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EC number: 219-330-3 | CAS number: 2416-94-6
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1993-10-25 to 1993-11-09 (In-life)
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- May 12, 1981
- Qualifier:
- according to guideline
- Guideline:
- other: EC Commission directive 92/69/EEC; July 31, 1992
- GLP compliance:
- yes
Test material
- Reference substance name:
- 2,3,6-trimethylphenol
- EC Number:
- 219-330-3
- EC Name:
- 2,3,6-trimethylphenol
- Cas Number:
- 2416-94-6
- Molecular formula:
- C9H12O
- IUPAC Name:
- 2,3,6-trimethylphenol
- Details on test material:
- - Name of test material (as cited in study report): 2,3,6-trimethylphenol
- Physical state: solid
- Analytical purity: 99.7%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: from continuous production "Sumpf K 304", 1990-11-16
- Expiration date of the lot/batch: no data
- Stability under test conditions: yes, confirmed by analysis
- Storage condition of test material: room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach/Riss, Germany
- Age at study initiation: 35 days (arrival); 42 days (start of dosing)
- Weight at study initiation: males: 204 (191-223)g; females: 155 (142-164) g
- Fasting period before study: no data
- Housing: individually in mesh wire cages
- Diet: ground Kliba maintenance diet rat/mouse/hamster, 343 meal, supplied by Klingentalmühle AG, Kaiseraugst, Switzerland; ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: October 04, 1993 (arrival of the animals) To: November 09, 1993 (necropsy)
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- acetone
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): standard diet
- Storage temperature of food: no data
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: no data
- Purity: no data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in the diet was determined analytically before the start of the study.
The homogeneous distribution of the test substance in the diet was proven at the start of the administration period in samples of the high and low concentration. These homogeneity analyses served also as concentration controls. Additionally, concentrational control analyses were performed in samples of the mid concentration at the beginning of the administration period. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- continuously in the diet
Doses / concentrations
- Remarks:
- Doses / Concentrations:
ca. 55, 273, 1346 mg/kg bw/d (600, 3000, 15000 ppm in the diet)
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 rats/sex/group
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale:
In a palatability study, the test substance was administered to groups of 3 male and 3 female Wistar rats at dietary concentrations of 0; 5000 and 15000 ppm for 2 weeks. Following substance-related findings were obtained:
- slight impairment of food consumption at both concentrations
- slight impaired of body weight at both concentrations: the values on day 14 were about 6%/7% (males/females) below control at the high concentration and about 5%/6% below control at the low concentration.
Therefore, the following concentrations were chosen for the present study:
15000 ppm: as highest concentration, corresponding to a test substance intake of at least 1000 mg/kg body weight
3000 ppm: as intermediate concentration
600 ppm: as expected "no observed adverse effect level "
- Rationale for animal assignment: randomly; identification by ear tattoo number
- Post-exposure recovery period: none - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): weekly
Food consumption was determined weekly over a period of 7 days and calculated as mean food consumption in grams per animal and day .
- 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
FOOD EFFICIENCY: No
WATER CONSUMPTION: determined weekly
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: no data
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: 5/sex/group
- Parameters examined:
leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, differential blood count, prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: no data
- Animals fasted: No
- How many animals: 5/sex/group
- Parameters examined:
alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-gamma-glutamyltransferase, sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium
URINALYSIS: Yes
- Time schedule for collection of urine: no data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined:
volume, color, turbidity, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, specific gravity, sediment
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The data were evaluated statistically on the computer systems of the Department of Toxicology of BASF Aktiengesellschaft
Means and standard deviations were calculated for variables.
Methods used (depending on the variable): KRUSKAL-WALLIS test, MANN-WHITNEY U-test.
Significance labels: p<0.05, p> 0.02, p<0.01, p<0.002; depending on method and variable.
Remark: Due to the limited maximum size of this field, no more details on statistics are given herein.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
no substance-related changes
BODY WEIGHT AND WEIGHT GAIN
substance-related changes in high-dose males and females; see below
FOOD CONSUMPTION
substance-related changes in high-dose males and females; see below
WATER CONSUMPTION
no substance-related changes
HAEMATOLOGY
substance-related changes in high-dose males and females and in mid dose females; see below
CLINICAL CHEMISTRY
no substance-related changes
URINALYSIS
no substance-related changes
ORGAN WEIGHTS
substance-related changes in high-dose males and females; see below
GROSS PATHOLOGY
no substance-related changes
HISTOPATHOLOGY: NON-NEOPLASTIC
substance-related changes in high-dose males and females; see below
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
no substance-related changes
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 273 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- haematology
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 55 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- haematology
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 1 346 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: highest dose tested
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 273 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: Decrease in hematocrit in females
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
- slightly decreased food consumption in males and females, especially during the first week of the study
- impairment of body weight in males and females; the values on day 28 were about 4% and 12% below controls, respectively
- impairment of body weight change in males and females ; the values on day 28 were about 9% and 41% below controls, respectively
- decrease in red blood cells, hemoglobin and hematocrit in both sexes
- decrease in mean corpuscular hemoglobin concentration in females
- increase in polychromasia and cholesterol in both sexes
- increase in mean corpuscular volume and mean corpuscular hemoglobin in females
- increase of absolute spleen weight in females and of relative spleen weights in males and females
- increase of extramedullary erythropoiesis and hemosiderosis of the spleen in males and females
- slight increase of erythropoiesis in the bone marrow of two males and two females
- decrease in hematocrit in females
- no substance-related changes
According to the authors, the following significant, substance-related findings were obtained in the respective dose groups:
15000 ppm (about 1,346 mg/kg body weight):
3000 ppm (about 273 mg/kg body weight):
600 ppm (about 55 mg/kg body weight) :
Thus, substance-related effects were seen at 15000 ppm in both sexes and at 3000 ppm in females. Target organs were spleen, bone marrow and erythron. The only toxic effects observed were signs of marked anemia at the high dose (> 1000 mg/kg body weight) with subsequent enhancement of hematopoiesis in bone marrow and spleen. Only a marginal sign of this effect was seen at the mid dose in females.
The no observed adverse effect level (NOAEL) under the conditions of this study was 3000 ppm (about 273 mg/kg body weight) in males and 600 ppm (about 55 mg/kg body weight) in females.
Applicant's summary and conclusion
- Executive summary:
The test substance was administered to rats for 4 weeks at concentrations of 600, 3000 and 15000 ppm for 4 weeks. The concentrations used provided dose levels of approximately 55, 273, and 1346 mg/kg bw/d, respectively. Control animals were administered plain diet.
Administration of the test substance at 15000 ppm adversely affected food consumption, body weight, body weight gain, hematological parameters, spleen weight and induced histological changes in the spleen and bone marrow of males and females. The mid dose level affected a single hematological parameter in females only. No adverse effects were seen in the rats administered 600 ppm.
Under the conditions of this study, the NOAEL was 3000 ppm in the diet (ca. 273 mg/kg bw/d) for males and 600 ppm in the diet (ca. 55 mg/kg bw/d) for females.
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