Toxicology of Industrial Compounds

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98 CARCINOGENIC POTENTIAL OF MAN-MADE VITREOUS FIBERS exposure group at 3, 6, 12 and 18 (rats only) months and held without further treatment until the end of the exposure period, when they were killed to assess progression or regression of lung lesions and lung retention and clearance of fibers after cessation of exposure. To assure quality control, the lofting technique and exposure level were consistently monitored during the study by both gravimetric measurement and fiber counting techniques. The terminal sacrifice was carried out when only 20 per cent of the animals survived. A complete necropsy was performed on each animal. Gross pathological examination and diagnoses were performed using a dissecting microscope. Uniform sections of the left lung and right diaphragmatic lobe were embedded in paraffin, cut at a thickness of 4 mm and replicate sections were routinely stained with hematoxylin and eosin (H&E) and Masson-Goldner’s trichrome stain for collagen staining to assess the presence of lung fibrosis. In addition, sections were made from all grossly visible lesions from that and other portions of the lung. Proliferative lesions of the pulmonary parenchyma were designated as bronchoalveolar hyperplasia, pulmonary adenoma or adenocarcinoma. Other types of lesions, including those in the pleura were noted where appropriate. All research and analyses were conducted using good laboratory practices. Lung fiber burden Immediately after necropsy, the infracardiac lobe of each animal’s lung was removed and frozen for later analysis of lung fiber burden. To recover fibers from the lung, the tissue was rapidly dehydrated with acetone and ashed using a low-temperature process. Recovered fibers were dispersed in distilled water and examined using scanning electron microscopy. Number, dimensions and other physical characteristics of the inhaled lung fibers were determined, and reported as fibers per mg of dry lung weight. Results from recent animal inhalation studies of MMVFs Refractory ceramic fibers In the first RCC studies, rodents were exposed to the MTD of the sizeselected RCF test fiber, 30 mg m −3 and approximately 200–250 fibers cm −3 . Rats were exposed for 6 h per day, 5 days a week to aerosols containing one of four different types of RCF: kaolin, RCF 1; zirconia, RCF 2; high purity kaolin, RCF 3; and ‘after service’ (a kaolin based ceramic fiber containing 27% crystalline silica that had previously been exposed to high temperature), RCF 4. Hamsters were exposed to only kaolin RCF fibers. Positive controls (chrysotile asbestos) and negative controls (filtered air)
Table 7.1 Summary of lung pathology findings in RCF hamster inhalation study a WHO fibers=fibers with length/diameter ≥3, length >5 µm, and diameter
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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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Page 104 and 105: PART THREE Pulmonary toxicology of
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148 MECHANISMS OF PULMONARY SENSITI
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150 OCCUPATIONAL ASTHMA INDUCED BY
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12 Biomarkers and Risk Assessment K
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160 BIOMARKERS AND RISK ASSESSMENT
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168 EXTRAPOLATION OF TOXICITY DATA
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14 Molecular Approaches to Assess C
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182 MOLECULAR APPROACHES TO ASSESS
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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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