Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 423-630-1 | CAS number: 62435-71-6
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Up to 52 day dosing period, extending to day 4 lactation
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Justification for type of information:
- Research working closely in line with OECD 415
Testing performed on major metabolite tetrahydrofurfuryl alcohol which is considered a suitable substitute for the ether.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Assessment made on result of testing to support registration of this substance and using test data from key metabolites
See report attached - Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Assessment made on result of testing to support registration of this substance and using test data from key metabolites
- GLP compliance:
- not specified
- Radiolabelling:
- no
- Species:
- other: Not applicable
- Route of administration:
- not specified
- Preliminary studies:
- The substance is soluble in water and is considered rapidly biodegradable (although along with other ethers and glycols, the results will depend on the type of method performed). A hydrolysis study has been performed and although apparently stable under environmental conditions, ethers will hydrolyse under gastric conditions to corresponding alcohols and aldehydes.
In view of the metabolic route being to tetrahydrofurfuryl alcohol (plus acetylaldehyde) and then on to hydroxybutanoic acid, date from these metabolites can be used to assess the potential toxicity of the ether. - Type:
- absorption
- Results:
- Yes, oral
- Type:
- distribution
- Results:
- Yes, target organs identified
- Type:
- metabolism
- Results:
- Yes, key metabolites estimated
- Type:
- excretion
- Results:
- No evidence of excretion, but metabolism is to substances found in nature
- Details on absorption:
- There was evidence of systemic effects reported for oral toxicity studies, with the repeat oral study and reproduction toxicity screening tests showing adverse effects at higher dose levels. Effects for both the ethyl ether and the alcohol include effects on liver function and organ weights, including testes.
There is no evidence of absorption following dermal or inhalation exposure, but in view of the low molecular weight, polarity and similarity to other ethers and alcohols, dermal absorption is considered likely. - Details on distribution in tissues:
- The impact on organs following oral ingestion and changes in chemistry parameters confirms distribution to key organs, even though some of the reported changes are possibly adaptive (ie metabolic processes) and not toxic adverse effects.
The low molecular weight and solubility in biological media would suggest transport of the substance and primary metabolites. - Details on excretion:
- There is limited evidence that furans and linear ethers are directly excreted, but in view of the potentially rapid metabolism to substances found naturally in the body, it is not expected that there will be excretion of the substance itself.
The ultimate metabolisms is to water and carbon dioxide that are excreted as part of natural biological systems. - Metabolites identified:
- yes
- Details on metabolites:
- Furans and linear ethers are well document for metabolic processes in biotic and in acidic media. The route of metabolism is illustrated below.
This route of degradation is the basis for validating the read-across between the ethyl ether and alcohol. Although the impact of acetaldehyde cannot be ignored, the reaction kinetics is thought to result in further degradation to acetate at a sufficiently high rate to ensure low levels of acetaldehyde. However, the slight, but significant, mutagenic potential from in-vitro gene mutation testing is consistent with low levels of acetaldehyde and furan.
In human metabolism, acetaldehyde forms naturally as part of the metabolism of ethanol. - Conclusions:
- Considered to be readily adsorbed and metabolised to alcohols, aldhehydes and acid salts.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 007
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Principles of method if other than guideline:
- Rats were given tetrahydrofurfuryl alcohol (THFA) by gavage.
Males were dosed for 47 days, beginning 14 days before mating, and females were dosed for 42–52 days beginning 14 days before mating to day 4 of lactation
throughout the mating and gestation period - GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- Follows accepted scientific principles
Test material
- Reference substance name:
- Tetrahydrofurfuryl alcohol
- EC Number:
- 202-625-6
- EC Name:
- Tetrahydrofurfuryl alcohol
- Cas Number:
- 97-99-4
- Molecular formula:
- C5H10O2
- IUPAC Name:
- Tetrahydrofurfuryl alcohol
Constituent 1
- Specific details on test material used for the study:
- 99.5% purity
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 21.9–22.4 C,
Relative humidity of 49–57%,
12-h light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- Twelve male and female rats per group were given tetrahydrofurfuryl alcohol (THFA) by gavage at 0, 15, 50, 150 or 500 mg/kg/day. Males were
dosed for 47 days, beginning 14 days before mating, and females were dosed for 42–52 days beginning 14 days before mating to day 4 of lactation
throughout the mating and gestation period - Details on mating procedure:
- After 14 days pre-,ating exposure, male and female rats (1:1) were placed in seperate cages
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations in the formulations were confirmed to be 97.7–103.0% of nominal (gas chromatography).
- Duration of treatment / exposure:
- 14 days prior to mating (males and females) and up to 4 days after birth (females)
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle only
- Dose / conc.:
- 15 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12 males and 12 females
- Control animals:
- yes, concurrent vehicle
- Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- All animals were observed for clinical signs at least twice a day.
The body weight was recorded at least once a week - Oestrous cyclicity (parental animals):
- Yes
- Sperm parameters (parental animals):
- Yes
- Litter observations:
- Yes
- Postmortem examinations (parental animals):
- Gross necropsy and more detailed pathology on reproductive organs
- Postmortem examinations (offspring):
- Viabilty, weight and gross necropsy
- Reproductive indices:
- Yes
- Offspring viability indices:
- Yes
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced activity in higher dose groups
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One male died on Day 15 in a mid group. Not considered to be treatment related.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced bodyweight gain at 500 mg/kg/day
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food consumptionin higher treatment levels
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced activity in higher groups
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increases in the incidence of seminiferous tubular atrophy and hyperplasia of interstitial cells in the testes, and cell debris and decreased sperm at 500 mg/kg/day
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- Oestrous cycle at 500 mg/kg prolonged
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced sperm parameters at 500 mg/kg/day
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- No young from highest doese goup and reduced at 150 mg/kg/day
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- gross pathology
- reproductive function (sperm measures)
- reproductive performance
Target system / organ toxicity (P0)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 150 mg/kg bw/day (nominal)
- System:
- male reproductive system
- Organ:
- kidney
- spleen
- testes
- Treatment related:
- yes
- Dose response relationship:
- yes
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Live pups survived until termination
- Body weight and weight changes:
- no effects observed
- Gross pathological findings:
- no effects observed
Effect levels (F1)
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 150 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to other toxic effects:
- reproductive effects in the absence of other toxic effects
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The research demonstrated a NOAEL for parental and reproductive/developmental toxicity to be 50 mg/kg/day.
The impact on testes and sperm parameters is consistent with other repeat dose toxicity studies in rats and dogs, suggesting reproductive toxicty
This result is consistent with furan (cyclic ether)
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.