Toxicology of Industrial Compounds

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194 MOLECULAR APPROACHES TO ASSESS CANCER RISKS or cancer in human populations. In contrast, risk coefficients have been established for the induction of cancer by low levels of -radiation in human populations within, approximately, a factor of 2. According to the basic presumptions (vide supra), the increased cancer risks in a human population caused by low-level exposures to radiation or to a genotoxic chemical are predominantly due to the mutagenic propensities of these genotoxic factors. It would, therefore, seem reasonable to suggest that cells that had been initiated by exposure to radiation or to genotoxic chemicals or combinations of factors (vide supra) would, nevertheless, be subject to the same general promoter and modulating influences acting on the population. On this basis, experimentally-determined rad-equivalence values for genotoxic chemicals may be used to convert target doses of the chemicals (determined in human populations receiving low-level exposures) into the equivalent doses of radiation (for the induction of mutation). The respective cancer risks associated with any particular monitored target dose of a genotoxic chemical may then be obtained by direct reference to the human cancer risk coefficients established for radiation. References ALBRECHT, W. and NEUMANN, H.-G., 1985, Biomonitoring of aniline and nitrobenzene. Haemoglobin binding in rats and analysis of adducts, Arch. Toxicol, 57, 1–5. AMES, B.N., 1989, Environmental pollution and the causes of human cancer: six errors, in DeVita, V.T., Jr, Hellman, S. and Rosenberg, S.A. (Eds) Important Advances in Oncology, pp. 237–47, Philadelphia, PA: Lippincott. AMES, B.N., DURSTON, W.E., YAMASAKI, E. and LEE, F.E., 1973, Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection, Proc. Nat. Acad. Sci. USA, 70, 2281–5. CALLEMAN, C.J., 1984, Haemoglobin as a dose monitor and its application to the risk estimation of ethylene oxide, PhD Thesis, p. 25, Stockholm: University of Stockholm. CALLEMAN, C.J., EHRENBERG, L., JANSSON, B., OSTERMAN-GOLKAR, S., SEGERBÄCK, D., SVENSSON, K. and WACHTMEISTER, C.A., 1978, Monitor ing and risk assessment by means of alkyl groups in haemoglobin in persons occupationally exposed to ethylene oxide, J. Environm. Pathol. Tox., 2, 427–42. COOPER, D.P., GRIFFIN, K.A. and POVEY, A.C., 1992, Immunoaffinity purification combined with 32 P-postlabelling for the detection of O 6 - methylguanine in DNA from human tissues, Carcinogenesis, 13, 469–75. EHRENBERG, L., 1974, Genotoxicity of environmental chemicals, Acta. Biol. Yugosl., Ser. F Genetika, 6, 367–98. EHRENBERG, L., 1976, Methods of Comparing Effects of Radiation and Chemicals, Brighton IAEA Consultant Meeting.
A.S.WRIGHT ET AL. 195 EHRENBERG, L., 1979, Risk assessment of ethylene oxide and other compounds, in McElheny, V.K. and Abrahamson, S. (Eds) Assessing Chemical Mutagens: The Risk to Humans (Banbury Report 1), pp. 157–90, Cold Spring Harbour, New York, CSH Press. EHRENBERG, L., 1980, Purposes and methods of comparing risks of radiation and chemicals, in Radiobiological Equivalents of Chemical Pollutants, pp. 11– 36, Vienna: International Atomic Energy Agency. EHRENBERG, L., HIESCHE, K.D., OSTERMAN-GOLKAR, S. and WENNBERG, I., 1974, Evaluation of genetic risks of alkylating agents: tissue doses in the mouse from air contaminated with ethylene oxide, Mutat. Res., 24, 83–103. EHRENBERG, L. and OSTERMAN-GOLKAR, S., 1980, Alkylation of macromolecules for detecting mutagenic agents, Teratogen., Carcinogen. Mutagen., 1, 105–27. FARMER, P.B., 1991, Analytical approaches for the determination of proteincarcinogen adducts using mass spectrometry, in Groopman, J.D. and Skipper, P. L. (Eds) Molecular Dosimetry and Human Cancer: Analytical, Epidemiological and Social Considerations, pp. 189–210, Boca Raton: CRC Press. GREEN, L.C., SKIPPER, P.L., TURESKY, R.J., BRYANT, M.S. and TANNENBAUM, S.R., 1984, In vivo dosimetry of 4-aminobiphenyl in rats via a cysteine adduct in haemoglobin, Cancer Res., 44, 4254–9. KOLMAN, A., NASLUND, M., OSTERMAN-GOLKAR, S., SCALIA-TOMBA, G.P. and MEYER, A.L., 1989, Comparative studies of in vitro transformation by ethylene oxide and gamma-radiation of cells, Mutagenesis, 4, 58–61. Lu, A-L. and Hsu, I-C., 1992, Detection of single DNA base mutations with mismatch repair enzymes, Genomics, 14, 249–55. OSTERMAN-GOLKAR, S., EHRENBERG, L., SEGERBÄCK, D. and HALLSTROM, I., 1976, Evaluation of genetic risks of alkylating agents. II. Haemoglobin as a dose monitor, Mutat. Res., 34, 1–10. RANDERATH, K., REDDY, M.V. and GUPTA, R.C., 1981, 32 P-labeling test for DNA damage, Proc. Natl Acad. Sci. USA, 78, 6126–9. SKIPPER, P. L and NAYLOR, S., 1991, Mass spectrometric analysis of proteincarcinogen adducts, in Garner, R.C, Farmer, P.B., Steel, G.T. and Wright, A.S. (Eds) Human Carcinogen Exposure: Biomonitoring and Risk Assessment, pp. 61–8, Oxford: Oxford University Press. THILLY, W.G., 1991, Mutational spectrometry: opportunities and limitations in human risk assessment, in Garner, R.C, Farmer, P.B., Steel, G.T. and Wright, A. S. (Eds) Human Carcinogen Exposure: Biomonitoring and Risk Assessment, pp. 127–33, Oxford: Oxford University Press. TÖRNQVIST, M. and OSTERMAN-GOLKAR, S., 1991, Monitoring of in vivo dose by macromolecular adducts: usefulness in risk estimation, in Groopman, J.D. and Skipper, P.L. (Eds) Molecular Dosimetry and Human Cancer: Analytical, Epidemi ological and Social Considerations, pp. 89–102, Boca Raton: CRC Press. TÖRNQVIST, M., MOWRER, J., JENSEN, S. and EHRENBERG, L., 1986a, Monitoring of environmental cancer initiators through haemoglobin adducts by a modified Edman degradation method, Analyt. Biochem., 154, 255–66.
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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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118 PULMONARY TOXICITY STUDIES WITH
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130 PULMONARY HYPERREACTIVITY TO IN
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10 Mechanisms of Pulmonary Sensitiz
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140 MECHANISMS OF PULMONARY SENSITI
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142 MECHANISMS OF PULMONARY SENSITI
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Page 164 and 165: 150 OCCUPATIONAL ASTHMA INDUCED BY
Page 172 and 173: 12 Biomarkers and Risk Assessment K
Page 174 and 175: 160 BIOMARKERS AND RISK ASSESSMENT
Page 182 and 183: 168 EXTRAPOLATION OF TOXICITY DATA
Page 194 and 195: 14 Molecular Approaches to Assess C
Page 196 and 197: 182 MOLECULAR APPROACHES TO ASSESS
Page 212 and 213: 198 EVALUATION OF TOXICITY TO THE I
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Page 252 and 253: 18 Neurotoxicity Testing of Industr
Page 254 and 255: 240 NEUROTOXICITY TESTING OF INDUST
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244 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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