Registration Dossier

Administrative data

Description of key information

ORAL 
LD50 male/female: ca. 3600 mg/kg bw, (rat, BASF-Test, similar to OECD 401, BASF 1967)
DERMAL
LD50 (male/female) > 2000 mg/kg bw (rat, Limit-Test, similar to OECD 402, HRC 1987)
INHALATION
LC50 (male/female) > 0.59 mg/L air (IRT, BASF-Test, similar to OECD 403, BASF 1969)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969 (march 14-19, and may 13-30)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles; pre-GLP study.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
20 animals/dose
Principles of method if other than guideline:
BASF-Test
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
acute toxic class method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals and environmental conditions:
day /night rhythmus 12/12h
Route of administration:
oral: gavage
Vehicle:
other: aqueous Traganth
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2, 16, and 30% (w/v)
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

No further data.
Doses:
200, 1600, 3200, 3600, 4000, 5000, 6400 mg/kg bw
No. of animals per sex per dose:
20 animals per dose (10/sex)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily (observations); body weight males: 215-250g, female 174-200g
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 3 600 mg/kg bw
Remarks on result:
other: after 7 days; 95% CL not given
Mortality:
Deaths occurred at all dose levels with exception of the lowest dose (200 mg/kg bw); see table below.
Clinical signs:
6400-1600 mg/kg bw:
Squatting posture or prone/lateral position (immediately after dosing), calm behaviour, accelerated or superficial respiration, piloerection, moderate secretion of the buccal cavity, masticatory movements, extended hind limbs, apathy, and weak tonus were observed in these groups.
At 5000 and 4000 mg/kg bw, narcosis was observed after approximately 15 minutes. At the day after dosing, surviving animals of these two dose groups exhibited intermittent respiration and piloerection.
The remaining animals were normal by days 3-4.

200 mg/kg bw:
No clinical symptoms were observed.
Body weight:
no data
Gross pathology:
Decedents:
hydrothorax (17 rats)
serous adhesions at the snout (14 rats)
plethora and serosa of the pleura (21 rats)
deposits of the test material in the stomach (2 rats)

Survivors: no pathological changes of the organs

Mortality rates after 1, 24, and 48 hours and after 7 days

Dose [mg/kg] conc. [%]  no. of rats 1 h 24 h 48 h 7 d
6400 30 20 0/20 19/20 19/20 19/20
5000 30 20 0/20 20/20 20/20 20/20
4000 30 20 0/20 15/20 16/20 16/20
3600 30 20 0/20 7/20 9/20  9/20
3200 30 20 0/20 6/20 6/20 6/20
1600 16 20  0/20 3/20 3/20 3/20
200 2 20 0/20 0/20 0/20 0/20
Executive summary:

10 male and 10 female rats were administered the test substance orally and were observed for 7 days. The acute oral LD50 was 3600 mg/kg bw for both males and females.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 600 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Inhalation Risk Test
Principles of method if other than guideline:
BASF-Test
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
other: Inhalation Risk Test (IRT)
Test material information:
Composition 1
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals and environmental conditions:
no data
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE
A continuous air flow (200 l/h) was conducted through a layer of the unchanged test substance in an exsiccator.

No further data on exposure procedure.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
no further data
Duration of exposure:
8 h
Concentrations:
0.59 mg/l; ca. 106.08 ppm (according to the authors)
No. of animals per sex per dose:
12 rats (males and females; no data on sex ratio)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
no data
Sex:
male/female
Dose descriptor:
discriminating conc.
Effect level:
> 0.59 mg/L air
Exp. duration:
8 h
Remarks on result:
other: no mortality
Mortality:
No deaths occurred.
Clinical signs:
No clinical signs of toxicity were noted.
Body weight:
no data
Gross pathology:
No findings were observed.

No mortality was observed when 12 rats were exposed for 8 hours to an atmosphere that had been saturated at room temperature with the volatile parts of the compound. According to the authors, test concentration was 0.59 mg/l (ca. 106.08 ppm). Formation of dust was not observed.

Executive summary:

No mortality was observed when 12 rats were exposed for 8 hours to an atmosphere that had been saturated at room temperature with the volatile parts of the compound. Test concentration was 0.59 mg/l (ca. 106.08 ppm).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
0.006 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral LD50 combined: ca. 3600 mg/kg bw (95% C.I. not given),

2,3,6-Trimethylphenol is of low toxicity based on the LD50 in rats. In an acute oral toxicity study (BASF, 1969), groups of 20 Gassner rats (no data on sex ratio) were given a single dose of 2,3,6-Trimethylphenol (purity not given) in aqueous Traganth at doses of 200, 1600, 3200, 3600, 4000, 5000, or 6400 mg/kg bw and observed for 7 days. Deaths and clinical symptoms were noted in all dose groups except the 200-mg/kg group. Clinical symptoms were unspecific in nature and included changes in posture, changes in respiration, calm behaviour, narcosis, and piloerection, moderate secretion of the buccal cavity, masticatory movements, extended hind limbs, apathy and weak tonus. The animals were normal by days 3-4. No data are given on changes in body weight. Gross pathology revealed hydrothorax, serous adhesions at the snout, plethora and serosa of the pleura and deposits of the test material in the stomach for decedents, whereas no pathological changes of the organs were detected in survivors.

Dermal LD50 combined > 2000 mg/kg bw,

Trimethylphenol is of low toxicity based on the LD50 in rats.

In an acute dermal toxicity study (HRC, 1987), rats were dermal exposed to Trimethylphenol. The study report is available as a secondary citation and therefore not assignable. Details on the study are lacking; no further data are available at the moment. No deaths and no clinical signs of toxicity were observed.

Inhalation: In an Inhalation Risk Test (BASF, 1969), totally 12 rats (males and females; no data on sex ratio) were exposed by inhalation route to unchanged 2,3,6-Trimethylphenol (purity not given) for 8 hours at a concentration of ca. 0.59 mg/L. The inhalation atmosphere was saturated with the volatile parts of the compound by bubbling a continuous air flow (200 L/h) through a layer of the unchanged test substance in an exsiccator. Animals then were observed for 7 days. No deaths and no clinical signs of toxicity were observed in the Inhalation Risk Test.

It was suggested, that the inhalation hazard test, is not suitable for testing solids, such as 2,3,6-Trimethylphenol (Cas No. 2416-94-6) with no dust formation. However, 2,3,6 -Trimethylphenol is produced and processed under elevated temperature as a melted mass. Thereby, due to the very low vapour pressure at 53.6 °C with 0.724 hPa, no significant exposure through the inhalation route is expected. Additionally, in another test using worst case conditions, where 12 rats were exposed for 8 hours to an atmosphere that had been saturated at 100°C with the volatile parts of the compound at a test concentration of 19.55 mg/l (ca. 3515.09 ppm), no mortality was observed. Therefore, no risk of significant acute inhalation toxicity, even at elevated temperatures, is expected. 

 

Justification for classification or non-classification

Based on the oral LD50in rats, classification of 2,3,6-Trimethylphenol for acute oral toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Based on the available data, classification of 2,3,6-Trimethylphenol for acute dermal and inhalation toxicity in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 is not possible.