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EC number: 219-268-7 | CAS number: 2399-48-6
- 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
Endpoint summary
Administrative data
Description of key information
No repeated toxicity study is available on the registered substance (THFA).
However a combined repeated dose and reproduction / developmental screening in available on the analogue substance (THFMA) : in which the NOAEL for the systemic effects is higher than 300 mg/kg bw/d.
And a 90 -day repeated toxicity study is available on a metabolite of THFA : THF alcohol, in which the NOAEL is of 35 and 84 mg/kg bw/day in male and female rats respectively.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1992-02-19 to 1993-01-25
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study was conducted according a method largely equivalent to the relevant OECD test guideline and in compliance with GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Labs, Portage, MI, USA
- Age at study initiation: approx 23 days
- Housing: 1/wire mesh cage
- Diet: standard diet (Purina Certified Rodent Chow #5002
- Water: drinking water ad libitum
- Acclimation period: 20 days, including pretest
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67-75 deg F
- Humidity (%): 29-88 (said not to have affected results)
- Air changes (per hr): 12h/ 12h
- Photoperiod (hrs dark / hrs light):
IN-LIFE DATES: From: 1992-02-19 To: 1992-05-22 - Route of administration:
- oral: feed
- Vehicle:
- other: standard diet
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): diet offered fresh weekly - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Three samples were taken from the 500 and 10,000 ppm diets to determine homogeneity, stability (for 7 and 14 days). Samples were taken from the middle of each control and test diet on the day of preparation during weeks 0, 1, 2, 3, 7 and 12 to determine concentration of test substance.
Individual food consumption was measured weekly and the mean daily dose calculated for each dose group using body weight. - Duration of treatment / exposure:
- 91-93 days
- Frequency of treatment:
- diet ad libitum
- Remarks:
- Doses / Concentrations:
0, 500, 1000, 5000, 10,000 ppm
Basis:
other: in the diet. Mean THFA dose: males 35, 69, 339, 673 mg/kg bw/day; females 42, 84, 401, 781 mg/kg bw/day - No. of animals per sex per dose:
- 20
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment: computer randomized - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly (from wk -1)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to treatment and week 12
- Dose groups that were examined: all groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necropsy (13 wk)
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: 10/sex/dose
- Parameters checked in table No.1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Yes
- How many animals: 10/sex/dose
- Parameters checked in table No.1 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 2) - Statistics:
- All analyses were conducted using 2-tailed tests for minimum significance levels 1% and 5% comparing treated groups with controls by sex. Body weights, food consumption, clinical laboratory parameters, absolute and relative organ weights: 1-way analyis of variance and Dunnett's test.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- no deaths, rectal mucous exudate.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- no deaths, rectal mucous exudate.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- significant reduction in final body weight in males at 1000 ppm and above and in females at 5000 ppm and above
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- reduced food consumption at 5000 ppm in males and 10000 ppm in both sexes
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- dose-related effects at 5000 ppm and above in both sexes
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- dose-related effects at 5000 ppm and above in both sexes
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- lower testis, epididimal and prostate weight (5000 and/or 10,000 ppm)
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- testis: small and/or soft at 5000 ppm and above
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- testis: dose-related degenerationof germinal epithelium of seminiferous tubules and interstitial oedema at 5000 ppm and above. Adhesions of the spleen at these doses and capsular fibrosis (focal) sporadically in all treated groups.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No deaths.
Rectal mucous exudate sporadically at 5000 ppm and above.
BODY WEIGHT AND WEIGHT GAIN
Significant reduction in final body weight in males at 1000 ppm and above and in females at 10,000 ppm (p<0.01 in both cases). Dose-related decreases (statistically significant in some cases) in mean body weights (compared to control) and body weight gains in all treated male groups (500 ppm and above) and in females in the top two dose groups.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Reduced food consumption at 5000 ppm in males and 10,000 ppm in both sexes. Dose-related decrease in mean food consumption in treated male groups.
OPHTHALMOSCOPIC EXAMINATION
No treatment-related effects.
HAEMATOLOGY
Dose-related effects at 5000 ppm and above in both sexes: decreased haemoglobin, MCH, MCHC and platelet counts. Slightly reduced MCV values in females at 5000 ppm and above.
CLINICAL CHEMISTRY
Dose-related effects at 5000 ppm and above in both sexes: dose-related reduction in total protein and globulin, and increased A/G ratio at 5000 ppm and above in both sexes. Albumin was reduced in females at 10,000 ppm.
ORGAN WEIGHTS
Reduced testis and epididimal weight (mean absolute and relative) at 5000 ppm and above in males, lower prostate weight (mean absolute and relative) at 10,000 ppm (all p<0.01 or 0.05, except mean relative testis weight at 5000 ppm). Absolute seminal vesicle weights were lower at 5000 ppm and above, and absolute prostate weight was lower at 1000 and above. Differences in liver weights were not considered treatment-related due to inconsistency between the responses of the sexes. No other treatment-related differences reported.
GROSS PATHOLOGY
Testis: small and/or soft at 5000 ppm and above
HISTOPATHOLOGY: NON-NEOPLASTIC
Testis: dose-related degeneration of germinal epithelium of seminiferous tubules and interstitial (peritubular) oedema at 5000 ppm and above.
Epididymides: empty or fluid filled tubules with accumulation of cellular debris seen in all 10,000 ppm males and some 5000 ppm males.
Spleen: adhesion to mesentery, abdominal wall or adipose tissue sporadically at 5000 ppm and above (both sexes). Capsular fibrosis (focal) sporadically in all treated groups. The investigators noted that while this effect may have been treatment-related its toxicological significance was not known. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 ppm
- Based on:
- other: in the diet
- Sex:
- male
- Basis for effect level:
- other: mean measured dose 35 mg/kg bw/day
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 ppm
- Based on:
- other: in the diet
- Sex:
- female
- Basis for effect level:
- other: mean measured dose 84 mg/kg bw/day
- Critical effects observed:
- not specified
- Conclusions:
- A well reported 90-day dietary study, conducted in the main according to the current guideline and in accordance with GLP, identified NOAELs of 500 ppm and 1000 ppm in the diet in male and female rats, respectively. This dietary intake was equivalent to mean measured intakes of 35 and 84 mg THFA/kg bw/day, in males and females. Reduced body weights were reported at the next highest dietary concentration in both cases. The testis was the major target organ.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 35 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The key study is considered to be reliable.
- System:
- male reproductive system
- Organ:
- testes
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Sub-chronic repeated toxicity study on a metabolite of THFA (1993):
A well reported 90 -day dietary study, conducted in the main according to the current guideline OECD 408 and in accordance with GLP, identified NOAELs of 500 and 1000 ppm in the diet in male and female rats, respectively. This dietary intake was equivalent to mean measured intakes of 35 and 84 mg/kg bw/day in males and females respectively. Reduced body weights were reported at the next highest dietary concentration in both cases. The testis was the major target organ.
Sub-acute repeated toxicity study on analogue substance (2015):
In a combined repeated toxicity study with a reproduction and developmental toxicity study according to OECD Guideline 422 (adopted on 22 March 1996) Tetrahydrofurfuryl methacrylate was administered to 10 Sprague Dawley rats / sex / dose by gavage at dose levels of 0 (control), 50, 120 and 300 mg/kg bw/day in corn oil at a constant volume of 5 mL/kg bw.
Males were treated for a total of 29 days including 2 weeks prior to pairing and continuously thereafter, up to the day before necropsy. Females were dosed throughout the study including 2 weeks before pairing, thereafter during pairing, gestation and lactation periods until the day of necropsy or Day 3 post partum for females with live pups at Day 4 post partum.
The following parameters were evaluated in parental animals: body weight, clinical signs (including neurotoxicity assessment, motor activity and sensory reaction to stimuli), food consumption, oestrous cycle, mating performance, clinical pathology investigations (haematology and clinical chemistry), litter data, macroscopic observations, organ weights and histopathological examination. Pup weight, pup clinical signs and pup macroscopic observations were also performed.
No mortality occurred in the study. Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item. No significant clinical signs were observed.
Males: No relevant changes were recorded during the study and at the post mortem examinations in males at any dose level investigated. In particular no effects were seen on body weight and body weight gain, clinical signs (including neurotoxicity assessment, motor activity and sensory reaction to stimuli), food consumption, clinical pathology investigations (haematology and clinical chemistry), macroscopic observations, organ weights and histopathological examination, including identification of the stages of the spermatogenic cycle. The mating performance including the pre-coital interval (i.e. the number of days paired to sperm positive day) and the copulatory evidence (i.e. the presence of sperm and/or copulation plug in situ or in the cage) did not show differences between groups.
Females: A total of 5 females were found not pregnant at necropsy: 4 in the control group and 1 in the mid-dose (120 mg/kg bw/day) group. Unilateral implantation was observed in one low dose (50 mg/kg bw/day) female. In the high dose group (300 mg/kg bw/day), 3 females had total resorption and 7 females had total litter loss within 1 day of parturition. Therefore, the number of females with live pups on Day 4 post partum was: 6 in the control, 10 in the low dose (50 mg/kg bw/day), 9 in the mid-dose (120 mg/kg bw/day) group and none in the high dose (300 mg/kg bw/day) group. On Day 20 post coitum, a decrease in body weight and body weight gain (statistically significant) was evident in females dosed at 300 mg/kg bw/day respect to controls. Decreases in food consumption were seen in high dose females (300 mg/kg bw/day) when compared with controls during the post coitum and post partum periods with statistically significance on Days 7 and 14 post coitum and 4 post partum. Gestation length of all treated groups was higher than controls and significantly increased at statistical analysis, in the high dose group. The pre-birth loss was significantly increased at statistical analysis, in high dose females. This increase could be attributable to the prolonged gestation period which caused most probably pup suffering and the death during or shortly after the birth.
On the basis of the results obtained in the study, the NOAEL (No Observed Adverse Effect Level) for systemic toxicity was considered 300 mg/kg bw/day for males and females.
Justification for classification or non-classification
Based on the available data, THFA does not need to be classified for repeated dose toxicity according to the criteria given in regulation (EC) 1272/2008.
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.
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