Toxicology of Industrial Compounds

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120 PULMONARY TOXICITY STUDIES WITH MAN-MADE ORGANIC FIBRES were increased from 3 µm in the original generated sample to 6 µm in the size-separated sample. In comparison to the chrysotile asbestos sample, there was a significantly greater proportion of long p-aramid fibrils which were used in the inhalation study with median lengths >9 µm. Lung burden analysis Although the aerosol fibre concentrations were similar throughout the study (p-aramid high conc.=772 f cm −3 , chrysotile high conc.=782 f cm −3 ; p-aramid low conc.=419 f cm −3 , chrysotile low conc.=458 f cm −3 ), measurement of lung fibre burdens from digested lung tissue at time 0 (i.e. immediately after exposure) demonstrated a substantial difference in lung burden between the two fibre-types as measured by phase contrast optical microscopy (PCOM). The mean lung fibre (>5 µm) burden from 3 rats/ dose group exposed to chrysotile asbestos was 3.7×10 7 (±7.4×10 6 ) fibres/ lung for the high dose group and 1.3×10 7 (±4×10 6 ) fibres/lung for the low dose group. In contrast, the mean lung fibre burden from 3 rats/dose group exposed to para-aramid fibres was 7.6×10 7 (±1.9×10 7 ) fibres per lung for the high dose group and 4.8×10 7 ( ±2.1×10 7 ) fibres/lung for the low dose group. In addition, the count median length of chrysotile fibres recovered from the lungs of exposed animals immediately after 2-week exposure was 3.5 µm, while the count median diameter was 0.15 µm. In contrast, the count median length of para-aramid fibres recovered from the lungs of exposed animals immediately after 2-week exposure was 8.6 µm, while the count median diameter was 0.3 µm (Figure 8.2(A) and (B); numerical data not shown). These data indicate that our attempts to size-separate Canadian chrysotile fibres were only partially successful. The lung burden data also suggest that comparisons of the effects of chrysotile vs paraaramid at high and low doses are difficult to make since the doses were not equivalent. Bronchoalveolar lavage data Two-week exposures to p-aramid fibrils or chrysotile asbestos fibres produced transient pulmonary inflammatory responses as measured by bronchoalveolar lavage fluid analysis (see Table 8.1). Light microscopic histopathology Exposures to p-aramid and chrysotile were associated with minimal to mild centriacinar inflammation and fibrosis (increased trichrome staining) immediately after and 5 days after 2-week exposures. Lesions were slightly more prominent in p-aramid-exposed rats due to increased inflammation. Lesions were less severe at 1 month and essentially resolved at 6 months
D.B.WARHEIT ET AL. 121 Figure 8.1 (A) Chrysotile asbestos lengths—original generated sample for 4 different experiments. The graph depicts the fibre length distributions as assessed by scanning electron microscopy from four aerosol exposures prior to attempts to size separate the fibres. Fifty percent of the fibres from all four groups are less than 3–4 µm. (B) Distributions of size-separated chrysotile asbestos lengths used in the inhalation study from the high-dose
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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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Page 84 and 85: 70 METABOLISM OF REACTIVE CHEMICALS
Page 86 and 87: 6 Methods for the Determination of
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Page 104 and 105: PART THREE Pulmonary toxicology of
Page 106 and 107: 92 CARCINOGENIC POTENTIAL OF MAN-MA
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Page 152 and 153: 10 Mechanisms of Pulmonary Sensitiz
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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
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170 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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Toxicology of Industrial Compounds

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