Toxicology of Industrial Compounds

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320 ANTIOXIDANTS AND LIGHT STABILISERS: TOXIC EFFECT Table 23.2 Parent equivalents and blood metabolites of [ 14 C]-labelled Compound B after single oral administration of 9.5 mg kg −1 body weight to male rats Note: bld: below the limit of detection. Blood was taken at the indicated time intervals and extracted with ethyl acetate for analysis. Compound B and its free carboxylic acid metabolite (Compound A, Table 23.1) were identified by thin-layer co-chromatography with authentic reference samples. Quantification of Compounds A and B was accomplished by radiometric scanning of the plates following thin-layer chromatography of the respective blood extracts. 1000 ppm, liver weights as well as the investigated biochemical parameters returned to control levels. Therefore, Compound B may be addressed as a reversible barbiturate- and peroxisome proliferator-type inducer in the rat, as characterised by its liver enzyme induction profile. Effects on serum thyrotropin and thyroid hormones When male rats were fed Compound B admixed in the diet for 14 days at dose levels of 50, 150, 500 and 1000 ppm, liver and thyroid weights were increased in a dose-dependent manner. Histopathological examination of the thyroid gland revealed hypertrophy of the follicular epithelium and thinning of colloid at 150, 500 and 1000 ppm. Morphological changes in the pituitary gland comprised enlarged thyrotropin (TSH)-producing cells with foamy or vacuolated cytoplasm. In addition, treatment resulted in markedly increased serum TSH and reverse triiodothyronine (rT 3) concentrations, whereas serum thyroxine (T 4) and triiodothyronine (T 3) levels were found slightly decreased. The effects observed at 1000 ppm were found to be reversible after a 28-day recovery period (Muakkassah- Kelly et al., 1991). In additional experiments, male rats were rendered hypothyroid, fed Compound B at 1000 ppm for 21 days and infused for the last 7 days with slightly supraphysiological concentrations of T 4. The observed changes in
H.THOMAS ET AL. 321 Table 23.3 The effect of Compound B on selected biochemical parameters in the male rat liver Notes: Values are means of 9 (14 days treatment) or 4 (14 days treatment/28-days recovery) animals. Standard deviations are given in parentheses. 0/0: Control recovery. 1000/0: High-dose recovery. * p
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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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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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Page 284 and 285: 270 ENDOCRINE TOXICOLOGY OF THE THY
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Page 314 and 315: PART SIX Toxicity of selected class
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Page 370 and 371: 25 Low Dose of a Genotoxic Carcinog
Page 372 and 373: 358 CARCINOGENESIS AT LOW DOSE Tabl
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Page 376 and 377: 26 Controversial Mechanistic and Re
Page 378 and 379: 364 CONTROVERSIAL ISSUES IN SAFETY
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370 CONTROVERSIAL ISSUES IN SAFETY
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372 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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