Toxicology of Industrial Compounds

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12 Biomarkers and Risk Assessment KARI HEMMINKI Karolinska Institute, Huddinge Introduction Many chemical carcinogens cause covalent DNA-binding products, adducts, which may induce mutations or other types of DNA damage in important growth-controlling genes or loci resulting in aberrant cellular growth and cancer (Harris, 1991; IARC 1992; Hemminki, 1993). Human exposure to compounds such as polycyclic aromatic hydrocarbons (PAH) can be determined, for example, by ambient air, biological or DNA adduct monitoring. The usefulness of a method for the determination of DNA adducts in human biomonitoring requires high sensitivity because the levels of adducts are low. Here the primary focus is on the assessment of exposure using the above indicators in industries where high exposure to PAHs occur, such as iron founding, coke production, aluminium production, garage work and engine overhauling with exposure to used lubricating oils. Biomonitoring of PAH exposure Literature on the application of DNA adduct studies in humans is extensive (Beach and Gupta, 1992; IARC, 1993, 1994; Hemminki et al., 1993a; Hemminki, 1994). A large majority of the 32 P-postlabelling studies on human samples focus on tobacco smoking, occupational exposures and cancer chemotherapy patients. Most occupational exposures studied relate to complex mixtures, including polycyclic aromatic hydrocarbons (PAHs). In exposure to complex mixtures multiple radioactive spots (called diagonal radioactive zones, DRZ) are detected. The adduct spots cannot be definitively identified nor quantitated. As it has turned out that for many adducts labelling is not completed, even among structural analogues such as PAHs, the adduct levels measured are likely to be underestimates (Segerbäck and Vodicka, 1993).
Table 12.1 Exposure and aromatic adducts in occupational populations, presented in simplified tabulated form K.HEMMINKI 159 Notes: a Total white blood cells. b Lymphocytes. c Not given. d No data. The types of occupational groups studied by postlabelling include foundry, coke oven and aluminium workers, roofers, garage and terminal workers, car mechanics and chimney sweeps. All these groups have had an
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Toxicology of Industrial Compounds
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This edition published in the Taylo
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8. Pulmonary Toxicity Studies with
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Preface A large number of chemical
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Contributors May Akrawi Department
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Beverly M.Kulig TNO Toxicology, Dep
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Richard A.Versen Schuller MTC, Heal
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1 Biomonitoring and Absorption of I
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4 BIOMONITORING AND ABSORPTION OF I
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10 BIOMONITORING AND ABSORPTION OF
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2 Toxicokinetics and Biodisposition
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14 TOXICOKINETICS AND BIODISPOSITIO
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3 Metabolic Activation of Industria
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38 METABOLIC ACTIVATION OF INDUSTRI
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4 Sizing up the Problem of Exposure
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46 SIZING UP THE PROBLEM OF EXPOSUR
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5 Metabolism of Reactive Chemicals
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62 METABOLISM OF REACTIVE CHEMICALS
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6 Methods for the Determination of
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74 METHODS FOR THE DETERMINATION OF
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PART THREE Pulmonary toxicology of
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92 CARCINOGENIC POTENTIAL OF MAN-MA
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100 CARCINOGENIC POTENTIAL OF MAN-M
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Page 152 and 153: 10 Mechanisms of Pulmonary Sensitiz
Page 154 and 155: 140 MECHANISMS OF PULMONARY SENSITI
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Page 174 and 175: 160 BIOMARKERS AND RISK ASSESSMENT
Page 182 and 183: 168 EXTRAPOLATION OF TOXICITY DATA
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Page 196 and 197: 182 MOLECULAR APPROACHES TO ASSESS
Page 212 and 213: 198 EVALUATION OF TOXICITY TO THE I
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208 USE OF LONG-TERM CULTURES OF HE
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PART FIVE Mechanisms of toxicity of
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224 PEROXISOME PROLIFERATION normal
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226 PEROXISOME PROLIFERATION demons
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228 PEROXISOME PROLIFERATION Specie
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230 PEROXISOME PROLIFERATION intend
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232 PEROXISOME PROLIFERATION BENTLE
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234 PEROXISOME PROLIFERATION KRAUPP
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236 PEROXISOME PROLIFERATION POPP,
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18 Neurotoxicity Testing of Industr
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240 NEUROTOXICITY TESTING OF INDUST
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256 ENDOCRINE TOXICOLOGY OF THE THY
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20 Testing and Evaluation for Repro
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282 TESTING AND EVALUATION FOR REPR
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PART SIX Toxicity of selected class
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302 SPECIAL POINTS IN THE TOXICITY
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310 TOXICOLOGY OF TEXTILE CHEMICALS
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318 ANTIOXIDANTS AND LIGHT STABILIS
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340 TOXICOLOGY OF SURFACTANTS Inter
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342 TOXICOLOGY OF SURFACTANTS Figur
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344 TOXICOLOGY OF SURFACTANTS probl
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346 TOXICOLOGY OF SURFACTANTS nonio
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348 TOXICOLOGY OF SURFACTANTS and t
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350 TOXICOLOGY OF SURFACTANTS long-
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352 TOXICOLOGY OF SURFACTANTS COULS
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354
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25 Low Dose of a Genotoxic Carcinog
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358 CARCINOGENESIS AT LOW DOSE Tabl
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360 CARCINOGENESIS AT LOW DOSE year
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26 Controversial Mechanistic and Re
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364 CONTROVERSIAL ISSUES IN SAFETY
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374 INDEX 2-bromo-glutathionyl 64 B
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376 INDEX Gas chromatography/mass s
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378 INDEX mRNA analysis 211 Mutagen
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380 INDEX Surfactants 338-55 acute
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Toxicology of Industrial Compounds

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