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Testing Status of Di(2-ethylhexyl) Phthalate 10188-J

 

CASRN: 117-81-7

Formula: C24-H38-O4

Synonyms/Common Names

  • 1,2-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester
  • Bis(2-ethylhexyl) phthalate
  • DEHP
  • Diethylhexyl phthalate

Short-Term Toxicity

  • 4 days (Gavage)  (C10188C)  Completed 
    • Liver Targeted Testing study of Toxcast Chemicals
    • Rats: Harlan Sprague-Dawley
    • Dose: MR: 0, 600 mg/kg/day.
  • 5 days (Gavage)  (C10188D)  Data in Review 
    • 5-Day Transcriptomic Dose-Response Studies
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley
    • Dose: MR: 0, 8, 16, 31.25, 62.5, 125, 250, 500, or 1000 mg/kg; N=4.
  • 14 days (IV Injection and Oral)  (C20526)  Completed 
    • Monkeys: Rhesus
    • Dose: 5 mg/kg D4-DEHP in 10% intralipid -- IV: 1, 5, or 9 weeks; oral: 10 weeks of age.
  • 14-Day (Dosed-Feed)  (C52733A)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R&M: 0, 6300, 12,500, 25,000, 50,000, 100,000 ppm. 5 per group.
  • 13-Week (Dosed-Feed)  (C52733A)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R: 0, 1600, 25,000 ppm. M: 0, 800, 12500 ppm. 10 per group.

Long-Term Carcinogenicity

  • Perinatal + 2 years (Dosed-Feed)  (C10188)  Completed 
    • TR-601 
      Toxicology and Carcinogenesis Studies of Di(2-ethylhexyl) Phthalate (CASRN 117-81-7) Administered in Feed to Sprague Dawley (Hsd:Sprague Dawley SD) Rats
    • Rats: Harlan Sprague-Dawley
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
    • Dose: R: 0, 300, 1000, 3000, or 10,000 ppm; 50/sex/group.
  • 2 years (Dosed-Feed)  (C10188B)  Completed 
    • TR-601 
      Toxicology and Carcinogenesis Studies of Di(2-ethylhexyl) Phthalate (CASRN 117-81-7) Administered in Feed to Sprague Dawley (Hsd:Sprague Dawley SD) Rats
    • Rats: Harlan Sprague-Dawley
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
    • Dose: R: 0, 300, 1000, 3000, or 10,000 ppm; 50/sex/group.
  • 2-Year (Dosed-Feed)  (C52733A)  Completed 
    • TR-217 (NIH Number: 82-1773)  (Peer Review Approval 10/15/1980A )
      Carcinogenesis Bioassay of Di(2-ethylhexyl)phthalate (CASRN 117-81-7) in F344 Rats and B6C3F1 Mice (Feed Studies)
    • Rats: F344/N; Mice: B6C3F1
    • Carcinogenesis Results
      • Male Rats Positive 
      • Female Rats Positive 
      • Male Mice Positive 
      • Female Mice Positive 
    • Dose: R: 0, 6000, 12,000 ppm. M: 0, 3000, 6000 ppm. 50 per group.

Special Studies

  • Absorption Distribution Metabolism Excretion (Topical Application)  (S0054)  Completed 
    • Male Rats: F344/N
  • Mechanisms (Gavage)  (S0678)  Completed 
    • Citation: Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB. Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect. 1982 Nov;45:19-25.Pubmed Abstract
    • Rats: F344/N; Rats: Sprague Dawley
    • Dose: 1.8, 18.0, 180.0 mg/kg.
  • Toxicokinetic Study (Gavage; Intravenous)  (S0974)  Completed 
    • Male Monkeys: Rhesus
    • Dose: 5 mg/kg bwt D4-DEHP. 5 mg/kg bwt D4-DEHP, 2 ml/kg of a 2.5 mg/ml dosing solution.

Genetic Toxicology

  • Chromosome Aberrations  (A15927)  Completed 
    • Mice
    •  Negative (Nonstandard Protocol) 
  • 4 days Comet Assay (Gavage)  (G10188)  Completed 
    • Rats: Sprague Dawley
  • Drosophila  (507426)  Completed 
    • Citation: Zimmering, S., Mason, J.M., and Valencia, R. Chemical mutagenesis testing in Drosophila. VII. Results of 22 coded compounds tested in larval feeding experiments. Environ. Molec. Mutagen. Vol. 14 (1989) 245-252
    • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
  • Drosophila  (967176)  Completed 
    • Citation: Yoon, J.S., Mason, J.M., Valencia, R., Woodruff, R.C., and Zimmering, S. Chemical mutagenesis testing in Drosophila: IV. Results of 45 coded compounds tested for the National Toxicology Program. Environ. Mutagen. Vol. 7 (1985) 349-367
    • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
  • In Vitro Cytogenetics (CA/SCE)  (008270)  Completed 
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Not Tested 
  • In Vitro Cytogenetics (CA/SCE)  (426348)  Completed 
    • Sister Chromatid Exchange Weakly Positive 
    • Chromosome Aberrations Not Tested 
  • In Vitro Cytogenetics (CA/SCE)  (515010)  Completed 
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Not Tested 
  • In Vitro Cytogenetics (CA/SCE)  (587571)  Completed 
    • Citation: Gulati, D., Witt, K., Anderson, B., Zeiger, E.,and Shelby, M. Chromosome aberration and sister chromatid exchange test in Chinese hamster ovary cells in vitro III: Results with 27 chemicals Environ. Molec. Mutagen. Vol. 13 (1989) 133-193
    • Sister Chromatid Exchange Equivocal 
    • Chromosome Aberrations Not Tested 
  • In Vitro Cytogenetics (CA/SCE)  (594940)  Completed 
    • Sister Chromatid Exchange Negative 
    • Chromosome Aberrations Weakly Positive 
  • In Vitro Cytogenetics (CA/SCE)  (759843)  Completed 
    • Sister Chromatid Exchange Negative 
    • Chromosome Aberrations Negative 
  • In Vitro Cytogenetics (CA/SCE)  (890544)  Completed 
    • Citation: Gulati, D., Witt, K., Anderson, B., Zeiger, E.,and Shelby, M. Chromosome aberration and sister chromatid exchange test in Chinese hamster ovary cells in vitro III: Results with 27 chemicals Environ. Molec. Mutagen. Vol. 13 (1989) 133-193
    • Sister Chromatid Exchange Equivocal 
    • Chromosome Aberrations Not Tested 
  • In Vitro Cytogenetics (CA/SCE)  (923560)  Completed 
    • Citation: Gulati, D., Sabharwal, P., and Shelby, M. Tests for the induction of chromosomal aberrations and sister chromatid exchanges in cultured Chinese hamster ovary (CHO) cells. In Evaluation of Short-Term Tests for Carcinogens, Elsevier/North Holland 413-426
    • Citation: Gulati, D., Witt, K., Anderson, B., Zeiger, E.,and Shelby, M. Chromosome aberration and sister chromatid exchange test in Chinese hamster ovary cells in vitro III: Results with 27 chemicals Environ. Molec. Mutagen. Vol. 13 (1989) 133-193
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Negative 
  • In Vitro Cytogenetics (CA/SCE)  (978423)  Completed 
    • Citation: Gulati, D., Witt, K., Anderson, B., Zeiger, E.,and Shelby, M. Chromosome aberration and sister chromatid exchange test in Chinese hamster ovary cells in vitro III: Results with 27 chemicals Environ. Molec. Mutagen. Vol. 13 (1989) 133-193
    • Sister Chromatid Exchange Equivocal 
    • Chromosome Aberrations Not Tested 
  • Micronucleus  (A04384)  Completed 
    • Mice: Tg.AC (FVB/N) Homozygous
    • Male Equivocal 
    • Female Positive 
  • Micronucleus  (A15851)  Completed 
    • Mice: Tg.AC (FVB/N) Homozygous
    • Male Negative 
    • Female Negative 
  • Micronucleus  (A15927)  Completed 
    • Mice: B6C3F1
    • Female Equivocal 
  • Mouse Lymphoma  (913224)  Completed 
    • Citation: Myhr, B., Bower, L., and Caspary, W. Assays for the induction of gene mutations at the thymine kinase locus in L1578Y mouse lymphoma cells in culture. In Evaluation of Short-Term Tests for Carcinogens, Elsevier/North Holland Vol. (1985) 555-568
    • Mice
    •  Negative 
  • Salmonella  (064176)  Completed 
    • Citation: Zeiger, E., Haworth, S., Mortelmans, K., and Speck, W. Mutagenicity testing of Di(2-ethylhexyl)phthalate and related chemicals in Salmonella Environ. Mutagen. Vol. 7 (1985) 213-232
    •  Negative 
  • Salmonella  (195347)  Completed 
    • Citation: Zeiger, E., Haworth, S., Mortelmans, K., and Speck, W. Mutagenicity testing of Di(2-ethylhexyl)phthalate and related chemicals in Salmonella Environ. Mutagen. Vol. 7 (1985) 213-232
    •  Negative 
  • Salmonella  (483211)  Completed 
    • Citation: Zeiger, E., Haworth, S., Mortelmans, K., and Speck, W. Mutagenicity testing of Di(2-ethylhexyl)phthalate and related chemicals in Salmonella Environ. Mutagen. Vol. 7 (1985) 213-232
    •  Negative 
  • Salmonella  (894518)  Completed 
    • Citation: Zeiger, E., and Haworth, S. Tests with a preincubation modification of the Salmonella/microsome assay. In Evaluation of Short-Term Tests for Carcinogens Elsevier/North Holland 187-199
    •  Negative 
  • Salmonella  (960176)  Completed 
    • Citation: Zeiger, E., Haworth, S., Mortelmans, K., and Speck, W. Mutagenicity testing of Di(2-ethylhexyl)phthalate and related chemicals in Salmonella Environ. Mutagen. Vol. 7 (1985) 213-232
    •  Negative 
  • Salmonella  (965968)  Completed 
    •  Negative 

Organ Systems Toxicity

  • 120 day minimum Continuous Breeding (Legacy) (Dosed-Feed)  (RACB82119)  Completed 
    • Citation: Lamb JC 4th, Chapin RE, Teague J, Lawton AD, Reel JR. Reproductive effects of four phthalic acid esters in the mouse. Toxicol Appl Pharmacol. 1987 Apr;88(2):255-69. doi: https://doi.org/10.1016/0041-008x(87)90011-1.
    • Mice: Swiss CD-1
    • Dose: [Task 1] 0, .01, .025, .05%. [Task 2] 0, .01, .025, .05%. [Task 3] 0, .01, .025, .05%. [Task 4] 0, .05%.
  • 0 to 20 GD Continuous Breeding (Legacy) (Dosed-Feed)  (RACB84118)  Completed 
    • Rats: F344/N
    • Dose: [Task 1] 0, .25, .5, 1.0%. [Task 2] 0, .25, .5, 1.0%. [Task 3] 0, .25, .5, 1.0%. [Task 4] N/A.
  • 3rd generation Continuous Breeding (Legacy) (Dosed-Feed)  (RACB98004)  Completed 
    • Citation: Blystone CR, Kissling GE, Bishop JB, Chapin RE, Wolfe GW, Foster PM. Determination of the di-(2-ethylhexyl) phthalate NOAEL for reproductive development in the rat: importance of the retention of extra animals to adulthood. Toxicol Sci. 2010 Aug;116(2):640-6. doi: https://doi.org/10.1093/toxsci/kfq147. Epub 2010 May 19.
    • Citation: National Toxicology Program (NTP). 2005. Diethylhexylphthalate (CASRN 117-81-7): Multigenerational reproductive assessment by continuous breeding when administered to Sprague-Dawley rats in the diet. Research Triangle Park, NC: National Toxicology Program. RACB Report 98004. https://ntp.niehs.nih.gov/go/racb98004abs
    • Male and Female Rats: Sprague Dawley
    • Dose: [Control] (1.5), 10, 30, 100, 300, 1000, 7500, OR 10,000 ppm.
  • 1 to 17 GD Continuous Breeding (Legacy) (Dosed-Feed)  (T0086E)  Completed 
    • Female Mice: Swiss
    • Dose: 0%, 0.010%, 0.025%, 0.050%.
  • 0 to 20 GD Conventional Teratology (Dosed-Feed)  (TER84063)  Completed 
    • Female Rats: F344/N
    • Rats Maternal Positive 
    • Rats Fetal Positive 
    • Dose: 0.5, 1.0, 1.5, 2.0 %.
  • 1 to 17 GD Conventional Teratology (Dosed-Feed)  (TER84064)  Completed 
    • Female Mice: Swiss
    • Mice Maternal Positive 
    • Mice Fetal Positive 
    • Dose: 0.025, 0.05, 0.10, 0.15 %.
  • 7 to 14 GD Short-Term in vivo Repro. Tox. (Gavage)  (T0086F)  Completed 
    • Citation: Screening of Priority Chemicals for Potential Reproductive Hazard
    • Female Mice: Swiss
    • Dose: 9860 mg (10 ml undiluted)/kg body wt.
  • Utero-Lactational (Gavage)  (R10188)   
    • Mice: B6C3F1
  • Utero-Lactational (Gavage)  (R10188)  Completed 
    • Mice: NIH Swiss

Toxicogenomics

  • 4 days Microarray Analysis (Gavage)  (T10188)  Completed 
    • Liver Targeted Testing study of Toxcast Chemicals
    • Rats: Harlan Sprague-Dawley
    • Dose: not provided; 6 rats.
  • 5 days Transcriptome Sequencing (Gavage)  (T10188B)  Data in Review 
    • 5-Day Transcriptomic Dose-Response Studies
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley