Table Of ContentABSTRACT
A novel strategy was used to assess the risk to health from exposure
to polycyclic aromatic hydrocarbons (PAHs), an important class of chemical
carcinogens, in workers in the paving and roofing industries using bitumen.
The aim was to evaluate the risk of exposure to PAHs at three
different stages: these were external exposure "external dose", internal
exposure "internal dose" and biological effect "biologically effective dose".
The approaches used for quantifying the risk at these stages were ambient
monitoring, biological monitoring and biological effect monitoring,
respectively.
Ambient monitoring was carried out by personal air sampling and
measurement of PAH-exposure. Excretion of thioethers (a non-selective
biomarker) and 1-hydroxypyrene (a selective biomarker of exposure to
pyrene) in urine were determined. Urinary d-glucaric acid, sister chromatid
exchange in peripheral blood lymphocytes and micronuclei in exfoliated cells
were use for biological effect monitoring. Seven groups of workers were
studied. These were office workers, departmental staff and manual workers
who were not occupationally exposed to PAHs and who were included as
controls, and two groups of payers and roofers who were exposed to bitumen
fumes during their work.
The ambient monitoring program revealed that concentrations of
PAHs in environmental air could be as high as those found in the payers' and
roofers' occupational environments. The contribution of these background
levels to the external dose of the pa yers and roofers was considerable. Payers
and roofers were occupationally exposed to low levels of PAHs. The PAH
profile in the personal air sample of the workers was different between the
two industries. This was attributed to the presence of PAH-emission sources
other than hot bitumen, such as vehicle exhaust. The concentration of
naphthalene measured in air samples was a good indicator for identifying the
existence of these sources. The quantitative evaluation of the carcinogenic risk
inherent in the external dose using the 8 hour TWA concentration as a
measuring stick did not seem to be effective due to the low "noise" levels of
carcinogenic PAHs present. A semi-quantitative measure of the external
exposure was suggested which appeared to be a better reflection of the
carcinogenic risk.
Urinary thioethers are not sensitive enough to be used as a non-
selective biomarker of exposure to low levels of PAHs; however, urinary 1-
hydroxypyrene was a good indicator of internal exposure to pyrene and
therefore PAHs in bitumen fume. The relationship between 1-hydroxypyrene
in urine and specific airborne PAH-exposure indices in the results of the
payers, but not the roofers, suggested that the route of exposure in the latter is
mainly dermal while that in the payers is more related to respiratory uptake.
This observation, however, did not agree with the subjective occupational
hygiene assessment where it was observed that the roofers were closer to the
source of PAH-emissions due to the nature of their job and both groups did
not use any respiratory or personal protective equipment.
The measurement of urinary d-glucaric acid excretion suggested, but
not strongly, that hepatic enzyme activity was induced in the occupationally
PAH-exposed groups in comparison to controls and reflected the internal
dose of pyrene or total PAHs. These observation; however, need further
investigation. Micronuclei in exfoliated epithelial cells could not be measured
in these populations as insufficient bladder epithelial cells were obtained for
analysis. Sister chromatid exchange in peripheral blood lymphocytes of
payers and roofers was significantly elevated in comparison to control and
manual worker group. The group mean frequencies of SCE were significantly
correlated with the external exposure to carcinogenic PAHs. This observation
suggested that sister chromatid exchange is a very sensitive cytogenetic
endpoint and is useful for evaluating the risk of exposure to low levels of
carcinogenic PAHs.
Risk assessment, such as the one conducted in this study, allows a
quantitative estimation of risk associated with long-term exposure to
moderate and low levels of airborne exposure to PAHs in bitumen fume.
Knowledge of dose response relationship may allow a review of current
Occupational Exposure Standards (OES) and Biological Exposure Limits,
which are at present either unavailable or based on poor background
scientific knowledge for most PAH compounds.
In this study we have suggested an Occupational Exposure Limit for
PAHs based on the sum of fourteen PAH-species.
I
PUBLICATIONS
Ambient, Biological, and Biological Effect Monitoring of Exposure to
Polycyclic Aromatic Hydrocarbons (PAHs), B.A. Hatjian, J.W. Edwards, J.
Harrison, F.M. Williams, P.G. Blain, Proceedings of the International
Symposium on Human Health and Environment, September 1994, p. 78.
Ambient, Biological, and Biological Effect Monitoring of Exposure to
Polycyclic Aromatic Hydrocarbons (PAHs), B.A. Hatjian, J.W. Edwards, J.
Harrison, F.M. Williams, P.G. Blain, Toxicology Letters, (Full article in press)
TABLE of CONTENTS
SECTION I: INTRODUCTION
CHAPTER 1: RISK ASSESSMENT
1.1 Risk Assessment 1
1.2 Risk Assessment in Occupational Health 3
CHAPTER 2: OCCUPATIONAL MONITORING
2.1 Monitoring Exposure to Occupational Hazards 7
2.2 Ambient Monitoring 7
2.2.1 Definition 7
2.2.2 Types 9
2.2.2.1 Area Sampling 9
2.2.2.2 Personal Air Sampling 9
2.2.3 Practical Considerations 10
2.3 Biological Monitoring (BM) 10
2.3.1 Background 10
2.3.2 Types of Biological Monitoring Activities 12
2.3.2.1 Biological Monitoring of Exposure 12
2.3.2.2 Biological Monitoring of Effect 14
2.3.2.3 Biological Monitoring of Susceptibility 16
2.3.3 Uses of Biological Monitoring 16
2.3.3.1 In Occupational Health 17
2.3.3.2 In Epidemiological Research 18
2.3.4 Current and Future Research 20
2.4 Biological Markers (Biomarkers) 22
2.4.1 Definition 22
2.4.2 Types 22
2.4.2.1 Biomarkers of Exposure 23
2.4.2.2 Biomarkers of Effect 23
2.4.2.3 Biomarkers of Susceptibility 24
2.4.3 Selection 24
2.4.4 Validation 26
2.4.5 Variability 27
2.4.6 Quality Assurance 31
2.4.7 Legal and Ethical Issues 33
2.4.8 Limitations 35
2.5 A Concluding Remark on Occupational Monitoring 37
CHAPTER 3: POLYCYCLIC AROMATIC HYDROCARBONS (PAHs)
3.1 Definition 39
3.2 Sources 39
3.3 Importance to Occupational Health 39
3.4 In the General and Occupational Environment 41
3.5 Toxicokinetics 41
3.5.1 Absorption 41
3.5.2 Distribution 45
3.5.3 Metabolism 45
3.5.3.1 Metabolism of Pyrene 46
3.5.3.2 Metabolism of Carcinogenic PAHs 47
3.5.4 Excretion 50
3.6 Effects of Exposure 51
3.6.1 Mutagenesis 52
3.6.2 Carcinogenesis 52
3.7 PAl-Is in Cancer Epidemiology 53
3.7.1 Skin Cancer 53
3.7.2 Lung Cancer 54
3.7.3 Bladder Cancer 55
3.7.4 Cancer of the Castro-intestinal Tract 55
3.7.5 Brain Cancer 55
3.7.6 Other Types of Cancer 56
CHAPTER 4: OVERVIEW ON BITUMEN
4.1 Definition of Bitumen and Asphalt 57
4.2 Bitumen: A Sources of PAHs 57
4.3 Types, Occurrence and Uses 59
4.4 Occupational Exposure 61
4.4.1 Occupational Exposure Limits 63
4.5 Occupational Monitoring of Exposure to Bitumen Fume 64
4.5.1 Ambient Monitoring 64
4.5.2 Biological Monitoring 65
4.6 Effects of Exposure to Bitumen/Bitumen Fumes 66
4.6.1 Acute Toxicity 66
4.6.1.1 Animal Studies 66
4.6.1.2 Human Studies 66
4.6.2 Mutagenicity 67
4.6.3 Carcinogenicity 68
4.6.3.1 Animal Studies 68
4.6.3.2 Human Studies 69
CHAPTER 5: THE STUDY
71
5.1 Background
75
5.2 Aims of the Study
SECTION II: GENERAL METHODOLOGY
CHAPTER 6: AMBIENT MONITORING OF PAHs
6.1 Ambient Monitoring of PAHs 78
6.2 Available Methods 78
6.2.1 Total Particulate Matter & Benzene Soluble Material 78
6.2.1.1 Advantages and Disadvantages 79
6.2.2 Analysis of PAH-Species 80
6.2.2.1 Advantages and Disadvantages 80
6.2,3 Biological Approach 81
6.2.3.1 Advantages and Disadvantages 81
6.3 Selection of Method (Analysis of PAH-Species) 82
6.3.1 Principle of Method 83
CHAPTER 7: BIOLOGICAL MONITORING OF PAHs-EXPOSURE
7.1 Biological Monitoring of PAHs 84
7.2 Non-Selective Biomonitoring of PAHs 85
7.2.1 Mutagenicity Assays 85
7.2.1.1 Advantages and Disadvantages 85
7.2.2 Urinary Thioethers 86
7.2.2.1 Advantages and Disadvantages 88
7.2.3 Other Methods 89
7.3 Selection of Method (Urinary Thioethers) 89
7.3.1 Principle of Method 90
7.4 Selective Biomonitoring of PAHs-Exposure 92
7.4.1 Analysis for Parent PAHs 92
7.4.1.1 Advantages and Disadvantages 93
7.4.2 Analysis for Metabolites of PAHs 93
7.4.2.1 Advantages and Disadvantages 94
7.4.3 DNA Adducts 96
7.4.3.1 Experimental Toxicology 97
7.4.3.2 Occupational Health 99
7.4.3.3 Advantages and Disadvantages 100
7.4.4 Protein Adducts 101
7.4.4.1 Advantages and Disadvantages 103
7.5 Selection of Method (Urinary 1-Hydroxypyrene) 104
7.5.1 Principle of Method 104
CHAPTER 8: BIOLOGICAL EFFECT MONITORING OF PAHs-EXPOSURE
8.1 Biological Effect Monitoring of PAHs 105
8.2 Biological Monitoring of Biochemical Changes 107
8.2.1 Urinary 61-Hydroxycortisol 108
8.2.1.1 Advantages and Disadvantages 108
8.2.2 Urinary D-Glucaric Acid 109
8.2.2.1 Advantages and Disadvantages 112
8.3 Selection of Method (Urinary D-Glucaric Acid) 112
8.3.1 Principle of Method 113
8.4 Biological Monitoring of Cytogenetic Effects 113
8.4.1 Chromosomal Aberrations 116
8.4.1.1 Background 116
8.4.1.2 Structural Chromosomal Aberrations 116
8.4.1.3 Numerical Chromosomal Aberrations 117
8.4.1.4 Advantages and Disadvantages 118
8.4.2 Micronuclei Test in Exfoliated Epithelial Cells 119
8.4.2.1 Background 119
8.4.2.2 Kinetics of Micronuclei Formation 119
8.4.2.3 Advantages and Disadvantages 121
8.4.3 Sister Chromatid Exchange 123
8.4.3.1 Background 123
8.4.3.2 Advantages and Disadvantages 127
8.4.3.3 Confounding Factors 128
8.5 Selection of Method (Micronuclei Test) 131
8.5.1 Principle of Method 131
8.6 Selection of Method (Sister Chromatid Exchange) 132
8.6.1 Principle of Method 132
CHAPTER 9: URINARY CONCENTRATIONS OF BIOMARKERS
9.1 Correction of Urinary Concentrations of Biomarkers 135
9.2 Available Methods for Correction 136
9.2.1 Specific Gravity of Urine 137
9.2.2 Urinary Creatinine 137
9.2.2.1 Advantages and Disadvantages 138
9.2.2.2 Appropriate Usage of Creatinine Results 139
9.3 Selection of Method (Urinary Creatinine) 141
CHAPTER 10: METHODS
10.1 Measurement of PAH-Species 143
10.1.1 Air Sampling 143
10.1.2 Chemical Analysis of Samples 145
10.1.3 Evaporation, Partitioning and Recovery 153
10.1.4 Characteristics of the Assay 158
10.1.5 Decontamination Process 160
10.2 Measurement of Urinary Thioethers 163
10.2.1 List of Material 163
10.2.2 Procedure 163
10.2.3 Characteristics of the Assay 164
10.3 Measurement of Urinary 1-Hydroxypyrene 166
10.3.1 List of Material 166
10.3.2 Procedure 166
10.3.3 Elution Flow Rate and Recovery Study 168
10.3.4 Enzyme Hydrolysis Study 168
10.3.5 Characteristics of the Assay 170
10.4 Measurement of Urinary D-Glucaric Acid 175
10.4.1 List of Material 175
10.4.2 Procedure 175
10.4.3 Characteristics of the Assay 176
10.5 Measurement of Micronuclei Frequency in Exfoliated Cells 178
10.5.1 List of Material 178
10.5.2 Procedure 178
10.5.3 Characteristics of the Assay 179
10.6 Measurement of SCEs in Human PBLs 182
10.6.1 List of Material 182
10.6.2 Procedure 182
10.6.3 Characteristics of the Assay 183
10.6 Measurement of Urinary Creatinine 188
10.6.1 List of Material 188
10.6.2 Procedure 188
10.6.3 Characteristics of the Assay 188
CHAPTER 11: STUDY DESIGN
11.1 Study Population 191
11.2 Sampling scheme 192
11.2.1 Static and Personal Air Sampling 192
11.2.2 Urine Sampling 192
11.2.3 Blood Sampling 193
11.3 Processes and Work Conditions 193
11.3.1 Survey A 195
11.3.2 Survey B 195
11.3.3 Survey C 196
11.3.4 SurveyD 197
11.4 Population Grouping 199
Description:3.7.5 Brain Cancer. 55. 3.7.6 Other Types of Cancer. 56. CHAPTER 4: OVERVIEW ON BITUMEN. 4.1 Definition of Bitumen and Asphalt. 57. 4.2 Bitumen: A Sources of PAHs. 57. 4.3 Types, Occurrence and Uses. 59. 4.4 Occupational Exposure. 61. 4.4.1 Occupational Exposure Limits. 63.
