Document ID: EPA-HQ-OAR-2007-0121-0482
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-12-22T05:00Z

DHHS (niosh) Publication No. 88-116CURRENT INTELLIGENCE BULLETIN 50

CARCINOGENIC EFFECTS OF
EXPOSURE TO DIESEL EXHAUST
August 1988
 
TABLE OF CONTENTS
  Foreword, J. Donald Millar Correspondence
  Abstract
  Acknowledgments
  Introduction
  Background
  Exposure Limits
  Evidence of Carcinogenicity in Animals
  Human Health Effects
  Conclusions
  Recommendations
  Research Needs
  Notes
  References

 
CARCINOGENIC EFFECTS OF
EXPOSURE TO DIESEL EXHAUST
August 1988
Foreword
Current Intelligence Bulletins (CIBs) are issued by the National Institute for 
Occupational Safety and Health (niosh), Centers for Disease Control, Atlanta, 
Georgia, to disseminate new scientific information about occupational hazards. A 
CIB may draw attention to a previously unrecognized hazard, report new data 
suggesting that a known hazard is either more or less dangerous than formerly 
thought, or disseminate information recommending specific controls for a hazard.
CIBs are prepared by the staff of the Division of Standards Development and 
Technology Transfer, niosh (Robert A. Taft Laboratories, 4676 Columbia Parkway, 
Cincinnati, Ohio 45226). They are distributed to representatives of academia, 
industry, organized labor, public health agencies, and public interest groups, 
as well as to Federal agencies that are responsible for ensuring the health and 
safety of workers. Our intention is to provide ready access to the information 
contained in CIBS. We welcome suggestions concerning their content, style, and 
distribution.
The purpose of this bulletin is to disseminate recent information on the 
potential carcinogenicity of diesel exhaust. In March 1986, niosh issued a 
document entitled "Evaluation of the Potential Health Effects of Occupational 
Exposure to Diesel Exhaust in Underground Coal Mines." This document stated that 
workers exposed to diesel exhaust experienced eye irritation and reversible 
decrements in pulmonary function. In the document, niosh concluded that no 
causal relationship had been established between exposure to whole diesel 
exhaust and cancer, but that such a relationship was plausible on the basis of 
animal studies in which extracts of diesel exhaust were used. Since the release 
of that document, reports of studies in animals have confirmed the potential 
carcinogenicity of whole diesel exhaust. 
On the basis of the results of these studies, niosh recommends that whole diesel 
exhaust be regarded as "a potential occupational carcinogen," as defined in the 
Cancer Policy of the Occupational Safety and Health Administration (OSHA) 
("Identification, Classification, and Regulation of Potential Occupational 
Carcinogens," 29 CFR 1990). This recommendation is based on findings of 
carcinogenic and tumorigenic responses in rats and mice exposed to whole diesel 
exhaust. Though the excess risk of cancer in diesel-exhaust-exposed workers has 
not been quantitatively estimated, it is logical to assume that reductions in 
exposure to diesel exhaust in the workplace would reduce the excess risk.
Diesel exhaust is a complex mixture of compounds, and its composition varies 
greatly with fuel and engine type, load cycle, engine maintenance, tuning, and 
exhaust gas treatment. This complexity is compounded by a multitude of 
environmental settings in which diesel-powered equipment is operated. Because of 
limitations in currently available technology and test methods, niosh cannot at 
this time confidently offer recommendations for environmental monitoring of 
exposures to diesel exhaust, or for generally applicable control measures that 
would assure adequate reduction of the carcinogenic risks associated with 
occupational exposure to diesel engine emissions. Continued investigation of 
these issues is clearly essential.
niosh recommends that producers of diesel engines disseminate this current 
information to their customers, and that users of diesel-powered equipment 
disseminate this current information to their workers. niosh also recommends 
that professional and trade associations and unions inform their members of the 
new findings of potential carcinogenic hazards of exposure to diesel engine 
emissions, and that all available preventive efforts (including available 
engineering controls and work practices) be vigorously implemented to minimize 
exposure of workers to diesel exhaust. Readers seeking more detailed information 
on the studies cited this bulletin are urged to consult the original 
publications.
      [signature]
      J. Donald Millar, M.D., D.T.P.H. (Lond.)
      Assistant Surgeon General
      Director, National Institute for
      Occupational Safety and Health
      Centers for Disease Control

 
Abstract
This bulletin presents recent information on the potential carcinogenicity of 
diesel exhaust. Included are discussions of recent animal studies that confirm 
the relationship between cancer and exposure to whole diesel exhaust. Also 
discussed is epidemiologic evidence that associates lung cancer with 
occupational exposure to diesel engine emissions. On the basis of the results of 
these studies, niosh recommends that whole diesel exhaust be regarded as a 
potential occupational carcinogen in conformance with the OSHA Cancer Policy (29 
CFR 1990). 
 
Acknowledgments
The following staff members of the Division of Standards Development and
Technology Transfer (DSDTT) were responsible for preparing this CIB:
Document Manager - Jane Brown McCammon
Chief, Senior Review Activity - William D. Wagner
Senior Review Staff - David H. Groth, M.D., G. Kent Hatfield, Ph.D., Laurence D. 
Reed
Editorial Staff - Vanessa L. Becks, Ruth E. Grubbs, Anne C. Hamilton
Secretarial Staff - Denise Hill
Assistant Chief, Document Development Branch - Ralph D. Zumwalde
Chief, Document Development Branch - Bryan D. Hardin, Ph.D.
Deputy Director - Richard W. Niemeier, Ph.D.
Director, DSDTT - Richard A. Lemen
Contributions by other niosh staff members are also gratefully acknowledged:
William J. Moorman
Division of Biomedical and Behavioral Science
Laurence J. Doemeny, Ph.D.
Division of Physical Sciences and Engineering
John F. Gamble, Ph.D.
Michael A. McCawley, Ph.D.
Rebecca Stanevich
William Wallace, Ph.D.
Division of Respiratory Disease Studies
Nancy J. Bollinger
Division of Safety Research
Barbara Carr
Howard R. Ludwig
Susan Marksberry
June Mefford
Theodore J. Meinhardt, Ph.D.
Vlasta Molak, Ph.D.
Division of Standards Development and Technology Transfer
Kyle Steenland, Ph.D.
Dennis D. Zaebst
Division of Surveillance, Hazard Evaluation, and Field Studies
Walter M. Haag, Jr.
Anne M. Stirnkorb
Division of Training and Manpower Development 
We wish to thank the following consultants for their contributions:
Dietrich Hoffman, Ph.D.
Naylor Dana Institute for Disease Prevention 
American Health Foundation
Bruce O. Stuart, Ph.D.
Department of the Air Force, Wright-Patterson Air Force Base 
James A. Swenberg, D.V.M., Ph.D.
Chemical Industry Institute of Toxicology
David D. Bayse, Ph.D., 
Office of the Director, niosh, provided the final policy review. 
 
Introduction
The purpose of this bulletin is to disseminate recent information on the 
potential carcinogenicity of diesel exhaust. A recent National Institute for 
Occupational Safety and Health (niosh) document entitled Evaluation of the 
Potential Health Effects of Occupational Exposure to Diesel Exhaust in 
Underground Coal Mines [niosh 1986] concluded that "Among workers exposed to 
diesel exhaust, irritation of the eyes, and reversible decrements in pulmonary 
function have been documented." The document also stated that "a causal 
association between exposure to whole diesel exhaust and cancer, although 
plausible on the basis of studies of extracts of diesel exhaust in animals," had 
not been established. Since publication of that document, results of animal 
studies have confirmed the potential carcinogenicity of whole diesel exhaust. 
This Bulletin describes the results of those animal ;studies and discusses the 
limited epidemiologic evidence of an association between lung cancer and 
occupational exposure to diesel engine emissions. 
Background
Diesel engines rely on heat generated during the compression cycle for ignition 
rather than on an electrical spark as in gasoline engines. Because of the higher 
compression required, diesel engines are heavier and bulkier than gasoline 
engines. However, diesel engines can operate with less highly refined fuel and 
consume less fuel per horsepower per hour. The diesel engine is the predominant 
source of industrial power throughout the world for units up to about 5,000 
horsepower [Encyclopaedia Britannica 1987]. 
Composition of Diesel Engine Emissions
Diesel engines function by facilitating the combustion of liquid fuel without 
spark ignition. In gasoline engines, a mixture of air and fuel is drawn into a 
combustion chamber, compressed, and then ignited by an electric spark. In diesel 
engines, air alone is compressed in the combustion chamber. Fuel is then 
introduced into the chamber, and ignition is accomplished by the heat of 
compression.
The emissions from diesel engines consist of both gaseous and particulate 
fractions. The gaseous constituents include carbon dioxide, carbon monoxide, 
nitric oxide, nitrogen dioxide, oxides of sulfur, and hydrocarbons (e.g., 
ethylene, formaldehyde, methane, benzene, phenol, 1,3-butadiene, acrolein, and 
polynuclear aromatic hydrocarbons) [Linnell and Scott 1962; Environmental Health 
Associates 1978; Schenker 1980; Travis and Munro 1983]. Particulates (soot) in 
diesel exhaust are composed of solid carbon cores that are produced during the 
combustion process and that tend to form chain or cluster aggregates. More than 
95% of these particulates are less than 1 micrometer in size [Travis and Munro 
1983; Vostal 1980; McCawley and Cocalis 1986]. Estimates indicate that as many 
as 18,000 different substances from the combustion process can be adsorbed onto 
diesel exhaust particulates [Weisenberger 1984]. The adsorbed material 
constitutes 15% to 65% of the total particulate mass and includes such compounds 
as polynuclear aromatic hydrocarbons (PAHs) [Travis and Munro 1983; Cuddihy et 
al. 1984]. 
Number of Exposed Workers
niosh estimates that approximately 1.35 million workers are occupationally 
exposed to the combustion products of diesel fuel in approximately 80,000 
workplaces in the United States [niosh 1983]. Workers who are likely to be 
exposed to diesel emissions include mine workers, bridge and tunnel workers, 
railroad workers, loading dock workers, truck drivers, fork-lift drivers, farm 
workers, and auto, truck, and bus maintenance garage workers. 
Exposure Limits
Permissible exposure limits (PELs) established by the Occupational Safety and 
Health Administration (OSHA) and the Mine Safety and Health Administration 
(MSHA) for some gases typically found in diesel exhaust are listed in Table 1 
along with the recommended exposure limits (RELs) established by niosh.
OSHA, MSHA, and niosh exposure limits relevant to the particulate fraction of 
diesel engine emissions are listed in Table 2. Because diesel emission 
particulates are of respirable size, the presence of diesel equipment 
contributes to the total burden of respirable dust present in an occupational 
environment. Existing limits for occupational exposures to other respirable 
dusts also limit exposures to the particulate fraction of diesel emissions. 
As much as 15% to 65% of the mass of particulate emissions (soot) of diesel 
engines is made up of organic compounds adsorbed onto the surface of the 
particulates [Travis and Munro 1983; Cuddihy et al. 1984]. Among these organic 
compounds is a group of compounds known as polynuclear aromatic hydrocarbons 
(PAHs), several of which are carcinogens [IARC 1983]. PAHs are produced as 
pyrolytic products during the combustion of any fossil fuel, including diesel 
fuel. Some readily condense onto the surface of the soot being expelled from 
diesel engines. Concentrations of PAHs can be determined by using solvents such 
as benzene or cyclohexane to extract these and other compounds from particulate 
samples. This analysis yields the solvent-soluble portion of the particulates 
(often referred to as coal tar pitch volatiles, or cyclohexane- or 
benzene-solubles), which can be further fractionated. 
 
Table 1.
Limits for Occupational Exposure to Selected Components of the Gaseous Fraction 
of Diesel Exhaust; OSHA, MSHA, niosh Compared
        MSHA PELs* 
      Component OSHA PEL Underground
      coal mines Metal and nonmetal
      mines niosh REL 
      Carbon dioxide (CO2) 5,000 ppm (9,000 mg/m3), 8-hr TWA† 5,000 ppm (9,000 
      mg/m3), 8-hr TWA;
      30,000 ppm (54,000 mg/m3), STEL§ 5,000 ppm (9,000 mg/m3), 8-hr TWA;
      15,000 ppm (27,000 mg/m3), STEL 10,000 ppm (18,000 mg/m3), 8-hr TWA;
      30,000 ppm (54,000 mg/m3), 10-min ceiling 
      Carbon monoxide (CO) 50 ppm (55 mg/m3), 8-hr TWA 50 ppm (55 mg/m3), 8-hr 
      TWA;
      400 ppm (440 mg/m3), STEL 50 ppm (55 mg/m3), 8-hr TWA;
      400 ppm (440 mg/m3), STEL 35 ppm (40 mg/m3), 8-hr TWA;
      200 ppm (230 mg/m3), ceiling (no minimum time) 
      Formaldehyde 1 ppm, 8-hr TWA;
      2 ppm, 15-minute STEL 1 ppm (1.5 mg/m3), 8-hr TWA;
      2 ppm (3 mg/m3), STEL 2 ppm (3 mg/m3), ceiling 0.016 ppm (0.020 mg/m3), 
      8-hr TWA;
      0.1 ppm (0.12 mg/m3), 15-min ceiling 
      Nitrogen dioxide (NO2) 5 ppm (9 mg/m3), ceiling 3 ppm (6 mg/m3), 8-hr TWA;
      5 ppm (10 mg/m3), STEL 5 ppm (9mg/m3), ceiling 1 ppm (1.8 mg/m3), 15-min 
      ceiling 
      Nitric oxide (NO) 25 ppm (30 mg/m3), 8-hr TWA 25 ppm (30 mg/m3), 8-hr TWA 
      25 ppm (30 mg/m3), 8-hr TWA; 37.5 ppm (46 mg/m3), STEL 25 ppm (30 mg/m3), 
      10-hr TWA 
      Sulfur dioxide (SO2) 5 ppm (13 mg/m3), 8-hr TWA 2 ppm (5 mg/m3), 8-hr TWA;
      5 ppm (10 mg/m3), STEL 5 ppm (13 mg/m3), 8-hr TWA;
      20 ppm (52 mg/m3), STEL (5 min) 0.5 ppm (1.3 mg/m3), 10-hr TWA 
*MSHA limits are based on threshold limit values (TLV®s) of the American 
Conference of Governmental Industrial Hygienists (ACGIH). 1973 TLV®s are used 
for metal and nonmetal mines. Current TLVs are used for underground coal mines. 
[return to table]
†-weighted average. [return to table]
§-term exposure limit. [return to table]
 
Table 2. 
OSHA, MSHA, and niosh Limits Relevant to Occupational Exposure to the 
Particulate Fraction of Diesel Exhaust
      MSHA PELs 
      Component OSHA PEL Underground
      coal mines Metal and nonmetal
      mines niosh REL 
      Respirable dust* 5 mg/m3 2 mg/m3† No Limit No REL 
      Respirable dust when quartz content is more than 5% of total* 10 mg/m3
      % SiO2 +2 10 mg/m3†
      % quartz 10 mg/m3§
      % quartz+2 REL is specific
      to quartz 
      Coal tar pitch volatiles (CTPV) Not applicable to diesel emissions Not 
      considered relevant Not considered relevant 0.1 mg/m3, 10-hr TWA
      (cyclohexane-extractables) 
      Polynuclear aromatic hydrocarbons No PEL No PEL No PEL No REL 
*These limits are not intended for diesel exhaust particulates, but they would 
inadvertenly limit airborne concentrations because diesel particulates would be 
included in respirable dust samples taken where diesel engines are operating. 
[return to table]
† equivalent concentration. [return to table]
§ limits are based on threshold limit values (TLV®s) of the American Conference 
of Governmental Industrial Hygienists (ACGIH). 1973 TLV®s are used for metal and 
nonmetal mines. [return to table]

Evidence of Carcinogenicity in Animals
Several reports of long-term animal inhalation studies [Brightwell et al. 1986; 
Heinrich et al. 1986; Ishinishi et al. 1986; Iwai et al. 1986; Mauderly et al. 
1987] regarding the health effects of exposure to whole diesel exhaust have been 
released since the publication of the niosh document entitled Evaluation of the 
Potential Health Effects of Occupational Exposure to Diesel Exhaust in 
Underground Coal Mines [niosh 1986]. Data from these reports serve as the basis 
for the current niosh conclusion that exposure to whole diesel exhaust is 
associated with the risk of cancer. Other health effects were examined in these 
studies, but only those related to carcinogenicity are presented here. The 
studies are summarized in Table 3 and discussed more fully in the following 
sections. The primary difference between the study designs of the recent 
positive studies and negative studies previously evaluated by [niosh 1986] is 
the length of the exposure period, which was up to 30 months for the positive 
studies and 24 months for the negative studies.
Heinrich et al. [1986]
Results of an extensive long-term inhalation study of cancer in mice, rats, and 
hamsters exposed to filtered and unfiltered light-duty diesel engine exhaust 
were reported by [Heinrich et al. 1986]. Equal numbers of male and female Syrian 
golden hamsters, female NMRI mice, and female Wistar rats were exposed to clean 
air, unfiltered diesel exhaust, or filtered diesel exhaust. Each group consisted 
of 96 animals. All experimental animals were 8 to 10 weeks old at the start of 
the study. Throughout the lifespan of the animals, exposure was for 19 hours per 
day, 5 days per week. The maximum duration of exposure was 120 weeks for 
hamsters and mice, and 140 weeks for rats.
A stationary 1.6-liter diesel engine operated according to EPA's US-72 driving 
cycle was used to generate the exhaust. The diesel fuel used was a European 
reference fuel with a sulfur content of 0.36%. The exhaust was diluted with 
filtered air to a volume rate of 1:17 (diesel exhaust/air) and was then directed 
into an exposure chamber. At this dilution rate, the measured concentration of 
the particulate fraction of diesel exhaust was approximately 4 mg/m3. To remove 
particulates from the exhaust, the diesel emissions were passed through a 
centrifugal separator and/or a particle filter. The concentrations of exhaust 
components in the inhalation chambers for both filtered and unfiltered exhaust 
are shown in Table 4. 
 
Table 3. 
Characteristics of recent studies* of carcinogenicity in animals
exposed to diesel exhaust by inhalation
      Study Type of engine Nature of exhaust Animal species Exposure time 
      Particulate exposure
      concentrations(mg/m3) Findings 
      Heinrich et al. [1986] 1.6-liter Volkswagen Unfiltered Female Wistar rats 
      19 hr/day, 5 days/week, max. of 140 weeks 4 Significantly increased 
      incidence of adenomas, benign squamous cell cysts, and squamous cell 
      carcinoma of the lung when compared with controls. 
      Filtered Female Wistar rats 19 hr/day, 5 days/week, max. of 140 weeks ---- 
      No significant differences in histopathological findings compared with 
      controls. 
      Unfiltered Female NMRI mice 19 hr/day, 5 days/week, max. of 120 weeks 4 
      Statistically significant increase in malignant and total lung tumors 
      (because of increases in adenocarcinomas) when compared with controls. 
      Filtered Female NMRI mice 19 hr/day, 5 days/week, max. of 120 ---- 
      Statistically significant increase in malignant and total lung tumors 
      (because of increases in adenocarcinomas) when compared with controls. 
      Unfiltered Male and female Syrian golden hamsters 19 hr/day, 5 days/week, 
      max. of 120 weeks 4 No significant differences in histopathological 
      findings compared with controls 
      Filtered Male and female Syrian golden hamsters 19 hr/day, 5 days/week, 
      max. of 120 weeks ---- No significant differences in histopathological 
      findings compared with controls. 
      Mauderly et al. [1987] 5.7-liter Oldsmobile Unfiltered Male and female 
      F344 rats 7 hr/day, 5 days/week, max. 30 months 0.35
      3.5
      7.0 High exposure led to statistically significant increases in benign 
      squamous cysts and malignant tumors (adenocarcinomas and squamous 
      carcinomas) compared with controls. Intermediate exposure led to a 
      statistically significant increase in adenomas and total tumors when 
      compared with controls. There were no statistically significant increases 
      in benign or malignant tumors in low-exposure animals. 
      Brightwell et al. [1986] 1.5-liter Volkswagen Unfiltered Male and female 
      F344 rats 16 hr/day, 5 days/week, 2 years† 0.7
      2.2
      6.6 Statistically significant increase in undefined tumors in both male 
      and female high-exposure animals compared with controls. Statistically 
      significant increase in undefined tumors in female intermediate-exposure 
      animals compared with controls. 
      Filtered Male and female F344 rats 16 hr/day, 5 days/week, 2 years† Below 
      the limit of detection No increase in tumor incidence in any exposure 
      group when compared with controls. 
      Unfiltered Male and female syrian hamsters 16 hr/day, 5 days/week, 2 years 
      0.7
      2.2
      6.6 No increase in tumor incidence in any exposure group when compared wth 
      controls. 
      Filtered Male and female Syrian hamsters 16 hr/day, 5 days/week, 2 years 
      Below the limit of detection No increase in tumor incidence in any 
      exposure group when compared with controls. 
      Ishinishi et al. [1986] Light-duty, 1.8-liter, 4-cylinder, swirl chamber 
      Unfiltered Male and female F344 rats 16 hr/day, 6 days/week, max. 30 
      months 0.1
      0.4
      1
      2 No statistically significant increase in lung tumors. Increase in 
      hyperplasia, squamous hyperplasia, interstitial fibrosis, hyperplastic 
      lesions. 
       Heavy-duty, 11-liter, 6-cylinder, direct injection Unfiltered Male and 
      female F344 rats 16 hr/day, 6 days/week, max. 30 months 0.4
      1
      2
      4 Statistically significant increase in lung tumors (adenoma, squamous 
      cell carcinoma, adenocarcinoma, adenosquamous carcinoma) in the 
      high-exposure group compared to controls. 
      Filtered Male and female F344 rats 16 hr/day, 6 days/week, max. 30 months 
      0.005
      0.019 No statistically significant increase in lung tumors. Increase in 
      hyperplasia, squamous hyperplasia, interstitial fibrosis, hyperplastic 
      lesions. 
      Iwai et al., 1986 2.4-liter Unfiltered Female F344 rats 8 hr/day, 7 
      days/week, 24 months§ 4.9 Statistically significant increase in total lung 
      tumors (adenomas, adenocarcinoma, adenosquamous carcinomas, squamous 
      carcinoma, and large cell carcinoma) compared with controls. Statistically 
      significant increase in splenic malignant lymphoma compared with controls. 
      Increased incidence of tumors other than lung, and multiplicity of tumors. 

      Filtered Female F344 rats 8 hr/day, 7 days/week, 24 months§ ---- Minimal 
      histopathologic changes. Statistically significant increase in splenic 
      malignant lymphoma compared with controls. Increased incidence of tumors 
      other than lung, and multiplicity of tumors 
*Since 1986
† period was 30 months for surviving animals
§ period was 30 months for some animals. 
In addition, some diesel-particle-associated PAHs were measured in the 
unfiltered exhaust. Concentrations of 13 ng/m3 of benzo(a)pyrene, 21 ng/m3 of 
benzo(e)pyrene, and 51 ng/m3 of a mixture of benzofluoranthenes were measured in 
batched samples. The authors did not specify the number of samples or the 
analytical method used to determine these concentrations. Interpretation of the 
hamster data is complicated by the fact that the animals were treated with 
antibiotics for several months during the study. Control hamsters were also 
treated with antibiotics. No significant differences in body weight developed 
between control and exposed hamsters over the entire length of the study. In 
contrast, mice and rats exposed to unfiltered diesel exhaust showed decrements 
in body weight after approximately 480 days. The median survival time of animals 
was not affected by exposure. Tissues from the nasal cavity, sinuses, larynx, 
trachea, esophagus, lungs, forestomach, glandular stomach, liver, kidneys, 
adrenals, and urinary bladder were subjected to histopathologic examination. In 
some cases, the salivary glands, thyroid, thymus, aorta, heart, spleen, lymph 
nodes, and ovaries were also subjected to histopathologic examination.
Histopathology of hamsters exposed to diesel exhaust failed to demonstrate the 
induction of tumors in the lung or upper respiratory tract. Significant deposits 
of soot particles were evident in the hamsters exposed to unfiltered diesel 
exhaust. The lungs of these animals exhibited an increased incidence (measured 
qualitatively) of thickened septa, bronchioalveolar hyperplasia, and emphysema 
compared with controls. No significant differences were found between the 
controls and the animals exposed to filtered diesel exhaust. 
Mice exposed to filtered or unfiltered diesel exhaust showed a 2.5-fold increase 
in lung tumor incidence compared with controls. Combined benign and malignant 
tumor incidences were as follows: 13% in the control group at the end of the 
study; 31% in the group exposed to filtered diesel exhaust; and 32% in the group 
exposed to unfiltered diesel exhaust. This increase was predominantly due to the 
induction of adenocarcinomas. Bronchioalveolar hyperplasia was more frequent 
(64%) in the group of mice exposed to unfiltered diesel exhaust than in mice 
exposed to filtered diesel exhaust (15%) and controls (5%). Furthermore, 
multifocal alveolar lipoproteinosis was found in 71% of the mice exposed to 
unfiltered diesel exhaust compared with 3% for filtered diesel exhaust and 4% 
for controls. Similar results were obtained for interstitial fibrosis that 
occurred almost exclusively in the mice exposed to unfiltered diesel exhaust. 
Of the 95 rats exposed to unfiltered diesel exhaust, 15 exhibited a total of 17 
lung tumors. These tumors were classified as 8 bronchiolo-alveolar adenomas and 
9 squamous cell tumors (8 benign keratinizing cysts and 1 squamous cell 
carcinoma). Hyperplasia was seen in the lungs of 94 of the 95 rats exposed to 
unfiltered diesel exhaust, and metaplasia occurred in 62 of these animals. Other 
severe inflammatory changes such as thickened septa, foci of macrophages, and 
cholesterol crystals were found in the lungs of rats exposed to unfiltered 
diesel exhaust. No changes were seen in the control animals or in those exposed 
to filtered diesel exhaust. No exposure-related changes were observed in the 
upper respiratory tracts of the rats exposed to unfiltered diesel exhaust. 
Exposure to filtered and unfiltered diesel exhaust resulted in a statistically 
significant increase in the incidence of lung adenocarcinomas in female NMRI 
mice. In hamsters, long-term exposure to unfiltered diesel exhaust led to 
broncho-alveolar hyperplasia and emphysematous lesions in the respiratory tract, 
but it did not produce tumors. In rats, long-term exposure to unfiltered diesel 
exhaust led to extensive hyperplasia and metaplasia of the broncho-alveolar 
epithelium and to a significantly increased incidence of adenomas and squamous 
cell tumors of the lung compared with controls.
 
Table 4.
Concentrations of Exhaust Components for Filtered and Unfiltered
Diesel Exhaust Measured in the Exposure Chambers
(mean ± standard deviation)
(Adapted from Heinrich et al., 1986)
      Component Control
      (clean air)Filtered exhaustUnfiltered exhaust
      Carbon monoxide (ppm)0.16 ± 0.2711.1 ± 1.9212.5 ± 2.18
      Carbon dioxide (vol.%)0.10 ± 0.010.35 ± 0.050.38 ± 0.05
      Sulfur dioxide (ppm)----1.02 ± 0.621.12 ± 0.89
      Oxides of nitrogen (ppm)----9.9 ± 1.8011.4 ± 2.09
      Nitric oxide (ppm)----8.7 ± 1.8410.0 ± 2.09
      Nitrogen dioxide (ppm)----1.2 ± 0.261.5 ± 0.33
      Alkanes (ppm)3.5 ± 0.295.2 ± 0.655.5 ± 0.69
      Methane (ppm)2.3 ± 0.172.4 ± 0.202.6 ± 0.19
      Alkanes without methane (ppm)1.3 ± 0.52.9 ± 0.503.1 ± 0.53
      Particles (mg/m3)--------4.24 ± 1.42

Mauderly et al. [1987]
Mauderly et al. [1987] reported the results of a carcinogenicity study in which 
F344 male and female rats were exposed to unfiltered diesel exhaust at three 
concentrations for up to 30 months. Diesel exhaust was generated by stationary 
light-duty diesel engines (1980 model, 5.7-liter, Oldsmobile V-8) operated by 
computer through continuously repeating U.S. Federal Test Procedure urban 
certification cycles. The exhaust effluents were diluted 10:1 with filtered air, 
serially diluted to the final concentrations, and then directed through exposure 
chambers. The average particulate concentrations for the low medium, and high 
exposures to diesel exhaust were 0.35, 3.5, and 7 mg/m3, respectively. 
Concentrations of key components identified in the diesel exhaust are shown in 
Table 5. 
Male and female F344 rats that were 15 weeks old were randomly divided by litter 
into four treatment groups. There were 365 rats in the control group, and 366, 
367, and 364 rats in the low-, intermediate-, and high-exposure groups, 
respectively. Rats were added to all treatment groups during February 1981; a 
second group of rats was added to all treatment groups 1 year later. Both groups 
of rats were derived from the same breeding colony and were exposed in the same 
chambers. The two added groups of rats were treated as one study population 
since the groups showed no differences in body weights or survival times. All 
animals were exposed to unfiltered diesel exhaust for 7 hours per day, 5 days 
per week for up to 30 months. 
All rats terminated for histopathology and all rats that died or were euthanized 
received a complete necropsy. All lesions except for soot macules and 
representative portions of each lung lobe were examined microscopically, as were 
samples of other respiratory tract tissues. Exposure to diesel exhaust did not 
cause overt signs of toxicity. No significant differences in body weight or life 
span were observed in either the males or females in the experimental groups 
compared with the controls. The physical condition of all groups of animals 
appeared to be similar. 
 
Table 5.
Concentrations of Key Components of Exposure Atmospheres*
(Adapted from Mauderly et al., 1987)
      ComponentControlLowMedium High
      Particulate (mg/m3)0.010 (0.010)†0.350 (0.070)3.470 (0.450)7.80 (0.810)
      Carbon monoxide (ppm)1 (1)3 (1)17 (7)30 (13)
      Nitric Oxide (ppm)00.6 (0.3)5.4 (1.5)10.0 (2.6)
      Nitrogen dioxide (ppm)00.1 (0.1)0.3 (0.2)0.7 (0.5)
      Hydrocarbons (ppm)3 (1)4 (1)9 (5)13 (8)
      Carbon dioxide (%)0.2 (0.04)0.2 (0.03)0.4 (0.06)0.7 (0.1)

*Mean of weekly mean values during 30 months of exposure. [return to table]
†Figures in parentheses are standard error. [return to table] 
Soot accumulated progressively and significantly in the lungs of all exposed 
rats. After 24 months of exposure, the mean lung burden of diesel exhaust 
particulate per rat was reported to be 0.6 ± 0.02 mg for the low exposure, 11.5 
± 0.5 mg for the intermediate exposure, and 20.8 ± 0.8 for the high exposure. 
These calculations were made by measuring the amount of light absorbed by lung 
homogenates from exposed rats and comparing those values with standard curves 
constructed from measurements made from known amounts of soot deposited in the 
lungs of unexposed rats.
Changes in the epithelial lining of the air spaces and progressive fibrosis 
occurred in the areas of soot accumulation. Hyperplasia and squamous metaplasia 
were seen in broncho-alveolar spaces. 
Broncho-alveolar adenomas, adenocarcinomas, benign squamous cysts, and squamous 
cell carcinomas were observed in the lungs of exposed rats. Rats exposed to the 
high concentration of diesel exhaust for up to 30 months experienced 
statistically significant increases in adenocarcinomas, benign squamous cell 
tumors, and squamous cell carcinomas in male and female rats. The increase in 
total tumor incidence for the high-exposure group was also statistically 
significant when compared with the control group. The percentages of rats with 
lung tumors (males and females combined) are listed by exposure group in Table 
6.
 
Table 6.
Percentages of Rats (Male and Female Combined)
with Lung Tumors, by Exposure Group
(Adapted from Mauderly et al., 1987)
      Exposure groupAdenomasAdenocarcinomas and
      squamous cell carcinomasSquamous cysts onlyAll tumors
      High0.47.5*4.9*12.8*
      Medium 2.3*0.50.93.6*
      Low01.301.3
      Control00.900.9

* Significantly higher than controls at p<0.05 by z statistic. [return to table] 

A statistically significant increase in adenomas occurred in the 
intermediate-exposure group. One adenocarcinoma and two squamous cysts were also 
observed in female animals in that group. The increase in all tumors in the 
intermediate-exposure group was statistically significant when compared with the 
control group.
No statistically significant increases in tumor incidence occurred in the 
low-exposure animals. Squamous tumors were always associated with focal areas of 
engine soot retention, epithelial cell alterations, and fibrosis. They are thus 
likely to represent a progression of squamous metaplasia. These tumors may have 
resulted from a generalized response to the accumulation of relatively insoluble 
particles.
None of the lung tumors had metastasized to pulmonary lymph nodes or other 
organs. Increased numbers of adducts were found in DNA extracted from the lungs 
of rats exposed to the highest concentration of diesel exhaust for 30 months.
Diesel exhaust inhaled chronically at the intermediate and high concentrations 
in this study induced a significant number of benign and malignant pulmonary 
tumors in male and female rats. The increased numbers of DNA adducts suggest 
that tumor development may have been initiated by the interaction of reactive 
metabolites of soot-associated organic compounds with lung cell DNA. In this 
study, the relationship between lung burden of diesel exhaust particulates and 
tumor prevalence was progressive rather than linear with time, rising rapidly 
late in the exposure regimen. 
Brightwell et al. [1986]
Brightwell et al. [1986] reported preliminary data on the chronic toxicity of 
diesel engine exhaust in Fischer 344 rats and Syrian hamsters. Each group of 
experimental animals was made up of 144 rats and 312 hamsters with approximately 
equal numbers of males and females. The animals were 6 to 8 weeks old at the 
start of the 2-year exposure period. 
The diesel exhaust emissions used in this study were generated by a 1.5-liter 
light-duty diesel engine. The emissions were diluted to yield particulate 
exposure concentrations of approximately 0.7, 2.2, and 6.6 mg/m3. The diesel 
emissions were either subjected to particle filtration or they were unaltered 
(unfiltered). Exposures were carried out overnight for 16 hours per day, 5 days 
per week.
The mean concentrations for carbon monoxide (CO) and nitrogen oxides (NOx) for 
both filtered and unfiltered diesel exhaust in the high-exposure groups were 32 
and 8 parts per million (ppm), respectively. Concentrations of those 
contaminants for the controls were 1 ppm CO and 0.1 ppm NOx. No data were 
presented for the concentrations of these contaminants in the intermediate- and 
low-exposure chambers. Similarly, no data were presented for exposure 
concentrations of other exhaust components, although regular analyses were 
conducted for particle size distributions, aldehydes, phenols, PAHs, sulfates, 
and individual hydrocarbons. 
Interim sacrifices of rats were conducted after 6, 12, 18, and 24 months of 
exposure, while hamsters had interim sacrifices at 6 and 16 months. All 
surviving hamsters were sacrificed at the end of 2 years of exposure. Rats that 
survived 2 years of exposure were maintained for up to 6 additional months 
without further exposure to exhaust.
Animals that died or were sacrificed were subjected to a full necropsy, and 
histopathology was carried out on the respiratory tracts (nasal passages, 
larynx, trachea, and lungs) of all animals in the high-exposure and control 
groups. Histologic examinations were also performed on the respiratory tracts of 
all animals in the groups with intermediate and low exposures to filtered and 
unfiltered diesel exhaust. Histopathology was carried out on all suspected 
tumors regardless of experimental treatment. 
The major histopathologic finding in the study was an increase in the incidence 
of primary lung tumors in rats exposed to the intermediate and high 
concentrations of unfiltered diesel exhaust. Table 7 summarizes the 
histopathologic findings for primary benign and malignant lung tumors in rats 
exposed to unfiltered diesel exhaust and to air alone. The incidence of primary 
lung tumors was 2%, 1%, 4%, and 23% for male rats in the control, low-, 
intermediate-, and high-exposure groups, respectively. Lung tumor incidence in 
female rats was 1%, 0%, 15%, and 54% for control and for low-, intermediate-, 
and high-exposure groups, respectively. However, a later analysis of these data 
[Fouillet and Brightwell 1987] points out that tumor incidence was based on the 
total number of animals examined in each treatment group. Since this total 
included some animals sacrificed after 6, 12, 18, and 24 months of exposure, 
some of them clearly were not exposed long enough to induce recognizable lung 
tumors. When tumor incidence was recalculated using only the data for rats 
surviving beyond 24 months, 44% of male and 99% of female rats exposed to 
unfiltered diesel exhaust developed lung tumors. 
 
Table 7.
Primary Benign and Malignant Lung Tumors in Rats
Exposed to Unfiltered Diesel Exhaust*
(Adapted from Brightwell et al., 1986)
        F344 rats that developed lung tumors 
      Exposure groupParticulate
      concentration (mg/m3)Males
      Number%Females
      Number%
      High6.616/71†2339/72†54
      Intermediate2.23.72411/72†15
      Low0.031/7210.720
      Control03/14021/1421

*These figures represent calculations that included animals sacrificed after 6, 
12, 18, and 24 months of exposure. [return to table]
† significant compared with controls (p<0.01). [return to table] 
No increase occurred in the incidence of primary lung tumors in any other 
treatment group. Respiratory tract tumors were rare in hamsters and were not 
attributed to treatment. 
The pathology description in this report [Brightwell et al. 1986] is very 
limited. It contains no specific diagnoses of the lung tumors, and no data on 
whether the tumors were single, multiple, lethal, or incidental. Data on degree 
of invasion are also absent. No comment is made on pathology of the nasal 
passages, larynx, or trachea. There is no description or discussion of chronic 
toxicity, hyperplasia, or the relationship of hyperplasia to neoplasia. Although 
the investigators did not present the full spectrum of their bioassay data, the 
information presented justifies the conclusion that long-term exposure to high 
concentrations of unfiltered diesel exhaust leads to a significant increase in 
the incidence of benign and malignant lung tumors in male and female F344 rats.
Ishinishi et al. [1986]
Ishinishi et al. [1986] studied F344 rats to determine the effects of long-term 
inhalation of exhausts from heavy- and light-duty diesel engines. Five-week-old 
female and male F344 rats were exposed to various concentrations of diesel 
exhausts for 6, 129 18, 24, and 30 months, 16 hours per day, 6 days per week. 
Three types of exposures were administered: exposure to filtered and unfiltered 
diesel exhaust from 11-liter heavy-duty engines, and exposure to unfiltered 
diesel exhaust from 1.8-liter light-duty engines.
For the carcinogenicity experiment, five groups of animals (each consisting of 
64 male and 59 female rats) were exposed for 30 months to unfiltered heavy-duty 
engine exhaust at a given particulate concentration originally designed to be 0, 
0.4, 1, 2, and 4 mg/m3 (see Table 8 for actual concentrations). Five additional 
groups (each consisting of 64 male and 54 female rats) were exposed for 30 
months to unfiltered light-duty engine exhaust at a given particulate 
concentration originally designed to be 0, 0.1, 0.4, 1, and 2 mg/m3 (see Table 8 
for actual concentrations). 
Two additional groups of 64 male rats were exposed to filtered exhaust from the 
heavy-duty engines. The 0.4- and 4-mg/m3 concentrations were filtered so that 
the animals were exposed only to the gaseous fraction of the exhaust. For 
comparison, three additional groups of 64 male rats were exposed to the 
unfiltered diesel exhaust from the same source at particulate concentrations of 
0, 0.4, and 4 mg/m3. Table 8 presents a summary of gas and particle 
concentrations for each exposure atmosphere.
A concentration-dependent decrease in body weight was observed, with the 
greatest effect observed in the 4-mg/m3 group exposed to exhaust from heavy-duty 
engines.
 
Table 8.
Summary of Gas and Particle Concentrations*
(Adapted from Ishinishi et al., 1986)
      Gaseous Concentration 

      Type of diesel exhaust (%)Particle concentration
      (mg/m)3NOx (ppm)NO (ppm)NO2 (ppm)CO (ppm)CO2 (%)SO2 (ppm)Formal-
      dehyde (ppm)SO4-2O2 (%)
       Target†Actual
      Unfiltered exhaust from heavy duty engine
      43.7237.4534.453.0012.910.3604.570.2936120.4
      21.84 21.67 19.99 1.68 7.75 0.215 2.82 0.18 198 20.6 
      1 0.96 13.13 12.11 1.02 4.85 0.140 1.79 0.11 111 20.7 
      0.4 0.46 6.17 5.71 0.46 2.65 0.084 0.98 0.05 62.9 20.8 
      0 0.002 0.061 0.042 0.021 0.63 0.035 0.06 0.003 0.49 20.8 

      Filtered and unfiltered exhaust from heavy-duty engine4 (unfiltered)2.99 
      36.45 31.50 4.95 12.90 0.412 4.03 0.20 358 20.3 
      4 (filtered) 0.019 36.76 32.81 3.96 13.00 0.391 4.50 0.24 1.61 20.4 
      0.4 (unfiltered) 0.39 5381 5.37 0.44 2.50 0.084 0.98 0.04 57.7 20.7 
      0.4 (filtered) 0.005 5.58 5.16 0.472 2.54 0.083 0.96 0.04 1.43 20.7 
      0 0.004 0.062 0.040 0.024 0.06 0.068 0.03 0.003 0.35 20.8 

      Unfiltered exhaust from light-duty engine 2 2.32 20.34 18.93 1.41 7.10 
      0.418 4.70 0.13 315 20.3 
      1 1.08 10.14 9.44 0.70 3.96 0.219 2.42 0.07 151 20.5 
      0.4 0.41 4.06 3.81 0.26 2.12 0.105 1.06 0.03 62.4 20.7 
      0.1 0.11 1.24 1.16 0.08 1.23 0.050 0.38 0.01 18.8 20.8 

*Exposures were for 30 months. [return to table] 
† are identified in the text by the design exposure. [return to table] 
After 6 months of exposure, "anthracosis"* was observed in all groups exposed to 
particle-containing exhausts. Severity was proportional to concentration and 
duration of exposure. Hyperplasia of type II epithelial cells and bronchiolar 
epithelium associated with anthracosis was observed after 18 months in the 
groups exposed to the higher particle concentrations. The extent of these 
conditions depended on exposure. Squamous metaplasia with focal interstitial 
fibrosis was often observed in hyperplastic lesions of the subpleural zone. 
Scanning electron microscopy revealed irregularity, shortening, and absence of 
cilia in the mucosal epithelia of the trachea and main bronchi. These lesions 
were also observed in rats exposed only to the gaseous components of the 
exhaust; the severity of the lesions increased in proportion to exhaust 
concentration and duration of exposure. 
A statistically significant increase occurred in the incidence of lung tumors in 
rats (male and female combined) exposed for 30 months to heavy-duty diesel 
engine exhaust with particulate concentrations of 4 mg/m3 compared with 
controls. Tumor incidence was 6.5% (8/124) for exposed rats and 0.8% (1/123) for 
controls. The majority of tumors were squamous cell carcinomas, adenosquamous 
carcinomas, and adenocarcinomas. 
Iwal et al, [1986]
Iwai et al. [1986] studied the effects of long-term inhalation exposure to 
filtered and unfiltered diesel exhaust in female F344 rats. Exhaust for this 
experiment was generated by a 2.4-liter light-duty diesel engine. Seven-week-old 
female rats (initially 24 animals/exposure group) were exposed to unfiltered 
exhaust, filtered exhaust, or clean air for 24 months, 8 hours/day, 7 days/week. 
Measured concentrations (mean ± standard deviation) of exhaust components were 
4.9 ± 1.6 mg/m3 for-particles, 30.9 ± 10.9 ppm for oxides of nitrogen (NOx), 1.8 
± 1.8 ppm for nitrogen dioxide (NO2), 13.1 ± 3.6 ppm for sulfur dioxide (SO2), 
and 7.0 ± 1.4 ppm for carbon monoxide (CO). Some animals were autopsied after 3, 
6, 12, and 24 months of exposure. Histologic and electron-microscopic 
examinations were performed on lungs, spleen, and other organs. Some of the rats 
exposed for 12 to 24 months were kept in clean air for an additional 3 or 6 
months and then examined.
After 6 months of exposure to unfiltered diesel exhaust, phagocytotic 
macrophages filled with black particles were distributed in an irregular pattern 
in the lungs. Areas where macrophages were gathered showed proliferations of 
Type II alveolar epithelial cells showing adenomatous metaplasia. More lesions 
were found after 1 year of exposure, but no neoplastic lesions were observed. 
Two adenomas were found in one of five rats kept in clean air for 3 months after 
1 year of exposure to unfiltered exhaust. After 2 years of exposure, the number 
of particles in the macrophages increased markedly. Fibrous thickening of 
alveolar walls was observed, and mast cell infiltration was found with 
epithelial hyperplasia where macrophages gathered. Neoplastic changes were 
observed after 2 years of exposure; some of these showed intra-lymphatic 
invasion indicative of malignant transformation. Two types of lung carcinoma 
(adenocarcinoma and squamous or adenosquamous carcinoma) were observed.
In the rats exposed to filtered diesel exhaust, histologic changes were minimal, 
and no heterotrophic hyperplasia was observed in the alveolar walls. 
Quantitative analysis of epithelial proliferative changes in the lung indicated 
an increase in affected areas that was associated with the length of exposure to 
unfiltered exhaust.
Rats exposed to unfiltered exhaust had a statistically significant increase in 
lung tumor incidence compared with controls. After 24 months of exposure, 4/14 
rats had tumors, 2 of which were malignant. After an additional 6 months in 
clean air, four of the five remaining rats had tumors, three of which were 
malignant. The combined incidence of tumors was 42% (8/19) in rats exposed to 
unfiltered diesel exhaust compared with 0% (0/16) in rats exposed to filtered 
exhausts and 4.5% (1/22) in the controls. The distribution of tumor types found 
in rats exposed to unfiltered diesel exhaust was as follows: 
      Adenomas 3 rats 
      Adenocarcinoma3 rats 
      Adenosquamous carcinomas2 rats 
      Squamous carcinoma1 rat 
      Large cell carcinoma1 rat 

The tumor found in the control rat was an adenoma. The authors concluded that 
the significantly higher incidence of lung tumors in the unfiltered exhaust 
exposure group could be attributed to the inhalation of particles. 
Another important observation in this study was a statistically significant 
increase in the incidence of splenic malignant lymphoma, with or without 
leukemia. After 24 months, the incidence rate was 25.0% (6/24) for rats exposed 
to unfiltered diesel exhaust, 37.3% (9/24) for rats exposed to filtered diesel 
exhaust, and 8.2% (2/24) for controls. The incidence of tumors in other organs 
also increased in rats exposed to filtered exhaust (25%, or 6/24) and unfiltered 
exhaust (29%, or 7/24) compared with controls (8.2%, or 2/24). The multiplicity 
of tumors increased both in rats exposed to unfiltered exhaust and in those 
exposed to filtered exhaust, with a quadrupled incidence of tumors noted only in 
the unfiltered exhaust group. 
Human Health Effects
The niosh document entitled Evaluation of the Potential Health Effects of 
Occupational Exposure to Diesel Exhaust in Underground Coal Mines [niosh 1986] 
contains discussions of all pertinent epidemiologic data available at the time. 
Although many epidemiologic studies of diesel-exposed populations had been 
conducted before 1986, the only documented health effects in humans were 
reversible pulmonary function changes (before and after a workshift) in salt 
miners [Gamble et al. 1979] and exposure-related eye irritation among men 
experimentally exposed to diesel exhaust [Battigelli 1965]. Past epidemiologic 
studies of occupational exposure to diesel exhaust and mortality from cancer 
have been inconclusive partly because of a myriad of methodologic problems 
[niosh 1986]. The problems included incomplete information on the extent of 
exposure, insufficient time from first exposure to allow for the appearance of 
exposure-related cancer, and confounding variables such as smoking and exposure 
to asbestos or ionizing radiation. These problems made it impossible to draw 
definitive conclusions about the cause of any observed excess of cancer 
incidence [niosh 1986]. 
Since the release of that document [niosh 1986], the final results of three 
epidemiologic studies have been released [Edling et al. 1987; Garshick et al. 
1987a; Garshick et al. 1988]. Preliminary reports of data from each of these 
studies were discussed in the niosh document [niosh 1986]. Two of these recently 
released final reports [Garshick et al. 1987a; Garshick et al. 1988] have 
indicated an increased risk of death from lung cancer among railroad workers 
exposed to diesel engine emissions. These studies are summarized in Table 9 and 
discussed more fully in this section. The validity of the results obtained in 
the study by Edling et al. [1987] was questionable because of the small size of 
the cohort analyzed (694 male employees of five different bus companies), and 
because no exposure measurements were taken (exposures were estimated by job 
title). For these reasons, the study by Edling et al. [1987] will not be 
discussed in detail in this bulletin.
Garshick et al. [1987a]
Garshick et al. [1987a] conducted a case-control study of deaths among U.S. 
railroad workers to test the hypothesis that lung cancer is associated with 
exposure to diesel exhaust. The study included only male railroad workers who 
had at least 10 years of railroad service, were vested in the railroad 
retirement program, were born on or after January 1, 1900, and died between 
March 1, 1981, and February 28, 1982. The investigators collected death 
certificates for 87% of the 15,059 deaths reported to the U.S. Railroad 
Retirement Board. Within the cohort, 1,256 workers who died from lung cancer 
were matched with two deceased comparison workers by age (± 2.5 years) and date 
of death (± 31 days). Deceased workers whose jobs had involved exposure to 
diesel exhaust (engineers and firemen, brakemen and conductors, diesel 
locomotive repair workers, and hostlers) were compared with deceased workers 
without occupational exposure to diesel exhaust (clerks and station agents). 
Work histories were determined from yearly job reports filed with the U.S. 
Railroad Retirement Board. These reports were used to classify workers as 
exposed or unexposed to diesel exhaust. The classifications were confirmed by 
measuring current exposures to respirable particulate matter for workers in 
selected jobs. Respirable particulate matter was chosen as a marker for exposure 
to the particulate fraction of diesel exhaust. The respirable particulate 
fraction was sampled because it included all of the diesel exhaust particulates 
and excluded some of the larger nondiesel particulates. Respirable dust 
exposures were corrected for cigarette smoke particulates by analyzing the 
nicotine content of composite samples [Woskie et al. 1988a; Woskie et al. 
1988b]. An adjusted respirable particulate concentration was then calculated for 
each job group by subtracting the applicable average fraction of cigarette smoke 
from each railroad's average respirable particulate concentration. Personal 
exposure to respirable particulate matter was measured for 39 common jobs in 
four U.S. railroads over a 3-year period. 
 
Table 9.
Characteristics of Epidemiologic Studies of Exposure to 
Diesel Exhaust and Carcinogenicity, Published Since 1986
      Investigator Population studied Observation period Findings Comments 
      Garshick et al. 1987a U.S. railroad workers born in 1900 or later with 10 
      or more years of service 1959-81 for diesel exhaust exposure; deaths that 
      occured between March 1, 1981, and February 28, 1982. Workers exposed 
      occupationally to diesel exhaust for 20 years had a significantly 
      increased relative odds ratio (1.41, 95% CI*=1.06, 1.88) of lung cancer 
      Population-based, case-control study that included industrial hygiene 
      characterization of exposures and multiple conditional logistic regression 
      analysis to adjust for confounders such as smoking and asbestos exposures. 
      Only 87% of death certificates were collected. 
      Garshick et al. 1988 U.S. railroad workers aged 40 to 64 in 1959 who 
      started railroad service 10 to 20 years earlier 1959-1980 for diesel 
      exposure; deaths that occurred before December 31, 1980 Workers aged 40-44 
      in 1959 had a significantly increased relative risk (1.45, 95% CI=1.11, 
      1.89) of lung cancer Retrospective cohort study. Only 88% of death 
      certificates were collected. Effects of smoking could not be eliminated. 
      The effect of asbestos exposures was addressed by considering 
      diesel-exposed workers separately from asbestos-exposed workers using a 
      proportional hazards regression model. 

*CI= confidence interval. [return to table]
According to the authors, diesel locomotives replaced steam locomotives over a 
short period (from 14% diesel use in 1947 to 95% in 1959). Thus the year 1959 
was chosen as the effective beginning of diesel exhaust exposure for this study. 
Workers who retired before that year were classified as unexposed to diesel 
exhaust. The authors acknowledged that some workers had additional earlier years 
of diesel exhaust exposure. Smoking histories were obtained by questionnaires 
from the deceased workers' closest relatives or by direct telephone contact if 
there was no response to the questionnaire. Asbestos exposures in railroad 
workers occurred primarily in the steam engine era. Asbestos exposure for this 
study was therefore categorized by the job held in 1959 (the end of the steam 
locomotive era) or by the last job held if retirement occurred before 1959.
The relative hazard of lung cancer attributable to diesel exhaust exposure was 
calculated using a multiple conditional logistic regression to adjust for 
smoking and asbestos exposure. A statistically significant increase in relative 
odds (1.41, 95% CI=1.06-1.88) was found for lung cancer among workers aged 64 or 
younger at the time of death who had worked in a [diesel-exposed] job with 
diesel exposure for 20 years. No increase was found in workers aged 65 or older. 
The authors felt that this finding reflected the fact that many of these men 
retired shortly after the transition to diesel-powered locomotives. 
Garshick et al. [1988]
To confirm the results of the case-control study, Garshick et al. [1988] 
evaluated the risk of lung cancer as a result of exposure to diesel exhaust from 
railroad locomotives. These investigators conducted a retrospective cohort study 
of 55,407 white male railroad workers who were aged 40 to 64 in 1959 and who had 
started railroad service 10 to 20 years earlier. The cohort was traced until the 
end of 1980. Death certificates were obtained for 88% of 19,396 deaths, and 
1,694 lung cancer cases were identified. Records of yearly job assignments 
obtained through the Railroad Retirement Board served as an index of diesel 
exhaust exposure. Workers were considered to be either exposed or unexposed to 
diesel exhaust, depending on the yearly job code. These classifications were 
confirmed by measurements of current exposures to respirable particulate matter 
for workers in selected jobs. These measurements were analyzed as described in 
the earlier discussion of the 1987 case-control study [Garshick et al. 1987a]. A 
proportional hazards model and directly standardized rates were used to 
calculate the relative risk of lung cancer for a worker whose job involves 
diesel exhaust exposure. The group of workers aged 40 to 44 in 1959 had a 
relative risk of 1.45 (95% CI=1.11-1.89) for lung cancer. This group consisted 
of workers with the longest possible duration of diesel exposure.
To control for the confounding effects of asbestos exposures in the cohort, the 
relative risk of lung cancer was not considered for groups of workers with 
possible exposures to asbestos in the past (shop workers and hostlers). When 
this analysis was conducted, the relative risk for lung cancer remained elevated 
at 1.57 (95% CI=1.19-2.05) in the group aged 40 to 44 in 1959, and it was 1.34 
(95% CI=1.02-1.76) in the workers aged 45 to 49 in 1959. These results confirmed 
those obtained with the proportional hazards regression model. 
The effects of cigarette smoking could not be eliminated because of the 
retrospective nature of the study. However, the prevalence of cigarette smoking 
was the same for workers with and without potential diesel exhaust exposure in a 
group of 517 current railroad workers who were surveyed in 1982 regarding past 
asbestos exposure [Garshick et al. 1987b]. 
Epidemiologic studies of lung cancer risk in diesel-exposed workers are 
inherently problematic because of (1) the difficulty in defining and quantifying 
exposure, (2) the relatively short time between initial exposures and analysis 
of risk in some studies, and (3) the need to control for cigarette smoking. The 
reports by Garshick et al. [1987a; 1988] are the most thorough epidemiologic 
studies conducted to date. Data on cigarette smoking were collected in the 
case-control study. An attempt was made to control for the confounding exposure 
to asbestos. Attempts were also made to characterize exposures to diesel exhaust 
through the collection of industrial hygiene data. The period between the first 
diesel exposure and data analysis was adequate to allow the observation of 
exposure-related cancer for some age groups of the cohort. The fact that the 
findings of the two studies were both independent (the two studies based their 
analyses on different lung cancer deaths) and consistent fortifies the 
conclusion that occupational exposure to diesel exhaust is associated with an 
increased risk of lung cancer.
The studies of Garshick et al. [1987a; 1988] are subject to a number of 
limitations, some of them inherent, that preclude them from providing definitive 
evidence that diesel exhaust is an occupational carcinogen. Ascertainment of 
death certificates was incomplete in both studies (87% in the case-control 
study, and 88% in the retrospective cohort study). In both reports of final 
data, the authors presented data on lung cancer risk only for separate-age 
subcohorts within the study population. Though there is merit in the authors' 
rationale for splitting the groups by age, the risk analysis should have 
considered diesel exposure for the combined cohort also. The investigators 
attempted to characterize exposures to diesel exhaust by collecting industrial 
hygiene data, but they were forced to use an experimental approach to collect 
them. Exposure to diesel exhaust is difficult to measure because of the complex 
nature of the exhaust. Measuring exposure to respirable particulate matter as a 
surrogate for diesel exhaust allows for a substantial error in classification of 
exposures, as there is no way to define the source of the particulates. 
Adjusting the measurements to exclude the contribution of cigarette smoke 
particulates eliminates only one extraneous source of respirable particulates. 
The classification of exposed and unexposed workers is particularly important to 
the outcome of the case-control study because the unexposed workers were used as 
the referent population. Furthermore, no attempts were made to control for 
potentially confounding exposures to pyrolysis products of fuels that were used 
to power locomotives before the use of diesel fuel. 
Conclusions
Recent animal studies in rats and mice confirm an association between the 
induction of cancer and exposure to whole diesel exhaust. The lung is the 
primary site identified with carcinogenic or tumorigenic responses following 
inhalation exposures. Limited epidemiologic evidence suggests an association 
between occupational exposure to diesel engine emissions and lung cancer. The 
consistency of these toxicologic and epidemiologic findings suggests that a 
potential occupational carcinogenic hazard exists in human exposure to diesel 
exhaust. Tumor induction is associated with diesel exhaust particulates. Limited 
evidence indicates that the gaseous fraction of diesel exhaust may be 
carcinogenic, as well. 
Recommendations
Classification systems for identifying a substance as a carcinogen have been 
developed by the National Toxicology Program (NTP) [NTP 1984], the International 
Agency for Research on Cancer (IARC) [IARC 1979], and OSHA in its 
"Identification, Classification, and Regulation of Potential Occupational 
Carcinogens" [29 CFR** 1990], also known as "The OSHA Cancer Policy." niosh 
considers the OSHA classification the most appropriate for use in identifying 
potential occupational carcinogens† [29 CFR** 1990]. Exposure to diesel exhaust 
has been shown to produce benign and malignant tumors in rats and mice. 
Therefore, niosh recommends that whole diesel exhaust be regarded as a potential 
occupational carcinogen in conformance with the OSHA Cancer Policy (29 CFR 
1990).
The excess cancer risk for workers exposed to diesel exhaust has not yet been 
quantified, but the probability of developing cancer should be decreased by 
minimizing exposure. As prudent public health policy, employers should assess 
the conditions under which workers may be exposed to diesel exhaust and reduce 
exposures to the lowest feasible limits. Although a substantial amount of 
information suggests that some component (or combination of components) of the 
particulate fraction of diesel exhaust is associated with tumor initiation, the 
relative roles of the particulate and gaseous phases of emissions need further 
characterization. 
Research Needs
The particulate exposures used in some of the studies summarized here may have 
inhibited pulmonary clearance mechanisms, resulting in unusually large particle 
deposits in the lung [Vostal 1986]. Research on how particle deposition and 
particle-associated organic compounds influence the carcinogenicity of inhaled 
diesel exhaust might clarify the roles of the particles themselves versus the 
chemicals associated with the particles. The fraction of diesel exhaust 
containing the causative agent (or combination of agents) needs to be further 
defined, and those agents need to be identified.
Engineering control techniques can be effective in reducing the production or 
toxicity of diesel engine emissions. Fuel and engine modifications and exhaust 
treatment all have been investigated, and each approach entails costs as well as 
benefits. No technique effectively reduces or controls all components of diesel 
exhaust. Research is needed to improve the efficacy of known engineering 
controls, to develop additional techniques, to evaluate the combined effects of 
engineering controls, and to identify which controls are most appropriate for 
various uses of diesel-powered equipment. A preferred engineering control 
technique is substitution (replacing a hazardous material or process with an 
alternative that has a lower health risk). However, the health and safety 
implications of any proposed alternatives to diesel power require careful 
evaluation before implementation. 
Diesel exhaust is a very complex mixture, and its composition varies greatly 
with fuel and engine type, load cycle, maintenance, tuning, and exhaust gas 
treatment. This complexity is compounded by the multitude of environmental 
backgrounds in which diesel-powered equipment is operated. Gases and 
particulates found in the workplace may emanate from a number of sources, 
including diesel engines. Methods have been developed and used for apportioning 
the contribution of highway vehicle emissions from various sources [Hampton et 
al. 1983] and for apportioning sources of occupational exposure to engine 
exhaust [Currie et al. 1981; Johnson et al. 1981; Cantrell et al. 1986]. 
Although niosh-validated sampling and analytical methods exist for components of 
diesel exhaust, none of these methods can be used to apportion sources of 
exposure. Quantitative risk estimates are yet to be developed for workers 
exposed to diesel exhaust. Studies involving measurement or careful estimation 
of the extent of exposure to diesel exhaust are urgently needed.  
Notes
*Anthracosis is assumed to mean discoloration of the lung. [return to text]
**Code of Federal Regulations. See CFR in references. 
†"'Potential occupational carcinogen' means any substance, or combination or 
mixture of substances, which causes an increased incidence of benign and/or 
malignant neoplasms, or a substantial decrease in the latency period between 
exposure and onset of neoplasms in humans or in one or more experimental 
mammalian species as the result of any oral, respiratory, or dermal exposure, or 
any other exposure which results in the induction of tumors at a site other than 
the site of administration. This definition also includes any substance which is 
metabolized into one or more potential occupational carcinogens by mammals" [29 
CFR 1990]. [return to text]
 
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