https://ntp.niehs.nih.gov/go/928469

Target Organs and Levels of Evidence for 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

Chemical
CASRN
(Study Title)		 Peer Review Date Route/Exposure Levels Study Laboratory
Di(2-ethylhexyl) Phthalate
117-81-7		 04/02/2021 Dosed-Feed
R: 0, 300, 1000, 3000, or 10,000 ppm; 50/sex/group		 Battelle Columbus Laboratory

Levels of Evidence

Male Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions Perinatal and Postweaning Study (Study 1)
  • Liver: hepatocellular adenoma (0/50, 1/49, 0/50, 3/50, 8/49); hepatocellular carcinoma (1/50, 0/49, 0/50, 0/50, 3/49); hepatocellular adenoma or carcinoma (combined) (1/50, 1/49, 0/50, 3/50, 11/49)
  • Pancreas Acinar Cell: acinar adenoma (10/50, 7/49, 8/50, 36/50, 22/49); acinar carcinoma (0/50, 0/49, 0/50, 3/50, 1/49); acinar adenoma or carcinoma (combined) (10/50, 7/49, 8/50, 38/50, 22/49)
Postweaning-Only Study (Study 2)
  • Liver: hepatocellular adenoma (0/50, 2/50, 0/50, 1/50, 6/50); hepatocellular carcinoma (0/50, 0/50, 0/50, 0/50, 6/50); hepatocellular adenoma or carcinoma (combined) (0/50, 2/50, 0/50, 1/50, 12/50)
  • Pancreas Acinar Cell: acinar adenoma (1/49, 4/50, 5/50, 23/50, 30/50); acinar carcinoma (0/49, 1/50, 0/50, 1/50, 5/50); acinar adenoma or carcinoma (combined) (1/49, 5/50, 5/50, 23/50, 33/50)
May Have Been Related Postweaning-Only Study (Study 2)
  • Testis: interstitial cell, adenoma (7/50, 3/50, 3/50, 6/50, 15/50)
Non-Neoplastic Lesions Perinatal and Postweaning Study (Study 1)
  • Liver: hepatocyte, cytoplasmic alteration; hepatocyte, hypertrophy; pigment; necrosis; eosinophilic focus; basophilic focus
  • Testis: germinal epithelium, degeneration (includes bilateral); interstitial cell, hyperplasia, focal (includes bilateral); seminiferous tubule, dysgenesis (includes bilateral)
  • Epididymis: hypospermia (includes bilateral)
  • Kidney: papilla, edema; papilla, hemorrhage; epithelium, papilla, hyperplasia; infarct
  • Heart: valve, fibrosis; valve, thrombus
  • Bone marrow: hypercellularity
  • Pituitary gland: pars distalis, hypertrophy
Postweaning-Only Study (Study 2)
  • Liver: hepatocyte, cytoplasmic alteration; hepatocyte, hypertrophy; pigment; necrosis; eosinophilic focus; clear cell focus
  • Pancreas: acinus, hyperplasia
  • Testis: germinal epithelium, degeneration (includes bilateral); edema (includes bilateral); interstitial cell, hyperplasia, focal (includes bilateral)
  • Epididymis: hypospermia (includes bilateral); duct, exfoliated germ cell (includes bilateral)
  • Heart: valve, fibrosis; valve, thrombus
  • Bone marrow: hypercellularity
  • Pituitary gland: pars distalis, hypertrophy
Other Considerations Perinatal and Postweaning Study (Study 1)
  • Testis: small (2/49, 2/49, 4/50, 2/50, 45/49); enlarged (or swelling) (0/49, 0/49, 0/50, 0/50, 1/49); fluid or blood filled (0/49, 1/49, 1/50, 1/50, 1/49); right or left, abdominal, undescended (1/49, 0/49, 0/50, 0/50, 19/49); right or left, inguinal, undescended (0/49, 1/49, 1/50, 0/50, 4/49); right or left, abdominal or inguinal, undescended (1/49, 1/49, 1/50, 0/50, 23/49); right, not present (0/49, 0/49, 0/49, 0/50, 1/49); cranial suspensory ligament (0/49, 0/49, 0/50, 0/50, 5/49)
  • Epididymis: small (0/49, 0/49, 2/50, 0/50, 14/49); right, cauda, agenesis (0/49, 0/49, 0/49, 0/50, 2/49); right or left, caput, agenesis (0/49, 0/49, 0/50, 0/50, 4/49); right or left, cauda, agenesis (0/49, 0/49, 0/50, 0/50, 2/49); right or left, corpus, agenesis (0/49, 0/49, 0/50, 0/50, 3/49
  • Levator ani/bulbocavernosus muscle: small (0/50, 0/49, 0/50, 0/50, 2/48)
  • Cowper’s glands: left, small (0/50, 0/49, 0/50, 0/50, 1/47); right, small (0/50, 0/49, 0/50, 0/50, 1/47)
  • Prostate glands: small (0/50, 0/49, 0/50, 0/50, 1/47)
  • Seminal vesicles/ coagulating glands: small (1/50, 0/49, 1/50, 1/50, 8/47)
  • Phallus: small (0/50, 0/49, 0/49, 0/50, 3/49); cleft (0/50, 0/49, 0/49, 0/50, 3/49)
  • Prepuce: cleft (0/50, 0/49, 0/50, 0/50, 1/49); incomplete preputial separation (0/50, 0/49, 0/50, 0/50, 7/49)
  • Gubernaculum: right or left, not present (0/47, 0/49, 0/49, 0/50, 18/41); ↑ right length
Female Rats: Clear Evidence
Type Organ/Tissue (Lesion)
Neoplastic Lesions Perinatal and Postweaning Study (Study 1)
  • Liver: hepatocellular adenoma (1/49, 0/50, 5/50, 9/50, 5/48); hepatocellular carcinoma (0/49, 0/50, 0/50, 0/50, 8/48); hepatocellular adenoma or carcinoma (combined) (1/49, 0/50, 5/50, 9/50, 13/48)
  • Pancreas Acinar Cell: acinar adenoma or carcinoma (combined) (0/49, 0/50, 0/50, 2/50, 1/48)
Postweaning-Only Study (Study 2)
  • Liver: hepatocellular adenoma (0/50, 0/50, 1/50, 1/50, 13/49); hepatocellular carcinoma (0/50, 0/50, 0/50, 0/50, 2/49); hepatocellular adenoma or carcinoma (combined) (0/50, 0/50, 1/50, 1/50, 14/49)
  • Pancreas Acinar Cell: acinar adenoma or carcinoma (combined) (0/50, 0/50, 0/50, 1/50, 2/47)
  • Uterus: adenoma, adenocarcinoma, squamous cell carcinoma, or squamous cell papilloma (combined) (2/50, 4/50, 1/50, 6/50, 13/50)
May Have Been Related Perinatal and Postweaning Study (Study 1)
  • Uterus: adenoma, adenocarcinoma, squamous cell carcinoma, or squamous cell papilloma (combined) (3/50, 1/50, 1/50, 3/50, 7/50)
Non-Neoplastic Lesions Perinatal and Postweaning Study (Study 1)
  • Liver: hepatocyte, cytoplasmic alteration; hepatocyte, hypertrophy; pigment; necrosis; eosinophilic focus; basophilic focus; bile duct hyperplasia
  • Pancreas: acinus, hyperplasia
  • Kidney: papilla, edema; epithelium, papilla, hyperplasia; infarct; renal tubule, cyst; renal tubule, dilation
Postweaning-Only Study (Study 2)
  • Liver: hepatocyte, cytoplasmic alteration; hepatocyte, hypertrophy; pigment
  • Pancreas: acinus, hyperplasia
  • Uterus: inflammation, chronic
Other Considerations Perinatal and Postweaning Study (Study 1)
  • Vagina: not patent (0/50, 0/50, 0/50, 0/50, 5/48)
  • Phallus: cleft (0/50, 0/50, 0/50, 2/50, 1/48)