['Book', 'of', 'dbstracts', '—', 'EUROTOX', "'94", 'Y', 'Key', 'words:', 'genotoxicity;', 'cytostatics;', 'nurses;', 'chromosomal', 'damage', 'Tne', 'Young', 'Rabbit', 'as', 'a', 'Promising', 'Animal', 'Model', 'fo', 'Screen', 'for', 'Potential', 'Arthrotoxicity', 'Pascata', 'Brunel,', 'Christine', 'Péric,', 'Henry', 'Baron,', 'Gerhard', 'J,', 'Nofwnek,', 'Syhia', 'Gosselin.', 'A#éne-Poulanc', 'Rorer', 'S.A.,', 'Drug', 'Satety', 'Department,', 'Centre', 'de', 'Recherche', 'de', 'Vity-Alfortville,', 'Fiance', 'At', 'the', 'preseat', 'time.', 'quinolone', 'antibacterials', 'are', 'not', 'approved', 'for', 'pediatric', 'use', 'dua', 'to', 'their', 'potential', 'arthrotoxic', 'effect', 'In', 'young', 'animals.', 'The', 'young', 'Beagle', 'dog', 'has', 'been', 'the', 'traditional', 'animal', 'madel', 'to', 'screan', 'for', 'potential', 'arthro-', 'toxicity', 'of', 'quinolones,', 'since', 'it', 'is', 'the', 'most', 'sensitive', 'species', 'among', 'the', 'standard', 'laboratary', 'animals,', 'kn', 'an', 'attempt', 'to', 'devetop', '2n', 'alternativa', 'animal', 'modal,', 'we', 'parformed', 'singla-dose', 'and', '7-day', 'repeatad-dose', 'oral', 'toxicity', 'studies', 'in', 'young', 'albino', 'rabbits', '(5', 'weeks', 'of', 'age},', 'using', '7', 'different', 'quinalones', '(nafidixic,', 'oxolinic', 'and', 'pipemidic', 'acids,', 'offoxacin,', 'ciprofloxaein,', 'and', 'pefioxacin}', 'which', 'are', 'known', 'to', 'be', 'arthrotoxic', 'in', 'the', 'young', 'Beagla', 'dog.', 'The', 'dose', 'lavels', 'to', 'the', 'approximate', 'maximal', 'tolerated', 'dose', 'in', 'young', 'rabbits.', 'The', 'arthratoxic', 'potential', 'of', 'these', 'in', 'young', 'rabbits', 'was', 'evaluatad', 'by', 'macroscopic', 'and', 'microscopic', 'exarmriinations', 'of', 'weight-bearing', 'joints.', 'I', 'these', 'studias,', 'we', 'confirmed', 'that', '6', 'of', 'the', '7', 'quinolones', 'tested', 'were', 'arthrataxia', '1', 'young', 'rabbits,', 'However,', 'arthrotoxicity', 'in', 'young', 'rabbits', 'cocurred', 'at', 'higher', 'dose', 'levels', '{10', 'to', '40x)', 'than', 'those', 'known', 'to', 'inducs', 'the', 'same', 'type', 'of', 'lesion', 'in', 'young', 'dogs.', 'This', 'indicates', 'that', 'young', 'rabbits', 'are', 'less', 'sensitive', 'to', 'the', 'arthrotoxic', 'potential', 'of', 'quinolones.', 'Although', 'high', 'doses', 'of', 'the', 'tested', 'compounds', 'are', 'required', 'to', 'produce', 'arthrotoxicity,', 'the', 'rabbit', 'madet', 'offers', 'substantial', 'advantages', 'over', 'the', 'dog', 'model,', 'such', 'as', 'reduced', 'compound', 'consumption,', 'easier', 'animal', 'keeping', 'and', 'raduced', 'ethical', 'concemns.', 'Key', 'words;', 'young', 'rabhit;', 'arthrotoxicity,', 'model', 'v', 'In', 'Vitro', 'Cylo!oxlclty', 'of', 'Organotln', 'Compaunds', 'tc', 'Flsh', 'Hepatoma', "Cell'Llne", "F'LHC-1", 'FE.Waorgler,', 'K.', 'Fert.', 'Swiss', 'Feders/', 'Instituta', 'for', 'Environmenta!', 'Scisnce', 'and', 'Technology', '{EAWAG),', 'Institute', 'of', 'Taxicology,', 'Swiss', 'Federal', 'Instute', 'of', 'Tachnology', 'and', 'yniVsmiW', 'of', 'Zorich,', 'Switzerlsnd', 'Cytotoxlcity', 'of', 'a', 'series', 'of', '21', 'organotin', 'compounds,', 'consisting', 'of', 'all', 'degreas', 'of', 'alkylation', 'and', 'arlation.', 'was', 'deter-', 'mined', 'in', 'fish', 'hepatome', 'cells', 'PLHC-1', 'in', 'the', 'neutral', 'red', '(NR)', 'assay', 'and', 'the', 'tetrazolium', 'salt', 'reduction', '{MTT7)', 'assay.', 'Cytotoxic', 'efiects', 'occurrad', 'at', 'concentrations', 'of', '108', 'M', 'to', '10-3', 'M.', 'Very', 'low', 'sffect', 'concentrations', 'in', 'the', 'range', 'of', '10-8', 'Mt', '10~8', 'M', 'were', 'observed', 'for', 'various', 'trisubstifuted', 'organotin', 'compounds', 'including', 'tributyltin', 'and', 'triph-', 'enyltin', 'which', 'ara', 'used', 'in', 'antifouling', 'paints', 'and', 'as', 'pesticides,', 'respactivaly.', 'Tributyltin', 'induced', 'effacts', 'on', 'cell', 'func-', 'tions', 'very', 'quickly,', 'as', '&', 'raduction', 'in', 'NR', 'uptake', 'by', '30%', 'was', 'recordad', 'after', '30', 'min', 'exposure', 'to', '4', 'x', '10-7', 'M.', 'For', 'tri-', 'and', 'disubstituted', 'organotin', 'compounds', 'a', 'significant', 'correlation', 'was', 'found', 'between', 'the', 'n-octanolwater', 'partition', 'coefficiont', 'Kow', 'and', 'the', 'NRsg', '{n', '=', '10,', 'r', '=', '0.85,', 'P', '=', '0.001}', 'and', 'the', 'MTTyp', 'values', '{n', '=', '11,1', '=', '0.85,', 'P', '=', '0.001},', 're-', 'spectively.', 'Comparison', 'of', 'the', 'cytotoxicity', 'data', 'with', 'i1', 'vivo', 'toxicity', 'data', 'of', 'fish', 'indicates', 'that', 'the', 'in', 'vitro', 'cytotoxicity', 'assays', 'using', 'PLHC-1', 'cells', 'are', 'useful', 'tools', 'for', 'the', 'assessment', '01', 'the', 'acute', 'toxicity', 'of', 'oraanohns', 'and', 'probably', 'other', 'compounds', 'to', 'fish.', 'Key', 'words:', 'cytotoxicity;', 'organotin', 'compounds;', 'neutial', 'red', 'assay;', 'MTT', 'assay;', 'i', 'vioo-in', 'vivo', 'comparison', 'Applications', 'for', 'Transgenic', 'Animals', 'in', 'Toxicology', 'David', 'J,', 'Brusick.', 'Hazfeton', 'Washingtan', 'Inc,', 'Vienna,', 'Virginia,', 'USA', 'Transgenic', 'animal', 'models', 'for', 'detection', 'of', 'mutagens', 'and', 'carcinogens', 'have', 'been', 'introduced', 'into', 'safety', 'testing', 'pregrams.Continued', 'improvement', 'in', 'models', 'designed', '1o', 'study', 'the', 'processes', 'of', 'cancer', 'and', 'mutation', 'is', 'expected', 'during', 'the', 'next', 'few', 'years.', 'Additional', 'applications', 'jor', 'transgenic', 'animal', 'models', 'are', 'also', 'proposed', 'for', 'immunotoxi-', 'cology,', 'neurotoxicology', 'and', 'other', 'rapidiy-expanding', 'areas', 'of', 'safety', 'testing.', 'Transgenic', 'animal', 'models', 'will', 'continues', '1o', 'be', 'developed', 'to', 'fil', 'the', 'gaps', 'which', 'exist', 'in', 'toxicology', 'testing', 'and', 'as', 'tools', 'to', 'provide', 'more', 'insight', 'regarding', 'the', 'celiufar', 'mechanism', 'leading', 'to', 'overt', 'toxicity.', 'The', 'results', 'will', 'be', 'improved', 'reliability', 'and', 'relevance', 'of', 'toxicologi-', 'cal', 'avaluations', 'neaded', 'prior', 'to', 'controlled', 'human', 'axposura', 'or', 'environmental', 'release.', 'A', 'survey', 'of', 'applications', 'with', 'advantages', 'and', 'limitations', 'will', 'be', 'reviewed.', 'Key', 'words:', 'transgenic,', 'toxicalogical', 'assessment', '6212861052']