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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Based on a weight of evidence (WoE) approach in accordance with REACH Annex XI Section 1.2 it can be concluded that there are no indications that exposure to 1,4 -dioxane affects reproductive organs or causes impairment of fertility functionality.
Link to relevant study records
- Endpoint:
- extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Justification for type of information:
- According to REACH Annex XI Section 1.2 data from studies other than required according to Annex IX and/or Annex X for a specific endpoint may be used to sufficiently conclude on this endpoint by an weight of evidence (WoE) assessment and taking into account the overall picture of all data sources available.
There are comprehensive data available with the registered substance investigating repeated dose toxicity under sub-chronic as well as chronic exposure conditions via the oral and inhalation route in two different species (rats and mice). None of these studies revealed a test item related impairment of the reproductive organs in either sex or species. Thus, there are no indications that fertility functions could be affected by the test item below maternal toxic concentrations.
Furthermore, a prenatal-developmental toxicity study in the rat is available with the registered substance. Results demonstrate that there is no concern in regards to developmantal toxicity / teratogenicity with the test item.
It should be noted that the registered substance has to be classified for carcinogenicity (cat. 1B) according to CLP and appropriate risk management measures are implemented. This legally binding classification makes further testing for toxicity to reproduction obsolete, also considering animal welfare reasons.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
There is no adequate fertility study available with 1,4-dioxane.
However, there is sufficient and reliable data from sub-chronic and chronic toxicity studies available in two different species and via the oral as well as the inhalation route.
Therefore, and in accordance with REACH Annex XI Section 1.2, a weight of evidence (WoE) approach was applied in order to address the endpoint of toxicity to reproduction.
In conclusion it can be stated that there are no indications that exposure to 1,4 -dioxane could affect reproductive organs in either sex based on pathological and histopathological evaluations after repeated dose exposure. Therefore, it is not expected that 1,4 -dioxane could cause any impairment of fertility functions in mammals.
Effects on developmental toxicity
Description of key information
In an oral teratogenicity study with rats the NOAEL for maternal and embryotoxicity can be established at 0.5 mL/kg/bw, equivalent to 517 mg/kg bw/day.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Calco Italy
- Weight at study initiation: 178-182 gram
- Housing: females caged overnight with males.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- daily administration by gavage at a constant volume (3 mL/kg)
- Details on mating procedure:
- Females were caged overnight with males. The day on which sperm was found in the vaginal smear was considered day 1 of gestation.
- Duration of treatment / exposure:
- gestation day 6-15
- Frequency of treatment:
- daily
- Duration of test:
- the animals were killed on day 21 of pregnancy
- Dose / conc.:
- 258 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 0.25 mL/kg bw/d
- Dose / conc.:
- 517 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 0.5 mL/kg bw/d
- Dose / conc.:
- 1 034 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 1.0 mL/kg bw/d
- No. of animals per sex per dose:
- 0 mL/kg bw/day (control): 18 (17 pregnant)
0.25 mL/kg bw/day: 18 (17 pregnant)
0.5 mL/kg bw/day: 19 (19 pregnant)
1.0 mL/kg bw/day: 20 (20 pregnant) - Control animals:
- yes
- Maternal examinations:
- Food consumption: daily
Weight determination: every three days - Ovaries and uterine content:
- corpora lutea, implantations, resorptions, live fetuses
- Fetal examinations:
- Examination of the viscera and skelatal obervations
- Statistics:
- The data were analysed using Student's f-test or analysis of variance, except for pre- and postimplantation loss and frequency of malformations, which were analysed using 2 x 2 contingency tables.
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The females treated with 1 mL/kg bw/d showed a slightly smaller weight gain during treatment, which continued during the second stage of gestation.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption in the females treated with 1mL/kg bw/d was decreased during treatment, especially evident in the first 2 days of treatment.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Number of implantations was slightly decreased at 1 mL/kg bw and preimplantation loss was slightly increased at this dose level.
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 517 mg/kg bw/day
- Basis for effect level:
- body weight and weight gain
- food efficiency
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The average weight of live foetuses from dams treated with 1 mL/kg bw was significantly less than controls.
- Reduction in number of live offspring:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Number of foetuses alive was slightly decreased at 1 mL/kg bw/d.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the dose level of 1mL/kg bw/d a delay of ossification was found in the area of the sternum. There was no indication for teratogenicity.
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 517 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: slightly decreased number of implantations and number of foetuses alive, slightly increased preimplantation loss, delay of ossification in the area of the sternum
- Remarks on result:
- other: effects seen only at dose levels inducing maternal toxicity, too
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 517 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
An acceptable teratogenicity study is available, in which rats were treated with 0, 0.25, 0.5 or 1.0 mL 1,4-dioxane/kg bw/day by gavage during gestation days 6 -15. At 1 mL/kg bw/day slight maternal toxicity was seen (decreased weight gain and food consumption) together with slight unspecific embryotoxicity (decreased weight of live foetuses, slightly decreased number of implantations and number of foetuses alive, slightly increased preimplantation loss, delay of ossification in the area of the sternum). Embryotoxicity can be atributed to maternal toxicity in this case. No teratogenic effects were observed. The NOAEL for maternal and embryotoxicity was established at 0.5 mL/kg bw/day (equivalent to 517 mg/kg bw/day).
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. The
available developmental toxicity study does not trigger classification
for developmental toxicity and no apparent effects on reproductive
organs or fertility functionality were observed in rats or mice in
several subchronic and chronic toxicity studies with 1,4 -dioxane. As a
result the substance does not require classification for toxicity to
reproduction under Regulation (EC) No 1272/2008, as amended for the
twelfth time in Regulation (EU) 2019/521.
Additional information
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.