Risk assessment of oral exposure to diisononyl phthalate from children's products

Regulatory Toxicology and Pharmacology

Volumn 40, Issue 2, 2004, Pages 151-167

  Babich, Michael A ^a   Chen, Shing Bong ^a   Greene, Michael A ^a   Kiss, Celestine T ^a   Porter, Warren K ^a   Smith, Timothy P ^a   Wind, Marilyn L ^a   Zamula, William W ^a  

^a US Consumer Product Safety Commission   (United States)

Author keywords

Children's mouthing behavior; Diisononyl phthalate; Phthalate ester plasticizers; Phthalate migration from PVC; Phthalates in children's toys; Probabilistic risk assessment; Risk assessment

Indexed keywords

PHTHALIC ACID DERIVATIVE; PLASTIC;

AGE DISTRIBUTION; ARTICLE; CANCER RISK; DEVELOPMENTAL DISORDER; ENDOCRINE DISEASE; EXPOSURE; GENOTOXICITY; HEALTH HAZARD; HEPATITIS; HUMAN; LIVER TOXICITY; LONG TERM EXPOSURE; NEPHROTOXICITY; NONHUMAN; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; RISK ASSESSMENT; STATISTICAL ANALYSIS; TOXICITY; TOXICOKINETICS;

EID: 4644241303     PISSN: 02732300     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.yrtph.2004.06.005     Document Type: Article

References (82)

1. P.W. Albro, and R.O. Thomas Enzymatic hydrolysis of di-(2-ethylhexyl) phthalate by lipases Biochimica et Biophysica Acta 306 1973 380 390
2. J. Ashby, A. Brady, C.R. Elcombe, B.M. Elliott, J. Ishmael, J. Odum, J.D. Tugwood, S. Kettle, and I.F.H. Purchase Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis Human and Experimental Toxicology 13 Suppl. 2 1994 S1 S117
3. 2U-globulin: association with chemically induced renal toxicity and neoplasia in the male rat. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC 20460, September 1991. EPA/625/3-91/019F
4. Bankston, J.R., 1992. Supplement: 13-Week Subchronic Dietary Oral Toxicity Study with Di(Isononyl) Phthalate in Mice with Cover Letter Dated 070692 and Attachments. Aristech Chimical Corporation, Pittsburgh, PA 15230. July 6, 1992. EPA document no. 89-920000303
5. P. Bannasch, M. Bloch, and H. Zerban Specific changes of the perisinusoidal liver cells induced in rats by N-nitrosomorpholine Laboratory Investigations 44 1981 252 264
6. E.D. Barber, B.D. Astill, E.J. Moran, B.F. Schneider, T.J.B. Gray, B.G. Lake, and J.G. Evans Peroxisome induction studies on 7 phthalate esters Toxicology and Industrial Health 3 1987 7 24
7. E.D. Barber, M. Cifone, J. Rundell, R. Przygoda, B.D. Astill, E. Moran, A. Mulholland, E. Robinson, and B. Schneider Results of the L5178Y mouse lymphoma assay and the Balb/3T3 cell in vitro transformation assay for eight phthalate esters Journal of Applied Toxicology 20 2000 69 80
8. D.J. Benford, S. Patel, H.J. Reavy, A. Mitchell, and N.J. Sarginson Species differences in the response of cultured hepatocytes to phthalate esters Food and Chemical Toxicology 24 1986 799 800
9. B.G. Blount, M.J. Silva, S.P. Caudill, L.L. Needham, J.L. Pirkle, E.J. Sampson, G.W. Lucier, R.J. Jackson, and J.W. Brock Levels of seven urinary phthalate metabolites in a human reference population Environmental Health Perspectives 108 2000 979 982
10. K. Bouma, and D.J. Schakel Migration of phthalates from PVC toys into saliva simulant by dynamic extraction Food Additives and Contaminants 19 2002 602 610
11. T.A. Braunbeck, S.J. Teh, S.M. Lester, and D.E. Hinton Ultrastructural alterations in liver of medaka (Oryzias latipes) exposed to diethylnitrosamine Toxicological Pathology 20 1992 179 196
12. British Industrial Biological Research Association (BIBRA), 1985. A 21-day feeding study of diisononyl phthalate to rats: effects on liver lipids. British Industrial Biological Research Association, Carshalton, Surrey, England. EPA Document No. 40+8626208
13. J.W. Brock, S.P. Caudill, M.J. Silva, L.L. Needham, and E.D. Hilborn Phthalate monoester levels in the urine of young children Bulletin of Environmental Contamination and Toxicology 68 2002 309 314
14. D.J. Caldwell, S. Eldridge, A.W. Lington, and R.H. McKee Retrospective evaluation of alpha 2u-globin accumulation in male rat kidneys following high doses of diisononyl phthalate Toxicological Sciences 51 1999 153 160
15. R.C. Cattley, J. DeLuca, C. Elcombe, P. Fenner-Crisp, B.G. Lake, D.S. Marsman, T.A. Pastoor, J.A. Popp, D.E. Robinson, B. Schwetz, J. Tugwood, and W. Wahli Do peroxisome proliferating compounds pose hepatocarcinogenic hazard to humans? Regulatory Toxicology and Pharmacology 27 1998 47 60
16. Chemical Manufacturers Association (CMA), 2000. Letter from Courtney M. Price, Vice-President, CHEMSTAR, Chemical Manufacturers Association, Arlington, VA 22209, to Ronald L. Medford, U.S. Consumer Product Safety Commission, Bethesda, MD 20814, with attachments. April 3, 2000. Information for the Consumer Product Safety Commission Chronic Hazard Advisory Committee regarding diisononyl phthalate (DINP). Part C. Information on the non-cancer no effect level
17. Chen, S.-B., 2002. Screening of toys for PVC and phthalates migration. U.S. Consumer Product Safety Commission, Bethesda, MD, June 20, 2002
18. Consumer Product Safety Commission (CPSC), 1992. Labeling requirements for art materials presenting chronic hazards: guidelines for determining chronic toxicity of products subject to the FHSA; supplementary definition of "toxic" under the Federal Hazardous Substances Act; final rules. Federal Register 57, 46626-46674, October 9, 1992
19. Consumer Product Safety Commission (CPSC), 1998. The risk of chronic toxicity associated with exposure to diisononyl phthalate (DINP) in children's products. U.S. CPSC, Bethesda, MD 20814, December 1998
20. Consumer Product Safety Commission (CPSC), 2001. Chronic hazard advisory panel on diisononyl phthalate (DINP). U.S. CPSC, Bethesda, MD 20814, June 2001
21. Consumer Product Safety Commission (CPSC), 2002. Updated risk assessment of oral exposure to diisononyl phthalate (DINP) in children's products. U.S. CPSC, Bethesda, MD 20814, June 2002
22. CSTEE, 2001. Opinion on the results of the risk assessment of: 1,2-benzenedicarboxylic acid, Di-C8-C10-branched alkyl esters, C9-rich and di-"isononyl" phthalate. CAS # 68515-48-0 and CAS # 28553-12-0; EINECS # 271-090-9 and EINECS # 249-079-5. Scientific Committee on Toxicity, Ecotoxicity, and the Environment, European Commission, Brussels, Belgium. Opinions expressed at the 27th CSTEE plenary meeting, October 30, 2001
23. R.M. David Exposure to phthalate esters Environmental Health Perspectives 108 2000 A440
24. Environmental Protection Agency EPA, 1997. Exposure Factors Handbook. Volume I. General Factors. Office of Research and Development, U.S. Environmental Protection Agency, Office of Toxic Substances, Washington, DC 20460, August 1997. EPA 600/P-95/002Fa
25. Experimental Protection Agency (EPA), 2000. Benchmark Dose Software, Version 1.20. US Environmental Protection Agency, Office of Research and Development, Washington, DC 20460
26. Experimental Pathology Laboratories, Inc. (EPL), 1999. Histopathology peer review and pathology working group review of selected lesions of the liver and spleen in male and female F344 rats exposed to di(isononyl)phthalate. Pathology Working Group Review. Pathology Report. Experimental Pathology Laboratories, Inc., Research Triangle Park, NC 27709. For the Chemical Manufacturers Association, Arlington, VA 22209, August 24, 1999
27. France, 2001. Risk assessment, 1,2-benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9 Rich and Di"Isononyl" Phthalate CAS # 68515-48-0 and CAS # 28553-12-0; EINECS # 271-090-9 and EINECS # 249-079-5, May 2001
28. L.E. Gray, J. Ostby, J. Furr, M. Price, D.N.R. Veeramachaneni, and L. Parks Perinatal exposure to phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat Toxicological Sciences 58 2000 350 365
29. Greene, M., 2002a. Mouthing times among young children from observational data. U.S. CPSC, Bethesda, MD 20814, June 17, 2002
30. Greene, M., 2002b. Oral DINP intake among young children. U.S. CPSC, Bethesda, MD 20814, June 18, 2002
31. Groot, M.E., Lekkerkerk, M.C., Steenbekkers, L.P.A., 1998. Mouthing behaviour of young children: an observational study. Wageningen: Agricultural University, Waginen, The Netherlands. Household and Consumer Studies Report # 3. September 1998 (ISBN 90-6754-548-1)
32. M. Hall, A. Matthews, L. Webley, and R. Harling Effects of di-isononyl phthalate (DINP) on peroxisomal markers in the marmosetâ€"DINP is not a peroxisome proliferator The Journal of Toxicological Sciences 24 1999 237 244
33. C.A. Harris, P. Henttu, M.G. Parker, and J.P. Sumpter The estrogenic activity of phthalate esters in vitro Environmental Health Perspectives 105 1997 802 811
34. J.K. Haseman, J. Arnold, and S.L. Eustis Tumor incidences in Fischer 344 rats: NTP historical data G.A. Boorman S.L. Eustis M.R. Elwell C.A. Montgomery Jr. W.F. MacKensie Pathology of the Fischer Rat 1990 Academic Press New York, NY
35. J.K. Haseman, J.R. Hailey, and R.W. Morris Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: A National Toxicology Program Update Toxicologic Pathology 26 1998 428 441
36. S.C. Hasmall, N.H. James, N. Macdonald, D. West, S. Chevalie, S.C. Cosulich, and R.A. Roberts Suppression of apoptosis and induction of DNA synthesis in vitro by the phthalates plasticizers monoethylhexylphthalate (MEHP) and diisononylphthalate (DINP): a comparison of rat and human hepatocytes in vitro Archives of Toxicology 73 1999 451 456
37. Health Canada, 1998. Updated. Risk Assessment on Diisononyl Phthalate in Vinyl Children's Products. Consumer Products Division, Product Safety Bureau, Environmental Health Directorate, Health Protection Branch, Ottawa, Ontario. November 14, 1998
38. J. Hellwig, H. Freudenberger, and R. Jackh Differential prenatal toxicity of branched phthalate esters in rats Food and Chemical Toxicology 35 1997 501 512
39. International Agency for Research on Cancer (IARC), 1995. Peroxisome proliferation and its role in carcinogenesis. International Agency for Research on Cancer, World Health Organization, Lyon. IARC Technical Report No. 24
40. International Agency for Research on Cancer (IARC), 2000. Di(2-ethylhexyl) phthalate. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 77, 41-148
41. Janssen, P., Van Veen, M., Van Apeldoorn, M., Speijers, G., 1998. Phthalates in teething-rings/animal figures for infants. National Institute of Public Health and the Environment (RIVM), Center for Substances and Risk Assessment, Bilthoven, The Netherlands, January 15, 1998
42. D.R. Juberg, K.M. Thompson, K. Alfano, and R.J. Coughlin An observational study of object mouthing behavior by young children Pediatrics 107 2001 135 142
43. E. Karbe, and R.L. Kerlin Cystic degeneration/spongiosis hepatis in rats Toxicologic Pathology 30 2002 216 227
44. W. Kaufmann, K. Deckardt, R.H. McKee, J.H. Butala, and R. Bahnemann Tumor induction in mouse liver: diisononyl phthalate (DINP) acts via peroxisomal proliferation Regulatory Toxicology and Pharmacology 60 2002 286
45. R. Kavlock, K. Boekelheide, R. Chapin, M. Cunningham, E. Faustman, P. Foster, M. Golub, R. Henderson, I. Hinberg, R. Little, J. Seed, K. Shea, S. Tabacova, R. Tyl, P. Williams, and T. Zacharewski NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-isononyl phthalate Reproductive Toxicology 16 2002 679 708
46. Kiss, C., 2002. A mouthing observation study of children under 6 years. U.S. CPSC, Bethesda, MD 20814, June 14, 2002
47. J.E. Klaunig, M.A. Babich, K.P. Baetcke, J.C. Cook, J.C. Corton, R.M. David, J.G. DeLuca, D.Y. Lai, R.H. McKee, J.M. Peters, R.A. Roberts, and P.A. Fenner-Crisp PPARα agonist-induced rodent tumors: modes of action and human relevance Critical Reviews in Toxicology 33 2003 655 780
48. M. Kohn, F. Parham, S. Masten, C. Portier, M. Shelby, J. Brock, and L. Needham Human exposure estimates for phthalates Environmental Health Perspectives 108 2000 A440 A442
49. A.W. Lington, M.G. Bird, R.T. Plutnick, W.A. Stubblefield, and R.A. Scala Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats Fundamental and Applied Toxicology 36 1997 79 89
50. Litton Bionetics, 1981. Evaluation of R-1218 in the primary rat hepatocyte unscheduled DNA synthesis assay - final report. Litton Bionetics, Kensington, MD 20795. February 1981. EPA doc. no. 878210229; microfiche no. OTS 206260
51. R.H. McKee, M. El-Hawari, M. Stoltz, F. Pallas, and A.W. Lington Absorption, disposition and metabolism of di-isononyl phthalate (DINP) in F-344 rats Journal of Applied Toxicology 22 2002 293 302
52. R.H. McKee, R.T. Przygoda, M.A. Chirdon, G. Engelhardt, and M. Stanley Di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP) are not mutagenic Journal of Applied Toxicology 20 2000 491 497
53. R.L. Melnick Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)? Environmental Health Perspectives 109 2001 437 442
54. R.L. Melnick The IARC evaluation of di(2-ethylhexyl)phthalate (DEHP): a flawed decision based on an untested hypothesis International Journal of Occupational and Environmental Health 8 2003 284 286
55. Mid-West Research Institute (MWRI), 1981. Acute oral toxicity study in rats of TCI compounds: R-1268, R-1272, R-1286 and R-1287. U.S. EPA Document No. 878211655
56. Microbiological Associates, 1981. Activity of T1646 in the in vivo cytogenetics assay in rodents. Microbiological Associates, Bethesda, MD 20816, November 8, 1981. EPA doc. no. 878210231; microfiche no. OTS 206260
57. Moore, M.R., 1998a. Oncogenicity study in rats with di(isononyl)phthalate including ancillary hepatocellular proliferation and biochemical analyses. Covance Laboratories, Inc., Vienna, VA 22182. For Aristech Chemical Corporation, Pittsburgh, PA 15230, May 13, 1998. Covance 2598-104. U.S. EPA Document No. 89980000308
58. Moore, M.R., 1998b. Oncogenicity study in mice with di(isononyl)phthalate including ancillary hepatocellular proliferation and biochemical analyses. Covance Laboratories Inc., Vienna, VA 22182. For Aristech Chemical Corporation, Pittsburgh, PA 15230, January 29, 1998. Covance 2598-105. U.S. EPA Document No. 89990000046
59. Moore, M.R., 2000. A 13-week subchronic dietary oral toxicity study in mice with di(isononyl)phthalate including ancillary hepatocellular proliferation and biochemical analyses. Hazleton Washington, Inc., Vienna, VA 22182, June 30, 2000. HWA 2598-103
60. Myers, B.A., 1991. A subchronic (13-week) dietary oral toxicity study of di(isononyl)phthalate in Fischer 344 rats. Hazleton Washington, Inc. Unpublished Laboratory Report. For Aristech Chemical Corporation, Pittsburgh, PA 15230, August 12, 1991. EPA Document No. 89-920000224
61. National Library of Medicine (NLM), 2001. Chemical identification file (ChemID). Medical Literature Analysis and Retrieval System (MEDLARS). National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, November 2001
62. 1 Mice (Feed Studies). National Toxicology Program, Research Triangle Park, NC 27709. March 1982. Technical Report No. 217
63. J.S. Ostby, A.K. Hotchkiss, J.R. Furr, and L.E. Gray Jr. Investigation of the ability of diisononyl phthalate (DINP) to alter androgen-dependent tissue development in Spragueâ€"Dawley rats The Toxicologist 60 2001 225
64. L.G. Parks, J.S. Ostby, C.R. Lambright, B.D. Abbott, G.R. Klinefelter, N.J. Barlow, and L.E. Gray The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat Toxicological Sciences 58 2000 339 349
65. J.M. Peters, M.W. Taubeneck, C.L. Keen, and F.J. Gonzalez Di(2-ethylhexyl)phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-α Teratology 56 1997 311 316
66. G. Pugh Jr., J.S. Isenberg, L.M. Kamendulis, D.C. Ackley, L.J. Clare, R. Brown, A.W. Lington, J.H. Smith, and J.E. Klaunig Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in Cynomolgus monkeys Toxicological Sciences 56 2000 181 188
67. Rijk, R., Ehlert, K., 1999. Validation of the method "Determination of Diisononyl Phthalate in Saliva Simulant" (1999). TNO Nutrition and Food Research Institute, Ultrechtseweg, The Netherlands, May 27, 1999. TNO Report V99.598
68. Rijksinstituut voor Volksgesondheid en Milieu (National Institute of Public Health and Environment) (RIVM), 1998. In: Könemann, W.H. (Ed.), Phthalate Release from Soft PVC Baby Toys, Report from the Dutch Consensus Group. RIVM, Bilthoven, The Netherlands. RIVM report 61 3320 002, September 1998
69. Schaeffer, V.H., 1991. Reassessment of the human relevance of the male rat kidney tumors induced by p-dichlorobenzene. In: Hazard Evaluation of Consumer Products Containing 1,4-Dichlorobenzene. U.S. Consumer Product Safety Commission, Washington, DC 20207
70. D. Shaw, R. Lee, and R.A. Roberts Species differences in response to phthalate plasticizer monoisononyl phthalate (MINP) in vitro: a comparison of rat and human hepatocytes Archives of Toxicology 76 2002 344 350
71. Simoneau, C., Geiss, H., Roncari, A., Zocchi, P., Hannaert, P., 2001. Validation of methodologies for the release of di-isononylphthalate (DINP) in saliva simulant from toys. European Commission, DG-Joint Research Center, Food Products Unit, Institute for Health and Consumer Protection, Ispra, Italy. 2001 EUR 19826 EN
72. 11 dialkyl phthalates on gap junctional intercellular communication (GJIC), peroxisomal beta-oxidation (PBOX), and DNA synthesis in rat and mouse liver Toxicological Sciences 54 2000 312 321
73. C.A. Staples, D.R. Peterson, T.F. Parkerton, and W.J. Adams The environmental fate of phthalate esters: a literature review Chemosphere 35 1997 67 749
74. T. Sugita, K. Hirayama, R. Nino, T. Ishibashi, and T. Yamada Contents of phthalate in polyvinyl toys Shokuhin Eiseigaku Zasshi 42 2001 48 55
75. Toy Manufacturers of America (TMA), 1986. Voluntary standard specification for the reduction of DEHP (di-[ethylhexyl]phthalate) in PVC pacifiers and teethers. Toy Manufacturers of America, Inc., New York, NY
76. E.G. Valles, A.R. Laughter, C.S. Dunn, S. Cannelle, C.L. Swanson, R.C. Cattley, and J.C. Corton Role of the peroxisome proliferator-activated receptor α in responses to diisononyl phthalate Toxicology 191 2003 211 225
77. S.J. Waterman, J.L. Ambroso, L.H. Keller, G.W. Trimmer, A.I. Nikiforov, and S.B. Harris Developmental toxicity of di-isodecyl and di-isononyl phthalates in rats Reproductive Toxicology 13 1999 1 6
78. S.J. Waterman, L.H. Keller, G.W. Trimmer, J.J. Freeman, A.I. Nikiforov, S.B. Harris, M.J. Nicolich, and R.H. McKee Two-generation reproduction study in rats given di-isononyl phthalate in the diet Reproductive Toxicology 14 2000 21 36
79. C.F. Wilkinson, and J.C. Lamb IV The potential health effects of phthalate esters in children’s toys: a review and risk assessment Regulatory Toxicology and Pharmacology 30 1999 140 155
80. T.R. Zacharewski, M.D. Meek, J.H. Clemons, Z.F. Wu, M.R. Fielden, and J.B. Matthews Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters Toxicological Sciences 46 1998 282 293
81. E. Zeiger, S. Haworth, K. Mortelmans, and W. Speck Mutagenicity testing of di(2-ethylhexyl)phthalate and related chemicals in Salmonella Environmental Mutagenesis 7 1985 213 232
82. H. Zerban, and P. Bannasch Spongiosis hepatis in rats treated with low doses of hepatotropic nitrosamines Cancer Letters 19 1983 247 252