: the Cr(VI) compounds 

to which they are exposed; the physical and 

chemical properties of these compounds; 

explanation of material safety data sheets 

(MSDSs), SDSs, and label elements; appropriate routine and emergency handling procedures; and recognition of the adverse health 

effects of Cr(VI) exposure. Training should be 

provided about the industrial hygiene hierarchy of controls, how to implement controls to 

prevent and reduce exposures, and the appropriate use, maintenance, and storage of PPE to 

minimize Cr(VI) exposure. Workers should 

be trained to report promptly to their supervisor any leaks observed, failures of equipment 

or procedures, wet or dry spills, cases of gross 

contact, and instances of suspected overexposure to Cr(VI) compounds. 

Employees should be trained to report to their 

supervisor or the director of the medical monitoring program any symptoms or illnesses associated with Cr(VI) exposure and any workplace events involving accidental or incidental 

exposures to Cr(VI) compounds. A medical 

monitoring program should be in place for 

workers exposed to Cr(VI) compounds in the 

workplace (see Section 8.6). 

Safety and health programs should also include workers involved in cleaning, repair, 

and maintenance procedures that may involve 

exposure to Cr(VI) compounds. When possible, these duties should be performed when 

the work area or facility is not in operation to 

minimize these workers’ airborne and dermal 

Cr(VI) exposures. 

8.2.2 Labeling and Posting

Receptacles containing Cr(VI) compounds 

used or stored in the workplace should carry 

a permanently attached label that is readily 

visible. The label should identify Cr(VI) compounds and provide information about their 

adverse health effects, including cancer, and 

appropriate emergency procedures. Labels 
Hexavalent Chromium 91

8 ■ Risk Management

should meet the requirements of the revised 

OSHA HCS (29 CFR 1910.1200).

Signs containing information about the health 

effects of Cr(VI) compounds should be posted 

at the entrances to work areas or building enclosures and in visible locations throughout the work 

areas where there is a potential for exposure to 

Cr(VI) compounds. Because Cr(VI) compounds 

are carcinogenic, the following warning sign, 

or a sign containing comparable information 

that is consistent with the workplace hazard 

communication program, should be posted:

DANGER; CHROMIUM(VI); MAY CAUSE 

CANCER; CAN DAMAGE SKIN, EYES, 

NASAL PASSAGES, AND LUNGS; 

AUTHORIZED PERSONNEL ONLY

In areas where respirators and/or chemical 

protective clothing are needed, the following 

statement should be added:

RESPIRATORY PROTECTION AND 

CHEMICAL PROTECTIVE CLOTHING 

REQUIRED IN THIS AREA

Information about emergency first-aid procedures and the locations of emergency showers and eyewash fountains should be provided 

where needed.

All signs should be printed both in English and 

in the language(s) of non-English-speaking 

workers. All workers who are unable to read 

should receive oral instruction on the content 

and instructions on any written signs. Signs 

using universal safety symbols should be used 

wherever possible.

8.3 Exposure Control 

Measures

Many exposure control measures are used to 

protect workers from potentially harmful exposures to hazardous workplace chemical, 

physical, or biological agents. These control 

measures include, in order of priority: elimination, substitution, engineering controls, administrative controls and appropriate work 

practices, and the use of protective clothing 

and equipment [NIOSH 1983b]. The occupational exposure routes of primary concern for 

Cr(VI) compounds are the inhalation of airborne Cr(VI) and direct skin contact. This section provides information on general exposure 

control measures that can be used in many 

workplaces and specific control measures for 

controlling Cr(VI) exposures that are effective 

in some workplaces.

8.3.1 Elimination and Substitution 

Elimination of a hazard from the workplace 

is the most effective control to protect worker 

health. Elimination may be difficult to implement in an existing process; it may be easier to 

implement during the design or re-design of a 

product or process.

If elimination is not possible, substitution is 

the next choice of control to protect worker 

health. Using substitution as a control measure 

may include substitution of equipment, materials, or less hazardous processes. Equipment 

substitution is the most common type of substitution [AIHA 2011; NIOSH 1973b]. It is often less costly than process substitution, and it 

may be easier than finding a suitable substitute 

material. An example that applies to Cr(VI) exposure reduction is the substitution of an enclosed and automated spray paint booth for a 

partially enclosed workstation. 

Material substitution is the second most common type of substitution after equipment substitution. It has been used to improve the safety 

of a process or lower the intrinsic toxicity of 

the material being used. However, evaluation 

of the potential adverse health effects of the 

substitute material is essential to ensure that 

one hazard is not replaced with a different one 

[AIHA 2011; NIOSH 1973b]. 
92 Hexavalent Chromium

8 ■ Risk Management

Blade et al. [2007] reported material substitution in some processes with potential worker 

exposures to Cr(VI) compounds investigated 

by NIOSH between 1999 and 2001. A reduction in the use of chromate-containing paints 

was reported in construction  (i.e., bridge repainting) and vehicle manufacturing (i.e., the 

manufacture of automobiles and most trucks 

reportedly no longer uses chromate paints). 

However, chromate-containing paints reportedly remained without satisfactory substitute in aircraft manufacture and refurbishing. 

Chromium electroplating industry representatives also reported steady demand for hard 

chrome finishes for mechanical parts such as 

gears, molds, etc., because of a lack of economical alternatives for this durable finish.

Many examples of process substitution have 

been considered. A change from an intermittent or batch-type process to a continuous-type 

process often reduces the potential hazard, particularly if the latter process is more automated  [AIHA 2011; NIOSH 1973b; Soule  1978]. 

Dipping objects into a coating material, such 

as paint, usually causes less airborne material 

and is less of an inhalation hazard than spraying the material. 

Reducing the Cr(VI) Content of Portland Cement. One example of substitution is using 

Portland cement with a reduced Cr(VI) content to reduce workers’ risk of skin sensitization. The trace amount of Cr(VI) in cement 

can cause allergic contact dermatitis that can 

be debilitating and marked by significant, 

long-term adverse effects [NIOSH 2005a]. The 

chromium in cement can originate from a variety of sources, including raw materials, fuel, 

refractory brick, grinding media, and additions 

[Hills and Johansen 2007]. The manufacturing 

process, including the kiln conditions, determines how much Cr(VI) forms. The Cr(VI) 

content of cement can be lowered by using 

materials with lower chromium content during production and/or by adding agents that 

reduce Cr(VI). The use of slag, in place of or 

blended with clinker, may decrease the Cr(VI) 

content [Goh and Gan 1996; OSHA 2008]. Ferrous sulfate is the material most often added to 

cement to reduce its Cr(VI) content. 

Since 2005, the European Union has restricted cement and cement-containing products 

with potential skin contact to a limit of 2 ppm 

soluble Cr(VI) [European Parliament and the 

Council of the European Union 2003]. Reducing the Cr(VI) content of cement has resulted 

in a reported decrease in the number of cases 

of allergic contact dermatitis [Avnstorp 1989; 

Geier et al. 2010; Roto et al. 1996]. Limiting the 

Cr(VI) content of cement in the United States 

warrants consideration. Further research on 

the potential impacts of this change in U.S. industry is needed. 

8.3.2 Engineering Controls

If elimination or substitution are not possible, 

engineering controls are the next choice for reducing worker exposure to Cr(VI) compounds. 

These controls should be considered when new 

facilities are being designed or when existing 

facilities are being renovated to maximize their 

effectiveness, efficiency, and economy. Engineering measures to control potentially hazardous workplace exposures to Cr(VI) compounds 

include isolation and ventilation. OSHA determined that the primary engineering control 

measures most likely to be effective in reducing employee exposure to airborne Cr(VI) are 

local exhaust ventilation (LEV), process enclosure, process modification, and improved general dilution ventilation  [71 Fed. Reg. 10099 

(2006)]. These and other engineering controls 

are described in the following sections.

8.3.2.1 Isolation 

Isolation as an engineering control may involve the erection of a physical barrier between 

the worker and the hazard. Isolation may also 
Hexavalent Chromium 93

8 ■ Risk Management

be achieved by the appropriate use of distance 

or time [Soule 1978]. Examples of hazard isolation include the isolation of potentially hazardous materials into separate structures, rooms, 

or cabinets; and the isolation of potentially 

hazardous process equipment into dedicated 

areas or rooms that are separate from other 

work areas [AIHA 2011; NIOSH 1973b]. Separate ventilation of the isolated area(s) may be 

needed to maintain the isolation of the hazard 

from the rest of the facility [Soule 1978]. Complete isolation of an entire process also may be 

achieved using automated, remote operation 

methods [AIHA 2011; NIOSH 1973b]. 

An example of an isolation technique to control Cr(VI) exposure is the use of a separate, 

ventilated mixing room for mixing batches 

of powdered materials containing chromate 

pigments.

8.3.2.2 Ventilation 

Ventilation may be defined as the strategic use 

of airflow to control the environment within 

a space—to provide thermal control within 

the space, remove an air contaminant near its 

source of release into the space, or dilute the 

concentration of an air contaminant to an acceptable level [Soule 1978]. When controlling 

a workplace air contaminant such as Cr(VI), a 

specific dedicated exhaust ventilation system 

or assembly might need to be designed for the 

task or process [AIHA 2011; NIOSH 1973b].

Local exhaust ventilation (LEV) is primarily 

intended to capture the contaminant at specific points of release into the workroom air 

through using exhaust hoods, enclosures, or 

similar assemblies. LEV is appropriate for the 

control of stationary point sources of contaminant release. It is important to assure proper 

selection, maintenance, placement, and operation of LEV systems to ensure their effectiveness [ACGIH 2010].

General ventilation, often called dilution ventilation, is primarily intended to dilute the concentration of the contaminant within the 

general workroom air. It controls widespread 

problems such as generalized or mobile emission 

sources [AIHA 2011; NIOSH 1973b]. Whenever 

practicable, point-source emissions are most effectively controlled by LEV, which is designed 

to remove the contaminant at the source before it emanates throughout the workspace. 

Dilution ventilation is less effective because it 

merely reduces the concentration of the contaminant after it enters the workroom air, rather than preventing much of the emitted contaminant from ever entering the workroom air. 

It also is much less efficient, requiring much 

greater volumetric airflow to reduce concentrations. However, for non-point sources of 

contaminant emission, dilution ventilation 

may be necessary to reduce exposures.

The air exhausted by a LEV system must be replaced, and the replacement air will usually be 

supplied by a make-up air system that is not associated with any particular exhaust inlet and/

or by simple infiltration through building openings (relying on infiltration for make-up air is 

not recommended). This supply of replacement 

air will provide general ventilation to the space 

even if all the exhaust is considered local. The 

designation of a particular ventilation system 

or assembly as local or general, exhaust or supply, is governed by the primary intent of the design [AIHA 2011; NIOSH 1973b]. 

Push-pull ventilation may be used to control 

exposures from open surface tanks such as electroplating tanks. Push-pull ventilation includes 

a push jet located on one side of a tank and a 

lateral exhaust hood on the other side [ACGIH 

2010]. The jet formed over the tank surface captures the emissions and carries them into the 

hood. Many other types of ventilation systems 

may be used to control exposures in specific 

workplace operations [ACGIH 2010].
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8 ■ Risk Management

8.3.2.3 Examples of engineering controls 

to reduce Cr(VI) exposures

Many types of engineering controls have been 

used to reduce workplace Cr(VI) exposures. 

Some of the engineering controls recommended by NIOSH in 1975 [NIOSH 1975a] are still 

valid and in use today. Some examples are included here, there are many others [ACGIH 

2010; AIHA 2011]. 

Closed systems and operations can be used for 

many processes, but it should be ensured that 

seals, joints, covers, and similar assemblies fit 

properly to maintain negative static pressure 

within the closed equipment, relative to the 

surroundings.

The use of LEV may be needed even with 

closed systems to prevent workers’ exposures 

during operations such as unloading, charging, 

and packaging. The use of protective clothing 

and equipment may also be needed. Ventilation systems should be regularly inspected and 

maintained to assure effective operation. Work 

practices that may obstruct or interfere with 

ventilation effectiveness must be avoided. Any 

modifications or additions to the ventilation 

system should be evaluated by a qualified professional to ensure that the system is operating 

at design specifications. 

The use of clean areas, such as control rooms 

supplied with uncontaminated air, is one 

method of isolating the workers from the hazard. An area to which workers may retreat for 

periods of time when they are not needed at 

the process equipment also may be configured 

as a clean area.

The most difficult exposures to control often 

are those of repair and maintenance workers 

who may be working in emergency conditions 

in close contact with contaminated equipment 

or surfaces. Their exposures may be variable 

in nature and irregular in frequency. Controls 

such as LEV should be used where practicable, 

but the use of PPE may be required when the 

use of engineering controls is not feasible or as 

effective as necessary.

From 1999 through 2001, NIOSH conducted 

field surveys in 21  workplaces across a variety of industrial operations and industry sectors with potential worker exposures to Cr(VI) 

compounds [Blade et al. 2007]. Many of the observed processes and equipment applications 

were typical of those throughout industry, such 

as dip tanks, paint booths, and grinding, sanding, and welding operations. The application 

of general or specialized engineering controls 

were observed or recommended to control exposures in these operations. 

The following are examples of industry processes or job tasks where different types of engineering control measures can be applied to 

reduce Cr(VI) exposures. The exposure data 

from these NIOSH field surveys is presented in 

Tables 2–4 through 2–7 (see Chapter 2).

Chromium electroplating. A combination of 

engineering measures may be needed to effectively control potential exposures during 

chromium electroplating processes, including 

hard chrome plating. Hard chrome is a relatively thick coating of chromium that provides 

an extremely durable, wear-resistant surface 

for mechanical parts. At one facility studied by 

NIOSH, push-pull ventilation systems, polyethylene tarpaulins, and a foam-blanket mistsuppressant product were used, but workers’ 

exposures still exceeded the existing NIOSH 

REL of 1  μg Cr(VI)/m3 [Blade et al. 2007]. 

Qualitative airflow visualization using smoke 

tubes suggested that the push-pull ventilation 

systems were generally effective in moving air 

away from workers’ breathing zones. However, maintenance problems with the ventilation system suggested that the system was not 

always operating effectively. Floating plastic 

balls had reportedly been used in the past but 

proved impractical. Mist suppressants that 
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reduce surface tension were not used because 

of concerns that they may induce pitting in the 

hard chrome-plated finish. 

In contrast with hard chrome plating tanks, 

control of bright chrome plating tank emissions is less problematic. Bright chrome plating provides a thin chromium coating for 

appearance and corrosion protection to nonmechanical parts. The use of a wetting agent 

as a fume suppressant that reduces surface 

tension provided effective control of emissions [Blade et al. 2007]. 

At another facility, a hard chrome-plating tank 

was equipped with a layer of a newly developed, proprietary viscous liquid and a system 

to circulate it [Blade et al. 2007]. This system 

effectively reduced mist emission containing 

Cr(VI) from the tank, but it was not durable.

Welding and thermal cutting involving chromium-containing metals. Many welding task 

variables affect the Cr(VI) content of welding fume and the associated Cr(VI) exposures. Both the base metal of the parts being 

joined and the consumable metal (welding rod 

or wire) added to create the joint have varying compositions of chromium. The welding 

process and shield-gas type, and the Cr content of both the consumable material and the 

base metal  affect the Cr(VI) content of the 

fume [Keane et al.  2009; Heung et al.  2007; 

EPRI  2009; Meeker et al.  2010]. When possible, process and material substitution may 

be effective in reducing welding Cr(VI) exposures. Evaluation of an exposure database from 

The Welding Institute indicated that welding of 

stainless steel or Inconel (a nickel-chromium 

alloy containing 14–23% Cr[VI]) resulted in 

median Cr(VI) exposures of 0.6  μg/m3 compared with the Cr(VI) exposures of the welding of other metals, which were less than the 

LOD (range 0.1–0.2  μg/m3) [Meeker et al. 

2010]. Processes such as gas-tungsten arc welding  (GTAW), submerged arc welding  (SAW), 

and gas-metal arc welding  (GMAW) tend to 

generate less fume [Fiore  2006]. Whenever 

appropriate, the selection of GTAW will help 

to minimize Cr(VI) exposures in welding 

fume  [EPRI  2009]. Cr(VI) exposures during 

shielded-metal arc welding  (SMAW) may be 

minimized by using consumables  (welding 

rod or wire) containing low chromium content (i.e., less than 3% Cr) [EPRI 2009].

Welding or thermal-cutting fumes containing 

Cr(VI) are often controlled using LEV systems 

[Blade et al. 2007]. Two common LEV systems 

are high-volume low-vacuum systems or lowvolume high vacuum systems. High-volume 

low-vacuum systems have large-diameter hoses or ducts that result in larger capture distances [Fiore 2006]. High-vacuum low-volume systems use smaller hoses and so have a smaller 

capture distance; they are often more portable 

[Fiore 2006]. In controlled welding trials, the 

use of a portable high-vacuum fume extraction 

unit reduced Cr(VI) exposures from a median 

of 1.93 μg/m3 to 0.62 μg/m3 (P = 0.02) [Meeker 

et al. 2010]. 

When welding outdoors, the effect of the wind 

and the position of the welder are important 

factors controlling the effectiveness of LEV 

[NIOSH 1997]. In the field setting LEV effectiveness is directly related to proper usage 

[Meeker et al. 2010]. Proper positioning of the 

ventilation inlet relative to the welding nozzle 

and the worker’s breathing zone is critical 

to exposure-control performance; this often 

requires frequent repositioning by the welder  [Fiore  2006]. Welders may keep the LEV 

inlet too far from the weld site to be effective, 

or they may be reluctant to use the LEV system 

because of concerns that the incoming ventilation air could adversely affect the weld quality by impairing flux or shield-gas effectiveness [EPRI 2009; Fiore 2006; Meeker et al. 2010]. 

Specialized systems called “fume extraction 

welding guns” can be used in many workplaces 
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(e.g., outdoors) to reduce worker exposure to 

welding fumes. These systems combine the 

arc-welding gun with a series of small LEV air 

inlets so that the air inlets are always at a close 

distance to the welding arc. These systems are 

heavier and more cumbersome than standard 

arc-welding guns, so ergonomic issues must be 

considered [Fiore 2006].

Spray application of chromate-containing paints. 

Blade et al. [2007] determined that the most effective measure for reducing workers’ Cr(VI) 

exposures at a facility where chromate-containing paints were applied to aircraft parts 

would be the substitution of paints with lower 

chromate content  (i.e., 1% to 5%) for those 

with higher content (i.e., 30%) wherever possible [Blade et al. 2007]. Results indicated that 

partially enclosed paint booths for large-part 

painting might not provide adequate contaminant capture. The facility also used fully 

enclosed paint booths with single-pass ventilation, with air entering one end and exhausted 

from the other. The average internal air velocities within these booths needed to exceed the 

speed with which the workers walked while 

spraying paint so that the plume of paint overspray moved away from the workers. 

Removal of chromate-containing paints. At a 

construction site where a bridge was to be repainted, the removal of the existing chromatecontaining paint was accomplished by abrasive 

blasting. An enclosure of plastic sheeting was 

constructed to contain the spent abrasive and 

paint residue and prevent its release into the surrounding environment [Blade et al. 2007]. No 

mechanical ventilation was provided to the containment structure. NIOSH recommended that 

this type of containment structure be equipped 

with general-dilution exhaust ventilation that 

discharges the exhausted air through a highefficiency particulate air (HEPA) filtration unit.

Other types of specialized engineering measures applicable for the control of exposures 

during chromate-paint removal have been investigated and recommended for selected applications.  These recommendations are often 

made in the context of lead exposure control 

[OSHA 1999b], but they are relevant to Cr(VI) 

control because lead chromate paints may be 

encountered during paint removal projects. 

Such control measures include high-pressure 

water blasting, wet-abrasive blasting, vacuum 

blasting, and the use of remotely controlled 

automated blasting devices [Meeker et al. 

2010].  High-pressure water blasting uses a 

blast of extremely focused water at high velocity to remove paint and corrosion, but it does 

not reprofile the underlying metal substrate for 

repainting. Wet-abrasive blasting uses a conventional blasting medium that is wetted with 

water to remove the paint and corrosion and to 

reprofile the metal. The wetted medium helps 

suppress the emission of dust that contains removed chromate-paint particles. Vacuum blasting uses a blasting nozzle surrounded by a vacuum shroud with a brush-like interfacing surface 

around  its opening, which  the operator keeps 

in contact with the metal surface being blasted. Large reductions in exposures have been 

reported with this system, but considerations 

include the following: good work practices are 

needed to assure proper contact with the surface is maintained; the full assembly is heavier 

than conventional nozzles and thus raises ergonomic concerns; and production (removal) 

rates reportedly are much lower than with conventional blast nozzles [Meeker et al. 2010].

Mixing of chromate-containing pigments. At a 

colored-glass manufacturing facility, pigments 

containing Cr(VI) were weighed in a separate 

room with LEV, then moved to a production 

area for mixing into batches of materials [Blade 

et al. 2007]. Cr(VI) exposures at the facility 

were very low to not detectable. 

At a screen printing ink manufacturing facility, there was no dedicated pigment-mixing 

room; LEV was used at the ink-batch mixing 
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and weighing operation, but capture velocities 

were inadequate [Blade et al. 2007]. Almost all 

the Cr(VI) exposures of the ink-batch weighers exceeded the existing REL. 

Operations creating concrete dust. Portland cement contains Cr(VI), so operations that create concrete dust have the potential to expose 

workers to Cr(VI). In one operation studied by 

NIOSH, the use of water to suppress dust during cleanup was observed to result in visibly 

lower dust concentrations [Blade et al. 2007]. All 

Cr(VI) exposures at the facility were low. At a 

construction-rubble crushing and recycling facility, a water-spray system was used on the crusher 

at various locations, and the operator also used 

a hand-held water hose [Blade et al. 2007]. All 

Cr(VI) exposures at this facility also were low. 

The exposure data from these examples from 

the NIOSH field surveys are presented in Tables 2–4 through 2–7 (see Chapter 2).

8.3.3 Administrative Controls

and Work Practices

Administrative controls are changes in work 

practices and management policies designed 

to minimize exposure times. Appropriate work 

practices include proper techniques to handle 

materials, good personal hygiene and sanitation practices, and good housekeeping in the 

work area. Employers should ensure that water 

and soap are available to promote good hand 

hygiene practices. 

Work areas with potential Cr(VI) exposures 

should have restricted access so that only those 

workers assigned to and trained for the task or 

process are allowed to enter. Workers should 

not be allowed to smoke, eat, or drink in work 

areas where Cr(VI) compounds are used or 

stored. Emergency showers and eye-flushing 

fountains should be provided by the employer 

in areas with the potential for skin or eye contact with Cr(VI). This equipment should be 

properly maintained and inspected regularly. 

If Cr(VI) gets on the skin, the affected area 

must be flushed promptly with large amounts 

of mild soap and running water for at least 

15 minutes. If the eyes are contaminated with 

Cr(VI), they should be flushed immediately for 

at least 15 minutes with a copious flow of water 

and promptly examined by a physician. 

Clean work clothing should be put on before each work shift. The clothing should be 

changed whenever it becomes wetted or grossly contaminated with compounds containing 

Cr(VI). Work clothing should not be worn 

home. Workers should be provided with showering and changing areas free from contamination, where they may store and change into 

street clothes before leaving the worksite. 

Employers should provide services for laundering work clothing so that contaminated 

clothes are not taken home. These precautions 

will protect the worker and people outside the 

workplace, including the worker’s family, from 

being exposed to clothing contaminated with 

Cr(VI). Laundry personnel should be informed 

about the potential hazards of handling contaminated clothing and should be instructed 

about measures to minimize their health risk.

8.3.3.1 Portland cement work practices

Clean water, non-alkaline soap, and clean towels should be available for workers exposed to 

Portland cement [OSHA 2008]. Wet clean-up 

methods (e.g., hose, then squeegee or mop) 

should be used rather than dry sweeping. The 

surfaces of all tools should be cleaned after use. 

Additional recommended work practices for 

preventing dermal exposure to Portland cement are provided by OSHA [2008].

8.3.4 Protective Clothing

and Equipment

The use of protective clothing and PPE is another way to create a physical barrier between 
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the worker and the hazard. It may be appropriate to use different types of protective clothing and PPE, such as chemically impervious 

gloves, clothing, and respirators. Employers 

are responsible for the selection of PPE, training in the proper use of PPE, ensuring the PPE 

is properly used, maintenance of PPE, and providing and paying for all PPE [NIOSH 1999]. 

The use of respirators to control inhalation 

exposures to air contaminants is considered 

a last resort for cases where engineering and 

other measures cannot provide sufficient control. Workers should be trained in the proper 

use, maintenance, and storage of all protective 

clothing worn in the workplace. 

Workers and persons responsible for worker 

health and safety should be informed that protective clothing might interfere with the body’s 

heat dissipation, especially during hot weather 

or in hot work situations. Additional monitoring is required to prevent heat-related illness 

when protective clothing is worn under these 

conditions [NIOSH 1986].

8.3.4.1 Protective clothing and gloves

NIOSH recommends the use of gloves, eye 

protection, and chemical protective clothing (CPC) for workers with potential skin or 

eye contact with Cr(VI) compounds. Dermal 

and mucous membrane contact with Cr(VI) 

compounds should be prevented by full-body 

protective clothing consisting of the following: head, neck, and face protection; coveralls 

or similar protective body clothing; impermeable gloves with gauntlets; and shoes and apron 

where solutions or dry materials containing 

Cr(VI) may be contacted. 

Protective clothing and gloves made from PVC 

or Saranex can be used for an 8-hour exposure, while those made from butyl or Viton 

can be used for a 4-hour exposure [Forsberg 

and Keith 1999]. Although the selection of this 

CPC is based on permeation properties, other 

selection factors, including size, dexterity, cut 

and tear resistance, and glove use with other 

chemicals should be considered. Contaminated CPC, gloves, and shoes should be discarded 

or decontaminated with proper methods before reuse. If Cr(VI) gets on the skin, the affected area must be flushed immediately with 

large amounts of mild soap and running water 

for at least 15 minutes. 

The proper use of protective clothing requires 

that all openings be closed and that all garments fit snugly about the neck, wrists, and 

ankles whenever the wearer is in an exposure 

area. Care must be exercised to keep work 

clothing separate from street clothing to avoid 

contamination. All protective clothing must 

be maintained properly in an uncontaminated 

environment. Protective clothing should be 

inspected before each use and cleaned or replaced regularly. 

Eye protection should be provided by the employer and used by the employees where eye 

contact with Cr(VI) is possible. Selection, use, 

and maintenance of eye protective equipment 

should be in accordance with the provisions of 

the American National Standard Practice for 

Occupational and Educational Eye and Face 

Protection, ANSI Z87.1-1989 [ANSI 1989]. In 

work environments where Cr(VI) levels are 

above the NIOSH REL and respiratory protection is required, NIOSH recommends that 

eye protection be incorporated into PPE by the 

use of tight-fitting full facepiece respirators, or 

tight-fitting half-mask respirators used in conjunction with safety spectacles or goggles. 

See Section 8.3.4.3 for PPE recommendations for workers with dermal contact with 

Portland cement. Further information on 

chemical protective clothing is available on 

the NIOSH Protective Clothing and Ensembles topic page (http://www.cdc.gov/niosh/

topics/protclothing) and in the OSHA Technical Manual, Section VIII, Chapter 1, “Chemical 
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8 ■ Risk Management

Protective Clothing” [OSHA 1999a] (http://

www.osha.gov/dts/osta/otm/otm_viii/otm_

viii_1.html).

8.3.4.2 Respiratory protection 

NIOSH recommends respirator use while performing any task for which the airborne exposure concentration is unknown or has been 

documented to be higher than the NIOSH REL 

of 0.2  μg Cr(VI)/m3 8-hr TWA. Respirators 

should not be used as the primary means of 

controlling worker exposures. Other exposure 

control methods such as elimination, substitution, engineering controls, administrative controls, and changes in work practices should be 

implemented in an attempt to keep exposures 

before the REL before the use of respirators 

is required. However, the use of respirators 

may be necessary when the airborne exposure 

concentration is unknown or when other control measures do not control airborne Cr(VI) 

concentrations to below the REL. NIOSH recognizes this may be a particular challenge in 

electroplating, spray painting, atomized-alloy 

spray-coating operations, some types of welding operations, and other industries or tasks 

with routinely or uncontrollably high Cr(VI) 

exposures. 

When respiratory protection is needed, the 

employer should establish a comprehensive 

respiratory protection program as described in 

the OSHA respiratory protection standard [29 

CFR 1910.134]. Elements of a respiratory protection program, established and described in 

a written plan that is specific to the workplace, 

must include the following:

■ Procedures for selecting respirators.

■ Medical evaluations of employees required 

to wear respirators.

■ Fit-testing procedures.

■ Routine-use procedures and emergency 

respirator use procedures.

■ Procedures and schedules for cleaning, 

disinfecting, storing, inspecting, repairing, 

discarding, and maintaining respirators.

■ When applicable, procedures for ensuring adequate air quality for supplied air 

respirators (respirable air should meet 

the requirements of Compressed Gas Association Specification G-7.1 Grade D or 

higher quality).

■ Training in respiratory hazards.

■ Training in proper use and maintenance 

of respirators.

■ Program evaluation procedures.

■ Procedures for ensuring that workers who 

voluntarily wear respirators (excluding 

filtering-facepiece respirators) comply with 

the medical evaluation and cleaning, storing, and maintenance requirements of the 

standard.

■ A designated program administrator who 

is qualified to administer the respiratory 

protection program.

The written program should be updated as 

necessary to account for changes in the workplace that affect respirator use. All equipment, 

training, and medical evaluations required under the respiratory protection program should 

be provided at no cost to workers.

NIOSH recommends that the selection of respiratory protection follow the guidance in NIOSH 

Respirator Selection Logic [NIOSH 2004]. Table 

8–1 provides respirator selection recommendations for Cr(VI). A comprehensive assessment 

of all workplace exposures should be performed 

to determine the presence of other possible contaminants to ensure that the proper respiratory 

protection is used. 

Further information about respiratory protection is available on the OSHA Respiratory 

Protection topic page (http://www.osha.gov/

SLTC/respiratoryprotection/index.html), the 
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8 ■ Risk Management

NIOSH Respirators topic page (http://www.

cdc.gov/niosh/topics/respirators/), the NIOSH 

Guide to Industrial Respiratory Protection

[NIOSH 1987a], the NIOSH Guide to the Selection and Use of Particulate Respirators Certified 

Under 42 CFR 84 [NIOSH 1996b], and NIOSH 

Respirator Selection Logic [2004].

8.3.4.3 PPE for Portland cement exposure

Employers should provide PPE, including 

gloves, boots, and eye protection for workers 

exposed to Portland cement [OSHA 2008]. 

Butyl or nitrile gloves are often recommended 

for caustic materials such as Portland cement. 

Cotton or leather gloves are not recommended. Employers should consult the cement manufacturer’s MSDS for information about the 

proper gloves to provide. Sturdy, slip-resistant, 

waterproof boots should be provided when 

needed to prevent wet cement from contacting workers’ skin. OSHA [2008] provides additional guidance on preventing skin problems 

from working with Portland cement.

8.4 Emergency Procedures

Emergency plans and procedures should be 

developed for all work areas where there is 

a potential for exposure to Cr(VI). Workers 

should be trained in the effective implementation of these plans and procedures. These plans 

should be reviewed regularly for their effectiveness and updated when warranted because 

of changes in the facility, operating procedures, 

or chemical types or uses. Necessary emergency equipment, including appropriate respiratory protective devices, should be kept in readily accessible locations. Appropriate respirators 

should be available for use during evacuation. 

A full facepiece respirator with a 100-level filter or any appropriate escape-type, self-contained breathing apparatus should be used for 

escape-only situations. If chromyl chloride is 

present, a full facepiece gas mask (14G) with 

canister providing organic vapor (OV) and 

acid gas (AG) protection with a 100-level filter 

or any appropriate escape-type, self-contained 

breathing apparatus should be used for escapeonly situations.

Any spills of Cr(VI) compounds should be 

promptly cleaned up by means that minimize 

the inhalation of, or contact with, the spilled 

material. No dry sweeping should be performed. Wet vacuuming is preferred for spills 

of dry material. Wet spills and flushing of 

wet or dry spills should be channeled for appropriate treatment or collection for disposal. 

They should not be channeled directly into the 

sanitary sewer system. Dry vacuuming is acceptable only if an adequately filtered system 

is used—either a HEPA-filtered system or a 

single-pass externally exhausted system.

8.5 Exposure Monitoring 

Program

The employer should establish a workplace 

program to monitor exposure to airborne 

Cr(VI). The program should include environmental and personal monitoring of airborne 

Cr(VI) exposure concentrations and focus on 

identifying potential exposures and assessing 

the effectiveness of exposure controls. The goal 

of the exposure monitoring program is to ensure a more healthful work environment where 

worker exposures do not exceed the REL. The 

exposure monitoring program should systematically (1) characterize the exposures of all 

workers; (2) identify those workers, processes, 

and tasks with the highest exposures; (3) identify processes or tasks where worker exposures 

exceed the REL; (4) assess the effectiveness of 

engineering controls and work practices; and 

(5) determine the need for PPE use. 

Historically, NIOSH has recommended an action level (AL) with the primary consideration 

of protecting workers from exposures above 

the REL [NIOSH 1975b]. Exposure concentrations measured at or above the AL were 
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8 ■ Risk Management

thought to indicate with a high degree of certainty that exposure concentrations exceeded 

the REL, which triggered additional controls 

and administrative actions to reduce worker 

exposures. Although the term “action level” 

was not used in the 1975 NIOSH Cr(VI) criteria document, occupational exposure to carcinogenic Cr(VI) was defined as “exposure to 

airborne Cr(VI) at concentrations greater than 

one-half of the workplace environmental limit 

for carcinogenic Cr(VI)” [NIOSH 1975a].

NIOSH is re-evaluating its policy of recommending an AL set at one-half the REL. Cr(VI) 

exposures are highly variable within and across 

diverse workplaces. Because of the great range 

and high variability of Cr(VI) exposures across 

workplaces, it is not possible to establish a specific AL for Cr(VI) compounds. Therefore, 

NIOSH is providing general exposure monitoring guidance for workplaces with Cr(VI) 

exposures rather than recommending one specific AL for all Cr(VI) compounds. This will allow each employer to determine a strategy to 

monitor exposure specific to each workplace 

that assures that worker exposures do not exceed the REL.

A strategy to monitor exposure should be 

developed and implemented for each specific process and group of workers exposed 

to Cr(VI) compounds. The details of the plan 

will depend on a number of factors, including 

the number of workers in the group and variability in exposure within the group. Workers’ 

airborne exposures vary from day to day, and 

the daily exposures are typically log normally 

distributed. Exposures in well-controlled processes and environmental conditions vary less 

than in poorly controlled processes and where 

the environmental conditions change considerably, such as outdoors. Greater day-to-day 

variability of 8-hr TWA exposures requires 

that more daily 8-hr exposures be assessed to 

achieve the specified level of confidence in the 

sampling results. 

The strategy to monitor exposure should provide enough information to adequately describe the distribution of workers’ exposures. 

It should include exposure-sampling surveys 

that produce a high degree of confidence that 

workers’ daily 8-hr TWA exposures are maintained below the REL. As part of the initial 

workplace hazard surveillance, the workers, 

tasks, and processes associated with the highest 

Cr(VI) exposures should be identified. A sampling strategy that focuses on these workers 

with the highest perceived exposure concentrations may be more practical than a random 

sampling approach. A focused sampling strategy is most efficient for identifying exposures 

above the REL if maximum-risk workers and 

time periods are accurately identified [NIOSH 

1977; Leidel and Busch 1994]. The exposuresampling survey should be performed by collecting representative personal samples over the 

entire work shift. Whenever possible, personal 

samples should be collected in the breathing 

zone of the worker. Periodic exposure monitoring should be performed at least annually, 

and whenever any major process change takes 

place or there is another reason to suspect that 

exposure concentrations may have changed. All 

workers should be notified of the results of their 

exposure monitoring and of any actions taken to 

reduce their exposure. More detailed information on developing exposure-monitoring plans 

for specific situations is available from NIOSH 

[1977] and the AIHA [2006].

For workers exposed to concentrations of 

Cr(VI) compounds above the REL, an evaluation of existing control measures should be 

conducted to determine if the measures are 

operating as expected. If existing control measures are inadequate, then additional control 

measures should be implemented to reduce 

8-hr TWA exposures to below the REL. After controls are implemented, an exposuresampling survey should be performed that 

can produce a high degree of confidence that 
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daily 8-hr TWA exposures are below the REL 

[NIOSH 1977; Leidel and Busch 1994]. Periodic exposure monitoring of workers should 

continue to ensure that workers’ exposures are 

maintained below the REL. 

NIOSH Method No. 7605 (or validated equivalents) should be used for the collection and 

analysis of airborne Cr(VI) samples in the 

workplace. Area sampling (environmental) 

may be useful to determine sources of airborne 

Cr(VI) exposures and assessing the effectiveness of engineering controls. Important air 

sampling considerations, including the possible reduction of Cr(VI) to Cr(III) during sampling and sample preparation, are presented in 

Section 3.1.2.

The exposure monitoring program should also 

include the assessment and monitoring of potential dermal exposure associated with any 

area, task, or process. Where there is the potential for dermal exposure to Cr(VI) compounds, 

controls should be implemented or administrative actions should be taken (e.g., PPE) to 

reduce potential exposures.

8.6 Medical Monitoring

The employer should establish a medical monitoring program for workers with occupational 

exposure to Cr(VI) compounds, including 

personnel involved with routine or emergency 

repair or maintenance, as specified in Section 

8.6.1 below. Medical monitoring represents 

secondary prevention and should not replace 

the primary prevention efforts mentioned in 

previous sections of this chapter to minimize 

occupational exposure to Cr(VI). The goal of 

a workplace medical monitoring program is 

the early identification of adverse health effects 

that may be related to Cr(VI) exposure, such 

as dermatitis, respiratory irritation, airway obstruction and other local or systemic effects. It 

is hoped that early detection of adverse health 

effects, subsequent treatment, and workplace 

interventions will minimize the adverse health 

effects of Cr(VI) exposure. Medical monitoring data may also be used for the purposes of 

medical surveillance to identify work areas, 

tasks, and processes that require additional 

primary prevention efforts. 

8.6.1 Worker Participation

Workers potentially exposed to Cr(VI) compounds as specified below may benefit by 

being included in an occupational medical 

monitoring program. Workers should be provided with information about the purposes of 

medical monitoring, the health benefits of the 

program, and the procedures involved. When 

possible, employers or the designated program 

director should characterize worker exposures 

to identify potential airborne and/or dermatologic Cr(VI) exposures. The following hierarchy describes workers with airborne Cr(VI) 

exposure who should be included in a medical monitoring program and could receive the 

greatest benefit from medical screening: 

■ Workers, including those using respiratory protective equipment, in workplace 

environments where airborne Cr(VI) concentrations cannot be controlled below the 

REL of 0.2 μg/m3.

■ Workers with unintended but potentially 

high airborne Cr(VI) exposures during situations such as emergencies or PPE failure.

■ Workers exposed to Cr(VI), regardless of 

airborne Cr(VI) concentration, who develop signs, symptoms, or respiratory changes apparently related to Cr(VI) exposure. 

■ Workers exposed to Cr(VI) in their current job who may have been previously 

exposed to asbestos or other respiratory 

hazards that place them at an increased 

risk of respiratory disease.

■ Workers with dermal exposure to Cr(VI) 

compounds.
Hexavalent Chromium 103

8 ■ Risk Management

Workers exposed to Cr(VI) by the dermatologic route (either with or without accompanying airborne Cr[VI] exposure) are at risk of 

adverse health effects such as dermatitis and 

other local effects and should be included in 

a medical monitoring program even if not exposed to Cr(VI) airborne concentrations above 

the REL. These workers may not need to be included in the respiratory effects portion of the 

monitoring program if they have no potential 

risk of airborne Cr(VI) exposure.

8.6.2 Medical Monitoring

Program Director

The employer should assign responsibility for 

the medical monitoring program to a qualified 

physician or other qualified health care provider (as determined by appropriate state laws and 

regulations) who is informed and knowledgeable about the following:

■ Administration and management of a 

medical monitoring program for occupational hazards.

■ Establishment of a respiratory protection 

program, based on an understanding of 

the requirements of the OSHA respiratory protection standard and types of respiratory protection devices available at 

the workplace.

■ Identification and management of occupational skin disease.

■ Identification and management of occupational respiratory effects or illnesses, 

including lung cancer.

8.6.3 Medical Monitoring

Program Elements

Recommended elements of a medical monitoring program for workers exposed to Cr(VI) 

compounds include worker education, a preplacement medical examination, and regularly 

scheduled follow-up medical examinations. 

Based on the findings from these examinations, more frequent and detailed medical examination may be necessary.

8.6.3.1 Worker education

All workers in the medical monitoring program 

should be provided with the purposes of the program, the potential health benefits of participation, and program procedures. Workers should be 

trained in the potential symptoms, findings, and 

diseases associated with Cr(VI) exposure. They 

should also be trained in procedures to avoid and 

minimize their Cr(VI) exposures. They should 

be instructed to report any accidental exposures 

to Cr(VI) or incidents involving potentially high 

exposure levels to their supervisor and the medical director. Workers should inform their health 

care provider about their workplace exposures 

and any possible work-related symptoms. They 

should be instructed to inform their supervisor 

or the medical director of any symptoms consistent with Cr(VI) exposure if the work-relatedness 

of the symptoms is confirmed or suspected by a 

health care provider.

8.6.3.2 Preplacement medical examination

A preplacement examination should be conducted. This examination should consist of a 

core examination and a respiratory examination. The core examination should be conducted on all workers included in the medical 

monitoring program. The respiratory examination should be conducted on all workers 

potentially exposed to Cr(VI) via an airborne 

route, as specified in Section 8.6.1 above. Routine blood and urine analysis is not recommended, as these tests are of uncertain value 

as early indicators of potential health effects 

related to Cr(VI) [NIOSH 2005a].

8.6.3.2.1 Core examination

■ A standardized occupational history questionnaire that gathers information on all 
104 Hexavalent Chromium

8 ■ Risk Management

past jobs, a description of all duties and 

potential exposures for each job, and a 

description of all protective equipment 

the worker has used.

■ A detailed medical history including 

information on conditions such as skin 

sensitization, occupational asthma, and 

other dermatologic or respiratory symptoms or disorders that may be exacerbated by exposure to Cr(VI).

■ A physical examination of all systems 

with careful inspection of the skin for 

evidence of irritation, ulceration, sensitization, or dermatitis, and the mucous 

membranes, and upper respiratory tract 

for evidence of irritation, bleeding, ulcerations, or perforation.

8.6.3.2.2 Respiratory examination

■ A standardized respiratory symptom questionnaire.

■ An evaluation of the worker’s ability to use 

negative or positive pressure respirators.

■ A preplacement or baseline spirometric 

test within 3 months of assignment. Anyone administering spirometric testing 

as part of the medical monitoring program should have completed a NIOSHapproved training course in spirometry 

or other equivalent training.

■ A baseline chest radiograph within 3 

months of assignment.

8.6.3.3 Follow-up medical examinations

All workers in the medical monitoring program should be provided with follow-up medical examinations conducted by a physician or 

other qualified health care provider. The following recommendations are suggested for 

workers in good health. Any worker with adverse health effects potentially associated with 

Cr(VI) exposure should be examined immediately and may require more frequent monitoring and extensive testing. 

8.6.3.3.1 Follow-up examination frequency

Each worker should have a thorough medical 

evaluation of the skin and respiratory tract (upper and lower) conducted every 6 months for 

the first 2 years of employment and annually 

thereafter, unless adverse health effects warrant 

more frequent monitoring. The annual medical examination should be conducted with emphasis on the skin and respiratory tract, and 

an occupational history update questionnaire 

should be completed annually. 

8.6.3.3.2 Follow-up respiratory examination

The follow-up respiratory examinations, conducted as noted above, should include the following. The respiratory symptom questionnaire 

should be updated at the time of examination. 

Spirometric testing should be conducted annually for the first 3 years and every 2 to 3 years 

thereafter, or as indicated by current medical 

recommendations and the scientific literature. 

Based on the findings from these examinations, 

more frequent and detailed medical examination or testing may be necessary. Interpretation 

of annual lung function changes within an individual worker are specified and updated by 

professional organizations, such as the American Thoracic Society (ATS) and the American 

College of Occupational and Environmental Medicine (ACOEM) [ATS 1995; ACOEM 

2011]. Spirometry resources for employers and 

workers are available on the NIOSH Spirometry 

Safety and Health Topic Page (http://www.cdc.

gov/niosh/topics/spirometry/) [NIOSH 2011]. 

The value of periodic chest radiographs in a 

medical surveillance program should be evaluated by a qualified health-care professional, in 

consultation with the worker, based on current medical recommendations and the scientific literature to assess whether the benefits 
Hexavalent Chromium 105

8 ■ Risk Management

of testing warrant the additional exposure to 

radiation. If the qualified health-care professional deems periodic chest radiographs useful, their timing and frequency should take 

into account the observed latency and natural 

history of occupational lung cancer associated 

with Cr(VI), symptoms reported by the worker, and other relevant findings.

Any worker may require more frequent and/or 

more detailed medical evaluation if he or she 

has any of the following indications:

■ A history of exposure to Cr(VI) compounds, asbestos, any other lung carcinogen, or other respiratory hazard.

■ A past or present history of smoking.

■ New or worsening dermatologic or respiratory symptoms.

■ Other medically significant reason(s) for 

more detailed assessment.

8.6.4 Medical Reporting

Following each medical examination, the physician or other qualified health-care provider 

should provide each worker with a written 

report containing the following:

■ The results of any medical tests performed on the worker.

■ A medical opinion in plain language 

about any medical condition that would 

increase the worker’s risk of impairment 

from exposure to Cr(VI) compounds.

■ Recommendations for limiting the worker’s exposure to Cr(VI) compounds including the use of appropriate respiratory 

protective devices or protective clothing.

■ Recommendations for further evaluation 

and treatment of medical conditions detected.

Following each medical examination, the physician should provide a written report to the 

employer that contains the following:

■ Occupationally pertinent results of the 

medical evaluation.

■ A medical opinion about any medical 

condition that would increase the worker’s 

risk of illness or disease as a result of exposure to Cr(VI) compounds.

■ Recommendations for limiting the worker’s exposure to Cr(VI) compounds that 

may include the use of appropriate respiratory protective devices or protective 

clothing or reassignment to another job, 

as warranted.

■ A statement that the worker has been 

informed about the results of the medical examination and about medical 

condition(s) that should have further 

evaluation or treatment.

Specific findings, test results, or diagnoses that 

have no bearing on the worker’s ability to work 

with Cr(VI) compounds should not be included in the report to the employer. Safeguards to 

protect the confidentiality of the worker’s medical records should be enforced in accordance 

with all applicable regulations and guidelines.

8.6.5 Employer Actions

The employer should ensure that the qualified 

health care provider’s recommended restriction of a worker’s exposure to Cr(VI) compounds or other workplace hazards is followed, 

and that the REL for Cr(VI) compounds is not 

exceeded without requiring the use of PPE. Efforts to encourage worker participation in the 

medical monitoring program and to report 

any symptoms promptly to the program director are important to the program’s success. 

Medical evaluations performed as part of the 

medical monitoring program should be provided by the employer at no cost to the participating workers. Where medical removal or job 

reassignment is indicated, the affected worker 

should not suffer loss of wages, benefits, or 

seniority. 
106 Hexavalent Chromium

8 ■ Risk Management

The employer should ensure that the program director regularly collaborates with the 

employer’s safety and health personnel (e.g. 

industrial hygienists) to identify and control 

work exposure and activities that pose a risk of 

adverse health effects.

8.7 Smoking Cessation

Smoking should be prohibited in all areas of 

any workplaces in which workers are exposed 

to Cr(VI) compounds. As cigarette smoking 

is an important cause of lung cancer, NIOSH 

recommends that smoking be prohibited in 

the workplace and all workers who smoke participate in a smoking cessation program. Employers are urged to establish smoking cessation programs that inform workers about the 

hazards of cigarette smoking and provide assistance and encouragement for workers who 

want to quit smoking. These programs should 

be offered at no cost to the participants. Information about the carcinogenic effects of smoking should be disseminated. Activities promoting physical fitness and other health lifestyle 

practices that affect respiratory and overall 

health should be encouraged through training, 

employee assistance programs, and/or health 

education campaigns.

8.8 Record Keeping

Employers should keep employee records on 

exposure and medical monitoring according to 

the requirements of 29 CFR 1910.20(d), Preservation of Records.

Accurate records of all sampling and analysis 

of airborne Cr(VI) conducted in a workplace 

should be maintained by the employer for at 

least 30 years. These records should include the 

name of the worker being monitored; Social 

Security number; duties performed and job 

locations; dates and times of measurements; 

sampling and analytical methods used; type of 

personal protection used; and number, duration, and results of samples taken. 

Accurate records of all medical monitoring 

conducted in a workplace should be maintained by the employer for 30 years beyond the 

employee’s termination of employment.
Hexavalent Chromium 107

8 ■ Risk Management

Table 8–1. Respiratory protection recommendations for exposure to Cr(VI)* compounds 

Airborne Cr(VI) concentration 

or condition of use† Minimum respiratory protection

< 2 μg/m3 (10 x REL) Any half mask particulate air-purifying respirator with a N100‡, R100, or P100 

filter worn in combination with eye protection.

If chromyl chloride is present, any half mask air-purifying respirator with canisters providing organic vapor (OV) and acid gas (AG) protection with a N100, 

R100, or P100 filter worn in combination with eye protection.

< 5 μg/m3 (25 x REL) Any supplied-air respirator with loose-fitting hood or helmet operated in a 

continuous-flow mode; any powered air-purifying respirator (PAPR) with a 

HEPA filter with loose-fitting hood or helmet.

If chromyl chloride is present, any PAPR providing OV and AG protection with a HEPA filter with loose-fitting hood or helmet.

< 10 μg/m3 (50 x REL) Any full facepiece particulate air-purifying respirator with a N100, R100, or 

P100 filter; any PAPR with full facepiece and HEPA filter; any full facepiece 

supplied-air respirator operated in a continuous-flow mode.

If chromyl chloride is present, any full facepiece air-purifying respirator providing OV and AG protection with a N100, R100, or P100 filter; any full facepiece PAPR providing OV and AG protection and a HEPA filter.

< 400 μg/m3 (2,000 x REL) Any supplied-air, pressure-demand respirator with full facepiece.

< 2000 μg/m3 (10,000 x REL) Any self-contained breathing apparatus that is operated in a pressure-demand 

or other positive-pressure mode, or any supplied-air respirator with a full facepiece that is operated in a pressure-demand or other positive-pressure mode 

in combination with an auxiliary self-contained positive-pressure breathing 

apparatus.

> 2000 μg/m3 §

Escape only

Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode.

Any air-purifying, full-facepiece respirator with a N100, R100, or P100 filter or 

any appropriate escape-type, self-contained breathing apparatus. 

If chromyl chloride is present, any full facepiece gas mask (14G) with a canister providing OV and AG protection with a N100, R100, or P100 filter or any 

appropriate escape-type, self-contained breathing apparatus.

*Abbreviations: AG= acid gas; APF = assigned protection factor; Cr(VI) = hexavalent chromium; HEPA = high efficiency particulate 

air; IDLH = immediately dangerous to life or health; OV=organic vapor; PAPR = powered air-purifying respirator. †

The protection offered by a given respirator is contingent upon (1) the respirator user adhering to complete program requirements 

(such as those required by OSHA in 29 CFR 1910.134), (2) the use of NIOSH-certified respirators in their approved configuration, 

and (3) individual fit testing to rule out those respirators with tight-fitting facepieces that cannot achieve a good fit on individual 

workers. ‡

N-100 series particulate filters should not be used in environments where there is potential for exposure to oil mists.

§

Immediately Dangerous to Life or Health (IDLH) value for chromic acid and chromates = 15 mg/m3.

Hexavalent Chromium 109

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Xie H, Holmes AL, Wise SS, Gordon N, Wise JP Sr. 

[2004]. Lead chromate-induced chromosome damage 

requires extracellular dissolution to liberate chromium 

ions but does not require particle internalization or intracellular dissolution. Chem Res Toxicol 17(10):1362–

1367. 
Hexavalent Chromium 125

References

Xie H, Holmes AL, Wise SS, Huang S, Peng C, Wise JP 

Sr. [2007]. Neoplastic transformation of human bronchial cells by lead chromate particles. Am J Resp Cell 

Mol Bio 37(5):544–552. 

Xie H, Wise SS, and Wise JP Sr. [2008]. Deficient repair 

of particulate chromate-induced DNA double strand 

breaks leads to neoplastic transformation. Mut Res 

649:230–238.

Xie H, Holmes AL, Young JL, Qin Q, Joyce K, Pelsue SC, Peng C, Wise SS, Jeevarajan A, Wallace WT, 

Hammond D, Wise JP Sr. [2009]. Zinc chromate induces chromosome instability and DNA double strand 

breaks in human lung cells. Toxicol App Pharmacol 

234(3):293–299.

Ye J, Shi X [2001]. Gene expression profile in response 

to chromium induced cell stress in A549 cells. Mol Cell 

Biochem 222(1–2):189–197.

Ye J, Wang S, Leonard SS, Sun Y, Butterworth L, Antonini J, Ding M, Rojanasakul Y, Vallyathan V, Castranova 

V, Shi X [1999]. Role of reactive oxygen species and 

p53 in chromium(VI)-induced apoptosis. J Biol Chem 

274(49):34974–34980.

Zhang Z, Leonard SS, Wang S, Vallyathan V, Castranova V, Shi X [2001]. Cr(VI) induces cell growth arrest 

through hydrogen peroxide-mediate reactions. Mol Cell 

Biochem 222(1–2):77–83.

Appendix A

Hexavalent Chromium and Lung Cancer 

in the Chromate Industry: A Quantitative 

Risk Assessment

Hexavalent Chromium 129

Appendix A

Hexavalent Chromium and Lung Cancer 

in the Chromate Industry: A Quantitative 

Risk Assessment*

Robert M. Park†

James F. Bena†

Leslie T. Stayner†

Randall J. Smith†

Herman J. Gibb‡

Peter S.J. Lees§

*This manuscript was submitted for publication to the peer-reviewed journal Risk Analysis. For the final publication 

see: Park RM, Bena JF, Stayner LT, Smith RJ, Gibb HJ, Lees PS [2004]. Hexavalent chromium and lung cancer in the 

chromate industry: a quantitative risk assessment. Risk Anal 24(5):1099–1108. †

U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 

National Institute for Occupational Safety and Health, 4676 Columbia Parkway, MS C-15, Cincinnati, OH 45226–

1998, USA; Phone: 513–533–8572; E-mail: rhp9@cdc.gov ‡

U.S. Environmental Protection Agency, Washington, DC

§

The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
130 Hexavalent Chromium

Appendix A

ABSTRACT 

Objectives: The purpose of this investigation was to estimate excess lifetime risk of lung cancer 

death resulting from occupational exposure to hexavalent chromium-containing dusts and mists. 

Methods: The mortality experience in a previously studied cohort of 2357 chromate chemical 

production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. 

Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response 

for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. 

Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks 

of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) 

were estimated using an actuarial calculation that accounts for competing causes of death. 

Results: A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a 

lag of 5 years, was RR = 2.44 (95% CI=1.54–3.83). The excess lifetime risk of lung cancer death from 

exposure to hexavalent chromium at the current OSHA Permissible Exposure Limit (0.10 mg/m3) 

was estimated to be 255 per 1000 (95% CI: 109–416). This estimate is comparable to previous estimates by U.S. EPA, California EPA and OSHA using different occupational data. 

Conclusions: Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent 

with previous risk assessments. 

Keywords: Excess lifetime risk, hexavalent chromium exposure-response, race interaction

INTRODUCTION

History of Hexavalent Chromium Hazard 

Chromium is commercially important in metallurgy, electroplating, and in diverse chemical applications such as pigments, biocides and strong oxidizing agents. Adverse health effects have long 

been known and include skin ulceration, perforated nasal septum, nasal bleeding, and conjunctivitis. Reports of bronchogenic carcinoma appeared prior to World War II in Germany and were 

subsequently confirmed in multiple studies.1 The International Agency for Research on Cancer 

(IARC) declared in 1980 that chromium and certain of its compounds are carcinogenic and, in 

1987, concluded that hexavalent chromium is a human carcinogen but that trivalent chromium was 

not yet classifiable. Recent studies updating chromium worker cohorts in Ohio2,3 and Maryland1

demonstrated an excess lung cancer risk from exposure to hexavalent chromium. 

Regulation of Chromium Exposures

The current Permissible Exposure Limit (PEL) of the U.S. Occupational Safety and Health 

Administration (OSHA) is 0.1 mg/m3 for soluble hexavalent chromium (as CrO3) as an 8 hour 
Hexavalent Chromium 131

Appendix A

time-weighted average.4 The American Conference of Governmental Industrial Hygienists has a 

similar recommendation.5 The U.S. National Institute for Occupational Safety and Health recommends a limit of 0.001 mg/m3 (as Cr).6 Due to continuing concerns over lung cancer risks from 

hexavalent chromium, OSHA is currently reviewing the distribution of chromium exposures in the 

U.S. workforce and the available estimates of excess risk. 

Present Objective

The goal of this investigation was to evaluate various models of exposure-response for lung cancer 

mortality and exposure to hexavalent chromium compounds and then conduct a risk assessment 

for lung cancer based on these models. The cohort of chromate workers analyzed by Hayes et al.7

and later updated and modified by Gibb et al.1 was used for the analysis. In addition to a detailed 

retrospective exposure assessment for chromium, this cohort had smoking information and is believed to be largely free of other potentially confounding exposures from this plant. Using logtransformed cumulative exposure estimates within a proportional hazards regression model, Gibb 

et al. observed the rate of lung cancer mortality in these chromate workers to increase by a factor of 

1.38 for each 10-fold increase in cumulative exposure to hexavalent chromium (p=0.0001).1

METHODS

The description of the cohort can be found in Gibb et al. and comprised 2372 men hired between 

August 1, 1950 and December 31, 1974 at a plant in Baltimore, MD.1,7 Fifteen workers lost to followup were excluded, leaving 2357 subjects for analysis. Followup began with date of hire and continued until December 31, 1992 or the date of death, whichever occurred first. The cohort consisted 

of 1205 men known to be white (51%), 848 known to be nonwhite (36%)—believed to be mostly 

African Americans—and 304 with unknown race (13%). The mean duration of employment was 

3.1 yr., but the median was 0.39 yr. Some smoking information was available at hire for 91% of the 

study population, including smoking level in packs per day for 70%. For those of unknown smoking status (9%), average levels were assigned; for known cigarette smokers with unknown cigarette 

usage (21%), the average level among known smokers was assigned. Cumulative smoking exposure, as packs/day–years, was calculated assuming workers smoked from age 18 until the end of 

followup, and using a 5 year lag (same as for chromium exposure).

Chromium Exposure History

This chromate manufacturing facility began operation in 1845 and continued until 1985. Because 

of facility and process changes and the limited availability of detailed early air sampling data, the 

study population was restricted to those who worked in the “new” plant and were hired between 

August 1, 1950 and December 31, 1974. A detailed retrospective exposure assessment was conducted for this population1 using contemporaneous exposure measurements. During 1950–61, 

short-term personal samples were collected using high volume pumps. From 1961 until 1985 approximately 70,000 systematic area air samples were collected at 154 fixed sites (27 sites after 1977). 

Based on these air samples and recorded observations of the fraction of time spent in these 
132 Hexavalent Chromium

Appendix A

exposure zones by each job title, the employer calculated exposures by job title. After 1977, fullshift personal samples were collected as well. Hexavalent chromium concentrations (as CrO3) were 

based on laboratory determinations of water-soluble chromate performed by the employer; results 

of the area sampling/time-in-zone system of calculating exposures were adjusted to the personal 

sample results. Exposure histories were then calculated for each worker based on the jobs held 

(defined by dates) and corresponding hexavalent chromium exposure estimate for that job title and 

time period. Total cumulative exposures to hexavalent chromium averaged 0.134 mg/m3-yr, with a 

maximum value of 5.3 mg/m3-yr.1

Mortality Analyses

A classification table for Poisson Regression analysis was calculated using a FORTRAN program 

developed previously8 which classified followup in 16 age (<20, 20–24, 25–29, 30–34,... , 85+), 

9 calendar (1950–54, 1955–59,...1990–94), and three race categories (0=nonwhite, 1=white, 2= 

unknown), together with 50 levels of time-dependent cumulative hexavalent chromium exposure 

and 10 levels of time-dependent cumulative smoking exposure and employment duration. The 50 

intervals of cumulative exposure were defined to be narrower at the low exposure end compared to 

the high end because observation time was concentrated at the low end. Although classified in discrete levels, cumulative exposures for chromium and smoking were entered into regression models 

as a continuous variable defined by the person-year weighted mean values of cumulative exposure 

in each of the classification strata. Cumulative exposure is a standard metric used in modeling carcinogenic risk in human populations. The unit of followup in this procedure was 30 days, i.e., every 

30-day interval of a worker’s observed person-time (and lung cancer death outcome) was classified 

as described above. To address latency, different lag periods were used and, for some analyses, cumulative exposures were calculated in three time periods: 5–9.99, 10–19.99, 20 or more years prior 

to observation. 

Relative rate models of the following forms (1a–1f) were evaluated for the effect of cumulative 

chromium exposure on lung cancer mortality:

Log-linear models 

Log-linear: rate = exp(â0 + âX) or ln[rate] = â0 + âX (1a)

Log-square root: rate = exp(â0 + âX0.5) (1b)

Log-quadratic: rate = exp(â0 + â1X + â2X2) (1c)

Power: rate = exp(â0 + â ln[X+1]) = exp(â0) × (X+1)â (1d)

Additive relative rate models

Linear relative rate: rate = exp(â0) × (1 + âX) (1e)

“Shape”: rate = exp(â0) × (1 + â1X â

2

) (1f)

where, â0 (intercept), â, â1, and â2 are parameters to be estimated. 
Hexavalent Chromium 133

Appendix A

External standardization on age, race and calendar time was accomplished using U.S. rates for lung 

cancer mortality during 1950–1994 9 as a multiplier of person-years. This approach makes use of 

well-known population rates and yields models of standardized rate ratios in which the intercept 

is an estimate of the (log) standardized mortality ratio (SMR) for workers without chromium or 

smoking exposures. The method permits departures from the reference rates by including explicit 

terms (e.g., age or race) in the model, and it enables internal comparisons on exposure. Those with 

unknown race (n=304) were assigned a composite expected rate as a weighted average of the external race-specific rates based on the distribution of race in their year of hire.

Poisson regression models were fit using Epicure software.10 Descriptive categorical analyses for 

chromium exposure-response were conducted using five levels of cumulative exposure defined 

to produce equal numbers of lung cancer cases in the upper levels for both races combined. The 

lowest category encompassed the most observation time and observed deaths because of the large 

number of short duration employees in this study population (median duration: 4.7 mos.). Files 

were also constructed for Cox proportional hazards models with continuous cumulative exposures 

and risk sets based on the attained age of the lung cancer case at death. Results using Cox proportional hazard analyses were similar to the Poisson analyses and are not shown.

The models with the largest decrease in deviance (i.e., decrease in –2log (likelihood) with addition of exposure terms) were considered to be the “best” fitting. The adequacy of the parametric 

forms for exposure and for smoking duration in these models was also investigated by fitting cubic 

splines11. The spline models were fit as generalized additive models with three degrees of freedom 

for the effect of exposure using S-Plus, version 4.5. 12 

Unlagged and lagged cumulative exposures were considered. Models with exposures lagged by 5 yrs 

or 10 yrs provided statistically equivalent fits to the data (based on minimizing the deviance) which 

were better than that obtained with the unlagged model; a 5 yr lag was chosen to conform to previous analyses of this cohort.1

 The cumulative smoking variable was included in the log-linear or linear 

terms of different models. However, in estimating the chromium effect for calculating excess lifetime 

risk, the smoking variable was placed in the loglinear term in order to produce a chromium risk estimate relative to an unexposed population without regard to smoking status. Finally, to better model 

the smoking exposure-response, a piece-wise linear spline was used with a knot chosen at 30 packs/

day–yrs). This choice was motivated by a cubic spline analysis of the smoking effect exhibiting a plateau above 30 pack-years. The final model chosen for estimating excess lifetime lung cancer risk had 

the following form, consisting of the product of “loglinear” and “linear” terms:

Rate = [exp(a0+a1Ind(w)+a2Ind(unk)+a3(Age-50)+a4Smk1+a5Smk2)] × [1+b1CumCr6]

where: Ind() are indicators of race (white or unknown), Smk1 and Smk2 are variables specified for the piece-wise linear terms on cumulative smoking, and CumCr6 is cumulative 

hexavalent chromium exposure.

Estimation of Working Lifetime Risks

Excess lifetime risk of death from lung cancer was estimated for a range of chromium air concentrations using an actuarial method that accounts for competing risks and was originally developed 
134 Hexavalent Chromium

Appendix A

for a risk analysis of radon.13 Excess lifetime risk was estimated by first applying cause-specific rates 

from an exposure-response model to obtain lifetime risk, and then subtracting the same expression 

with exposures set to zero:

Excess lifetime risk =

∑i { [Ri(X)/R+i(X)] × S(X,i) × [qi(X)] } - ∑i { [Ri(0)/R+i(0)] × S(0,i) × [qi(0)] 

where R+i (X)= all cause age-specific mortality rate for exposed population; qi = Pr(death in 

year i given alive at the start of year i); and S(X,i) = (1-q1) × (1-q2) × ... × (1-qi-1), probability 

of survival to year i

For specified hexavalent chromium concentrations, excess lifetime risks were estimated making the 

assumption that workers were occupationally exposed to constant concentrations between the ages 

of 20 and 65, or 45 years (less if dying before age 65). Annual excess risks were accumulated up to 

age 85; risk among those surviving past age 85 was not calculated because of small numbers and 

unstable rates. Rate ratios for lung cancer mortality corresponding to work at various chromium 

concentrations were derived from the final linear relative rate Poisson regression model. Agespecific all-cause death rates came from a life table for the U.S. population.14

RESULTS

Lung Cancer Mortality

Lung cancer was the underlying cause for 122 deaths in the chromate cohort. Fitting a Poisson 

regression model with indicator terms for race produced similar lung cancer SMRs for white 

(SMR=1.85, 95%CI=1.45–2.31) and nonwhite (SMR=1.87, 95%CI=1.39–2.46) workers that were 

close to those reported by Gibb et al. (1.86, 1.88, respectively, using different reference rates).1

Results from fitting models with five categorical chromium exposure levels and unadjusted for 

smoking reveal a clear upward trend for the lung cancer SMR with cumulative chromium exposure 

but the trends differed by race (Table 1). The same patterns were observed using internally standardized rate ratios (SRRs, Table 1). The nonwhite workers exhibited a strong overall increasing 

trend of lung cancer risk except for a deficit in the 2nd exposure category (based on two deaths). 

The white workers exhibited an erratic exposure-response relationship, with elevated risks in the 

1st, 2nd and 5th categories, but a declining trend across the 2nd, 3rd and 4th categories. 

Initially several specifications of exposure-response were examined within the family of log-linear 

models: 1a–1d above. Models with linear, square root, quadratic and log-transformed representations of cumulative chromium exposure performed about the same (Table 2, models 1–3,4.1) but a 

model in which smoking cumulative exposure was log-transformed performed considerably better (Table 2, model 4.2). Use of a piece-wise linear specification for smoking exposure resulted 

in further improvement (Table 2, model 4.3). For a saturated model containing both the logtransformed and piece-wise linear smoking terms, the model deviance was almost identical to 

that with the piece-wise terms alone (1931.39 vs. 1931.57). Cubic splines applied to cumulative 

chromium exposure in log-linear models did not detect significant smooth departures from any 

of the specified models. 
Hexavalent Chromium 135

Appendix A

The linear model within the class of additive relative rate models (form 1e, above), with both chromium and smoking in the linear term without log transformation, suggested a superior fit (Table 3, 

model 1) compared to the best log-linear model with log-transformed exposures (Table 2, model 

4.2). This was particularly evident in the contribution of the cumulative chromium exposure term 

(Δ[–2 lnL]= 15.5 vs. 13.8). As in the log-linear case, the fit of this model further improved when 

the piece-wise linear estimation was applied to cumulative smoking (Table 3, models 1 vs. 2; these 

are nested models: the sum of the smoking piece-wise terms equals smoking cumulative exposure). 

The contribution of the cumulative chromium exposure term also increased (Δ[–2 lnL]= 16.3). 

The negative intercept in these models results from comparing observed rates of lung cancer death 

against the national reference rates incorporated into the model. With smoking included in the 

model a negative intercept parameter describes the lowered mortality rates among nonsmoking 

cohort members as compared to the national population which includes smokers. Adding a product term for chromium and smoking cumulative exposures identified a negative but nonsignificant 

interaction in this model (Δ[–2 lnL]= 1.7, 2df). Allowing for some nonlinearity for the chromium 

exposure-response in this model (form 1f) did not significantly improve the fit (data not shown). 

With only chromium exposure in the linear term and smoking exposure in the log-linear term of 

the linear relative rate model, the fit of the model was slightly reduced (Table 3, models 3, 4), but 

this specification permitted the smoking effect to be incorporated into the estimated background 

rate. Using this “final model” (Table 3, model 4) allowed a calculation of excess lifetime risk of 

hexavalent chromium exposure that did not distinguish smoking status; the estimate for each exposure level applied to all workers regardless of smoking. Furthermore, to calculate excess lifetime 

risk in the U.S. population using the model with a non-smoking baseline (Table 3, model 2) would 

require general population mortality data specific to age, race and smoking history, which are not 

available. With this model (Table 3, model 4), there was again a non-significant negative interaction between smoking and chromium cumulative exposures (interaction included in linear term); 

Δ[–2 lnL]= 2.1, 2df). On fit, this final model was essentially identical to the log-linear model using 

log-transformed chromium cumulative exposure (power model) and the piece-wise linear smoking terms (Table 2, model 4.3); the model deviances were 1931.60 and 1931.57 respectively. For the 

saturated model including both representations of chromium exposure together with the piecewise linear smoking terms, the model deviance was 1931.26 (data not shown). 

In the final model, the rate ratio estimated for 1 mg/m3-yr cumulative exposure to hexavalent chromium was 2.44 (= estimated coefficient +1.0) with a 95% confidence interval of 1.54–3.83 (Δ[–2 

lnL]= 15.1) (Table 4, model 1). At the mean cumulative exposure experienced by the lung cancer 

cases (0.28 mg/m3-yr), the rate ratio estimate was 1.40; extrapolating to the maximum cumulative 

exposure of the cases (4.09 mg/m3-yr), it was 6.9. The estimated rate ratio for 45 years of exposure 

at the OSHA PEL (0.10 mg/m3) was 7.5.

The different exposure-response relationships by race observed in the categorical analysis (Table 1) 

were evident in regression models as strong chromium-race interactions. For the preferred linear 

relative rate model (Table 3, model 4; Table 4, model 1), addition of the race-chromium interaction 

term resulted in reductions in deviance of greater than 10.0, a highly statistically significant result 
136 Hexavalent Chromium

Appendix A

(X2=10.6, p=0.001) (Table 4, model 1 vs. 2). This interaction was observed whether age, race 

and calendar time were adjusted by stratification (internal adjustment) or by using external

population rates. The chromium exposure-response for white men was diminished with the interaction (RR=1.18, 95% CI=0.43–1.92, for 1 mg/m3-yr cumulative exposure) but an overall lung 

cancer excess remained for that group. 

Cumulative smoking was used in the final models despite absence of detailed smoking histories 

because, in comparison with models using a simple categorical classification (smoking at hire: yes, 

no, unknown), the models using cumulative smoking fit better. The changes in –2ln(Likelihood) 

for the cumulative smoking piece-wise linear terms versus the categorical terms (both with two 

degrees of freedom) were 28.42 and 25.83 respectively in the final model. 

A significant departure of the estimated background rate (for unexposed workers) from the U.S. 

reference rate was observed with age and with race, but not with calendar time. The age effect corresponded to a reduction of 8–10% (RR=0.92, 0.90) for each 5 yr. of age (Table 4, models 1, 2 respectively). When chromium cumulative exposure was partitioned into three distinct latency intervals 

(5–9.99,10–19.99, 20 or more yrs), there was no improvement in fit, and the chromium exposure 

interaction with race remained. 

Estimates of Excess Lifetime Risk

Estimates of excess lifetime mortality from lung cancer resulting from up to 45 years of chromium 

exposure at concentrations 0.001–0.10 mg/m3 were calculated based on the preferred model without the chromium-race interaction (Table 4, model 1). At 0.10 mg/m3 (the current OSHA standard 

for total hexavalent chromium as CrO3), 45 years of exposure corresponds to a cumulative exposure of 4.5 mg/m3-yr and a predicted lifetime excess risk for lung cancer mortality of 255 per thousand workers (95% CI: 109-416) (Table 5). At 0.01 mg/m3, one tenth of the current standard, 45 

years of exposure corresponds to a lifetime excess risk of 31 per thousand workers (95% CI: 12–59). 

When the alternate log-linear model (Table 2, model 4.3) was used, the estimates of lifetime excess 

risk for lung cancer mortality were very similar (Table 5).

DISCUSSION

Model Choice 

After consideration of a variety of log-linear and additive relative rate forms for modeling both 

smoking and chromium effects, a linear relative rate model with highly statistically significant exposure effects was selected to describe the lung cancer-chromium exposure response and for calculating excess lifetime risk. An equivalently fitting power model produced a slightly larger but less 

precise estimate of lifetime risk at the current PEL. The current findings are consistent with but not 

directly comparable to the results of Gibb et al. in the same population.1 Gibb et al. used a log transformation of cumulative exposure: ln(cumX+d), where d was the smallest measured background 

exposure in the study (d=1.4×10-6 mg/m3-yr). That metric was then used in a log-linear Cox regression model to estimate exposure-response. 
Hexavalent Chromium 137

Appendix A

Exposure Assessment

Extensive and systematic historical environmental air-sampling data were available covering the 

entire period of employment for this study population. Over 70,000 measurements collected between 1950 and 1985 were available for the exposure assessment.1 These measurements were taken 

with the objective of characterizing typical rather than highest exposure scenarios, the latter being 

more commonly measured in industrial settings. The extent and quality of the exposure data are 

unique among chromium exposed populations and far exceed what is typically available for historical cohort studies of occupational groups. Although the exposure information in this study has 

clear advantages over previous studies of chromium workers, it also has its limitations including a 

lack of information on particle size and also on variability of exposures of individual workers having the same job title. Nonetheless, the measurement methodology used in the exposure surveys 

was generally consistent with what has been required by OSHA. 

Potential Confounding 

Although asbestos was identified as a potential exposure in this cohort, we do not believe that it 

is likely to have been an important confounder in this investigation. As in most plants of this period, asbestos was widely used and might have resulted in exposures among part of the workforce, 

particularly among skilled trades and maintenance workers (e.g., pipefitters, steamfitters, furnace 

or kiln repair and laborers). Asbestos exposure would not be expected to be generally correlated 

with chromium exposure in this population and thus should not have biased the internal exposureresponse analysis. Furthermore, no cases of mesothelioma were reported.

Although cigarette smoking was controlled for in this analysis, there is a possibility of residual 

confounding by smoking because of the crudeness of the smoking data which pertained only to the 

time of hire. However, this was considerably more smoking information than is usually found in 

occupational studies. Furthermore, for smoking to have been a strong confounder in this analysis, 

its intensity (packs per day) would have needed to vary by level of hexavalent chromium exposure 

concentration. Our assumption that smokers started at 18 years of age and continued until the end 

of follow-up permitted the estimation of a time-dependent smoking cumulative exposure. A piecewise linear fitting of smoking cumulative exposure considerably improved model fit. It also indicated that cumulative smoking greater than 30 pack-years, where smoking misclassification would 

be greater due to unknown lifetime smoking history, was not a significant predictor of further 

increased risk (Tables 2–4). Observing a plateau in the smoking cumulative exposure response was 

consistent with the pattern observed in previous studies of smoking.16 When smoking was modeled 

using the piece-wise linear terms, the parameter estimate of the chromium affect was increased by 

10 percent, compared with use of the categorical specification for smoking.

Exposure-Race Interaction

As indicated above, an exposure-race interaction was observed in our analyses. Because the source 

of this interaction is unknown, we chose not to include an interaction term in the final risk assessment model. Discussion in the scientific literature of differential cancer rates and risks by race, 

focuses almost exclusively on socioeconomic, occupational and life-style risk factor differences 
138 Hexavalent Chromium

Appendix A

and diagnostic bias.17 We are not aware of examples establishing that occupational lung cancer 

susceptibility varies between African-Americans (majority of the nonwhite study population) and 

white Americans, and thus, in our opinion, it is unlikely that the chromium-race interaction that 

we observed has a biological basis. More plausible explanations include, but are not limited to: misclassification of smoking status, misclassification of chromium exposures, or chance. We have no 

evidence to support any of these explanations, however, and we believe that the exposure-response 

relationship derived for the entire study population provides the best basis for predicting risk.

Excess Lifetime Risk and Prior Risk Assessments

Our analysis predicts, based on the preferred model (Table 4, Model 1), that workers exposed at the 

current OSHA PEL of 0.1 mg/m3 for 45 years will have approximately 25% excess risk of dying from 

lung cancer due to their exposure. Very few workers in this study had cumulative exposures corresponding to 45 years at the PEL, and thus our estimates of risk are based on an upward extrapolation from most of the data (less than 2% of person-years but 10% of lung cancer deaths occurred 

with cumulative exposures greater than 1.0 mg/m3-yr (Table 1)). However, even workers exposed 

at one tenth of the PEL (i.e., to 0.01 mg/m3) would experience 3% excess deaths (Table 5).

There have been several other risk assessments for hexavalent chromium exposure and lung cancer, and it is informative to compare the predictions from these assessments with those from this 

investigation. In a 1995 review that included an earlier assessment of this cohort and the Mancuso 

study2, OSHA identified point estimates of lifetime risk at the current PEL (0.1 mg/m3) in the 

range of 88 to 342 per thousand.18 Conversion¶ of a U.S. Environmental Protection Agency risk assessment19 for ambient chromium exposures based on the Mancuso study, to predict occupational 

risks, produces estimated lifetime risks of 90 per thousand for 45 years of exposure to 0.1 mg/

m3. The State of California EPA published a risk assessment based on best estimates also from the 

Mancuso study with different assumptions about chromium exposures which, when converted for 

occupational exposures, result in a predicted lifetime occupational risk of 90 to 591 per thousand 

for exposure at the PEL.20 Thus the predicted occupational risks for lifetime exposure to the current 

OSHA PEL developed from these previous risk assessments, which ranged from 88 to 591 per 1000 

workers, are quite consistent and bracket the estimate presented in this paper of 255 per 1000 workers. Thus the estimates of risk for 45 years of exposure at the current OSHA PEL from previous risk 

assessments are all within a factor of 3 of the estimates provided in this paper, which is reasonably 

consistent given the uncertainties involved in the risk assessment process. 

CONCLUSION

This study clearly identifies a linear trend of increasing risk of lung cancer mortality with increasing 

cumulative exposure to water-soluble hexavalent chromium. Our analysis predicts that exposure 

¶

The U.S. and California EPA risk assessments reported unit lifetime risks for hexavalent chromium exposure of 0.012 

(per μg/m3). To convert this to occupational risk and exposure to chromium as chromic acid, the unit risk was multiplied by 240/365 days to correct for differences in number of days exposed per week, 8/24 to correct for number 

of hours per day exposed, 45/70 to correct for number of years of exposure, and by 0.52 to convert from chromium 

to CrO3.
Hexavalent Chromium 139

Appendix A

at the current OSHA PEL for hexavalent chromium permits a lifetime excess risk of lung cancer 

death that exceeds 1 in 10. Exposures at 1/10th the PEL (0.01 mg/m3 or 10 μg/m3, as CrO3), would 

confer a 3 per hundred lifetime risk. The risk estimates from this analysis are consistent with those 

of other assessments.

ACKNOWLEDGEMENTS

The authors would like to acknowledge the contributions of the following in providing helpful 

commentary: Drs. John Bailer, Kyle Steenland, Christopher Portier, Chao Chen, David Dankovic 

and Paul Pinsky, Ms. Caroline Freeman, and two journal referees. 

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3. Luippold RS, Mundt KA, Panko J, Liebig E, Crump C, Crump K, Paustenbach D, Proctor D. Lung cancer 

mortality among chromate production workers. Occup Environ Med 2003; 60:451–457.

4. U.S. Occupational Safety and Health Administration. 2000. 29CFR1910.1000, Table Z-2

5. American Conference of Government and Industrial Hygienists. 1999. 1999 TLVs and BEIs. Cincinnati, 

OH: ACGIH.

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Boston, MA, 1997.

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11. Chambers JM, Hastie TJ. Statistical Models in S. Pacific Grove, CA: Wadsworth, Inc., 1992.

12. Mathsoft, Inc. S-Plus 4 Guide to Statistics. Seattle, WA: Mathsoft, Inc., 1997.

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alpha-emitters. Committee on the Biological Effects of Ionizing Radiation, Board of Radiation Effects 

Research, Commission on Life Sciences, National Research Council. National Academy Press, Washington, D.C., 1988.

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Washington: Public Health Service, 1996. DHHS Publication No. (PHS) 96–1101. 

15. Braver ER, Infante P, Chu K. An analysis of lung cancer risk from exposure to hexavalent chromium. 

Teratogenesis, Carcinogenesis, and Mutagenesis 1985; 5:365–378.
140 Hexavalent Chromium

Appendix A

16. Vineis P, Kogevinas M, Siminato L, Brennan P, Boffetta P. Leveling off of the risk of lung and bladder 

cancer in heavy smokers: an analysis based on multicentric case-control studies and a metabolic interpretation. Mutat Res 2000; 463:103–110. 

17. Schottenfeld D, Fraumeni JF, eds, Cancer Epidemiology and Prevention, 2nd Edition, Oxford University 

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NW, Washington DC, 20210; May, 1995.

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Agency, Washington, D.C.

20. Cal EPA: http://www.oehha.ca.gov/air/toxic_contaminants/pdf1/ hexavalent%20chromium.pdf 
Hexavalent Chromium 141

Appendix A

Table 1. SMRs for lung cancer in five strata of cumulative exposure

to hexavalent chromium (mg/m3-yr, as CrO3)

Cum. exposure P-yrs Obs Exp SMR 95%CI SRR 95% CI

All workers (includes 4 lung cancer cases with unknown race)

1 [0.0000–0.0282] 51348 72 47.93 1.50 1.18–1.88 1.0 —

2 [0.0282–0.0944] 7837 14 7.64 1.83 1.03–2.97 1.29 0.69–2.22

3 [0.0944–0.3715] 6859 12 6.09 1.97 1.06–3.31 1.38 0.71–2.46

4 [0.3715–1.0949] 3841 12 5.13 2.34 1.25–3.93 1.70 0.87–3.03

5 [1.0949–5.2600] 950 12 1.90 6.32 3.39–10.60 4.53 2.32–8.13

Total 122 68.68 1.78 1.50–2.11

White workers

1 [0.0000–0.0282] 27962 45 27.32 1.65 1.21–2.18 1.0 —

2 [0.0282–0.0944] 4088 12 3.93 3.06 1.64–5.13 1.85 0.92–3.43

3 [0.0944–0.3715] 3409 6 2.98 2.01 0.80–4.08 1.21 0.46–2.70

4 [0.3715–1.0949] 2188 4 3.22 1.24 0.39–2.89 0.86 0.26–2.15

5 [1.0949–5.2600] 495 4 1.03 3.87 1.20–8.98 2.55 0.76–6.38

Total 71 38.48 1.85 1.45–2.31

Nonwhite workers

1 [0.0000–0.0282] 16384 24 16.16 1.49 0.97–2.16 1.0 —

2 [0.0282–0.0944] 3118 2 3.31 0.60 0.10–1.86 0.41 0.07–1.41

3 [0.0944–0.3715] 3125 5 2.93 1.71 0.61–3.67 1.24 0.41–3.04

4 [0.3715–1.0949] 1589 8 1.87 4.23 1.96–7.98 3.03 1.24–6.64

5 [1.0949–5.2600] 434 8 0.85 9.41 4.30–17.5 6.76 2.76–15.0

Total 47 25.12 1.87 1.39–2.46

Workers (unknown race)

1 [0.0000–0.0282] 7002 3 4.45 0.67 0.17–1.75 1.0 —

2 [0.0282–0.0944] 631 0 0.40 0.00 0.00–4.78 0.00 0.00–55.1

3 [0.0944–0.3715] 326 1 0.17 5.73 0.33–25.2 11.2 0.52–117.7

4 [0.3715–1.0949] 64 0 0.04 0.00 0.00–47.8 0.00 —

5 [1.0949–5.2600] 22 0 0.01 0.00 0.00–143.9 0.00 —

Total 4 5.08 0.79 0.24–1.83
142 Hexavalent Chromium

Appendix A

Table 2. Log-linear Poisson regression model forms with different specifications for chromium exposure 

Models1

Exposure effect 

ln(RR) Deviance Δ-2ln(L) (df)2 p

1 Log-linear (1a)

Intercept 0.0980 1946.79

Cumulative smoking 0.0225

Cumulative chromium-6 0.4950 9.813 (1) 0.0017

2 Log-square root (1b)

Intercept 0.0073 1946.49

Cumulative smoking 0.0211

Sqrt(Cum. chromium-6 ) 0.7884 10.12 (1) 0.0015

3 Log-quadratic (1c)

Intercept 0.0942 1945.10

Cumulative smoking 0.0207

Cumulative chromium-6 0.8935 11.51 (2) 0.0032

Square(Cum. chromium-6 ) -0.1280

4 Power (1d)

4.1 Intercept 0.0850 1945.74

Cumulative smoking 0.0211

Ln(Cum. chromium-6+1) 1.048 10.87 (1) 0.0010

4.2 Intercept -0.9661 1934.67 

Ln(Cumulative smoking+1) 0.5139 

Ln(Cum. chromium-6+1) 1.178 13.81 (1) 0.0002

4.3 Intercept -0.7804 1931.57

Smoking < 30 pack-years3 0.0613

Smoking > 30 pack-years4 -0.0053

Ln(Cum. chromium-6+1) 1.253 15.08 (1) 0.0001

1

Models include race as a categorical (3-level) variable, and allow for a linear departure of the baseline from reference rates with 

age, centered at 50 years; cumulative smoking is in packs/day-years (lag=5 years), and cumulative chromium as CrO3 is in mg/

m3-years (lag=5 years) 2

Change in -2ln(L) for terms involving chromium, basis for chi-sq statistical test

3

Specified as: minimum(cumulative smoking, 30 pack-yrs) 

4

Specified as: maximum(cumulative smoking—30 pack-yrs, 0)
Hexavalent Chromium 143

Appendix A

Table 3. Linear relative rate Poisson regression model forms for chromium exposure 

Models1

Estimate of 

exposure effect Deviance Δ-2ln(L) (df)2 p

Model (1e): linear relative rate in smoking and chromium; loglinear rate in race, age 

1 Intercept -1.377 1933.71

Cumulative smoking 0.2833

Cumulative chromium-6 8.994 15.46 (1) < 0.0001

2 Intercept -1.636 1930.51

Smoking < 30 pack-years3 0.402

Smoking > 30 pack-years4 0.031

Cumulative chromium-6 10.95 16.25 (1) < 0.0001

Model (1e): linear relative rate in chromium; log-linear rate in smoking, race, age

3 Intercept -0.965 1934.75

Ln(Cumulative smoking+1) 0.513

Cumulative chromium-6 1.269 13.73 (1) 0.0002

4 Intercept -0.786 1931.60

Smoking < 30 pack-years 0.061

Smoking > 30 pack-years -0.006

Cumulative chromium-6 1.444 15.05 (1) 0.0001

1

Models include race as a categorical (3-level) variable, and allow for a linear departure of the baseline from reference rates with age, 

centered at 50; cumulative smoking is in packs/day-years (lag=5 years), and cumulative chromium as CrO3 is in mg/m3-years 

(lag=5 years) 2

Change in -2ln(L) for terms involving chromium, basis for chi-sq statistical test

3

Specified as: minimum(cumulative smoking, 30 pack-yrs) 

4

Specified as: maximum(cumulative smoking—30 pack-yrs, 0)
144 Hexavalent Chromium

Appendix A

Table 4. Final Poisson regression model and model including chromium-race interaction (lag=5 years)

Model1

Estimate of 

exposure 

effect

Δ-2ln(L)

(df)2 SMR3 RR4

RR,

95% CI Reference5

Model (1e): linear relative rate in chromium, log-linear in smoking, race, age

1 Race: nonwhite men -0.786 0.46 US NW men

Race: white men -0.901 0.41 US W men

Race: unknown 5 -1.515 0.22 US men

Age -0.082 0.92 5 yr of age

Smoking < 30 pack-years6 0.061 1.06 1.04,1.09 pack-yrs

Smoking > 30 pack-years7 -0.006 0.99 0.97,1.01 pack-yrs

Cumulative chromium-6 1.444 15.05 (1) 2.44 1.54,3.83 mg/m3-yr

(Model deviance: -2ln(L) =1931.60)

2 Race: nonwhite men -1.121 0.33 US NW men

Race: white men -0.834 0.43 US W men

Race: unknown -1.557 0.21 US men

Age -0.100 0.90 5 yr of age

Smoking < 30 pack-years 0.064 1.07 1.04,1.07 pack-yrs

Smoking > 30 pack-years 0.001 1.00 0.98,1.02 pack-yrs

Cum. chrom-6, NW men 4.312 25.63 (2) 5.31 2.78,10.1 mg/m3-yr

Cum. chromium-6, W men 0.176 1.18 0.43,1.92 mg/m3-yr

(Model deviance: -2ln(L) =1921.02)

1

The baseline from reference rates with age, centered at 50 years; cumulative smoking is in packs/day-years (lag=5 years), andcumulative chromium as CrO3

 is in mg/m3-yr (lag=5 years) 2

Change in -2ln(L) for terms involving chromium, basis for chi-sq statistical test

3

Estimated SMR adjusted for terms in model, i.e., unexposed, in race strata, at age 50

4

R, relative rate, for cum. exposure of 1.0 mg/m3-yr 5

W=white, NW=nonwhite; for unknown race, US rates applied in proportion to those with known race by year of hire

6

Specified as: minimum(cumulative smoking, 30 pack-yrs) 

7

Specified as: maximum(cumulative smoking—30 pack-yrs, 0)
Hexavalent Chromium 145

Appendix A

Table 5. Excess lifetime risk of lung cancer mortality for specified concentrations

of hexavalent chromium (as CrO3) assuming 45 year exposure

Hexavalent

chromium exposure

Excess lifetime risk

Linear relative rate model1 Log-linear model2

(as CrO3, mg/m3) Excess risk3 95% CI Excess risk 95% CI

0.000 0.000 — 0.000 —

0.001 0.003 0.001–0.006 0.003 0.001–0.004

0.002 0.006 0.003–0.012 0.005 0.003–0.008

0.005 0.016 0.006–0.030 0.014 0.007–0.020

0.010 0.031 0.012–0.059 0.028 0.013–0.043

0.020 0.060 0.023–0.113 0.057 0.025–0.093

0.050 0.141 0.057–0.251 0.145 0.056–0.264

0.1004 0.255 0.109–0.416 0.281 0.096–0.516

1

Based on Table 4, model 1

2

Based on Table 2, model 4.3

3

Probability of chromium-attributable lung cancer death in lifetime with exposure starting at age 20 and lasting up to 45 years (calculated through age 85) 4

OSHA PEL for total hexavalent chromium 


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