Advertisement

Experimental Pharmacology and Toxicology of Antituberculosis Drugs

  • D. Tettenborn
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 84)

Abstract

The anti-tuberculosis agents are, chemically, a very heterogeneous group exhibiting a wide spectrum of pharmacological and toxicological effects on the various organ systems. These range from the very early recognized ototoxicity and nephrotoxicity of the aminoglycosides, to the question of neurotoxicity, carcinogenicity and mutagenicity of INH, to the oculotoxicity of ethambutol and to effects on neuro-muscular transmission of the aminoglycosides. Whilst for some substances there are enormous numbers of publications, there are other substances where there is a noticeable lack of published pharmacological and toxicological data. With regard to the latter substances it was possible, in some cases, to include in this review previously unpublished results of studies carried out by the manufacturing companies. Since most of the anti-tuberculosis agents were introduced 20 years–30 years ago, it is practically impossible to assess the old publications on the basis of modern standards. It would be misguided, however, to ignore the results of the early studies since they provided important basic data.

Keywords

Hair Cell Acute Toxicity Neuromuscular Blockade Aminoglycoside Antibiotic Fatty Degeneration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bavin EM, James B (1952) Further aspects of the pharmacology of para-aminosalicylic acid. J Pharm Pharmacol 4: 856–870PubMedGoogle Scholar
  2. Beattie J, Chambers RD (1953) The anti-thyroid action of para-aminosalicylic acid. J Endocrinol 10: 65–72PubMedGoogle Scholar
  3. Cauwenberge H van (1951) The effect of salicylates on the pituitary and suprarenal glands. Lancet 2: 686–687Google Scholar
  4. Cronheim G, King JS, Hyder N (1952) Effect of salicylic acid and similar compounds on the adrenal-pituitary system. Proc Soc Exp Biol Med 80: 51–55PubMedGoogle Scholar
  5. Hetzel BS, Hine DC (1951) The effect of salicylates on the pituitary and suprarenal glands. Lancet 2: 94–97PubMedGoogle Scholar
  6. Kjerulf-Jensen K, Wolffbrandt G (1951) Antithyroid effect of p-aminosalicylic acid and maminophenol. Acta Pharmacol Toxicol (Copenh) 7: 376–380Google Scholar
  7. Koelzer PP, Giesen J (1951) Untersuchungen zur Toxizität der p-Aminosalicylsäure und ihrer Derivate. Z Naturforsch 6 B: 183–190Google Scholar
  8. Mehrotra RML, Chandra S, Singh MP, Gupta NN (1959) Changes in the liver of albino rats after administration of para-aminosalicylic acid. Indian J Med Res 47: 500–506Google Scholar
  9. Schonholzer G (1951) Comments on the toxicity of P.A.S. preparations. Aust J Pharm 32: 1359–1363Google Scholar
  10. Tettenborn D (1970) Unpublished investigationsGoogle Scholar
  11. Thoma F (1962) Stabilität von PAS-Infusionslösungen und ihre Prüfung durch Papier-und Dünnschichtchromatographie. Tuberk Arzt 16: 362–368Google Scholar
  12. Adams HR, Goodman FR, Lupean VA, Weiss GB (1973) Effects of neomycin on tension and 45Ca movements in rabbit aortic smooth muscle. Life Sci Part I Physiol Pharmacol 12: 279–287Google Scholar
  13. Akiyoshi M, Sato K (1970) Reevaluation of the pinna reflex test as screening for ototoxicity of antibiotics. In: Progress in Antimicrobiol and Anticancer Chemotherapy; Proc 6th Intern Congr Chemotherapy, Vol 1: 621–627Google Scholar
  14. Alleva FR, Balazs T, Morris SO, Crowley WR, O’Donohue TL, Jacobowitz DM (1979) Reversal of streptomycin-induced dyskinesia in rats by dopaminergic agonists. Toxicol Appl Pharmacol 48:A 36Google Scholar
  15. Amann R, Radenbach KL (1961) Akute Kanamycin-Nebenwirkungen und Histaminfreisetzung. Beitr Klin Tuberk 123: 208–210Google Scholar
  16. André T (1956) Studies on the distribution of tritium-labelled dihydrostreptomycin and tetracyclin in the body. Acta Radiol Suppl 142: 1–89PubMedGoogle Scholar
  17. Bacharach AL, Clark BJ, McCulloch M, Tomich EG (1959) Comparative toxicity studies on ten antibiotics in current use. J Pharm Pharmacol 11: 737–741PubMedGoogle Scholar
  18. Beck Ch, Krahl P (1962) Experimentelle und feingewebliche Untersuchungen über die Ototoxizität von Kanamycin. Arch Otorhinolaryngol 179: 594–610Google Scholar
  19. Berg K (1951) The toxic effect of streptomycin on the vestibular and cochlear apparatus. Acta Otolaryng Suppl 97: 5–77Google Scholar
  20. Bezzi G, Gessa GL (1959) Neuromuscular blocking action of some antibiotics. Nature 184: 905–906PubMedGoogle Scholar
  21. Bezzi G, Gessa GL (1961) Influence of antibiotics on the neuromuscular transmission in mammals. Antibiot Chemotherap 11: 710–714Google Scholar
  22. Boucher D, Delost P (1964) Développement post-natal des descendants issus de mères traitées par la streptomycine au cours de la gestation chez la souris. CR Soc Biol (Paris) 158: 2065–2069Google Scholar
  23. Brigham RS, Nielsen JK (1958) The effect of calcium pantothenate on the acute and chronic toxicity of streptomycin and dihydrostreptomycin in mice. Anbiot Chemother 8: 122–129Google Scholar
  24. Catalano GB, Madonia T (1956) Ulteriore contributo sperimentale sulle lesioni istologiche labyrinthiche da streptomicina. Clin Otorinolaryng 8:51Google Scholar
  25. Caussé R, Gondet I, Vallancien B (1949) Action de la streptomycine sur les cellules ciliées des organes vestibulaires de la souris. CR Soc Biol 144: 619–620Google Scholar
  26. Child KJ, Davis B, Sharpe HM, Tomich EG (1957) Toxicologic studies on the sulfates and pantothenates of streptomycin and dihydrostreptomycin. Antibiot Annu 1956–1957: 574–580Google Scholar
  27. Christensen E, Hertz H, Riskaer N, Vraa-Jensen G (1950) Experiments on the neurotoxic effect of streptomycin. Acta Otolaryng Suppl 95: 165–176Google Scholar
  28. Cohen LS, Wechsler AS, Mitchell JH, Glick G (1970) Depression of cardiac function by streptomycin and other antimicrobial agents. Am J Cardiol 26: 505–511PubMedGoogle Scholar
  29. Corrado AP (1958) Ganglioplegic action of streptomycin. Arch Int Pharmacodyn 114: 166–178PubMedGoogle Scholar
  30. Corrado AP (1963) Respiratory depression due to antibiotics: calcium in treatment. Anesth Analg 42: 1–5PubMedGoogle Scholar
  31. Corrado AP, Ramos AO, De Escobar CT (1959) Neuro-muscular blockade by neomycin potentiation by ether anesthesia and d-tubocurarine and antagonism by calcium and prostigmine Arch Int Pharmacodyn Ther 121: 380–394Google Scholar
  32. Courvoisier S, Leau O (1956) Study of the onset of deafness in rats treated with streptomycin, dihydrostreptomycin and neomycin. Antibiot Chemother 6: 411–419Google Scholar
  33. DeSalva SJ, Evans RA, Marcussen HW (1969) Lethal effects of antibiotics in hamsters. Toxicol Appl Pharmacol 14: 510–514PubMedGoogle Scholar
  34. Dretchen KL, Sokoll MD, Gergis SD, Long JP (1973) Relative effects of streptomycin on motor nerve terminal and endplate. Eur J Pharmacol 22: 10–16PubMedGoogle Scholar
  35. Ducrot R, Leau O, Cosar C (1956) Protective action of pantothenic acid against toxic effects of streptomycin and dihydrostreptomycin. Antibiot Chemother 6: 404–410Google Scholar
  36. Duvall AJ, Wersäll J (1964) Site of action of streptomycin upon inner ear sensory cells. Acta Otolaryng 57: 581–598PubMedGoogle Scholar
  37. Dzoljié M, Babié M (1967) Action of streptomycin on the uterus. Eur J Pharmacol 2: 123–126Google Scholar
  38. Edison AO, Frost BM, Graessle OE, Hawkins JE Jr, Kuna S, Mushett CW, Silber RH, Solotorovsky M (1948) An experimental evaluation of dihydrostreptomycin. Am Rev Tuberc 58: 487–493PubMedGoogle Scholar
  39. Engström H (1967) The pathological sensory cell in the cochlea. Acta Otolaryng Appendix to Vol 63: 20–26Google Scholar
  40. Ericson-Strandvik B, Gyllenstein L (1963) The central nervous system of foetal mice after administration of streptomycin. Acta Pathol Microbiol Scand 59: 292–300PubMedGoogle Scholar
  41. Escher F (1949) Das Streptomycin in der Otolaryngologie unter besonderer Berücksichtigung der Vestibularisstörungen. Praxis: 141–146Google Scholar
  42. Farkashidy J, Black RG, Briant TDR (1963) The effect of kanamycin on the internal ear: an electrophysiological and electron microscopic study. Laryngoscope 73: 713–727PubMedGoogle Scholar
  43. Flohberg C, Hamberger CA, Hyden H (1949) Inhibition of nucleic acid production in vestibular nerve cells by streptomycin. Acta Otolaryng Suppl 75: 36Google Scholar
  44. Garcia-Quiroga J, Norris CH, Glade L, Bryant GM, Tachibana M, Guth PS (1978) The relationship between kanamycin ototoxicity and glucose transport. Res Commun Chem Pathol Pharmacol 22: 535–547PubMedGoogle Scholar
  45. Goodman FR, Weiss GB, Adams HR (1974) Alterations by neomycin of 45Ca movements and contractile responses in vascular smooth muscle. J Pharmacol Exp Ther 188: 472–480PubMedGoogle Scholar
  46. Gray JE, Purmalis A (1958) The acute toxicity of procaine penicilline G and of dihydro-streptomycin sulfate in the pigeon and the chicken. Avian Dis 2: 187–196Google Scholar
  47. Greven H (1953) Die toxische Wirkung von Streptomycin auf den Cochlear-und Vestibu-larapparat. Z Laryng Rhinol 32: 109–117Google Scholar
  48. Gross A, Legait E, Delabroise AM (1969) Etude de la néphrotoxicité de la streptomycine et de la dihydrostreptomycine chez le rat blanc porteur d’une insufficance rénale expérimentale. Thérapie 24: 327–341PubMedGoogle Scholar
  49. Hawkins JE Jr (1959) The ototoxicity of kanamycin. Ann Otol 68: 698–715Google Scholar
  50. Hawkins JE Jr (1970) Biochemical aspects of ototoxicity. In: Paparella MM (ed) Biochemical mechanisms in hearing and deafness. Thomas Publ, pp 323–339Google Scholar
  51. Hawkins JE Jr (1973) Ototoxic mechanisms. A working hypothesis. Audiology 12: 383–393PubMedGoogle Scholar
  52. Hawkins JE Jr, Wolcott H, O’Shanny WJ (1957) Ototoxic effects of streptomycin and di- hydrostreptomycin pantothenates in the cat. Antibiot Annu 1956–1957: 554–563Google Scholar
  53. Hinshaw HC, Feldman WH (1945) Streptomycin in treatment of clinical tuberculosis: A preliminary report. Mayo Clin Proc 20: 313Google Scholar
  54. Hoffmann K (1970) unpublished investigationsGoogle Scholar
  55. Holz E, Hoffmann M, Beck Ch (1967) Morphologische und bakteriologische Befunde zur Minderung der Ototoxicität basischer Streptomycesantibiotika. Arch Otorhinolaryngol 188: 236–242Google Scholar
  56. Linuma T, Mizukoshi O, Daly JF (1976) Possible effects of various ototoxic drugs upon the ATP-hydrolyzing system in the stria vascularis and spiral ligament of the guinea pig. Laryngoscope 77: 159–169Google Scholar
  57. Iwatsuki K, Ueda T, Yamada A, Nishimura S, Kanemura K (1958) Effects of certain antibiotics on the action of muscle relaxants. Far East J Anesth 2:106–115; cited from Ber Ges Physiol 213 (1960): 121Google Scholar
  58. Jindal MN, Desphande VR (1960) Neuromuscular blockade by streptomycin and dihydrostreptomycin. Brit J Pharmacol 15: 506–509PubMedGoogle Scholar
  59. Johnsson L-G, Wright CG, Preston RE, Henry PJ (1980) Streptomycin-induced efects of the otoconial membrane. Acta Otolaryngol (Stockh) 89: 401–406Google Scholar
  60. Keller H, Krüpe W, Sous H, Mückter H (1955) Versuche zur Toxizitätsminderung basischer Streptomyces-Antibiotika. 1. Mitt. Arzneimittelforsch 5: 170–176PubMedGoogle Scholar
  61. Keller H, Krüpe W, Sous H, Mückter H (1956a) Versuche zur Toxizitätsminderung basischer Streptomyces-Antibiotika 2 Mitt. Arzneimittelforsch 6: 61–66Google Scholar
  62. Keller H, Krüpe W, Sous H, Mückter H (1956b) Versuche zur Toxizitätsminderung basischer Streptomyces-Antibiotika. 3. Mitt. Arzneimittelforsch 6: 585–591Google Scholar
  63. Kellerhals B, Engström H, Ades HW (1967) Die Morphologie des Ganglion spirale cochleae. Acta Otolaryng (Stockh) Suppl 226: 1–78Google Scholar
  64. Kellerhals B (1973) Zur Ototoxizität der Aminoglykosid-Antibiotika. MMW 115: 1667–1672Google Scholar
  65. Kimmerle G, Gösswald R (1956) Versuche zur Entgiftung von Streptomycin und Dihydrostreptomycin. Arzneimittelforsch 6: 379–383PubMedGoogle Scholar
  66. Kohonen A (1965) Effect of some ototoxic drugs upon the pattern and innervation of cochlear sensory cells in the guinea pig. Acta Otolaryngol (Stockh) Suppl 208: 1–70Google Scholar
  67. Kohonen A, Tarkkanen JV (1966) Dihydrostreptomycin and kanamycin ototoxicity. An experimental study by surface preparation technique. Laryngoscope 76: 1671–1680PubMedGoogle Scholar
  68. Kraus H, Doenning G (1969) Cytophotometrische RNA- und Eiweißbestimmungen am häutigen Innenohr des Meerschweinchens als Grundlage zur Beurteilung des Eiweißstoffwechsels und der Streptomycinototoxizität. Arch Otorhinolaryngol 194: 1551Google Scholar
  69. Kubikowski P, Srzeniawski Z (1963) The mechanism of the neuromuscular blockade by antibiotics. Arch Int Pharmacodyn Ther 146: 549–560PubMedGoogle Scholar
  70. Kuschinsky G, Lüllmann H, Pracht W (1959) Über den Einfluß von Pantothensäure auf die vestibularisschädigende Wirkung von Streptomycin. Dtsch Med Wochenschr 84: 363–366Google Scholar
  71. Kuschinsky G, Lüllmann H (1963) Tierexperimentelle Untersuchungen zur Abhängigkeit der Ototoxicität von der Dosierung des Kanamycin und zur Schutzwirkung durch Vitamine Klin Wochenschr 41: 230–233Google Scholar
  72. Lagler F, Osterloh G, Mückter H (1960) Studies on the pharmacology of kanamycin. Antibiot Annu 1959–1960: 862–867Google Scholar
  73. Lange G (1968) Die quantitative Auswertung von Streptomycinschäden des vestibulären Sinnesepithels beim Meerschweinchen mit Hilfe des Cytovestibulogramms und der calorischen Erregbarkeitsprüfung. Arch Otorhinolaryngol 192: 249–257Google Scholar
  74. Leaders F, Pittinger CB, Long JP (1960) Some pharmacological properties of selected antibiotics. Antibiot Chemotherap 10: 503–507Google Scholar
  75. Lindeman HH (1969) Regional differences in sensitivity of the vestibular sensory epithelia to ototoxic antibiotics. Acta Otolaryngol (Stockh) 67: 177–189Google Scholar
  76. Lodhi S, Weiner ND, Mechigian J, Schacht J (1980) Ototoxicity of aminoglycosides correlated with their action on monomolecular films of polyphosphoinositides. Biochem Pharmacol 29: 597–601PubMedGoogle Scholar
  77. Lüllmann H, Reuter H (1960a) Über die Hemmung der neuromuskulären Übertragung durch einige Antibiotika. Chemotherapia 1: 375–383Google Scholar
  78. Lüllmann H, Reuter H (1960b) Die curare-artigen Nebenwirkungen einiger Antibiotika. Klin Wochenschr 38: 771–772Google Scholar
  79. Lundquist P-G, Wersäll J (1966) Kanamycin-induced changes in cochlear hair cells of the guinea pig. Z Zellforsch 72: 543–561PubMedGoogle Scholar
  80. Mascitelli-Coriandoli E (1962) Der Einfluß basischer Antibiotica auf das Coenzym A-System. Arzneimittelforsch 12: 597–601PubMedGoogle Scholar
  81. Mahady SCF, Armstrong FL, Monroe J (1956) Purified dihydrostreptomycin. Am Rev Tuberc 73: 776–778PubMedGoogle Scholar
  82. Marquardt P, Ziegler E (1956) Zur Pharmakologie von Streptomycinsulfat und -pantothenat. Arzneimittelforsch 6: 213–214PubMedGoogle Scholar
  83. McGee TM, Olszewski J (1962) Streptomycin sulfate and dihydrostreptomycin toxicity. Arch Otolaryngol 75: 295–311Google Scholar
  84. Mendelsohn M, Katzenberg I (1972) The effect of kanamycin on the cation content of the endolymph. Laryngoscope 82: 397–403PubMedGoogle Scholar
  85. Merkle U, Plattig KH, Keidel UO (1968) Histologische Untersuchungen zur ototoxischen Wirkung des Kanamycins am Cortischen Organ der Katze. Zschr Mikrosk Anat Forsch 78: 441–460Google Scholar
  86. Meyer zum Gottesberge A, Stupp HF (1969) Streptomycinspiegel in der Perilymphe des Menschen. Acta Otolaryngol 67: 171–176PubMedGoogle Scholar
  87. Michael AF, Sutherland JM (1961) Antibiotic testing in newborn and adult rats. Am J Dis Child 101: 442–446Google Scholar
  88. Molgó J, Lemeignan M, Uchiyama T, Lechat P (1979) Inhibitory effect of kanamycin on evoked transmitter release. Reversal by 3,4-diaminopyridine. Eur J Pharmacol 57: 9397Google Scholar
  89. Molitor H, Graessle OE, Kuna S, Mushett ChW, Silber RH (1946) Some toxicological and pharmacological properties of streptomycin. J Pharmacol Exp Ther 86: 151–173PubMedGoogle Scholar
  90. Molitor H, Kuna S (1949) Pharmacologic studies of the neurotoxic properties of streptomycin. Arch Int Pharmacodyn Ther 76: 197–202Google Scholar
  91. Mosonyi L, Pollak L, Zulik R, Kârolyhâzi G (1956) Streptomycin and endocrine system. Experientia 12: 311–313PubMedGoogle Scholar
  92. Mückter H (1961) Zur Pharmakologie der basischen Streptomyces-Antibiotika. Antibiotica et Chemotherapia Separatum Vol 9: 83–144Google Scholar
  93. Müsebeck K, Schätzle W (1962) Experimentelle Studien zur Ototoxicität des Dihydrostreptomycins. Arch Otorhinolaryngol 181: 41–48Google Scholar
  94. Mushett ChW, Maitland HS (1946) Pathologic changes resulting from the administration of streptomycin. Arch Pathol 42: 619–629Google Scholar
  95. Mushett ChW, Stebbins RB (1949) Renal cytoplasmic inclusions following the administration of large doses of streptomycin. Fed Proc 8: 363Google Scholar
  96. Nagaba M (1968) Electron microscopic study of semicircular canal organs and otolith organs of squirrel monkeys after administration of streptomycin sulfate. Acta Otolaryngol (Stockh) 66: 541–552Google Scholar
  97. Neumann G, Neubert K (1958) Die Sensularien des Innenohres unter der Einwirkung von Streptomycin — Experimentelle Untersuchungen am Corti’schen Organ and an der Macula utricula des Meerschweinchens. Arzneimittelforsch 8: 63–72PubMedGoogle Scholar
  98. Osterberg AC, Oleson JJ, Yuda NN, Rauh CE, Parr HG, Will LW (1957) Cochlear, vestibular and acute toxicity studies of streptomycin and dihydrostreptomycin pantothenate salts. Antibiot Annu 1956–1957: 564–573Google Scholar
  99. Pfaltz CR, Piffko P (1972) Central compensation of retrolabyrinthine vestibular lesions. Acta Otolaryngol (Stockh) 73: 183–189Google Scholar
  100. Pittinger CB (1970) pH and streptomycin influences upon ionic calcium in serum. Anesth Analg 49:540–545PubMedGoogle Scholar
  101. Pittinger CB, Long JP (1958) Neuromuscular blocking action of neomycin sulfate. Antibiot Chemother 8: 198–203Google Scholar
  102. Pittinger CB, Long JP, Miller JR (1958) The neuromuscular blocking action of neomycin. Anesth Analg 37: 276–282PubMedGoogle Scholar
  103. Pittinger C, Adamson R (1972) Antibiotic blockade of neuromuscular function. Annu Rev Pharmacol 12: 169–184PubMedGoogle Scholar
  104. Plattig KH, Keidel UO, David E (1967) Minderung der Ototoxizität des Kanamycins durch Pantothensäure. Dtsch Med Wochenschr 92: 1391–1397Google Scholar
  105. Plester D (1963) Discussion remark. Arch otorhinolaryngol 182: 587Google Scholar
  106. Popovici GG, Moisä L, Negoitä M, Manoilâ V, Botez E, Hafner R, Gumeni N (1965) The influence of certain antibiotics on intestinal motor activity. Arch Int Pharmacodyn Ther 154: 374–381PubMedGoogle Scholar
  107. Popovici GG, Negoitâ M, Moisä L, Manoilä V, Hafner R, Botez E (1967) The influence of some antibiotics on uterine motor activity in the guinea pig. Arch Int Pharmacodyn Ther 166: 20–25PubMedGoogle Scholar
  108. Popovici GG, Mungiu C, Filip M, Botez E, Ababei L (1970) Influence of some antibiotics on stationary NAD and NADP concentrations in rat liver and kidney. Arch Int Pharmacodyn Ther 188: 73–78PubMedGoogle Scholar
  109. Prado WA, Corrado AP, Marseillan RF (1978) Competitive antagonism between calcium and antibiotics at the neuromuscular junction. Arch Int Pharmacodyn Ther 231: 297307Google Scholar
  110. Prescott B, Kauffmann G, James WD, Stone HJ (1959) Means of increasing the tolerated dose of streptomycin in mice. Antibiot Chemother 9: 369–375Google Scholar
  111. Raab WP (1970) Renal effects of streptomycin in rats. Clin Chim Acta 29: 451–454PubMedGoogle Scholar
  112. Ritter R, Chou J, v Ilberg C, Wagner WH (1971) Eine neue Möglichkeit zur Verhinderung der Ototoxizität des Streptomycins. Arch Otorhinolaryngol 199: 573–577Google Scholar
  113. Robson JM, Sullivan FM (1963) Antituberculous drugs. Pharmacol Rev 15: 169–223PubMedGoogle Scholar
  114. Rudnick MD (1979) A quantitative and qualitative study of aminoglycoside antibiotic ototoxicity in the vestibulo-cochlear apparatus following intratympanic administration in guinea pig (Cavia cobaya). Dissertation Abstr Intern B 39: 4145–4146Google Scholar
  115. Saito H, Daly JF (1971) Quantitative analysis of acid mucopolysaccharides in the normal and kanamycin intoxicated cochlea. Acta Otolaryngol (Stockh) 71: 22–26Google Scholar
  116. Secondi U (1954) Ancora sull’effetto neurotossico della streptomicina. L’importanza del fattore dose-tempo. Arch Ital Otol 65: 165PubMedGoogle Scholar
  117. Singh YN, Harvey AL, Marshall IG (1978) Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine. Anesthesiology 48: 418–424PubMedGoogle Scholar
  118. Sokoll MD, Diecke FPJ (1969) Some effects of streptomycin on frog nerve in vitro. Arch Int Pharmacodyn Ther 177: 332–339PubMedGoogle Scholar
  119. Spoendlin H (1966) Zur Ototoxizität des Streptomycins. Pract Oto-Rhino-Laryng (Basel) 28:305–322; 374–375Google Scholar
  120. Spoendlin H (1967) Acute streptomycin intoxication of the labyrinth. Acta Otolaryngol (Stockh) 63: 26–38Google Scholar
  121. Stange G (1969) Minderung bzw. Verhütung der Ototoxizität basischer Streptomyzes-Antibiotika. Therapiewoche 19: 106–117Google Scholar
  122. Stange G, Soda T, Beck Ch (1967) Elektrophysiologische Ergebnisse bei Ototoxizitätsmin- derung basischer Streptomyces-Antibiotika. Arch Otorhinolaryngol 188: 242–249Google Scholar
  123. Stupp HF (1970) Untersuchung der Antibiotikaspiegel in den Innenohrflüssigkeiten und ihre Bedeutung für die spezifische Ototoxizität der Aminoglykosidantibiotika. Acta Otolaryngol (Stockh) Suppl 262Google Scholar
  124. Stupp H, Rauch S, Sous H, Lagler F (1966) Untersuchungen über die Ursache der spezifisch ototoxischen Wirkung der basischen Streptomycesantibiotika unter besonderer Berücksichtigung des Kanamycins. Acta Otolaryngol (Stockh) 61: 435–444Google Scholar
  125. Stupp H, Rauch S, Sous H, Brun JP, Lagler F (1967) Kanamycin dosage and levels in ear and other organs. Arch Otolaryngol 86: 515–521PubMedGoogle Scholar
  126. Stupp H, Küpper K, Lagler F, Sous H, Quante M (1973) Inner ear concentrations and ototoxicity of different antibiotics in local and systemic application. Audiology 12: 350–363PubMedGoogle Scholar
  127. Suzuki Y, Takeuchi S (1961) Etude expérimentale sur l’influence de la streptomycine sur l’appareil auditif du foetus après administration de doses variées a la mère enceinte. Keio. J Med 10: 31–41Google Scholar
  128. Swain HH, Kiplinger GF, Brody TM (1956) Action of certain antibiotics on the isolated dog heart. J Pharmacol Exp Ther 117: 151–159PubMedGoogle Scholar
  129. Tettenborn D (1971) Unpublished investigationsGoogle Scholar
  130. Thalmann R, Miyoshi T, Kusakari J, Thalmann J (1973) Quantitative approaches to the ototoxicity problem. Audiology 12: 364–382PubMedGoogle Scholar
  131. Timmerman JC, Long JP, Pittinger CB (1959) Neuromuscular blocking properties of various antibiotic agents. Toxicol Appl Pharmacol 1: 299–304Google Scholar
  132. Tisch DE, Huftalen JB, Dickison HL (1958) Pharmacological studies with kanamycin. Ann NY Acad Sci 76: 44–65PubMedGoogle Scholar
  133. Tyberghein J (1962) Influence of some streptomyces antibiotics on the cochlear micro-phonics in the guinea pig. Acta Otolaryngol (Stockh) Suppl 171Google Scholar
  134. Tyberghein J (1967) Einfluß der Pantothensäure auf die Ototoxizität des Kanamycins beim Meerschweinchen. Med Welt: 2017–2020Google Scholar
  135. Tyberghein J, Ostjin F (1961) L’ototoxicité de la streptomycine. Acta Tuberc Pneumol Belg 52: 139–146PubMedGoogle Scholar
  136. Vernier VG, Alleva FR (1968) The bioassay of kanamycin auditory toxicity. Arch Int Pharmacodyn Ther 176: 59–73PubMedGoogle Scholar
  137. Vital Brazil O (1961) Streptomycin effect on the skeletal muscle stimulation produced by acetylcholine. Arch Int Pharmacodyn Ther 130: 136–140Google Scholar
  138. Vital Brazil O, Corrado AP (1957) The curariform action of streptomycin. J Pharmacol Exp Ther 120: 452–459Google Scholar
  139. Vital Brazil O, Corrado AP, Berti FA (1959) Neuromuscular block produced by streptomycin and some of its degradation products. In: Bovet D, Bovet-Nitti F, Marini-Bettolo (eds) Curare and curare-like agents. Elsevier, AmsterdamGoogle Scholar
  140. Vital Brazil O, Prado-Franceschi J (1969) The nature of neuromuscular block produced by neomycin and gentamicin. Arch Int Pharmacodyn Ther 179: 78–85Google Scholar
  141. Voldhch L (1965) The kinetics of streptomycin, kanamycin and neomycin in the inner ear. Acta Otolaryngol (Stockh) 60: 243–248Google Scholar
  142. Vrabec DP, Cody DT, Ulrich JA (1965) A study of the relative concentrations of antibiotics in the blood, spinal fluid, and perilymph in animals. Ann Otol Rhinol Laryngol 74: 688–703Google Scholar
  143. Wagner WH, Chou JTY, Ilberg v. C, Ritter R, Vosteen KH (1971) Untersuchungen zur Pharmakokinetik von Streptomycin. Arzneimittelforsch 21: 2006–2016PubMedGoogle Scholar
  144. Watanuki K, Meyer zum Gottesberge A (1971) Toxic effect of streptomycin and kanamycin upon the sensory epithelium of the crista ampullaris. Acta Otolaryngol (Stockh) 72: 59–67Google Scholar
  145. Watanuki K, Stupp H (1971) Haarzellenschädigungsmuster an Crista and Maculae bei Ototoxikose durch Antibiotika. Arch Otorhinolaryngol 199: 569–573Google Scholar
  146. Watanuki K, Stupp H-F, Meyer zum Gottesberge A (1972) Toxic effects of gentamycin upon the peripheral vestibular sensory organs. Laryngoscope 82: 363–371PubMedGoogle Scholar
  147. Wersäll J, Hawkins JE Jr (1962) The vestibular sensory epithelia in the labyrinth and their reactions in chronic streptomycin intoxication. Acta Otolaryngol (Stockh) 54: 1–23Google Scholar
  148. Winston J, Lewey FH, Parentease A, Marden PA, Cramer FB (1948) An experimental study of the toxic effects of streptomycin on the vestibular apparatus of the cat. Ann Otol Rhinol Laryngol 57: 738–753PubMedGoogle Scholar
  149. Wolf GL, Wigton RS (1971) Vasodilatation induced by streptomycin in the perfused canine kidney. Arch Int Pharmacodyn Ther 194: 285–289PubMedGoogle Scholar
  150. Domagk G (1948) Die experimentellen Grundlagen einer Chemotherapie der Tuberkulose. Beitr KIM Tuberk 101: 372–394Google Scholar
  151. Emmrich R, Petzold H (1952) Experimentelle Untersuchungen zur Frage der Leberschädigung durch TB I. Z Ges Inn Med 7: 625–628PubMedGoogle Scholar
  152. Ginoulhiac E (1950) Toxicity of certain chemotherapeutics. Boll Soc Ital Biol Sper 26: 574–577PubMedGoogle Scholar
  153. Gülzow M (1950) Experimentelles zur TB I-Wirkung. I. Mitteilung: Intoxikationserscheinungen. Z Ges Exp Med 116: 26–39PubMedGoogle Scholar
  154. Gülzow M, Schlicht A (1950) Experimentelles zur TB I-Wirkung. II. Mitteilung: Aminosäure-Untersuchungen des Serum-und Organeiweiß im Verlauf von TB I (Conteben)Intoxikationen. Z Ges Exp Med 116: 40–55PubMedGoogle Scholar
  155. Hecht G (1950) Unpublished InvestigationsGoogle Scholar
  156. Moyer JH, Perkins RB (1951) Experimental studies on the toxicity of amithiozone in dogs. Am Rev Tuberc 64: 659–668PubMedGoogle Scholar
  157. Râvnay TH, Forró L, Szegö L (1954) Untersuchungen über den Wirkungsmechanismus der Thiosemikarbazone. Z Tuberk 104: 249–255PubMedGoogle Scholar
  158. Savini E (1950) Recherches expérimentales sur la toxicité du thiosemicarbazone. CR Soc Biol 144: 1310–1313Google Scholar
  159. Bonati F, Bertoni L (1962) Derivati basici dell’acido pirazin-2-carbonico ad azione antimicobatterica. Minerva Med 53: 1704–1708PubMedGoogle Scholar
  160. Celikovskâ G, Stastnâ J, Zitkovâ L, Brezinovâ H, Kürti V (1970) Leberschädigung nach Verabreichung von Pyrazinamid im Tierversuch. III. Biochemische Veränderungen im Lebergewebe und im Blutserum. Arzneimittelforsch 20: 155–157PubMedGoogle Scholar
  161. Gruss JD, Nickling HG (1967) Vergleichende funktionelle und bioptische Untersuchungen der normalen Kaninchenleber während der Applikation von Pyrazincarbonsäureamid. Arzneimittelforsch 17: 1565–1568Google Scholar
  162. Mori K, Yasuno A, Matsumoto K (1960) Induction of pulmonary tumors in mice with isonicotinic acid hydrazid. Gann 51: 83–89PubMedGoogle Scholar
  163. Robinson HJ, Siegel H, Pietrowski JJ (1954) Toxicity of pyrazinamide. Am Rev Tuberc 70: 423–429PubMedGoogle Scholar
  164. Stastnâ J, Celikovskâ G, Zitkovâ L, Viklickÿ J (1970) Leberschädigung nach Verabreichung von Pyrazinamid im Tierversuch. II. Untersuchungen über die zeitlichen Veränderungen der Konzentrationen von Pyrazinamid im Blut und der Aktivität der SerumTransaminasen. Arzneimittelforsch 20: 153–155PubMedGoogle Scholar
  165. Zitkovâ L, Stastnâ J, Celikovskâ G, Kürti V (1970) Leberschädigung nach Verabreichung von Pyrazinamid im Tierversuch I. Änderungen des Körpergewichtes von Ratten unter Einwirkung von Pyrazinamid. Arzneimittelforsch 20: 151–153PubMedGoogle Scholar
  166. Allmark MG, Lu FC, Carmichael E, Lavallee A (1953) Some pharmacological observations on isoniazid and iproniazid. Am Rev Tuberc 68: 199–206PubMedGoogle Scholar
  167. Ashby J, Purchase IFH (1977) The selection of appropriate chemical class controls for use with short term tests for potential carcinogenicity. Ann Occup Hyg 20: 297–301PubMedGoogle Scholar
  168. Ata S, Tanaka K (1952) Vitamin B12 and isoniazid. Lancet II: 589Google Scholar
  169. Balzer H, Holtz P, Palm D (1960) Untersuchungen über die biochemischen Grundlagen der konvulsiven Wirkung von Hydraziden. Naunyn Schmiedebergs Arch Pharmacol 239: 520–552Google Scholar
  170. Barreto RCR, Mano DB (1961) Prevention of the convulsant and lethal effects of isonicotinic acid hydrazide by pyruvic acid. Biochem Pharmacol 8: 409–412PubMedGoogle Scholar
  171. Benson WM, Stefko PL, Roe MD (1952) Pharmacologic and toxicologic observations on hydrazine derivatives of isonicotinic acid (Rimifon, Marsilid). Am Rev Tuberc 65: 376–391PubMedGoogle Scholar
  172. Berencsi G, Entz A, Vajkóczy A (1957) Kongreß der Ungarischen Phthisiolog Gesellsch, Szeged 1952, cited from Juhâsz J, Baló J, Kendrey G. Z Krebsforsch 62: 188–196Google Scholar
  173. Beyer E, Braun R, Schöneich J (1979) Genetic activity of isoniazid in the mammalian spot test. Mutat Res 64: 152Google Scholar
  174. Bhide SV, Marti GB, Sawai MM, Ranadive KJ (1978) Isoniazid tumorigenicity in mice under different experimental conditions. Int J Cancer 21: 381–386PubMedGoogle Scholar
  175. Biancifiori C, Ribacchi R (1962) Pulmonary tumors in mice induced by oral isoniazid and its metabolites. Nature 194: 488–489PubMedGoogle Scholar
  176. Biancifiori C, Severi L (1966) The relation of isoniazid (INH) and allied compounds to carcinogenesis in some species of small laboratory animals. A review. Br J Cancer 20: 528–538PubMedGoogle Scholar
  177. Black SLD (1977) Hepatic triglyceride metabolism and aminoacid pools in isonicotinic acid hydrazide treated rats. Dissertation Abstr Intern B 38: 1668–1669Google Scholar
  178. Blakemore WF, Palmer AC, Noel PRB (1972) Ultrastructural changes in isoniazid-induced brain oedema in the dog. J Neurocytol 1: 263–278PubMedGoogle Scholar
  179. Botta JA Jr, Carlton WW (1967a) Studies of the toxicity of isonicotinic acid hydrazide (Isoniazid) to ducklings. Toxicol Appl Pharmacol 11: 35–48Google Scholar
  180. Botta JA Jr, Carlton WW (1967b) Isoniazid toxicosis in ducklings-studies on pyridoxine, niacin, glutamic acid, and arginine supplementation. Avian Dis 11: 621–633Google Scholar
  181. Brambilla G, Baldini L (1959) Azione inibitrice dell’acido isonicotinico sullo sviluppo del sarcoma Galliera del ratto. Boll Soc Ital Biol Sper 35: 1169–1171PubMedGoogle Scholar
  182. Braun R, Schubert J, Schöneich J (1976) On the mutagenicity of isoniazid. Biol Zbl 95: 423–436Google Scholar
  183. Bucher O (1953) Zur Frage der cytotoxischen Wirkung von Rimifon. Schweiz Med Wochenschr 83: 1206–1208PubMedGoogle Scholar
  184. Bürgin H, Schmid B, Zbinden G (1979) Assessment of DNA damage in germ cells of male rabbits treated with isoniazid and procarbazine Toxicology 12: 251–257Google Scholar
  185. Carlton WW (1967) Neural toxicity of isonicotinic acid hydrazide (isoniazid) for chickens. Avian Dis 11: 241–254PubMedGoogle Scholar
  186. Carlton WW, Hunt CE, Newberne PM (1965) Neural lesions induced by isonicotinic acid hydrazide and semicarbazide hydrochloride. Exp Mol Pathol 4: 438–448Google Scholar
  187. Carlton WW, Kreutzberg G (1966) Isonicotinic acid hydrazide-induced spongy degeneration of the white matter in the brains of peking ducks. Am J Pathol 48: 91–105PubMedGoogle Scholar
  188. Casey RE, Wood JD (1973) Isonicotinic acid hydrazide-induced changes in the metabolism of y-aminobutyric acid in the brain of four species. Comp Biochem Physiol B 45: 741–748PubMedGoogle Scholar
  189. Cavanagh JB (1967) On the pattern of change in peripheral nerves produced by isoniazid intoxication in rats. J Neurol Neurosurg Psychiat 30: 26–33Google Scholar
  190. Cavanagh JB (1973) Peripheral neuropathy caused by chemical agents. CRC Crit Rev Toxicol 2: 365–417PubMedGoogle Scholar
  191. Cedrangolo F, Gioia A, Bagnulo R (1953) Un meccanismo enzimatico, per il quale si puo’abbassare in vivo la tossicità dell’ idrazide dell’ac. isonicotinico. Enzymologia 16: 41–50PubMedGoogle Scholar
  192. Ceriotti G, Franceschini J (1953) Dati biologici e microbiologici su un nuvo derivato della idrazide dell’acido isonicotinico a bassa tossicatà e ad alta attività (metansulfonato dell’ idrazide isonicotinica). Arch Int Pharmacodyn Ther 93: 105–117PubMedGoogle Scholar
  193. Chin L, Sievers ML, Laird HE, Herrier RN, Picchioni AL (1978) Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs. Toxicol Appl Pharmacol 45: 713–722PubMedGoogle Scholar
  194. Chin L, Sievers M, Herrier RN, Picchioni AL (1979) Convulsions as the etiology of lactic acidosis in acute isoniazide toxicity in dogs. Toxicol Appl Pharmacol 49: 377–384PubMedGoogle Scholar
  195. Cirnu-Georgian L, Lenghel V (1971) Isoniazid-induced chromosome aberrations. Lancet 2: 93PubMedGoogle Scholar
  196. Crema A, Fabris L (1954) Sulla tossicatà per il vestibolo dell’idrazide dell’ acido isonicotinico. Boll Soc Ital Biol Sper 30: 120–121PubMedGoogle Scholar
  197. Dauphinee KR, Paynters S, Russell DW (1975) Failure of pyruvate to counteract isonazid toxicity in rabbits. J Pharm Pharmacol 27: 884–886PubMedGoogle Scholar
  198. Dienemann G, Simon K (1953) Mitteilung eines Todesfalles nach kombinierter Verabreichung von Irgapyrin und Neoteben (INH). MMW 95: 221–222Google Scholar
  199. Dixon RH, Williams HL (1962) The toxicity of pyridoxal and pyridoxal phosphate hydra-zones in mice. Fed Proc 21: 338Google Scholar
  200. Dubnick B, Leeson GA, Scott CC (1960) Effect of forms of vitamin B6 on acute toxicity of hydrazines. Toxicol Appl Pharmacol 2: 403–409PubMedGoogle Scholar
  201. Emmrich R, Petzold H (1952) Tierexperimentelle Untersuchungen zur Frage einer Leber-schädigung durch Rimifon (Isonicotinylhydrazin) Klin Wochenschr 30: 1081–1083Google Scholar
  202. Engbaek HC, Bentzon H, Heegârd H, Christensen O (1965) Har isoniazid en tumorfrem-kaldende virkning? Nord Med 74: 13–26Google Scholar
  203. Földi M, Zoltan ÖT, Maurer M (1970) Die Wirkung von Isonicotinsäurehydrazid (INH) auf das Zentralnervensystem und der Antagonismus zwischen dieser Substanz und Pyridoxin, Pantothensäure sowie Cumarin aus Melilotus officinalis bei Ratten. Arzneimittelforsch 20: 1620–1623PubMedGoogle Scholar
  204. Frei H-H (1976) Elevation of central y-aminobutyric acid levels by isoniazid in mice and convulsant thresholds. Biochem Pharmacol 25: 1216–1219Google Scholar
  205. Fust B, Studer A, Böhni E (1952) Experimentelle Erfahrungen mit dem Antituberculotikum „Rimifon“. Schweiz Z Tuberk 9: 226–242Google Scholar
  206. Glass F, Gossow H, Mallach HJ (1964) Beobachtungen und Untersuchungen über die gemeinsame Wirkung von Alkohol und Isonicotinsäurehydrazid. Arzneimittelforsch 14: 1203–1208PubMedGoogle Scholar
  207. Glass F, Mallach HJ (1965) Tierexperimentelle Untersuchungen über die Alkoholwirkung nach längerer Belastung mit Isonicotinsäurehydrazid. Arzneimittelforsch 15: 1069–1070PubMedGoogle Scholar
  208. Goldin A, Dennis D, Venditti JM, Humphreys SR (1955) Potentiation of pentobarbital anesthesia by isonicotinic acid hydrazide and related compounds. Science 121: 364–365PubMedGoogle Scholar
  209. Grasso P, Crampton RF (1972) The value of the mouse in carcinogenicity testing. Fd Cosmet Toxicol 10: 418–426Google Scholar
  210. Gross W (1956) Ein Beitrag zur cytostatischen Wirkung des Isonicotinsäurehydrazids (INH). Klin Wochenschr 34: 495Google Scholar
  211. Hackmann CH (1957) Unpublished dataGoogle Scholar
  212. Hammond EC, Selikoff IJ, Robitzek EK (1967) Isoniazid therapy in relation to later occurence of cancer in adults and infants. Br Med J 2: 792–795PubMedGoogle Scholar
  213. Harper KH, Worden AN (1966) Comparative toxicity of isonicotinic acid hydrazide and its methanosulfonate derivative. Toxicol Appl Pharmacol 8: 325–333PubMedGoogle Scholar
  214. Hecht G (1953) Unpublished dataGoogle Scholar
  215. Hellriegel W, Kraus R (1955) Über die zytostatische Wirkung des Isonikotinsäurehydrazins. Tuberk Arzt 9: 653–660Google Scholar
  216. Herbold B, Buselmaier W (1976) Induction of point mutations by different chemical mechanisms in the liver microsomal assay. Mutat Res 40: 73–84PubMedGoogle Scholar
  217. Hess M (1954) Über den Einfluß von Isonicotinsäurehydrazid (Neoteben) auf die Genitalfunktion und die Gestation. Arch Gynäkol 185: 315–324PubMedGoogle Scholar
  218. Holtz P, Palm D (1964) Pharmacological aspects of Vitamin B6. Pharmacol Rev 16: 113–178PubMedGoogle Scholar
  219. IARC (1974) Monographs on the evaluation of carcinogenic risk of chemicals to man, vol 4. International Agency for Research on Cancer, LyonGoogle Scholar
  220. Jansen JD, Clemmesen J, Sundaram K (1980) Isoniazid–an attempt at retrospective prediction. Mutat Res 76: 85–112Google Scholar
  221. Jones LD, Fairchild DG, Morse WC (1971) The induction of pulmonary neoplasms in mice by isonicotinic acid hydrazide. Am Rev Respir Dis 103: 612–617PubMedGoogle Scholar
  222. Juhâsz J, Baló J, Kendrey G (1957) Über die geschwulsterzeugende Wirkung des Isonicotinsäurehydrazid (INH). Z Krebsforsch 62: 188–196PubMedGoogle Scholar
  223. Juhâsz J, Baló J, Szende B (1963) Neue experimentelle Angaben zur geschwulsterzeugenden Wirkung des Isonicotinsäurehydrazid (INH). Z Krebsforsch 65: 434–438PubMedGoogle Scholar
  224. Kelly MG, O’Gara RW, Yancey ST, Gadekar K, Botkin C, Oliviero VT (1969) Comparative carcinogenicity of N-isopropyl-a-(2-methylhydrazino)-p-toluamide HC1 (procarbazine hydrochloride), its degradation products, other hydrazines, and isonicotinic acid hydrazide. J Natl Cancer Inst 42: 337–344PubMedGoogle Scholar
  225. Kimball RF (1977) The mutagenicity of hydrazine and some of its derivatives. Mutation Res 39: 111–126PubMedGoogle Scholar
  226. Klinghardt GW (1954) Experimentelle Nervenfaserschädigung durch Isonicotinsäurehydrazid und ihre Bedeutung für die Klinik. Verh Dtsch Ges Inn Med 60: 764–768 (Kongress München)Google Scholar
  227. Krnjevic K (1971) Synaptic transmission in the brain. Klin Wochenschr 49: 519–523PubMedGoogle Scholar
  228. Lechat P, Deleau D, Devillechabrolle A (1963) Etude expérimentale du pouvoir protecteur de la pyridoxine vis-à-vis des effets toxique de l’isoniazide. Thérapie 18: 63–67PubMedGoogle Scholar
  229. Leopold D, Röthig W, Wehran H-J, Wolf P (1966) Verteilung und Wirkung des Isoniazid nach Applikation therapeutischer und toxischer Dosen im Tierversuch. Arch Toxicol 22: 80–91Google Scholar
  230. Levene CJ (1961) The lathyrogenic effect of isonicotinic acid hydrazide (INAH) on the chick embryo and its reversal by pyridoxal. J Exp Med 113: 795–811PubMedGoogle Scholar
  231. Loscalzo B (1964) Hydrazide de l’acide isonicotinique et neoplasies. Arch Int Pharmacodyn Ther 152: 249–251PubMedGoogle Scholar
  232. Lüers H, Obe G (1971) Action of isoniazid on human chromosomes in vitro. EMS Newsletter: 36Google Scholar
  233. Manthei RW (1957) Effect of calcium pantothenate on isoniazid toxicity in the guinea pig. Proc Soc Exp Biol Med 95: 402–404PubMedGoogle Scholar
  234. Manthei RW (1960) Vitamin B6 and isoniazid toxicity. Fed Proc 19: 414Google Scholar
  235. Matsumoto K, Mori K, Yasuno A (1960) Effect of isonicotinic acid hydrazide on hepatocarcinogenesis. Gann 51: 91–95Google Scholar
  236. McCormick DB, Snell EE (1961) Pyridoxal phosphokinases. J Biol Chem 236: 2085–2088PubMedGoogle Scholar
  237. Miller CT, Stoltz DR (1978) Mutagenicity induced by lyophilization or storage of urine from isoniazid-treated rats. Mutat Res 56: 289–293PubMedGoogle Scholar
  238. Mori K, Yasuno A (1959) Preliminary note on the induction of pulmonary tumors in mice by isonicotinic acid hydrazide feeding. Gann 50: 107–110Google Scholar
  239. Mori K, Yasuno A, Matsumoto K (1960) Induction of pulmonary tumors in mice with isonicotinic acid hydrazide. Gann 51: 83–89PubMedGoogle Scholar
  240. Nelson SD, Snodgrass WR, Mitchell JR (1976) Chemical reaction mechanisms responsible for the tissue injury caused by monosubstituted hydrazines and their hydrazide drug precursors. In: De Serres, Fouts, Bend and Philpot (eds) In vitro metabolic activation in mutagenesis testing. Elsevier, Amsterdam, pp 257–276Google Scholar
  241. Noda A, Goromaru T, Matsuyama K, Sogabe K, Hsu KY, Iguchi S (1978) Quantitative determination of hydrazines derived from isoniazid in patients. J Pharmacol Dyn 1: 132–141Google Scholar
  242. Noel PRB, Worden AN, Palmer AC (1967) Neuropathologic effects and comparative toxicity for dogs of isonicotinic acid hydrazide and its methanosulfonate derivative. Toxicol Appl Pharmacol 10: 183–198Google Scholar
  243. Orlowski EH, Rosenfeld M, Wolter H, Schunk R (1976) Experimentelle vergleichende Untersuchung der tuberkulostatischen Wirksamkeit und Toxizität von INH, INHG und INHG-Na. Arzneimittelforsch 26: 409–416PubMedGoogle Scholar
  244. Palmer AC, Noel PRB (1965) Neuropathological effects of dosing dogs with isonicotinic hydrazide and with its methanosulphonate derivative. Nature 205: 506–507PubMedGoogle Scholar
  245. P’an SY, Markaroglu L, Reilly J (1952) The effects of barbiturates on the toxicity of isoniazid (isonicotinic acid hydrazide). Am Rev Tuberc 66: 100–103PubMedGoogle Scholar
  246. Pansa E, Bikfalvi A (1960) Ober die Wirkung hoher Dosen Isonikotinsäure-Hydrazid (INH) auf die Bronchusschleimhaut der Kaninchen. Thoraxchirurgie 8: 451–457PubMedGoogle Scholar
  247. Pansa E, Picco A, Gnavi M (1962) Sul problema del supposto effecto carcinogenetico dell’idrazide dell’acido isonicotinico (IAI). Richerchi sperimentali sul ratto. Minerva Med 53: 3162–3168Google Scholar
  248. Peacock A, Peacock PR (1966) The results of prolonged administration of isoniazid to mice, rats and hamsters. Br J Canc 20: 307–325Google Scholar
  249. Prescott B, Kauffmann G, James WD (1954) A means of increasing the tolerated dose of isoniazid in mice. Proc Soc Exp Biol Med 86: 682–685PubMedGoogle Scholar
  250. Prescott B, Kauffmann G, James WD (1957a) Increase in tolerated dose of isoniazid in mice by use of cycloserine. Proc Soc Exp Biol Med 94: 94–96Google Scholar
  251. Prescott B, Kauffmann G, James WD (1957b) Effect of glycerine on toxicity of isoniazid in mice. Proc Soc Exp Biol Med 94: 272–276Google Scholar
  252. Prescott B, Kauffmann G, James WD (1957c) Means of increasing the tolerated dose of isoniazid in mice. II. Certain amino acids. Proc Soc Exp Biol Med 95: 687–690Google Scholar
  253. Prescott B, Kauffmann G, James WD (1957d) Means of increasing the tolerated dose of isoniazid in mice. III. Certain vitamins. Proc Soc Exp Biol Med 95: 705–708Google Scholar
  254. Prescott B, Stone HJ (1969) Glycerol formol as a solvent for detoxification of isoniazid. Chemotherapy 14: 227–231PubMedGoogle Scholar
  255. Quadbeck G, Sartori GD (1957) Über den Einfluß von Pyridoxin und Pyridoxal-5-Phosphat auf den Thiosemicarbazid-Krampf der Ratte. Naunyn Schmiedebergs Arch Pharmacol 230: 457–461Google Scholar
  256. Raisfeld IH (1975) Drug-induced liver disease: guinea pig model for isoniazid (INH) hepatitis — the predictive value of urinary d-glucaric acid excretion. Gastroenterology 69: A54 /854Google Scholar
  257. Reilly RH, Killam KF, Jenney EH, Marshall WH, Tausig T, Apter NS, Pfeiffer CC (1953) Convulsant effect of isoniazid. JAMA 152: 1317–1321Google Scholar
  258. Reinhardt JF, Kimura ET, Schachter RJ (1952) Some pharmacologic characteristics of isonicotinyl hydrazide (Pyricidin®), a new antituberculosis drug. Science 116: 166–167Google Scholar
  259. Roberts E (1974) y-Aminobutyric acid and nervous system function a perspective. Biochem Pharmacol 23:2637–2649PubMedGoogle Scholar
  260. Röhrborn G, Propping P, Buselmaier W (1972) Mutagenic activity of isoniazid and hydrazine in mammalian test systems. Mutat Res 16: 189–194PubMedGoogle Scholar
  261. Röhrborn G et al. (1978) A correlated study of the cytogenetic effect of isoniazid (INH) on cell systems of mammals and man conducted by thirteen laboratories. Hum Genet 42: 1–60Google Scholar
  262. Rosen F (1955) Effect of isonicotinic acid hydrazide on niacin and pyridoxine metabolism in rats. Proc Soc Exp Biol Med 88: 243–246PubMedGoogle Scholar
  263. Rosenkranz HS, Carr HS (1971) Hydrazine antidepressants and isoniazid: potential carcinogens. Lancet I: 1354–1355Google Scholar
  264. Rubin B, Hassert GL, Jr, Thomas BGH, Burke JC (1952) Pharmacology of isonicotinic acid hydrazide (Nydrazid). Am Rev Tuberc 65: 392–401PubMedGoogle Scholar
  265. Rubin B, Burke JC (1952) Vitamin B12 and isoniazid. Lancet II: 937Google Scholar
  266. Rubin B, Burke JC (1953) Further observations on the pharmacology of isoniazid. Am Rev Tuberc 67: 644–651PubMedGoogle Scholar
  267. Said AH, Ahmed AAS (1967) Connective tissue changes induced in the chick embryo by isonicotinic acid hydrazide and vitamin K. Zbl Veterinarmed (A) 14: 78–84Google Scholar
  268. Schlaepfer WW, Hager H (1964a) Ultrastructural studies of INH-induced neuropathy in rats. I. Early axonal changes. Am J Pathol 45: 209–219Google Scholar
  269. Schlaepfer WW, Hager H (1964b) Ultrastructural studies of INH-induced neuropathy in rats. II. Alteration and decomposition of the myelin sheath. Am J Pathol 45: 423–433Google Scholar
  270. Schlaepfer WW, Hager H (1964c) Ultrastructural studies of INH-induced neuropathy in rats. III. Repair and Regeneration. Am J Pathol 45: 679–689Google Scholar
  271. Schmidt LH, Hoffmann R, Hughes HB (1953) The toxicity of isoniazid for the rhesus monkey. Am Rev Tuberc 67: 798–807PubMedGoogle Scholar
  272. Schöneich J (1976) Safety evaluation based on microbial assay procedures. Mutat Res 41: 89–94PubMedGoogle Scholar
  273. Schröder JM (1970a) Zur Pathogenese der Isoniazid-Neuropathie. I. Eine feinstrukturelle Differenzierung gegenüber der Wallerschen Degeneration. Acta Neuropath 16: 301–323Google Scholar
  274. Schröder JM (1970b) Zur Pathogenese der Isoniazid-Neuropathie. II. Phasenkontrast-und elektronenmikroskopische Untersuchungen am Rückenmark, an Spinalganglien und Muskelspindeln. Acta Neuropathol 16: 324–341Google Scholar
  275. Seifert S (1966) Die teratogene Wirkung von Isonikotinséurehydrazid (INH) auf den Héhnerembryo. Diss Freiburg i BrGoogle Scholar
  276. Severi L, Biancifiori C (1968) Hepatic carcinogenesis in CBA/Cb/Se mice and Cb/Se rats by isonicotinic acid hydrazide and hydrazine sulfate. J Natn Cancer Inst 41: 331–340Google Scholar
  277. Siegel D, Iwainsky H (1960) Über den Einfluß von Iso-Nicotinsäure-Hydrazid (INH) auf die Metastasierungsquote des Ehrlichschen Ascitescarcinom der Maus. Klin Wochenschr 38: 769Google Scholar
  278. Siegel D (1960) Beitrag zur Frage der cytostatischen Wirkung des Iso-Nicotinsäure-Hydrazids (INH). Naturwissenschaften 47: 307–308Google Scholar
  279. Siegel D (1961) Veränderungen des Nucleinsäuregehaltes tumorösen Gewebes durch IsoNikotinsäure-Hydrazid (INH). Naturwissenschaften 48: 55–56Google Scholar
  280. Siegel D, Berschneider F (1960) Untersuchungen zum Nucleinsäurestoffwechsel der regenerierenden Leber nach Isonicotinsäurehydrazid (INH). Z Gesamte Exp Med 134: 59–64Google Scholar
  281. Simon K (1952) Untersuchungen von Derivaten des Hydrazins auf ihre cytostatische Wirkung am Ascitestumor der Maus. Z Naturforsch 7 b: 531–536Google Scholar
  282. Steinbrück P (1959) Der Einfluß über lange Zeit fortgeführter INH-Gaben auf die Fruchtbarkeit der weißen Maus. Z Tuberk 113: 281–284Google Scholar
  283. Tiboldi T, David M, Kovacs K, Molnar P (1955) Die Wirkung des Isonikotinsäurehydrazid auf das Brown-Pearce-Karzinom des Kaninchens. Z Tuberk 106: 257–260PubMedGoogle Scholar
  284. Timbrell JA, Mitchell JR, Snodgrass WR, Nelson SD (1980) Isoniazid hepatotoxicity: the relationship between covalent binding and metabolism in vivo. J Pharmacol Exp Ther 213: 364–369PubMedGoogle Scholar
  285. Tirunarayanan MO, Vischer WA (1956) Effect of vitamines on the acute toxicity of hydrazine derivatives. Experientia 12: 291–292PubMedGoogle Scholar
  286. Tosk J, Schmeltz I, Hoffmann D (1979) Hydrazines as mutagenes in a histidine — requiring auxotroph of Salmonella typhimurium. Mutat Res 66: 247–252PubMedGoogle Scholar
  287. Toth B, Shubik P (1966a) Inhibition of tumor development and carcinogenesis by isonicotinic acid hydrazide (INH) in C3H und AKR mice. Abstract, p 124. Presented at the IX International Cancer Congress, TokyoGoogle Scholar
  288. Toth B, Shubik P (1966b) Mammary tumor inhibition and lung adenoma induction by isonicotinic acid hydrazide. Science 152: 1376–1377Google Scholar
  289. Toth B, Shubik P (1966c) Carcinogenesis in swiss mice by isonicotinic acid hydrazide. Cancer Res 26: 1473–1475Google Scholar
  290. Toth B, Rustja A (1967) The effect of isonicotinic acid hydrazide on the development of tumors. Int J Cancer 2: 413–420PubMedGoogle Scholar
  291. Toth B, Shubik P (1969) Lack of carcinogenic effects of isonicotinic acid hydrazide in the syrian golden hamster. Tumori 55: 127–135PubMedGoogle Scholar
  292. Toth B, Boreisha J (1969) Tumorigenesis with isonicotinic acid hydrazide and urethan in the syrian golden hamsters. Eur J Cancer 5: 165–171Google Scholar
  293. Toth B, Toth T (1970) Investigation on the tumor producing effect of isonicotinic acid hydrazide in ASW/Sn mice and MCR rats. Tumori 56: 315–324PubMedGoogle Scholar
  294. Toth B, Shimizu H (1973) Lung carcinogenesis with 1-Acetyl-2-Isonicotinoylhydrazine, the major metabolite of isoniazid. Eur J Cancer 9: 285–289PubMedGoogle Scholar
  295. Viallier J, Casanova F (1960) L’isoniazide a-t-il des propriétés cancérigènes? Essai sur l’animal. CR Soc Biol 154: 985–987Google Scholar
  296. Wade DR, Lohman PHM, Mattem IE, Berends F (1980) The mutagenicity of isoniazid in Salmonella and its effects on DNA repair and synthesis in human fibroblasts. Mutat Res 89: 9–20Google Scholar
  297. Wagner H, Moritz R (1962) Beeinflussung des Tumorwachstums durch INH in Tierversuch und Gewebekultur. Arch Geschwulstforsch 19: 123–129Google Scholar
  298. Weinstein HJ, Kinosita R (1963) Isoniazid induction of pulmonary tumors in mice. Am Rev Respir Dis 88: 124–125Google Scholar
  299. Weiss P, Gâti T, Forrai G (1954) Die Wirkung von Isonikotinsäurehydrazid auf das Hypophysen-Nebennierenrindensystem bei weißen Ratten. Z Inn Med 9: 808–809Google Scholar
  300. Whitehouse LW, Tryphonas L, Thomas BH, Paul CP, Zeitz W (1978) Isoniazid toxicity alone and in combination with ethanol in the rabbit. I. Pathologic and biochemical factors. Toxicol Appl Pharmacol 45: 351Google Scholar
  301. Wiezorek WD, Kermes U, Wolf P (1977) Experimentelle Untersuchungen über die Wirkung von Barbituraten, Methaqualon und Benzodiazepinen bei der akuten Isoniazidintoxikation. Pharmazie 32: 37–39PubMedGoogle Scholar
  302. Williams HL, Wiegand RG (1960) Xanthurenic acid excretion and possible pyridoxine deficiency produced by isonicotinic acid hydrazide and other convulsant hydrazides. J Pharmacol Exp Ther 128: 344–348PubMedGoogle Scholar
  303. Williams HL, Bain JA (1961) Convulsive effects of hydrazides: relationship to pyridoxine. Int Rev Neurobiol 3: 319–348Google Scholar
  304. Wolf P, Ellert T, Gröger H (1965) Zur Frage der Beeinflußbarkeit der Isoniazid-Intoxikation durch einige Barbiturate, Chloralhydrat und Methylpentinol im Tierexperiment. Acta Biol Med German 15: 184–186PubMedGoogle Scholar
  305. Worden AN, Palmer AC, Noel PRB, Mawdesley-Thomas LE (1967) Lesions in the brain of the dog induced by prolonged administration of mono-amine oxidase inhibitors and isoniazid. Proc Eur Soc Study Drug Tox 8: 149–161Google Scholar
  306. Yamamoto RS, Weisburger JH (1970) Failure of arginine glutamate to inhibit lung tumour formation by isoniazid and hydrazine in mice. Life Sci 9 (II): 285–289Google Scholar
  307. Zbinden G, Studer A (1955a) Zur Wirkung von Vitaminen der B-Gruppe auf die experimentelle Isoniazid-„Neuritis“. Schweiz Z Path Bakt 18: 1198–1211Google Scholar
  308. Zbinden G, Studer A (1955b) Experimenteller Beitrag zur Frage der Isoniazid-Neuritis und ihrer Beeinflussung durch Pyridoxin. Z Tuberk 107: 97–107Google Scholar
  309. Zbinden G, Studer A (1955c) Vergleichende Untersuchungen über die Wirkung von Pyridoxin, Pyridoxal-5’-phosphat und Pyridoxal-isonicotinylhydrazon auf die experimentelle Isoniazid-„Neuritis” der Ratte. Int Z Vitaminforsch 26: 130–137Google Scholar
  310. Zbinden G, Studer A (1956) Wirkung der Glutaminsäure auf die experimentelle IsoniazidSchädigung peripherer Nerven bei Ratten. Experientia 12: 442–443PubMedGoogle Scholar
  311. Zeller EA, Barsky J, Fouts JR, Kirchheimer WF, Van Orden LS (1952) Influence of isonicotinic acid hydrazide (INH) and 1-isonicotinyl-2-isopropyl hydrazide (IIH) on bacterial and mammalian enzymes. Experientia 8: 349–350Google Scholar
  312. André T (1956) Studies on the distribution of tritium-labeled dihydrostreptomycin and tetracycline in the body. Acta Radiol Suppl 142: 52–73Google Scholar
  313. Bacharach AL, Clark BJ, McCulloch M, Tomich EG (1959) Comparative toxicity studies on ten antibiotics in current use. J Pharm Pharmacol 11: 737–741PubMedGoogle Scholar
  314. Barkalaya AJ (1964), Transplacental effect of antibiotics of tetracycline group on kidneys of fetuses of pregnant rats. Fed Proc 23: T753–754Google Scholar
  315. Benitz K-F, Diermeier HF (1964) Renal toxicity of tetracycline degradation products. Proc Soc Exp Biol 115: 930–935PubMedGoogle Scholar
  316. Bevelander G (1963) Effect of tetracycline on crystal growth. Nature 198: 1103Google Scholar
  317. Bevelander G, Nakahara H, Rolle GK (1960) The effect of tetracycline on the development of the skeletal system of the chick embryo. Dev Biol 2: 298–312PubMedGoogle Scholar
  318. Bevelander G, Rolle GK, Cohlan SQ (1961) The effect of the administration of tetracycline on the development of teeth. J Dent Res 40: 1020–1024Google Scholar
  319. Bevelander G, Cohlan SQ (1962) The effect on the rat fetus of transplacentally acquired tetracycline. Biol Neonat 4: 365–370PubMedGoogle Scholar
  320. Bevelander G, Goss RJ (1962) Influence of tetracycline on calcification in normal and regenerating teleost scales. Nature 193: 1098–1099PubMedGoogle Scholar
  321. Bezzi G, Gessa GL (1961) Influence of antibiotics on the neuromuscular transmission in mammals. Antibiot Chemotherap 11: 710–714Google Scholar
  322. Breen KJ, Schenker S, Heimberg M (1972a) Pathogenesis of tetracycline fatty liver. Clin Res 20: 74Google Scholar
  323. Breen K, Schenker S, Heimberg M (1972b) The effect of tetracycline on the hepatic secretion of triglyceride. Biochem Biophys Acta 270: 74–80Google Scholar
  324. Breen KJ, Schenker S, Heimberg M (1975) Fatty liver induced by tetracycline in the rat. Dose-response relationship and effect of sex. Gastroenterology 69: 717–723Google Scholar
  325. Brown DM, Harper KH, Palmer AK, Tesh SA (1968) Effects of antibiotics upon pregnancy in the rabbit. Toxicol Appl Pharmacol 12: 295Google Scholar
  326. Du Buy HG, Showacre JL (1961) Selective localization of tetracycline in mitochondria of living cells. Science 133: 196–197Google Scholar
  327. Clausen G, Nagy Z, Szalay L, Aukland K (1975) Mechanism in acute oliguric renal failure induced by tetracycline infusion. Scand J Clin Lab Invest 35: 625–633PubMedGoogle Scholar
  328. Cohen LS, Wechsler AS, Mitchell JH, Glick G (1970) Depression of cardiac function by streptomycin and other antimicrobial agents. Am J Cardiol 26: 505–511PubMedGoogle Scholar
  329. Cohlan SQ, Bevelander G, Tiamsic T (1963) Growth inhibition of prematures receiving tetracycline. Am J Dis Child 105: 453–461Google Scholar
  330. Cullen SJ, Catalano PM, Helfman RJ (1966) Tetracycline sun sensitivity. Arch Derm 93: 77PubMedGoogle Scholar
  331. Cunningham RW, Hines LR, Stokey EH, Vessey RE, Yuda NN (1953) Pharmacology of tetracycline. Antibiot Annu 1953–1954: 63–69Google Scholar
  332. Damjanov J, Solter D (1971) Ultrastructure of acute tetracycline induced liver change. Experientia 27: 1204–1205PubMedGoogle Scholar
  333. Detyuk ES, Vdovichenko IA, Kartysh GA (1971) Tetracycline effect on embryogenesis of albino rats. Antibiotiki (Moskau) 16: 923–926Google Scholar
  334. Eger W, Ilbagian K (1962) Untersuchungen über die Wirkung von Tetracyclinen auf die Leber. Arzneimittelforsch 12: 285–289PubMedGoogle Scholar
  335. English AR, P’an SY, McBride TJ, Gardocki JF, Van Halsema G, Wright WA (1953) Tetracycline-microbiologic, pharmacologic and clinical evaluation. Antibiot Annu 19531954: 70–80Google Scholar
  336. Farhat SM, Schelhart DL, Musselman MM (1958) Clinical toxicity of antibiotics correlated with animal studies. AMA Arch Surg 76: 762–765PubMedGoogle Scholar
  337. Fillippi B, Mela V (1957) Malformazioni congenite facciali e degli arti da tetraciclina. Minerva Chir 12: 1–15Google Scholar
  338. Fillippi B (1967) Antibiotics and congenital malformations: Evaluation of the teratogenicity of antibiotics. Adv Teratol 2: 239–256Google Scholar
  339. Franklin TJ (1963) The inhibition of incorporation of leucine into protein of cell-free systems from rat liver and Escherichia coli by chlortetracycline. Biochem J 87: 449–453PubMedGoogle Scholar
  340. Franklin TJ (1964) The effect of chlortetracycline on the transfer of leucine and “transfer” ribonucleic acid to rat-liver ribosomes in vitro. Biochem J 90: 624–628PubMedGoogle Scholar
  341. Giovannini M (1962) Toxizität (der Tetracycline). In: Brunner R, Machek G (eds) Die Antibiotika, Band I, Teil 2. Carl, Nürnberg, pp 506–510Google Scholar
  342. Gray JE, Weaver RN, Skinner P, Mathews J, Day CE, Stern K (1974) Effects of tetracycline on ultrastructure and lipoprotein secretion in the rat hepatocyte. Toxicol Appl Pharmacol 30: 317–322Google Scholar
  343. Greenberger NJ, Perkins RL, Cuppage FE, Ruppert RD (1967) Severe metabolic acidosis in the rat induced by toxic doses of tetracycline. Proc Soc Exp Biol Med 125: 11941197Google Scholar
  344. Greenberger NJ (1967) Inhibition of protein synthesis in rat intestinal slices by tetracycline. Nature 214: 702–703PubMedGoogle Scholar
  345. Hahn KJ, Morgenstern E, von Puttkamer K, Weber E (1970) Schädigungen der Mitochondrien von Darmepithelzellen bei oraler Therapie mit Tetrazyklinen. Naunyn Schmiedebergs Arch Pharmacol 266: 347PubMedGoogle Scholar
  346. Hakkinen JPT (1958) The fluorescence of tetracycline in rats treated with dihydrotachysterol, AT 10. Acta Physiol Scand 42: 282–287PubMedGoogle Scholar
  347. Halme J, Aer J (1968) Inhibition of collagen synthesis and bone calcification in the foetal rat by tetracycline. Scand J Clin Lab Invest 21, Suppl 101: 4Google Scholar
  348. Halme J, Kivirikko KJ, Kaitila J, Saxen L (1969) Effect of tetracycline on collagen biosynthesis in cultured embryonic bones. Biochem Pharmacol 18: 827–836PubMedGoogle Scholar
  349. Hansen CH, Pearson LH, Schenker S, Combes B (1968) Impaired secretion of triglycerides by the liver; a cause of tetracycline-induced fatty liver. Proc Soc Exp Biol Med 128: 143–146PubMedGoogle Scholar
  350. Hanson DJ (1961) Local toxic effects of broad-spectrum antibiotics following injection. Antibiot Chemotherap 11: 390–404Google Scholar
  351. Harcourt JK, Johnson NW, Storey E (1962) Incorporation of tetracycline antibiotics in bone, teeth, and egg shells. J Dent Res 41: 511Google Scholar
  352. Hash JH (1963) Effects of tetracyclines on the incorporation of C14-alanine into staphylococcus aureus. Fed Proc 22: 301Google Scholar
  353. Helander S, Böttiger L (1953) On the distribution of terramycin in different tissues. Acta Med Scand 147: 71–75PubMedGoogle Scholar
  354. Hughes WH, Lee WR, Flood DJ (1965) A comparative study of the actions of six tetracy-clines on the development of the chick embryo. Br J Pharmacol 25: 317–323Google Scholar
  355. Hurley LS, Tuchmann-Duplessis H (1963) Influence de la tétracycline sur le développement pré-et post-natal du rat. CR Acad Sci 257: 302–304Google Scholar
  356. Ibsen KH, Urist MR (1963) Complexes of calcium and magnesium with oxytetracycline. Proc Soc Exp Biol Med 109: 797–801Google Scholar
  357. Ison A, Blank H (1967) Testing drug phototoxicity in mice. J Invest Dermatol 49: 508–511PubMedGoogle Scholar
  358. Kämmerer H, Eger W (1956) Tetracycline and Knochenstoffwechsel. Med Welt 1: 986–991Google Scholar
  359. Kelly RG, Buyske D (1960) Metabolism of tetracycline in the rat and the dog. J Pharmacol Exp Ther 130: 144–149PubMedGoogle Scholar
  360. Kohonen J, Guile EE, Plosila A (1968) Effects of tetracycline on osteogenesis in embryos of mice. Scand J Clin Lab Invest 21, Suppl 101: 4Google Scholar
  361. Kubikowski P, Szreniawski Z (1963) The mechanism of the neuromuscular blockade by antibiotics. Arch Int Pharmacodyn Ther 146: 549–560PubMedGoogle Scholar
  362. Kuck NA, Redin GS (1960) Comparison of demethylchlortetracycline with tetracycline in the control of experimental infections in mice. J Pharmacol Exp Ther 129: 350–355PubMedGoogle Scholar
  363. Küpper K, Stupp H, Orsulakova A, Quante M (1970) Vergleichende Untersuchungen der Ototoxizität verschiedener antibiotischer Substanzen bei lokaler Applikation am Innenohr des Meerschweinchens. Arch Otorhinolaryngol 196: 169–172Google Scholar
  364. Leaders F, Pittinger CB, Long JP (1960) Some pharmacological properties of selected antibiotics. Antibiot Chemotherap 10: 503–507Google Scholar
  365. Lewis M, Schenker S (1966) Studies on the pathogenesis of tetracycline-induced fatty liver. Clin Res 14: 48Google Scholar
  366. Lewis M, Schenker S, Combee B (1967) Studies on the pathogenesis of tetracycline-induced fatty liver. Am J Digest Dis 12: 429–438PubMedGoogle Scholar
  367. Lindquist RR, Fellers FX (1966) Degraded tetracycline nephropathy. Lab Invest 15: 864–876PubMedGoogle Scholar
  368. Lowe MB, Tapp E (1966) Renal damage caused by anhydro-4-epitetracycline. Arch Pathol 81: 362–364PubMedGoogle Scholar
  369. Maffii G, Semenza F, Soncin E (1957) Saline solutions as a factor affecting the toxicity of intravenously injected tetracyclines in mice. J Pharm Pharmacol 9:105–112PubMedGoogle Scholar
  370. McColl JD, Globus M, Robinson S (1965) Effect of some therapeutic agents on the developing rat fetus. Toxicol Appl Pharmacol 7: 409–417PubMedGoogle Scholar
  371. McIntosh HA, Storey E (1970) Tetracycline-induced tooth changes, Part 4. Discoloration and hypoplasia induced by tetracycline analogues. Med J Aust 1: 114–119PubMedGoogle Scholar
  372. Mennie AT (1962) Tetracycline and congenital limb abnormalities. Br Med J II: 480Google Scholar
  373. Mikaelyan NP, Ulyanov MI (1971) On some shifts in thrombocytopoiesis systems in rabbits treated with tetracyclin. Antibiotiki 16: 624–626Google Scholar
  374. Mikaelyan NP, Eingorn AG, Ulyanov MI (1973) Morphological changes induced by tetracycline in rabbits. Antibiotiki 18: 906–910Google Scholar
  375. Milch RA, Rall DP, Tobie JE (1957) Bone localization of the tetracyclines. J Natl Cancer Inst 19: 87–93PubMedGoogle Scholar
  376. Milch RA, Rall DP, Tobie JE (1958) Fluorescence of tetracycline antibiotics in bone. J Bone Joint Surg 40 A: 897–910PubMedGoogle Scholar
  377. Milch RA, Tobie JE, Robinson J (1961) A microscopic study of tetracycline localization in skeletal neoplasms. J Histochem Cytochem 9: 261–270PubMedGoogle Scholar
  378. Miller SEP, MacSween RNM, Glen ACA, Tribedi K, Moore FML (1967) Experimental studies on the hepatic effects of tetracycline. Br J Exp Pathol 48: 51–57PubMedGoogle Scholar
  379. Mukherjee D, Mukherjee S (1969) Studies on the effect of tetracycline on triglyceride synthesis in experimental rats. J Antibiotics 22: 45–48Google Scholar
  380. Mukherjee D, Ghosh H, Mukherjee S (1969) Studies on the effect of administration of tetracycline on free fatty acid metabolism in adrenalectomised and control rats. J Antibiotics 22: 480–483Google Scholar
  381. Mukherjee D, Ghosh HN, Mukherjee S (1971) The effect of tetracycline on synthesis of fatty acid and cholesterol in the liver of control and experimental rats. J Antibiotics 24: 263–265Google Scholar
  382. Nelson AA, Radomski JL (1954) Comparative pathological study in dogs of feeding of six broadspectrum antibiotics. Antibiotics Chemother 4: 1174Google Scholar
  383. Owen LN (1961) Fluorescence of tetracyclines in bone tumors, normal bone teeth. Nature 190: 500–502PubMedGoogle Scholar
  384. P’an SY, Scaduto L, Cullen M (1950) Pharmacology of terramycin in experimental animals. Ann New York Acad Sci 53: 238–244Google Scholar
  385. Parker FL, James GWL (1978) The effect of various topical antibiotics and antibacterial agents on the middle and inner ear of the guinea-pig. J Pharm Pharmacol 30: 236–239PubMedGoogle Scholar
  386. Pittinger Ch, Adamson R (1972) Antibiotic blockade of neuromuscular function. Annu Rev Pharmacol 12: 169–184PubMedGoogle Scholar
  387. Polec RB, Yeh SDJ, Shils ME (1971) Protective effect of ascorbic acid, isoascorbic acid and mannitol against tetracycline-induced nephrotoxicity. J Pharmacol Exp Ther 178: 152–158PubMedGoogle Scholar
  388. Rall DP, Loo TL, Lane M, Kelly MG (1957) Appearance and persistence of fluorescent material in tumor tissue after tetracycline administration. J Natl Cancer Inst 19: 79–85PubMedGoogle Scholar
  389. Rendi R, Ochoa S (1961) Enzyme specificity in activation and transfer of amino acids to ribonucleoprotein particles. Science 133: 1367Google Scholar
  390. Savini EC, Moulin MA, Herrou MFJ (1968) Effets tératogènes de l’oxytetracycline. Thérapie 23: 1247–1260PubMedGoogle Scholar
  391. Saxén L (1966) Effect of tetracycline on osteogenesis in vitro. J Exp Zool 162: 269–294Google Scholar
  392. Schenker S, Hansen C, Combes B (1968) Impaired secretion of hepatic triglycerides - a cause of tetracycline-induced fatty liver. Gastroenterology 54: 1268Google Scholar
  393. Schoenbach EM, Bryer MS, Long PH (1950–1951) The pharmacology of terramycin in animals and man with reference to its clinical trial. Ann NY Acad Sci 53:245–252Google Scholar
  394. Shauer BA, Lukacs L, Zimmerman HJ (1974) Biochemical indices of tetracycline hepatic injury in rats. Proc Soc Exp Biol Med 147: 868–872PubMedGoogle Scholar
  395. Schorr WF, Monash S (1963) Photo-irradiation studies of two tetracyclines. Arch. Dermatol 88: 440–444PubMedGoogle Scholar
  396. Smith H, Chapman IV (1963) Use of the living chick embryo as a biological indicator of the effectiveness of chelating agents. Nature 198: 32–33PubMedGoogle Scholar
  397. Steiner G, Bradford W, Craig JM (1965) Tetracycline-induced abortion in the rat. Lab Invest 14: 1456–1463PubMedGoogle Scholar
  398. Suarez G, Nathans D (1965) Inhibition of aminoacyl-sRNA binding to ribosomes by tetracycline. Biochem Biophys Res Comm 18: 743–750Google Scholar
  399. Surgen RC, Nielsen JK (1960) Some factors influencing the toxicity (safety) test for antibiotics. Antibiot Chemotherap 10: 169–173Google Scholar
  400. Swain HH, Kiplinger GF, Brody TM (1956) Actions of certain antibiotics on the isolated dog heart. J Pharmacol Exp Ther 117: 151–159PubMedGoogle Scholar
  401. Tubaro E (1964) Possible relationship between tetracycline stability and effect on foetal skeleton. Br J Pharmacol 23: 445–448Google Scholar
  402. Tubaro E, Barletta M, Banci F (1964) Some pharmacological aspects of a new water-soluble tetracycline. J Pharm Pharmacol 16: 33–37PubMedGoogle Scholar
  403. Urist MR, Ibsen KH (1963) Chemical reactivity of mineralized tissue with oxytetracycline. Arch Pathol 76: 484–496PubMedGoogle Scholar
  404. Verret MJ, Mutchier MK (1964) Teratogenic effects of antibiotics in the chick embryo. Fed Proc 23: 104Google Scholar
  405. Wivagg RT, Jaffe JM, Colaizzi JL (1976) Influence of pH and route of injection on acute toxicity of tetracycline in mice. J Pharm Sci 65: 916–918PubMedGoogle Scholar
  406. Yeh SDJ, Shils ME (1966) Tetracycline and incorporation of amino acids into proteins of rat tissues. Proc Soc Exp Biol Med 121: 729–734PubMedGoogle Scholar
  407. Zolotukhin SI (1958) The effect of the tetracycline group of antibiotics on the coagulation of the blood. Antibiotics 4: 324–327Google Scholar
  408. Adamson RH, Marshall FN, Long JP (1960) Neuromuscular blocking properties of various polypeptide antibiotics. Proc Soc Exp Biol Med 105: 494–497PubMedGoogle Scholar
  409. Caesar R (1965) Die Bedeutung der Lysosomen für die formale Genese der Viomycin-Nephrose. Verh Dtsch Ges Pathol 49: 157–161PubMedGoogle Scholar
  410. Gössner W (1963) Nebenwirkungen der modernen Chemotherapeutika vom Standpunkt des Pathologen. Antibiot Chemother 11: 285–300Google Scholar
  411. Kanda T, Igarashi M (1969) Ultra-structural changes in vestibular sensory and organs after viomycin sulfate intoxication. Acta Otolaryngol 68: 474–488PubMedGoogle Scholar
  412. Keller H, Krüpe W, Sous H, Mückter H (1956) Versuche zur Toxizitätsminderung basischer Streptomyces-Antibiotica. 2. Mitteilung. Arzneimittelforsch 6: 61–66PubMedGoogle Scholar
  413. Klein HJ, Steinbach E, Schümmelfeder N (1966) Ultrastrukturelle und histochemische Untersuchungen zur Entstehung der Viomycin-Nephrose. Frankfurter Z Pathol 75: 432–445Google Scholar
  414. Kubikowski P, Szreniawski Z (1963) The mechanism of the neuromuscular blockade by antibiotics. Arch Int Pharmacodyn Ther 146: 549–560PubMedGoogle Scholar
  415. Moyer JH, Handley CA (1953) Renal function during viomycin administration to dogs. Proc Soc Exp Biol Med 82: 761–763PubMedGoogle Scholar
  416. Mückter H (1961) Zur Pharmakologie der basischen Streptomyces-Antibiotika. Antibiot Chemother 9 Sep: 83–144Google Scholar
  417. P’an SY, Halley TV, Reilly JC, Pekich AM (1951) Viomycin. Acute and chronic toxicity in experimental animals. Am Rev Tuberc 63: 44–48PubMedGoogle Scholar
  418. Staemmler M, Karhoff B (1956) Die akuten Nephrosen. II. Mitteilung. Nierenschäden durch Antibiotica. Virchows Arch 328: 481–502PubMedGoogle Scholar
  419. Staemmler M (1957) Die akuten Nephrosen. IV. Mitteilung. Tubuläre Schädigung und Wiederherstellung. Virchows Arch 330: 139–155PubMedGoogle Scholar
  420. Vital Brazil O, Ramos AO, Sperandio LG, Martinez AL (1961) Viomycin. Pharmacological actions on myoneural junction, ganglionic synapse and smooth muscle. Chemotherapia 3: 521–531Google Scholar
  421. Anderson RC, Worth HM, Welles JS, Harris PN, Chen KK (1956) Pharmacology and toxicology of cycloserine. Antibiot Chemother 6: 360–368Google Scholar
  422. Bonati F, Bertoni L, Rosati G, Zanichelli V (1963) Caratteristiche biologiche ed attività antibatterica del teridizone. Il Farmaco Prat 20: 381–395Google Scholar
  423. Bonavita V, Lettieri M, Monaco P (1964) Behavioural studies on rats injected with L-cycloserine and other compounds. Psychopharmacologia 5: 234–238PubMedGoogle Scholar
  424. Bykova MA, Storozhev IA, Berezin EA (1965) Zur Pharmakologie des D-Cycloserin. Antibiotiki 10: 626–629PubMedGoogle Scholar
  425. Dengler HJ (1962) Zur Hemmung der L-Glutaminsäure-und L-Dopadecarboxylase durch D-Cycloserin und andere Isoxazolidone. Naunyn Schmiedebergs Arch Pharmacol 243: 366–381Google Scholar
  426. Epstein IG, Nair KGS, Mulinos MG, Haber A (1959) Pyridoxine and its relation to cycloserin neurotoxicity. Antibiot Annu 1958–1959: 472–481Google Scholar
  427. Fust B, Böhni E, Pellmont B, Zbinden G, Studer A (1958) Experimentelle Untersuchungen mit D-Cycloserin. Schweiz Z Tuberk 15: 129–157PubMedGoogle Scholar
  428. Glass F, Mallach HJ, Simsch A (1965) Beobachtungen und Untersuchungen über die gemeinsame Wirkung von Alkohol und D-Cycloserin. Arzneimittelforsch 15: 684–688PubMedGoogle Scholar
  429. Lange P, Oehme P (1964) Zentralnervöse Wirkungen von D- und D,L-Cycloserin. Arch Int Pharmacodyn Ther 152: 466–473PubMedGoogle Scholar
  430. Mayer O, Jankü I, Krsiak M (1971) Die zentralen Wirkungen des Cycloserins im Tierexperiment. Arzneimittelforsch 21: 298–303Google Scholar
  431. Prescott B, Kauffmann G, James WD (1957) Increase in tolerated dose of isoniazid in mice by use of cycloserine. Proc Soc Exp Biol Med 94: 94–96PubMedGoogle Scholar
  432. Robinson HJ, Mason RC, Siegel H (1956) Toxicity and pharmacology of cycloserine. Am Rev Tuberc 74: 972–976PubMedGoogle Scholar
  433. Spencer JN, Payne HG (1956) Cycloserine. Experimental Studies. Antibiot Chemother 6: 708–716Google Scholar
  434. Baeder DH, Ledaux G, Marier G (1962) The pharmacology and toxicology of ethionamide. Fed Proc 21: 452Google Scholar
  435. Bargeton D (1964) Etude toxicologique du 1321 TH. Unpublished investigations Biancifiori C, Milia U, Di Leo FP (1964) Lay Ist Anat Istol patol Univ Perugia 24:145Google Scholar
  436. Biancifiori C, Severi C (1966) The relationship of isoniazid (INH) and allied compounds to carcinogenesis in some species of small laboratory animals: A review. Br J Cancer 20: 528–538PubMedGoogle Scholar
  437. Dubost P, Fournel J, Ganter P, Julou L, Laville J, Myon J, Pascal S (1964) Produits 1314 TH (8.545 R.P.) ou ethionamide (Trecator, N.D. Theraplix) et 1321 TH (9.778 R.P.). Toxicité aigue et toxicité terme (3 mois). Unpublished investigationsGoogle Scholar
  438. Iliin AM (1975) Pharmaco-toxicogical study of the antituberculous preparation prothionamide Farmakol Toksikol 38: 471–472Google Scholar
  439. Ingham B (1963) Personal communicationGoogle Scholar
  440. Khan J, Azam A (1969) Study of teratogenic activity of trifluorperazine, amitriptyline, ethionamide and thalidomide in pregnant rabbits and mice. Proc Eur Soc Study Drug Tox 10: 235–241Google Scholar
  441. Lorke D (1963/64) Bericht über die Prüfung der embryotoxischen Wirkung von Iridocin (1314 TH). Unpublished investigationsGoogle Scholar
  442. Maral R, Ganter P (1967) Etude de l’activité cancerogène de: l’isoniazide (5.015 R.P.), du prothionamide (9.778 R.P. =1321 TH), de l’urethane (10.506 R.P.) et de l’hydrazine (14.377 R.P.). Unpublished investigationsGoogle Scholar
  443. Roux CH (1962) Rapport sur l’ètude du pouvoir teratogène du 1314 TH et du 2162 TH. Unpublished investigationsGoogle Scholar
  444. Roux CH (1963) Rapport sur l’ètude du pouvoir teratogène du 1314 TH et du 2162 TH. Unpublished investigationsGoogle Scholar
  445. Roux CH (1965) Rapport sur l’ètude du pouvoir teratogène du 1314 TH et du 2162 TH. Unpublished investigationsGoogle Scholar
  446. Roux CH (1965) Rapport sur l’ètude de l’effect teratogène du 1321 TH. Unpublished investigationsGoogle Scholar
  447. Woodard G (1960) Toxicity of TH-1314 following single and repeated daily doses in rats and dogs. Unpublished investigationsGoogle Scholar
  448. Akiyoshi M, Sato K (1970) Reevaluation of the pinna reflex test as screening for otoxicity of antibiotics. In: Progress in antimicrobial and anticancer chemotherapy. Proc 6th Intern Congr Chemotherapy, Vol I: 621–627Google Scholar
  449. Amann R, Radenbach KL (1961) Akute Kanamycin-Nebenwirkungen und Histaminfreisetzung. Beitr Klin Tuberk 123: 208–210Google Scholar
  450. Beck CHL, Krahl P (1962) Experimentelle und feingewebliche Untersuchungen über die Otoxicität von Kanamycin. Arch Otorhinolaryngol 179: 594–610Google Scholar
  451. Bevelander G, Cohlan SQ (1962) The effect on the rat of transplacentally aquired tetracycline. Biol Neonate 4: 365–370Google Scholar
  452. Brown JJ, Brummett RE, Fox KE (1979) Combined effects of noise and kanamycin: Cochlear pathology and pharmacokinetics in the guinea pig. Pharmacologist 21: 144Google Scholar
  453. Brummett RE, Traynor J, Brown R, Himes D (1975) Cochlear damage resulting from kanamycin and furosemide. Acta Oto-Laryngol (Stockh) 80: 86–92Google Scholar
  454. Cohen LS, Wechsler AS, Mitchell JH, Glick G (1970) Depression of cardiac function by streptomycin and other antimicrobial agents. Am J Cardiol 26: 505–511PubMedGoogle Scholar
  455. Farkashidy J, Black RG, Briant TDR (1963) The effect of kanamycin on the internal ear: an electrophysiological and electron microscope study. Laryngoscope 73: 713–727PubMedGoogle Scholar
  456. Goldberg LE (1964) Pharmakologische Prüfung des Antibiotikums Kanamycin (russ.). Antibiotiki (Moskau) 9: 414–420Google Scholar
  457. Goldberg LE, Ilyushina NG (1968) Experimental investigation of kanamycin circulation between mother and fetus. Byul Eksp Biol Med 66: 994–996Google Scholar
  458. Hawkins JE Jr (1959) The otoxicity of kanamycin. Ann Otol 68: 698–715Google Scholar
  459. Kinoshita Y, Yamasaku F, Takeda H, Usuda Y, Kitahara K (1970) Nephrotoxicity of kanamycin with a combination of plasma expander. In: Progress in antimicrobiol and anticancer chemotherapy. Proc 6th Intern Congr Chemotherapy, Vol I: 586–590Google Scholar
  460. Kohonen A (1965) Effect of some ototoxic drugs upon the pattern and innervation of cochlear sensory cells in the guinea pig. Acta Otolaryng (Stockh) Suppl 208: 9–70Google Scholar
  461. Lagler F, Osterloh G, Mückter H (1960) Studies on the pharmacology of kanamycin. Antibiot Annu 1959–1960: 862–867Google Scholar
  462. Luft F, Bloch R, Sloan RS, Yum MN, Costello R, Maxwell DR (1978) Comparative nephrotoxicity of aminoglycoside antibiotics in rats. J Infect Dis 138: 541–545PubMedGoogle Scholar
  463. Mückter H (1961) Zur Pharmakologie der basischen Streptomyces-Antibiotika. Antibiot Chemotherap 9 Sep: 83–114Google Scholar
  464. Nakazono M, Naide Y, Ohkoshi M (1970) Biochemical studies on nephrotoxicity of kanamycin. In: Progress in antimicrobial Chemotherapy. Vol I: 591–595Google Scholar
  465. Orr JL (1980) Behavioral toxicology of kanamycin. Dissertation Abstr Intern B 40: 50–68Google Scholar
  466. Osaka S, Tokimoto T, Matsuura S (1979) Effects of kanamycin on the auditory evoked responses during postnatal development of the hearing of the rat. Acta Oto-Laryngol (Stockh) 88: 359–368Google Scholar
  467. Owada K (1962) Experimental studies on the toxicity of kanamycin, its hydrolyzed products and neomycin. Chemotherapia 5: 277–293PubMedGoogle Scholar
  468. Pindell MH, Lein J (1964) Comparison of biological and toxicological properties of meth- ane sulfonate and sulfonate derivatives of antibiotics Chemotherapia 8: 163–174Google Scholar
  469. Plattig KH, Keidel UO, David E (1967) Minderung der Otoxizität des Kanamycin durch Panthothensäure. Elektrophysiologische Untersuchungen an der Katze. Dtsch Med Wochenschr 92: 1391–1397Google Scholar
  470. Raphael Y, Fein A (1980) Kanamycin otoxicity in utero. Isr J Med Sci 16: 554–555Google Scholar
  471. Renaud S (1960) The toxicity of kanamycin and bacitracin as influenced by stress and sodium chloride. Toxicol Appl Pharmacol 2: 708–714PubMedGoogle Scholar
  472. Sack K, Züllich B (1978) Differenzierung der nephrotoxischen Potenzen von Aminoglykosiden und Cephalosporinen im Tierexperiment. Therapiewoche 28: 2107–2114Google Scholar
  473. Singh YN, Harvey AL, Marshall IG (1978) Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine. Anesthesiology 48: 418–424PubMedGoogle Scholar
  474. Staemmler M, Dudkowiak V (1961) Über Wirkungen des Kanamycin auf die Nieren. Med Welt: 1296–1299Google Scholar
  475. Stebbins WC, Miller JM, Johnsson L-G, Hawkins JE Jr (1969) Ototoxic hearing loss and cochlear pathology in the monkey. Ann Otol 78: 1007–1025Google Scholar
  476. Tisch DE, Huftalen JB, Dickison HL (1958) Pharmacological studies with kanamycin. Ann NY Acad Sci 76: 44–65PubMedGoogle Scholar
  477. Toyada Y, Saito H, Matsuoka H, Takenaka H, Oshima W, Mizukoshi O (1978) Quanti- tative analysis of kanamycin ototoxicosis. Acta Oto-Laryngol (Stockh) 84: 202–212Google Scholar
  478. Russel NJ, Fox KE, Brummett RE (1979) Ototoxic effects of the interaction between kanamycin and ethacrynic acid. Cochlear ultrastructure correlated with cochlear potentials and kanamycin levels. Acta Oto-Laryngol (Stockh) 88: 369–381Google Scholar
  479. Tyberghein J (1962) Influence of some streptomyces antibiotics on the cochlear microphonics in the guinea pig. Acta Otolaryng (Stockh) Suppl 171Google Scholar
  480. West BA, Brummett RE, Himes DL (1973) Interaction of kanamycin and ethacrynic acid. Arch Otolaryngol 98: 32–37PubMedGoogle Scholar
  481. Lambelin G (1970) Pharmacology and toxicology of Isoxyl. Antibiotica et Chemotherapia 16: 84–95Google Scholar
  482. Lambelin G, Parmentier R (1963) Etude toxicologique de l’Isoxyl sur l’animal. Acta Tuberc Pneumol Be1g 54: 476–493Google Scholar
  483. Lambelin G, Parmentier R (1966) Study of the toxicity of isoxyl. Arzneimittelforsch 16: 881–886PubMedGoogle Scholar
  484. Akiyoshi M, Sato Y, Shoji T, Sugahiro K, Tamura H (1971) Histological changes in the stria vascularis of the inner ear in the case of auricular toxicosis by antibiotics (in Japanese). J Otolaryngol (Jap) 74: 476–477Google Scholar
  485. Muraoka Y, Hayashi Y, Minesita T (1968) Studies of capreomycin nephrotoxicity. Toxicol Appl Pharmacol 12: 350–359Google Scholar
  486. Welles JS, Harris PN, Small RM, Worth HM, Anderson RC (1966) The toxicity of capreomycin in laboratory animals. Ann NY Acad Sci 135: 960–973PubMedGoogle Scholar
  487. Asole A, Panu R, Palmieri G (1976) Effetti dell’etambutolo sull’epitelio seminale di ratto e pollo. Boll Soc Ital Biol Sper 52: 846–848PubMedGoogle Scholar
  488. Borchard U (1974) Untersuchungen über den Einfluß von Ethambutol auf peripheres and zentralnervöses Gewebe. Thesis, University of CologneGoogle Scholar
  489. Botticelli A, Trentini GP, Barbolini G (1971) Lesioni testicolari nel ratto trattato con etambutolo. Boll Soc Ital Biol Sper 47: 72–75PubMedGoogle Scholar
  490. Bruckschen EG (1970) Myambutol. Experimentelle and klinische Ergebnisse. Arzneimittelforsch, 20. Beiheft 2. Aufl.Google Scholar
  491. Buyske DA, Sterling W, Peets E (1966) Pharmacological and biochemical studies on ethambutol in laboratory animals. Ann NY Acad Sci 135: 711–725PubMedGoogle Scholar
  492. Cappiello VP, Layton WM Jr (1965) A one-year study of the toxicity of ethambutol in dogs: results of gross and histopathologic examinations. Toxicol Appl Pharmacol 7: 844–849PubMedGoogle Scholar
  493. Diermeier HF, Kaiser JA, Yuda N (1966) Safety evaluation of ethambutol. Ann NY Acad Sci 135: 732–746PubMedGoogle Scholar
  494. Fantoli U, Sebastiani M, Cattaneo C, Sbampato M (1968) Comportamento dell’ attività colinesterasica sierica in soggeti trattati con Etambutolo. Ann Inst C Forlanini 28: 164Google Scholar
  495. Figueroa R, Weiss H, Smith JC Jr, Hackley BM, McBean LD, Swassing ChR, Halsted JA (1971) Effect of ethambutol on the ocular zinc concentrations in dogs. Am Rev Resp Dis 104: 592–594PubMedGoogle Scholar
  496. Grifa P, Jotti D, Benatti G (1967) Ricereche sperimentali sulla tossicità dell’ Etambutolo sul sistema nervoso centrale di alcuni animali. Giorn It Chemiother 14: 65Google Scholar
  497. Hara T, Baba H (1970) Incorporation and metabolism of ethambutol in rat organs. Kekkaku 45: 129PubMedGoogle Scholar
  498. Kaiser JA (1964) A one-year study of the toxicity of ethambutol in dogs: results during life. Toxicol Appl Pharmacol 6: 557–567PubMedGoogle Scholar
  499. Schmidt J, Schmidt LH (1964) Neurotoxicity of ethambutol, an anti-tuberculosis drug. Anat Rec 148: 333Google Scholar
  500. Schmidt JG (1966) Central nervous system effects of ethambutol in monkeys. Ann NY Acad Sci 135: 759–774PubMedGoogle Scholar
  501. Thomas JP, Baughn CO, Wilkinson RG, Sheperd RG (1961) A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2’-(ethylenediimino)-di-lbutanol). Am Rev Respir Dis 83: 891–893PubMedGoogle Scholar
  502. Vogel AW, Kaiser JA (1963) Ethambutol-induced transient change and reconstitution (in vivo) of the tapetum lucidum color in the dog. Exp Mol Pathol Suppl 2: 136–149Google Scholar
  503. Anufrieva RG, Zeltser IZ, Svinogeeva TP (1980a) Placenta permeability by rifampicin (Russ.). Antibiotiki 25: 199–201Google Scholar
  504. Anufrieva RG, Zeltser IZ, Balabanova EL, Lapchinskaya AV, Baru RV, Svinogeeva TP (1980b) Experimental study of rifampicin effect on albino rat embryo genesis (Russ.). Antibiotiki 25: 280–284Google Scholar
  505. Balea T, Marche C, Marche J (1970) Effets hépato-biliaires de l’association rifarnpicineisoniazide. II. Etude histologique chez la souris tuberculisée. Thérapie 25: 125–130PubMedGoogle Scholar
  506. Bichl J (1973) Rifampicin in a carcinogenic experiment. Lancet 2: 1209Google Scholar
  507. Della Porta G, Cabral JR, Rossi L (1978) Carcinogenicity study of rifampicin in mice and rats. Toxicol Appl Pharmacol 43: 293–302Google Scholar
  508. Epstein SS, Arnold E, Andrea J, Bass W, Bishop Y (1972) Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol 23: 288–325PubMedGoogle Scholar
  509. Felgenhauer F, Lagler F (1970) Experimental animal investigations with rifampicin on the question of its influence on the vestibular system and its period of retention in the peri-lymph of the inner ear. Antibiot Chemother 16: 361–368PubMedGoogle Scholar
  510. Furesz S (1970) Chemical and biological properties of rifampicin. Antibiot Chemother 16: 316–351PubMedGoogle Scholar
  511. Hugues F-C, Marche C, Marche J (1969) Effets hépato-biliaires de l’association rifampicine-isoniazide. I. Etude histologique chez le rat. Thérapie 24: 899–906PubMedGoogle Scholar
  512. Hugues F-C, Marche C, Marche J (1970) Effets hépato-biliaires de l’association rifampicine-prothionamide. I. Etude histologique chez le rat. Thérapie 25: 131–136PubMedGoogle Scholar
  513. Jaeger E, Merker HJ, Bass R (1974) Investigations on the mode of teratogenic action of high doses of rifampicin. Teratology 10: 312Google Scholar
  514. Jezequel AM, Orlandi F, Tenconi LT (1971) Changes of the smooth endoplasmic reticulum induced by rifampicin in human and guinea-pig hepatocytes. Gut 12: 984–987PubMedGoogle Scholar
  515. Kluyskens P (1969) Recherches expérimentales de toxicité otovestibulaire des rifamycines. Acta Tuberc Pneumol Belg 60: 323–326PubMedGoogle Scholar
  516. Piriou A, Warnet JM, Jacqueson A, Claude JR, Truhaut R (1979) Fatty liver induced by high doses of rifampicin in the rat: possible relation with an inhibition of RNA polymerase in eukaryotic cells. Arch Toxicol Suppl 2: 333–337PubMedGoogle Scholar
  517. Schiatti P, Maggi N, Sensi P, Maffei G (1967) Biliary excretion rate of semisynthetic rifamycins in the rat. Chemotherapia 12: 155–171Google Scholar
  518. Sensi P, Maggi N, Füresz S, Maffei G (1967) Chemical modifications and biological properties of rifamycins. Antimicrob Agents Chemother 1966: 699–714Google Scholar
  519. Srb V, Puza V, Spurna V, Kerptova J (1974) The action of rifampicin on stabilized cell lines HEp-2 and HeLa. Experientia 30: 484–486PubMedGoogle Scholar
  520. Tuchmann-Duplessis H, Mercier-Parot L (1969) Influence d’un antibiotique, la rifampicine, sur le développement prénatal des rongeurs. CR Acad Sc (Paris) Série D 269: 2147–2149Google Scholar
  521. Vogel E, Obe G (1973) Testing of rifampicin on possible genetic effects on Drosophila melanogaster and human leukocyte chromosomes in vitro. Experientia 29: 124–125PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • D. Tettenborn

There are no affiliations available

Personalised recommendations