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EC number: 217-752-2 | CAS number: 1948-33-0
- 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: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Repeated dose oral toxicity study of the test chemical
- Author:
- DHHS
- Year:
- 1 997
- Bibliographic source:
- NTP
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Male and female F344/N rats were fed diets containing 0, 2500, 5000 or 10000 ppm of the test chemical for 13 weeks after weaning to study the cumulative toxic effects of the substance.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 2-tert-butylhydroquinone
- EC Number:
- 217-752-2
- EC Name:
- 2-tert-butylhydroquinone
- Cas Number:
- 1948-33-0
- Molecular formula:
- C10-H14-O2
- IUPAC Name:
- 2-tert-butylbenzene-1,4-diol
- Details on test material:
- - Name of test material: tert-Butyl hydroquinone (TBHQ)
- IUPAC name: 2-tert-Butylhydroquinone
- Molecular formula: C10H14O2
- Molecular weight: 166.219 g/mol
- Substance type: Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Male and female F344/N rats in the F0 generation were obtained from Taconic Farms (German-town, NY). Offspring (F 1 generation) of the breeders from the perinatal phase of the study.
- Age at study initiation: 34 days
- Housing: Rats were housed five per cage in polycarbonate cages with bedding
- Diet (e.g. ad libitum): NIH-07 open formula mash diet, ad libitum
- Water (e.g. ad libitum): Tap water via automatic watering system; available ad libitum
- Acclimation period: None
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7°C to 24.2°C
- Humidity (%): 35.8 %-79.3 %
- Air changes (per hr): minimum of 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours/day
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: NIH-07 open formula mash diet
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Storage temperature of food: The dose formulations were stored in sealed containers in the dark at 5°C for no longer than 3 weeks. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and stability analyses of the dose formulations were conducted by the analytical chemistry laboratory using high-performance liquid chromatography.
- Duration of treatment / exposure:
- 13 weeks after weaning
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 2500, 5000, or 10000 ppm (0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females)
Basis:
other: Approx 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females
- No. of animals per sex per dose:
- Control: 10 males and 10 females
2500 ppm: 10 males and 10 females
5000 ppm: 10 males and 10 females
10000 ppm: 10 males and 10 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: No F1 offspring resulted from F0 females fed diets containing 20000 or 40000 ppm, so these exposure levels were not used in the 13-week rat study
- Rationale for animal assignment: Animals were distributed randomly into groups of approximately equal initial mean body weights
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
Animals were observed twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
Clinical findings were recorded
BODY WEIGHT: Yes
- Time schedule for examinations: The animals were weighed initially, weekly, and at the end of the study
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
Feed consumption was recorded as an average of grams per animal per day.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 13 weeks
- Parameters examined: Hematocrit level, hemoglobin concentration, erythrocyte count, reticulocyte count, nucleated erythrocyte count, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, and leukocyte count and differential.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 13 weeks
- Parameters examined: Blood urea nitrogen, creatinine, total protein, albumin, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
Sperm Motility and Vaginal Cytology Evaluation:
Sperm and vaginal fluid samples were evaluated in all groups at the end of the studies. The parameters evaluated in males were sperm count and motility. The right cauda, right epididymis, and right testis were weighed. Vaginal fluid samples were collected for up to 7 consecutive days prior to the end of the studies for vaginal cytology evaluations. The parameters evaluated in females were relative frequency of estrous stages and estrous cycle length - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organs weighed were the heart, right kidney, liver, lungs, right testis, and thymus
HISTOPATHOLOGY: Yes
Complete histopathologic examinations were performed. In addition to gross lesions, tissue masses, and associated lymph nodes, the tissues examined included: adrenal gland, bone and marrow, brain, clitoral gland, esophagus, heart (with aorta), large intestine (cecum, colon, rectum), kidneys, liver, lungs and main stem bronchi, lymph nodes (mandibular and mesenteric), mammary gland, nasal cavity and turbinates, ovaries, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skeletal muscle, skin, small intestine (duodenum, jejunum, ileum), spinal cord and sciatic nerve, spleen, stomach (fore stomach and glandular stomach), testis with epididymis and seminal vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus. - Statistics:
- Williams' or Dunnett' s test (organ and body weights) or Dunn's test (spermatid and epididymal spermatozoal parameters)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The final mean body weights of males and females in the 5000 and 10000 ppm groups were significantly lower than those of the controls
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Feed consumption by exposed groups was lower than that by controls at week 2, and, feed consumption by 5000 and 10000 ppm males and 10000 ppm females was slightly lower than that consumed by controls at the end of the study
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- The increases observed in the Serum bile acid levels and Serum alanine aminotransferase activity were marginal, and as histopathologic evaluation did not reveal evidence of liver toxicity, these increases were not considered to be biologically significant
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The organ weight differences were associated with histopathologic lesions and in many cases were secondary to lower body weights of exposed groups. Therefore, they were not considered clearly related to t-butylhydroquinone exposure
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased incidences of splenic pigmentation were observed in males and females exposed to 5000 or 10000 ppm, and incidences of atrophy of the red pulp were observed in these groups of females
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Details on results:
- The mean spermatid count, spermatid heads per testis, and spermatid heads per gram of testis were significantly decreased in males exposed to 5000 ppm. The estrous cycles of females exposed to 2500 or 5000 ppm were significantly longer than that of the controls. There were no biologically significant changes in clinical pathology parameters or in organ weights.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Significantly longer estrous cycles
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Body weight, feed consumption, sperm analysis
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The LOAEL value of the test chemical when administered in diet was found to be 200 mg/kg/day in female rats, as significantly longer estrous cycles were observed at this dose as compared to controls. The NOAEL value in male rats was determined to be 200 mg/kg/day, based on no effects observed during analysis of body weight, feed consumption and sperm parameters.
- Executive summary:
The cumulative toxic effects of the test chemical in rats were evaluated in the 13 week study. The test substance was administered in diet to male and female F344/N rats at a dose level of 0, 2500, 5000 or 10000 ppm for 13 weeks after weaning. This dose level is equivalent to a daily dose of approximately 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females.
The following parameters were evaluated: body weight and feed consumption, hematology, clinical chemistry and coagulation analysis, sperm motility and vaginal cytology. A complete histopathological examination was conducted. The LOAEL value of 2-tert-butylhydroquinone was found to be 200 mg/kg/day in female rats due to effect on length ofestrous cycles. The NOAEL value in male rats was determined to be 200 mg/kg/day,based on no effects observed during analysis of body weight, feed consumption and sperm parameters.
At various time points there were increases in serum bile acid levels and serum alanine aminotransferase activity levels in male and female rats exposed to the test chemical. Such increases are generally associated with liver toxicity and since histopathologic evaluation did not reveal any evidence of liver toxicity, these marginal increases were not considered to be biologically significant. The effect of the test chemical on reproductive parameters in male rats were observed only at dose level of 5000 ppm. Histopathologic changes were observed in rats exposed to 5000 or 10000 ppm the test chemical which included increased incidences of nasal respiratory epithelial hyperplasia, nasal exudate (males only), splenic pigmentation, splenic atrophy of the red pulp (females only), and kidney mineralization (females only).
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