Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in cynomolgus monkeys

Toxicological Sciences

Volumn 56, Issue 1, 2000, Pages 181-188

  Pugh Jr , George ^a   Isenberg, Jason S ^b   Kamendulis, Lisa M ^b   Ackley, David C ^b   Clare, Lisa J ^c   Brown, Ray ^d   Lington, Arthur W ^a   Smith, Jacqueline H ^a   Klaunig, James E ^b  

^a Exxon Biomedical Science Inc   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TPS Inc   (United States)

^d Research Pathology Services   (United States)

Author keywords

Gap junctions; Hepatocytes; Intercellular communication; Nongenotoxic carcinogens; Peroxisomes; Phthalate esters; Tumor promotion

Indexed keywords

CALCIUM; CELL DNA; CLOFIBRATE; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; PHTHALIC ACID DERIVATIVE; PHTHALIC ACID DIISONONYL ESTER; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CELL COMMUNICATION; CLINICAL CHEMISTRY; CONTROLLED STUDY; DNA SYNTHESIS; DOSE RESPONSE; FATTY ACID OXIDATION; HISTOPATHOLOGY; HYPERTRIGLYCERIDEMIA; HYPOCALCEMIA; LIVER CARCINOMA; LIVER TOXICITY; LIVER WEIGHT; MACACA; MALE; NONHUMAN; PEROXISOME; RODENT; SPECIES DIFFERENCE; TESTIS WEIGHT; THYROID WEIGHT; TISSUE SPECIFICITY; VOMITING;

ANIMALIA; EMESIS; MACACA; MACACA FASCICULARIS; PRIMATES; RODENTIA;

EID: 0342733424     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/56.1.181     Document Type: Article

References (51)

1. Ashby, J., Brady, A., Elcomhe, C. R., Elliot, B. M., Ishmael, J., Odum, J., Tugwood, J. D., Kettle, S., and Purchase, I. F. (1994). Mechanistically-bused human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. Exp. Toxicol. 13(Suppl. 2), S1-S117.
2. Astill, B. D. (1989). Metabolism of DEHP: Effects of prefeeding and dose variation, and comparative studies in rodents and the cynomolgus monkey (CMA studies). Drug Metab. Rev. 21, 35-53.
3. ATSDR (1993). Toxicological profile for di(2-ethylhexyl) phthalate. US Dept. Health & Human Services, TP-92/05, 147 pages.
4. Baker, T. K., Kalimi, G. H., Lington, A. W., Isenberg, J. S., Klaunig, J. E., and Nikiforov, A. I. (1996). Gap junctional intercellular communication (GJIC) studies on 5 phthalate monoesters in hepatocytes of four species: Implications for cancer risk assessment. Toxicologist 30, 208.
5. Benford, D. J., Patel, S., Reavy, H. J., Mitchell, A., and Sarginson, N. J. (1986). Species differences in the response of cultured hepatocytes to phthalate esters. Food Chem. Toxicol. 24, 799-800.
6. Bichet, N., Cahard, D., Fabre, G., Remandet, B., Gouy, D., and Cano, J.-P. (1990). Toxicological studies on a benzofuran derivative: III. Comparison of peroxisome proliferation in rat and human hepatocytes in primary culture. Toxicol. Appl. Pharmacol. 106, 509-517.
7. Blaauboer, B. J., van Hosteijn, C. W., Bleumink, R., Mennes, W. C., van Pelt, F. N., Yap, S. H., van Pelt, J. F., Van Iersel, A. A., Timmerman, A., and Schmid, B. P. (1990). The effect of beclobric acid and clofibric acid on peroxisomal oxidation and peroxisome proliferation in primary cultures of rat, monkey, and human hepatocytes. Biochem. Pharmacol. 40, 521-528.
8. Brown, M. S., and Goldstein, J. L. (1990). Drugs used in the treatment of hyperlipoproteinemias. In The Pharmacological Basis of Therapeutics, 8th Ed. (A. G. Gilman, T. W. Rall, A. S. Nies, and P. Taylor, Eds.), pp. 874-896. Pergamon Press, New York.
9. Butala, J. H., Moore, M. R., Cifone, M. A., Bankston, J. R., and Astill, B. (1996). Oncogenicity study of di (isononyl) phthalate in rats. Toxicologist 30, 202.
10. Butala, J. H., Moore, M. R., Cifone, M. A., Bankston, J. R., and Astill, B. (1997). Oncogenicity study of di (isononyl) phthalate in mice. Toxicologist 36, 173.
11. Cattley, R. C., DeLuca, J., Elcombe, C., Fenner-Crisp, P., Lake, B. G., Marsman, D. S., Pastoor, T. A., Popp, J. A., Robinson, D. E., Schwetz, B., Tugwood, J., and Wahli, W. (1998). Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans? Regul. Toxicol. Pharmacol. 27, 47-60.
12. Cattley, R. C., Marsman, G., and Popp, J. A. (1990). Cell proliferation and promotion in the hepatocarcinogenicity of peroxisome proliferating chemicals. In Mutation and the Environment, Part D (M. L. Mendelsohn, Ed.), pp. 1123-1132. Wiley-Liss, New York.
13. Chen, H., Huang, C., Wilson, M. W., Lay, L. T., Robertson, L. W., Chow, C. K., and Glauert, H. P. (1994). Effect of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on hepatic cell proliferation and toxicity in Sprague-Dawley rats. Carcinogenesis 15, 2847-2850.
14. Cohen, A. J., and Grasso, P. (1981). Review of the hepatic response to hypolipidaemic drugs in rodents and assessment of its toxicological significance to man. Food Cosmet. Toxicol. 19, 585-605.
15. David, R. M., Moore, M. R., Cifone, M. A., Finney, D. C., and Guest, D. (1999). Chronic peroxisome proliferation and hepatomegaly associated with the hepatocellular tumorigenesis of di(2-ethylhexyl)phthalate and the effects of recovery. Toxicol. Sci. 50, 195-205.
16. De La Iglesia, F. A., Lewis, J. E., Buchanan, R. A., Marcus, E. L., and McMahon, G. (1982). Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment. Atherosclerosis 43, 19-37.
17. Dirven, H. A., van den Broek, P. H., Peeters, M. C., Peters, J. G., Mennes, W. C., Blaauboer, B. J., Noordhoek, J., and Jongeneelen, F. J. (1993). Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies. Biochem. Pharmacol. 45, 2425-2434.
18. Doull, J., Cattley, R., Elcombe, C., Lake, B. G., Swenberg, J., Wilkinson, C., Williams, G., and van Gemert, M. (1999). A cancer risk assessment of di(2-ethylhexyl)phthalate: application of the new U.S. EPA risk assessment guidelines. Regul. Toxicol. Pharmacol. 29, 327-357.
19. Durnford, J. M., Brodey, R. S., Hejtmancik, M. R., Kurtz, P. J., Renne, R. A., Gideon, K. M., and Marsman, D. S. (1995). Differential enzyme-inducing activity of peroxisome proliferators in the male Syrian hamster. Int. Toxicol. VII 47, 4.
20. Elcombe, C. R., Bell, D. R., Elias, E., Hasmall, S. C., and Plant, N. J. (1996). Peroxisome proliferators: species differences in response of primary hepatocyte cultures. Ann. N Y Acad. Sci. 804, 628-635.
21. Elcombe, C. R., and Mitchell, A. M. (1986). Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms. Environ. Health Perspect. 70, 211-219.
22. Foley, J., Ton, T., Maronpot, R., Butterworth, B., and Goldsworthy, T. L. (1993). Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats. Environ. Health Perspect. 101(Suppl. 5), 199-205.
23. Foxworthy, P. S., White, S. L., Hoover, D. M., and Eacho, P. I. (1990). Effect of ciprofibrate, bezafibrate and LY171883 on peroxisomal beta-oxidation in cultured rat, dog, and rhesus monkey hepatocytes. Toxicol. Appl. Pharmacol. 104, 386-394.
24. Gad, S., and Weil, C. S. (1988). Statistics and Experimental Design for Toxicologists. Telford Press, New Jersey.
25. Gray, R. H., and de la Iglesia, F. A. (1984). Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species. Hepatology 4, 520-530.
26. Hall, M., Matthews, A., Webley, L., and Harling, R. (1999). Effects of di-isononyl phthalate (DINP) on peroxisomal markers in the marmoset-DINP is not a peroxisome proliferator. Toxicol. Sci. 24, 237-244.
27. Hanefeld, M., Kemmer, C., Leonhardt, W., Kunze, K. D., Jaross, W., and Haller, H. (1980). Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. Atherosclerosis 36, 159-172.
28. Hartig, F. Stegmeir, K., and Hebold, G. (1982). Study of liver enzymes: Peroxisome proliferation and tumour rates in rats at the end of carcinogenicity studies with bezafibrate and clofibrate. Ann. N. Y. Acad. Sci. 386, 464-467.
29. Holloway, B. R., Thorp, J. M., Smith, G. D., and Peters, T. J. (1982). Analytical subcellular fractionation and enzymic analysis of liver homogenates from control and clofibrate-treated rats, mice, and monkeys with reference to the fatty acid-oxidizing enzymes. Ann. N.Y. Acad. Sci. 386, 453-454.
30. Huber, W. W., Grasl-Kraupp, B., Schulte-Hermann, R. (1996). Hepatocarcinogenic potential of di(2-ethylhexyl)phthalate in rodents and its implications on human risk. Crit. Rev. Toxicol. 26, 365-481.
31. International Agency for Research on Cancer (IARC) (1995). Peroxisome proliferation and its role in carcinogenesis. IARC Technical Report No. 24. IARC, Lyon, France.
32. International Agency for Research on Cancer (IARC) (1996). Clofibrate, In IARC Monographs, Some Pharmaceutical Drugs, Vol. 66, pp. 391-426, IARC, Lyon, France.
33. Isenberg, J. S., Kamendulis, L. M., Smith, J. H. Ackley, D. C., Pugh, G., Jr., Lington, A. W., and Klaunig, J. E. (2000). Effects of di-2-ethylhexyl phthalate (DEHP) on gap junction intercellular communication (GJIC), DNA synthesis and peroxisomal beta-oxidation in rat, mouse, and hamster liver. Toxicol. Sci. (in press).
34. Kluwe, W. M., Haseman, J. K., Douglas, J. F., and Huff, J. E. (1982). The carcinogenicity of dietary di(ethylhexyl)phthalate (DEHP) in Fischer 344 rats and B6C3F1 mice. J. Toxicol. Environ. Health 10, 797-815.
35. Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M., and Katoh, M. (1998). Subchronic toxicity of di(2-ethylhexyl)phthalate (DEHP) in common marmosets: lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci. 42, 49-56.
36. Lake, B. G., Evans, J. G., Cunninghame, M. E., and Price, R. J. (1993). Comparison of the hepatic effects of nafenopin and WY-14,643 on peroxisome proliferation and cell replication in the rat and Syrian hamster. Environ. Health Perspect. 101(Suppl. 5), 241-247.
37. Lake, B. G., Rijcken, W. R., Gray, T. J., Foster, J. R., and Gangolli, S. D. (1984). Comparative studies of the hepatic effects of di- and mono-n-octyl phthalates, di-(2-ethylhexyl) phthalate and clofibrate in the rat. Acta. Pharmacol. Toxicol. 54, 167-176.
38. Lazarow, P. B., and De Duve, C. (1976). A fatty acyl-CoA oxidizing system in rat liver peroxisomes: enhancement by clofibrate, a hypolipidemic drug. Proc. Natl. Acad. Sci. U S A 73, 2043-2046.
39. Lington, A. W., Bird, M. G., Plutnick, R. T., Stubblefield, W. A., and Scala, R. A. (1997). Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats. Fundam. Appl. Toxicol. 36, 79-89.
40. Peijnenburg, W. J. G. M., Ewijk, M, de Hann, M. W. A., Janus, J. A., Ros, J. P. M., Slooff, W., and Velde, E. G. (1991). Update of the exploratory report: Phthalates. Report no. 710401008. National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
41. Perrone, C. E., Shao, L., and Williams, G. M. (1998). Effect of rodent hepatocarcinogenic peroxisome proliferators on fatty acyl-CoA oxidase, DNA synthesis, and apoptosis in cultured human and rat hepatocytes. Toxicol. Appl. Pharmacol. 150, 277-286.
42. Rao, M. S., and Reddy, J. K. (1991). An overview of peroxisome proliferator-induced hepatocarcinogenesis. Environ. Health Perspect. 93, 205-209.
43. Reddy, J. K., and Qureshi, S. A. (1979). Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-a-p-chlorophenoxyisobutyrate (clofibrate) in rats. Br. J. Cancer 40, 476-482.
44. Reddy, J. K., and Rao, M.S. (1986). Peroxisome proliferators and cancer: mechanisms and implications. Trends Pharmacol. Sci. 7, 438-443.
45. Rhodes, C., Orton, T. C., Pratt, I. S., Batten, P. L., Bratt, H., Jackson, S. J., and Elcombe, C. R. (1986). Comparative pharmacokinetics and subacute toxicity of di-(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: Extrapolation of effects in rodents to man. Environ. Health Perspect. 65, 299-307.
46. Roberts, R. A., Soames, A. R., Gill, J. H., James, N. H., and Wheeldon, E. B. (1995). Non-genotoxic hepatocarcinogens stimulate DNA synthesis and their withdrawal induces apoptosis, but in different hepatocyte populations. Carcinogenesis 16, 1693-1698.
47. Short, R. D., Robinson, E. C., Lington, A. W., and Chin, A. E. (1987). Metabolic and peroxisome proliferation studies with di(2-ethylhexyl)phthalate in rats and monkeys. Toxicol. Ind. Health 3, 185-195.
48. 11 dialkyl phthalates on gap junctional intercellular communication (GJIC), peroxisomal beta-oxidation (PBOX), and DNA synthesis in rat and mouse liver. Toxicol. Sci. 54, 312-321.
49. Svoboda, D. J., and Azamoff, D. L. (1979). Tumors in male rats fed ethyl chlorophenoxyisobutyrate, a hypolipidemic drug. Cancer Res. 39, 3419-3428.
50. Tucker, M. J., and Orton, T. C. (1993). Toxicological studies in primates with three fibrates. In Peroxisomes: Biology and Importance in Toxicology and Medicine (G. Gibson and B. Lake, Eds.), pp. 425-447. Taylor and Francis, Washington, DC.
51. Wada, N., Marsman, D. S., and Popp, J. A. (1992). Dose-related effects of the hepatocarcinogen. WY-14,643, on peroxisomes and cell proliferation. Fundam. Appl. Toxicol. 18, 149-154.