Hepatocarcinogenic Potential of Di(2-Ethylhexyl)phthalate in Rodents and its Implications on Human Risk

References

• Klöpffer W. Environmental hazard, assessment of chemicals and products. II. Persistence and degradability of organic chemicals. Environ. Sci. Pollut. Res. 1994; 1: 108–116
   PubMedGoogle Scholar
• Aso D., Migita M., Tomoda M. Production of phthalic acid by azotobacter. Proc. 2nd Int. Congr. Soll. 1932; 3: 40–41
   Google Scholar
• Schmid H., Karrer P. Über wasserlösliche Inhaltsstoffe von Papaver somniferum. Zürich. Chem. Instiut Universitát. 1945; 722–740
   Google Scholar
• Mathur S. P. Phthalate esters in the environment: pollutants or natural products?. J. Environ. Qual. 1974; 3: 189–196
   Web of Science ®Google Scholar
• Lützel G. Weichmacher. Kunststoffe 1984; 74: 632–635
   Google Scholar
• Blass C. R., Jones C., Coutney J. M. Biomaterials for blood tubing: the application of plasticised poly(vinyl chloride). Int. J. Artif. Organs. 1992; 15: 220–203
   Google Scholar
• Berndtsson S. 1984 as cited in Beratergremium für umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker Di(2-ethylhexyl)phthalat. BUA-Stoffbericht 1986; 4
   Google Scholar
• Alarie Y., Iwasaki M., Sock M. F., Person R. C., Shane B. S., Lisk D. J. Effect of inhaled municipal refuse incinerator fly ash in the guinea pig. J. Toxicol. Environ. Health 1989; 28: 13–25
   PubMed Web of Science ®Google Scholar
• Quackenboss H. M. Plasticizers in PVC-resins: migration of plasticizers. Ind. Eng. Chem. 1954; 46: 1335
   Google Scholar
• Warns T. J. Diethylhexylphthalate as an environmental contaminant — a review. Sci. Total Environ. 1987; 66: 1–16
   PubMedGoogle Scholar
• Giam C. S., Chan H. S., Naff G. S., Atlas E. L. Phthalate ester plasticizers: a new class of marine pollutant. Science 1978; 199: 419–421
   PubMed Web of Science ®Google Scholar
• IPCS/WHO. International Programme on Chemical Safety/World Health Organization, Diethylhexyl phthalate. Environ. Health Criteria 1992; 131: 1–141
   Google Scholar
• Beratergremium für umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker. Di-(2-ethylhexyl)phthalate, BUA-Stoffbericht 1986; 4
   Google Scholar
• Mayer F. L., Stalling D., Johnson J. L. Phthalate esters as environmental contaminants. Nature (London) 1972; 238: 411–413
   PubMed Web of Science ®Google Scholar
• Takahashi M., Ohgane J., Sato H., Sone M. Esters of phthalic acid in the water of Miyashiro Prefecture (Jpn.). Miyagi-ken Kogai Gijutsu Senta Hokoku 1976; 4: 39–41, (Chem. Abstr., 88: 78840k)
   Google Scholar
• Hrudey S. E., Sergy G. A., Thackeray T. Toxicity of oil sands plant wastewaters and associated organic contaminants. Water Pollut. Res. Can. 1976; 76: 34–45
   Google Scholar
• Mori S. Identification and determination of phthalate esters in river water by high-performance liquid chromatography. J. Chromatogr. 1976; 129: 53–60
   PubMed Web of Science ®Google Scholar
• Schouten M. J., Copius Peereboom J. W., Brinkman U. A. T. Liquid chromatographic analysis of phthalate esters in Dutch river water. Int. J. Environ. Anal. Chem. 1979; 7: 13–23
   Web of Science ®Google Scholar
• 1986; 4, IAWR-Rheinbericht, 1981/82, as cited in Beratergremium für umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker.Di-(2-ethylhexyl)phthalat, BUA-Stoffbericht
   Google Scholar
• Schwartz H. E., Anzion C. J. M., Van Vliet H. P. M. Copius Peereboom, J. W., and Brinkman, U. A. T., Analysis of phthalate esters in sediments from Dutch rivers by means of high performance liquid chromatography. Int. J. Environ. Anal. Chem. 1979; 6: 133–144
   Web of Science ®Google Scholar
• Malisch R., Schulte E., Acker L. Chloroorganische Pestizide, polychlorierte Biphenyle und Phthalate in Sedimenten aus Rhein und Neckar. Chem. Zeitung 1981; 105: 187–194
   Google Scholar
• 1980; 912–926, EPA, U.S. Environmental Protection Agency, Paint formulating-point source category: effluent limitations guidelines, pretreatment standards, and new source performance standards. U.S. Code Fed. Regul., Title 40, Part 446, Fed. Regist., 45 (No.2)
   Google Scholar
• 1980; 928–939, EPA, U.S. Environmental Protection Agency, Ink formulating-point source category: effluent limitations guidelines, pretreatment standards, and new source performance standards. U.S. Code Fed. Regul.; Title 40, Part 447, Fed. Regist., 45 (No. 2)
   Google Scholar
• Jaeger R. J., Rubin R. J. Contamination of blood stored in plastic packs. Lancet 1970; 2: 151
   PubMed Web of Science ®Google Scholar
• Jaeger R. J., Rubin R. J. Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tis. N. Engl. J. Med. 1972; 287: 1114–1118
   PubMed Web of Science ®Google Scholar
• Piechocki J. T., Purdy W. C. Determination of di-(2-ethylhexyl)-phthalate (DEHP) in human plasma. Clin. Chim. Acta 1973; 48: 385–391
   PubMed Web of Science ®Google Scholar
• Rock G., Secours V. E., Franklin C. A., Chu I., Villeneuve D. C. The accumulation of mono-2-ethylhexylphthalate (MEHP) during storage of whole blood and plasma. Transfusion 1978; 18: 553–558
   PubMed Web of Science ®Google Scholar
• Pik J., Braier J., Kalman Z., Jozef M. Determination of bis(2-ethylhexyl)phthalate (DEHP) in blood preparations stored in poly(vinyl chloride) bags (Rum.). Probl. Gematol. Per. Krovi. 1979; 24: 49–51, (Chem. Abstr., 91:27213n)
   Google Scholar
• 1982, NTP, National Toxicology Program, Carcinogenesis bioassay of di(2-ethylhexyl)phthalate (CAS No. 117–81–7) in F344 rats and B6C3F1 mice (feed study). Tech. Rep. Ser., 217
   Google Scholar
• Ganning A. E., Brunk U., Dallner G. Phthalate esters and their effect on the liver. Hepatology 1984; 4: 541–547
   PubMed Web of Science ®Google Scholar
• Griffiths W. C., Camara P. D., Saritelli A., Gentile J. The in vitro serum protein-binding characteristics of bis-(2-ethylhexyl)phthalate and its principal metabolite, mono-(2-ethylhexyl)phthalate. Environ. Health Perspect. 1988; 77: 151–156
   PubMed Web of Science ®Google Scholar
• Plonait S. L., Nau H., Maier R. F., Wittfoht W., Obladen M. Exposure of newborn infants to di-(2-ethylhexyl)-phthalate and 2-ethylhexanoic acid following exchange transfusion with poly vinylchloride catheters. Transfusion 1993; 33: 598–605
   PubMed Web of Science ®Google Scholar
• Rock G., Labow R. S., Franklin C., Burnett R., Tocchi M. Hypotension and cardiac arrest in rats following infusion of mono(2-ethylhexyl)phthalate (MEHP), a contaminant of stored blood. N. Engl. J. Med. 1987; 316: 1218–1219
   PubMed Web of Science ®Google Scholar
• Labow R. S., Card R. T., Rock G. The effect of the plasticizer di(2-ethylhexyl) phthalate on red cell deformability. Blood 1987; 70: 319–323
   PubMed Web of Science ®Google Scholar
• Rubin R. J., Schiffer C. A. Fate in humans of the plasticizer, di-2-ethylhexylphthalate, arising from transfusion of platelets stored in vinyl plastic bags. Transfusion 1976; 16: 330–335
   PubMed Web of Science ®Google Scholar
• Labow R. S., Tocchi M. Contamination of platelet storage bags by phthalate esters. J. Toxicol. Environ. Health 1986; 19: 591–598
   PubMed Web of Science ®Google Scholar
• Shimizu T., Kouketsu K., Morishima Y., Goto S., Hasegawa I., Kamiya T., Tamura Y., Kora S. A new polyvinylchloride blood bag plasti-cized with less-leachable phthalate ester analogue, di-n-decyl phthalate, for storage of platelets. Transfusion 1989; 29: 292–297
   PubMed Web of Science ®Google Scholar
• Vessman J., Rietz G. Determination of di(ethylhexyl)phthalate in human plasma and plasma proteins by electron capture gas chromatography. J. Chromatogr. 1974; 100: 153–163
   PubMed Web of Science ®Google Scholar
• Dine T., Luyckx M., Cazin M., Brunet C., Cazin J. C., Goudaliez F. Rapid determination by high performance liquid chromatography of di-2-ethylhexyl phthalate in plasma stored in plastic bags. Biomed. Chromatogr. 1991; 5: 94–97
   PubMed Web of Science ®Google Scholar
• Nässberger L., Arbin A., Östelius J. Exposure of patients to phthalates from polyvinyl chloride tubes and bags during dialysis. Nephron 1987; 45: 286–290
   PubMed Web of Science ®Google Scholar
• Pearson S. D., Trissel L. A. Leaching of diethylhexyl phthalate from polyvinyl chloride containers by selected drugs and formulation components. Am. J. Hosp. Pharm. 1993; 50: 1405–1409
   PubMedGoogle Scholar
• Easterling R. E., Johnson E., Napier E. A. Plasma extraction of plasticizers from “medical grade” polyvinylchloride tubing (38389). Proc. Soc. Exp. Biol. Med. 1974; 147: 572–574
   PubMedGoogle Scholar
• Lewis L. M., Flechtner T. W., Kerkay J., Pearson K. H., Nakamoto S. Bis(2-ethylhexyl)phthalate concentrations in the serum of hemodialysis patients. Clin. Chem. 1978; 24/5: 741–746
   Web of Science ®Google Scholar
• Gerstoft J., Christiansen E., Nielsen I. L., Nielsen B. The migration of plasticizers from PVC haemodialysis tubes. Proc. Eur. Dial. Transplant. Assoc. 1980; 16: 739–740
   Google Scholar
• Bommer J., Waldherr R., Gastner M., Lemmes R., Ritz E. Iatrogenic multiorgan silicone inclusions in dialysis patients. Klin Wochenschr. 1981; 59: 1149–1157
   PubMedGoogle Scholar
• Ono K., Tatsukawa R., Wakimoto T. Migration of plasticizer from hemodialysis blood tubing. J. Am. Med. Assoc. 1975; 234: 948–949
   PubMed Web of Science ®Google Scholar
• Sjöberg P., Bondesson U., Sedin G., Gustafsson J. Dispositions of di- and mono-(2-ethylhexyl)phthalate in newborn infants subjected to exchange transfusions. Eur. J. Clin. Invest. 1985; 15: 430–436
   PubMedGoogle Scholar
• Shneider B., Schena J., Truog R., Jacobson M., Kevy S. Exposure to di(2-ethylhexyl) phthalate in infants receiving extracorporal membrane oxygen-ation. N. Engl. J. Med. 1989; 320: 1563
   PubMed Web of Science ®Google Scholar
• Labow R. S., Tocchi M., Rock G. Effects of leachable materials on morphology and function. Transfusion 1986; 26: 351–357
   PubMed Web of Science ®Google Scholar
• Martis L., Freid E., Woods E. Ti distribution and excretion of tri-(2-ethylhexyl)trimellitate in rats. J. Toxicol. Environ. Health 1987; 20: 357–366
   PubMed Web of Science ®Google Scholar
• Hoenich N. A., Thompson J., Varini E., McCabe J., Appleton D. Particle spallation and plasticizer (DEHP) release from extracorporeal circuit tubing materials. Int. J. Artif. Organs 1990; 13: 55–62
   PubMedGoogle Scholar
• Rock G., Labow R. S., Tocchi M. Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components. Environ. Health Perspect. 1986; 65: 309–316
   PubMed Web of Science ®Google Scholar
• Seidl S., Gosda W., Repucci A. J. The in vitro and in vivo evaluation of whole blood and red cell concentrates drawn on CPDA-1 and stored in a non-DEHP plasticized PVC container. Vox. Sang. 1991; 61: 8–13
   PubMed Web of Science ®Google Scholar
• Gibson T. P., Briggs W. A., Boone B. J. Delivery of di-2-ethylhexyl phthalate to patients during hemodialysis. J. Lab. Clin. Med. 1976; 87: 519–524
   PubMed Web of Science ®Google Scholar
• 1985, CPSC. U.S. Consumer Product Safety Commission. Report to the U.S. Consumer Product Safety Commission by the Chronic Hazard Advisory Panel on Di(2-ethylhexyl)phthalate (DEHP), U.S. Consumer Product Safety Commission, Washington, D.C.
   Google Scholar
• Bommer J., Ritz E., Andrassy K. Side effects due to materials used in hemodialysis equipment. Adv. Nephrol. 1985; 14: 409–438
   PubMedGoogle Scholar
• Pollack G. M., Buchanan J. F., Slaughter R. L., Kohli R. K., Shen D. D. Circulating concentrations of di(2-ethylhexyl)phthalate and its de-esterified phthalic acid products following plasticizer exposure in patients receiving hemodialysis. Toxicol. Appl. Pharmacol. 1985; 79: 257–267
   PubMed Web of Science ®Google Scholar
• Flaminio L. M., Bergia R., De Angelis L., Ferazza M., Marinovich M., Galli G., Galli C. L. The fate of leached di-(2-ethylhexyl)-phthalate (DEHP) in patients on chronic haemodialysis. Int. J. Artif. Organs. 1988; 11: 428–434
   PubMed Web of Science ®Google Scholar
• Jacobson M. S., Kevy S. V., Grand R. J. Effects of plasticizer leached from polyvinyl chloride on the subhuman primate: a consequence of chronic transfusion therapy. J. Lab. Clin. Med. 1977; 89: 1066–1079
   PubMed Web of Science ®Google Scholar
• Sjöberg P. O., Bondesson U. G., Sedin E. G., Gustafsson J. P. Exposure of newborn infants to plasticizers. Plasma levels of di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate during exchange transfusion. Transfusion 1985; 25: 424–428
   PubMed Web of Science ®Google Scholar
• Peck C. C., Albro P. W., Haas J. R., Odom D. G., Barrett B. B., Bailey F. J. Metabolism and excretion of the plasticizer di-(2-ethylhexyl)-phthal-ate in man. Clin. Res. 1978; 26: 101A
   Google Scholar
• Barry Y. A., Labow R. S., Keon W. J., Tocchi M., Rock G. Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg. 1989; 97: 900–905
   PubMed Web of Science ®Google Scholar
• Roth B., Herkenrath P., Lehmann H.-J., Ohles H.-D., Hömig H. J., Benz-Bohm G., Kreuder J., Younossi-Hartenstein A. Di-(2-ethylhexyl)-phthalate as plasticizer in PVC respiratory tubing system: indications of hazardous effects on pulmonary function in mechanically ventilated, preterm infants. Eur. J. Pediatr. 1988; 147: 41–46
   PubMed Web of Science ®Google Scholar
• Milkow L. E., Aldyreva M. V., Popova T. B., Lopukhova K. A., Makarenko Y. L., Malyar L. M., Shakova T. K. Health status of workers exposed to phthalate plasticizers in the manufacture of artificial leather and films based on PVC resins. Environ. Health Perspect. 1973; 3: 175–178
   PubMedGoogle Scholar
• Gilioli R., Bulgheroni C., Terrana T., Filippini G., Massetto N., Boeri R. Studio neurologico transversale e longitudinale di una popolazione operaia addetta alla produzione di ftalati. Med. Lav. 1978; 69: 620–631
   PubMedGoogle Scholar
• Thiess A. M., Fleig I. Chromosomenunter-suchungen bei Mitarbeitern mit Exposition gegenüber Di-(2-ethylhexyl)phthalat (DOP). Zentralbl. Arbeitsmed. Arbeitsschutz 1978; 28: 351–356
   Google Scholar
• Thiess A. M. 1978, as cited in Beratergremium für umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker. Di-(2-ethylhexyl)phthalat, BUA-Stoffbericht, 4, 1986
   Google Scholar
• Ruhe R. L., Donohue M. 1979, Health Hazard Evaluation Determination Report HE 78–91–621, Dresser Industries, Inc., Bradford, PA, U.S. Department of Health, Education, and Welfare, National Institute for Occupational Safety and Health, Cincinnati, OH
   Google Scholar
• Nielsen J., Akesson B., Skerfving S. Phthalate ester exposure — air levels and health of workers processing polyvinylchloride. Am. Ind. Hyg. Assoc. J. 1985; 46: 643–647
   PubMed Web of Science ®Google Scholar
• Liss G. M., Albro P. W., Hartle R. W., Stringer W. T. Urine phthalate determinations as an index of occupational exposure to phthalic anhydride and di(2-ethylhexyl) phthalate. Scand. J. Work Environ. Health 1985; 11: 381–387
   PubMed Web of Science ®Google Scholar
• Vainiotalo S., Pfäffli P. Air impurities in the PVC-plastics processing industry. Ann. Occup. Hyg. 1990; 34: 585–590
   PubMedGoogle Scholar
• Dirven H. A. A.M., van den Broek P. H. H., Jongeneelen F. J. Determination of four metabolites of the plasticizer di(2-ethylhexyl)phthalate in human urine samples. Int. Arch. Occup. Environ. Health 1993; 64: 549–554
   PubMed Web of Science ®Google Scholar
• Natow M. Über das Auswandern von Weichmachern aus Polyvinylchloriderzeugnissen. Plaste Kautschuk 1981; 28: 459–460
   Google Scholar
• Mieure J. P., Dietrich M. W. Determination of trace organics in air and water. J. Chromatogr. Sci. 1973; 11: 559–570
   PubMed Web of Science ®Google Scholar
• NRC, National Research Council, Drinking Water and Health. National Academy of Sciences, Washington, D.C. 1977; 727
   Google Scholar
• Sheldon L. S., Hites R. A. Sources and movement of organic chemicals in the Delaware River. Environ. Sci. Technol. 1979; 13: 574–579
   Web of Science ®Google Scholar
• 1981, NIH/EPA Chemical Information System, Data Bases. Distribution Register of Organic Pollutants in Water (WDROP), Washington, D.C., CIS Project, Information Sciences Corporation
   Google Scholar
• Fishbein L. Exposure from occupational versus other sources. Scand. J. Work Environ. Health 1992; 18(Suppl. 1)5–16
   PubMedGoogle Scholar
• Thuren A., Larsson P. Phthalate esters in the Swedish atmosphere (abstract). Environ. Sci. Technol. 1990; 24: 554
   Web of Science ®Google Scholar
• Antonyuk O. K. Toxicology of complex ethers of phthalic acid (a review of literature). Hyg. Labour Occup. Dis. 1975; 1: 32–35
   Google Scholar
• Cohen H., Charrier C., Sarfaty J. Extraction and identification of a plasticizer, di-(2-ethyl-hexyl)phthalate, from a plastic bag containing contaminated corn. Arch. Environ. Contain. Toxicol. 1991; 20: 437–440
   Web of Science ®Google Scholar
• Hartung R. Toxicological and environmental is associated with phthalic acid esters — an update since 1974. Manufacturing Chemists Association, Washington, D.C. 1976; 4
   Google Scholar
• Musial C. J., Uthe J. F. Studies on phthalate esters in western atlantic finfish. 1980; 11, Report to the Intern. Council of the Expl. of the Sea. ICES, D.M.
   Google Scholar
• 1980, EPA, U.S. Environmental Protection Agency, Ambient Water Quality Criteria for Phthalate Esters (NTIS Publication No. PB81–117780), Washington, D.C. C-4-C-5
   Google Scholar
• 1988, USATSDR, Toxicological profile for di(2-ethyl-hexyl) phthalate, Atlanta, Georgia, Agency for Toxic Substances and Disease Registry, U.S. Public Health Service (Draft for public comment)
   Google Scholar
• Castle L., Mayo A., Gilbert J. Migration of plasticizers from printing inks into foods. Food Addit. Contam. 1989; 6: 437–443
   PubMedGoogle Scholar
• 1991, EC-Commission, Directorate General for Industrial Affairs and International Market, Consolidated report of the scientific committee for food on certain additives used in the manufacture of plastic materials intended to come into contact with foodstuffs; CS/PM/1023
   Google Scholar
• Nakamura Y., Yagi Y., Tomita I., Tsuchikawa K. Teratogenicity of di-(2-ethyl-hexyl)phthalate in mice. Toxicol. Lett. 1979; 4: 113–117
   Web of Science ®Google Scholar
• Shiota K., Chou M. J., Nishimura H. Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice. Environ. Res. 1980; 22: 245–253
   PubMed Web of Science ®Google Scholar
• 1987, MAFF, Survey of plasticiser level in food contact materials and in foods, London, Ministry of Agriculture, Fisheries and Food (Food Surveillance Paper No. 21)
   Google Scholar
• 1994, ECETOC: Tech. Rep. No. 18, Assessment of non-occupational exposure to chemicals
   Google Scholar
• Scott R. C., Dugard P. H., Ramsey J. D., Rhodes C. In vitro absorption of some o-phtha-late diesters through human and rat skin. Environ. Health Perspect. 1987; 74: 223–227
   PubMed Web of Science ®Google Scholar
• Little A. D. 1982, Phthalates in consumer products. Contr. CPSC-C-80–1001. Consumer Product Safety Commission
   Google Scholar
• Rodricks J., Turnbull D. Assessment of possible carcinogenic risk resulting from exposure to di-(2-ethylhexyl)phthalate (DEHP) in children's products. Prepared for Chemical Manufacturers Association, Washington, D.C. 1984
   Google Scholar
• 1987, U.S. Department of Health and Human Services, 1983, quoted in: Bronsch, C. J. T., Untersuchungen zur Exposition und zurn renalen Ausscheidungsverhalten des Kunsstoffweichmachers Di(2-Ethylhexyl)Phthalat (DEHP) beim Menschen, Ph.D. thesis no. 8459, ETH Zürich, Switzerland
   Google Scholar
• Turnbull D., Rodricks J. V. Assessment of possible carcinogenic risk to humans resulting from exposure to di(2-ethylhexyl)phthalate (DEHP). J. Am. College Toxicol. 1985; 4: 111–145
   Google Scholar
• Bronsch C. J. T. 1987, Untersuchungen zur Exposition und zum renalen Ausscheidungsverhalten des Kunsstoffweichmachers Di(2-Ethylhexyl)Phthalat (DEHP) beirn Menschen, Ph.D. thesis, no. 8459, ETH Zürich, Switzerland
   Google Scholar
• Labow R. S., Meek E., Adams G. A., Rock G. Inhibition of human platelet phospholipidase A2 by mono(2-ethylhexyl)phthalate. Environ. Health Perspect. 1988; 78: 179–183
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Lalwani N. D. Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit. Rev. Toxicol. 1983; 12: 1–58
   PubMed Web of Science ®Google Scholar
• Albro P. W. Absorption, metabolism, and excretion of di(2-ethylhexyl) phthalate by rats and mice. Environ. Health Perspect. 1986; 65: 293–298
   PubMed Web of Science ®Google Scholar
• Albro P. W., Corbett J. T., Schroeder J. L., Jordon S., Matthews H. B. Pharmacokinetics, interactions with macromolecules, and species differences in metabolism of DEHP. Environ. Health. Perspect. 1982; 45: 19–25
   PubMed Web of Science ®Google Scholar
• Chu I., Villeneuve D. C., Secours V., Franklin C., Rock G., Viau A. Metabolism and ti distribution of mono-2-ethylhexyl phthalate in the rat. Drug Metab. Dispos. 1978; 6: 146–149
   PubMed Web of Science ®Google Scholar
• Albro P. W., Thomas R., Fishbein L. Metabolism of di-ethylhexylphthalate by rats. Isolation and characterization of the urinary metabolites. J. Chromatogr. 1973; 76: 321–330
   PubMed Web of Science ®Google Scholar
• Astill B. D. Metabolism of DEHP: effects of prefeeding and dose variation, and comparative studies in rodents and the cynomolgus monkey (CMA studies). Drug Metab. Rev. 1989; 21: 35–53
   PubMed Web of Science ®Google Scholar
• Albro P. W. Metabolism of di(2-ethylhexyl)phthalate. Drug Metab. Rev. 1989; 21: 13–34
   PubMed Web of Science ®Google Scholar
• Lake B. G., Gray T. J. B., 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Schmid P., Schlatter C. Excretion and metabolism of di-(2-ethylhexyl)phthalate in man. Xenobiotica. 1985; 15: 251–256
   PubMed Web of Science ®Google Scholar
• Dirven H. A. A.M., van den Broek P. H. H., Jongeneelen F. J. Determination of four metabolites of the plasticizer di(2-ethylhexyl)phthalate in human urine samples. Int. Arch. Occup. Environ. Health. 1993; 64: 555–560
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Peck C. C., Odorn D. G., Friedman H. T., Albro P. W., Mass J. R., Brady J. T., Tess D. Di-(2-ethylhexyl)phthalate (DEHP) and mono-(2-ethyl-hexyl)phthalate (MEHP) accumulation in whole blood and red cell concentrates. Transfusion. 1979; 19: 137–146
   PubMed Web of Science ®Google Scholar
• Albro P. W., Hass J. R., Peck C. C., Odam D. G., Corbett J. T., Bailey F. J., Blatt H. E., Barrett B. B. Identification of the metabolites of di(2-ethylhcxyl)phthalate in urine from the African Green monkey. Drug Metab. Dispos. 1979; 9: 223–225
   Web of Science ®Google Scholar
• Teirlynck O. A., Belpaire F. Disposition of orally administered di(2-ethylhexyl)phthaiate and mono-(2-ethylhexyl)phthalate in the rat. Arch. Toxicol. 1985; 57: 226–230
   PubMed Web of Science ®Google Scholar
• Pollack G. M., Li R. C. K., Ermer J. C., Shen D. D. Effects of route of administration and repetitive dosing on the disposition kinetics of di(2-ethylhexyl)phthalate and its mono-de-esterified metabolite in rats. Toxicol. Appl. Pharmacol. 1985; 79: 246–256
   PubMed Web of Science ®Google Scholar
• Elsisi A. E., Carter I. E., Sipes I. G. Dermal absorption of phthalate diesters in rats. Fundum. Appl. Toxicol. 1989; 12: 70–77
   PubMedGoogle Scholar
• Barber E. D., Teetsel N., Kolberg K. F., Guest D. A comparative study of the rates of in vitro percutaneous absorption of eight chemicals using rat and human skin. Fundam. Appl. Toxicol. 1992; 19: 493–497
   PubMedGoogle Scholar
• Tanaka A., Adachi T., Takahashi T., Yamaha T. Biochemical studies on phthalic esters. I. Elimination, distribution and metabolism of di-(2-ethyl-hexyl)phthalate in rats. Toxicology. 1975; 4: 253–264
   PubMed Web of Science ®Google Scholar
• Daniel J. W., Bratt H. The absorption, metabolism and ti distribution of di(2-ethylhexyl)phthalate in rats. Toxicology 1974; 2: 51–65
   PubMed Web of Science ®Google Scholar
• Oishi S., Hiraga K. Distribution and elimination of di-2-ethylhexyl phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) after a single oral administration of DEHP in rats. Arch. Toxicol. 1982; 51: 149–155
   Web of Science ®Google Scholar
• Oishi S. Effects of phthalic acid esters on testicular mitochondrial functions in the rat. Arch. Toxicol. 1990; 64: 143–147
   PubMed Web of Science ®Google Scholar
• Sjöberg P., Bodesson U., Gray T. J. B., Plöen L. Effects of di-(2-ethylhexyl) phthalate and five of its metabolites on rat testis in vivo and in vitro. Acta Pharmacol. Toxicol. 1986; 58: 225–233
   PubMedGoogle Scholar
• Oishi S. Effects of co-administration of di(2-ethylhexyl)phtha!ate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite. Arch. Toxicol. 1989; 63: 289–295
   PubMed Web of Science ®Google Scholar
• Sjöberg P., Bodesson U., Kjellen L., Lindquist N.-G., Montin G., Ploen L. Kinetics of di-(2-ethylhexyl) in immature and mature rats and effect on testis. Acta Pharmacol. Toxicol. 1986; 56: 30–37
   Google Scholar
• Sjöberg P., Bodesson U., Hammarlund M. Non-linearities in the pharmakokinetics of di-(2-ethyl-hexyl) phthalate in metabolites in male rats. Arch. Toxicol. 1985; 58: 72–77
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Chen W. S., Kerkay J., Pearson K. H., Paganini E. P., Nakamoto S. Tibis(2-ethyl-hexyl)phthalate levels in uremic subjects. Anal. Lett. 1979; 12: 1517–1535
   Web of Science ®Google Scholar
• Christensson A., Ljunggren L., Nilsson-Thorell C., Arge B., Diehl U., Hagstam K. E., Lundberg M. In vivo comparative evaluation of hemodialysis tubing plasticized with DEHP and TETHM. Int. J. Artif. Organs 1991; 14: 407–410
   PubMed Web of Science ®Google Scholar
• Shneider B., Cronin J., Van Marter L., Mailer E., Truog R., Jacobson M., Kevy S. A prospective analysis of cholestasis in infant supported with extracorporeal membrane oxygenation. J. Pediatr. Gastroenterol Nutr. 1991; 13: 285–289
   PubMed Web of Science ®Google Scholar
• Mes J., Coffin D. E., Campbell D. S. Di-n-butyl and di-2-ethylhexyl phthalate in human adipose ti. Bull Environ. Contam. Toxicol. 1974; 12: 721–725
   PubMed Web of Science ®Google Scholar
• Stott W. T. Chemically induced proliferation of peroxisomes. Regul. Toxicol. Pharmacol. 1988; 8: 125–159
   PubMed Web of Science ®Google Scholar
• 1992, ECETOC: Monograph No. 17, Hepatic peroxisome proliferation
   Google Scholar
• Lock E. A., Mitchell A. M., Elcombe C. R. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu. Rev. Pharmacol. Toxicol. 1989; 29: 145–163
   PubMed Web of Science ®Google Scholar
• Reubsaet F. A. G., Veerkamp J. H., Bukkens S. G. F., Trijbels J. M. F., Monnens L. A. H. Acyl-CoA oxidase activity and peroxisomal fatty acid oxidation in rat tis. Biochim. Biophys. Acta. 1988; 958: 434–442
   PubMedGoogle Scholar
• Ganning A. E., Olsson M. J., Brunk C., Dallner G. Effects of prolonged treatment with phthalate ester on rat liver. Pharmacol. Toxicol. 1991; 68: 392–401
   Google Scholar
• 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 plastieizer di(2-ethylhexyl)phthalate. Toxicol. Appl. Pharmacol. 1985; 81: 371–392
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Reddy M. K., Usman M. I., Lalwani N. D., Rao M. S. Comparison of hepatic peroxi-some proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-efhyl-hexyl)phthalate and di(2-ethylhexyl)adipate, with a hypolipidemic drug. Environ. Health Perspect. 1986; 65: 317–327
   PubMed Web of Science ®Google Scholar
• Osumi T., Hashimoto T. Enhancement of fatty acyl-CoA oxidizing activity in rat liver peroxisomes by di(2-ethylhexyl)phthalate. J. Biochem. (Tokyo) 1978; 83: 1361–1365
   PubMed Web of Science ®Google Scholar
• Khaliq M. A., Srivastava S. P. Induction of hepatic polyamines by di(2-ethylhexyl)phthalate in rats. Toxicol. Lett. 1993; 66: 317–321
   PubMed Web of Science ®Google Scholar
• Dirven H. A. A. M., van den Broek P. H. H., Jongeneelen F. J. Effect of di(2-ethylhexyl)phthalate on enzyme activity levels in liver and serum of rats. Toxicology 1990; 65: 199–207
   PubMed Web of Science ®Google Scholar
• Tomaszewski K. E., Derks M. C., Melnick R. L. Acyl CoA oxidase is the most suitable marker for hepatic peroxisomal changes caused by treatment of F344 rats with di(2-ethylhexyl)phthalate. Toxicol. Lett. 1987; 37: 203–212
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Sharma R., Lake B. G., Gibson G. G. Co-induction of microsomal cytochrome P-452 and the peroxisomal fatty acid β-oxidation pathway in the rat by clofibrate and di-(2-ethylhexyl)phthalate. Biochem. Pharmacol. 1988; 37: 1203–1206
   PubMed Web of Science ®Google Scholar
• Dirven H. A. A. M., van den Broek P. H. H., Peters J. G. P., Noordhoek J., Jongeneelen F. J. Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P-450 inducers and peroxisome proliferating compounds. Biochem. Pharmacol. 1992; 43: 2621–2629
   PubMed Web of Science ®Google Scholar
• Dirven H. A. A.M., de Bruijn A. A. G.M., Sessink P. J. M., Jongeneelen F. J. Determination of the cytochrome P-450 IV marker, omega-hydroxy-lauric acid, by high-performance liquid chromatogra-phy and fluorimetric detection. J. Chromatogr. 1991; 564: 266–271
   PubMed Web of Science ®Google Scholar
• 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 two years. Cancer Lett. 1987; 38: 15–22
   PubMed Web of Science ®Google Scholar
• Barber E. D., Astill B. D., Moran E. J., Schneider B. F., Gray T. J. B., Lake B. G., Evans J. G. Peroxisome induction studies on seven phthalate esters. Toxicol. Ind. Health 1987; 3: 7–24
   PubMed Web of Science ®Google Scholar
• Ochs J. B. L. A. B., Leonard D. A., Calabrese E. J. Effects of joint exposures to selected peroxisome proliferators on hepatic acyl-CoA oxidase activity in male B6C3F1 mice. Hum. Exp. Toxicol. 1992; 11: 83–88
   PubMed Web of Science ®Google Scholar
• Tomaszewski K. E., Montgomery C. A., Melnick R. L. Modulation of 2, 3, 7, 8-tetrachloridi-benzo-p-dioxin toxicity in F344 rats by di(2-ethyl-hexyl)phthalate. Chem. Biol. Interact. 1988; 65: 205–222
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Tamura H., Iida T., Watanabe T., Suga T. Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats. Carcinogenesis 1990; 11: 445–450
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Ganning A. E., Dallner G. Induction of peroxisomes and mitochondria by di(2-ethylhexyl)phthalate. FEBS Lett. 1981; 130: 77–79
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Cattley R. C., Smith-Oliver T., Butterworth B. E., Popp J. A. Failure of the peroxisome proliferator WY-14,643 to induce unscheduled DNA synthesis in rat hepatocytes following in vivo treatment. Carcinogenesis 1988; 9: 1179–1183
   PubMed Web of Science ®Google Scholar
• 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, immunohistochemi-cal, and biochemical evidence for levels of DNA synthesis not associated with carcinogenesis or tumor promotion. Toxicol. Appl. Pharmacol. 1988; 96: 494–506
   PubMed Web of Science ®Google Scholar
• Nixon J., Jackson S. J. 1982, Bis(2-ethylhexyl)-phthalate: a comparative subacute toxicity study in the rat and marmoset. Tech. Rep. No. CTL/P/690. Prepared for CEFIC (European Council of the Federation of the Chemical Industry)
   Google Scholar
• Elliott B. M., Elcombe C. R. Lack of DNA damage or lipid peroxidation measured in vivo in the rat liver following treatment with peroxisome proliferators. Carcinogenesis 1987; 8: 1213–1287
   PubMed Web of Science ®Google Scholar
• Tomaszewski K. E., Agarwal D. K., Melnick R. L. In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and female B6C3F1 mice to hepatic peroxisome proliferators. Carcinogenesis 1986; 7: 1871–1876
   PubMed Web of Science ®Google Scholar
• Elliott B. M., Dodd N. J. F., Elcombe C. R. Increased hydroxyl radical production in peroxisomal fractions from rats treated with peroxisome proliferators. Carcinogenesis. 1986; 7: 795–799
   PubMed Web of Science ®Google Scholar
• Badr M. Z. Induction of peroxisomal enzyme activities bi di-(2-ethylhexyl)phthalate in thyroid-ectomized rats with parathyroid replants. J. Pharmacol. Exp. Ther. 1992; 263: 1105–1110
   PubMed Web of Science ®Google Scholar
• Sharma R., Lake B. G., Foster J. G. G. G. Microsomal cytochrome P-452 induction and peroxisome proliferation by hypolipidemic agents in rat liver. A mechanistic inter-relationship. Biochem. Pharmacol. 1988; 37: 1193–1201
   PubMed Web of Science ®Google Scholar
• Okita R. T., Rice Okita J. Characterization of a cytochrome P450 from di(2-ethylhexyl) phthalate-treated rats which hydroxylates fatty acids. Arch. Biochem. Biophys. 1992; 294: 475–481
   PubMed Web of Science ®Google Scholar
• Nair N., Kurup R. A comparative study of the effects of administration of diethylhexyl phthalate on hepatic mitochondria of the rat and the mouse. Indian J. Biochem. Biophys. 1986; 23: 270–273
   PubMed Web of Science ®Google Scholar
• Nair N., Kurup R. Are the hypocholesterolaemic action and metabolic effects of diethylhexyl phthalate mediated by thyroxine?. Indian J. Biochem. Biophys. 1986; 23: 76–79
   PubMed Web of Science ®Google Scholar
• Yanagita T., Satoh M., Nomura H., Enomoto N., Sugano M. Alteration of hepatic phospholipids in rats and mice by feeding di-(2-ethylhexyl)adipate and di-(2-ethylhexyl)phthalate. Lipids. 1987; 22: 572–577
   PubMed Web of Science ®Google Scholar
• Lake B. G., Gray T. J. B., Gangolli S. D. Hepatic effects of phthalate esters and related compounds — in vivo and in vitro correlations. Environ. Health Perspect. 1986; 67: 283–290
   PubMed Web of Science ®Google Scholar
• Reubsaet F. A. G., Veerkamp J. H., Dirven H. A. A.M., Brückwilder M. L. P., Hashimoto T., Trijbels J. M. F., Monnens L. A. H. The effect of di(ethylhexyl) phthalate on fatty acid oxidation and carnitine palmitoyltransferase in various rat tis. Biochim. Biophys. Acta 1990; 1047: 264–270
   PubMedGoogle Scholar
• Reubsaet F. A. G., Veerkamp J. H., Dirven H. A. A. M., Brückwilder M. L. P., Trijbels J. M. F., Monnens L. A. H. Peroxisomal oxi-dases and catalase in liver and kidney homogenates of normal and di(ethylhexyl)phthalate-fed rats. Int. J. Biochem. 1991; 23: 961–967
   PubMedGoogle Scholar
• Ghesquier D., Cook L., Nagi M. N., MacAlister T. J., Cinti D. L. Source of the hepatic microsomal trans-2-enoyl CoA hydratase bifunctional pro-tein: endoplasmic reticulum or peroxisomes. Arch. Biochem. Biophys. 1987; 252: 369–381
   PubMed Web of Science ®Google Scholar
• Kawashima Y., Nakagawa S., Tachibana Y., Kozuka H. Effects of peroxisome proliterators on fatty acid-binding protein in rat liver. Biochim. Biophys. Acta. 1983; 754: 21–27
   PubMedGoogle Scholar
• Kawashima Y., Matsunaga T., Hirose A., Ogata T., Kozuka H. Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliterators in rat kidney; co-induction with peroxisomal β-oxidation. Biochim. Biophys. Acta 1989; 1006: 214–218
   PubMedGoogle Scholar
• Hodgson J. R. Results of peroxisome induction studies on tri(2-ethylhexyl)-trimellitate and 2-ethylhexanol. Toxicol. Ind. Health 1987; 3: 49–61
   PubMed Web of Science ®Google Scholar
• Topping D. C., Ford G. P., Evans J. G., Lake B. G., O'Donoghue J. L., Lockhart H. B. J. Peroxisome induction studies on di(2-ethylhexyl)-terephthalate. Toxicol. Ind. Health 1987; 3: 63–77
   PubMedGoogle Scholar
• Takagi A., Sai K., Umemura T., Hasegawa R., Kurokawa Y. Hepatomegaly is an early biomarker for hepatocarcinogenesis induced by peroxisome proliterators. J. Environ. Pathol. Toxicol. Oncol. 1992; 11: 145–149
   PubMedGoogle Scholar
• Butterworth B. E., Bermudez E., Smith-Oliver T., Earle L., Cattley R., Martin J., Popp J. A., Strom S., Jirtle R., Michalopoulos G. Lack of genotoxic activity of di(2-ethylhexyl)phthalate (DEHP) in rat and human hepatocytes. Carcinogenesis 1984; 5: 1329–1335
   PubMed Web of Science ®Google Scholar
• Rao M. S., Yeldandi A. V., Subbarao V. Quantitative analysis of hepatocellular lesions induced by di(2-ethylhexyl)phthalate in F-344 rats. J. Toxicol. Environ. Health 1990; 30: 85–89
   PubMed Web of Science ®Google Scholar
• Osumi T., Hashimoto T. Subcellular distribution of the enzymes of the fatty acyl-CoA β-oxidation system and their induction by di(2-ethylhexyl) phthalate in rat liver. J. Biochem. (Tokyo) 1979; 85: 131–139
   PubMed Web of Science ®Google Scholar
• Lake B. G. L. K. S., Evans J. G., Gray T. J. B., Young P. J., Gangolli S. D. Effect of prolonged administration of clofibric acid and di(2-ethyl-hexyl)phthalate on hepatic enzyme activities and lipid peroxidation in the rat. Toxicology 1987; 44: 213–228
   PubMed Web of Science ®Google Scholar
• Jayaraman S., Anila Kumar K. R., Rama Rao M. V. Di-2-ethylhexylphthalate induced peroxtdative stress in rat liver. Bull. Environ. Contam. Toxicol. 1988; 41: 360–364
   PubMed Web of Science ®Google Scholar
• 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 rats and mice. Life Sci. 1976; 18: 941–946
   PubMed Web of Science ®Google Scholar
• Hashimoto T. Individual peroxisomal β-oxidation enzymes. Ann. N.Y. Acad. Sci. 1982; 386: 5–12
   PubMed Web of Science ®Google Scholar
• Gibson G. G., Orton T. C., Tamburini P. P. Cytochrome P-450 induction by clofibrate. Purification of a hepatic cytochrome P-450 relatively specific for the 12- and 11-hydroxylation of dodecanoic acid (lauric acid). Biochem. J. 1982; 203: 161–168
   PubMed Web of Science ®Google Scholar
• Tamburini P. P., Masson H. A., Bains S. K., Makowski R. J., Morris B., Gibson G. G. Multiple forms of hepatic cytochrome P-450. Purification, characterisation and comparison of a novel clofibrate-induced isozyme with other major forms of cytochrome P-450. Eur. J. Biochem. 1984; 139: 235–246
   PubMedGoogle Scholar
• Sundseth S. S., Waxman D. J. Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Male specificity of liver and kidney CYP4A2 mRNA and ti-specific regulation by growth hormone and testosterone. J. Biol. Chem. 1992; 267: 3915–3921
   PubMed Web of Science ®Google Scholar
• Okita J. R., Castle P. J., Okita R. T. Characterization of cytochromes P450 in liver and kidney of rats treated with di(2-ethylhexyl)phthalate. J. Biochem. Toxicol. 1993; 8: 135–144
   PubMedGoogle Scholar
• Levine W. G., Ord M. G., Stocken L. A. Some biochemical changes associated with nafenopin-induced liver growth in the rat. Biochem. Pharmacol. 1977; 26: 939–942
   PubMed Web of Science ®Google Scholar
• Moody D. E., Rao M. S., Reddy J. K. Mito-genic effect in mouse liver induced by a hypolipidemic drug, nafenopin. Virchows Arch. [B] 1977; 23: 291–296
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Butterworth B. E., Loury D. J., Smith-Oliver T., Cattley R. C. The potential role of chemically-induced hyperplasia in the carcinogenic activity of the hypolipidemic carcinogens. Toxicol. Ind. Health 1987; 3: 129–149
   PubMed Web of Science ®Google Scholar
• I-Kuei Lin L. The use of multivariate analysis to compare peroxisome induction data on phthalate esters in rats. Toxicol. Ind. Health 1987; 3: 25–47
   PubMed Web of Science ®Google Scholar
• Wada N., Marsman D. S., Popp J. A. Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication. Fundam. Appl. Toxicol. 1992; 18: 149–154
   PubMedGoogle Scholar
• Bieri F., Staeubli W., Waechter F., Muakkassah-Kelly S., Bentley P. Stimulation of DNA synthesis but not of peroxisomal β-oxidation by nafenopin in primary cultures of marmoset hepatocytes. Cell Biol. Int. Rep. 1988; 12: 1077–1087
   PubMedGoogle Scholar
• Dwivedi R. S., Alvares K., Nemali M. R., Subbarao V., Reddy M. K., Usman M. I., Rademaker A. W., Reddy J. K., Rao M. S. Comparison of the peroxisome proliferator-induced pleiotropic response in the liver of nine strains of mice. Toxicol Pathol. 1989; 17: 16–26
   PubMed Web of Science ®Google Scholar
• Budroe J. D., Umemura T., Angeloff K., Williams G. M. Dose-response relationships of hepatic acyl-CoA oxidase and catalase activity and liver mitogenesis induced by the peroxisome proliferator ciprofibrate in C57BL/6N and BALB/c mice. Toxicol. Appl. Pharmacol. 1992; 113: 192–198
   PubMedGoogle Scholar
• Kraupp-Grasl B., Huber W., Just W., Gibson G., Schulte-Hermann R. Enhancement of peroxisomal enzymes, cytochrome P-452, and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin. Carcinogenesis 1993; 14: 1007–1012
   PubMed Web of Science ®Google Scholar
• Grasl-Kraupp B., Huber W., Timmermann-Trosiener I., Schulte-Hermann R. Peroxisomal enzyme induction uncoupled from enhanced DNA synthesis in putative preneoplastic liver foci of rats treated with a single dose of the peroxisome proliferator nafenopin. Carcinogenesis 1993; 14: 2435–2437
   PubMedGoogle Scholar
• Lake B., Evans J. G., Gray T. J. B., Körösi S. A., North C. J. Comparative studies on nafenopin-induced hepatic peroxisome proliferation in the rat, Syrian hamster, guinea pig, and marmoset. Toxicol. Appl. Pharmacol. 1989; 99: 148–160
   PubMed Web of Science ®Google Scholar
• Gibson G. G., Lake B. G. Induction protocols for the cytochrome P450IVA subfamily in animals and primary hepatocyte cultures. Methods Enzymol. 1991; 206: 353–364
   PubMed Web of Science ®Google Scholar
• Huber W., Kraupp-Grasl B., Esterbauer H., Schulte-Hermann R. Role of oxidative stress in age dependent hepatocarcinogenesis by the peroxisome proliferator nafenopin in the rat. Cancer Res. 1991; 51: 1789–1792
   PubMed Web of Science ®Google Scholar
• Huber W. W., Kraupp-Grasl B., Gschwentner C. Influence of circadian rhythm, feeding rhythm and fat charge on lipid peroxidation under peroxisome proliferation by nafenopin (abstract). Naunyn-Schmiedebergs Arch. Pharmacol. 1992; 345(Suppl. 153)
   Google Scholar
• Eacho P. I., Lanier T. L., Brodhecker C. A. Hepatocellular DNA synthesis in rats given peroxisome proliferating agents: comparison of WY-14,643 to clofibric acid, nafenopin and LY171883. Carcinogenesis 1991; 12: 1557–1561
   PubMed Web of Science ®Google Scholar
• Makowska J. M. C. A., Goldfarb P. S., Bonner F., Bonner G. G. G. Characterization of the hepatic responses to the short-term administration of ciprofibrate in several rat strains. Biochem. Pharmacol. 1990; 40: 1083–1093
   PubMed Web of Science ®Google Scholar
• Lake B. G., Gray T. J. B., Lewis D. F. V., Beamand J. A., Hodder K. D., Purchase R., Gangolli S. D. Structure-activity relationships for induction of peroxisomal enzyme activities by phthalate monoesters in primary rat hepatocyte cultures. Toxicol. Ind. Health 1987; 3: 165–183
   PubMed Web of Science ®Google Scholar
• Mitchell F. E., Bridges J. W., Hinton R. H. Effects of mono (2-ethylhexyl) phthalate and its straight chain analogues mono-n-hexylphthalate and mono-n-octylphthalate on lipid metabolism in isolated hepatocytes. Biochem. Pharmacol. 1986; 35: 2941–2947
   PubMedGoogle Scholar
• Mann A. H., Price S. C., Mitchell F. E., Grasso P., Hinton R. H., Bridges J. W. Comparison of the short-term effects of di(2-ethylhexyl) phthalate, di(n-hexyl) phthalate, and di(n-octyl) phthalate in rats. Toxicol. Appl. Pharmacol. 1985; 77: 116–132
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., Lake B. G., Beamand J. A., Foster J. R., Gangolli S. D. Peroxisomal effects of phthalate esters in primary cultures of rat hepatocytes. Toxicology 1983; 28: 167–179
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Yeldandi A. V., Milano M., Subbarao V., Reddy J. K., Rao M. S. Evaluation of liver cell proliferation during ciprofibrate-induced hepatocarcinogen-esis. Cancer Lett. 1988; 47: 21–27
   Google Scholar
• Barrass N. C., Price R. J., Lake B. G., Orton T. C. Comparison of the acute and chronic mitogenic effects of the peroxisome proliferators methylclofena-pate and clofibric acid in rat liver. Carcinogenesis 1993; 14: 1451–1456
   PubMed Web of Science ®Google Scholar
• Pill J., Völkl A., Hartig F., Fahimi H. D. Differences in the response of Sprague-Dawley and Lewis rats to bezafibrate: the hypolipidemic effect and the induction of peroxisomal enzymes. Arch. Taxicol. 1992; 66: 327–333
   PubMed Web of Science ®Google Scholar
• Pacot C., Petit M., Caira F., Rollin M., Behechti N., Gregoire S., Malki M. C., Cavatz C., Moisant M., Moreau C., Thomas C., Descotes G., Gallas J.-F., Deslex P., Althoff J., Zahnd J.-P., Lhuguenot J.-C, Latruffe N. Response of genetically obese Zucker rats to ciprofibrate, a hypolipidemic agent, with peroxisome proliferation activity as compared to Zucker lean and Sprague-Dawley rats. Biol. Cell 1993; 77: 27–35
   PubMedGoogle Scholar
• Lundgren B., DePierre J. W. Proliferation of peroxisomes and induction of cytosolic and microso-mal epoxide hydrolase in different strains of mice and rats after dietary treatment with clofibrate. Xenobiotica 1989; 19: 867–881
   PubMed Web of Science ®Google Scholar
• DeAngelo A. B., Daniel F. B., McMillan L., Wemsing P., Savage R. E., Jr. Species and strain sensitivity to the induction of peroxisome proliferation by chloroacetic acids. Toxicol. Appl. Pharmacol. 1989; 101: 285–298
   PubMed Web of Science ®Google Scholar
• Biegel L. B., Hurtt M. E., Frame S. R., Applegate M., O'Connor J. C., Cook J. C. Comparison of the effects of Wyeth-14,643 in Crl:CD BR and Fisher-344 rats. Fundam. Appl. Toxicol. 1992; 19: 590–597
   PubMedGoogle Scholar
• Nourooz-Zadeh J., Winder B. S., Dietze E. C., Giometti C. S., Tollaksen S. L., Hammock B. D. Biochemical characterization of a variant form of cytosolic epoxide hydrolase induced by parental exposure toN-ethyl-n-nitrosurea. Comp. Biochem. Physiol. [C] 1992; 103: 207–214
   PubMed Web of Science ®Google Scholar
• Butler E. G., England P. J., Williams G. M. Genetic differences in enzymes associated with peroxisome proliferation and hydrogen peroxide metabolism in inbred mouse strains. Carcinogenesis 1988; 9: 1459–1463
   PubMed Web of Science ®Google Scholar
• Small G. M., Burdett K., Connock N. V. Clofibrate-induced changes in enzyme activities in liver, kidneys, and small intestine of male mice. Ann. N.Y. Acad. Sci. 1982; 386: 460–463
   Web of Science ®Google Scholar
• Issemann I., Issemann S. G. Activation of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347: 645–650
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Azarnoff D. K., Hignite C. E. Hypolipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 1980; 283: 397–398
   PubMed Web of Science ®Google Scholar
• Jäckh R., Rhodes C., Grasso P., Carter J. T. Genotoxicity studies on di-(2-ethylhexyl) phthalate and toxicity studies on di-(2-ethyl-hexyl)phtha!ate in the rat and marmoset. Food. Chem. Toxicol. 1984; 22: 151–155
   PubMed Web of Science ®Google Scholar
• Cerutti P. A. Prooxidant states and tumor promotion. Science 1985; 227: 375–381
   PubMed Web of Science ®Google Scholar
• Schulte-Hermann R. A review: tumor promotion in the liver. Arch. Toxicol. 1985; 57: 147–158
   PubMed Web of Science ®Google Scholar
• Schulte-Hermann R., Timmermann Trosiener I., Barthel G., Bursch W. DNA synthesis, apop-tosis, and phenotypic expression as determinants of growth of altered foci in rat liver during phenobarbital promotion. Cancer Res. 1990; 50: 5127–5135
   PubMed Web of Science ®Google Scholar
• Marsman D. S., Barrett J. C. Apoptosis and chemical carcinogenesis. Risk. Anal. 1994; 14: 321–326
   PubMedGoogle Scholar
• Kikuta Y., Kusunose E., Okumoto T., Kubota I., Kusunose M. Purification and characterization of two forms of cytochrome P-450 with omega-hydroxylase activities toward prostaglandin A and fatty acids from rabbit liver microsomes. J. Biochem. (Tokyo) 1990; 107: 280–286
   PubMed Web of Science ®Google Scholar
• Makowska J. M., Bonner F. W., Gibson G. G. Comparative action of cytochrome P450IVAI and peroxisome proliferation by ciprofibrate in the rat and marmoset. Arch. Toxicol. 1991; 65: 106–113
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Lalwani N. D., Qureshi S. A., Reddy M. K., Moehle C. M. Induction of hepatic peroxisome proliferation in nonrodent species, including primates. Am. J. Pathol. 1984; 114: 171–183
   PubMed Web of Science ®Google Scholar
• Makowska J. M., Gibson G. G., Bonner F. W. Species differences in ciprofibrate induction of hepatic cytochrome P450 4A1 and peroxisome proliferation. J. Biochem. Toxicol 1992; 7: 183–191
   PubMedGoogle Scholar
• Orton T. C., Adam H. K., Bentley M., Holloway B., Tucker M. J. Clobuzarit: species differences in the morphological and biochemical response of the liver following chronic administration. Toxicol. Appl. Pharmacol. 1984; 73: 138–151
   PubMed Web of Science ®Google Scholar
• Blane G. F., Pinaroli F. Fenofibrate: etudes de toxicologie animal en rapport avec les effets secondaires chez les malades. Presse Med. 1980; 9: 3737–3746
   Google Scholar
• Orton T. C., Parker G. L. 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. 1982; 10: 110–115
   PubMed Web of Science ®Google Scholar
• Holloway B. R., Thorp J. M. Analytical sub-cellular fractionation and enzymic analysis of liver homogenates from control and clofibrate-treated rats, mice and monkeys with reference to the fatty acidoxidizing enzymes. Ann. N.Y. Acad. Sci. 1982; 386: 453–455
   Google Scholar
• Reddy M. K., Lalwani N. D., Qureshi S. A., Reddy J. K. Induction of hamster hepatic peroxiso-mal beta-oxidation and peroxisome proliferation associated 80,000 mol. wt. polypeptide by hypolipidemic drugs. Hum. Toxicol. 1982; 1: 135–147
   PubMedGoogle Scholar
• Pourbaix S., Heller F., Harvengt C. Effect of fenofibrate and LF 2151 on hepatic peroxisomes in hamsters. Biochem. Pharmacol. 1984; 33: 3661–3666
   PubMed Web of Science ®Google Scholar
• Gray R. H., De la Iglesia F. A. Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species. Hepatology 1984; 4: 520–530
   PubMed Web of Science ®Google Scholar
• Eacho P. I., Foxworthy P. S., Johnson W. D., Hoover D. M., White S. L. Hepatic peroxiso-mal changes induced by a tetrazole-substituted alkoxyacetophenone in rats and comparison with other species. Toxicol. Appl. Pharmacol. 1986; 83: 430–437
   PubMed Web of Science ®Google Scholar
• Styles J. A., Kelly M., Pritchard N. R., Elcombe C. R. A species comparison of acute hyperplasia induced by the peroxisome proliferator methylclofenapate: involvement of the binucleated hepatocyte. Carcinogenesis 1988; 9: 1647–1655
   PubMedGoogle Scholar
• Platt D. S., Thorp J. M. Changes in the weight and composition of the liver in the rat, dog and monkey treated with ethyl chlorophenoxyisobutyrate. Biochem. Pharmacol. 1966; 15: 915–925
   PubMed Web of Science ®Google Scholar
• Svoboda D., Grady H., Azarnoff D. Microbodies in experimentally altered cells. J. Cell Biol. 1967; 35: 127–152
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Jirtle R. L., Watanabe T. K., Reddy N. K., Michalopoulos G., Qureshi S. A. Response of hepatocytes transplanted into syngeneic hosts and heterotransplanted into athymic nude mice to peroxisome proliferators. Cancer Res. 1984; 44: 2582–2589
   PubMed Web of Science ®Google Scholar
• Jirtle R. L., Reddy J. K., Michalopoulos G. Induction of peroxisome proliferation in transplanted dog, cat, rat, and human hepatocytes. AACR Abstracts 1984; 25: 117
   Google Scholar
• Hanefeld M., Kemmer C., Leonhardt W., Kunze K. D., Jaross W., Haller H. Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. Atherosclerosis 1980; 36: 159–172
   PubMed Web of Science ®Google Scholar
• Hanefeld M., Kemper C., Kadner E. Relationship between morphological changes and lipid-lowering action of p-chlorophenoxyisobutyric acid (CPIB) on hepatic mitochondria and peroxisomes in man. Atherosclerosis 1983; 46: 239–246
   PubMed Web of Science ®Google Scholar
• De La Iglesia F. A. L. J. E., Buchanan R. A., Marcus E. L., McMahon G. Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment. Atherosclerosis 1982; 43: 19–37
   PubMed Web of Science ®Google Scholar
• Blümcke S., Schwartzkopff W., Lobeck H., Edmondson N. A., Prentice D. E., Blane G. F. Influence of fenofibrate on cellular and subcellular liver structure in hyperlipidemic patients. Atherosclerosis 1983; 46: 105–116
   PubMed Web of Science ®Google Scholar
• Gariot P., Barrat E., Mejean L., Pointel J. P., Drouin P., Debry G. Fenofibrate and human liver — lack of proliferation of peroxisomes. Arch. Toxicol. 1983; 53: 151–163
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Hinton R. H., Price S. C., Grasso P. 1991, as cited in ECETOC: Monograph No. 17, Hepatic peroxisome proliferation
   Google Scholar
• Ishii H., Fukumori N., Horie S., Suga T. Effects of fat content in the diet on hepatic peroxisomes of the rat. Biochim. Biophys. Acta 1980; 617: 1–11
   PubMed Web of Science ®Google Scholar
• Christiansen E. N., Flatmark T., Kryvi H. Effects of marine oil diet on peroxisomes and mitochondria of rat liver: a combined biochemical and morphometric study. Eur. J. Cell Biol. 1981; 26: 11–20
   PubMed Web of Science ®Google Scholar
• Bronfman M., Inestrosa N. C., Leighton F. Fatty acid oxidation by human liver peroxisomes. Biochem. Biophys. Res. Commun. 1979; 88: 1030–1036
   PubMedGoogle Scholar
• Büsser M.-T., Lutz W. K. Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters. Carcinogenesis 1987; 8: 1433–1437
   PubMedGoogle Scholar
• Makowska J. M., Bonner F. W., Gibson G. G. Hepatic induction potency of hypolipidaemic drugs in the rat following long-term administration: influence of different dosing regimens. Xenobiotica 1990; 20: 1121–1128
   PubMed Web of Science ®Google Scholar
• Kawashima Y., Hirose A., Hirose Y., Adachi T., Kozuka H. Inducing effects of clofibric acid on 1-acylglycerophosphorylcholine acyltransferase in kidney and intestinal mucosa of rats. Biochim. Biophys. Acta 1986; 875: 549–553
   PubMedGoogle Scholar
• Oesch F., Hartmann R., Timms C., Strolin-Benedetti M., Dostert P., Wörner W., Schladt L. Time dependence and differential induction of rat and guinea pig peroxisomal β-oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxide hydrolase after treatment with hypolipidemic drugs. J. Cancer Res. Clin. Oncol. 1988; 114: 341–346
   PubMed Web of Science ®Google Scholar
• Frick H., Elo O., Haapa K., Heinonen O. P., Heinsalmi P., Helo P., Huttunen J. K., Kaitaniemi P., Koskinen P., Manninen V., Mäenpää H., Mälkönen M., Mänttäri M., Norola S., Pasternack A., Pikkarainen J., Romo M., Sjöblom T., Nikkiä E. A. 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: 1235–1247
   Web of Science ®Google Scholar
• Fitzgerald J. E., Sanyer J. L., Schardein J. L., Lake R. S. E. J., M., Lake F. A. D. I.I. Carcinogen bioassay and mutagenicity studies with the hypolipidemic agent gemfibrozil. J. Natl. Cancer Inst. 1981; 67: 1105–1116
   PubMed Web of Science ®Google Scholar
• Pill J., Wolff S., Stegmeier K., Schmidt F. H. Effect of bezafibrate on serum lipids in normo- and spontaneously hyperlipidemic rats. Methods Find. Exp. Clin. Pharmacol. 1988; 10: 487–492
   PubMedGoogle Scholar
• Mitchell A. M., Bridges J. W., Elcombe C. R. Factors influencing peroxisome proliferation in cultured rat hepatocytes. Arch. Toxicol. 1984; 55: 239–246
   PubMedGoogle Scholar
• Garberg P., Högberg J. Selenium metabolism in isolated hepatocytes: inhibition of incorporation in proteins by mono(2-ethylhexyl)phthalate, a metabolite of the peroxisome proliferator di(2-ethylhexyl)-phthalate. Carcinogenesis 1991; 12: 7–12
   PubMedGoogle Scholar
• Foxworthy P. S., Eacho P. I. Conditions influencing the induction of peroxisomal β-oxidation in cultured rat hepatocytes. Toxicol. Lett. 1986; 30: 189–196
   PubMedGoogle Scholar
• Feller D. R. S.Y., Shirhatti V. R., Kocarek T. A., Liu C.-T., Krisna G. Characterization of ciprofibrate and clofibric acid as peroxisomal proliferators in primary cultures of rat hepatocytes. Hepatology 1987; 7: 508–516
   PubMed Web of Science ®Google Scholar
• Muakkassah-Kelly S. F., Bieri F., Waechter F., Bentley P., Stäubli W. Long-term maintenance of hepatocytes in primary culture in the presence of DMSO. Further characterization and effect of nafenopin, a peroxisome proliferator. Exp. Cell Res. 1987; 171: 37–51
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• Butterworth B. E., Smith-Oliver T., Earle L., Lowry J. J., White R. D., Doolittle D. J., Working P. K., Cattley R. C., Jirtle R., Michalopoulos G., Strom S. S. Use of primary cultures of human hepatocytes in toxicology studies. Cancer Res. 1989; 49: 1075–1084
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., 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
   PubMed Web of Science ®Google Scholar
• Watanabe T., Okawa S., Itoga H., Imanaka T., Suga T. Involvement of calmodulin- and protein kinase C-related mechanism in an induction process of peroxisomal fatty acid oxidation-related enzymes by hypolipidemic peroxisome proliferators. Biochim. Biophys. Acta 1992; 1135: 84–90
   PubMedGoogle Scholar
• Elcombe C. R., Mitchell A. M. Peroxisome proliferation due to di(2-ethylhexyl)phthalate (DEHP): species differences and possible mechanisms. Environ. Health Perspect. 1986; 70: 211–219
   PubMed Web of Science ®Google Scholar
• Dirven H. A. A.M., Van den Broek P. H. H., Peeters M. C. E., 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. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies. Biochem. Pharmacol. 1993; 45: 2425–2434
   PubMed Web of Science ®Google Scholar
• Garberg P., Högberg J. Studies on Se incorporation in selenoproteins; effects of peroxisome proliferators and hydrogen peroxide generating system. Chem. Biol. Interact. 1992; 81: 291–306
   PubMedGoogle Scholar
• Lake B. G., Gray T. J. B., Pels-Rijcken W. R., Beamand J. A., Gangolli S. D. The effect of hypolipidemic agents on peroxisomal β-oxidation and mixed function oxidase activities in primary cultures of rat hepatocytes. Relationship between induction of palmitoyl-CoA oxidation and lauric acid hydroxyla-tion. Xenobiotica 1984; 14: 269–276
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., 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
   PubMed Web of Science ®Google Scholar
• Lake B. G., Lewis D. F. V., Gray T. J. B., Beamand J. A. Structure-activity relationship for induction of peroxisomal enzyme activities in primary rat hepatocyte cultures. Toxicol. in Vitro 1993; 7: 605–614
   PubMed Web of Science ®Google Scholar
• Bieri F., Muakkassah-Kelly S., Waechter F., Stäubli W. Use of primary cultures of adult rat hepatocytes to study the mode of action of the peroxisome proliferator nafenopin. Peroxisomes in Biology and Medicine, H. D. Fahimi, H. Sies. Springer-Verlag, Berlin, Heidelberg 1986; 286–294
   Google Scholar
• Bieri F., Bentley P., Waechter F., Stäubli W. Use of primary cultures of adult rat hepatocytes to investigate mechanisms of action of nefenopin, a hepatocarcinogenic peroxisome proliferator. Carcinogenesis 1984; 5: 1033–1039
   PubMed Web of Science ®Google Scholar
• Muakassah-Kelly S. F., Bieri F., Waechter F., Bentley P., Stäubli W. The use of primary cultures of adult rat hepatocytes to study induction of enzymes and DNA synthesis: effect of nafenopin and electroporation. Experientia 1988; 44: 823–827
   PubMedGoogle Scholar
• Bichet N., Cahard D., Fabre G., Remandet B. D. G., Cano J. P. Toxicological studies on a benzofuran derivative. III. Comparison of peroxisome proliferation in rat and human hepatocytes in primary culture. Toxicol. Appl. Pharmacol. 1990; 106: 509–517
   PubMedGoogle Scholar
• Mitchell A. M., Lhuguenot J. C., Bridges J. W., Elcombe C. R. Identification of the proximate peroxisome proliferator(s) derived from di(2-ethylhexyl)phthalate. Toxicol. Appl. Pharmacol. 1985; 80: 23–32
   PubMed Web of Science ®Google Scholar
• Allen K. L., Green C. E., Tyson C. A. Comparative studies of peroxisomal enzyme induction in hepatocytes from rat, cynomolgus monkey and human by hypolipidemic drugs (Abstract). Toxicologist 1987; 7: 253
   Google Scholar
• Blaauboer B. J., van Holsteijn C. W. M., Bleumink R., Mennes W. C., van Pelt F. N. M.A., Yap S. H., van Pelt J. F., van Iersel A. A. J. Timmerman, A., and Schmid, B. P., The effect of beclobric acid and clofibric acid on peroxiso-mal β-oxidation and peroxisome proliferation in primary cultures of rat, monkey and human hepa-tocytes. Biochem. Pharmacol. 1990; 40: 521–528
   PubMed Web of Science ®Google Scholar
• Parzefall W., Erber E., Sedivy R., Schulte-Hermann R. Testing for induction of DNA synthesis in human hepatocyte primary cultures by rat liver tumor promoters. Cancer Res. 1991; 51: 1143–1147
   PubMed Web of Science ®Google Scholar
• Mikalsen S. O., Holen I., Sanner T. Morphological transformation and catalase activity of Syrian hamster embryo cells treated with hepatic peroxisome proliferators, TPA and nickel sulphate. Cell Biol. Toxicol. 1990; 6: 1–13
   PubMedGoogle Scholar
• Mikalsen S.-O., Ruyter B., Sanner T. Effects of hepatic peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on catalase and other enzyme activities of embryonic cells in vitro. Biochem. Pharmacol. 1990; 39: 527–535
   PubMedGoogle Scholar
• Phillips B. J., Anderson D., Gangolli S. D. Studies on the genetic effects of phthalic acid esters on cells in culture. Environ. Health Perspect. 1986; 65: 263–266
   PubMed Web of Science ®Google Scholar
• Glauert H. P., Hennig B., Chow H. S. Induction of peroxisomal enzymes in cultured porcine en-dothelial cells by the hypolipidemic drug ciprofibrate. J. Biochem. Toxicol. 1990; 5: 115–118
   PubMedGoogle Scholar
• Berg R. K., Lillehaug J. R. Tiadenol-mediated induction of peroxisomal enzymes in cultured C3H/ 10T1/2CL8 cells and in chemically transformed C3H/ 10T1/2MCA16 cells. Int. J. Cancer 1985; 36: 489–494
   PubMedGoogle Scholar
• Lillehaug J. R., Berge R. K. The tumour promoter 12-O-tetradecanoylphorbol-13-acetate increases the activities of some peroxisome associated enzymes in in vitro cell culture. Br. J. Cancer 1986; 53: 121–127
   PubMedGoogle Scholar
• Lhuguenot J.-C, Mitchell A. M., Milner G., Lock E. A., Elcombe C. R. The metabolism of di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism. Toxicol. Appl. Pharmacol. 1985; 80: 11–22
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Behrens M. I., Soza M. A., Inestrosa N. C. Increase of muscle peroxisomal enzymes and myotonia induced by nafenopin, a hypolipidemic drug. Muscle Nerve 1983; 6: 154–159
   PubMedGoogle Scholar
• Sharma R. K., Lake B. G., Makowski R., Bradshaw T., Earnshaw D., Dale J. W., Gibson G. G. Differential induction of peroxisomal and microsomal fatty-acid-oxidising enzymes by peroxisome proliferators in rat liver and kidney, characterisation of a renal cytochrome P-450 and implications for peroxisome proliferation. Eur. J. Biochem. 1989; 184: 69–78
   PubMedGoogle Scholar
• Nemali M. R., Usuda N., Reddy M. K., Oyasu K., Hashimoto T., Osumi T., Rao M. S., Reddy J. K. Comparison of constitutive and induc-ible levels of expression of peroxisomal β-oxidation and catalase genes in liver and extrahepatic ti of rat. Cancer Res. 1988; 48: 5316–5324
   PubMed Web of Science ®Google Scholar
• Vamecq J., Draye J.-P. Peroxisomal and mito-chondrial β-oxidation of monocarboxylyl-CoA, omega-hydroxymonocarboxylyl-CoA and dicar-boxylyl-CoA esters in tis from untreated and clofibrate-treatedrats. J. Biochem. 1989; 106: 216–222
   PubMedGoogle Scholar
• Mittal B., Kurup C. K. R. Induction of car-nitine acetyltransferase by clofibrate in rat liver. Biochem. J. 1981; 194: 249–255
   PubMed Web of Science ®Google Scholar
• Veerkamp J. H., van Moerkerk H. T. B. Peroxisomal fatty acid oxidation in rat and human tis. Effect of nutritional state, clofibrate treatment and postnatal development in the rat. Biochim. Biophys. Acta 1986; 875: 301–310
   PubMedGoogle Scholar
• Katoh H., Kawashima Y., Watanuki H., Kozuka H., Isono H. Effects of clofibric acid and tiadenol on cytosolic long-chain acyl-CoA hydrolase and peroxisomal β-oxidation in liver and extrahepatic tis of rats. Biochim. Biophys. Acta 1987; 920: 171–179
   PubMed Web of Science ®Google Scholar
• Yamada J., Sakunia M., Suga T. Assay of fatty acid omega-hydroxylation using high-performance liquid chromatography with fluorescence labeling reagent, 3-bromomethyl-7-methoxy-1, 4-benzoaxin-2-one (BrMB). Anal. Biochem. 1991; 199: 132–136
   PubMed Web of Science ®Google Scholar
• Lalwani N. D., Reddy M. K., Mangkornkanok-Mark M., Reddy J. K. Induction, immu-nochemical identity and immunofluorescence localization of an 80,000-molecular-weight peroxi-some-proliferation-associated polypeptide (polypep-tide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex. Biochem. J. 1981; 198: 177–186
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Warren J. R., Reddy M. K., Lalwani N. D. Hepatic and renal effects of peroxisome proliferators: biological implications. Ann. N.Y. Acad. Sci. 1982; 386: 81–110
   PubMed Web of Science ®Google Scholar
• Hawkins J. M., Jones W. E., Bonner F. W., Gibson G. G. The effect of peroxisome proliferators on microsomal, peroxisomal, and mitochondrial enzyme activities in the liver and kidney. Drug Metab. Rev. 1987; 18: 441–515
   PubMed Web of Science ®Google Scholar
• Ohno H. Peroxisomes of the kidney. Int. Rev. Cytol. 1985; 95: 131–162
   PubMedGoogle Scholar
• Zaar K. Structure and function of peroxisomes in the mammalian kidney. Eur. J. Cell Biol. 1992; 59: 233–254
   PubMed Web of Science ®Google Scholar
• van Veldhoven P., Mannaerts G. P. Comparison of the activities of some peroxisomal and extraperoxisomal lipid-metabolizing enzymes in liver and extrahepatic tis of the rat. Biochem. J. 1985; 227: 737–741
   PubMedGoogle Scholar
• Takagi A., Sai K., Umemura T., Hasegawa R., Kurokawa Y. Short-term exposure to the peroxisome proliferators, perfluorooctanoic acid and perfluorodecanoic acid, causes significant increase of 8-hydroxydeoxyguanosine in liver DNA of rats. Cancer Lett. 1991; 57: 55–60
   PubMed Web of Science ®Google Scholar
• Walusimbi-Kisutu M., Walusimbi-Kisutu E. H. H. Fluorimetric assay for rat liver peroxisomal fatty acyl-coenzyme A oxidase activity. J. Lipid Res. 1983; 24: 1077–1084
   PubMed Web of Science ®Google Scholar
• MacDonald R. S., Swan P. B. The effect of three hypolipidemic drugs on catalase activity and peroxisomal and mitochondrial palmitate oxidation in rat cardiac and skeletal muscle. Biochim. Biophys. Acta. 1986; 880: 153–160
   PubMedGoogle Scholar
• Glatz J. F. C., Wagenmakers J. M., Veerkamp J. H., van Moerkerk H. T. B. Effect of clofibrate feeding on palmitate and branched-chain 2-oxo acid oxidation in rat liver and muscle. Biochem. Pharmacol. 1983; 32: 2489–2493
   PubMed Web of Science ®Google Scholar
• Norseth J., Thomassen M. S. Stimulation of microperoxisomal β-oxidation in rat heart by high-fat diets. Biochim. Biophys. Acta 1983; 751: 312–320
   PubMed Web of Science ®Google Scholar
• Kremser K., Schön H. J., Lohninger A., Prager C. M., Kramar R., Böck P. Response to thy-roxine of lamellar bodies, peroxisomes and peroxisomal enzymes in the adult rat lung. Eur. J. Clin. Chem. Clin. Biochem. 1991; 29: 151–158
   PubMedGoogle Scholar
• Osumi T., Hashimoto T. The inducible fatty acid oxidation system in mammalian peroxisomes. Trends Biochem. Sci. 1984; 317–319
   Web of Science ®Google Scholar
• Fringes B., Reith A. Time course of peroxisome biogenesis during adaptation to mild hyperthy-roidism in rat liver. Lab. Invest. 1982; 47: 19–26
   PubMed Web of Science ®Google Scholar
• Rao M. S., Lalwani N. D., Watanabe T. K., Reddy J. K. Inhibitory effect of antioxidants ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate. a peroxisomal proliferator. Cancer Res. 1984; 44: 1072–1076
   PubMed Web of Science ®Google Scholar
• Rao M. S., Scarpelli D. G., Reddy J. K. Transdifferentiated hepatocytes in rat pancreas. Curr. Top. Dev. Biol. 1986; 20: 63–78
   PubMed Web of Science ®Google Scholar
• Lalwani N. D., Reddy M. K., Qureshi S. A., Reddy J. K. Development of hepatocellular carcinomas and increased peroxisomal fatty acid β-oxidation in rats fed (4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio)acetic acid (WY-14,643) in the semipurified diet. Carcinogenesis 1981; 2: 645–650
   PubMed Web of Science ®Google Scholar
• Rao M. S., Reddy M. K., Reddy J. K. Response of chemically induced hepatocyte-like cells in hamster pancreas to methyl clofenapate, a peroxisome proliferator. J. Cell Biol. 1982; 95: 50–56
   PubMed Web of Science ®Google Scholar
• 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., Rao M. S. Transcriptional 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
   PubMed Web of Science ®Google Scholar
• Nemali M. R., Reddy M. K., Usuda N., Reddy P. G., Corneau L. D., Rao M. S., Reddy J. K. Differential induction and regulation of peroxisomal enzymes: predictive value of peroxisome proliferation in identifying certain nonmutagenic carcinogens. Toxicol. Appl. Pharmacol. 1989; 97: 72–87
   PubMed Web of Science ®Google Scholar
• Fukami M. H., Eikholm T. S., Ekanger R., Flatmark T., Nilsson A. Relation between induction of ornithin decarboxylase and specific gene expression in rat liver in response to the promoter agent clofibrate. Carcinogenesis 1986; 7: 1441–1446
   PubMedGoogle Scholar
• McQuaid S., Russel S. E. H., White S. A., Pearson C. M., Elcombe C. R., Humphries P. Analysis of transcripts homologous to acyl-CoA oxidase and enoyl-CoA-hydratase 3-hydroxyacyl-CoA dehydrogenase induced rat liver by methylclofenapate. Cancer Lett. 1987; 37: 115–121
   PubMedGoogle Scholar
• Bell D. R., Plant N. J., Rider C. G., Na L., Brown S., Ateitalla I., Acharya S. K., Davies M. H., Elias E., Jenkins N. A., Gilbert D. A., Copeland N. G., Elcombe C. R. Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4a cDNAs. Biochem. J. 1993; 294: 173–180
   PubMed Web of Science ®Google Scholar
• Hardwick J., Song B. J., Huberman E., Gonzalez F. J. Isolation, complementary DNA-se-quence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450 LA omega). Identification of a new cytochrome P-450 gene family. J. Biol. Chem. 1987; 262: 801–810
   PubMed Web of Science ®Google Scholar
• Bieri F., Nemali M. R., Muakassah-Kelly S., Weachter F., Stäubli W., Reddy J. K., Bentley P. Increased peroxisomal enzyme mRNA levels in adult rat hepatocytes cultured in a chemically defined medium and treated with nafenopin. Toxicol. in Vitro 1988; 2: 235–240
   PubMed Web of Science ®Google Scholar
• Gibson G. G. Comparative aspects of the mammalian cytochrome P450 IV gene family. Xenobiotica 1989; 10: 1123–1148
   Google Scholar
• Roman L. J., Palmer C. N., Clark J. E., Muerhoff A. S., Griffin K. J., Johnson E. F., Masters B. S. Expression of rabbit cytochromes P4504A which catalyze the omega-hydroxylation of arachidonic acid, fatty acids, and prostaglandins. Arch. Biochem. Biophys. 1993; 307: 57–65
   PubMed Web of Science ®Google Scholar
• Furuta S., Miyazawa S., Hashimoto T. Biosynthesis of enzymes of peroxisomal β-oxidation. J. Biochem. 1982; 92: 319–326
   PubMed Web of Science ®Google Scholar
• Bell C. R., Elcombe C. R. Induction of acyl-CoA oxidase and cytochrome P450IVA1 RNA in rat primary hepatocyte culture by peroxisome prolifera-tors. Biochem. J. 1991; 280: 249–253
   PubMed Web of Science ®Google Scholar
• Thangada S., Alvares K., Mangino M., Usman M. I., Rao M. S., Reddy J. K. An in vitro demonstration of peroxisome proliferation and increase in peroxisomal β-oxidation system mRNAs in cultured rat hepatocytes treated with ciprofibrate. FEBS Lett. 1989; 250: 205–210
   PubMedGoogle Scholar
• Chaterjee B., Murty C. V. R., Olson M. J., Roy A. K. Cloning and expression of the rat liver cDNA for peroxisomal enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase in lambda-GT11. Transcriptional regulation of enzyme activity by WY-14,643 in primary cultures of rat hepatocytes. Eur. J. Biochem. 1987; 166: 273–278
   PubMedGoogle Scholar
• Shaffer C. B., Carpenter C. P., Smyth H. F., Jr. Acute and subacute toxicity of di(2-ethylhexyl)-phthalate with note upon its metabolism. J. Ind. Hyg. Toxicol. 1945; 27: 130–135
   Google Scholar
• Gray T. J. B., Butterworth K. R., Gaunt I. F., Grasso P., Gangolli S. D. Short-term toxicity study of di(2-ethylhexyl)phthalate in rats. Food Cosmet. Toxicol. 1977; 15: 389–399
   PubMedGoogle Scholar
• Krauskopf L. G. Studies on the toxicity of phthalate via ingestion. Environ. Health Perspect. 1973; 3: 61–72
   PubMedGoogle Scholar
• Singh A. R., Lawrence W. H., Autian J. Teratogenicity of phthalate esters in rat. J. Pharm. Sci. 1972; 61: 51–55
   PubMed Web of Science ®Google Scholar
• Lawrence W. H., Malik M., Turner J. E., Singh A. R., Autian J. A toxicological investigation of some acute, short-term, and chronic effects of administering di-2-ethylhexyl phthalate (DEHP) and other phthalate esters. Environ. Res. 1975; 9: 1–11
   PubMed Web of Science ®Google Scholar
• Calley D., Autian J., Gues W. L. Toxicology of a series of phthalate esters. J. Pharm. Sci. 1966; 55: 158–162
   PubMed Web of Science ®Google Scholar
• Harris R. S., Hodge H. C., Maynard E. A., Blanchet H. J. J. Chronic oral toxicity of 2-ethylhexyl-phthalate in rats and dogs. Arch. Ind. Health 1956; 13: 259–264
   PubMedGoogle Scholar
• Carpenter C. P., Weil C. S., Smith H. F. J. Chronic oral toxicity of di(2-ethylhexyl)phthalate for rats, guinea pigs, and dogs. Am. Med. Assoc. Arch. Ind. Hyg. Occup. Med. 1953; 8: 219–226
   PubMedGoogle Scholar
• Röckel A., Klinke B., Hertel J., Bauer X., Thiel C., Abdelhamid S., Fiegel P., Walb D. Allergy to dialysis materials. Nephrol. Dial. Transplant. 1989; 4: 646–652
   PubMed Web of Science ®Google Scholar
• Lamb J. C., Chapin R. E., Teague J., Lawton A. D., Reel J. R. Reproductive effects of four phthalic acid esters in the mouse. Toxicol. Appl. Pharmacol. 1987; 88: 255–269
   PubMed Web of Science ®Google Scholar
• Agarwal D. K., Lawrence W. H., Turner J. E., Autian J. Effects of parenteral di(2-ethylhexyl)-phthalate (DEHP) on gonadal biochemistry, pathology, and reproductive performance of mice. J. Toxicol. Environ. Health 1989; 26: 39–59
   PubMed Web of Science ®Google Scholar
• Nikonorow M., Mazur H., Peikacz H. Effect of orally administered plasticizers and poly vinyl chloride stabilizers in the rat. Toxicol. Appl. Pharmacol. 1973; 26: 253–259
   PubMed Web of Science ®Google Scholar
• Yagi Y., Nakamura Y., Tomita I., Tsuchikawa K., Shimoi N. Teratogenic potential of di- and mono-2-ethylhexylphthalate in mice. J. Environ. Pathol. Toxicol. 1980; 4: 533–544
   PubMed Web of Science ®Google Scholar
• Tomita I., Nakamura Y., Yagi Y., Tutikawa K. Teratogenicity/fetotoxicity of DEHP in mice. Environ. Health Perspect. 1982; 45: 71–75
   PubMed Web of Science ®Google Scholar
• Tyl R. W., Price C. J., Marr M. C., Kimmel C. A. Developmental toxicity evaluation of dietary di(2-ethylhexyl)phthalate in Fischer 344 rats and CD-1 mice. Fundam. Appl. Toxicol. 1988; 10: 395–412
   PubMedGoogle Scholar
• Thomas J. A., Schein L. G., Gupta P. K., McCafferty R. E., Felice P. R., Donovan M. P. Failure of mono-ethylhexyl phthalate to cause teratogenic effects in offspring of rabbits. Toxicol Appl. Pharmacol. 1979; 51: 523–528
   PubMed Web of Science ®Google Scholar
• Shiota K., Mima S. Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice. Arch. Toxicol. 1985; 56: 263–266
   PubMed Web of Science ®Google Scholar
• Faustmann E. M., Wellington D. G., Smith W. P., Kimmel C. A. Characterization of a developmental toxicity dose-response model. Environ. Health Perspect. 1989; 79: 229–241
   PubMed Web of Science ®Google Scholar
• McDonald A. D., Lavoie J., Cote R., McDonald J. C. Spontaneous abortion in women employed in plastics manufacture. Am. J. Ind. Med. 1988; 14: 9–14
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., Gangolli S. Aspects of the testicular toxicity of phthalate esters. Environ. Health Perspect. 1986; 65: 229–235
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., Butterworth K. R. Testicular atrophy produced by phthalate esters. Arch. Toxicol., Suppl. 1980; 4: 452–455
   PubMedGoogle Scholar
• Curto K. A., Thomas J. A. Comparative effects of diethylhexyl phthalate or monoethylhexyl phthalate on male mouse and rat reproductive organs. Toxicol Appl. Pharmacol. 1982; 62: 121–125
   PubMed Web of Science ®Google Scholar
• Oishi S. Testicular atrophy induced by di(2-ethylhexyl)phthalate: changes in histology, cell specific enzyme activities and zinc concentrations in rat testis. Arch. Toxicol. 1986; 59: 290–295
   PubMed Web of Science ®Google Scholar
• Seth P. K., Srivastava S. P., Agarwal D. K., Chandra S. V. Effect of di-2-ethylhexyl phthalate (DEHP) on rat gonads. Environ. Res. 1976; 12: 131–138
   PubMed Web of Science ®Google Scholar
• Siddiqui A., Srivastava S. P. Effect of di(2-ethylhexyl)phthalate on rat sperm count and on sperm metabolic enzymes. Bull. Environ. Contam. Toxicol. 1992; 48: 115–119
   PubMedGoogle Scholar
• Oishi S., Higara K. Testicular atrophy induced by di-(2-ethylhexyl)phthalate. Effect of zinc supplement. Toxicol Appl. Pharmacol. 1983; 70: 43–48
   PubMed Web of Science ®Google Scholar
• Oishi S., Hiraga K. Testicular atrophy induced by phthalic acid monoesters: effects of zinc and testosterone concentrations. Toxicology 1980; 15: 197–202
   PubMed Web of Science ®Google Scholar
• Oishi S., Hiraga K. Testicular atrophy induced by phthalic acid esters: effect on testosterone and zinc concentrations. Toxicol. Appl. Pharmacol. 1980; 53: 35–41
   PubMed Web of Science ®Google Scholar
• Gangolli S. D. Testicular effects of phthalate esters. Environ. Health Perspect. 1982; 45: 77–84
   PubMed Web of Science ®Google Scholar
• Gray T. J. B., Rowland I. R., Foster P. M. D., Gangolli S. D. Species differences in the testicular toxicity of phthalate esters. Toxicol. Lett. 1982; 11: 141–147
   PubMed Web of Science ®Google Scholar
• Jones H. B., Garside D. A., Liu R., Roberts J. C. The influence of phthalate esters on Leydig cell structure and function in vitro and in vivo. Exp. Mol. Pathol. 1993; 58: 179–193
   PubMed Web of Science ®Google Scholar
• Srivastava S., Srivastava S. P. Effect of di(2-ethylhexyl)phthalate on 17 β-hydroxysteroid dehydro-genase activity in testis of rat. Toxicol. Lett. 1991; 57: 235–239
   PubMed Web of Science ®Google Scholar
• Oishi S., Hiraga K. Effects of phthalic acid monoesters on mouse testes. Toxicol. Lett. 1980; 6: 239–242
   PubMed Web of Science ®Google Scholar
• Oishi S., Hiraga K. Effect of phthalic acid esters on mouse testes. Testicular atrophy induced by phthalic acid monoesters: effects of zinc and testosterone concentrations. Toxicol. Lett. 1980; 5: 413–416
   PubMed Web of Science ®Google Scholar
• Oishi S. Strain differences in susceptibility to di-2-ethylhexyl phthalate-induced testicular atrophy in mice. Toxicol. Lett. 1993; 66: 47–52
   PubMed Web of Science ®Google Scholar
• Rhodes C., Elcombe C. R., Batten P. L., Bratt H., Jackson S. J., Pratt I. S., Orton I. C. Comparative toxicity of di-(2-ethylhexyl)phthalate (DEHP) in rats and marmosets. Toxicol. Lett. 1983; 18 Suppl. 1: 63
   Google Scholar
• Crocker J. F. S., Safe S. H., Acott P. Effect of chronic phthalate exposure on the kidney. J. Toxicol. Environ. Health 1988; 23: 433–444
   PubMed Web of Science ®Google Scholar
• Woodward K. N. Phthalate esters, cystic kidney disease in animals and possible effect on human health: a review. Hum. Exp. Toxicol. 1990; 9: 397–401
   PubMedGoogle Scholar
• Gaunt J. F., Colley J., Grasso P., Landsdown A. B. G. Acute (rat and mouse) and short-term (rat) toxicity study on dialkyl 7+9 phthalate (a mixture of phthalate esters of alcohols having 7–9 carbon atoms). Food Cosmet. Toxicol. 1968; 6: 609–618
   PubMedGoogle Scholar
• Omori Y. Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan. Environ. Health Perspect. 1976; 17: 203–209
   PubMed Web of Science ®Google Scholar
• Schulz C. O., Rubin R. J., Hutchins G. M. Acute lung toxicity and sudden death in rats following the intravenous administration of the plasticizer, di(2-ethylhexyl)-phthalate, solubilized with Tween surfactants. Toxicol. Appl. Pharmacol. 1975; 33: 514
   PubMed Web of Science ®Google Scholar
• Rubin R. J., Chang J. C. F. Effect of the intravenous administration of the solubilized plasticizer, di(2-ethylhexyl) phthalate on the lung and on survival of transfused rats (abstract). Toxicol. Appl. Pharmacol. 1978; 45: 230
   Google Scholar
• Klimisch H. J., Gamer A. O., Hellwig J., Kaufmann W., Jäckh R. Di-(2-efhylhexyl) phthalate: a short-term repeated inhalation toxicity study including fertility assessment. Food Chem. Toxicol. 1992; 30: 915–919
   PubMedGoogle Scholar
• Doelman C. J. A., Borm P. J. A., Bast A. Plasticizers, another burden for asthmatics?. Agents Actions Suppl. 31 1990; 81–84
   Google Scholar
• Doelman C. J. A., Borm P. J. A., Bast A. Plasticizers and bronchial hyperreactivity. Lancet 1990; 335: 725
   PubMed Web of Science ®Google Scholar
• Labow R. S., Barry Y. A., Tocchi M., Keon W. J. The effect of mono(2-ethylhexyl)phthalate on an isolated perfused rat heart-lung preparation. Environ. Health Perspect. 1990; 89: 189–193
   PubMedGoogle Scholar
• Barry Y. A., Labow R. S., Rock G., Keon W. J. Cardiotoxic effects of the plasticizer metabolite, mono(2-ethylhexyl)phthalate (MEHP), on human myocardium. Blood 1988; 72: 1438–1439
   PubMed Web of Science ®Google Scholar
• Fassett D. W. Esters. Industrial Hygiene and Toxicology, 2nd rev. ed., F. A. PattyInterscience, New York 1963; 1904–1907
   Google Scholar
• Tobe M., Suzuki Y., Ikeda Y., Naito K. A study on toxicity of phthalates and adipate. Chronic toxicity test in mice. 1984, FDA FAP No. 1T3573:O1O623–010676
   Google Scholar
• Rao M. S., Usuda N., Subbarao V., Reddy J. K. Absence of gamma-glutamyl transpeptidase activity in neoplastic lesions induced in the liver of male F-344 rats by di-(2-ethylhexyl)phthalate, a per-oxisome proliferator. Carcinogenesis 1987; 8: 1347–1350
   PubMed Web of Science ®Google Scholar
• Ganning A. E. 1987, quoted in: Stephen Hsia, M. T., The Relationship between carcinogenesis and peroxi-some proliferation in rodent liver after exposure to the plasticizer DEHP and DEHA, Mitre Corporation, McLean, VA
   Google Scholar
• Tamura H., Iida T., Watanabe T., Suga T. Lack of induction of hepatic DNA-damage on long-term administration of peroxisome proliferators in male F-344 rats. Toxicology 1991; 69: 55–62
   PubMed Web of Science ®Google Scholar
• Schmezer P., Pool B. L., Klein R. G., Komitowski D., Schmahl D. Various short-term assays and two long-term studies with the plasticizer di(2-ethyl-hexyl)phthalate in the Syrian Golden hamster. Carcinogenesis 1988; 9: 37–43
   PubMed Web of Science ®Google Scholar
• Parzefall W., Schuppler J., Barthel G., Meyer-Rogge B., Schulte-Hermann R. Toxicological studies on a benzofurane derivative. I. A comparative study with phenobarbital on rat liver. Toxicol. Appl. Pharmacol. 1990; 106: 482–499
   PubMedGoogle Scholar
• Kraupp-Grasl B., Huber W., Taper H., Schulte-Hermann R. Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome proliferator nafenopin and the possible involvement of altered liver foci occurring spontaneously. Cancer Res. 1991; 51: 666–671
   PubMed Web of Science ®Google Scholar
• Goodman D. G., Ward J. M., Squire R. A., Chu K. C. Neoplastic and nonneoplastic lesions in aging F344 rats. Toxicol. Appl. Pharmacol. 1979; 48: 237–248
   PubMed Web of Science ®Google Scholar
• 1982, NTP, National Toxicology Program: Carcinogenesis bioassay of di(2-ethylhexyl)adipate (CAS No. 103–23–1) in F344 rats and B6C3F1 mice (feed study). Tech. Rep. Series, 212
   Google Scholar
• Svoboda D. J., Azarnoff D. L. Tumors in male rats fed ethyl chlorophenoxyisobutyrate, a hypolipi-demic drug. Cancer Res. 1979; 39: 3419–3428
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Qureshi S. A. Tumorigenicity of the hypolipidemic peroxisome proliferator ethyl-a-p-chlorophenoxyisobutyrate (clofibrate) in rats. Br. J. Cancer 1979; 40: 476–482
   PubMed Web of Science ®Google Scholar
• Reddy J. K., Reddy M. S. R. Malignant tumors in rats fed nafenopin, a hepatic peroxisome proliferator. J. Natl. Cancer Inst. 1977; 59: 1645–1650
   PubMed Web of Science ®Google Scholar
• Kraupp-Grasl B., Huber W., Putz B., Gerbracht U., Schulte-Hermann R. Tumor promotion by the peroxisome proliferator nafenopin involving a specific subtype of altered foci in rat liver. Cancer Res. 1990; 50: 3701–3708
   PubMed Web of Science ®Google Scholar
• Rao M. S., Lalwani N. D., Reddy J. K. Sequential histologic study of rat liver during peroxisome proliferator (4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio)acetic acid (WY-14,643)-induced carcinogenesis. J. Natl. Cancer Inst. 1984; 73: 983–990
   PubMed Web of Science ®Google Scholar
• Reddy J. K. M. S. R., Azarnoff D. L., Sell S. Mitogenic and carcinogenic effects of a hypolipidemic peroxisome proliferation, (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio)acetic acid (WY-14,643) in rat and mouse liver. Cancer Res. 1979; 39: 152–161
   PubMed Web of Science ®Google Scholar
• Kluwe W. M., Huff J. E., Matthews H. B., Irwin R., Haseman J. K. Comparative chronic toxicities and carcinogenic potentials of 2-ethylhexyl-containing compounds in rats and mice. Carcinogenesis 1985; 6: 1577–1583
   PubMedGoogle Scholar
• Kluwe W. M., McConnell E. E., Huff J. E., Haseman J. K., Douglas J. F., Hartwell W. V. Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. Environ. Health Perspect. 1982; 45: 129–133
   PubMed Web of Science ®Google Scholar
• Exxon Corporation, Chronic toxicity/carcinogenic-ity study of diisononyl phthalate (DINP) in the rat. 1986, Research and Environmental Health Division, Exxon Corporation, Baton Rouge, LA
   Google Scholar
• Ashby J., de Serres F. J., Draper M., Ishidate M., Margolin B. H., Matter B. E., Shelby M. D. Progress in Mutation Research 1985; 5: 1–752, IPCS-study, International Programme on Chemical Safety, Evaluation of short-term tests for carcinogens. Report of the international programme on chemical safety's collaborative study on in vitro assays
   Google Scholar
• Simmon V. F., Kauhanen K., Tardiff R. G. Mutagenic activity of chemicals identified in drinking water. Dev. Toxicol. Environ. Sci. 1977; 2: 249–258
   Google Scholar
• Ruddick J. A., Villeneuve D. C., Chu I., Nestman E., Miles D. An assessment of the teratogenicity in the rat and mutagenicity in Salmonella of mono-(2-ethylhexyl)phthalate. Bull. Environ. Contam. Toxicol. 1981; 27: 181–186
   PubMed Web of Science ®Google Scholar
• Kozumbo W. J., Kroll R., Rubin R. J. Assessment of the mutagenicity of phthalate esters. Environ. Health Perspect. 1982; 45: 103–109
   PubMed Web of Science ®Google Scholar
• Kirby P. E., Pizzarello R. F., Lawlor T. E., Haworth S. R., Hodgson J. R. Evaluation of di(2-ethylhexyl)phthalate and its major metabolites in the Ames test and L5178Y mouse lymphoma mutagenicity assay. Environ. Mutagen. 1983; 5: 657–663
   PubMedGoogle Scholar
• Barber E. D., Mulholland A., Jagannath D. R., Cifone M., Cimino M., Myhr B., Rundell J. The testing of di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)phthalate (MEHP), di(2-ethyl-hexyl)adipate (DEHA), and 2-ethylhexanol (2-EH) in a battery of genotoxicity assays. Paper presented at the Society of Toxicology Meeting. 1985
   Google Scholar
• Tennant R. W. B. H. M., Shelby M. D., Zeiger E., Haseman J. K., Spalding J., Caspary W., Resnick M., Stasiewicz S., Anderson B., Minor R. Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science 1987; 236: 933–940
   PubMed Web of Science ®Google Scholar
• Tomita I., Nakamura Y., Aoki N., Inui N. Mutagenic/carcinogenic potential of DEHP and MEHP. Environ. Health Perspect. 1982; 45: 119–125
   PubMed Web of Science ®Google Scholar
• Seed J. L. Mutagenic activity of phthalate esters in bacterial liquid suspension assays. Environ. Health Perspect. 1982; 45: 111–114
   PubMed Web of Science ®Google Scholar
• Yoon J. S., Mason J. M., Valencia R., Woodruff R. C., Zimmering S. Chemical mutagenesis testing in Drosophila. IV. Results of 45 coded compounds tested for the National Toxicology Program. Environ. Mutagen. 1985; 7: 349–367
   PubMedGoogle Scholar
• Hodgson J. R., Myhr B. C., McKeon M., Brusick D. J. Evaluation of di(2-ethylhexyl)phthalate and its major metabolites in the primary rat hepato-cyte unscheduled DNA synthesis assay. Environ. Mutagen. 1982; 4: 388
   Google Scholar
• Kornbrust D. J., Barfknecht T. R., Ingram P., Shelburne J. D. Effect of di(2-ethylhexyl)-phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells. J Toxicol. Environ. Health 1984; 13: 99–116
   PubMed Web of Science ®Google Scholar
• Abe S., Sasaki M. Chromosome aberrations and sister chromatid exchanges in Chinese hamster cells exposed to various chemicals. J. Natl. Cancer Inst. 1977; 58: 1635–1641
   PubMed Web of Science ®Google Scholar
• Phillips B. J., James T. E. B., Gangolli S. D. Genotoxicity studies of di(2-ethylhexyl)phthalate and its metabolites in CHO cells. Mutat. Res. 1982; 102: 297–304
   PubMed Web of Science ®Google Scholar
• Turner J. H., Petricciani J. C., Crouch M. L., Wenger S. An evaluation of the effects of di-ethylhexyl-phthalate (DEHP) on mitotically capable cells in blood packs. Transfusion 1974; 14: 560
   PubMedGoogle Scholar
• Stenchever M. A., Allen M. A., Jerominski L., Petersen R. V. Effects of bis(2-ethyl hexyl)phthalate on chromosomes of human leukocytes and human fetal lung cells. J. Pharm. Sci. 1976; 65: 1648–1651
   PubMed Web of Science ®Google Scholar
• Tsuchiya K., Hattori K. Chromosomal study on human leukocyte cultures treated with phthalate acid esters (Jpn.). Hoeka 1976; 26: 114
   Google Scholar
• Sanchez J. H., Abernethy D. J., Boreiko C. J. Lack of di-(2-ethylhexyl)phthalate activity in the C3H/10T1/2 cell transformation system. Toxic. In Vitro 1987; 1: 49–53
   PubMed Web of Science ®Google Scholar
• CMA, Chemical Manufacturers Association. Phthalate Esters Program Panel, Voluntary Test Program. Health Effects Testing, Phase 1: Validation Results, G. V. Cox, E. J. Moran. CMA, Washington, D.C. 1982; 1
   Google Scholar
• Astill B., Barber E., Lington A., Moran E., Mulholland A., Robinson E., Schneider B. Chemical industry voluntary test program for phthalate esters: health effect studies. Environ. Health Perspect. 1986; 65: 329–336
   PubMed Web of Science ®Google Scholar
• Diwan B. A., Ward J. M., Rice J. M., Colburn N. H., Spangler E. F. Tumor-promoting effects of di(2-ethylhexyl)phthalate in JB6 mouse epidermal cells and mouse skin. Carcinogenesis 1985; 6: 343–347
   PubMed Web of Science ®Google Scholar
• Malcolm A. R., Mills L. J., McKenna E. J. Inhibition of metabolic cooperation between Chinese hamster V79 cells by (tumor promoters and other chemicals). Ann. N.Y. Acad. Sci. 1983; 407: 448
   Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Klaunig J. E., Ruch R. J., De Angelo A. B., Kaylor W. H. Inhibition of mouse hepatocyte intercellular communication by phthalate mo-noesters. Cancer Lett. 1988; 43: 65–71
   PubMed Web of Science ®Google Scholar
• Malcolm A. R. Mutagenicity and tumor-promoting potential of di-(2-ethylhexyl)phthalate in Chinese hamster cells. 1982
   Google Scholar
• Von Däniken A., Lutz W. W., Jäckh R., Schlatter C. Investigation of the potential of binding of di-(2-ethylhexyl)phthalate and di-(2-ethylhexyl)adipate to liver DNA in vivo. Toxicol. Appl. Pharmacol. 1984; 73: 373–387
   PubMed Web of Science ®Google Scholar
• Gupta R. C., Goel S. K., Earley K., Singh B., Reddy J. K. 32P-Postlabeling analysis of peroxi-some proliferator-DNA adduct formation in rat liver in vivo and hepatocytes in vitro. Carcinogenesis 1985; 6: 933–936
   PubMed Web of Science ®Google Scholar
• Lutz W. K. Investigation of the potential for binding of di(2-ethylhexyl)phthalate (DEHP) to rat liver DNA in vivo. Environ. Health Perspect. 1986; 65: 267–269
   PubMedGoogle Scholar
• Elliott B. M., Elcombe C. R. Effects of reactive oxygen species produced by peroxisome proliferation in the livers of rats. Proc. Am. Assoc. Cancer Res. 1985; 26: 72
   Google Scholar
• Takagi A. S. K., Umemura T., Hasegawa R., Kurokawa Y. Relationship between hepatic peroxisome proliferation and 8-hydroxyde-oxyguanosine 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
   PubMed Web of Science ®Google Scholar
• Cattley R. C., Glover S. E. Elevated 8-hydrox-ydeoxyguanosine in hepatic DNA of rats following exposure to peroxisome proliferators: relationship to carcinogenesis and nuclear localization. Carcinogenesis 1993; 14: 2495–2499
   PubMed Web of Science ®Google Scholar
• Putman D. L., Moore W. A. M. S. L., Hodgson J. R. Cytogenetic evaluation of di(2-ethyl-hexyl)phthalate and its major metabolites in Fischer 344 rats. Environ. Mutagen. 1983; 5: 227
   PubMedGoogle Scholar
• Hamano Y., Inoue K., Oda Y., Yamamoto H., Kunita N. Studies on toxicity of phthalic acid esters. 2. Dominant lethal test of DEHP and MEHP in mice. Toxicology 1980; 92: 145
   Google Scholar
• Rushbrook C. J. A. J. T., Hodgson J. R. Dominant lethal study of di-(2-ethylhexyl)phthalate and its major metabolites in lCR/SIM mice (Abstract). Environ. Mutagen. 1982; 5: 387
   Google Scholar
• Singh A. R., Lawrence W. H., Autian J. Mutagenic and antifertility sensitivities of mice to di-(2-ethylhexyl)phthalate (DEHP) and dimethoxyethyl phthalate (DMEP). Toxicol. Appl. Pharmacol. 1974; 29: 35–46
   PubMed Web of Science ®Google Scholar
• Autian J. Antifertility effects and dominant lethal assays for mutagenic effects of DEHP. Environ. Health Perspect. 1982; 45: 115–118
   PubMed Web of Science ®Google Scholar
• Douglas R. G., Hugenholtz A. P., Blakey D. H. Genetic toxicology of phthalate esters: mutagenic and genotoxic effects. Environ. Health Perspect. 1986; 65: 255–262
   PubMed Web of Science ®Google Scholar
• Adler I. D., Ashby J. The present lack of evidence for unique rodent germ-cell mutagens. Mutat. Res. 1989; 212: 55–66
   PubMed Web of Science ®Google Scholar
• Kasai H., Okada Y., Nishimura S., Rao M. S., Reddy J. K. Formation of 8-hydroxydeoxygua-nosine in liver DNA of rats following long-term exposure to a peroxisome proliferator. Cancer Res. 1989; 49: 2603–2605
   PubMed Web of Science ®Google Scholar
• Hegi M. E., Ulrich D., Sagelsdorff P., Rich-ter C., Lutz W. K. No measurable increase in thymidine glycol or 8-hydroxydeoxy-guanosine in liver DNA of rats treated with nafe-nopin or choline-devoid low-methionine diet. Mutat. Res. 1990; 238: 325–329
   PubMed Web of Science ®Google Scholar
• Denda A. S. K., Tang Q., Tsujiuchi T., Tsutsumi M., Amanuma T., Murata Y., Nakae D., Maruyama H., Kurokawa Y., Konishi Y. Induction of 8-hydroxydeoxyguanosine but not initiation of carcinogenesis by redox enzyme modulations with or without menadione in rat liver. Carcinogenesis 1991; 12: 719–726
   PubMedGoogle Scholar
• Ames B. N. Measuring oxidative damage in humans: relation to cancer and aging. IARC Sci. Publ. 1988; 89: 407–416
   Google Scholar
• Ames B. N. Endogenous DNA damage as related to cancer and aging. Mutat. Res. 1989; 214: 41–46
   PubMed Web of Science ®Google Scholar
• Pitot H. C., Beer D. G., Hendrich S. Multistage carcinogenesis of the rat hepatocyte. Banbury Report 25: Nongenotoxic Mechanisms in Carcinogenesis. Cold Spring Harbor Press, Cold Spring Harbor 1987; 41–51
   Google Scholar
• Pitot H. C., Dragan Y. P. Facts and theories concerning the mechanism ofCarcinogenesis. FASEB J. 1991; 5: 2280–2286
   PubMed Web of Science ®Google Scholar
• Pitot H. C. Altered hepatic foci: their role in murine hepatocarcinogenesis. Annu. Rev. Pharmacol. Toxicol. 1990; 39: 465–500
   Google Scholar
• Garvey L. K., Swenberg J. A., Hamm T. E., Jr., Popp J. A. Di(2-ethylhexyl)phthalate: lack of initiating activity in the liver of female F-344 rats. Carcinogenesis 1987; 8: 285–290
   PubMed Web of Science ®Google Scholar
• Williams G. M., Maruyama H., Tanaka T. Lack of rapid initiating, promoting, or sequential syncarcinogenic effects of di(2-ethylhexyl)phthalate in rat liver carcinogenesis. Carcinogenesis 1987; 8: 875–880
   PubMed Web of Science ®Google Scholar
• Ward J. M., Rice J. M., Creasia D., Lynch P., Riggs C. Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepa-tocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice. Carcinogenesis 1983; 4: 1021–1029
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Preat V., Lans M., de Gerlache J., Taper H., Roberfroid M. Comparison of the biological effects of phenobarbital and nafenopin on rat hepatocarcino-genesis. Jpn. J. Cancer Res. 1986; 77: 629–638
   PubMedGoogle Scholar
• Cattley R. C., Marsman D. S., Popp J. A. Failure of the peroxisome proliferator WY-14,643 to initiate growth-selectable foci in rat liver. Toxicology 1989; 56: 1–7
   PubMedGoogle Scholar
• Glauert H. P., Clark T. D. Lack of initiating activity of the peroxisome proliferator ciprofibrate in two-stage hepatocarcinogenesis. Cancer Lett. 1989; 43: 95–100
   Google Scholar
• Popp J. A., Garvey L. K., Hamm J. T. E., Swenberg J. A. Lack of hepatic promotional activity by the peroxisomal proliferating hepatocarcinogen di(2-ethylhexyl)phthalate. Carcinogenesis 1985; 6: 141–144
   PubMed Web of Science ®Google Scholar
• Oesterle D., Deml E. Promoting activity of di(2-ethylhexyl)phthalate in rat liver foci bioassay. J. Cancer Res. Clin. Oncol. 1988; 114: 133–136
   PubMed Web of Science ®Google Scholar
• Maruyama H., Tanaka T., Williams G. M. Effects of the peroxisome proliferator di(2-ethylhexyl)-phthalate on enzymes in rat liver and on carcinogen-induced liver altered foci in comparison to the promoter phenobarbital. Toxicol. Pathol. 1990; 18: 257–267
   PubMed Web of Science ®Google Scholar
• Ward J. M., Ohshima M., Lynch P., Riggs C. Di(2-ethylhexyl)phthalate but not phenobarbital promotes N-nitrosodiethylamine-initiated hepatocel-lular proliferative lesions after short-term exposure in male B6C3F1 mice. Cancer Lett. 1984; 24: 49–55
   PubMed Web of Science ®Google Scholar
• Hagiwara A., Diwan B. A., Ward J. M. Modifying effects of butylated hydroxyanisole, di(2-ethylhexyl)phthalate or indomethacin on mouse hepatocarcinogenesis initiated by N-nitrosodiethylamine. Jpn. J. Cancer Res. 1986; 77: 1215–1221
   PubMedGoogle Scholar
• Ward J. M., Konishi N., Diwan B. A. Renal tubular cell or hepatocyte hyperplasia is not associated with tumor promotion by di(2-ethylhexyl)phthalate in B6C3F1 mice after trans-placental initiation with N-nitrosoethylurea. Exp. Pathol. 1990; 40: 125–138
   PubMedGoogle Scholar
• Reddy J. K., Rao M. S. Enhancement of Wy-14,643, a hepatic peroxisome proliferator of diethylnitrosamine-initiated hepatic tumorigenesis in the rat. Br. J. Cancer 1978; 38: 537–543
   PubMed Web of Science ®Google Scholar
• Mochizuki Y., Furukawa K., Sawada N. Effects of various concentrations of ethyl-alpha-p-chlorophenoxy-isobutyrate (clofibrate) on diethylni-trosamine-induced hepatic tumorigenesis in the rat. Carcinogenesis 1982; 3: 1027–1029
   PubMed Web of Science ®Google Scholar
• Glauert H. P., Beer D., Rao M. S., Schwarz M., Xu Y., Goldworthy T. L., Coloma J., Pitot H. C. Induction of altered foci in rats by the administration of hypolipidemic peroxisome proliferators alone or following a single dose of diethylnitrosamine. Cancer Res. 1986; 46: 4601–4606
   PubMed Web of Science ®Google Scholar
• Preat V., de Gerlache J., Lans M., Taper H., Roberfroid M. Comparative analysis of the effect of phenobarbital, dichlorodiphenyltri-chlorethane, butylated hydroxytoluene, and nafenopin on rat hepatocarcinogenesis. Carcinogenesis 1986; 7: 1025–1028
   PubMed Web of Science ®Google Scholar
• Preat V., Roberfroid M. Modulation of rat hepatocarcinogenesis by peroxisome proliferators. Second International Conference on Anticarcinogen-esis and Radiation Protection, Gaithersburg, MD, March 8–12, 1987
   Google Scholar
• Cattley R. C., Popp J. A. Differences between the promoting activities of the peroxisome proliferator WY-14,643 and phenobarbital in rat liver. Cancer Res. 1989; 49: 3246–3251
   PubMed Web of Science ®Google Scholar
• Hosokawa S., Tatematsu M., Aoki T., Nakano-watari J., Igarashi T., Ito N. Modulation of diethylnitrosamine-initiated placental glutathioneS-transferase positive preneoplastic and neoplastic lesions by clofibrate, a hepatic peroxisome proliferator. Carcinogenesis 1989; 10: 2237–2241
   PubMed Web of Science ®Google Scholar
• Greaves P., Irissari E., Monro A. M. Hepatic foci of cellular alteration and nodules in rats treated with clofibrate or diethylnitrosamine followed by phenobarbital: their rate of onset and their reversibility. J. Natl. Cancer Inst. 1986; 76: 475–484
   PubMedGoogle Scholar
• Cattley R. C., Marsman D. S., Popp J. A. Age-related susceptibility to the carcinogenic effect of the peroxisome proliferator WY-14,643 in rat liver. Carcinogenesis 1991; 12: 469–473
   PubMed Web of Science ®Google Scholar
• Marsman D. S., Popp J. A. Biological potential of basophilic hepatocellular foci and hepatic adenoma induced by the peroxisome proliferator, Wy-14,643. Carcinogenesis 1994; 15: 111–117
   PubMed Web of Science ®Google Scholar
• Kurokawa Y., Takamura N., Matushima Y., Imazawa T., Hayashi Y. Promoting effect of peroxisome proliferators in two-stage rat renal tumorigenesis. Cancer Lett. 1988; 43: 145–149
   PubMed Web of Science ®Google Scholar
• Hagiwara A., Tamano S., Ogiso T., Asakawa E., Fukushima S. Promoting effect of the peroxisome proliferator, clofibrate, but not di(2-ethyl-hexyl)phthalate, on urinary bladder carcinogenesis in F344 rats initiated byN-butyl-N-(4-hydroxybutyl)-nitrosamine. Jpn. J. Cancer Res. 1990; 81: 1232–1238
   PubMedGoogle Scholar
• Fukushima S., Hagiwara A., Hirose M., Yamaguchi S., Tiwawech D., Ito N. Modifying effects of various chemicals on preneoplastic lesion development in a wide-spectrum organ-carcinogenesis model using F344 rats. Jpn. J. Cancer Res. 1991; 82: 642–649
   PubMedGoogle Scholar
• Mitchell F. E., Price S. C., Grasso P., Hinton R. H., Bridges J. W. Effects of di(2-ethyl-hexyl)phthalate on male and female rats (abstract). Poster given at the International Conference on Ph-thalic Acid Esters. University of Surrey, August 6–7, 1984, Abstracts: 10
   Google Scholar
• Lington A., Schneider B., Moran E., Stoltz M., Windels J., El-hawari M. Liver and lipid effects of diethylhexyl phthalate (DEHP) and diethyl-hexyl adipate (DEHA) in Fischer 344 rats. Toxicolo-gist 1985; 5: 159
   Google Scholar
• Conway G. C., Tomaszewski K. E., Olson M. J., Cattley R. C., Marsman D. S., Popp J. A. Relationship of oxidative damage to the hepatocarci-nogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and Wy-14,643. Carcinogenesis. 1989; 10: 513–519
   PubMed Web of Science ®Google Scholar
• Perera M. I. R., Katyal S. L., Shinozuka H. Suppression of choline-deficient diet-induced hepato-cyte membrane lipid peroxidation in rats by the peroxisome proliferators 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-β-hydroxyethyl)acetamide and di(2-ethylhexyl)phthalate. Cancer Res. 1986; 46: 3304–3308
   PubMed Web of Science ®Google Scholar
• Perera M. I. R., Betschart J. M., Virji M. A., Katyal S. L., Shinozuka H. Free radical injury and liver tumor promotion. Toxicol. Pathol. 1987; 15: 51–59
   PubMed Web of Science ®Google Scholar
• Cohen M. Briefing package on DEHP in children's products to the commissioners of the Product Safety Commission. Section III: Dose response assessment. USCPSC, Washington, D.C. 1983, as cited in Belilies, R., Salinas, J. A., and Kluwe, W. M., A review of di(2-ethylhexyl)phthalate (DEHP) risk assessments, Drug Metab. Rev.1989, 21, 3 12
   Google Scholar
• NRC. National Research Council, Toxicity of selected toxicants: di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate (MEHP). Drinking Water and Health. National Research Council, National Academy Press, Washington, D.C. 1986; Vol. 6: 338–359; 409–437
   Google Scholar
• Drug Metab. Rev. 1989; 21: 3–12, EPA, U.S. Environmental Protection Agency, 1987, Draft; Health and Environmental Effects Profile for Phthalic Acid Alkyl, Aryl, and Alkyl/aryl Esters, Cincinnati, OH: USEPA, cited in Beliles, R., Salinas, J. A., and Kluwe, W. M., A review of di(2-ethylhexyl)-phthalate (DEHP) risk assessments
   PubMed Web of Science ®Google Scholar
• Drug Metab. Rev. 1989; 21: 3–12, EPA, U.S. Environmental Protection Agency, 1988, Draft; Drinking Water Criteria Document for Phthalic Acid Esters (PAEs), Cincinnati, OH: USEPA, cited in Beliles, R., Salinas, J. A., and Kluwe, W. M., A review of di(2-ethylhexyl)phthalate (DEHP) risk assessments
   PubMed Web of Science ®Google Scholar
• 1987, IARC Monographs on the evaluation of carcinogenic risks to humans Suppl. 7
   Google Scholar
• Drug Metab. Rev. 1989; 21: 111–120, EPA, U.S. Environmental Protection Agency, 1986, cited in Schulz, C. O., Assessing human health risks from exposure to di(2-ethylhexyl)phthalate (DEHP) and related phthalates: scientific is
   PubMed Web of Science ®Google Scholar
• Lancet 1984; 2: 600–604, Committee of Principal Investigators, WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up
   PubMed Web of Science ®Google Scholar
• Br. Med. J. 1971; 4: 775–784, Research Committee of the Scottish Society of Physicians, Ischaemic heart disease: a secondary prevention trial using clofibrate
   PubMedGoogle Scholar
• J. Am. Med. Assoc. 1975; 231: 360–381, The Coronary Drug Project Research Group, Clofibrate and niacin in coronary heart disease
   PubMed Web of Science ®Google Scholar
• Saracci R., Kogevinas M., Bertazzi P. A., Bueno de Mesquita B. H., Coggon D., Green L. M., Kauppinen T., Ka L. A., Littorin M., Lynge E., et al. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols [see comments]. Lancet 1991; 338: 1027–1032
   PubMed Web of Science ®Google Scholar
• Bueno de Mesquita H. B., Doombos G., Van der Kuip D. A., Kogevinas M., Winkelmann R. Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands. Am. J. Ind. Med. 1993; 23: 289–300
   PubMed Web of Science ®Google Scholar
• Asp S., Riihimäki V., Hernberg S., Pukkala E. Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up. Am. J. Ind. Med. 1994; 26: 243–253
   PubMed Web of Science ®Google Scholar