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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 403-140-4 | CAS number: 103694-68-4 MAJANTOL; MAJANTOL R
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1987-11-10
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 1981
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 3-(2,2-dimethyl-3-hydroxypropyl)toluene
- EC Number:
- 403-140-4
- EC Name:
- 3-(2,2-dimethyl-3-hydroxypropyl)toluene
- Cas Number:
- 103694-68-4
- Molecular formula:
- C12H18O
- IUPAC Name:
- 2,2-dimethyl-3-(3-methylphenyl)propan-1-ol
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ca. 4 weeks
- Fasting period before study: not specified
- Housing: 5 per sex per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 + /-2 °C
- Humidity: at least 40 %
- Air changes: ca. 10 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was added to the stock diet to provide the concentrations wanted. The intended concentrations of the test substance in the diets were 0 (control), 800, 3000 or 10000 ppm. The diet with the highest concentration was prepared first by adding the appropriate amount of the test substance (liquidized at ambient temperature) to the stock diet. The diets with the lower concentrations were obtained by diluting the top-dose diet with stock diet. Homogeneity of the diets was achieved by mixing for 2 minutes in a mechanical blender (Stephan cutter). One batch of 6 kg of each of the diets was prepared on the starting day of the study. The diets were stored at -20°C until use. Twice a week the diets in the feeders were refreshed with portions of the test- or control diets (thawed immediately before use). Immediately after preparation of the diets, samples were taken and subsequently stored at -20°C.
DIET PREPARATION
- Rate of preparation of diet (frequency): once
- Storage temperature of food: -20 °C
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Immediately after preparation of the batch of diets, Samples were taken and subsequently stored at -20°C. The content of test item in each diet was determined in triplicate. The stability of the test item in the test diets was established by reanalyzing samples after storage for 2, 4 and 7 days in an open Container at room temperature. For the low-dose diet a liniar regression line was calculated. From this line, the mean actual daily concentrations during the 3 and 4 day feeding periods in a week, were calculated as well as the overall actual dietary concentration in the low-dose group. The analyses were carried out by TNO, Institute CIVO-Analysis according to an HPLC method provided by the sponsor (HPLC column: stainless steel, 120 x 4.6 mm i.d., packed with 5 um Hypersil ODS).
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily, 7 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Remarks:
- control group
- Dose / conc.:
- 800 ppm
- Dose / conc.:
- 3 000 ppm
- Dose / conc.:
- 10 000 ppm
- No. of animals per sex per dose:
- Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 86.4 mg/kg bw/day
Male: 5 animals at 317.5 mg/kg bw/day
Male: 5 animals at 1102 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 82.5 mg/kg bw/day
Female: 5 animals at 310 mg/kg bw/day
Female: 5 animals at 1074.25 mg/kg bw/day - Control animals:
- yes, plain diet
- Details on study design:
- - Rationale for animal assignment: random
- Fasting period before blood sampling for clinical biochemistry: not specified
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: initially and ond day 7, 14, 21, 28
FOOD CONSUMPTION AND FOOD EFFICIENCY:
Food intake was measured per cage (5 animals) weekly, and the efficiency of food utilization was calculated and expressed as gram weight gain per gram food consumed.
WATER CONSUMPTION AND COMPOUND INTAKE: Yes
Water intake was measured on a cage basis (5 animals) daily, during the first and the third week of the study.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 23
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: all
- Parameters checked: haemoglobin; packed cell volume; red blood cells; white blood cells; differential white blood cell count; thrombocytes; mean corpuscular volume (MCV); mean corpuscular haemoglobin (MCH); mean corpuscular haemoglobin concentration (MCHC)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 25 (glucose), day 28 (other parameters indicated below)
- Animals fasted: yes
- How many animals: all
- Parameters checked: glucose (day 25); alkaline phosphatase (ALP); glutamic-axalacetic transaminase (GOT)/ aspartate amino transferase (ASAT); glutamic-pyruvic transaminase (GPT)/alanine amino transferase (ALAT); gamma glutamyl transpeptidase; total protein; albumin; urea; ceatinine; bilirubin total; sodium (Na); potassium (K); Calcium (Ca); Chloride (Cl); inorganic phosphate
URINALYSIS: Yes
- Time schedule for collection of urine: day 25
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked: volume; density
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
adrenals; spleen; heart; testes; kidneys; thymus; liver; thyroid (with parathyroids); mesenteric lymph nodes; urinary bladder; ovaries; gross lesions
HISTOPATHOLOGY: Yes
Tissue samples required for microscopic examination were processed and embedded in paraffin wax. Sections were cut at 5 µm, stained with haematoxylin and eosin and then examined macroscopically. Histopathological examination was carried out on the liver, kidneys, heart,
adrenals, spleen and mesenteric lymph node of all animals of the control group and of the top-dose group, and on organs showing gross alterations at autopsy. - Statistics:
- Data on body weights were evaluated by one-way analysis of co-variance followed by Dunnett's multiple comparison test. Data an red blood cell variables, clinical chemistry values, volume and density of the urine, and organ weights were evaluated by one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. Differential white blood cell counts were analyzed by the Mann Whitney U-test.,The histopathological changes were examined by Fisher's exact probability test.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no noticeable differences in appearance or behaviour between the treated rats and the controls.
- Mortality:
- no mortality observed
- Description (incidence):
- None of the rats died in the course of the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights were relatively low in males of the mid- and top-dose group and in females of all treatment groups. The differences with the controls did, however, not reach the level of statistical significance.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food intake was relatively low in males of the mid- and top-dose group and in females of all treatment groups.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Food conversion efficiency was generally slightly decreased in the top-dose group in both sexes.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- There were no outstanding differences in water intake among the various groups, but in the top-dose group the figures were generally higher than in the other groups.
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight, though statistically significant decrease in MCV and MCH was observed in males of the top-dose group. Total white blood cell count was decreased in males of the top-dose group, and in females of the mid-dose group. The latter change was considered to be incidental. The differential white blood cell count did not reveal significant changes in the distribution of the individual cells.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Plasma sodium concentration showed a dose-related increase in females of the mid- and top-dose group. There were no other statistically significant changes in clinical chemistry parameters, except for an incidental decrease in glucose concentration in males of the low-dose group.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- The urine concentration test did not indicate treatment-related changes in renal function.
- 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):
- The relative weight of the liver was statistically significantly increased in males of the mid- and top-dose group and in females of the top-dose group. The relative weight of the kidneys was statistically significantly increased in females of the mid- and top-dose group. There were
no statistically significant changes in absolute organ weights. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Gross examination at autopsy did not reveal any treatment related changes, either in males or in females.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Upon microscopic examination, special attention was paid to the liver and kidneys, in view of their increased relative weight. However, neither in these organs nor in any of the other organs examined, histopathological changes were observed that could be related to treatment. Most changes observed are common findings in the strain of rats used. Moreover, the lesions were about equally distributed between the top-dose rats and the controls, or they occurred in a single animal only.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- haematology
- organ weights and organ / body weight ratios
- other: corresponding to 317.5 mg/kg bw (m) and 310 mg/kg bw/d (f)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 800 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: corresponding to 86.4 mg/kg bw (m) and 82.5 mg/kg bw/d (f)
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, the 28 d NOAEL in male and female rats was determined to be 317.5 or 310 mg/kg bw/d, respectively, based on body weight and food consumption decrease as well as liver and kidney organ weight changes and haematological changes.
- Executive summary:
The toxicity of the test item was examined in a sub-acute oral toxicity study with four groups of 5 male and 5 female Wistar rats, which received the test substance in the diet for a period of 4 weeks. The intended dietary levels of the test item were 0 (control), 800, 3000 or 10000 ppm, but the actual levels were lower due to disappearance of the test substance from the diet. General condition and behaviour were not adversely affected by the administration of the test item. None of the rats died in the course of the study. There were no statistically significant differences in body weights among the various groups, although body weights and food intake were relatively low in males of the mid- and top-dose group and in females of all dose groups. In males of the top-dose group decreases were observed in total white blood cell counts and in MCV and MCH. Plasma sodium concentration was increased in females of the mid- and top-dose group. There were no treatment-related changes in volume and density of the urine among the various groups. The relative weight of the liver was increased in males of the mid- and top-dose group and in females of the top-dose group. The relative weight of the kidneys was increased in females of the mid- and top-dose group. Gross examination at autopsy and histopathological examination did not reveal any treatment-related changes. From the present study it was concluded that certainly the low-dose level was a clear no-effect level. However, as the changes observed at the mid-dose level were not considered to be of obvious toxicological significance, even the mid-dose level was not a clear effect level. The NOAEL was thus considered to be 3000 ppm, corresponding to 317.5 or 310 mg/kg bw/d in males or females, respectively.
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.