National Toxicology Program

CASRN: 1746-01-6

Related: TRANSGENIC MODEL EVALUATION (2,3,7,8-TETRACHLORODIBENZODIOXIN)

Formula: C12 H4 CL4 O2

Synonyms/Common Names:

• TCDD
• 2,3,7,8-TETRACHLORODIBENZO(B,E)(1,4)DIOXIN (9CI)
• 2,3,7,8-TETRACHLORODIBENZO-1,4-DIOXIN

Known Uses:

PRESENT IN CERTAIN HERBICIDE AND FUNGICIDE FORMULATIONS, SUCH AS 2,4,5-T AND PENTACHLOROPHENOLS; IT HAS BEEN TESTED FOR USE IN FLAMEPROOFING POLYESTERS & AGAINST INSECTS AND WOOD-DESTROYING FUNGI. A CONTAMINANT CREATED IN THE MFR OF AGENT ORANGE.

Short-Term Toxicity

• 14-Day (Gavage)  (C03714A) Completed 
  • NTIS No. PB82-163445  (Peer Review 06/27/1980)
    Citation: Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6C3F1 Mice (Gavage Study)
  • Rats: Osborne Mendel; Mice: B6C3F1
• 14-Day (Topical Application)  (C03714B) Completed 
  • NTIS No. PB82-163684  (Peer Review 06/27/1980)
    Citation: Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Swiss-Webster Mice (Dermal Study)
  • Mice: Swiss Webster
• 13-Week (Gavage)  (C03714A) Completed 
  • NTIS No. PB82-163445  (Peer Review 06/27/1980)
    Citation: Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6C3F1 Mice (Gavage Study)
  • Rats: Osborne Mendel; Mice: B6C3F1
  • Dose: R: 0,.5,8, M: 0,1,20 UG/KG/WK/10 PER GROUP
• 13-WEEK (Topical Application)  (C03714B) Completed 
  • NTIS No. PB82-163684  (Peer Review 06/27/1980)
    Citation: Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Swiss-Webster Mice (Dermal Study)
  • Mice: Swiss Webster
  • Dose: 0,.005,10 UG/10 PER GROUP

Long-Term Carcinogenicity

• 2-Year (Gavage)  (C03714A) Report Complete 
  • TR-209 (NTIS No. PB82-163445)  (Peer Review 06/27/1980)
    Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Osborne-Mendel Rats and B6C3F1 Mice (Gavage Study)
  • Rats: Osborne Mendel; Mice: B6C3F1
  • Carcinogenesis Results
  • Male Rats Positive 
  • Female Rats Positive 
  • Male Mice Positive 
  • Female Mice Positive 
  • Dose: R&MM: 0,.01,.05,.5 UG/KG/WK/50 PER GROUP FM: 0,.04,.2,2.0 UG/KG/WK/50 PER GROUP
• 2-YEAR (Topical Application)  (C03714B) Report Complete 
  • TR-201 (NTIS No. PB82-163684)  (Peer Review 06/27/1980)
    Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Swiss-Webster Mice (Dermal Study)
  • Mice: Swiss Webster
  • Carcinogenesis Results
  • Male Mice Equivocal 
  • Female Mice Positive 
  • Dose: FM: 0,.005, MM: 0,.001 UG/60 PER GROUP

Special Studies

• Absorption Disposition Metabolism Elimination (Topical Application)  (S0680) Completed 
  • Citation: BREWSTER, D.W., BANKS, Y.B., CLARK, A.M., BIRNBAUM, L.S., COMPARATIVE DERMAL ABSORPTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN & THREE POLYCHLORINATED DIBENZOFURANS: TOXICOLOGY & APPLIED PHARMACOLOGY 97, 156-166, 1989
  • M Rats: F344/N
• Absorption Disposition Metabolism Elimination (Topical Application)  (S0684) Completed 
  • Citation: ANKS, Y.B., BREWSTER, D.W., & BIRNBAUM, L.S. AGE-RELATED CHANGES IN DERMAL ABSORPTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AND 2,3,4,7,8-PENTACHLORODIBENZOFURAN FUNDAMENTAL & APPLIED TOXICOLOGY 15, 163-173, 1990
  • M Rats: F344/N
• Absorption Disposition Metabolism Elimination (Topical Application)  (S0685) Completed 
  • Citation: BANKS, Y.B. & BIRNBAUM, L.S., ABSORPTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) AFTER LOW DOSE DERMAL EXPOSURE, TOXICILOGY & APPLIED PHARMACOLOGY, 107, 302-3210 (1991)
  • M Rats: F344/N
  • Dose: 1 nmol/kg
• Absorption Disposition Metabolism Elimination  (S0691) Completed 
  • Citation: HEBERT, C.D., & BIRNBAUM, L.S. THE INFLUENCE OF AGING ON INTESTINAL ABSORPTION OF TCDD IN RATS TOXICOLOGY LETTERS, 37, 47-55, 1987
  • M Rats: F344/N
• Cell Proliferation  (S0692) Completed 
  • Citation: HEBERT ET AL. INHIBITION OF HIGH-DENSITY GROWTH ARREST IN HUMAN SQUAMOUS CARCINOMA CELLS BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) CARCINOGENESIS (LOND) 11:1335-1342, 1990. HEBERT ET AL. ROLE OF TRANSFERING GROWTH FACTOR B IN THE PROLIFERATIVE EFFECT OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON HUMAN SQUAMOUS CARCINOMA CELLS. CANCER RESEARCH 50, 7190-7197 11/15/90
  • Human
• Mechanisms (Gavage)  (S0681) Completed 
  • Citation: HARRIS, MW., URAIH, L.C., BIRNBAUM, L.S. ACUTE TOXICITY OF PERFLUORODECANOIC ACID IN C57BL/6 MICE DIFFERS FROM 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN , FUNDAMENTAL & APPLIED TOXICOLOGY 13, 723-736, 1989
  • F Mice: C57BL/6
  • Dose: 0 to 320 mg/kg
• Mechanisms (Gavage)  (S0682) Completed 
  • Citation: ABBOTT, B.D., & BIRNBAUM, L.S., CELLULAR ALTERATIONS & ENHANCED INDUCTION OF CLEFT PALATE AFTER COADMINISTRATION OF RETINOIC ACID AND TCDD, TOXICOLOGY & APPLIED PHARMACOLOGY 99, 287-301, 1989
  • M/F Mice: C57BL/6
• Mechanisms (Gavage)  (S0683) Completed 
  • Citation: BREWSTER, D.W. & BIRMBAUM, L.S. THE BIOCHEMICAL TOXICITY OF PERFLUORODECANOIC ACID IN THE MOUSE IS DIFFERENT FROM THAT OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TOXICOLOGY & APPLIED PHARMACOLOGY 99, 544-554, 1989
  • F Mice: C57BL/6
  • Dose: Ahb/b strain 0, 40, 80, 100, 120, 160 mk/kg: Ahb/d strain 0, 40, 80, 160 mg/kg: Ahd/d strain 0, 40, 80, 120 mk/kg
• Mechanisms (Topical Application)  (S0690) Completed 
  • Citation: STOHS, S.J., ABBOTT, B.D., LIN, F.H., & BIRNBAUM, L.S. INDUCTION OF ETHOXYRESORUFIN-O-DEETHYLASE AND INHIBITION OF GLUCOCORTICOID RECEPTOR BINDING IN SKIN AND LIVER OF HAIRED AND HAIRLESS HRS/J MICE BY TOPICALLY APPLIED TCDD TOXICOLOGY, 65, 123-136, 1990
  • F Mice
  • Dose: 12µg/kg
• Toxicokinetic Study (Gavage)  (S0621) Completed 
  • Citation: PART OF TWO YEAR TECHNICAL REPORT C96007G
  • M/F Rats: Sprague Dawley
  • Dose: FEMALE RATS: 0, 1, 3, 10, 30, 100 NG/KG MALE RATS TO BE USED AS SENTINELS.

Genetic Toxicology

• Chromosome Aberrations  (163229) Completed 
  • Mice
  • Chromosome Aberation  Negative 
• In Vitro Cytogenetics (CA/SCE)  (764904) Completed 
  • Citation: Galloway, S., Armstrong, M., Reuben, C., Colman, S., Brown, B., Cannon, C., Bloom, A., Nakamura, F., Ahmed, M., Duk, S., Rimpo, J., Margolin, B., Resnick, M., Anderson, B., and Zeiger, E. Chromosome aberration and sister chromatid exchanges in Chinese hamster ovary cells: Evaluations of 108 chemicals. Environ. Molec. Mutagen. Vol. 10 (Suppl 10) (1987) 1-176
  • Chromosome Aberation Negative 
  • Sister Chromatid Exchange Negative 
• Drosophila  (601370) Completed 
  • Citation: Zimmering, S., Mason, J.M., Valencia, R., and Woodruff, R.C. Chemical mutagenesis testing in Drosophila. II. Results of 20 coded compounds tested for the National Toxicology Program. Environ. Mutagen. Vol. 7 (1985) 87-100
  • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
• Mouse Lymphoma  (056688) Completed 
  • Citation: McGregor, D., Brown, A., Howgate, S., McBride, D., Riach, C., and Caspary, W. Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay. IV: 27 coded chemicals. Environ. Molec. Mutagen. Vol. 17 (1991) 196-219
  •  Negative 
• Salmonella  (904370) Completed 
  • Citation: Mortelmans, K., Haworth, S., Speck, W., and Zeiger, E. Mutagenicity testing of Agent Orange components and related chemicals Toxicology and Applied Pharmacology Vol. 75 (1984) 137-146
  •  Negative 
• Sister Chromatid Exchanges  (163229) Completed 
  • Mice
  • Sister Chromatid  Not Tested 

Organ Systems Toxicity

• Immunotoxicity  (IMM95007) Completed 
• Teratology Pilot Studies (Gavage & Intraperitoneal Injection)  (TRP92026) Completed 
  • M/F Mice: C57BL/6
  • Dose: 0, 9, 12, OR 15 UG/KG + 10 MG/KG PYRAN
• Teratology Pilot Studies (Gavage & Intraperitoneal Injection)  (TRP92061) Completed 
  • M/F Mice: C57BL/6
  • Dose: 0, 12, OR 15 UG/KG + PYRAN 0, 10, 50, OR 100 MG/KG
• Teratology Pilot Studies (Gavage & Intraperitoneal Injection)  (TRP92063) Completed 
  • M/F Mice: C57BL/6
  • Dose: 0, 6, 12, OR 24 UG/KG TCDD; PYRAN 0, 10 MG/KG