The Registry of Toxic Effects of Chemical Substances

p - Dioxane

RTECS #: JG8225000

CAS #: 123-91-1

UPDATE: May 2005 MW: 88.12 MF: C4H8O2


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. Dioxan
  2. Dioxan - 1,4 (German)
  3. p - Dioxan (Czech)
  4. Dioxane
  5. Dioxane - 1,4
  6. Glycol ethylene ether
  7. NCI - C03689
  8. RCRA waste number U108
  9. Tetrahydro - p - dioxin
  10. Tetrahydro - 1,4 - dioxin
  11. 1,4 - Dioxane
  12. Dioxane (ACGIH:OSHA)
  13. 1,4 - Dioxacyclohexane
  1. Diethylene dioxide
  2. 1,4 - Diethylene dioxide
  3. Diethylene dioxide (OSHA)
  4. Diethylene ether
  5. Di (ethylene oxide)
  6. Diokan
  7. Dioksan (Polish)
  8. Diossano - 1,4 (Italian)
  9. Dioxaan - 1,4 (Dutch)
  10. Dioxanne (French)
  11. p - Dioxin, tetrahydro -
  12. Dioxyethylene ether


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
guinea pig 		10 µg moderate JPPMAB 11,150,1959
eye
human 		300 ppm/15 minute moderate JIHTAB 28,262,1946
eye
rabbit 		100 mg severe AJOPAA 29,1363,1946
eye
rabbit 		100 mg/24 hour moderate 85JCAE -,810,1986
skin
rabbit 		515 mg open irritation test mild UCDS** 12/17/1971


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
DNA damage oral
rat 		2,550 mg/kg CALEDQ 53,67,1990
DNA damage rat liver 300 µmol/L SinJF# 26OCT1982
DNA inhibition human HeLa cell 400 mmol/L CRNGDP 13,2389,1992
unscheduled DNA synthesis oral
rat 		20 mg/kg TXAPA9 60,287,1981
micronucleus test oral
mouse 		900 mg/kg MUREAV 322,142,1994
micronucleus test oral
mouse 		3 gm/kg MUREAV 322,145,1994
morphological transform mouse fibroblast 1 gm/L EMMUEG 11,41,1988
other mutation test systems intravenous
rat 		50 mg/kg ARTODN 49,29,1981
sister chromatid exchange hamster ovary 10,500 mg/L EMMUEG 10(Suppl 10),1,1987


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
rat 		lowest published toxic dose: 10 gm/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		TOLED5 26,85,1985


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
rat 		lowest published toxic concentration: 111 ppm/7 hour/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Tumors

Blood: Lymphoma including Hodgkin's disease 		TXAPA9 30,287,1974
intraperitoneal
mouse 		lowest published toxic dose: 12 gm/kg/8 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		TXAPA9 82,19,1986
oral
mouse 		lowest published toxic dose: 239 gm/kg/90 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		NCITR* NCI-TR-80,1978
oral
mouse 		toxic dose : 523 gm/kg/90 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		NCITR* NCI-TR-80,1978
oral
rat 		lowest published toxic dose: 185 gm/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors 		NCITR* NCI-TR-80,1978
oral
rat 		toxic dose : 416 gm/kg/57 week- continuous Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors

Liver: Tumors 		BJCAAI 24,164,1970
oral
rat 		toxic dose : 408 gm/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors 		NCITR* NCI-TR-80,1978
oral
rat 		toxic dose : 416 gm/kg/57 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors 		BJCAAI 24,164,1970
oral
rat 		toxic dose : 528 gm/kg/63 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Kidney, Ureter, and Bladder: Kidney tumors 		JNCIAM 35,949,1965
skin
mouse 		lowest published toxic dose: 14 gm/kg/60 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors 		EVHPAZ 5,163,1973


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
cat 		lowest published lethal concentration: 44 gm/m3/7 hour Behavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea 		KDPU** -,-,1937
inhalation
human 		lowest published toxic concentration: 470 ppm Behavioral: Convulsions or effect on seizure threshold

Vascular: BP elevation not characterized in autonomic section

Gastrointestinal: Other changes 		AMIHAB 20,445,1959
inhalation
human 		lowest published toxic concentration: 5,500 ppm/1 minute Eye: Lacrimation

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Other changes 		PHRPA6 45,2023,1930
inhalation
human 		lowest published lethal concentration: 470 ppm/3 day Brain and Coverings: Other degenerative changes

Lung, Thorax, or Respiration: Other changes

Liver: Other changes 		PLENBW 7(9),22,1975
inhalation
mammal (species unspecified) 		lethal concentration (50 percent kill): 20,500 mg/m3 N/R GISAAA 51(5),61,1986
inhalation
mouse 		lethal concentration (50 percent kill): 37 gm/m3/2 hour N/R 85GMAT -,63,1982
inhalation
rat 		lethal concentration (50 percent kill): 46 gm/m3/2 hour Eye: Other eye effects KBAMAJ 11(6),53,1977
intraperitoneal
mouse 		lethal dose (50 percent kill): 790 mg/kg Lung, Thorax, or Respiration: Other changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		FEPRA7 6,342,1947
intraperitoneal
rat 		lethal dose (50 percent kill): 799 mg/kg N/R ENVRAL 40,411,1986
intravenous
cat 		lowest published lethal dose: 1,500 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Irritability 		JOHYAY 35,540,1935
intravenous
rabbit 		lowest published lethal dose: 1,500 mg/kg Kidney, Ureter, and Bladder: Urine volume increased

Kidney, Ureter, and Bladder: Urine volume decreased or anuria

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		JOHYAY 35,540,1935
oral
cat 		lethal dose (50 percent kill): 2 gm/kg N/R JIHTAB 21,173,1939
oral
guinea pig 		lethal dose (50 percent kill): 3,150 mg/kg Behavioral: General anesthetic

Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Other changes 		JIHTAB 23,259,1941
oral
mouse 		lethal dose (50 percent kill): 5,300 mg/kg N/R IJEBA6 16,54,1978
oral
rat 		lethal dose (50 percent kill): 4,200 mg/kg N/R INHEAO 32,145,1994
oral
rabbit 		lethal dose (50 percent kill): 2 gm/kg N/R JIHTAB 21,173,1939
skin
rabbit 		lethal dose (50 percent kill): 7,600 µL/kg N/R UCDS** 12/17/1971


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
rat 		lowest published toxic concentration: 6,000 ppm/4 hour/2 week- intermittent Behavioral: Change in psychophysiological tests AIHAAP 25,369,1964
inhalation
rat 		lowest published toxic concentration: 20,500 µg/m3/13 week- intermittent Kidney, Ureter, and Bladder: Proteinuria

Nutritional and Gross Metabolic: Changes in: Cl

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		KBAMAJ 11(6),53,1977


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 20 ppm (skin) DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Confirmed Animal Carcinogen with Unknown DTLVS* TLV/BEI,2003
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 11,247,1976
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 71,589,1999
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMSUDL 7,201,1987
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 71,589,1999
International Agency for Research on Cancer (IARC) Cancer Review Group 2B IMEMDT 71,589,1999
TOXICOLOGY REVIEW
TOLED5 127,111,2002
TOXICOLOGY REVIEW
ECIET* (2),-,1983
TOXICOLOGY REVIEW
MUREAV 543,201,2003
TOXICOLOGY REVIEW
MUREAV 567,227,2004
TOXICOLOGY REVIEW
MUREAV 567,109,2004
TOXICOLOGY REVIEW
MUREAV 567,151,2004


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD - air time-weighted average 100 ppm (360 mg/m3) (skin) DTLVS* 3,94,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) 8 hour time-weighted average 100 ppm (360 mg/m3) (skin) CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) 8 hour time-weighted average 100 ppm (360 mg/m3) (skin) CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) 8 hour time-weighted average 100 ppm (360 mg/m3) (skin) CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) 8 hour time-weighted average 100 ppm (360 mg/m3) (skin) CFRGBR 41,50-204.50,1994
Occupational Exposure Limit - AUSTRALIA time-weighted average 25 ppm (90 mg/m3), Skin, JAN1993
Occupational Exposure Limit - AUSTRIA MAK 50 ppm (180 mg/m3), Skin, Suspected Carcinogen, JAN1999
Occupational Exposure Limit - BELGIUM time-weighted average 25 ppm (90 mg/m3), Skin, JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 10 ppm (36 mg/m3), Skin, JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 25 ppm (90 mg/m3), short term exposure limit 40 ppm (135 mg/m3), Skin, JAN1999
Occupational Exposure Limit - FRANCE VME 10 ppm (35 mg/m3), VLE 40 ppm, continuous3 Carcinogen, JAN1999
Occupational Exposure Limit - GERMANY MAK 50 ppm (180 mg/m3), Skin, Carcinogen, JAN1999
Occupational Exposure Limit - HUNGARY short term exposure limit 10 mg/m3, Skin, Carcinogen, JAN1993
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 40 mg/m3, Skin, 2003
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 100 ppm (360 mg/m3), Skin, JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 10 mg/m3, MAC(short term exposure limit) 80 mg/me, JAN1999
Occupational Exposure Limit - RUSSIA time-weighted average 10 ppm, short term exposure limit 10 mg/m3, Skin, JAN1993
Occupational Exposure Limit - SWEDEN NGV 25 ppm (90 mg/m3), KTV 50 ppm, Skin, Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 25 ppm (90 mg/m3), short term exposure limit 50 ppm, Skin, JAN1999
Occupational Exposure Limit - TURKEY time-weighted average 100 ppm (360 mg/m3), Skin, JAN1993
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 25 ppm (91 mg/m3), short term exposure limit 100 ppm, Skin, SEP2000
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Confirmed Animal Carcinogen with Unknown
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Confirmed Animal Carcinogen with Unknown


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO DIOXANE-air Carcinogen ceiling concentration 1 ppm/30 minute NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 25145;
Number of Industries 135;
Total Number of Facilities 12,911;
Number of Occupations 101;
Total Number of Employees Exposed 147,783
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 25145;
Number of Industries 181;
Total Number of Facilities 20,994;
Number of Occupations 137;
Total Number of Employees Exposed 429,330;
Total Number of Female Employees Exposed 149,697


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Negative: Cell transform.-SA7/SHE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a stabilizer in chlorinated solvents, and as a solvent for CELLULOSE ACETATE
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Dioxane, 1602
NCI Carcinogenesis Bioassay (oral);clear evidence:mouse,rat NCITR* NCI-TR-80,1978
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen


REFERENCES:

CODEN
REFERENCE
85GMAT "Toxicometric Parameters of Industrial Toxic Chemicals Under Single Exposure," Izmerov, N.F., et al., Moscow, Centre of International Projects, GKNT, 1982
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
AIHAAP American Industrial Hygiene Association Journal. (AIHA, 475 Wolf Ledges Pkwy., Akron, OH 44311) V.19- 1958-
AJOPAA American Journal of Ophthalmology. (Ophthalmic Pub. Co., 435 N. Michigan Ave., Suite 1415, Chicago, IL 60611) Series 3: V.1- 1918-
AMIHAB AMA Archives of Industrial Health. (Chicago, IL) V.11-21, 1955-60. For publisher information, see AEHLAU.
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974-
BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947-
CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975-
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
ECIET* European Chemical Industry Ecology and Toxicology Centre. Joint Assessment of Commodity Chemicals. (Avenue Louise 250, B-63, B-1050 Brussels, Belgium)
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENVRAL Environmental Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1967-
EVHPAZ EHP, Environmental Health Perspectives. (U.S. Government Printing Office, Supt of Documents, Washington, DC 20402) No.1- 1972-
FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87.
GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936-
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
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-
INHEAO Industrial Health. (National Institute of Industrial Health, 6-21-1 Nagao, Tama-ku, Kawasaki, 213 Japan) V.1- 1963-
JIHTAB Journal of Industrial Hygiene and Toxicology. (Cambridge, MA) V.18-31, 1936-49. For publisher information, see AEHLAU.
JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8.
JOHYAY Journal of Hygiene. (Cambridge Univ. Press, 32 E. 57th St., New York, NY 10022) V.1- 1901-
JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949-
KBAMAJ Kosmicheskaya Biologiya I Aviakosmicheskaya Meditsina. Space Biology and Aerospace Medicine. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.8- 1974-
KDPU** "Beitrag zur Toxikologischen Wirkung Technischer Losungsmittel, Dissertation," Klimmer, O., Pharmakologischen Institut der Universitat Wurzburg, Fed. Rep. Ger., 1937
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*.
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
PHRPA6 Public Health Reports. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1878-
PLENBW Pollution Engineering. (P.O. Box 1151, Skokie, IL 60077) V.1- 1969-
SinJF# Personal Communication from J.F. Sina, Merck Institute for Therapeutic Research, West Point, PA 19486, Oct. 26, 1982
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-
UCDS** Union Carbide Data Sheet. (Union Carbide Corp., 39 Old Ridgebury Rd., Danbury, CT 06817)

Used as a stabilizer in chlorinated solvents, and as a solvent for CELLULOSE ACETATE

NIOSH PROFILE (DIMETHYL SULFATE), SRC, 12/79

RTECS Compound Description:
   Tumorigen
   Mutagen
   Reproductive Effector
   Human Data
   Primary Irritant

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