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EC number: 211-806-9 | CAS number: 697-82-5
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- Ecotoxicological Summary
- Aquatic toxicity
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Effects on fertility
Description of key information
NOAEL was considered to be 300 mg/kg bw for P and F1 generation when Crj: CD(SD) male and female rats were treated with 2,3,5-trimethylphenol orally by gavage for 42 days.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- 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 Toxicity Study with the Reproduction / Developmental Toxicity Screening Test of 2,3,5-trimethylphenol in 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: 136.193 g/mole
- Substance type: Organic
- Physical state: Solid
- Purity: No data available
- Impurities (identity and concentrations): No data available - Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Age at study initiation: 10 weeks old
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- olive oil
- Details on 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
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 - Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- 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
- Details on study schedule:
- No data available
- Remarks:
- 0, 100, 300, 1000 mg/kg bw/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:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- 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: No data available
- 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 - Oestrous cyclicity (parental animals):
- Irregularity in Estrous cyclicity were examined.
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- Number of pups born and number of live pups were examined.
- Postmortem examinations (parental animals):
- Absolute and relative organ weight, gross pathology and histopathology were examined.
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Reproductive indices:
- gestation length, copora lutea and number of implantations were examined.
- Offspring viability indices:
- viability index postnatal day 4 were examined.
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation (if dermal study):
- not specified
- 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
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- haematology
- clinical biochemistry
- urinalysis
- histopathology: non-neoplastic
- reproductive function (oestrous cycle)
- reproductive performance
- other: No effect observed
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- 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:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- haematology
- clinical biochemistry
- urinalysis
- histopathology: non-neoplastic
- reproductive function (oestrous cycle)
- reproductive performance
- other: No effect
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- gross pathology
- other: No effect
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- 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:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 1 000 mg/kg bw/day
- Treatment related:
- yes
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- NOAEL was considered to be 300 mg/kg bw for P and F1 generation when Crj: CD(SD) male and female rats were treated with 2,3,5-trimethylphenol orally by gavage for 42 days.
- Executive summary:
Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test, Crj: CD(SD) male and female rats were treated with2,3,5-trimethylphenol in the concentration of 0, 100, 300, 1000 mg/kg /day orally by gavage. One female animal each were died during the study at300 and 1000 mg/kg/day as compared to control. In male and female rats, soiled perigenitalia with urine was observed at 300 and 1000 mg/kg/day, and in male rats at 1000 mg/Kg/day and in female rats at 300 and 1000 mg/kg/day, transient lethargy and ataxic gait after dosing was observed as compared to control. Decrease in the body weight gain was observed in male rat at 300 mg/kg/day and in male and female rats in recovery at 1000 mg/kg/day as compared to control. Decreased in food consumption were observed at 300 mg/kg /day in male and at 1000 mg/kg/day in male and female rats and increased in 1000 mg/kg/day recovery as compared to control. Similarly, increase in the RET level were observed in male rat at 300 mg/kg/day and increase in the RET and MCV level were observed male rats and decrease in the RBC, Hgb and MCHC level in female rats during dosing at 1000 mg/kg/day as compared to control. Increase in the MCV and decrease in the MCHC were observed at 1000 mg/kg/day in male rats and decrease in RBC and Hgb in female rats in recovery as compared to control. increase in the TCho, PL and ALT in male and TP, Alb, TCho, PL, ALP and TBil in female and a decrease in K in male rats were observed at 1000 mg/kg/day and increase in TP and Alb level were observed at 300 mg/kg/day in female rat as compared to control. Increase in the AST and ALT were observed in female rats at 1000 mg/kg/day in recovery as compared to control. Decrease in the protein and ketone body was observed at 300 and 1000 mg/kg/day in male rat and Decrease in the ketone body in recovery were observed as compared to control. increase in the kidney and spleen weight (Absolute and relative) at 300 mg/kg/day and increase in the kidney, spleen, liver, adrenal weight (Absolute and relative), Increase in Relative testis and brain weight and Decrease in Absolute epididymides weight were observed at 1000 mg/kg/day in male rat as compared to control. In female rats increase in Absolute and relative kidney weight, Relative liver weight and Relative brain weight were observed at 300 mg/kg/day and at 1000 mg/kg/day increase in Absolute and relative kidney weight, Relative liver, heart and brain weight and Absolute and Relative spleen weight were observed as compared to control. In Recovery at 1000 mg/kg/day, increase in Absolute and relative adrenal, Relative brain weight and Decrease in Absolute epididymides weight were observed in male rat and In female rats at 300 and 1000 mg/kg/day, increase in Absolute and relative kidney weight were observed as compared to control. Centrilobular hypertrophy of hepatocytes in the liver, Deposit of hemosiderin in the spleen, Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis and Inflammatory infiltration in the mucosa and the lamina propria of small and large intestines were observed in male rats at 1000 mg/kg/day and In female rats at 1000 mg/kg/day, Increase in the extramedullary hematopoiesis in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen, Inflammation in forestomach, Squamous cell hyperplasia in forestomach, Atrophy of the thymus and Deposit of hemosiderin in the spleen were observed as compared to control. In female rats when treated with 300 mg/kg/day, Atrophy of the thymus and spleen were observed as compared to control.In Recovery, Inflamma tory cell nest in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen and Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis were observed in male rats at 1000 mg/kg/day and in female rats, inflammatory cell nest in the liver, Deposit of hemosiderin in the spleen were observed as compared to control. In addition, Abnormal estrous cycle and Decrease in the gestation length, number of copora lutea, and number of implantations were observed in 1000 mg/kg bw treated female rats as compared to control. Significant change in viability of pups on PND 4 and Body weight: Significant change in Body weight of pups were observed in treated rats at 1000 mg/kg bw as compared to control. No external abnormality were observed in pups at 100, 300, 1000 mg/kg /day as compared to control. Therefore, NOAEL was considered to be 300 mg/kg bw for P and F1 generation when Crj: CD(SD) male and female rats were treated with 2,3,5-trimethylphenol orally by gavage for 42 days.
Reference
Mortality: when treated with 300 and 1000 mg/kg/day, One female animal each were died mg/kg/day during the study as compared to control.
Body weight and weight gain: In male rat when treated with 300 mg/kg/day and in male and female rats in recovery at 1000 mg/kg/day, decrease in the body weight gain was observed as compared to control.
Food consumption and compound intake:
In male rats when treated with 300 and 1000 mg/kg/day, decreased in food consumption was observed and increased in 1000 mg/kg/day recovery as compared to control.
In Female rats when treated with 1000 mg/kg/day, decrease in food consumption was observed during dosing and increase in recovery as compared to control.
Haematology:
In treatment:
When treated with 300 mg/kg/day, increase in the RET level were observed in male rat.
When treated with 1000 mg/kg/day, increase in the RET and MCV level were observed male rats and decrease in the RBC, Hgb and MCHC level in female rats during dosing as compared to control.
Recovery:
In male rats when treated with 1000 mg/kg/day, increase in the MCV and decrease in the MCHC were observed as compared to control.
In Female rat when treated with 1000 mg/kg/day, decrease in RBC and Hgb were observed as compared to control.
Clinical chemistry:
In male rats when treated with 1000 mg/kg/day, increase in the TCho, PL and ALT and a decrease in K at were observed as compared to control.
In Female rat when treated with 300 mg/kg/day, increase in TP and Alb level were observed.
When treated with 1000 mg/kg/day, increase in the TP, Alb, TCho, PL, ALP and TBil were observed.
Recovery:
In female rat when treated with 1000 mg/kg/day, increase in the AST and ALT were observed as compared to control.
Urinanalysis:
In male rats when treated with 300 and 1000 mg/kg/day, decrease in the protein and ketone body were observed as compared to control.
Recovery:
In male rats when treated with 1000 mg/kg/day, Decrease in the ketone body were observed as compared to control.
FOB: No effect were observed in treated mael and femaler rats.
Organ weights:
In male rats when treated with 300 mg/kg/day, increase in the kidney and spleen weight (Absolute and relative)
When treated with 1000 mg/kg/day, increase in the kidney and spleen, liver, adrenal weight (Absolute and relative), Increase in Relative testis and brain weight and Decrease in Absolute epididymides weight were observed as compared to control.
In female rats when treated with 300 mg/kg/day, increase in Absolute and relative kidney weight, Relative liver weight and Relative brain weight were observed as compared to control.
When treated with 1000 mg/kg/day, increase in Absolute and relative kidney weight, Relative liver, heart and brain weight and Absolute and Relative spleen weight were observed as compared to control.
Recovery:
In male rats when treated with 1000 mg/kg/day, increase in Absolute and relative adrenal, Relative brain weight and Decrease in Absolute epididymides weight were observed as compared to control.
In female rats when treated with 300 and 1000 mg/kg/day, increase in Absolute and relative kidney weight were observed as compared to control.
Histopathology:
In male rats when treated with 1000 mg/kg/day, Centrilobular hypertrophy of hepatocytes in the liver, Deposit of hemosiderin in the spleen, Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis and Inflammatory infiltration in the mucosa and the lamina propria of small and large intestines
In female rats when treated with 1000 mg/kg/day, Increase in the extramedullary hematopoiesis in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen, Inflammation in forestomach, Squamous cell hyperplasia in forestomach, Atrophy of the thymus and Deposit of hemosiderin in the spleen were observed as compared to control.
In female rats when treated with 300 mg/kg/day, Atrophy of the thymus and spleen were observed as compared to control.
Recovery:
In male rats when treated with 1000 mg/kg/day, Inflamma tory cell nest in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen and Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis were observed as compared to control.
In female rats when treated with 1000 mg/kg/day, In flammatory cell nest in the liver, Deposit of hemosiderin in the spleen were observed as compared to control.
Estrous cycle: Abnormal estrous cycle was observed in 1000 mg/kg bw treated female rats as compared to control.
Reproductive performance
Decrease in the gestation length, number of copora lutea, and number of implantations were observed in 1000 mg/kg bw treated female rats as compared to control.
Reproductive performance
Decrease in the gestation length, number of copora lutea, and number of implantations were observed in 1000 mg/kg bw treated female rats as compared to control.
Significant change in viability of pups on PND 4 were observed in treated rats at 1000 mg/kg bw as compared to control.
Body weight: Significant change in Body weight of pups were observed in treated rats at 1000 mg/kg bw as compared to control.
Gross pathology:
No external abnormality were observed in pups at 100, 300, 1000 mg/kg /day as compared to control.
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
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from peer-reviewed journal
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Toxicity to reproduction:
Ina study, 2,3,5-trimethylphenol has been investigated for reproductive toxicity to a greater or lesser extent. Study based on in vivo experiments data in rodents, i.e. most commonly in rats for 2,3,5-trimethylphenol.
In a experimental study given by National Institute of Technology and Evaluation (Japan Chemicals Collaborative Knowledge database, 2016), Crj: CD(SD) male and female rats were treated with2,3,5-trimethylphenol in the concentration of 0, 100, 300, 1000 mg/kg /day orally by gavage. One female animal each were died during the study at300 and 1000 mg/kg/day as compared to control. In male and female rats, soiled perigenitalia with urine was observed at 300 and 1000 mg/kg/day, and in male rats at 1000 mg/Kg/day and in female rats at 300 and 1000 mg/kg/day, transient lethargy and ataxic gait after dosing was observed as compared to control. Decrease in the body weight gain was observed in male rat at 300 mg/kg/day and in male and female rats in recovery at 1000 mg/kg/day as compared to control. Decreased in food consumption were observed at 300 mg/kg /day in male and at 1000 mg/kg/day in male and female rats and increased in 1000 mg/kg/day recovery as compared to control. Similarly, increase in the RET level were observed in male rat at 300 mg/kg/day and increase in the RET and MCV level were observed male rats and decrease in the RBC, Hgb and MCHC level in female rats during dosing at 1000 mg/kg/day as compared to control. Increase in the MCV and decrease in the MCHC were observed at 1000 mg/kg/day in male rats and decrease in RBC and Hgb in female rats in recovery as compared to control. increase in the TCho, PL and ALT in male and TP, Alb, TCho, PL, ALP and TBil in female and a decrease in K in male rats were observed at 1000 mg/kg/day and increase in TP and Alb level were observed at 300 mg/kg/day in female rat as compared to control. Increase in the AST and ALT were observed in female rats at 1000 mg/kg/day in recovery as compared to control. Decrease in the protein and ketone body was observed at 300 and 1000 mg/kg/day in male rat and Decrease in the ketone body in recovery were observed as compared to control. increase in the kidney and spleen weight (Absolute and relative) at 300 mg/kg/day and increase in the kidney, spleen, liver, adrenal weight (Absolute and relative), Increase in Relative testis and brain weight and Decrease in Absolute epididymides weight were observed at 1000 mg/kg/day in male rat as compared to control. In female rats increase in Absolute and relative kidney weight, Relative liver weight and Relative brain weight were observed at 300 mg/kg/day and at 1000 mg/kg/day increase in Absolute and relative kidney weight, Relative liver, heart and brain weight and Absolute and Relative spleen weight were observed as compared to control. In Recovery at 1000 mg/kg/day, increase in Absolute and relative adrenal, Relative brain weight and Decrease in Absolute epididymides weight were observed in male rat and In female rats at 300 and 1000 mg/kg/day, increase in Absolute and relative kidney weight were observed as compared to control. Centrilobular hypertrophy of hepatocytes in the liver, Deposit of hemosiderin in the spleen, Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis and Inflammatory infiltration in the mucosa and the lamina propria of small and large intestines were observed in male rats at 1000 mg/kg/day and In female rats at 1000 mg/kg/day, Increase in the extramedullary hematopoiesis in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen, Inflammation in forestomach, Squamous cell hyperplasia in forestomach, Atrophy of the thymus and Deposit of hemosiderin in the spleen were observed as compared to control. In female rats when treated with 300 mg/kg/day, Atrophy of the thymus and spleen were observed as compared to control.In Recovery, Inflamma tory cell nest in the liver, Deposit of hemosiderin in the spleen, Increase in the extramedullary hematopoiesis in the spleen and Vacuolization in the seminiferous tubule, germ cell necrosis and multinucleated giant cell formation in the testis were observed in male rats at 1000 mg/kg/day and in female rats, inflammatory cell nest in the liver, Deposit of hemosiderin in the spleen were observed as compared to control. In addition, Abnormal estrous cycle and Decrease in the gestation length, number of copora lutea, and number of implantations were observed in 1000 mg/kg bw treated female rats as compared to control. Significant change in viability of pups on PND 4 and Body weight: Significant change in Body weight of pups were observed in treated rats at 1000 mg/kg bw as compared to control. No external abnormality were observed in pups at 100, 300, 1000 mg/kg /day as compared to control. Therefore, NOAEL was considered to be 300 mg/kg bw for P and F1 generation when Crj: CD(SD) male and female rats were treated with 2,3,5-trimethylphenol orally by gavage for 42 days.
Thus, based on the above study on 2,3,5-trimethylphenol, it can be concluded that LD50 2,3,5-trimethylphenol is not toxic at dose level 300 mg/kg bw/day. Thus, comparing this value with the criteria of CLP regulation, 2,3,5-trimethylphenol can be “Not classified” for reproductive toxicity.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the above study on 2,3,5-trimethylphenol, it can be concluded that LD50 2,3,5-trimethylphenol is not toxic at dose level 300 mg/kg bw/day. Thus, comparing this value with the criteria of CLP regulation, 2,3,5-trimethylphenol can be “Not classified” for reproductive toxicity.
Additional information
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