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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
Endpoint summary
Administrative data
Description of key information
Based on all data available (including human experience) it can be concluded that 1,4-dioxane is irritating to the eye and the respiratory tract, but not to the skin. However, being a fat solvent, 1,4-dioxane can cause eczema upon prolonged or repeated contact.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- study was conducted before OECD 404 TG was established
- Principles of method if other than guideline:
- BASF Test
Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test). Two white Vienna rabbits were treated for 1, 5 and 15 minutes and for 20 hours using occlusive conditions. - GLP compliance:
- no
- Species:
- rabbit
- Strain:
- Vienna White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Weight at study initiation: male 3.11 kg; female 3.18 kg
ENVIRONMENTAL CONDITIONS
no data - Type of coverage:
- occlusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: approx. 1 mL - Duration of treatment / exposure:
- 1, 5, 15 min and 20 h
- Observation period:
- 8 days
- Number of animals:
- 2
- Details on study design:
- TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: patch, no further data
REMOVAL OF TEST SUBSTANCE
- Washing: yes (exposure 1, 5, 15 min) first with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %); no (exposure 20 h)
- Time after start of exposure: 1, 5, and 15 min, respectively
SCORING SYSTEM:
The original BASF grading was converted into the numerical grading according to the OECD Draize system. - Irritation parameter:
- erythema score
- Remarks:
- Exposure time: 15 min
- Basis:
- mean
- Remarks:
- (2 animals)
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: desquamation, parchment-like necrosis
- Irritation parameter:
- edema score
- Remarks:
- Exposure time: 15 min
- Basis:
- mean
- Remarks:
- (2 animals)
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: no effects
- Irritation parameter:
- erythema score
- Remarks:
- Exposure time: 20 h
- Basis:
- mean
- Remarks:
- (2 animals)
- Time point:
- 24/48/72 h
- Score:
- 1.34
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: desquamation, parchment-like necrosis
- Irritation parameter:
- edema score
- Remarks:
- Exposure time: 20 h
- Basis:
- mean
- Remarks:
- (2 animals)
- Time point:
- 24/48/72 h
- Score:
- 0.84
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 days
- Interpretation of results:
- GHS criteria not met
Reference
Table 1 Mean erythema score after 24, 48 and 72 h (2 animals)
Exposure time |
24 h |
48 h |
72 h |
mean |
1 min |
1/1 |
0/1 |
0/1 |
0.33/1 |
5 min |
0/1 |
0/1 |
0/1 |
0/1 |
15 min |
0/2* |
0/2** |
0/2** |
0/2 |
20 h |
1/2* |
0/2* |
1/2 |
0.67/2 |
* brownish
** parchment-like
*** leather-like necrosis
Table 2 Mean edema score after 24, 48 and 72 h (2 animals)
Exposure time |
24 h |
48 h |
72 h |
mean |
1 min |
0/0 |
0/0 |
0/0 |
0/0 |
5 min |
0/0 |
0/0 |
0/0 |
0/0 |
15 min |
0/0 |
0/0 |
0/0 |
0/0 |
20 h |
0/2 |
0/3 |
0/0 |
0/1.67 |
Table 3 Findings after 8 days (2 animals)
Exposure time |
Skin finding |
1 min |
no skin findings*/desquamation |
5 min |
no skin findings*/desquamation |
15 min |
no skin findings*/desquamation, parchment-like necrosis fallen off |
20 h |
no skin findings*/desquamation, parchment-like necrosis |
*transient desquamation observed 6 days after application
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- Application volume 50 µL, 2 animals, 8 days observation period
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- Vienna White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: 2.99 kg (male); 3.21 kg (male)
ENVIRONMENTAL CONDITIONS
no data - Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 50 µL - Duration of treatment / exposure:
- eye remaind unwashed after application
- Observation period (in vivo):
- 8 days
- Number of animals or in vitro replicates:
- 2
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing: no washing
SCORING SYSTEM:
Discriptive scoring system comparable to draize
TOOL USED TO ASSESS SCORE: fluorescein - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal: #1 & #2
- Time point:
- 24/48/72 h
- Remarks on result:
- not measured/tested
- Irritant / corrosive response data:
- Mucous deposits on the eye were observed the 1st day after application.
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
Reference
Descriptive scores of the raw data have been converted to Draize numerical scores.
Animal 1 (male): day 1: 2.99 kg; day 8: 3.11 kg
Animal 2 (male): day 1: 3.21 kg; day 8: 3.19 kg
Animal |
Reading |
Opacity |
Redness |
Chemosis |
Comment |
1 |
1 h |
1 |
1 |
2 |
mucous deposits |
2 |
1 h |
1 |
1 |
1 |
mucous deposits |
1 |
24 h |
1 |
1 |
2 |
mucous deposits |
2 |
24 h |
1 |
1 |
1 |
mucous deposits |
1 |
48 h |
2 |
2 |
1 |
blood and scar (scraching) |
2 |
48 h |
1 |
1 |
0 |
blood (scraching) |
1 |
72 h |
1 |
1 |
1 |
blood and scar (scraching) |
2 |
72 h |
0 |
0 |
0 |
|
1 |
8 d |
0 |
1 |
0 |
|
2 |
8 d |
0 |
0 |
0 |
|
mean |
24 - 72 h |
1 |
1 |
0.8 |
|
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
Very limited human data regarding skin irritation is available. Regarding animal data, the BASF study (1973) was the only study considered acceptable for assessment. The study showed some indication of an irritant property to the intact skin. However, the findings were not considered sufficient to classify the substance for skin irritation. In an epicutaneous study in rabbits (1 male and 1 female) a cotton patch sized 2.5x2.5 cm was soaked with undiluted 1,4 -dioxane (approximately 0.5 mL) and applied to the shaven back ( for 1, 5 and 15 minutes as well as for 20 hours) under occlusive conditions. Application to the skin during 1 -15 minutes caused very slight erythema after 24 hours and slight scale formation after 8 days. This scale formation is most likely caused by the defatting properties of 1,4 -dioxane. 24 hours after the 20 -hour application, slight erythema and slight edema were observed on the back of 1 animal. Seven days later moderate scale formation was seen. The results do not trigger classification for skin irritation (BASF AG, 1973).
Regarding eye irritation, an animal study is available (BASF AG, 1973). Two male White Vienna rabbits received an instillation of 0.05 mL undiluted 1,4 -dioxane (eye remained unwashed after application). 24 hours after instillation, slight corneal opacity and conjunctival redness as well as slight to severe chemosis were observed in both rabbits. Additionally, smeary deposition was noted. 8 Days after application, when the study was terminated, slight conjunctival redness was observed in one animal. This finding was expected to would have reversed if the observation period had been prolonged. This animal showed small retraction of the eyelid. Because the chosen dose level is very low in comparison to the current guidelines and only 2 animals were used, 1,4 -dioxane is considered as an eye irritant (BASF AG, 1973).
Human data also indicated that 1,4 -dioxane can cause eye irritation.
Young et al. (1977) reported irritation of the eyes at 50 ppm (180 mg/m³) in 4 healthy volunteers during an inhalation study regarding toxicokinetics (exposure over 6 hours, see section 5.1.2). Eye irritation was a frequent complaint throughout exposure.
Furthermore, in a study by Silverman et al. (1946), twelve subjects were exposed to 1,4 -dioxane for 15 minutes. A concentration of 720 mg/m3 showed to be the highest concentration acceptable. At 1080 mg/m3 irritation of eyes was reported.
Available human and animal acute data regarding the inhalation route of exposure show that 1,4-dioxane can cause respiratory tract irritation. For DNEL derivation human data is used: twelve subjects were exposed to 1,4-dioxane for 15 minutes to observe olfactory fatigue. A concentration of 720 mg/m³ showed to be the highest concentration acceptable. At 1,080 mg/m³ irritation of the nose and throat was reported (Silverman et al., 1946).
In
addition, 1,4-dioxane is a fat solvent and prolonged and repeated
contact can cause eczema.
Justification for classification or non-classification
Classification,
Labelling, and Packaging Regulation (EC) No 1272/2008
The
available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. Based
on all data available (including human experience) it can be concluded
that 1,4-dioxane is irritating to the eye, but not to the skin.
Therefore, the test item is classified
as Eye irritation Cat.2 (H319:"Causes
serious eye irritation")
according to EU Classification, Labelling and Packaging of Substances
and Mixtures (CLP) Regulation (EC) No 1272/2008,
as amended for the twelfth time in Regulation (EU) 2019/521.
Based on practical observations in humans it is concluded that 1,4 -dioxane is irritating to the respiratory system. Therefore, the test item is classified as STOT SE 3 (H335: "May cause respiratory irritation") according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation).
In addition, being a fat solvent, 1,4-dioxane can cause eczema upon prolonged or repeated contact. However, this property is not covered by the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and should be indicated as supplemental hazard information as listed in Annex II to the CLP Regulation. In this case Section 1.2.4. EUH066.
The above classifications are also in accordance with harmonised classification of the registered substance according to Annex VI of the CLP Regulation.
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