Subchronic toxicity study with ethylene-bis-(oxyethylene)-bis(3-tert- butyl-4-hydroxy-5-methylhydrocinnamate) in the Cynomolgus monkey: Lack of stimulation of the pituitary-thyroid-liver axis

Toxicological Sciences

Volumn 51, Issue 1, 1999, Pages 36-43

  Waechter, Felix ^a   Beilstein, Paul ^a   Burger, Albert G ^b   O'Connell, Maureen ^b   Fabreguettes, Catherine ^c   Forster, Roy ^c   Weideli, Hansjoerg ^d  

^a NOVARTIS PHARMA AG   (Switzerland)

^b Hôpital Cantonal   (Switzerland)

^c Centre International de Toxicologie   (France)

^d CIBA GEIGY LTD   (Switzerland)

Author keywords

Antioxidant; Cynomolgus monkey; Liver; Liver enzymes; Primate; Rat; Species differences; Thyroid; Thyroid hormone; Thyroid tumors

Indexed keywords

ANTIOXIDANT; HYDROCINNAMIC ACID DERIVATIVE; LIOTHYRONINE; MESSENGER RNA; PHENOBARBITAL; TESTOSTERONE; THYROTROPIN; THYROXINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FATTY ACID OXIDATION; HYDROXYLATION; LIVER HYPERTROPHY; MACACA; MALE; NONHUMAN; PEROXISOME; SPECIES DIFFERENCE; THYROID FOLLICULAR CARCINOMA; TOXICITY TESTING;

ANIMALS; ANTIOXIDANTS; ARYL HYDROCARBON HYDROXYLASES; BODY WEIGHT; CYTOCHROME P-450 ENZYME SYSTEM; IODIDE PEROXIDASE; LIVER; MACACA FASCICULARIS; MALE; MICROSOMES, LIVER; ORGAN SIZE; PITUITARY GLAND; POLYETHYLENE GLYCOLS; RATS; RNA, MESSENGER; SPECIES SPECIFICITY; STEROID HYDROXYLASES; THYROID GLAND; THYROID HORMONES; THYROTROPIN; TOXICITY TESTS;

EID: 0032823322     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/51.1.36     Document Type: Article

References (37)

1. Ashby, J., Brady, A., Elcombe C. R., Elliot, B. M., Ishmael, J., Odum, J., Tugwood, J. D., Kettle, S., and Purchase, I. F. H. (1994). Mechanistically based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. Exp. Toxicol. 13(suppl. 2), S1-117.
2. Atterwill, C. K., Jones, C., and Brown, C. G. (1992). Thyroid gland: II. Mechanisms of species-dependent thyroid toxicity, hyperplasia, and neoplasia induced by xenobiotics. In Endocrine Toxicology (C. K. Atterwill and J. D. Flack, Eds.), pp. 137-182. Cambridge University Press, Cambridge, U.K.
3. Barter, R. A., and Klaassen, C. D. (1992). UDP-glucuronosyltransferase inducers reduce thyroid hormone levels in rats by an extrathyroidal mechanism. Toxicol. Appl. Pharmacol. 113, 36-42.
4. Bentley, P., Calder, I., Elcombe, C., Grasso, P., Stringer, D., and Wiegand, H.-J. (1993). Hepatic peroxisome proliferation in rodents and its significance for humans. Food Chem. Toxicol. 31, 859-907.
5. Bullock, P., Pearce, R., Draper, A., Podval, J., Bracken, W., Veltman, J., Thomas, P., and Parkinson, A. (1995). Induction of liver microsomal cytochrome P450 in cynomolgus monkeys. Drug Metab. Dispos. 23, 736-748.
6. Burke, M. D., Thompson, S., Elcombe, C. R., Halpert, J., Haaparanta, T., and Mayer, R. T. (1985). Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: A series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol. 34, 3337-3345.
7. Curran, P. G, and DeGroot, L. J. (1991). The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr. Rev. 12, 135-150.
8. 125I-labelled thyroxine glucuronide by reversed-phase high-performance liquid chromatography using on-line radiochemical detection to determine UDP glucuronosyltransferase activity. J. Chromatogr. 566, 415-426.
9. Dunnett, C. W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1096-1121.
10. EPA (1998). Assessment of thyroid follicular cell tumors. Risk Assessment Forum. U.S. Environmental Protection Agency, Washington, DC.
11. Gibson, G. G. (1993). Peroxisome proliferators as cytochrome P450 inducers. In Peroxisomes. Biology and Importance in Toxicology and Medicine. (G. Gibson and B. Lake, Eds.), pp 119-136. Taylor & Francis, London.
12. Gopinath, C. (1991). Causes and interpretation of thyroid tumours in rodent bioassays. In Proceedings of Current Issues in Drug Development, pp 35-41. HRC Information Press, Eynsham, Oxford.
13. Grasso, P., Sharrat, M., and Cohen, A. J. (1991). Role of persistent non-genotoxic tissue damage in rodent cancer and relevance to humans. Annu. Rev. Pharmacol. Toxicol. 31, 253-287.
14. Habig, W. H., Pabst, M. J., and Jakoby, W. B. (1974). Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130-7139.
15. Hill, R. N., Erdreich, L. S., Paynter, O. E., Roberts, P. A., Rosenthal, S. L., and Wilkinson, C. F. (1989). Thyroid follicular cell carcinogenesis. Fundam. Appl. Toxicol. 12, 629-697.
16. Johnson, S., McKillop, D., Mille, J., and Smith, I. K. (1993). The effect on rat thyroid function of an hepatic microsomal enzyme inducer. Hum. Exp. Toxicol. 12, 153-158.
17. Kaiser, C. A., Goumaz, M. O., and Burger, A. G. (1986). In vivo inhibition of the 5′-deiodinase type II in brain cortex and pituitary by reverse triiodothyronine. Endocrinology 119, 762-770.
18. Lazarow, P. B. (1981). Assay of peroxisomal β-oxidation of fatty acids. Meth. Enzymol. 72, 315-319.
19. Liang, H., Morin, O., and Burger, A. G. (1993). Effect of the antioxidant TK 12627 (Irganox) on monodeiodination and on the levels of messenger ribonucleic acid of 5′-deiodinase type I and spot 14. Acta Endocrinol. (Copenh) 128, 451-458.
20. McClain, R. M. (1989). The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: Implications for thyroid gland neoplasia. Toxicol. Pathol. 17, 294-306.
21. McClain, R. M., Levin, A. A., Posch, R., and Downing, J. C. (1989). The effect of phenobarbital on the metabolism and excretion of thyroxine in rats. Toxicol. Appl. Pharmacol. 99, 216-228.
22. Molitor, E., Thomas, H., Weymann, J., and Waechter, F. (1994). The effect of phenobarbitone and β-naphthoflavone on selected biochemical liver parameters following subchronic administration to female beagle dogs. In Cytochrome P450, 8th International Conference. (M.C. Lechner, Ed.), pp 563-566. John Libbey Eurotext, Paris.
23. Muakkassah-Kelly, S. F., Krinke, A.-L., Malinowsky, W., Stäubli, W., Bentley, P., Waechter, F., Juge-Aubry, C., and Burger, A. G. (1991). The effect of short-term feeding of the antioxidant triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5-methyl)propionate on serum thyrotropin and thyroid hormones in the male rat. Toxicol. Appl. Pharmacol. 107, 129-140.
24. +-linked assay for microsomal uridine diphosphate glucuronosyltransferase of rat liver and some observations on substrate specificity of the enzyme. Biochem. J. 151, 131-140.
25. Omura, T., and Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239, 2370-2378.
26. Orton, T. C., and Parker, G. L. (1992). The effect of hypolipidemic agents on the hepatic microsomal drug-metabolizing enzyme system of the rat. Induction of cytochrome(s) P-450 with specificity toward terminal hydroxylation of lauric acid. Drug Metab. Dispos. 10, 110-115.
27. Paynter, O. E., Burin, G. J., Jeager, R. B., and Gregaria, C. A. (1988). Goitrogens and thyroid follicular cell neoplasia: Evidence for a threshold process. Regul. Toxicol. Pharmacol. 8, 102-119.
28. Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. (1985). Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76-85.
29. Thomas, G. A., and Williams, E. D. (1991). Evidence for and possible mechanism of non-genotoxic carcinogenesis in the rodent thyroid. Mutat. Res. 248, 357-370.
30. Thomas, H., Dollenmeier, P., Persohn, E., Weideli, H., and Waechter, F. (1995). Antioxidants and light stabilizers: Toxic effects of 3,5-di-alkyl-4-hydroxy-phenyl propionic acid derivatives in the rat and their relevance for human safety evaluation. In Toxicology of Industrial Compounds (H. Thomas, R. Hess, and F. Waechter, Eds.), pp 319-339. Taylor & Francis, London.
31. Thomas, H., Sagelsdorff, P., Molitor, E., Skripsky, T., and Waechter, F. (1994). Bromopropylate: Induction of hepatic cytochromes P450 and absence of covalent binding to DNA in mouse liver. Toxicol. Appl. Pharmacol. 129, 155-162.
32. Ullrich, V., and Weber, P. (1972). The O-dealkylation of 7-ethoxycoumarin by liver microsomes. Hoppe-Seyler's Z. Physiol. Chem. 353, 1171-1177.
33. Van der Hoeven, T. (1984). Assay of hepatic microsomal testosterone hydroxylases by high-performance liquid chromatography. Anal. Biochem. 138, 57-65.
34. Visser, T. J., Kaptein, E., Van Toor, H., Van Raaij, A. G. M., Van den Berg, K. J., Tjong-Tjin Joe, C., Van Engelen, J. G., and Brouwer, A. (1993). Glucuronidation of thyroid hormone in rat liver: Effects of in vivo treatment with microsomal enzyme inducers and in vitro assay conditions. Endocrinology 133, 2177-2186.
35. Waechter, F., Bentley, P., Bieri, F., Muakkassah-Kelly, S., Staeubli, W., and Villermain, M. (1988). Organ distribution of epoxide hydrolases in cytosolic and microsomal fractions of normal and nafenopin-treated male DBA/2 mice. Biochem. Pharmacol. 37, 3897-3903.
36. Weaver, R. J., Thompson, S., Smith, G., Dickins, M., Elcombe, C. R., Mayer, R. T., and Burke, M. D. (1994). A comparative study of constitutive and induced alkoxyresorufin O-dealkylation and individual cytochrome P450 forms in cynomolgus monkey (Macaca fascicularis), human, mouse, rat, and hamster liver microsomes. Biochem. Pharmacol. 47, 763-73.
37. Zbinden, G. (1987). Assessment of hyperplastic and neoplastic lesions of the thyroid gland. Trends Pharmacol. Sci. 8, 511-515.