Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate

Mutation Research - Reviews in Mutation Research

Volumn 750, Issue 2, 2012, Pages 141-158

  Rusyn, Ivan ^a   Corton, J Christopher ^b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Cancer; DEHP; Liver

Indexed keywords

CARCINOGEN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; PLASTICIZER; POLYMER; POLYVINYLCHLORIDE; TRANSCRIPTION FACTOR;

APOPTOSIS; CARCINOGENICITY; CELL TYPE; ENZYME INDUCTION; GAP JUNCTION; GENETIC POLYMORPHISM; GENITAL SYSTEM; HEPATOBLASTOMA; HUMAN; IMMUNE SYSTEM; KIDNEY; LIVER; LIVER CELL; LIVER PARENCHYMA; LIVER TOXICITY; LUNG TOXICITY; NEWBORN PERIOD; NONHUMAN; OCCUPATION; OXIDATIVE STRESS; PRIMATE; PRIORITY JOURNAL; REVIEW; RODENT; TESTIS;

ANIMALS; CARCINOGENS; DIETHYLHEXYL PHTHALATE; HUMANS; IMMUNE SYSTEM; KIDNEY; LIVER; LIVER NEOPLASMS; LUNG; MALE; MICE; PEROXISOME PROLIFERATORS; PLASTICIZERS; RATS; TESTICULAR NEOPLASMS; TESTIS;

ANIMALIA; MUS; MUS MUSCULUS; RATTUS; RODENTIA;

EID: 84859105906     PISSN: 13835742     EISSN: 13882139     Source Type: Journal    
DOI: 10.1016/j.mrrev.2011.12.004     Document Type: Review

References (214)

1. Wittassek M., Wiesmuller G.A., Koch H.M., Eckard R., Dobler L., Muller J., Angerer J., Schluter C. Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study. Int. J. Hyg. Environ. Health 2007, 210:319-333.
2. Colacino J.A., Harris T.R., Schecter A. Dietary intake is associated with phthalate body burden in a nationally representative sample. Environ. Health Perspect. 2010, 118:998-1003.
3. Selenskas S., Teta M.J., Vitale J.N. Pancreatic cancer among workers processing synthetic resins. Am. J. Ind. Med. 1995, 28:385-398.
4. Dell L., Teta M.J. Mortality among workers at a plastics manufacturing and research and development facility: 1946-1988. Am. J. Ind. Med. 1995, 28:373-384.
5. Hardell L., Ohlson C.G., Fredrikson M. Occupational exposure to polyvinyl chloride as a risk factor for testicular cancer evaluated in a case-control study. Int. J. Cancer 1997, 73:828-830.
6. Hagmar L., Akesson B., Nielsen J., Andersson C., Linden K., Attewell R., Moller T. Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. Am. J. Ind. Med. 1990, 17:553-565.
7. Riboli E., Bai E., Berrino F., Merisi A. Mortality from lung cancer in an acetylene and phthalic anhydride plant. A case-referent study. Scand. J. Work Environ. Health 1983, 9:455-462.
8. Heineman E.F., Olsen J.H., Pottern L.M., Gomez M., Raffn E., Blair A. Occupational risk factors for multiple myeloma among Danish men. Cancer Causes Control 1992, 3:555-568.
9. Lopez-Carrillo L., Hernandez-Ramirez R.U., Calafat A.M., Torres-Sanchez L., Galvan-Portillo M., Needham L.L., Ruiz-Ramos R., Cebrian M.E. Exposure to phthalates and breast cancer risk in northern Mexico. Environ. Health Perspect. 2010, 118:539-544.
10. Reynolds P., Urayama K.Y., Von Behren J., Feusner J. Birth characteristics and hepatoblastoma risk in young children. Cancer 2004, 100:1070-1076.
11. Maruyama K., Ikeda H., Koizumi T., Tsuchida Y. Prenatal and postnatal histories of very low birthweight infants who developed hepatoblastoma. Pediatr. Int. 1999, 41:82-89.
12. Oue T., Kubota A., Okuyama H., Kawahara H., Nara K., Kawa K., Kitajima H. Hepatoblastoma in children of extremely low birth weight: a report from a single perinatal center. J. Pediatr. Surg. 2003, 38:134-137.
13. Melnick R.L., Morrissey R.E., Tomaszewski K.E. Studies by the National Toxicology Program on di(2-ethylhexyl)phthalate. Toxicol. Ind. Health 1987, 3:99-118.
14. David R.M., Moore M.R., Finney D.C., Guest D. Chronic toxicity of di(2-ethylhexyl)phthalate in mice. Toxicol. Sci. 2000, 58:377-385.
15. David R.M., Moore M.R., Finney D.C., Guest D. Chronic toxicity of di(2-ethylhexyl)phthalate in rats. Toxicol. Sci. 2000, 55:433-443.
16. Voss C., Zerban H., Bannasch P., Berger M.R. Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats. Toxicology 2005, 206:359-371.
17. Wilson V.S., Blystone C.R., Hotchkiss A.K., Rider C.V., Gray L.E. Diverse mechanisms of anti-androgen action: impact on male rat reproductive tract development. Int. J. Androl. 2008, 31:178-187.
18. Karle V.A., Short B.L., Martin G.R., Bulas D.I., Getson P.R., Luban N.L., O'Brien A.M., Rubin R.J. Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate. Crit. Care Med. 1997, 25:696-703.
19. von Rettberg H., Hannman T., Subotic U., Brade J., Schaible T., Waag K.L., Loff S. Use of di(2-ethylhexyl)phthalate-containing infusion systems increases the risk for cholestasis. Pediatrics 2009, 124:710-716.
20. Backes J.M., Gibson C.A., Ruisinger J.F., Moriarty P.M. Fibrates: what have we learned in the past 40 years?. Pharmacotherapy 2007, 27:412-424.
21. Huttunen J.K., Heinonen O.P., Manninen V., Koskinen P., Hakulinen T., Teppo L., Manttari M., Frick M.H. The Helsinki Heart Study: an 8.5-year safety and mortality follow-up. J. Intern. Med. 1994, 235:31-39.
22. Frick M.H., Elo O., Haapa K., Heinonen O.P., Heinsalmi P., Helo P., Huttunen J.K., Kaitaniemi P., Koskinen P., Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N. Engl. J. Med. 1987, 317:1237-1245.
23. Anonymous WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Report of the Committee of Principal Investigators. Lancet 1984, 2:600-604.
24. Anonymous A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. Br. Heart J. 1978, 40:1069-1118.
25. Anonymous W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Report of the Committee of Principal Investigators. Lancet 1980, 2:379-385.
26. Lash L.H., Fisher J.W., Lipscomb J.C., Parker J.C. Metabolism of trichloroethylene. Environ. Health Perspect. 2000, 108(Suppl. (2)):177-200.
27. Lash L.H., Qian W., Putt D.A., Hueni S.E., Elfarra A.A., Krause R.J., Parker J.C. Renal and hepatic toxicity of trichloroethylene and its glutathione-derived metabolites in rats and mice: sex-, species-, and tissue-dependent differences. J. Pharmacol. Exp. Ther. 2001, 297:155-164.
28. Ramdhan D.H., Komijima M., Wang D., Ito Y., Naito H., Yanagiba Y., Hayashi Y., Tanaka N., Aoyama T., Gonzalez F.J., Nakajima T. Differential response to trichloroethylene-induced hepatosteatosis in wild-type and PPARa-humanized mice. Environ. Health Perspect. 2010, 118:1557-1563.
29. National Toxicology Program Carcinogenesis studies of trichloroethylene (without epichlorohydrin) (CAS No. 79-01-6) in F344/N rats and B6C3F1 mice (gavage studies). Natl. Toxicol. Program. Tech. Rep. Ser. 1990, 243:1-174.
30. National Research Council Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues 2006, The National Academies Press, Washington, DC.
31. Scott C.S., Jinot J. Trichloroethylene and cancer: systematic and quantitative review of epidemiologic evidence for identifying hazards. Int. J. Environ. Res. Public Health 2011, 8:4238-4271.
32. Jacobson M.S., Kevy S.V., Grand R.J. Effects of a plasticizer leached from polyvinyl chloride on the subhuman primate: a consequence of chronic transfusion therapy. J. Lab. Clin. Med. 1977, 89:1066-1079.
33. Kevy S.V., Jacobson M.S. Hepatic effects of a phthalate ester plasticizer leached from poly(vinyl chloride) blood bags following transfusion. Environ. Health Perspect. 1982, 45:57-64.
34. Pugh G., Isenberg J.S., Kamendulis L.M., Ackley D.C., Clare L.J., Brown R., Lington A.W., Smith J.H., Klaunig J.E. Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in cynomolgus monkeys. Toxicol. Sci. 2000, 56:181-188.
35. Miura Y., Katayama H., Goto M. Studies on the metabolism of rat ascites hepatoma, with special reference of the metabolic difference between nitrogen mustard sensitive and insensitive strains. Acta Unio. Int Contra. Cancrum. 1959, 15(Suppl. (1)):199-202.
36. Ward J.M., Peters J.M., Perella C.M., Gonzalez F.J. Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha-null mice. Toxicol. Pathol. 1998, 26:240-246.
37. Nair K.G., Deepadevi K.V., Arun P., Kumar V.M., Santhosh A., Lekshmi L.R., Kurup P.A. Toxic effect of systemic administration of low doses of the plasticizer di-(2-ethyl hexyl) phthalate [DEHP] in rats. Indian J. Exp. Biol. 1998, 36:264-272.
38. Ito Y., Yamanoshita O., Asaeda N., Tagawa Y., Lee C.H., Aoyama T., Ichihara G., Furuhashi K., Kamijima M., Gonzalez F.J., Nakajima T. Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway. J. Occup. Health 2007, 49:172-182.
39. Hays T., Rusyn I., Burns A.M., Kennett M.J., Ward J.M., Gonzalez F.J., Peters J.M. Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis. Carcinogenesis 2005, 26:219-227.
40. National Toxicology Program Carcinogenesis bioassay of di(2-ethylhexyl)phthalate (CAS No. 117-81-7) in F344 rats and B6C3F1 mice (feed studies). Natl. Toxicol. Program. Tech. Rep. Ser. 1982, 217:1-127.
41. David R.M., Moore M.R., Cifone M.A., Finney D.C., Guest D. Chronic peroxisome proliferation and hepatomegaly associated with the hepatocellular tumorigenesis of di(2-ethylhexyl)phthalate and the effects of recovery. Toxicol. Sci. 1999, 50:195-205.
42. Klaunig J.E., Babich M.A., Baetcke K.P., Cook J.C., Corton J.C., David R.M., Deluca J.G., Lai D.Y., McKee R.H., Peters J.M., Roberts R.A., Fenner-Crisp.P.A. PPARalpha agonist-induced rodent tumors: modes of action and human relevance. Crit. Rev. Toxicol. 2003, 33:655-780.
43. Roberts R.A. Peroxisome proliferators: mechanisms of adverse effects in rodents and molecular basis for species differences. Arch. Toxicol. 1999, 73:413-418.
44. Peters J.M. Mechanistic evaluation of PPARa-mediated hepatocarcinogenesis: are we there yet?. Toxicol. Sci. 2008, 101:1-3.
45. Guyton K.Z., Chiu W.A., Bateson T.F., Jinot J., Scott C.S., Brown R.C., Caldwell J.C. A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants. Environ. Health Perspect. 2009, 117:1664-1672.
46. Issemann I., Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990, 347:645-650.
47. Dreyer C., Krey G., Keller H., Givel F., Helftenbein G., Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992, 68:879-887.
48. Sher T., Yi H.F., McBride O.W., Gonzalez F.J. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993, 32:5598-5604.
49. Lapinskas P.J., Brown S., Leesnitzer L.M., Blanchard S., Swanson C., Cattley R.C., Corton J.C. Role of PPARalpha in mediating the effects of phthalates and metabolites in the liver. Toxicology 2005, 207:149-163.
50. Maloney E.K., Waxman D.J. Trans-activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicol. Appl. Pharmacol. 1999, 161:209-218.
51. Hurst C.H., Waxman D.J. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol. Sci. 2003, 74:297-308.
52. Lampen A., Zimnik S., Nau H. Teratogenic phthalate esters and metabolites activate the nuclear receptors PPARs and induce differentiation of F9 cells. Toxicol. Appl. Pharmacol. 2003, 188:14-23.
53. Bility M.T., Thompson J.T., McKee R.H., David R.M., Butala J.H., Vanden Heuvel J.P., Peters J.M. Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters. Toxicol. Sci. 2004, 82:170-182.
54. Feige J.N., Gelman L., Rossi D., Zoete V., Metivier R., Tudor C., Anghel S.I., Grosdidier A., Lathion C., Engelborghs Y., Michielin O., Wahli W., Desvergne B. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J. Biol. Chem. 2007, 282:19152-19166.
55. Rotroff D.M., Beam A.L., Dix D.J., Farmer A., Freeman K.M., Houck K.A., Judson R.S., LeCluyse E.L., Martin M.T., Reif D.M., Ferguson S.S. Xenobiotic-metabolizing enzyme and transporter gene expression in primary cultures of human hepatocytes modulated by ToxCast chemicals. J. Toxicol. Environ. Health B Crit. Rev. 2010, 13:329-346.
56. Martin M.T., Dix D.J., Judson R.S., Kavlock R.J., Reif D.M., Richard A.M., Rotroff D.M., Romanov S., Medvedev A., Poltoratskaya N., Gambarian M., Moeser M., Makarov S.S., Houck K.A. Impact of environmental chemicals on key transcription regulators and correlation to toxicity end points within EPA's ToxCast program. Chem. Res. Toxicol. 2010, 23:578-590.
57. Ito Y., Yamanoshita O., Kurata Y., Kamijima M., Aoyama T., Nakajima T. Induction of peroxisome proliferator-activated receptor alpha (PPARalpha)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets. Arch. Toxicol. 2007, 81:219-226.
58. Palmer C.N., Hsu M.H., Griffin K.J., Raucy J.L., Johnson E.F. Peroxisome proliferator activated receptor-alpha expression in human liver. Mol. Pharmacol. 1998, 53:14-22.
59. Walgren J.E., Kurtz D.T., McMillan.J.M. Expression of PPAR(alpha) in human hepatocytes and activation by trichloroacetate and dichloroacetate. Res. Commun. Mol. Pathol. Pharmacol. 2000, 108:116-132.
60. Choudhury A.I., Sims H.M., Horley N.J., Roberts R.A., Tomlinson S.R., Salter A.M., Bruce M., Shaw P.N., Kendall D., Barrett D.A., Bell D.R. Molecular analysis of peroxisome proliferation in the hamster. Toxicol. Appl. Pharmacol. 2004, 197:9-18.
61. Mukherjee R., Jow L., Noonan D., McDonnell.D.P. Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. J. Steroid Biochem. Mol. Biol. 1994, 51:157-166.
62. Tugwood J.D., Aldridge T.C., Lambe K.G., Macdonald N., Woodyatt N.J. Peroxisome proliferator-activated receptors: structures and function. Ann. N. Y. Acad. Sci. 1996, 804:252-265.
63. Gervois P., Torra I.P., Chinetti G., Grotzinger T., Dubois G., Fruchart J.C., Fruchart-Najib J., Leitersdorf E., Staels B. A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity. Mol. Endocrinol. 1999, 13:1535-1549.
64. Hanselman J.C., Vartanian M.A., Koester B.P., Gray S.A., Essenburg A.D., Rea T.J., Bisgaier C.L., Pape M.E. Expression of the mRNA encoding truncated PPAR alpha does not correlate with hepatic insensitivity to peroxisome proliferators. Mol. Cell. Biochem. 2001, 217:91-97.
65. Rosen M.B., Abbott B.D., Wolf D.C., Corton J.C., Wood C.R., Schmid J.E., Das K.P., Zehr R.D., Blair E.T., Lau C. Gene profiling in the livers of wild-type and PPARalpha-null mice exposed to perfluorooctanoic acid. Toxicol. Pathol. 2008, 36:592-607.
66. Ganning A.E., Brunk U., Dallner G. Phthalate esters and their effect on the liver. Hepatology 1984, 4:541-547.
67. Ganning A.E., Brunk U., Edlund C., Elhammer A., Dallner G. Effects of prolonged administration of phthalate ester on the liver. Environ. Health Perspect. 1987, 73:251-258.
68. Huber W.W., Grasl-Kraupp B., Schulte-Hermann.R. Hepatocarcinogenic potential of di(2-ethylhexyl)phthalate in rodents and its implications on human risk. Crit. Rev. Toxicol. 1996, 26:365-481.
69. Tomonari Y., Kurata Y., David R.M., Gans G., Kawasuso T., Katoh M. Effect of di(2-ethylhexyl) phthalate (DEHP) on genital organs from juvenile common marmosets: I. Morphological and biochemical investigation in 65-week toxicity study. J. Toxicol. Environ. Health A 2006, 69:1651-1672.
70. Lake B.G., Gangolli S.D., Grasso P., Lloyd A.G. Studies on the hepatic effects of orally administered di-(2-ethylhexyl) phthalate in the rat. Toxicol. Appl. Pharmacol. 1975, 32:355-367.
71. Reddy J.K., Moody D.E., Azarnoff D.L., Rao M.S. Di-(2-ethylhexyl)phthalate: an industrial plasticizer induces hypolipidemia and enhances hepatic catalase and carnitine acetyltransferase activities in rat and mice. Life Sci. 1976, 18:941-945.
72. Reddy J.K., Goel S.K., Nemali M.R., Carrino J.J., Laffler T.G., Reddy M.K., Sperbeck S.J., Osumi T., Hashimoto T., Lalwani N.D. Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc. Natl. Acad. Sci. U.S.A. 1986, 83:1747-1751.
73. Yamazaki T., Hirose A., Sakamoto T., Okazaki M., Mitsumoto A., Kudo N., Kawashima Y. Peroxisome proliferators attenuate free arachidonic acid pool in the kidney through inducing lysophospholipid acyltransferases. J. Pharmacol. Sci. 2009, 111:201-210.
74. Wong J.S., Gill S.S. Gene expression changes induced in mouse liver by di(2-ethylhexyl) phthalate. Toxicol. Appl. Pharmacol. 2002, 185:180-196.
75. Currie R.A., Bombail V., Oliver J.D., Moore D.J., Lim F.L., Gwilliam V., Kimber I., Chipman K., Moggs J.G., Orphanides G. Gene ontology mapping as an unbiased method for identifying molecular pathways and processes affected by toxicant exposure: application to acute effects caused by the rodent non-genotoxic carcinogen diethylhexylphthalate. Toxicol. Sci. 2005, 86:453-469.
76. Dostal L.A., Jenkins W.L., Schwetz B.A. Hepatic peroxisome proliferation and hypolipidemic effects of di(2-ethylhexyl)phthalate in neonatal and adult rats. Toxicol. Appl. Pharmacol. 1987, 87:81-90.
77. Dostal L.A., Weaver R.P., Schwetz B.A. Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland. Toxicol. Appl. Pharmacol. 1987, 91:315-325.
78. Cimini A.M., Sulli A., Stefanini S., Serafini B., Moreno S., Rossi L., Giorgi M., Ceru M.P. Effects of di-(2-ethylhexyl)phthalate on peroxisomes of liver, kidney and brain of lactating rats and their pups. Cell. Mol. Biol. (Noisy. -le-grand) 1994, 40:1063-1076.
79. Kurata Y., Kidachi F., Yokoyama M., Toyota N., Tsuchitani M., Katoh M. Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets: lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci. 1998, 42:49-56.
80. Gray T.J., Beamand J.A., Lake B.G., Foster J.R., Gangolli S.D. Peroxisome proliferation in cultured rat hepatocytes produced by clofibrate and phthalate ester metabolites. Toxicol. Lett. 1982, 10:273-279.
81. Gray T.J., Lake B.G., Beamand J.A., Foster J.R., Gangolli S.D. Peroxisome proliferation in primary cultures of rat hepatocytes. Toxicol. Appl. Pharmacol. 1983, 67:15-25.
82. Grolier P., Elcombe C.R. In vitro inhibition of carnitine acyltransferase activity in mitochondria from rat and mouse liver by a diethylhexylphthalate metabolite. Biochem. Pharmacol. 1993, 45:827-832.
83. Osumi T., Hashimoto T. Enhancement of fatty acyl-CoA oxidizing activity in rat liver peroxisomes by di-(i-ethylhexyl)phthalate. J. Biochem. 1978, 83:1361-1365.
84. Hasmall S.C., James N.H., Macdonald N., Soames A.R., Roberts R.A. Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression. Arch. Toxicol. 2000, 74:85-91.
85. Lake B.G., Gray T.J., Foster J.R., Stubberfield C.R., Gangolli S.D. Comparative studies on di-(2-ethylhexyl) phthalate-induced hepatic peroxisome proliferation in the rat and hamster. Toxicol. Appl. Pharmacol. 1984, 72:46-60.
86. Rhodes C., Orton T.C., Pratt I.S., Batten P.L., Bratt H., Jackson S.J., Elcombe C.R. 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. 1986, 65:299-307.
87. Short R.D., Robinson E.C., Lington A.W., Chin A.E. Metabolic and peroxisome proliferation studies with di(2-ethylhexyl)phthalate in rats and monkeys. Toxicol. Ind. Health 1987, 3:185-195.
88. Mitchell F.E., Price S.C., Hinton R.H., Grasso P., Bridges J.W. Time and dose-response study of the effects on rats of the plasticizer di(2-ethylhexyl) phthalate. Toxicol. Appl. Pharmacol. 1985, 81:371-392.
89. Lake B.G., Gray T.J., Gangolli S.D. Hepatic effects of phthalate esters and related compounds - in vivo and in vitro correlations. Environ. Health Perspect. 1986, 67:283-290.
90. Dirven H.A., van den Broek P.H., Peeters M.C., Peters J.G., Mennes W.C., Blaauboer B.J., Noordhoek J., Jongeneelen F.J. Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit, and monkey. Biochem. Pharmacol. 1993, 45:2425-2434.
91. Cornu M.C., Lhuguenot J.C., Brady A.M., Moore R., Elcombe C.R. Identification of the proximate peroxisome proliferator(s) derived from di(2-ethylhexyl)adipate and species differences in response. Biochem. Pharmacol. 1992, 43:2129-2134.
92. Goll V., Alexandre E., Viollon-Abadie C., Nicod L., Jaeck D., Richert L. Comparison of the effects of various peroxisome proliferators on peroxisomal enzyme activities, DNA synthesis, and apoptosis in rat and human hepatocyte cultures. Toxicol. Appl. Pharmacol. 1999, 160:21-32.
93. Zacharewski T.R., Meek M.D., Clemons J.H., Wu Z.F., Fielden M.R., Matthews J.B. Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters. Toxicol. Sci. 1998, 46:282-293.
94. Ghisari M., Bonefeld-Jorgensen.E.C. Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions. Toxicol. Lett. 2009, 189:67-77.
95. Takeuchi S., Iida M., Kobayashi S., Jin K., Matsuda T., Kojima H. Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology 2005, 210:223-233.
96. Kang S.C., Lee B.M. DNA methylation of estrogen receptor alpha gene by phthalates. J. Toxicol. Environ. Health A 2005, 68:1995-2003.
97. Parks L.G., Ostby J.S., Lambright C.R., Abbott B.D., Klinefelter G.R., Barlow N.J., Gray L.E. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci. 2000, 58:339-349.
98. Kruger T., Long M., Bonefeld-Jorgensen.E.C. Plastic components affect the activation of the aryl hydrocarbon and the androgen receptor. Toxicology 2008, 246:112-123.
99. Takeshita A., Koibuchi N., Oka J., Taguchi M., Shishiba Y., Ozawa Bisphenol-A.Y. an environmental estrogen, activates the human orphan nuclear receptor, steroid and xenobiotic receptor-mediated transcription. Eur. J. Endocrinol. 2001, 145:513-517.
100. Takeshita A., Inagaki K., Igarashi-Migitaka J., Ozawa Y., Koibuchi N. The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells. J. Endocrinol. 2006, 190:897-902.
101. Cooper B.W., Cho T.M., Thompson P.M., Wallace A.D. Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression. Toxicol. Sci. 2008, 103:268-277.
102. Mnif W., Pascussi J.M., Pillon A., Escande A., Bartegi A., Nicolas J.C., Cavailles V., Duchesne M.J., Balaguer P. Estrogens and antiestrogens activate hPXR. Toxicol. Lett. 2007, 170:19-29.
103. Auerbach S.S., Dekeyser J.G., Stoner M.A., Omiecinski C.J. CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics. Drug Metab. Dispos. 2007, 35:428-439.
104. Dekeyser J.G., Stagliano M.C., Auerbach S.S., Prabhu K.S., Jones A.D., Omiecinski C.J. Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant CAR2. Mol. Pharmacol. 2009, 75:1005-1013.
105. Eveillard A., Mselli-Lakhal L., Mogha A., Lasserre F., Polizzi A., Pascussi J.M., Guillou H., Martin P.G., Pineau T. Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): a novel signalling pathway sensitive to phthalates. Biochem. Pharmacol. 2009, 77:1735-1746.
106. Dekeyser J.G., Laurenzana E.M., Peterson E.C., Chen T., Omiecinski C.J. Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor. Toxicol. Sci. 2011, 120:381-391.
107. Seree E., Villard P.H., Pascussi J.M., Pineau T., Maurel P., Nguyen Q.B., Fallone F., Martin P.M., Champion S., Lacarelle B., Savouret J.F., Barra Y. Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites. Gastroenterology 2004, 127:1436-1445.
108. Voskoboinik I., Ooi S.G., Drew R., Ahokas J.T. Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes. Toxicology 1997, 122:81-91.
109. Shaban Z., El Shazly S., Ishizuka M., Kimura K., Kazusaka A., Fujita S. PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats. Arch. Toxicol. 2004, 78:496-507.
110. Eagon P.K., Chandar N., Epley M.J., Elm M.S., Brady E.P., Rao K.N. Di(2-ethylhexyl)phthalate-induced changes in liver estrogen metabolism and hyperplasia. Int. J. Cancer 1994, 58:736-743.
111. Yang Q., Ito S., Gonzalez F.J. Hepatocyte-restricted constitutive activation of PPAR alpha induces hepatoproliferation but not hepatocarcinogenesis. Carcinogenesis 2007, 28:1171-1177.
112. Weglarz T.C., Sandgren E.P. Cell cross-talk mediates PPARalpha null hepatocyte proliferation after peroxisome proliferator exposure. Carcinogenesis 2004, 25:107-112.
113. Cheung C., Akiyama T.E., Ward J.M., Nicol C.J., Feigenbaum L., Vinson C., Gonzalez F.J. Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res. 2004, 64:3849-3854.
114. Morimura K., Cheung C., Ward J.M., Reddy J.K., Gonzalez F.J. Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor {alpha} to Wy-14,643-induced liver tumorigenesis. Carcinogenesis 2006, 27:1074-1080.
115. Fan L.Q., You L., Brown-Borg H., Brown S., Edwards R.J., Corton J.C. Regulation of phase I and phase II steroid metabolism enzymes by PPAR alpha activators. Toxicology 2004, 204:109-121.
116. Howroyd P., Swanson C., Dunn C., Cattley R.C., Corton J.C. Decreased longevity and enhancement of age-dependent lesions in mice lacking the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Toxicol. Pathol. 2004, 32:591-599.
117. Takashima K., Ito Y., Gonzalez F.J., Nakajima T. Different mechanisms of DEHP-induced hepatocellular adenoma tumorigenesis in wild-type and Ppar alpha-null mice. J. Occup. Health 2008, 50:169-180.
118. Ren H., Aleksunes L.M., Wood C., Vallanat B., George M.H., Klaassen C.D., Corton J.C. Characterization of peroxisome proliferator-activated receptor alpha - independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor. Toxicol. Sci. 2010, 113:45-59.
119. Kim N.Y., Kim T.H., Lee E., Patra N., Lee J., Shin M.O., Kwack S.J., Park K.L., Han S.Y., Kang T.S., Kim S.H., Lee B.M., Kim H.S. Functional role of phospholipase D (PLD) in di(2-ethylhexyl) phthalate-induced hepatotoxicity in Sprague-Dawley rats. J. Toxicol. Environ. Health A 2010, 73:1560-1569.
120. Baldwin W.S., Roling J.A. A concentration addition model for the activation of the constitutive androstane receptor by xenobiotic mixtures. Toxicol. Sci. 2009, 107:93-105.
121. Shen O., Du G., Sun H., Wu W., Jiang Y., Song L., Wang X. Comparison of in vitro hormone activities of selected phthalates using reporter gene assays. Toxicol. Lett. 2009, 191:9-14.
122. Parmar D., Srivastava S.P., Seth P.K. Effect of di(2-ethylhexyl)phthalate (DEHP) on hepatic mixed function oxidases in different animal species. Toxicol. Lett. 1988, 40:209-217.
123. Hurst C.H., Waxman D.J. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription. Toxicol. Appl. Pharmacol. 2004, 199:266-274.
124. Hasmall S.C., James N.H., Macdonald N., West D., Chevalier S., Cosulich S.C., Roberts R.A. Suppression of apoptosis and induction of DNA synthesis in vitro by the phthalate plasticizers monoethylhexylphthalate (MEHP) and diisononylphthalate (DINP): a comparison of rat and human hepatocytes in vitro. Arch. Toxicol. 1999, 73:451-456.
125. Smith-Oliver T., Butterworth B.E. Correlation of the carcinogenic potential of di(2-ethylhexyl)phthalate (DEHP) with induced hyperplasia rather than with genotoxic activity. Mutat. Res. 1987, 188:21-28.
126. Marsman D.S., Cattley R.C., Conway J.G., Popp J.A. Relationship of hepatic peroxisome proliferation and replicative DNA synthesis to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) in rats. Cancer Res. 1988, 48:6739-6744.
127. Ward J.M., Hagiwara A., Anderson L.M., Lindsey K., Diwan B.A. The chronic hepatic or renal toxicity of di(2-ethylhexyl) phthalate, acetaminophen, sodium barbital, and phenobarbital in male B6C3F1 mice: autoradiographic, immunohistochemical, and biochemical evidence for levels of DNA synthesis not associated with carcinogenesis or tumor promotion. Toxicol. Appl. Pharmacol. 1988, 96:494-506.
128. Shah Y.M., Morimura K., Yang Q., Tanabe T., Takagi M., Gonzalez F.J. Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation. Mol. Cell. Biol. 2007, 27:4238-4247.
129. Roberts R.A., James N.H., Cosulich S.C. The role of protein kinase B and mitogen-activated protein kinase in epidermal growth factor and tumor necrosis factor alpha-mediated rat hepatocyte survival and apoptosis. Hepatology 2000, 31:420-427.
130. Rusyn I., Yamashina S., Segal B.H., Schoonhoven R., Holland S.M., Cattley R.C., Swenberg J.A., Thurman R.G. Oxidants from nicotinamide adenine dinucleotide phosphate oxidase are involved in triggering cell proliferation in the liver due to peroxisome proliferators. Cancer Res. 2000, 60:4798-4803.
131. Wheeler M.D., Smutney O.M., Check J.F., Rusyn I., Schulte-Hermann R., Thurman R.G. Impaired Ras membrane association and activation in PPARalpha knockout mice after partial hepatectomy. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 284:G302-G312.
132. Roberts R.A., Ganey P.E., Ju C., Kamendulis L.M., Rusyn I., Klaunig J.E. Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol. Sci. 2007, 96:2-15.
133. Yokoyama Y., Okubo T., Kano I., Sato S., Kano K. Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells. Toxicol. Lett. 2003, 144:371-381.
134. O'Shea S.H., Schwarz J., Kosyk O., Ross P.K., Ha M.J., Wright F.A., Rusyn I. In vitro screening for population variability in chemical toxicity. Toxicol. Sci. 2011, 119:398-407.
135. James N.H., Soames A.R., Roberts R.A. Suppression of hepatocyte apoptosis and induction of DNA synthesis by the rat and mouse hepatocarcinogen diethylhexylphlathate (DEHP) and the mouse hepatocarcinogen 1,4-dichlorobenzene (DCB). Arch. Toxicol. 1998, 72:784-790.
136. Kim I.Y., Han S.Y., Moon A. Phthalates inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer cells. J. Toxicol. Environ. Health A 2004, 67:2025-2035.
137. Martinasso G., Maggiora M., Trombetta A., Canuto R.A., Muzio G. Effects of di(2-ethylhexyl) phthalate, a widely used peroxisome proliferator and plasticizer, on cell growth in the human keratinocyte cell line NCTC 2544. J. Toxicol. Environ. Health A 2006, 69:353-365.
138. Rusyn I., Peters J.M., Cunningham M.L. Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit. Rev. Toxicol. 2006, 36:459-479.
139. Lake B.G., Kozlen S.L., Evans J.G., Gray T.J., Young P.J., Gangolli S.D. Effect of prolonged administration of clofibric acid and di-(2-ethylhexyl)phthalate on hepatic enzyme activities and lipid peroxidation in the rat. Toxicology 1987, 44:213-228.
140. Cattley R.C., Conway J.G., Popp J.A. Association of persistent peroxisome proliferation and oxidative injury with hepatocarcinogenicity in female F-344 rats fed di(2-ethylhexyl)phthalate for 2 years. Cancer Lett. 1987, 38:15-22.
141. Hinton R.H., Mitchell F.E., Mann A., Chescoe D., Price S.C., Nunn A., Grasso P., Bridges J.W. Effects of phthalic acid esters on the liver and thyroid. Environ. Health Perspect. 1986, 70:195-210.
142. Conway J.G., Tomaszewski K.E., Olson M.J., Cattley R.C., Marsman D.S., Popp J.A. Relationship of oxidative damage to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and Wy-14,643. Carcinogenesis 1989, 10:513-519.
143. Seo K.W., Kim K.B., Kim Y.J., Choi J.Y., Lee K.T., Choi K.S. Comparison of oxidative stress and changes of xenobiotic metabolizing enzymes induced by phthalates in rats. Food Chem. Toxicol. 2004, 42:107-114.
144. Takagi A., Sai K., Umemura T., Hasegawa R., Kurokawa Y. Significant increase of 8-hydroxydeoxyguanosine in liver DNA of rats following short-term exposure to the peroxisome proliferators di(2-ethylhexyl)phthalate and di(2-ethylhexyl)adipate. Jpn. J. Cancer Res. 1990, 81:213-215.
145. Takagi A., Sai K., Umemura T., Hasegawa R., Kurokawa Y. Relationship between hepatic peroxisome proliferation and 8-hydroxydeoxyguanosine formation in liver DNA of rats following long-term exposure to three peroxisome proliferators; di(2-ethylhexyl) phthalate, aluminium clofibrate and simfibrate. Cancer Lett. 1990, 53:33-38.
146. Rusyn I., Kadiiska M.B., Dikalova A., Kono H., Yin M., Tsuchiya K., Mason R.P., Peters J.M., Gonzalez F.J., Segal B.H., Holland S.M., Thurman R.G. Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells. Mol. Pharmacol. 2001, 59:744-750.
147. Woods C.G., Burns A.M., Maki A., Bradford B.U., Cunningham M.L., Connor H.D., Kadiiska M.B., Mason R.P., Peters J.M., Rusyn I. Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-alpha, but not NADPH oxidase. Free Radic. Biol. Med. 2007, 42:335-342.
148. Powell C.L., Swenberg J.A., Rusyn I. Expression of base excision DNA repair genes as a biomarker of oxidative DNA damage. Cancer Lett. 2005, 229:1-11.
149. Rusyn I., Denissenko M.F., Wong V.A., Butterworth B.E., Cunningham M.L., Upton P.B., Thurman R.G., Swenberg J.A. Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency. Carcinogenesis 2000, 21:2141-2145.
150. Rusyn I., Asakura S., Pachkowski B., Bradford B.U., Denissenko M.F., Peters J.M., Holland S.M., Reddy J.K., Cunningham M.L., Swenberg J.A. Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators. Cancer Res. 2004, 64:1050-1057.
151. Tomaszewski K.E., Heindel S.W., Jenkins W.L., Melnick R.L. Induction of peroxisomal acyl CoA oxidase activity and lipid peroxidation in primary rat hepatocyte cultures. Toxicology 1990, 65:49-60.
152. Isenberg J.S., Kamendulis L.M., Smith J.H., Ackley D.C., Pugh G., Lington A.W., Klaunig J.E. Effects of di-2-ethylhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), DNA synthesis, and peroxisomal beta oxidation (PBOX) in rat, mouse, and hamster liver. Toxicol. Sci. 2000, 56:73-85.
153. Isenberg J.S., Kamendulis L.M., Ackley D.C., Smith J.H., Pugh G., Lington A.W., McKee R.H., Klaunig J.E. Reversibility and persistence of di-2-ethylhexyl phthalate (DEHP)- and phenobarbital-induced hepatocellular changes in rodents. Toxicol. Sci. 2001, 64:192-199.
154. Malcolm A.R., Mills L.J. Inhibition of gap-junctional intercellular communication between Chinese hamster lung fibroblasts by di(2-ethylhexyl) phthalate (DEHP) and trisodium nitrilotriacetate monohydrate (NTA). Cell Biol. Toxicol. 1989, 5:145-153.
155. Mikalsen S.O., Sanner T. Intercellular communication in colonies of Syrian hamster embryo cells and the susceptibility for morphological transformation. Carcinogenesis 1993, 14:251-257.
156. Cruciani V., Mikalsen S.O., Vasseur P., Sanner T. Effects of peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on intercellular communication and connexin43 in two hamster fibroblast systems. Int. J. Cancer 1997, 73:240-248.
157. Kamendulis L.M., Isenberg J.S., Smith J.H., Pugh G., Lington A.W., Klaunig J.E. Comparative effects of phthalate monoesters on gap junctional intercellular communication and peroxisome proliferation in rodent and primate hepatocytes. J. Toxicol. Environ. Health A 2002, 65:569-588.
158. Rose M.L., Rivera C.A., Bradford B.U., Graves L.M., Cattley R.C., Schoonhoven R., Swenberg J.A., Thurman R.G. Kupffer cell oxidant production is central to the mechanism of peroxisome proliferators. Carcinogenesis 1999, 20:27-33.
159. Rose M.L., Rusyn I., Bojes H.K., Germolec D.R., Luster M., Thurman R.G. Role of Kupffer cells in peroxisome proliferator-induced hepatocyte proliferation. Drug Metab. Rev. 1999, 31:87-116.
160. Rusyn I., Rose M.L., Bojes H.K., Thurman R.G. Novel role of oxidants in the molecular mechanism of action of peroxisome proliferators. Antiox. Redox Signal. 2000, 2:607-621.
161. Flavell D.M., Pineda Torra I., Jamshidi Y., Evans D., Diamond J.R., Elkeles R.S., Bujac S.R., Miller G., Talmud P.J., Staels B., Humphries S.E. Variation in the PPARalpha gene is associated with altered function in vitro and plasma lipid concentrations in Type II diabetic subjects. Diabetologia 2000, 243:673-680.
162. Lacquemant, B., Staels, P.Froguel C., Lepretre F., Pineda Torra I., Manraj M., Charpentier G., Ruiz J., Staels B., Froguel P. Mutation screening of the PPARalpha gene in type 2 diabetes associated with coronary heart disease. Diabetes Metab. 2000, 26:393-401.
163. Tai E.S., Demissie S., Cupples L.A., Corella D., Wilson P.W., Schaefer E.J., Ordovas J.M. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler. Thromb. Vasc. Biol. 2002, 22:805-810.
164. Sapone A., Peters J.M., Sakai S., Tomita S., Papiha S.S., Dai R., Friedman F.K., Gonzalez F.J. The human peroxisome proliferator-activated receptor alpha gene: identification and functional characterization of two natural allelic variants. Pharmacogenetics 2000, 10:321-333.
165. Yamakawa-Kobayashi K., Ishiguro H., Arinami T., Miyazaki R., Hamaguchi H. A Val227Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPARalpha) gene is associated with variations in serum lipid levels. J. Med. Genet. 2002, 39:189-191.
166. Chan E., Tan C.S., Deurenberg-Yap M., Chia K.S., Chew S.K., Tai E.S. The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women. Atherosclerosis 2006, 187:309-315.
167. Liu M.H., Li J., Shen P., Husna B., Tai E.S., Yong E.L. A natural polymorphism in peroxisome proliferator-activated receptor-alpha hinge region attenuates transcription due to defective release of nuclear receptor corepressor from chromatin. Mol. Endocrinol. 2008, 22:1078-1092.
168. James N.H., Gill J.H., Brindle R., Woodyatt N.J., Macdonald N., Rolfe M., Hasmall S.C., Tugwood J.D., Holden P.R., Roberts R.A. Peroxisome proliferator-activated receptor (PPAR) a-regulated growth responses and their importance to hepatocarcinogenesis. Toxicol. Lett. 1998, 102-103:91-96.
169. Lyche J.L., Gutleb A.C., Bergman A., Eriksen G.S., Murk A.J., Ropstad E., Saunders M., Skaare J.U. Reproductive and developmental toxicity of phthalates. J. Toxicol. Environ. Health B Crit. Rev. 2009, 12:225-249.
170. Toppari J., Virtanen H.E., Main K.M., Skakkebaek N.E. Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): environmental connection. Birth Defects Res. A Clin. Mol. Teratol. 2010, 88:910-919.
171. Sathyanarayana S. Phthalates and children's health. Curr. Prob. Pediatr. Adolesc. Health Care 2008, 38:34-49.
172. Stefanini S., Serafini B., Nardacci R., Vecchioli S.F., Moreno S., Sartori C. Morphometric analysis of liver and kidney peroxisomes in lactating rats and their pups after treatment with the peroxisomal proliferator di-(2-ethylhexyl)phthalate. Biol. Cell 1995, 85:167-176.
173. Maranghi F., Lorenzetti S., Tassinari R., Moracci G., Tassinari V., Marcoccia D., Di Viglio A., Eusepi A., Romeo A., Magrelli A., Salvatore M., Tosto F., Viganotti M., Antoccia A., Di Masi A., Azzalin G., Tanzarella C., Macino G., Taruscio D., Mantovani A. In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. Reprod. Toxicol. 2010, 29:427-432.
174. Pak V.M., Nailon R.E., McCauley.L.A. Controversy: neonatal exposure to plasticizers in the NICU. MCN Am. J. Matern. Child Nurs. 2007, 32:244-249.
175. Jaakkola J.J., Knight T.L. The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environ. Health Perspect. 2008, 116:845-853.
176. Hoppin J.A., Ulmer R., London S.J. Phthalate exposure and pulmonary function. Environ. Health Perspect. 2004, 112:571-574.
177. Klimisch H.J., Gamer A.O., Hellwig J., Kaufmann W., Jackh R. Di-(2-ethylhexyl) phthalate: a short-term repeated inhalation toxicity study including fertility assessment. Food Chem. Toxicol. 1992, 30:915-919.
178. Doleman C.J., Borm P.J., Bast A. Plasticisers and bronchial hyperreactivity. Lancet 1990, 335:725.
179. Pan G., Hanaoka T., Yoshimura M., Zhang S., Wang P., Tsukino H., Inoue K., Nakazawa H., Tsugane S., Takahashi K. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ. Health Perspect. 2006, 114:1643-1648.
180. Rozati R., Reddy P.P., Reddanna P., Mujtaba R. Role of environmental estrogens in the deterioration of male factor fertility. Fertil. Steril. 2002, 78:1187-1194.
181. Zhang Y.H., Zheng L.X., Chen B.H. Phthalate exposure and human semen quality in Shanghai: a cross-sectional study. Biomed. Environ. Sci. 2006, 19:205-209.
182. Hauser R., Meeker J.D., Singh N.P., Silva M.J., Ryan L., Duty S., Calafat A.M. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum. Reprod. 2007, 22:688-695.
183. Meeker J.D., Calafat A.M., Hauser R. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J. Androl. 2009, 30:287-297.
184. Colon I., Caro D., Bourdony C.J., Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ. Health Perspect. 2000, 108:895-900.
185. Cobellis L., Latini G., De Felice C., Razzi S., Paris I., Ruggieri F., Mazzeo P., Petraglia F. High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis. Hum. Reprod. 2003, 18:1512-1515.
186. Reddy B.S., Rozati R., Reddy B.V., Raman N.V. Association of phthalate esters with endometriosis in Indian women. BJOG 2006, 113:515-520.
187. Kim S.H., Chun S., Jang J.Y., Chae H.D., Kim C.H., Kang B.M. Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: a prospective case-control study. Fertil. Steril. 2011, 95:357-359.
188. Poon R., Lecavalier P., Mueller R., Valli V.E., Procter B.G., Chu I. Subchronic oral toxicity of di-n-octyl phthalate and di(2-ethylhexyl) phthalate in the rat. Food Chem. Toxicol. 1997, 35:225-239.
189. Howdeshell K.L., Wilson V.S., Furr J., Lambright C.R., Rider C.V., Blystone C.R., Hotchkiss A.K., Gray L.E. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague-Dawley rat in a cumulative, dose-additive manner. Toxicol. Sci. 2008, 105:153-165.
190. Ishihara M., Itoh M., Miyamoto K., Suna S., Takeuchi Y., Takenaka I., Jitsunari F. Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat. Int. J. Androl. 2000, 23:85-94.
191. Moffit J.S., Bryant B.H., Hall S.J., Boekelheide K. Dose-dependent effects of sertoli cell toxicants 2,5-hexanedione, carbendazim, and mono-(2-ethylhexyl)phthalate in adult rat testis. Toxicol. Pathol. 2007, 35:719-727.
192. Lahousse S.A., Wallace D.G., Liu D., Gaido K.W., Johnson K.J. Testicular gene expression profiling following prepubertal rat mono-(2-ethylhexyl) phthalate exposure suggests a common initial genetic response at fetal and prepubertal ages. Toxicol. Sci. 2006, 93:369-381.
193. Richburg J.H., Boekelheide K. Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes. Toxicol. Appl. Pharmacol. 1996, 137:42-50.
194. Ge R.S., Chen G.R., Tanrikut C., Hardy M.P. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod. Toxicol. 2007, 23:366-373.
195. Ward J.M., Diwan B.A., Ohshima M., Hu H., Schuller H.M., Rice J.M. Tumor-initiating and promoting activities of di(2-ethylhexyl) phthalate in vivo and in vitro. Environ. Health Perspect. 1986, 65:279-291.
196. Ward J.M., Konishi N., Diwan B.A. Renal tubular cell or hepatocyte hyperplasia is not associated in B6C3F1 mice after transplacental initiation with N-nitrosoethylurea. Exp. Pathol. 1990, 40:138.
197. Ohno S., Fujii Y., Usuda N., Murata F., Nagata T. Peroxisomal proliferation in rat kidney induced with DEHP. I. Numerical change by light microscopic morphometry. Acta Histochem. Cytochem. 1982, 15:40-57.
198. Reubsaet F.A., Veerkamp J.H., Bruckwilder M.L., Trijbels J.M., Monnens L.A. Peroxisomal oxidases and catalase in liver and kidney homogenates of normal and di(ethylhexyl)phthalate-fed rats. Int. J. Biochem. 1991, 23:961-967.
199. Lington A.W., Bird M.G., Plutnick R.T., Stubbefield W.A., Scala R.A. Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats. Fundam. Appl. Toxicol. 1997, 36:79-89.
200. Jepsen K.F., Abildtrup A., Larsen S.T. Monophthalates promote IL-6 and IL-8 production in the human epithelial cell line A549. Toxicol. In Vitro 2004, 18:265-269.
201. Glue C., Millner A., Bodtger U., Jinquan T., Poulsen L.K. In vitro effects of monophthalates on cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells from allergic and non-allergic donors. Toxicol. In Vitro 2002, 16:657-662.
202. Glue C., Platzer M.H., Larsen S.T., Nielsen G.D., Skov P.S., Poulsen L.K. Phthalates potentiate the response of allergic effector cells. Basic Clin. Pharmacol. Toxicol. 2005, 96:140-142.
203. Larsen S.T., Hansen J.S., Thygesen P., Begtrup M., Poulsen O.M., Nielsen G.D. Adjuvant and immuno-suppressive effect of six monophthalates in a subcutaneous injection model with BALB/c mice. Toxicology 2001, 169:37-51.
204. Larsen S.T., Nielsen G.D. The adjuvant effect of di-(2-ethylhexyl) phthalate is mediated through a PPARalpha-independent mechanism. Toxicol. Lett. 2007, 170:223-228.
205. Dearman R.J., Beresford L., Bailey L., Caddick H.T., Betts C.J., Kimber I. Di-(2-ethylhexyl) phthalate is without adjuvant effect in mice on ovalbumin. Toxicology 2008, 244:231-241.
206. Larsen S.T., Hansen J.S., Hammer M., Alarie Y., Nielsen G.D. Effects of mono-2-ethylhexyl phthalate on the respiratory tract in BALB/c mice. Hum. Exp. Toxicol. 2004, 23:537-545.
207. Bally M.B., Opheim D.J., Shertzer H.G. Di-(2-ethylhexyl) phthalate enhances the release of lysosomal enzymes from alveolar macrophages during phagocytosis. Toxicology 1980, 18:49-60.
208. 2+ response of RBL-2H3 mast cells. Immunol. Lett. 2002, 80:119-124.
209. Corton J.C., Lapinskas P.J., Gonzalez F.J. Central role of PPARalpha in the mechanism of action of hepatocarcinogenic peroxisome proliferators. Mutat. Res. 2000, 448:139-151.
210. Reddy J.K., Azarnoff D.L., Hignite C.E. Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 1980, 283:397-398.
211. Marsman D.S., Goldsworthy T.L., Popp J.A. Contrasting hepatocytic peroxisome proliferation, lipofuscin accumulation and cell turnover for the hepatocarcinogens Wy-14,643 and clofibric acid. Carcinogenesis 1992, 13:1011-1017.
212. International Agency for Research on Cancer Some Industrial Chemicals 2000, IARC Press, Lyon, France.
213. Peters J.M., Cattley R.C., Gonzalez F.J. Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis 1997, 18:2029-2033.
214. Grosse Y., Baan R., Secretan-Lauby B., Ghissassi F., Bouvard V., Benbrahim-Tallaa L., Guha N., Islami F., Galichet L., Straif K. WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of chemicals in industrial and consumer products, food contaminants and flavourings, and water chlorination byproducts. Lancet Oncol. 2011, 12:328-329.