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EC number: 204-661-8 | CAS number: 123-91-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- carcinogenicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Method: A lifetime 2-year study with rats, with a treated and a control group
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dow
- Housing: in groups of 4 or 8 during and between exposure
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
No data - Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Seven-hour daily exposures were given 5 days/week under dynamic exposure conditions in five 3.7 m3 stainless-steel vault-type chambers. A constant air flow of 373 liters/min nitrogen was maintained by means of rotary pump connetcted to the exhaust side of each chamber. The airflow was monitored with calibrated flow meters. The vapour was generated by metering liquid dioxane into an evaporation flaks heated to 100 dergees C.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- (on-line) infrared analysis
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- 7 hours/day, 5 days/week
- Post exposure period:
- none
- Dose / conc.:
- 0.4 mg/L air (analytical)
- Remarks:
- SD = 0.018 mg/L (5 ppm); corresponding to 111 ppm
- No. of animals per sex per dose:
- treatment group: 288 male and 288 female animals
control group: 192 male and 192 female animals - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Since the threshold limit value for dioxane at the time of this study was started and up until 1971 was set by the American Conference of Governmental Industrial Hygienists (1971) at 0.36 mg/L (100 ppm v/v), this concentration was selected for the 2-year study.
Selection of this concentration was also supported by previous studies in our laboratory, in which groups of 24 male and 24 female rats, 3 male and 3 female rabbits, and 2 female dogs received 130-136 7-hr exposures in 180-195 days to 50 ppm dioxane vapour in air. In addition, 7 male and 8 female guinea pigs received 82 exposures in 1 1.8 days to 50 ppm dioxane vapor in air, and groups of 12 rats and 2 rabbits of each sex received. 133-136 7-hr exposures to 100 ppm. There were no adverse effects when the exposed groups were compared to control groups on the basis of appearance, demeanor, growth, mortality, hematological and clinical chemical studies, organ weights, or gross and microscopic pathological examination. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes: signs of toxicity including alternations in activity, demeanor, eye and nasal irritation, skin condition, respiratory distress, and tumour formation.
- Time schedule: not excatly indicated; throughout the exposure period.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 16 or 23 months of exposure
- Anaesthetic used for blood collection: No data
- Animals fasted: yes
- How many animals: after 16 months: 232 control rats and 340 exposed rats
after 23 months:115 control rats and 185 exposed rats
Parameters checked : PCV, RBC, Hb, WBC, WBC different; Neut, Lymph, Mono, Eosin, Baso
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination of the study (after 2 years on all surviving rats)
- Animals fasted: Yes
- How many animals:103 control, 151 exposed rats
- Parameters checked: BUN, SGPT, AP and total protein
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
on succumbed and moribund rats, whenever possible moribund rats were killed for for gross examination and tissues were saved for microscopic
examination, with special attention to abnormal growths. Following gross examination body weights of liver, spleen and kidneys were recorded.
HISTOPATHOLOGY: Yes:
lungs, trachea, thoracic lymph nodes, heart, liver, pancreas, stomach, intestine, spleen, thyroid, mesentric lumph nodes, kidneys, urinary bladder, pituary, adrenals, tetstes, ovaries, oviduct, uterus, mammary gland, lacrimals gland, lymph nodes, brain, vagina, bone marrow, and any
abnormal growths. - Statistics:
- Control and experimental groups were compared statistically using:
Student's T-test (heamatology, clinical chemistry),
Fisher exact probability test (morphological classification of tumours),
Yates corrected Chi-Square test (survival) - Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
- Details on results:
- No effects were seen on clinical signs (including activity, demeanour, eye and nasal irritation, skin condition and respiratory distress), body weights or mortality.
Some slight changes were observed in haematological values, but these were within the normal physiological limits and not considered of toxicological importance.
BUN and AP values in treated male rats were slightly decreased.
Changes in liver, kidney or spleen weights were not observed.
Upon gross and microscopic examination, no treatment-related non-neoplastic effects were found in tissues/organs, including the reproductive organs. Regarding neoplastic effects, no 1,4-dioxane characteristic nasal and liver tumours, as observed after oral administration, were seen. It is however not clear from the text whether or not the nasal cavity was adequately examined. The incidence of tumours observed in other organs/tissues appeared to be unrelated to exposure. The only difference from the control groups was an increase in lymphoreticular cell sarcomas in males (18% (37/206) versus 12% (18/150)) and in mammary gland adenoma in females (13% (29/217) versus 8% (11/139)), which were not statistically significant. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- > 400 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects were observed
- Key result
- Critical effects observed:
- no
Data source
Reference
- Reference Type:
- publication
- Title:
- 1,4-Dioxane. II. Results of a 2-year inhalation study in rats
- Author:
- Torkelson TR, Leong BKJ, Kociba RJ, Richter WA and Gehring PJ
- Year:
- 1 974
- Bibliographic source:
- Toxicol. Appl. Pharmacol. 30, 287-298
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A lifetime 2-year study with rats, with a treated and a control group
- GLP compliance:
- no
- Limit test:
- yes
Test material
- Reference substance name:
- 1,4-dioxane
- EC Number:
- 204-661-8
- EC Name:
- 1,4-dioxane
- Cas Number:
- 123-91-1
- Molecular formula:
- C4H8O2
- IUPAC Name:
- 1,4-dioxane
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dow
- Housing: in groups of 4 or 8 during and between exposure
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
No data
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- Seven-hour daily exposures were given 5 days/week under dynamic exposure conditions in five 3.7 m3 stainless-steel vault-type chambers. A constant air flow of 373 liters/min nitrogen was maintained by means of rotary pump connetcted to the exhaust side of each chamber. The airflow was monitored with calibrated flow meters. The vapour was generated by metering liquid dioxane into an evaporation flaks heated to 100 dergees C.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- (on-line) infrared analysis
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- 7 hours/day, 5 days/week
Doses / concentrations
- Dose / conc.:
- 0.4 mg/L air (analytical)
- Remarks:
- SD = 0.018 mg/L (5 ppm); corresponding to 111 ppm
- No. of animals per sex per dose:
- treatment group: 288 male and 288 female animals
control group: 192 male and 192 female animals - Control animals:
- yes
- Details on study design:
- Since the threshold limit value for dioxane at the time of this study was started and up until 1971 was set by the American Conference of Governmental Industrial Hygienists (1971) at 0.36 mg/L (100 ppm v/v), this concentration was selected for the 2-year study.
Selection of this concentration was also supported by previous studies in our laboratory, in which groups of 24 male and 24 female rats, 3 male and 3 female rabbits, and 2 female dogs received 130-136 7-hr exposures in 180-195 days to 50 ppm dioxane vapour in air. In addition, 7 male and 8 female guinea pigs received 82 exposures in 1 1.8 days to 50 ppm dioxane vapor in air, and groups of 12 rats and 2 rabbits of each sex received. 133-136 7-hr exposures to 100 ppm. There were no adverse effects when the exposed groups were compared to control groups on the basis of appearance, demeanor, growth, mortality, hematological and clinical chemical studies, organ weights, or gross and microscopic pathological examination.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes: signs of toxicity including alternations in activity, demeanor, eye and nasal irritation, skin condition, respiratory distress, and tumour formation.
- Time schedule: not excatly indicated; throughout the exposure period.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 16 or 23 months of exposure
- Anaesthetic used for blood collection: No data
- Animals fasted: yes
- How many animals: after 16 months: 232 control rats and 340 exposed rats
after 23 months:115 control rats and 185 exposed rats
Parameters checked : PCV, RBC, Hb, WBC, WBC different; Neut, Lymph, Mono, Eosin, Baso
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination of the study (after 2 years on all surviving rats)
- Animals fasted: Yes
- How many animals:103 control, 151 exposed rats
- Parameters checked: BUN, SGPT, AP and total protein
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
on succumbed and moribund rats, whenever possible moribund rats were killed for for gross examination and tissues were saved for microscopic examination, with special attention to abnormal growths. Following gross examination body weights of liver, spleen and kidneys were recorded.
HISTOPATHOLOGY: Yes:
lungs, trachea, thoracic lymph nodes, heart, liver, pancreas, stomach, intestine, spleen, thyroid, mesentric lumph nodes, kidneys, urinary bladder, pituary, adrenals, tetstes, ovaries, oviduct, uterus, mammary gland, lacrimals gland, lymph nodes, brain, vagina, bone marrow, and any
abnormal growths. - Statistics:
- Control and experimental groups were compared statistically using:
Student's T-test (heamatology, clinical chemistry),
Fisher exact probability test (morphological classification of tumours),
Yates corrected Chi-Square test (survival)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
- Details on results:
- No effects were seen on clinical signs (including activity, demeanour, eye and nasal irritation, skin condition and respiratory distress), body weights or mortality.
Some slight changes were observed in haematological values, but these were within the normal physiological limits and not considered of toxicological importance.
BUN and AP values in treated male rats were slightly decreased.
Changes in liver, kidney or spleen weights were not observed.
Upon gross and microscopic examination, no treatment-related non-neoplastic effects were found in tissues/organs, including the reproductive organs. Regarding neoplastic effects, no 1,4-dioxane characteristic nasal and liver tumours, as observed after oral administration, were seen. It is however not clear from the text whether or not the nasal cavity was adequately examined. The incidence of tumours observed in other organs/tissues appeared to be unrelated to exposure. The only difference from the control groups was an increase in lymphoreticular cell sarcomas in males (18% (37/206) versus 12% (18/150)) and in mammary gland adenoma in females (13% (29/217) versus 8% (11/139)), which were not statistically significant.
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- > 400 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: no adverse health effects were observed
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.