Bis(2‐ethylhexyl)phthalate: Evaluation of risks to health from environmental exposure in Canada

References

• Albro , P.W. , Hass , J.R. , Peck , C.C. , Odam , D.G. , Corbett , J.T. , Bailey , F.J. , Blatt , H.E. and Barrett , B.B. 1981 . Identification of the metabolites of DEHP in urine from the African green monkey . Drug Metab. Dispos. , 9 : 223 – 225 .
   PubMed Web of Science ®Google Scholar
• ATSDR (Agency for Toxic Substances and Disease Registry) . 1989 . Toxicological Profile for Di‐(2‐Ethylhexyl)Phthalate. , 119 U.S. Public Health Service .
   Google Scholar
• ATSDR (Agency for Toxic substances and Disease Registry) . 1992 . Toxicological Profile for Di‐(2‐Ethylhexyl)Phthalate , 131 U.S. Public Health Service . (Update) Draft for Public Comment
   Google Scholar
• Barber , E.D. , Astill , B.D. , Moran , E.J. , Schneider , B.F. , Gray , T.J.B. and Gray , B.G. 1987 . Peroxisome induction studies on seven phthalate esters . Toxicol. Ind. Health. , 3 : 7 – 22 .
   PubMed Web of Science ®Google Scholar
• Busser , M.T. and Lutz , W.K. 1987 . Stimulation of DNA synthesis in rat and mouse liver by various tumour promoters . Carcinogenesis. , 8 : 1433 – 1437 .
   PubMedGoogle Scholar
• Butterworth , B.E. 1987 . “ Genetic toxicology of di(2‐ethylhexyl)phthalate ” . In Nongeniotoxic mechanisms in carcinogenesis. , Banbury Report 25 257 – 276 .
   Google Scholar
• Butterworth , B.E. , Smith‐Oliver , T. , Earle , L. , Loury , D.J. , White , R.D. , Doouttle , D.J. , Working , P.K. , Cattley , R.C. , Jirtle , R. , Michalopoulos , G. and Strom , S. 1989 . Use of primary cultures of human hepatocytes in toxicology studies . Cancer Res. , 49 : 1075 – 1084 .
   PubMed Web of Science ®Google Scholar
• Carpenter , C.P. , Weil , C.J. and Smyth , H.F. 1953 . Chronic oral toxicity of DEHP for rats, guinea pigs and dogs . Am. Med. Assoc. Arch. Ind. Hyg. , 8 : 219 – 226 .
   PubMedGoogle Scholar
• Cattley , R.C. , Conway , J.G. and Popp , J.A. 1987 . Association of persistent peroxisome proliferation and oxidative injury with hepatocarcinogenicity in female F344 rats fed di(2‐ethylhexyl)phthalate for 2 years . Cancer Lett. , 38 : 15 – 22 .
   PubMed Web of Science ®Google Scholar
• CCAC (Consumer and Corporate Affairs Canada) . 1992 . A Survey of Bis[2‐ethylhexyl] Phthalate (DEHP) in Children's Products. , Ottawa, Ontario : Scientific and Laboratory Services Division, Product Safety Branch . Project No. 91–0358 (Unpublished)
   Google Scholar
• CMA (Chemical Manufacturers Association) . 1984 . A 21‐Day Dose Relationship Study of DEHP in rats. , Report No. 0512/1/84 Prepared by the British Industrial Biological Research Association .
   Google Scholar
• CPSC (U.S. Consumer Product Safety Commission) . 1985 . Report to the U.S. Consumer Product Safety Commission by the Chronic Hazard Advisory Panel on Di‐(2‐ethylhexyl)phthalate (DEHP). 20 Washington, D.C.
   Google Scholar
• Crocker , J.F.S. , Safe , S.H. and Acott , P. 1988 . Effects of chronic phthalate exposure on the kidney . J. Toxicol. Environ. Health. , 23 : 433 – 444 .
   PubMed Web of Science ®Google Scholar
• Dabholkar , A.S. 1988 . Peroxisomes in the rat brain and the effects of di‐(2‐ethylhexyl)phthalate during postnatal development . Acta Anat. , 131 : 218 – 221 .
   PubMedGoogle Scholar
• Dostal , L.A. , Jenkins , W.L. and Schwetz , B.A. 1987 . Hepatic peroxisome proliferation and hypolipidemic effects of DEHP in neonatal and adult rats . Toxicol. Appl. Pharmacol. , 87 : 81 – 90 .
   PubMed Web of Science ®Google Scholar
• Dostal , L.A. , Chapin , R.E. , Stefanski , S.A. , Harris , M.W. and Schwetz , B.A. 1988 . Testicular toxicity and reduced sertoli cell numbers in neonatal rats by di(2‐ethylhexyl)phthalate and the recovery of fertility as adults . Toxicol. Appl. Pharmacol. , 95 : 104 – 121 .
   PubMed Web of Science ®Google Scholar
• EHD (Environmental Health Directorate) . 1992 . Determination of “toxic”; under Paragraph 11)c of the Canadian Environmental Protection Act , Ottawa, Ontario, , Canada : Bureau of Chemical Hazards, Environmental Health Directorate, Health Protection Branch, Department of National Health and Welfare . Unpublished
   Google Scholar
• Elsenrelch , S.J. , Looney , B.B. and Thornton , J.D. 1981 . Airborne organic contaminants in the Great Lakes ecosystem . Environ. Sci. Tech. , 15 : 30 – 38 .
   Google Scholar
• Elcombe , C.R. and Mitchell , A.M. 1986 . Peroxisome proliferation due to Di(2‐ethylhexyl) phthalate (DEHP): species differences and possible mechanisms . Environ. Health Perspect. , 70 : 211 – 219 .
   PubMed Web of Science ®Google Scholar
• Elslsi , A.E. , Carter , D.E. and Slpes , I.G. 1985 . Dermal absorption and tissue distribution of phthalate esters . Toxicologist. , 5 : 246
   Google Scholar
• Eriksson , P. and Darnerud , P.O. 1985 . Distribution and retention of some chlorinated hydrocarbons and a phthalate in the mouse brain during the pre‐weaning period . Toxicology. , 37 : 189 – 203 .
   PubMed Web of Science ®Google Scholar
• Frick , M.H. , Elo , O. , Haapa , K. , Henonen , O.P. , Heinsalmi , P. , Helo , P. , Huttunen , J.K. , Kaitaniemi , P. , Koskinen , P. , Manninen , V. , Maenpaa , H. , malkonen , M. , Manttari , M. , Norola , S. , Pasternack , A. , Pikkarainen , J. , Romo , M. , Sjoblom , T. and Nikkila , E.A. 1987 . 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 . New Engl. J. Med. , 317 : 1237 – 1245 .
   PubMed Web of Science ®Google Scholar
• Ganning , A.E. , Brunk , U. , Edlund , C. , Elhammer , A. and Dallner , G. 1987 . Effects of prolonged administration of phthalate ester on the liver . Environ. Health Perspect. , 73 : 251 – 258 .
   PubMed Web of Science ®Google Scholar
• Ganning , A.E. , Olsson , M.J. , Brunk , U. and Dallner , G. 1991 . Effects of prolonged treatment with phthalate ester on rat liver . Pharmacol. Toxicol. , 68 : 392 – 401 .
   Google Scholar
• Golder Associates . 1987 . Testing of Specific Organic Compounds in Soils in Background Urban Areas. Port Credit and Oakville/Burlington Ontario. , Working paper to Shell Canada and Texaco Canada Limited .
   Google Scholar
• Gray , T.J. and Butterworth , K.R. 1980 . Testicular atrophy produced by phthalate esters . Arch. Toxicol. (Suppl.). , 4 : 452 – 455 .
   PubMedGoogle Scholar
• Gray , T.J.B. , Butterworth , K.R. , Gaunt , I.F. , Grasso , P. and Gangolli , S.D. 1977 . Short‐termtoxicity study of di(2‐ethylhexyl)phthalate in rats . Fd. Cosmet. Toxicol. , 15 : 389 – 399 .
   PubMedGoogle Scholar
• Gray , T.J. , Rowland , I.R. , Foster , P.M. and Gangolu , S.D. 1982 . Species differences in the testicular toxicity of phthalate esters . Toxicol. Lett. , 11 : 141 – 147 .
   PubMed Web of Science ®Google Scholar
• Halina , G.P. 1993 . Alberta Environment , (personal communication)
   Google Scholar
• Hamano , Y. , Kuwano , A. , Inoue , K. , Oda , Y. , Yamamoto , H. , Mitsuda , B. and Kunita , N. 1977 . Studies on toxicity of phthalic acid esters, 1st Report ‐ Teratogenic effects in mice administered orally . Osaka‐furitsu Koshu Esei kenkyusho Kenkyu Hokoka Shokukhim Eisei Hen. , 8 : 29 – 33 .
   Google Scholar
• Harris , R.S. , Hodge , H.C. , Maynard , E.A. and Blanchat , H.J. 1956 . Chronic oral toxicity of 2‐ethylhexyl phthalate in rats and dogs . Arch. Ind. Health. , 3 : 259 – 264 .
   Google Scholar
• Hinton , R.H. , Mitchell , F.E. , Mann , A. , Chescoe , D. , Price , S.C. , Nunn , A. , Grasso , P. and Bridges , J.W. 1986 . Effects of phthalic acid esters on the liver and thyroid . Environ. Health Perspect. , 70 : 195 – 210 .
   PubMed Web of Science ®Google Scholar
• Hsia , M.T.S. 1990 . The Relationship Between Cara'nogenesis and Peroxisome Proliferation in Rodent Liver after Exposure to the Plasticizer DEHP and DEHA , Contract report prepared by The MITRE Corporation for U.S. Food and Drug Administration . MTR‐90W00034
   Google Scholar
• IPCS (International Programme on Chemical Safety) . 1992 . Diethylhexyl Phthalate. , Environmental Health Criteria 131 141 Geneva : World Health Organization .
   Google Scholar
• Kluwe , W.M. , Haseman , J.K. , Douglas , J.F. and Huff , J.E. 1982 . The carcinogenicity of dietary DEHP in Fischer 344 rats and B6C3F1 mice . J. Toxicol. Environ. Health. , 10 : 797 – 815 .
   PubMed Web of Science ®Google Scholar
• Kluwe , W.M. , Haseman , J.K. and Huff , J.E. 1983 . The carcinogenicity of di(2‐ethylhexyl)phthalate (DEHP) in perspective . J. Toxicol. Environ. Health. , 12 : 159 – 169 .
   PubMed Web of Science ®Google Scholar
• Krauskopf , L.G. 1973 . Studies on the toxicity of phthalates via ingestation . Environ. Health Perspect. , 3 : 61 – 72 .
   PubMedGoogle Scholar
• Lake , B.G. , Gray , T.J.B. , Foster , J.R. , Stubberfield , C.R. and Gangolu , S.D. 1984 . Comparative studies on di(2‐ethylhexyl)phthalate induced hepatic peroxisome proliferation in the rat and hamster . Toxicol. Appl. Pharmacol. , 72 : 46 – 60 .
   PubMed Web of Science ®Google Scholar
• Lake , B.G. , Cook , W.M. , Worrell , N.R. , Cunninghame , M.E. , Evans , J.G. , Price , R.J. , Young , P.J. and Carpanini , F.M.B. 1991 . Dose‐response relationships for induction of hepatic peroxisome proliferation and testicular atrophy by phthalate esters in the rat [abstract] . Hum. Exp. Toxicol. , 10 : 67
   Google Scholar
• Marsman , D.S. , Cattley , R.C. , Conway , J.G. and Popp , J.A. 1988 . 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. , 48 : 6739 – 6744 .
   PubMed Web of Science ®Google Scholar
• Meek , M.E. , Newhook , R. , Liteplo , R.G. and Armstrong , V.C. 1994 . Approach to assessment of risk to human health for Priority Substances under the Canadian Environmental Protection Act . J. Environ. Sci Health , C12 (2) : 105 – 134 .
   Web of Science ®Google Scholar
• Mitchell , A.M. , Lhuguenot , J.C. , Bridges , J.W. and Elcombe , C.R. 1985a . Identification of the proximate peroxisome proliferator(s) derived from di(2‐ethylhexyl)phthalate . Toxicol. Appl. Pharmacol. , 80 : 23 – 32 .
   PubMed Web of Science ®Google Scholar
• Mitchell , F.E. , Price , S.G. , Hinton , R.H. , Grasso , P. and Bridges , J.W. 1985b . Time and dose‐response study of the effects on rats of the plasticizer di(2‐ethylhexyl) phthaiate . Toxicol. Appl. Pharmacol. , 81 : 371 – 392 .
   PubMed Web of Science ®Google Scholar
• MOE (Ontario Ministry of The Environment) . 1984 . Drinking Water Survey of Selected Municipalities in the Niagara Area and Lake Ontario.
   Google Scholar
• Morton , S.J. 1979 . The Hepatic Effects of Dietary Di‐2‐ethyl‐hexyl Phthaiate , 120 Ann Arbor, Michigan : The Johns Hopkins University. UMI Dissertation Information Service . Ph.D. Dissertation
   Google Scholar
• Nagasaki , H. , Tomii , S. , Mega , T. , Hirao , K. , Shinohara , Y. and Ito , N. 1974 . Chronic toxicity of dioctyl phthaiate (DOP) in male rats and mice . J. Nara Med. Assoc. , 25 : 649 – 654 .
   Google Scholar
• NHW (National Health and Welfare) . 1992 . Market Basket Survey of Foods from Halifax. , Ottawa : Food Research Division, Food Directorate, Health Protection Branch . (unpublished results)
   Google Scholar
• Nielsen , J. , Akesson , B. and Skerfving , S. 1985 . Phthaiate ester exposure‐air levels and health of workers processing polyvinylchloride . Am. Ind. Hyg. Assoc. J. , 46 : 643 – 647 .
   PubMed Web of Science ®Google Scholar
• Northup , S. , Martis , L. , Ulbricht , R. , Garber , J. , Miripol , J. and Schmitz , T. 1982 . Comment on the carcinogenic potential of di(2‐ethylhexyl)phthalate . J. Toxicol. Environ. Health. , 10 : 493 – 518 .
   PubMed Web of Science ®Google Scholar
• NTP (National Toxicology Program) . 1982 . Carcinogenesis Bioassay of Di(2‐ethylhexyl)phthalate (CASNo. 117–81–7) in F344 Rats and B6C3F, Mice (Feed Study). , NTP‐80–37 127 Research Triangle Park, NC NIH Publication No. 82–1773
   Google Scholar
• Oliver , M.F. , Heady , J.A. , Morris , J.N. and Cooper , J. 1984 . WHO cooperative trial on primary prevention of ischaemic heart disease with ciofibrate to lower serum cholesterol: final mortality follow‐up . The Lancet. , 8403 : 600 – 604 .
   Google Scholar
• OTA , H. , Onda , H. , Kodama , H. and Yamada , N. 1974 . Biological effects of phthaiate esters: histopathological investigation by experiments on mice . Nippon Eiseigaku Zasshi. , 25 : 519 – 524 .
   Google Scholar
• Otson , R. and Benoit , F.M. Indoor Air Quality in Cold Climates. An Air Pollution Control Association Speciality Conference . Surveys of selected organics in residential air , Edited by: Walkinshaw , D.S. pp. 224 – 236 .
   Google Scholar
• PEGG , D.G. 1988 . Disposition of Di‐2‐ethyihexyl Phthaiate Following Inhalation and Perorai Exposure in Rats OTS 8(d) submission. Microfiche No. 0206189 (unpublished). In USEPA (1991)
   Google Scholar
• Pollack , G.M. , LI , R.C. , Ermer , J.C. and Shen , D.D. 1985 . Effects of route of administration and repetitive dosing on the disposition kinetics of DEHP and its mono‐de‐esterified metabolite in rats . Toxicol. Appl. Pharmacol. , 79 : 246 – 256 .
   PubMed Web of Science ®Google Scholar
• Popp , J.A. , Garvey , L.K. and Cattley , R.C. 1987 . In vivo studies on the mechanism of di(2‐ethylhexyl)phthalate carcinogensis . Toxicol. Ind. Health. , 3 : 151 – 163 .
   PubMed Web of Science ®Google Scholar
• Price , S.C. , Chescoe , D. , Grasso , P. , Wright , M. and Hinton , R.H. 1988 . Alterations in the thyroids of rats treated for long periods with di‐(2‐ethylhexyl)phthalate or with hypolipidaemic agents . Toxicology Lett. , 40 : 37 – 46 .
   PubMed Web of Science ®Google Scholar
• Rao , M.S. and Reddy , J.K. 1987 . Peroxisome proliferation and hepatocarcinogenesis . Carcinogenesis. , 8 : 637 – 645 .
   PubMedGoogle Scholar
• Rao , M.S. , Yeldandi , A.V. and Subbbarao , V. 1990 . Quantitative analysis of hepatocellular lesions induced by di(2‐ethylhexyl) phthalate in F‐344 rats . J. Toxicol. Environ. Health , 30 : 85 – 89 .
   PubMed Web of Science ®Google Scholar
• Reel , J.R. , Lawton , A.D. and Lamb , J.C. 1982 . Diethylhexyl Phthalate (DEHP): Reproduction and Fertility Assessment in CD‐1 Mice when Administered in the Feed , Report ISS RTI‐31U‐2344, RTI‐72, NTP‐84–079 221 NTIS Publication No. PB84–181734
   Google Scholar
• Reubsaet , F.A.G. , Veerkamp , J.H. , Dirven , H.A.A.M. , Bruckwilder , M.L.P. , Hashimoto , T. , Trijbels , J.M.F. and Monnens , L.A.H. 1990 . The effect of di(ethylhexyl)phthalate on fatty acid oxidation and carnitine palmitoyltransferase in various rat tissues . Biochim. Biophys. Acta. , 1047 : 264 – 270 .
   PubMedGoogle Scholar
• Rhodes , C. , Orton , T.C. , Pratt , I.S. , Batten , P.L. , Bratt , H. and Jackson , S.J. 1986 . Comparative pharmacokinetics and subacute toxicity of DEHP in rats and marmosets: extrapolation of effects in rodents to man . Environ. Health Perspect. , 65 : 299 – 308 .
   PubMed Web of Science ®Google Scholar
• Rodricks , J.V. and Turnbull , D. 1984 . Assessment of Possible Carcinogenic Risk Resulting from Exposure to Di(2‐ethylhexyt)phthalate (DEHP) in Children's Products , 122 Washington, D.C. : Prepared for the Phthalate Esters Panel, Chemical Manufacturers Association .
   Google Scholar
• Schmezer , P. , Pool , B.L. , Klein , R.G. , Komitowski , D. and Schmahl , D. 1988 . Various short‐term assays and two long‐term studies with the plasticizer di(2‐ethylhexyl) phthalate in the Syrian golden hamster . Carcinogenesis. , 9 : 37 – 43 .
   PubMed Web of Science ®Google Scholar
• Schmid , P. and Schlatter , C. 1985 . Excretion and metabolism of DEHP in man . Xenobiotica. , 15 : 251 – 256 .
   PubMed Web of Science ®Google Scholar
• Shaffer , C.B. , Carpenter , C.P. and Smyth , H.F. 1945 . Acute and subacute toxicity of DEHP with note upon its metabolism . J. Indust. Hyg. Toxicol. , 27 : 130 – 135 .
   Google Scholar
• Shiota , K. , Chou , M.J. and Nishimura , H. 1980 . Embryotoxic effects of DEHP and di‐n‐butyl phthalate (DBP) in mice . Environ. Res. , 22 : 245 – 253 .
   PubMed Web of Science ®Google Scholar
• Shiota , K. and Nishimura , H. 1982 . Teratogenicity of di(2‐ethylhexyl)phthalate (DEHP) and di‐n‐butyl phthalate (DBP) in mice . Environ. Health Perspect. , 45 : 65 – 70 .
   PubMed Web of Science ®Google Scholar
• Shiota , K. and Mima , S. 1985 . Assessment of the teratogenicity of DEHP and MEHP in mice . Arch. Toxicol. , 56 : 263 – 266 .
   PubMed Web of Science ®Google Scholar
• Short , R.D. , Robinson , E.C. , lington , A.W. and Chin , A.E. 1987 . Metabolic and peroxisome proliferation studies with di(2‐ethylhexyl)phthalate in rats and monkeys . Toxicol. Ind. Health. , 3 : 185 – 194 .
   PubMed Web of Science ®Google Scholar
• Smith‐Oliver , T. and Butterworth , B.E. 1987 . Correlation of the carcinogenic potential of di(2‐ethylhexyl)phthalate (DEHP) with induced hyperplasia rather than with genotoxic activity . Mutation Res. , 188 : 21 – 28 .
   PubMed Web of Science ®Google Scholar
• Spink , D. 1986 . Alberta Environment , (unpublished data)
   Google Scholar
• Thiess , A.M. and Flieg , I. 1978 . Chromosomal studies in workers exposed to di‐2‐ethylhexyl phthalate (DOP) . Zentralbl. Arbeitsmed. , 28 : 351 – 355 . (in German, in IPCS, 1992)
   Google Scholar
• Thiess , A.M. , Korte , A. and Fueg , H. Mortality study in workers exposed to di‐2‐ethylhexyl phthalate (DOP) . Possibilities and Limits of Biological Monitoring ‐ Problems in Occupational Medicine of the Industrial Occupational Health Services. Proceedings of a conference . May 1978 , Frankfurt. pp. 155 – 164 . A.W. Gertner . Stuttgart (in German, in IPCS, 1992)
   Google Scholar
• Thiess , A.M. , Korte , A. and Flieg , H. Morbidity study in workers exposed to di‐2‐ethylhexyl phthalate (DEHP) . Possibilities and Limits of Biological Monitoring ‐ Problems in Occupational Medicine of the Industrial Occupational Health Services. Proceedings of a conference . May 1978 , Frankfurt. pp. 137 – 154 . A.W. Gertner . Stuttgart (in German, in IPCS, 1992)
   Google Scholar
• Tyl , R.W. , Price , C.J. , Marr , M.C. and Kimmel , C.A. 1988 . Developmental toxicity evaluation of dietary di(2‐ethylhexyl)phthalate in Fischer 344 rats and CD‐1 mice . Fund. Appl. Toxicol. , 10 : 395 – 412 .
   PubMedGoogle Scholar
• USEPA (U.S. Environmental Protection Agency) . 1991 . Drinking Water Criteria Document for Phthalic Acid Esters (PAESJ. , Final Report 321 Cincinnati, Ohio : Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office .
   Google Scholar
• Wolkowski‐Tyl , R. , Jones‐Price , C. and Marr , M.C. 1984a . Teratologic Evaluation of Diethylhexyl Phthalate (CAS No. 117–81–7) in Fischer 344 Rats , Report: ISS RTI‐60, FDA/NCTR‐84/135 NTIS Publication No. PB85–105658
   Google Scholar
• Wolkowski‐Tyl , R. , Jones‐Price , C , Marr , M.C. and Kinmel , C.A. 1984b . Teratologic Evaluation of Diethylhexyl Phthalate in CD‐1 Mice , Final Report Jefferson, Arkansas : National Center for Toxicological Research . NTIS Publication No. PB85–105674
   Google Scholar
• Woodward , K.N. 1988 . Phthalate Esters Toxicity and Metabolism , Vol I & II , Boca Raton, Florida : CRC Press Inc. .
   Google Scholar
• Author to whom correspondence or requests for the complete Assessment Report and (unpublished) Supporting Documentation should be addressed.
   Google Scholar