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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 211-806-9 | CAS number: 697-82-5
- 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
Repeated dose toxicity: Oral
Combined repeated dose repro-devp. Screen was performed for 2,3,5 Trimethylphenol to determine its repeated oral toxic nature upon repeated exposure to 12 male and 12 female Crl: CD (SD) rats. The test chemical in olive oil was dosed at dose levels of 0, 100, 300, 1000 mg/kg/day for 42 days in males and 42 -46 days (from 14 days before mating to day 4 of lactation) for females. A recovery group was also included in the study at a dose level of 0 or 1000 mg/Kg/day consisting of 5 males and 5 females. The animals were observed for clinical signs, mortality, body weight and food consumption, urinanalysis, hematology, blood chemistry, organ weights and histopathology parameters.
Soiled perigenitalia with urine was noted in male and female animals at 300 and 1000 mg/kg/day, transient lethargy and ataxic gait after dosing was noted in 1000 mg/Kg/day dosed males and 300 and 1000 mg/Kg/day dosed female animals. One female animal each (n: 12) at 300 and 1000 mg/kg/day was found dead during the study. A decrease in body weight gain was observed at 300 mg/kg/day (test group) and 1000 mg/kg/day (test and recovery group) in male animals and at 1000 mg/kg/day in female animals. Food consumption was decreased in 300 and 1000 mg/kg/day test groups and increased in 1000 mg/kg/day recovery group in male rats and a decrease in food consumption was noted in 1000 mg/kg/day test group and an increase was noted in 1000 mg/kg/day recovery group in female rats.
Male rats showed an increase in the RET at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day, increase in the MCV at 1000mg/kg/day, increase in the MCV at Recovery at 1000 mg/kg/day and decrease in the MCHC at recovery at 1000 mg/kg/day while female rats showed a decrease in the RBC at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, decrease in the Hgb at 1000 mg/kg/day and Recovery at 1000 mg/kg/day concentration, decrease in the MCHC at 1000 mg/kg/day and an increase in the MCV, MCH and RET at 1000 mg/kg/day. An increase in the TCho, PL and ALT at 1000 mg/kg/d and a decrease in K at 1000 mg/kg/ day dose level was noted in male animals and an increase in the TP at 300 and 1000 mg/kg/day, increase in the Alb at 300 and 1000 mg/kg/day, increase in the TCho,PL and ALP at 1000 mg/kg/day, increase in the AST at Recovery 1000 mg/kg/day, increase in the ALT at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and an increase in the TBil at 1000 mg/kg/day dose level was noted in female animals.
Male rats showed an increase in the absolute and relative kidney weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 300 and 1000 mg/kg/day, increase in the absolute and relative liver weight at 1000 mg/kg/day, increase in the absolute and relative adrenal weight at 1000 mg/kg/day concentration and Recovery at 1000 mg/kg/day, increase in the relative weight of testis at 1000 mg/kg/day, increase in the relative brain weight at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and a decrease in the absolute epididymides weight at 1000 mg/kg/day and at Recovery 1000 mg/kg/day dose levels. Female rats showed an increase in the absolute and relative kidney weight at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day (tendency), increase in the relative weight of liver at 300 and 1000 mg/kg/day, increase in the relative brain weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 1000 mg/kg/day and an increase in the relative heart weight at 1000 mg/kg/day.
Centrilobular hypertrophy of hepatocytes in the liver in 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoietic in the spleen (Recovery 1000 mg/kg/day), vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis (1000mg/kg/day and Recovery 1000 mg/kg/day), inflammatory infiltration in the mucosa and the lamina propria of small and large intestines at 1000 mg/kg/day was noted in male rats and an increase in the extramedullary hematopoiesis in the liver at 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoiesis in the spleen at 1000 mg/kg/day, inflammation in forestomach at 1000 mg/kg/day, squamous cell hyperplasia in forestomach at 300 and 1000 mg/kg/day and atrophy of the thymus at 300 and 1000 mg/kg/day was observed in female rats.
Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for 2,3,5 Trimethylphenol upon repeated oral exposure in male and female Crl:CD (SD) rats is 100 mg/Kg/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Combined repeated dose repro-devp. Screen
- 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 J check
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Combined repeated dose repro-devp. Screen was performed for 2,3,5 Trimethylphenol to determine its repeated oral toxic nature upon repeated exposure to Crl:CD (SD) rats
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: 2,3,5 Trimethylphenol
- Molecular formula: C9H12O
- Molecular weight: 136.19 g/mol
- Substance type: Organic
- Physical state: White light yellow powder
- Purity: 99.8%
- Impurities (identity and concentrations): No data available - Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: 10 weeks old
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Details on route of administration:
- No data
- Vehicle:
- olive oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: 2,3,5 Trimethylphenol was dissolved in olive oil to give a dose level of 0, 100, 300 or 1000 mg/Kg/day for the test group and 0 or 1000 mg/Kg/day for recovery group
DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data
VEHICLE
- Justification for use and choice of vehicle (if other than water): Olive oil
- Concentration in vehicle: Test group: 0, 100, 300 or 1000 mg/Kg/day and Recovery group: 0 or 1000 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- Male: 42 days
Female: 42-46 days (from 14 days before mating to day 4 of lactation) - Frequency of treatment:
- Daily
- Remarks:
- Test group- 0, 100, 300 or 1000 mg/kg/day
Recovery group- 0 or 1000 mg/kg/day - No. of animals per sex per dose:
- Total: 116
Test group:
0 mg/Kg/day: 12 males and 12 females
100 mg/Kg/day: 12 males and 12 females
300 mg/Kg/day: 12 males and 12 females
1000 mg/Kg/day: 12 males and 12 females
Recovery group:
0 mg/Kg/day: 5 males and 5 females
1000 mg/Kg/day: 5 males and 5 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: No data
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data - Positive control:
- No data
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: No data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- 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: No data available
FOOD EFFICIENCY:
- 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: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data available
- Anesthetic 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. RBCm hematocrit, hemoglobin, RET, MCV, MCHC and MCH, platelet, PT. APTT, WBC, Differential WBCs like neutrophil, lymphocytes, monocytes, eosinophil, basophil and others
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. T-Cho, PL, ALT, ALP, K, TP, Alb, AST and T-Bil, A/G ratio, T-Bil, glucose, Triglyceride, phospholipid, LDH, GTP, CK, BUN, creatinine, NA, Cl, Ca, IP
URINALYSIS: Yes
- 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 in table [No.?] were examined. Protien content, ketone body, ph, urobilinogen, glucose, bilirubin, occlut blood
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER: No data available - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Gross necropsy was performed and absolute and relative kidney, spleen, liver, adrenal, testes, brain, epididymides weight was measured
HISTOPATHOLOGY: Yes, histopathology was performed for kidney, spleen, liver, adrenal, testes, brain, epididymides, mucosa, small and large intestine - Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- 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
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality:
Clinical signs:
Males: At 300 and 1000 mg/kg/day soiled perigenitalia with urine was observed and transient lethargy and ataxic gait after dosing was noted at 1000 mg/Kg/day
Females: At 300 and 1000 mg/kg/day concentrations soiled perigenitalia with urine and transient lethargy and ataxic gait after dosing was observed
Mortality:
Males: No data
Female: One female animal each (n: 12) at 300 and 1000 mg/kg/day was found dead during the study
Body weight and weight gain:
Males: At 300 mg/kg/day (test group) and 1000 mg/kg/day (test and recovery group) decrease in the body weight gain was observed
Females: At 1000 mg/kg/day ( test and recovery group), a decrease in the body weight gain was observed.
Food consumption and compound intake:
Males: Food consumption was decreased in 300 and 1000 mg/kg/day test groups and increased in 1000 mg/kg/day recovery group
Females: A decrease in food consumption was noted in 1000 mg/kg/day test group and an increase was noted in 1000 mg/kg/day recovery group
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology:
Males: An increase in the RET at 300, 1000 mg/kg/day and in recovery group at 1000 mg/kg/day, increase in the MCV at 1000mg/kg/day, increase in the MCV at recovery in 1000 mg/kg/day and a decrease in the MCHC at recovery in 1000 mg/kg/day was noted
Females: A decrease in the RBC at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, decrease in the Hgb at 1000 mg/kg/day and at recovery in 1000 mg/kg/day concentration, decrease in the MCHC at 1000 mg/kg/day and an increase in the MCV, MCH and RET at 1000 mg/kg/day was noted
Clinical chemistry:
Males: An increase in the TCho, PL and ALT at 1000 mg/kg/d and a decrease in K at 1000 mg/kg/ day dose level was noted
Female: An increase in the TP at 300 and 1000 mg/kg/day, increase in the Alb at 300 and 1000 mg/kg/day, increase in the TCho,PL and ALP at 1000 mg/kg/day, increase in the AST at recovery in 1000 mg/kg/day, increase in the ALT at 1000 mg/kg/day and at recovery in 1000 mg/kg/day and an increase in the TBil at 1000 mg/kg/day dose level was noted
Urinanalysis:
Male: A decrease in the protein at 300 mg/kg/day, decrease in the protein at 1000 mg/kg/day, decrease in the ketone body at 300, 1000 mg/kg/day and in recovery group at 1000 mg/kg/day was observed
Females: No data
Neurobehaviour: No effects were noted in the functional battery examination performed
Organ weights:
Male: An increase in the kidney weight (Absolute and relative) at 300 and 1000 mg/kg/day, increase in the spleen weight (Absolute and relative) at 300 and 1000 mg/kg/day( tendency), increase in the liver weight (Absolute and relative) at 1000 mg/kg/day (tendency), increase in the adrenal weight (Absolute and relative) at 1000 mg/kg/day concentration and at Recovery in 1000 mg/kg/day, increase in the testis weight (Relative) at 1000 mg/kg/day, increase in the brain weight (Relative) at 1000 mg/kg/day and at recovery in 1000 mg/kg/day, decrease in the epididymides weight (Absolute) at 1000 mg/kg/day and at recovery 1000 mg/kg/day dose levels was noted
Female: An increase in the kidney weight (Absolute and relative) at 300, 1000 mg/kg/day and at recovery in 1000 mg/kg/day (tendency), increase in the liver weight (Relative) at 300 and 1000 mg/kg/day, increase in the brain weight (Relative) at 300 and 1000 mg/kg/day, increase in the spleen weight (Absolute and Relative) at 1000 mg/kg/day and an increase in the heart weight (Relative) at 1000 mg/kg/day was observed.
Gross pathology: No data available
Histopathology:
Male: Centrilobular hypertrophy of hepatocytes in the liver in 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and at recovery in 1000 mg/kg/day, increase in the extramedullary hematopoietic in the spleen (Recovery 1000 mg/kg/day), vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis (1000mg/kg/day and Recovery 1000 mg/kg/day), inflammatory infiltration in the mucosa and the lamina propria of small and large intestines at 1000 mg/kg/day was noted.
Female: An increase in the extramedullary hematopoiesis in the liver at 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoiesis in the spleen at 1000 mg/kg/day, inflammation in forestomach at 1000 mg/kg/day, squamous cell hyperplasia in forestomach at 300 and 1000 mg/kg/day and atrophy of the thymus at 300 and 1000 mg/kg/day was observed - Dose descriptor:
- NOAEL
- Effect level:
- 100 other: mg/Kg/day (actual dose)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effects were observed for clinical signs, mortality, body weight and food consumption, urinanalysis, hematology, blood chemistry, organ weights and histopathology at 100 mg/Kg/day
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for 2,3,5 Trimethylphenol upon repeated oral exposure in male and female Crl:CD (SD) rats is 100 mg/Kg/day.
- Executive summary:
Combined repeated dose repro-devp. Screen was performed for 2,3,5 Trimethylphenol to determine its repeated oral toxic nature upon repeated exposure to 12 male and 12 female Crl: CD (SD) rats. The test chemical in olive oil was dosed at dose levels of 0, 100, 300, 1000 mg/kg/day for 42 days in males and 42 -46 days (from 14 days before mating to day 4 of lactation) for females. A recovery group was also included in the study at a dose level of 0 or 1000 mg/Kg/day consisting of 5 males and 5 females. The animals were observed for clinical signs, mortality, body weight and food consumption, urinanalysis, hematology, blood chemistry, organ weights and histopathology parameters.
Soiled perigenitalia with urine was noted in male and female animals at 300 and 1000 mg/kg/day, transient lethargy and ataxic gait after dosing was noted in 1000 mg/Kg/day dosed males and 300 and 1000 mg/Kg/day dosed female animals. One female animal each (n: 12) at 300 and 1000 mg/kg/day was found dead during the study. A decrease in body weight gain was observed at 300 mg/kg/day (test group) and 1000 mg/kg/day (test and recovery group) in male animals and at 1000 mg/kg/day in female animals. Food consumption was decreased in 300 and 1000 mg/kg/day test groups and increased in 1000 mg/kg/day recovery group in male rats and a decrease in food consumption was noted in 1000 mg/kg/day test group and an increase was noted in 1000 mg/kg/day recovery group in female rats.
Male rats showed an increase in the RET at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day, increase in the MCV at 1000mg/kg/day, increase in the MCV at Recovery at 1000 mg/kg/day and decrease in the MCHC at recovery at 1000 mg/kg/day while female rats showed a decrease in the RBC at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, decrease in the Hgb at 1000 mg/kg/day and Recovery at 1000 mg/kg/day concentration, decrease in the MCHC at 1000 mg/kg/day and an increase in the MCV, MCH and RET at 1000 mg/kg/day. An increase in the TCho, PL and ALT at 1000 mg/kg/d and a decrease in K at 1000 mg/kg/ day dose level was noted in male animals and an increase in the TP at 300 and 1000 mg/kg/day, increase in the Alb at 300 and 1000 mg/kg/day, increase in the TCho,PL and ALP at 1000 mg/kg/day, increase in the AST at Recovery 1000 mg/kg/day, increase in the ALT at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and an increase in the TBil at 1000 mg/kg/day dose level was noted in female animals.
Male rats showed an increase in the absolute and relative kidney weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 300 and 1000 mg/kg/day, increase in the absolute and relative liver weight at 1000 mg/kg/day, increase in the absolute and relative adrenal weight at 1000 mg/kg/day concentration and Recovery at 1000 mg/kg/day, increase in the relative weight of testis at 1000 mg/kg/day, increase in the relative brain weight at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and a decrease in the absolute epididymides weight at 1000 mg/kg/day and at Recovery 1000 mg/kg/day dose levels. Female rats showed an increase in the absolute and relative kidney weight at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day (tendency), increase in the relative weight of liver at 300 and 1000 mg/kg/day, increase in the relative brain weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 1000 mg/kg/day and an increase in the relative heart weight at 1000 mg/kg/day.
Centrilobular hypertrophy of hepatocytes in the liver in 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoietic in the spleen (Recovery 1000 mg/kg/day), vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis (1000mg/kg/day and Recovery 1000 mg/kg/day), inflammatory infiltration in the mucosa and the lamina propria of small and large intestines at 1000 mg/kg/day was noted in male rats and an increase in the extramedullary hematopoiesis in the liver at 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoiesis in the spleen at 1000 mg/kg/day, inflammation in forestomach at 1000 mg/kg/day, squamous cell hyperplasia in forestomach at 300 and 1000 mg/kg/day and atrophy of the thymus at 300 and 1000 mg/kg/day was observed in female rats.
Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for 2,3,5 Trimethylphenol upon repeated oral exposure in male and female Crl:CD (SD) rats is 100 mg/Kg/day.
Reference
Table 1: Urinalysis of male rats treated orally with 2,3,5-trimethylphenol
|
|
Administration period |
Recovery period |
||||
Dose (mg/Kg) |
|
0 |
100 |
300 |
1000 |
0 |
1000 |
No. of animals examined |
|
12 |
12 |
12 |
11 |
5 |
5 |
pH |
6.0 |
0 |
0 |
0 |
1 |
0 |
0 |
|
8.0 |
3 |
3 |
2 |
3 |
3 |
0* |
|
8.5 |
9 |
9 |
10 |
7 |
2 |
5* |
Protein |
- |
0 |
0 |
0 |
0 |
0 |
0 |
|
± |
0 |
0 |
0 |
0 |
1 |
0 |
|
+ |
4 |
0* |
8 |
9* |
0 |
2 |
|
2+ |
8 |
12* |
4 |
2* |
4 |
3 |
Glucose |
- |
12 |
12 |
12 |
11 |
5 |
5 |
Ketone body |
- |
3 |
1 |
6 |
8 |
1 |
3 |
|
± |
8 |
11 |
6 |
3 |
0 |
2 |
|
+ |
1 |
0 |
0 |
0 |
3 |
0 |
|
2+ |
0 |
0 |
0 |
0 |
1 |
0 |
Bilirubin |
- |
12 |
12 |
12 |
11 |
5 |
5 |
Occult blood |
- |
11 |
12 |
12 |
11 |
5 |
5 |
|
2+ |
1 |
0 |
0 |
0 |
0 |
0 |
Urobilinogen |
± |
12 |
12 |
12 |
11 |
5 |
5 |
Grade; -: negative, ±: trace, +: slight, 2+: moderate, 3+: marked.
Data represent the number of animals.
Significant difference from the control group, * p≦0.05.
Table 2: Hematology of rats treated orally with 2,3,5-trimethylphenol
|
Administration period |
Recovery period |
||||
|
0 |
100 |
300 |
1000 |
0 |
1000 |
Males |
|
|||||
No. of animals examined |
7 |
12 |
12 |
6 |
5 |
5 |
MCV (fL) |
49.2±1.6 |
48.3±1.5 |
50.0±1.1 |
51.3±2.1* |
48.6±1.1 |
50.6±2.3 |
MCHC (g/dL) |
38.8±0.3 |
38.9±0.8 |
38.4±0.8 |
38.1±0.7 |
37.8±0.2 |
37.1±0.5* |
Reticulocyte (%) |
1.6±0.3 |
1.7±0.3 |
2.3±0.2** |
2.4±0.4** |
1.8±0.4 |
2.1±0.4 |
Females (dam) |
|
|||||
RBC (×106/μL) |
6.57±0.43 |
6.27±0.77 |
6.33±0.65 |
5.50±0.74** |
7.98±0.22 |
7.52±0.31* |
Hemoglobin (g/dL) |
13.3±0.8 |
13.1±1.1 |
13.1±0.8 |
11.9±1.4 ** |
15.6±0.3
|
15.0±0.3 * |
MCV (fL) |
53.1±1.8 |
54.6±3.8 |
55.3±3.7 |
59.9±4.5 ** |
50.8±1.6
|
52.4±1.5 |
MCH (pg) |
20.2±0.7 |
21.0±1.2 |
20.8±1.2 |
21.6±0.8 ** |
19.6±0.6 |
19.9±0.6 |
MCHC (g/dL) |
38.2±.4 |
38.5±0.9 |
37.7±1.1 |
36.2±2.1 * |
38.5±0.4 |
38.1±0.8 |
Reticulocyte (%) |
5.9±1.7 |
7.0±3.7 |
6.7±3.3 |
11.3±5.0 * |
1.6±0.5 |
1.7±0.5 |
Monocyte |
2.7±1.0 |
3.5±1.5 |
4.5±2.0 * |
3.7±1.1 |
2.5±0.7 |
3.0±0.7 |
Data represent mean ± S.D.
Significant difference from the control group, * p≦0.05, ** p≦0.01.
Table 3 Biochemistry of rats treated orally with 2,3,5-trimethylphenol
|
Administration period |
Recovery period |
||||
|
0 |
100 |
300 |
1000 |
0 |
1000 |
Males |
|
|||||
No. of animals examined |
7 |
12 |
12 |
6 |
5 |
5 |
A/G ratio |
1.2±0.1 |
1.2±0.1 |
1.3±0.1 |
1.3±0.1 |
1.0±0.1 |
1.3±0.2* |
Total cholesterol (mg/dL) |
63±12 |
64±12 |
61±10 |
86±14 ** |
73±11 |
58±11 |
Phospholipid (mg/dL) |
110±20 |
110±15 |
105±15 |
155±30 ** |
113±9 |
97±17 |
ALT (IU/L) |
28±4 |
24±4 |
59±19 ** |
32±5 |
29±7 |
39±26 |
K (mEq/L) |
4.2±0.3 |
4.2±0.4 |
4.2±0.3 |
3.7±0.2 * |
3.7±0.3 |
3.8±0.3 |
IP (mg/dL) |
6.8±0.4 |
7.2±1.0 |
7.5±1.0 |
6.9±0.7 |
6.7±0.3 |
7.9±0.7 ** |
Females (dam) |
|
|||||
Total protein (g/dL) |
6.3±0.3 |
6.4±0.3 |
6.5±0.6 * |
6.6±0.2 * |
7.1±0.2 |
6.9±0.7 |
Albumin (g/dL) |
3.5±0.1 |
3.7±0.2 |
3.8±0.3 ** |
3.7±0.3 * |
4.1±0.4 |
4.0±0.3 |
Total cholesterol (mg/dL) |
70±9 |
70±9 |
74±17 |
87±15 * |
73±13 |
76±17 |
Phospholipid (mg/dL) |
140±16 |
145±16 |
160±34 |
179±30 ** |
135±21 |
137±23 |
AST (IU/L) |
92±23 |
85±14 |
84±17 |
93±26 |
48±6 |
60±7 * |
ALT (IU/L) |
48±11 |
47±7 |
61±20 |
80±20 ** |
17±2 |
23±5 * |
ALP (IU/L) |
256±69 |
267±49 |
348±157 |
394±107 ** |
140±58 |
169±51 |
K (mEq/L) |
3.5±0.5 |
3.4±0.4 |
3.0±0.3** |
3.6±0.3 |
3.3±0.4 |
3.7±0.2 |
Data represent mean ± S.D.
Significant difference from the control group, * p≦0.05, ** p≦0.01.
Table 4: Organ weights of rats treated orally with 2,3,5-trimethylphenol
|
Administration period |
Recovery period |
||||
|
0 |
100 |
300 |
1000 |
0 |
1000 |
Males |
|
|||||
No. of animals examined |
7 |
12 |
12 |
6 |
5 |
5 |
Body weight (g) |
497±28 |
496±30 |
476±26 |
431±36 ** |
537±34
|
466±30 ** |
Adrenals (g) |
0.071± 0.007 |
0.072± 0.009 |
0.073± 0.005 |
0.071± 0.005 |
0.072± 0.007 |
0.084± 0.006 * |
(%) |
0.014± 0.001
|
0.015± 0.002
|
0.015± 0.001
|
0.016± 0.001 *
|
0.014± 0.002
|
0.018± 0.002 ** |
Kidneys (g) |
2.898± 0.257 |
2.955± 0.258 |
3.107± 0.205 |
3.110± 0.151 |
3.113± 0.314 |
3.030± 0.290 |
(%) |
0.583± 0.031 |
0.596 ± 0.053 |
0.653± 0.036 ** |
0.724± 0.035 ** |
0.580± 0.052 |
0.651± 0.061 |
Spleen (g) |
0.707± 0.129 |
0.677± 0.076 |
0.811± 0.118 |
0.777± 0.164 |
0.765± 0.142 |
0.780± 0.099 |
(%) |
0.142± 0.023 |
0.137± 0.017 |
0.171± 0.028 * |
0.179± 0.027 * |
0.142± 0.023 |
0.167± 0.020 |
Liver (g) |
12.899± 1.704 |
13.245± 0.927 |
12.922± 0.756 |
13.378± 1.795 |
13.670± 1.439 |
11.982± 1.293 |
(%)
|
2.589± 0.216 |
2.669± 0.104 |
2.717± 0.152 |
3.099± 0.260 ** |
2.541± 0.165 |
2.564± 0.142 |
Brain (g) |
2.126± 0.084 |
2.131± 0.086 |
2.142± 0.094 |
2.118± 0.057 |
2.091± 0.106 |
2.187± 0.067 |
(%) |
0.429± 0.027 |
0.430± 0.024 |
0.451± 0.030 |
0.495± 0.051 ** |
0.390± 0.013 |
0.470± 0.021 ** |
Testes (g) |
3.296± 0.297 |
3.260± 0.241 |
3.420± 0.268 |
3.251± 0.472 |
3.307± 0.521 |
3.304± 0.243 |
(%)
|
0.664± 0.056 |
0.658± 0.053 |
0.719± 0.056 |
0.758± 0.117 * |
0.615± 0.085 |
0.709± 0.049 |
Epididymides (g) |
1.312± 0.053 |
1.296± 0.105 |
1.326± 0.095 |
1.112± 0.121 ** |
1.347± 0.110 |
1.184± 0.091 * |
Females (dam) |
|
|||||
No. of animals examined |
12 |
12 |
11 |
10 |
5 |
5 |
Body weight (g) |
300±16 |
293±20 |
279±32 |
264±20 ** |
286±10 |
270±14 |
Heart (g) |
0.949± 0.076 |
0.951± 0.097 |
0.961± 0.113 |
0.944± 0.091 |
0.964 ±0.068 |
0.923± 0.137 |
(%) |
0.341± 0.035 |
0.337± 0.020 |
0.359± 0.033 ** |
0.345± 0.034 |
0.325± 0.032 |
0.317± 0.024 |
Kidneys (g) |
1.754± 0.143 |
1.706± 0.160 |
1.820± 0.155 |
1.817± 0.149 |
1.706± 0.091 |
1.806± 0.158 |
(%) |
0.585± 0.038 |
0.583± 0.047 |
0.659± 0.099 ** |
0.690± 0.045 ** |
0.596± 0.038 |
0.669± 0.034 * |
Spleen (g) |
0.628± 0.085 |
0.666 ±0.180 |
0.659± 0.162 |
0.907± 0.221 ** |
0.533± 0.073 |
0.480± 0.069 |
(%) |
0.210± 0.028 |
0.228± 0.064 |
0.236± 0.057 |
0.345± 0.083 ** |
0.186± 0.028 |
0.177± 0.017 |
Liver (g) |
9.325± 0.765 |
9.666± 0.672 |
9.714± 1.333 |
9.609± 1.199 |
6.881± 0.657 |
6.944± 0.811 |
(%) |
3.111± 0.174 |
3.309± 0.265 |
3.475± 0.316 ** |
3.639± 0.310 ** |
2.404± 0.235 |
2.568± 0.181 |
Brain (g) |
1.939± 0.046 |
1.893± 0.084 |
1.970± 0.053 |
1.978± 0.078 |
1.991± 0.071 |
1.992± 0.090 |
(%)
|
0.649± 0.032 |
0.648± 0.043 |
0.714± 0.085 * |
0.755± 0.078 ** |
0.695± 0.03 |
0.740± 0.040 |
Data represent mean ± S.D.
Significant difference from the control group, * p≦0.05, ** p≦0.01
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is from J check
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
Repeated dose toxicity: Oral
Data for repeated dose oral toxicity was reviewed to determine the toxic nature of 2,3,5 Trimethylphenol upon repeated application by oral route. The study is as mentioned below:
Combined repeated dose repro-devp. Screen was performed for 2,3,5 Trimethylphenol to determine its repeated oral toxic nature upon repeated exposure to 12 male and 12 female Crl: CD (SD) rats. The test chemical in olive oil was dosed at dose levels of 0, 100, 300, 1000 mg/kg/day for 42 days in males and 42 -46 days (from 14 days before mating to day 4 of lactation) for females. A recovery group was also included in the study at a dose level of 0 or 1000 mg/Kg/day consisting of 5 males and 5 females. The animals were observed for clinical signs, mortality, body weight and food consumption, urinanalysis, hematology, blood chemistry, organ weights and histopathology parameters.
Soiled perigenitalia with urine was noted in male and female animals at 300 and 1000 mg/kg/day, transient lethargy and ataxic gait after dosing was noted in 1000 mg/Kg/day dosed males and 300 and 1000 mg/Kg/day dosed female animals. One female animal each (n: 12) at 300 and 1000 mg/kg/day was found dead during the study. A decrease in body weight gain was observed at 300 mg/kg/day (test group) and 1000 mg/kg/day (test and recovery group) in male animals and at 1000 mg/kg/day in female animals. Food consumption was decreased in 300 and 1000 mg/kg/day test groups and increased in 1000 mg/kg/day recovery group in male rats and a decrease in food consumption was noted in 1000 mg/kg/day test group and an increase was noted in 1000 mg/kg/day recovery group in female rats.
Male rats showed an increase in the RET at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day, increase in the MCV at 1000mg/kg/day, increase in the MCV at Recovery at 1000 mg/kg/day and decrease in the MCHC at recovery at 1000 mg/kg/day while female rats showed a decrease in the RBC at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, decrease in the Hgb at 1000 mg/kg/day and Recovery at 1000 mg/kg/day concentration, decrease in the MCHC at 1000 mg/kg/day and an increase in the MCV, MCH and RET at 1000 mg/kg/day. An increase in the TCho, PL and ALT at 1000 mg/kg/d and a decrease in K at 1000 mg/kg/ day dose level was noted in male animals and an increase in the TP at 300 and 1000 mg/kg/day, increase in the Alb at 300 and 1000 mg/kg/day, increase in the TCho,PL and ALP at 1000 mg/kg/day, increase in the AST at Recovery 1000 mg/kg/day, increase in the ALT at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and an increase in the TBil at 1000 mg/kg/day dose level was noted in female animals.
Male rats showed an increase in the absolute and relative kidney weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 300 and 1000 mg/kg/day, increase in the absolute and relative liver weight at 1000 mg/kg/day, increase in the absolute and relative adrenal weight at 1000 mg/kg/day concentration and Recovery at 1000 mg/kg/day, increase in the relative weight of testis at 1000 mg/kg/day, increase in the relative brain weight at 1000 mg/kg/day and Recovery at 1000 mg/kg/day and a decrease in the absolute epididymides weight at 1000 mg/kg/day and at Recovery 1000 mg/kg/day dose levels. Female rats showed an increase in the absolute and relative kidney weight at 300, 1000 mg/kg/day and Recovery 1000 mg/kg/day (tendency), increase in the relative weight of liver at 300 and 1000 mg/kg/day, increase in the relative brain weight at 300 and 1000 mg/kg/day, increase in the absolute and relative spleen weight at 1000 mg/kg/day and an increase in the relative heart weight at 1000 mg/kg/day.
Centrilobular hypertrophy of hepatocytes in the liver in 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoietic in the spleen (Recovery 1000 mg/kg/day), vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis (1000mg/kg/day and Recovery 1000 mg/kg/day), inflammatory infiltration in the mucosa and the lamina propria of small and large intestines at 1000 mg/kg/day was noted in male rats and an increase in the extramedullary hematopoiesis in the liver at 1000 mg/kg/day, inflammatory cell nest in the liver at Recovery 1000 mg/kg/day, deposit of hemosiderin in the spleen at 1000 mg/kg/day and Recovery at 1000 mg/kg/day, increase in the extramedullary hematopoiesis in the spleen at 1000 mg/kg/day, inflammation in forestomach at 1000 mg/kg/day, squamous cell hyperplasia in forestomach at 300 and 1000 mg/kg/day and atrophy of the thymus at 300 and 1000 mg/kg/day was observed in female rats.
Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for 2,3,5 Trimethylphenol upon repeated oral exposure in male and female Crl:CD (SD) rats is 100 mg/Kg/day.
Based on the information available for target chemical, 2,3,5 Trimethylphenol does not exhibit toxic nature upon repeated exposure by oral route. Thus the chemical is not likely to be toxic upon repeated oral exposure as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the information available for target chemical, 2,3,5 Trimethylphenol does not exhibit toxic nature upon repeated exposure by oral route. Thus the chemical is not likely to be toxic upon repeated oral exposure as per the criteria mentioned in CLP regulation.
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.