Toxicology of Industrial Compounds

Recommendations

Info

214 USE OF LONG-TERM CULTURES OF HEPATOCYTES IN TOXICITY TESTING that 1-naphthol UDP-GT activity is maintained well in co-cultures whereas this is not true for morphine UDP-GT, although for both a steady state situation was reached. These data point to a shift towards a more differentiated pattern since 1-naphthol is considered to be more specific for the late foetal form of UDP-GT and morphine for the neonatal form. The maintenance of 1-naphthol UDP-GT has been confirmed by Utesch and Oesch (1992). Other studies on preservation of phase 2 enzymatic activity in co-cultures have dealt with the identification of the metabolites formed when drugs are added to the culture medium. In human co-culture it could be shown that the glucuronide metabolite of ketotifen was still present after 3 weeks whereas it became undetectable after 6 days in mono-culture (Bégué et al., 1984b). Similar observations have been made for other drugs such as caffeine and theophylline (Ratanasavanh et al., 1990). Conclusions At present no ideal culture system for hepatocytes can be proposed. In all models reported in the literature, phenotypic changes occur, affecting the various components of phase 1 and phase 2 xenobiotic metabolism to a different extent. An interesting conclusion, however, remains from the observation that, when co-cultures and mono-cultures of hepatocytes are compared, cocultures exhibit higher biotransformation capacities which are better and preserved for longer than is the case for mono-cultures. The inducibility by common inducers is fairly well maintained and seems, to a certain extent, comparable with the in vivo situation. In addition, hormonal regulation of phase 1 and phase 2 key enzymes seems to be well maintained and comparable with the in vivo situation. Co-cultures of hepatocytes with rat liver epithelial cells are therefore already of importance as an alternative model for risk assessment. In particular, when long-term effects of a chemical are to be expected. Some experience already exists concerning the application of co-cultured hepatocytes for the study of pharmaceuticals. As far as chemical products other than pharmaceuticals are concerned, experience is lacking although interesting results are to be expected particularly in those cases where chemicals can interfere with the human organism via the food chain or by occupational exposure. In vitro exploration of this new field in toxicology is a challenge for the coming years. Notes 1a. 88/379/EEC Directive du Conseil du 7 juin 1988 concernant le rapprochement des dispositions législatives, réglementaires et administratives des Etats membres
elatives à la classification, à l’emballage et à 1’étiquetage des préparations dangereuses. Journal Officiel des Communautés européennes no L187, 16 juillet 1988, p. 14. 1b. 93/18/EEC Directive 93/18/CEE de la Commission du 5 avril 1993 portant troisième adaptation au progrès technique de la directive 88/379/CEE du Conseil concernant le rapprochement des dispositions législatives, réglementaires et administratives des Etats membres relatives à la classification, à l’emballage et à 1'étiquetage des preparations dangereuses. Journal Officiel des Communautés européennes no L104, 29 Avril 1993, p. 46. 2a. 91/414/EEC Richtlijn van de Raad van 15 juli 1991 betreffende het op de markt brengen van gewasbeschermingsmiddelen. Publikatieblad van de Europese Gemeenschappen no L230, 19 Augustus 1991, p. 1. 2b. 93/71/EEC Directive 93/71/CEE de la Commission du 27 juillet 1993 modifiant la directive 91/414/CEE du Conseil concernant la mise sur le marché des produits phytopharmaceutiques. Journal Officiel des Communautés européennes no L221, 31 Août 1993, p. 27. 3. 93/C239/03 Voorstel voor een richtlijn van de Raad betreffende het op de markt brengen van biociden. Publicatieblad van de Europese Gemeenschappen no C239, 3 September 1993, p. 3. 4a. 76/768/EEC Richtlijn van de Raad van 27 juli 1976 betreffende de onderlinge aanpassing van de wetgevingen der Lid-Staten inzake kosmetische produkten. Publikatieblad van de Europese Gemeenschappen no L262, 27 juli 1976, p. 169. 4b. 93/35/EEC Directive 93/35/CEE du Conseil du 14 juin 1993 modifiant pour la sixième fois la directive 76/768/CEE concernant le rapprochement des lé-gislations des Etats membres relatives aux produits cosmétiques. Journal Officiel des Communautés européennes no L151, 23 juin 1993 p. 32. References V.ROGIERS ET AL. 215 AKRAWI, M., ROGIERS, V., VANDENBERGHE, Y., PALMER, C., VERCRUYSSE, A., SHEPHARD, E. and PHILLIPS I., 1993a, Maintenance and induction in cocultured rat hepatocytes of components of the cytochrome P450 mediated monooxygenase, Biochemical Pharmacology, 45, 1583–91. AKRAWI, M., SHEPHARD, E.A., PHILLIPS, I.R., VERCRUYSSE, A. and ROGIERS, V., 1993b, Effects of phenobarbital and valproate on the expression of cytochrome P-450 mediated mono-oxygenases in co-cultured rat hepatocytes, Toxicology In Vitro, 7, 477–80. AKRAWI, M., ROGIERS, V., VERCRUYSSE, A., PHILLIPS, I.R. and SHEPHARD, E.A., 1994, Long-term preservation and induction of drug metabolizing
Page 2 and 3:
Toxicology of Industrial Compounds
Page 4 and 5:
This edition published in the Taylo
Page 6 and 7:
8. Pulmonary Toxicity Studies with
Page 8 and 9:
Preface A large number of chemical
Page 10 and 11:
Contributors May Akrawi Department
Page 12 and 13:
Beverly M.Kulig TNO Toxicology, Dep
Page 14 and 15:
Richard A.Versen Schuller MTC, Heal
Page 16 and 17:
1 Biomonitoring and Absorption of I
Page 18 and 19:
4 BIOMONITORING AND ABSORPTION OF I
Page 20 and 21:
Page 22 and 23:
Page 24 and 25:
10 BIOMONITORING AND ABSORPTION OF
Page 26 and 27:
2 Toxicokinetics and Biodisposition
Page 28 and 29:
14 TOXICOKINETICS AND BIODISPOSITIO
Page 30 and 31:
Page 32 and 33:
Page 34 and 35:
Page 36 and 37:
Page 38 and 39:
Page 40 and 41:
Page 42 and 43:
Page 44 and 45:
Page 46 and 47:
Page 48 and 49:
Page 50 and 51:
3 Metabolic Activation of Industria
Page 52 and 53:
38 METABOLIC ACTIVATION OF INDUSTRI
Page 54 and 55:
Page 56 and 57:
Page 58 and 59:
4 Sizing up the Problem of Exposure
Page 60 and 61:
46 SIZING UP THE PROBLEM OF EXPOSUR
Page 62 and 63:
Page 64 and 65:
Page 66 and 67:
Page 68 and 69:
Page 70 and 71:
Page 72 and 73:
Page 74 and 75:
5 Metabolism of Reactive Chemicals
Page 76 and 77:
62 METABOLISM OF REACTIVE CHEMICALS
Page 78 and 79:
Page 80 and 81:
Page 82 and 83:
Page 84 and 85:
Page 86 and 87:
6 Methods for the Determination of
Page 88 and 89:
74 METHODS FOR THE DETERMINATION OF
Page 90 and 91:
Page 92 and 93:
Page 94 and 95:
Page 96 and 97:
Page 98 and 99:
Page 100 and 101:
Page 102 and 103:
Page 104 and 105:
PART THREE Pulmonary toxicology of
Page 106 and 107:
92 CARCINOGENIC POTENTIAL OF MAN-MA
Page 108 and 109:
Page 110 and 111:
Page 112 and 113:
Page 114 and 115:
100 CARCINOGENIC POTENTIAL OF MAN-M
Page 116 and 117:
Page 118 and 119:
Page 120 and 121:
Page 122 and 123:
Page 124 and 125:
Page 126 and 127:
Page 128 and 129:
Page 130 and 131:
Page 132 and 133:
118 PULMONARY TOXICITY STUDIES WITH
Page 134 and 135:
Page 136 and 137:
Page 138 and 139:
Page 140 and 141:
Page 142 and 143:
Page 144 and 145:
130 PULMONARY HYPERREACTIVITY TO IN
Page 146 and 147:
Page 148 and 149:
Page 150 and 151:
Page 152 and 153:
10 Mechanisms of Pulmonary Sensitiz
Page 154 and 155:
140 MECHANISMS OF PULMONARY SENSITI
Page 156 and 157:
Page 158 and 159:
Page 160 and 161:
Page 162 and 163:
Page 164 and 165:
150 OCCUPATIONAL ASTHMA INDUCED BY
Page 166 and 167:
Page 168 and 169:
Page 170 and 171:
Page 172 and 173:
12 Biomarkers and Risk Assessment K
Page 174 and 175:
160 BIOMARKERS AND RISK ASSESSMENT
Page 176 and 177:
162 BIOMARKERS AND RISK ASSESSMENT
Page 178 and 179: 164 BIOMARKERS AND RISK ASSESSMENT
Page 180 and 181: 166 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
Page 222 and 223: 208 USE OF LONG-TERM CULTURES OF HE
Page 236 and 237: PART FIVE Mechanisms of toxicity of
Page 238 and 239: 224 PEROXISOME PROLIFERATION normal
Page 240 and 241: 226 PEROXISOME PROLIFERATION demons
Page 242 and 243: 228 PEROXISOME PROLIFERATION Specie
Page 244 and 245: 230 PEROXISOME PROLIFERATION intend
Page 246 and 247: 232 PEROXISOME PROLIFERATION BENTLE
Page 248 and 249: 234 PEROXISOME PROLIFERATION KRAUPP
Page 250 and 251: 236 PEROXISOME PROLIFERATION POPP,
Page 252 and 253: 18 Neurotoxicity Testing of Industr
Page 254 and 255: 240 NEUROTOXICITY TESTING OF INDUST
Page 270 and 271: 256 ENDOCRINE TOXICOLOGY OF THE THY
Page 278 and 279:
264 ENDOCRINE TOXICOLOGY OF THE THY
Page 280 and 281:
Page 282 and 283:
Page 284 and 285:
Page 286 and 287:
Page 288 and 289:
Page 290 and 291:
Page 292 and 293:
Page 294 and 295:
20 Testing and Evaluation for Repro
Page 296 and 297:
282 TESTING AND EVALUATION FOR REPR
Page 298 and 299:
Page 300 and 301:
Page 302 and 303:
Page 304 and 305:
Page 306 and 307:
Page 308 and 309:
Page 310 and 311:
Page 312 and 313:
Page 314 and 315:
PART SIX Toxicity of selected class
Page 316 and 317:
302 SPECIAL POINTS IN THE TOXICITY
Page 318 and 319:
Page 320 and 321:
Page 322 and 323:
Page 324 and 325:
310 TOXICOLOGY OF TEXTILE CHEMICALS
Page 326 and 327:
Page 328 and 329:
Page 330 and 331:
Page 332 and 333:
318 ANTIOXIDANTS AND LIGHT STABILIS
Page 334 and 335:
Page 336 and 337:
Page 338 and 339:
Page 340 and 341:
Page 342 and 343:
Page 344 and 345:
Page 346 and 347:
Page 348 and 349:
Page 350 and 351:
Page 352 and 353:
Page 354 and 355:
340 TOXICOLOGY OF SURFACTANTS Inter
Page 356 and 357:
342 TOXICOLOGY OF SURFACTANTS Figur
Page 358 and 359:
344 TOXICOLOGY OF SURFACTANTS probl
Page 360 and 361:
346 TOXICOLOGY OF SURFACTANTS nonio
Page 362 and 363:
348 TOXICOLOGY OF SURFACTANTS and t
Page 364 and 365:
350 TOXICOLOGY OF SURFACTANTS long-
Page 366 and 367:
352 TOXICOLOGY OF SURFACTANTS COULS
Page 368 and 369:
354
Page 370 and 371:
25 Low Dose of a Genotoxic Carcinog
Page 372 and 373:
358 CARCINOGENESIS AT LOW DOSE Tabl
Page 374 and 375:
360 CARCINOGENESIS AT LOW DOSE year
Page 376 and 377:
26 Controversial Mechanistic and Re
Page 378 and 379:
364 CONTROVERSIAL ISSUES IN SAFETY
Page 380 and 381:
Page 382 and 383:
Page 384 and 385:
Page 386 and 387:
Page 388 and 389:
374 INDEX 2-bromo-glutathionyl 64 B
Page 390 and 391:
376 INDEX Gas chromatography/mass s
Page 392 and 393:
378 INDEX mRNA analysis 211 Mutagen
Page 394 and 395:
380 INDEX Surfactants 338-55 acute
show all

Toxicology of Industrial Compounds

Create successful ePaper yourself

Delete template?

Save as template?