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Administrative data

Description of key information

2-(2H-benzotriazol-2-yl)-p-cresol is of low acute oral toxicity with an LD50 of higher than 10000 mg/kg bw as shown in a valid study performed similar to OECD 423. Acute dermal toxicity is higher than 2000 mg/kg bw as derived from experimental data both the actual substance and a read-across substance. Upon 4h-inhalation exposure to dust at a concentration of 590 ± 72 mg/m3, each two of nine  males and two of nine females were found dead within 24h after exposure. Ethanol was used as vehicle and 72% of the particles had a diameter of less than 7 mcirometer.  As higher concentrations were technically not possible, the LC50 is reported as > 590 mg/m3. 

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:
From Jan. 23, 1978 to Jan. 23, 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
: no individual data reported, animals were acclimatized for 4 days, no rational for the selection of the doses , signs and symptoms of toxicity were noted but not discussed, and final body weights were not reported
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10047
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: Not reported
Species:
rat
Strain:
other: Tif; RAIF(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 160 to 180 g
- Housing: groups of 5 in macrolon 5 cages
-Fasting prior to adminstration: overnight
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Photoperiod (hrs dark / hrs light): 10/14


Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
4640, 7750, 10,000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
none
Preliminary study:
No preliminary study
Sex:
male/female
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
Mortality:
1 animal in the high dose group died at 48 hrs, 2 animals in the high dose group died at 7 days and 2 animals died at 14 days
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. Sedation became more accentuated as the dose was increased. The surviving animals recovered within 8 to 10 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.
Body weight:
Not performed
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 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:
supporting study
Study period:
From Nov. 11, 1964 to Jun. 1, 1965
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study design appears to follow latest OECD Guideline 403 (1981) with deviations: test concentration was 163 mg/L, instead of 5 mg/L; air flow rate was not reported; duration of exposure was 1.2 hours instead of at least 4 hours; particle size distribution was not reported. Study pre-dates GLP requirements.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
-strain, temperature, humidity, light-dark cycles, and information on diet, particle size distribution, air flow rate not reported; test concentration was 163 mg/L instead of 5 mg/L; duration of exposure was 1.2 hours instead of at least 4 hours.
GLP compliance:
no
Remarks:
Study pre-dates GLP requirements.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories.
- Age at study initiation: Not reported.
- Weight at study initiation: 278 to 310 g (males); 191 to 212 g (females).
- Fasting period before study: Not reported.
- Housing: Individual cages.
- Diet (e.g. ad libitum): Provided food (no other details reported), ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: Not reported.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported.
- Humidity (%): Not reported.
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): Not reported.
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: no data
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Chamber, Rochester design.
- Exposure chamber volume: 30 litre.
- Method of holding animals in test chamber: Not reported.
- Source and rate of air: Not reported.
- Method of conditioning air: Membrane filters.
- System of generating particulates/aerosols: Wright Dust Feed.
- Method of particle size determination: No data.
- Treatment of exhaust air: Not reported.
- Temperature, humidity, pressure in air chamber: 78°F, humidity not reported, Positive pressure in air chamber.


TEST ATMOSPHERE
- Brief description of analytical method used: Not reported.
- Samples taken from breathing zone: Not reported.


VEHICLE
- Composition of vehicle (if applicable): No data.
- Concentration of test material in vehicle (if applicable): No data.
- Justification of choice of vehicle: No data.
- Lot/batch no. (if required): No data.
- Purity: No data.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: No data.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1.2 h
Remarks on duration:
None
Concentrations:
163 mg/L of air (Ct = 195.6 mg hour/L).
Range of chamber concentration = 151 to 176 mg/L.
No. of animals per sex per dose:
5 animals per sex.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Body weights were obtained prior to exposure and at 7 and 14 days. The rats were observed closely during exposure period and daily thereafter for signs of toxicity.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:  Fourteen days after the exposure, the animals were sacrificed, examined for gross changes and the lungs, heart, liver, kidney, spleen, adrenals, gonads, and brain were weighed. 
Statistics:
Not reported.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 163 mg/L air
Exp. duration:
1.2 h
Remarks on result:
other: None
Mortality:
No deaths occurred within the 14-day observation period following the exposure to test substance.
Clinical signs:
other: None reported.
Body weight:
Satisfactory weight gains were noted in all animals during the two weeks following exposure.
Gross pathology:
No changes in gross appearance of the internal organs were noted at the time of autopsy. 
Other findings:
- Organ weights: The organ-to-body-weight ratios were essentially the same as for normal untreated rats of this age in this testing facility. 
Interpretation of results:
not classified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
590 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for acute oral toxicity (Sachsse 1978) was performed and reported similar to the requirements of OECD testing guideline 423. It was not performed prior to the introduction of GLP. The test item was suspended in PEG 400 and was given by gavage to each five male and five female Tif: RAIf (SPF) rats at doses of 4640, 7750 and 10000 mg/kg bw.

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. Sedation became more accentuated as the dose was increased. Mortality was only observed at the highest dose group: Each one male was found dead after 48h and 7 days, respectively. The surviving animals recovered within 8 to 10 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period. No gross related organ changes were observed upon necropsy.

For most of the other data, information is limited to LD50values, all of them being higher than 5000 mg/kg bw. One study of these studies was performed in mice (Heller 1957). One study was performed at a contract institute that was known to have falsified study reports (Paa 1976).

 

 

The study for acute dermal toxicity rin rats used 1000 mg/kg bw as a single dose which is lower than the limit dose prescribed in the OECD testing guideline 402, but is otherwise valid in regard to procedure and reporting detail (Thomann 1972). In that study, the substance caused no adverse effects. No indication of dermal toxicity was observed in a poorly documented 5-day screening study using approximately 2000 mg/kg bw/d (Heller 1957b). Testing for acute dermal toxicity may be omitted if a substance was found to be non hazardous upon acute oral dosing at the limit dose. The available experimental data confirms the absence of an acute dermal toxicity hazard.

 

The key study for inhalation toxicity (Sachsse 1973) follows the latest OECD guideline 403 (1981) with some deviations such as a shorter observation period and no reporting for individual animals. It was performed prior to GLP, but is reported in sufficient detail. Nose-only exposure to aerosol was applied and the highest achievable concentration was 590 ± 72 mg/m3. Each nine male and nine female rats for exposed for 4h. A 20% suspension in ethanol was sprayed into the exposure chamber by means of a pressure nozzle. The liquid was injected by a motor-driven syringe at a rate of 60 mL/h into a stream of compressed air (2 atm.) Flowing through a spray nozzle at a rate of 10 L/min. The aerosol mist thus produced was discharged into the exposure chamber and the ethanol evaporated prior to reaching the rats. The particle-size distribution in the aerosol was determined gravimetrically on Selectron-Filters, pore size 0.2 µm and 72% of the material had a particle size of less than 7 µm.

After the 4-hour exposure all rats showed tachypnoea, asynchronisms of the extremities, lateral or ventral position and apathy. Two male and two females died within 24h. All other animals were recovered within 48h. Hemorrhage in the lungs and congested organs were observed in dead animals.  No substance related gross organ changes were seen in animals killed at the end of observation period of 7 days. No individual animal data were provided.

Two other studies are available, but their results are not reliable. The first study was performed at a test laboratory that was known to have falsified reports (Myers 1975) and is therefore not taken into account. The design of the second study (Beliles 1965) appears to follow latest OECD Guideline 403 (1981) with deviations: The test concentration was 163 mg/L; air flow rate was not reported; duration of exposure was 1.2 hours instead of at least 4 hours. Most importantly, the particle size distribution was not reported. 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.