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EC number: 204-442-7 | CAS number: 121-00-6
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-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 journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Repeated dose oral toxicity study of the test chemical
- Author:
- Liang et al
- Year:
- 2 014
- Bibliographic source:
- The Journal of Toxicological Sciences
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-tert-butyl-4-methoxyphenol
- EC Number:
- 204-442-7
- EC Name:
- 2-tert-butyl-4-methoxyphenol
- Cas Number:
- 121-00-6
- Molecular formula:
- C11H16O2
- IUPAC Name:
- 2-tert-butyl-4-methoxyphenol
- Test material form:
- solid: bulk
- Details on test material:
- - Name of test material: tert-butyl-4-methoxyphenol
- Common name: Phenol, (1,1-dimethylethyl)-4-methoxy-
- Molecular formula: C11H16O2
- Molecular weight: 180.2454 g/mol
- Smiles notation: COc1ccc(O)c(c1)C(C)(C)C
- InChI=1S/C11H16O2/c1-11(2,3)9-7-8(13-4)5-6-10(9)12/h5-7,12H,1-4H3
- Substance type: Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- Source: Chongqing Medical University Lab Animal Center (Chongqing, China)
- Age at study initiation: 8 weeks
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were evenly distributed into 16 cages in controlled environment and marked with a number on their ears using non-toxic ink. All care and experimental procedures for the rats were conducted in accordance with guidelines published in the Guide for the Care and Use of Laboratory Animals of Chongqing Medical University.
- Diet (e.g. ad libitum): Standard laboratory rodent food, ad libitum (?)
- Water (e.g. ad libitum): Tap water, ad libitum (?)
- Acclimatization period: One week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C (± 2°C)
- Humidity (%): 50% (± 20%)
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- peanut oil
- Details on oral exposure:
- Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: BHA is poorly water soluble and to make it soluble, BHA was mixed with peanut oil to provide consistent absorption and was then subjected to sonication for 30 min at 40°C. This was performed on a weekly basis. The daily reagent dosage (50 mg/kg/day) was determined individually for each rat based on body weight.
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Peanut oil (20 mg/mL)
- Concentration in vehicle: BHA: 50 mg/kg/day, and B(a)P-BHA combination group: B(a)P 2 mg/kg/day + BHA 50 mg/kg/day.
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50 BHA or 2 B(a)P +50 BHA mg/kg/day
Basis:
no data
- No. of animals per sex per dose:
- Total: 72
0 mg/kg/day : 24 male
50 mg/kg/day : 24 male
2 (B(a)P) + 50 (BHA) mg/kg/day: 24 male - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations: No data available
DETAILED CLINICAL OBSERVATIONS: Yes, swimming ability of each rat was observed.
- Time schedule: Prior to the Morris Water Maze (MWM) test.
BODY WEIGHT: Yes
- Time schedule for examinations: No data available
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: Yes, visual ability was observed.
- Time schedule for examinations: Prior to the MWM test.
- Dose groups that were examined: All dose groups were examined.
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked: No data available
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked: No data available
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Prior to the MWM test.
- Dose groups that were examined: All 72 dose groups animals were examined.
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Yes, motor activity was tested.
OTHER: No data available - Sacrifice and pathology:
- GROSS PATHOLOGY: No data available
HISTOPATHOLOGY: No data available - Other examinations:
- Following the WMW test, malonaldehyde (MDA) content and superoxide dismutase (SOD) activity were measured to determine the oxidative damage induced by B(a)P and the protective effect of BHA.
The activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase was also measured after the MWM to determine the energy metabolism damage induced by B(a)P and the protective effect of BHA.
In addition, following the WMW test, the Ca2+-content was measured to detect the damage in the hippocampus induced by B(a)P and the protective effect of BHA. - Statistics:
- All data analyses were performed with SPSS v.20.0 (SPSS, Inc., Chicago, IL, USA) and the quantitative data were expressed as mean ± S.D. The data were analyzed using analysis of variance (ANOVA). Data obtained over training days from the hidden platform trial were analyzed by ANOVA for repeated measurement. The remaining data were analyzed by one-way ANOVA. When appropriate, post hoc comparisons were assessed using the Least
Significant Difference (LSD). A probability of P < 0.05 was considered significant for all analyses.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No change were observed in visual ability of treated rats as compare to control.
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No change were observed in motor activity of treated rats as compare to control.
- 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:
- not specified
- Details on results:
- BHA was chosen to prevent the neurotoxicity on oxidative stress caused by B(a)P.
In the B(a)P-BHA-combination group, the rats had a better performance significantly in MWM compared to the rats in the B(a)P group. This demonstrates that in behavior tests BHA has protective action against the harmful effect of B(a)P.
The MDA level of rats in B(a)P-BHA-combination group is lower, and SOD activity is higher than in the B(a)P-group. This is a further sign of the positive effect against B(a)P damage.
The activity of ATPase has a significant improvement, which indicates that BHA also plays a positive role in energy metabolism.
There is no significant difference of Ca2+ content between the B(a)P group and the B(a)P-BHA-combination group.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Effect on motor activity, and levels of MDA and SOD, ATPase activity and Ca2+ concentration in rat brain.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) was considered to be 50 mg/kg body weight/ day in male Sprague-Dawley rat when exposed to the test chemical.
- Executive summary:
In a 90 days repeat dose toxicity study, male Sprague-Dawley rats were exposed to the test chemical by oral gavage in the concentrations of 0 or 50 mg/kg/day. The results showed only effect in Morris Water Maze (Hidden platform MWM and Probe trial), MDA content and SOD activity when exposed to 50 mg/kg/day the test chemical alone. In combination with 2 mg/kg/day B(a)P, the results showed an improved performance in MWM compared to the rats in the B(a)P group, demonstrating that the test chemical has a protective action against the harmful effect of B(a)P. The MDA level of rats in B(a)P-test chemical-was lower, and SOD activity was higher than in the B(a)P-group, thus also showing positive effect against B(a)P damage. The activity of ATPase improved significantly in B(a)P-test chemical-treated rats, which indicates that the test chemical plays a positive role in energy metabolism. Therefore, no observed adverse effect level (NOAEL) was considered to be 50 mg/kg body weight/ day in male Sprague-Dawley rat when exposed to the test chemical by oral gavage on a daily basis for 90 days.
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