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EC number: 911-254-5 | CAS number: -
- 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
Oral: Key study: Read-across from experimental results on the substance 6-tert-Butyl-2,4-xylenol: Test according to OECD guideline 422. GLP study.
Repeated dose oral:
NOAEL= 6 mg/kg/day (male)
NOAEL= 30 mg/kg/day (female)
Oral: Data waiving: In accordance with column 2 of REACH Annex IX, a subchronic toxicity study (90-days) does not need to be conducted since a reliable short-term toxicity study is available showing severe toxicity effects according to the criteria for classifying the substance, for which the observed NOAEL, with the application of an appropriate uncertainty factor, allows the extrapolation towards the NOAEL-90 days for the same route of exposure.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- (combined repeated dose and reproduction / developmental screening)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
The substance CAS No. 1879-09-0 is one of the main components of the reaction mass of 2-tertbutyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol and it is present in a concentration of more than 70%. Therefore, the results obtained with the substance CAS No. 1879-09-0 can be used for the read-across approach.
See attached the reporting format. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 6 mg/kg bw/day (actual dose received)
- Based on:
- other: Read-across from an analogue
- Sex:
- male
- Basis for effect level:
- other: Read-across from an analogue for which effects in clinical chemistry, liver and kidney weights and histopathological examination were observed.
- Remarks on result:
- other: read-across from an analogue for which NOEL = 6 mg/kg bw/day
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- other: Read-across from an analogue
- Sex:
- female
- Basis for effect level:
- other: Read-across from an analogue for which effects in liver and kidney weights and histopathological examination were observed.
- Remarks on result:
- other: read-across from an analogue for which NOEL = 30 mg/kg bw/day
- Critical effects observed:
- not specified
- Conclusions:
- Based on read-across approach from experimental data on analogue substance 6-tert-butyl-2,4-xylenol (CAS 1879-09-0), NOAELs for repeat dose toxicity of the reaction mass of 2-tert-butyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol are considered to be 6 mg/kg/day in males and 30 mg/kg/day in females.
- Executive summary:
In a experimental study the NOELs of 6-tert-butyl-2,4-xylenol were found to be 6 mg/kg/day in males and 30 mg/kg/day in females. Based on these results, the read-across approach was applied and the NOAELs of the reaction mass of 2-tert-butyl-4,6- dimethylphenol and 4-tert-butyl-2,5-dimethylphenol are considered to be 6 mg/kg/day in males and 30 mg/kg/day in females.
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- (combined repeated dose and reproduction / developmental screening)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Meets the requirements of GLP. There are no deviations from the recommended guideline.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Duration of treatment / exposure:
- Males: 45 days including 14 days before mating
Females: from 14 days before mating to day 3 of lactation - Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- (vehicle)
- Dose / conc.:
- 6 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Males,12; females, 12/group
- Control animals:
- yes, concurrent vehicle
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes
HAEMATOLOGY: Yes
CLINICAL CHEMISTRY: Yes - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: Yes
HISTOPATHOLOGY: Yes - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- There were no clinical abnormal signs attributable to the administration of the test substance. However, two female animals given 150 mg/kg died at the end of gestation period (one of them during the delivery).
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Two female animals given 150 mg/kg died at the end of gestation period (one of them during the delivery).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The body weight gain of females given 150 mg/kg was lower than that of the controls during the gestation period. However, body weights of males did not demonstrate any effects attributable to the administration of test substance.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption of both males and females did not demonstrate any effects attributable to the administration of test substance.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Hematological examination revealed decreases in hematocrit, hemoglobin and red blood cells, increases in reticulocytes and a slight tendency for anemia in males given 150 mg/kg. Blood clinical examination revealed decreases in GOT and increases in gamma-GTP in the 30 and 150 mg/kg males.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver and kidney weights showed increases or a tendency for increase in males given 30 mg/kg or more and females given 150 mg/kg. At necropsy enlargement of the liver in males given 30 and 150 mg/kg, and of the liver and kidneys in females given 150 mg/kg was noted.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination revealed swelling of centrilobular hepatocytes in males given 150 mg/kg and swelling and necrosis of centrilobular hepatocytes, and single cell necrosis in females given 150 mg/kg. The dead females and females with pups which all died showed increased incidences of parakeratosis of the tongue, esophageal swelling and necrosis of centrilobular hepatocytes, as well as a variety of degenerative charges, single cell necrosis and mitosis in the liver. Degeneration and protein cast in the proximal tubules and PAS positive granules deposited in the renal papilla, were observed in the kidneys of females given 150 mg/kg.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 6 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Changes in clinical chemistry, liver and kidney weights, histopathological examination.
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Changes in liver and kidney weights and histopathological examination.
- Critical effects observed:
- not specified
- Conclusions:
- NOELs for repeat dose toxicity are considered to be 6 mg/kg/day in males and 30 mg/kg/day in females.
- Executive summary:
The substance 6-tert-Butyl-2,4-xylenol was studied in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 6, 30 and 150 mg/kg/day. With regard to repeat dose toxicity, two female rats given 150 mg/kg died at the end of the gestation period (one of them during delivery). Body weight gain of females given 150 mg/kg was lower than that of the control during the gestation period. Hematological examination showed decreases of hematocrit, hemoglobin and red blood cells, and increases of reticulocytes and a slight tendency for anemia in male rats given 150 mg/kg. Blood chemical examination revealed decreases in levels of GOT and increases in γ-GTP in males given 30 and 150 mg/kg. Liver and kidney weights showed increases or a tendency for increase in the male rats given 30 mg/kg or more and in the females given 150 mg/kg. As gross findings, enlargement of the liver was observed in males given 30 and 150 mg/kg, and enlargement of the liver and kidneys was observed in females given 150 mg/kg. Histopathological examination revealed swelling of liver cells in the centrilobular zone in males and females of the 150 mg/kg group, and degeneration of liver cells, necrosis of centrilobular hepatocytes and single cell necrosis in the females of the same group. NOELs for repeat dose toxicity are considered to be 6 mg/kg/day in males and 30 mg/kg/day in females of the group.
- Endpoint:
- sub-chronic toxicity: oral
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- a sub-chronic toxicity study (90 days) does not need to be conducted because a reliable short-term toxicity study (28 days) is available showing severe toxicity effects according to the relevant criteria for classifying the substance, for which the observed NOAEL-28 days, with the application of an appropriate uncertainty factor, allows the extrapolation towards the NOAEL-90 days for the same route of exposure
- Justification for type of information:
- JUSTIFICATION FOR DATA WAIVING
In accordance with column 2 of REACH Annex IX, a subchronic toxicity study (90-days) does not need to be conducted since a reliable short-term toxicity study is available showing severe toxicity effects according to the criteria for classifying the substance, for which the observed NOAEL, with the application of an appropriate uncertainty factor, allows the extrapolation towards the NOAEL-90 days for the same route of exposure. - Critical effects observed:
- not specified
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 6 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Klimisch 1. This study was carried out in accordance with internationally valid GLP principles.
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
Oral: Key study: In a experimental study the NOELs of 6-tert-butyl-2,4-xylenol were found to be 6 mg/kg/day in males and 30 mg/kg/day in females. Based on these results, the read-across approach was applied and the NOAELs of the reaction mass of 2-tert-butyl-4,6- dimethylphenol and 4-tert-butyl-2,5-dimethylphenol are considered to be 6 mg/kg/day in males and 30 mg/kg/day in females.
Oral: Data waiving: In accordance with column 2 of REACH Annex IX, a subchronic toxicity study (90-days) does not need to be conducted since a reliable short-term toxicity study is available showing severe toxicity effects according to the criteria for classifying the substance, for which the observed NOAEL, with the application of an appropriate uncertainty factor, allows the extrapolation
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one study available.
Justification for classification or non-classification
Based on the available data, the substance is classified as STOT Rep. Exp. Category 2.
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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