The Registry of Toxic Effects of Chemical Substances

Disulfide, bis (diethylthiocarbamoyl)

RTECS #: JO1225000

CAS #: 97-77-8

UPDATE: November 2004 MW: 296.56 MF: C10H20N2S4


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. TUMORIGENIC DATA:
  6. ACUTE TOXICITY DATA:
  7. OTHER MULTIPLE DOSE DATA:
  8. REVIEWS:
  9. STANDARDS AND REGULATIONS:
  10. NIOSH DOCUMENTATION AND SURVEILLANCE:
  11. STATUS IN FEDERAL AGENCIES:
  12. REFERENCES:

SYNONYMS:

  1. 1,1' - Dithiobis (N,N - diethylthioformamide)
  2. Abstensil
  3. Abstinil
  4. Abstinyl
  5. Alcophobin
  6. Antabus
  7. Antabuse
  8. Antaenyl
  9. Antaethyl
  10. Antalcol
  11. Antetan
  12. Antetil
  13. Anti - ethyl
  14. Antietil
  15. Antikol
  16. Antivitium
  17. Aversan
  18. Averzan
  19. Bis ( (diethylamino) thioxomethyl) disulphide
  20. Bis (N,N - diethylthiocarbamoyl) disulfide
  21. Bis (N,N - diethylthiocarbamoyl) disulphide
  22. Bis (diethylthiocarbamoyl) disulfide
  23. Bis (diethylthiocarbamoyl) disulphide
  24. Contralin
  25. Cronetal
  26. Dicupral
  27. Disulfiram
  28. Disulfiram (ACGIH)
  29. Disulfuram
  30. Disulphuram
  31. Dupon 4472
  32. Dupont fungicide 4472
  33. ENT 27,340
  34. Ekagom TEDS
  35. Ephorran
  36. Espenal
  37. Esperal
  1. Etabus
  2. Ethyl TUEX
  3. Ethyl thiram
  4. Ethyl thiurad
  5. Ethyl tuads
  6. Ethyldithiourame
  7. Ethyldithiurame
  8. Exhoran
  9. Formamide, 1,1' - dithiobis (N,N - diethylthio -
  10. HOCA
  11. Krotenal
  12. N,N,N',N' - Tetraethylthiuram disulphide
  13. NCI - C02959
  14. NSC 190940
  15. Nocbin
  16. Noxal
  17. Refusal
  18. Ro - Sulfiram
  19. Stopetyl
  20. TETD
  21. Tenurid
  22. Tenutex
  23. Tetidis
  24. Tetradin
  25. Tetradine
  26. Tetraethylthioperoxydicarbonic diamide
  27. Tetraethylthiram disulphide
  28. Tetraethylthiuram
  29. Tetraethylthiuram disulfide
  30. Tetraethylthiuram disulphide
  31. Tetraetil
  32. Teturam
  33. Teturamin
  34. Thiuram E
  35. Thiuram disulfide, tetraethyl -
  36. Thiuranide
  37. USAF B - 33


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
rabbit 		100 mg mild FCTOD7 20,573,1982


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
DNA inhibition chicken embryo 120 nmol/L BBACAQ 519,65,1978
DNA inhibition human HeLa cell 100 µmol/L CRNGDP 13,2389,1992
DNA inhibition mouse embryo 10 mg/L JJATDK 5,1,1985
mutation in microorganisms Salmonella typhimurium 25 µg/plate (+enzymatic activation step) CBINA8 49,329,1984
mutation in microorganisms Salmonella typhimurium 20 µg/plate (-enzymatic activation step) PCBRD2 141,407,1984
morphological transform hamster embryo 20 µg/L MUREAV 356,85,1996
morphological transform oral
rat 		12,600 mg/kg/6 week CRNGDP 9,387,1988
other mutation test systems chicken embryo 120 nmol/L BBACAQ 519,65,1978
sister chromatid exchange hamster ovary 5 µmol/L SWEHDO 9(Suppl 2),27,1983
sister chromatid exchange oral
mouse 		200 mg/kg FCTOD7 37,757,1999
specific locus test mouse lymphocyte 16 µg/L EMMUEG 17,196,1991


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 13,200 mg/kg (15 day prior to copulation/1-18 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JJATDK 5,1,1985
oral
mouse 		lowest published toxic dose: 39,200 mg/kg (7-14 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) NTIS** PB86-197605
oral
rat 		lowest published toxic dose: 5 gm/kg (3-12 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) 		JRPFA4 39,375,1974
oral
rat 		lowest published toxic dose: 310 mg/kg (31 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct TXAPA9 107,164,1991
oral
rat 		lowest published toxic dose: 2,800 mg/kg (14 day male) Reproductive: Effects on newborn: Biochemical and metabolic FATOAO 48,86,1985
parenteral
rat 		lowest published toxic dose: 400 mg/kg (4-11 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death 		BEXBAN 93,107,1982
parenteral
rat 		lowest published toxic dose: 800 mg/kg (2 day male/2 day prior to copulation) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death 		BEXBAN 93,107,1982
subcutaneous
mouse 		lowest published toxic dose: 1,278 mg/kg (6-14 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) 		NTIS** PB223-160
subcutaneous
mouse 		lowest published toxic dose: 1,278 mg/kg (6-14 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		NTIS** PB223-160


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 35 gm/kg/78 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Liver: Tumors 		NTIS** PB223-159
subcutaneous
mouse 		lowest published toxic dose: 1,000 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Blood: Tumors 		NTIS** PB223-159


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lethal dose (50 percent kill): 75 mg/kg N/R NTIS** AD691-490
intraperitoneal
rat 		lethal dose (50 percent kill): 248 mg/kg Behavioral: Change in motor activity (specific assay)

Nutritional and Gross Metabolic: Body temperature decrease 		JNPHAG 9,35,1978
oral
child 		lowest published toxic dose: 150 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Hallucinations, distorted perceptions

Gastrointestinal: Nausea or vomiting 		34ZIAG -,230,1969
oral
dog 		lowest published lethal dose: 3,500 mg/kg Peripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Ataxia

Nutritional and Gross Metabolic: Body temperature decrease 		APTOA6 8,305,1952
oral
human 		lowest published lethal dose: 160 mg/kg Behavioral: Coma

Gastrointestinal: Ulceration or bleeding from large intestine

Liver: Hepatitis, fibrous (cirrhosis, post- necrotic scarring) 		BMJOAE 2,94,1977
oral
human 		lowest published toxic dose: 14 mg/kg Endocrine: Change in gonadotropins SWEHDO 4,66,1978
oral
human 		lowest published toxic dose: 18 mg/kg Endocrine: Change in gonadotropins

Endocrine: Change in LH 		SWEHDO 4,66,1978
oral
man 		lowest published toxic dose: 450 mg/kg/6 week- intermittent Brain and Coverings: Encephalitis

Liver: Hepatitis (hepatocellular necrosis), diffuse

Skin: After systemic exposure: Dermatitis, other 		AJGAAR 93,830,1998
oral
man 		lowest published toxic dose: 150 mg/kg/6 week- intermittent Musculoskeletal: Joints ARHEAW 25,1494,1982
oral
man 		lowest published lethal dose: 150 mg/kg/6 week- intermittent Liver: Hepatitis (hepatocellular necrosis), diffuse AIMDAP 143,1271,1983
oral
mouse 		lethal dose (50 percent kill): 1.013 mg/kg N/R TCMUD8 22,83,2001
oral
rat 		lethal dose (50 percent kill): 500 mg/kg N/R ATXKA8 22,12,1966
oral
rat 		lowest published toxic dose: 200 mg/kg Brain and Coverings: Other degenerative changes

Cardiac: Cardiomyopathy including infarction

Liver: Multiple effects 		FATOAO 50,52,1987
oral
rabbit 		lethal dose (50 percent kill): 1,800 mg/kg Peripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Ataxia

Nutritional and Gross Metabolic: Body temperature decrease 		APTOA6 8,305,1952
oral
woman 		lowest published lethal dose: 90 mg/kg/18 day- intermittent Behavioral: Coma

Liver: Jaundice, other or unclassified

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		DMWOAX 118,1355,1993
oral
woman 		lowest published toxic dose: 140 mg/kg/2 week Behavioral: Hallucinations, distorted perceptions

Behavioral: Convulsions or effect on seizure threshold 		SMJOAV 80,1577,1987
oral
woman 		lowest published toxic dose: 90 mg/kg/18 day- intermittent Liver: Jaundice, other or unclassified JCLPDE 46,67,1985
subcutaneous
mouse 		lethal dose (50 percent kill): 2,600 mg/kg N/R NIIRDN -,523,1995
subcutaneous
rat 		lethal dose : >4 gm/kg N/R APTOA6 8,305,1952


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
dog 		lowest published toxic dose: 1,750 mg/kg/7 day- intermittent Autonomic Nervous System: Other (direct) parasympathomimetic

Liver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in spleen 		APTOA6 8,305,1952
oral
man 		lowest published toxic dose: 39.3 mg/kg/11 day- intermittent Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) BCPHBM 53,155,2002
oral
rat 		lowest published toxic dose: 7 gm/kg/7 day- intermittent Autonomic Nervous System: Other (direct) parasympathomimetic

Gastrointestinal: Ulceration or bleeding from stomach

Blood: Changes in spleen 		APTOA6 8,305,1952
oral
rat 		lowest published toxic dose: 6,750 mg/kg/6 week- intermittent Brain and Coverings: Other degenerative changes

Nutritional and Gross Metabolic: Changes in: Other metals 		TOLED5 75,235,1995
oral
rat 		lowest published toxic dose: 7,770 mg/kg/3 week- intermittent Peripheral Nerve and Sensation: Recording from peripheral motor nerve

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		APTOA6 55,339,1984
oral
rat 		lowest published toxic dose: 6,545 mg/kg/13 week- intermittent Autonomic Nervous System: Parasympatholytic

Gastrointestinal: Contraction (isolated tissue)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		APTOA6 55,339,1984
oral
rat 		lowest published toxic dose: 720 mg/kg/60 day- intermittent Brain and Coverings: Other degenerative changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases 		EPEPEG 292,89,1994
oral
rat 		lowest published toxic dose: 44,640 mg/kg/2 year- continuous Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPMSAE 59,1267,1970
oral
rabbit 		lowest published toxic dose: 280 mg/kg/18 day- intermittent Spinal Cord: Demyelination

Autonomic Nervous System: Other (direct) parasympathomimetic

Liver: Hepatitis (hepatocellular necrosis), zonal 		APTOA6 8,305,1952


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 2 mg/m3 DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Not Classifiable as a Human Carcinogen DTLVS* TLV/BEI,2003
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 12,85,1976
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 12,85,1976
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMSUDL 7,56,1987
TOXICOLOGY REVIEW
CRTXB2 2,365,1973


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - AUSTRALIA time-weighted average 2 mg/m3, JAN1993
Occupational Exposure Limit - AUSTRIA MAK 2 mg/m3, JAN1999
Occupational Exposure Limit - BELGIUM time-weighted average 2 mg/m3, JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 2 mg/m3, JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 2 mg/m3, short term exposure limit 6 mg/m3, JAN1999
Occupational Exposure Limit - FRANCE VME 2 mg/m3, JAN1999
Occupational Exposure Limit - GERMANY MAK 2 mg/m3, JAN1999
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 1 mg/m3, 2003
Occupational Exposure Limit - SWEDEN time-weighted average 1 mg/m3, short term exposure limit 2 mg/m3, JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 2 mg/m3, JAN1999
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Not Classifiable as a Human Carcinogen
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Not Classifiable as a Human Carcinogen


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO DISULFIRAM-air 10 hour time-weighted average 2 mg/m3 NIOSH* DHHS #95-121,1995
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 80219;
Number of Industries 4;
Total Number of Facilities 209;
Number of Occupations 24;
Total Number of Employees Exposed 4,441
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 80219;
Number of Industries 28;
Total Number of Facilities 2,688;
Number of Occupations 51;
Total Number of Employees Exposed 53,525;
Total Number of Female Employees Exposed 6,305


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Negative: Carcinogenicity-mouse/rat
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as an accelerator in compounding natural, STYRENE-BUTADIENE, and NEOPRENE W rubbers
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH CURRENT INTELLIGENCE BULLETIN 23, 1978
NCI Carcinogenesis Bioassay (feed);no evidence:mouse,rat NCITR* NCI-TR-166,1979


REFERENCES:

CODEN
REFERENCE
34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969
AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908-
AJGAAR American Journal of Gastroenterology. (American College of Gastroenterology, Inc., 428 E. Preston St., Baltimore, MD 21202) V.21- 1954-
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH
ARHEAW Arthritis and Rheumatism. (Arthritis Foundation, 1314 Spring St., NW, Atlanta, GA 30309) V.1- 1958-
ATXKA8 Archiv fuer Toxikologie. (Berlin, Fed. Rep. Ger.) V.15-31, 1954-74. For publisher information, see ARTODN.
BBACAQ Biochimica et Biophysica Acta. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1947-
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974-
BEXBAN Bulletin of Experimental Biology and Medicine (English Translation). Translation of BEBMAE. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.41- 1956-
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
CBINA8 Chemico-Biological Interactions. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1969-
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971-
DMWOAX Deutsche Medizinische Wochenschrift. (Stuttgart, Fed. Rep. Ger.) V.1-104, 1875-1979.
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
EPEPEG European Journal of Pharmacology, Environmental Toxicology and Pharmacology Section. (Elsevier Science Publishers B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.228- 1992-
FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982-
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978-
JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981-
JNPHAG Journal de Pharmacologie. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1970-
JPMSAE Journal of Pharmaceutical Sciences. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.50- 1961-
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan)
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
PCBRD2 Progress in Clinical and Biological Research. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1975-
SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446, Birmingham, AL 35205) V.1- 1908-
SWEHDO Scandinavian Journal of Work, Environment and Health. (Haartmaninkatu 1, SF-00290 Helsinki, 29, Finland) V.1- 1975-
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

Used as an accelerator in compounding natural, STYRENE-BUTADIENE, and NEOPRENE W rubbers

NIOSH PROFILE (RUBBER MANUFACTURING, SYNTHETIC), SRI, 2/77

NIOSH PROFILE (RUBBER MANUFACTURING, SYNTHETIC), FIRL, 4/78

FDA-proprietary drug

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data
   Hormone
   Primary Irritant

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