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Description of key information

The data indicate that benzyl toluene is of low toxicity after single oral, dermal or inhalation exposures.

 

Acute oral toxicity

Three studies are available for this endpoint: Petra, 1981 (key study) and Mürmann, 1984 and 1995 (supporting studies).

 

Benzyl toluene was administered as such at the dose level of 3.0 to 3.5 ml/kg in groups of 10 Sprague-Dawley rats (5 males and 5 females) (Petra, 1981). The mortality and general behavior of the animals were observed for a period of 14 days after the administration. The mortality rate was 10%, 60%, 70% and 100% at the dose levels of 3, 3.1, 3.2, 3.5 ml/kg, respectively. Prostration and sedation were observed after treatment. The bodyweight of the animals were not influenced by the treatment. Under these experimental conditions, the LD50 of benzyl toluene administered by oral route in the rat was 3015 mg/kg (2962-3068 mg/kg).

 

The Mürmann (1995) study was performed according to OECD guideline 401 and according to GLP. Initially 2000 mg/kg b.w. of benzyl toluene was administered orally to two male and female rats. Since no mortality was observed within 48 hours, 2000 mg/kg b.w. of benzyl toluene was administered to a further three male and three female animals. No deaths occurred during exposure or during the 14 days recovery period. Two animals showed symptoms (ataxia, staggering, abnormal gait). One female animal showed a low weight gain at day 14, all other animals showed normal changes in body weight.no gross organ lesions related to test substance were evident in all animals. At necropsy, no gross organ lesions related to test substance were evident in all animals. Under these experimental conditions, the LD0 of benzyl toluene by oral route is expected to be more than 2000 mg/kg bw.

 

The third one (Mürmann (1984) was also an OECD 401 guideline study but not GLP; its results are in line with those of the previous studies. The LD50 was 3100 mg/kg bw.

 

Acute inhalation toxicity

The acute toxicity of benzyl toluene vapors generated at 70°C was tested in a group of 10 Sprague-Dawley rats (5 males and 5 females) (Delhomme and Traynard, 1983). Exposure duration were 4 hours and the maximum concentration reached was 1.88 mg/l. The mortality and general behavior of the animals were observed for a period of 14 days after the administration of the test substance. Under these experimental conditions, benzyl toluene did not induce any mortality, toxic effects and decrease of the body-weight gain.

 

Acute dermal toxicity:

Two studies are available for this endpoint.

 

The acute dermal toxicity of benzyl toluene was determined in rabbits in a limit test performed according to recognized national procedure (no data on GLP) similar to OECD 402 procedure (Guillot, 1981). No mortality was observed at the dose-level of 2000 mg/kg. The general behavior and the bodyweight of the animals were not influenced by the treatment. Under these experimental conditions, the LD0 was higher than 2000 mg/kg. Only local signs of toxicity were recorded.

 

In the Kaufmann study (1990) (OECD 402, GLP), the acute dermal toxicity was tested in Wistar rats in a limit test (2000 mg/kg); no clinical signs of toxicity was observed -included local toxicity as irritation-; no death occurred.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliance and test procedure in accordance with national standard methods (AFNOR norm) with few deviations but no restrictions
Qualifier:
according to
Guideline:
other: AFNOR T03-021
Deviations:
yes
Remarks:
The age of animals at study initiation was not reported; individual results (bodyweight, clinical signs) were not reported.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: not reported
- Weight at study initiation:
Males: 189 g (mean)
Females: 157 g (mean)
- Fasting period before study: yes, animals without food from 17 to 22 hours before treatment
- Housing: 5/polycarbonate cage (40.8 cm x 33.3 cm x 15 cm)
- Diet: rodent diet ad libitum
- Water (e.g. ad libitum): ad libitum in 500- or 800-mL feeding bottle
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 50 +/- 20
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES:
The experiments started on April 27, 1981. The sacrifice date of the animals was not reported.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUME APPLIED:
From 1 to 10 mL/kg

Doses:
0, 2913, 3010, 3107 and 3399 mg/kg administered as 0, 3, 3.1, 3.2, 3.5 mL/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation; weighing on days 0, 6 and 14
- Necropsy of survivors performed: yes
Statistics:
Derivation of the DL50 using Litchfield and Wilcoxon method.
Preliminary study:
10 animals/dose level were administered 1, 5 and 10 mL/kg (equivalent to approximately 971, 4855 and 9710 mg/kg, respectively).
At 1 mL/kg, no animal died, whereas at 5 and 10 mL/kg, all animals died.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 015 mg/kg bw
95% CL:
2 962 - 3 068
Mortality:
Mortality was observed at all tested levels, from 1/10 animals at the first dose level to 10/10 animals at the highest dose level. See table 1 in the field "Remark on results including tables and figures" for further details.
Clinical signs:
- At the 2913 mg/kg dose level, animals exhibited a slight sedation, 2 to 3 hours after the test substance administration. On day 1, they were prostrated with mid-shut eyes. No additional symptoms were noticed from day 2 and thereafter.
- At the 3010 and 3107 mg/kg dose levels, sedation, prostration and palpebral ptosis were observed one hour after administration. It persisted for approximately 30 hours. From day 2, no others findings were noted.
- At the 3399 mg/kg dose level, a deep sedation and a prostration preceded death.
Body weight:
Body weight gain was normal and no differences were noted between treated and control groups.
Gross pathology:
No abnormalitites were revealed at necropsy.

Table 1 Mortality results

Treatment

Cumulated Mortality

J0 (1 h)

J0 (3 h)

J1

J4

J7

J14

Males

Vehicle

0

0

0

0

0

0

TS at 2913 mg/kg bw

0

0

1

1

1

1

TS at 3010 mg/kg bw

0

0

1

2

2

2

TS at 3107 mg/kg bw

0

0

4

5

5

5

TS at 3399 mg/kg bw

0

0

5

5

5

5

Females

Vehicle

0

0

0

0

0

0

TS at 2913 mg/kg bw

0

0

0

0

0

0

TS at 3010 mg/kg bw

0

0

3

4

4

4

TS at 3107 mg/kg bw

0

0

2

2

2

2

TS at 3399 mg/kg bw

0

0

5

5

5

5

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 value for the substance was calculated to be 3015 mg/kg in both sexes with a confidence interval (p<0.05) of 2962-3068 mg/kg.
Executive summary:

The possible acute oral toxicity of BENZYL TOLUENES was evaluated in Sprague-Dawley rats according to the AFNOR guideline #T03-021401 and GLP. In this study, groups of 5 Sprague-Dawley rats/sex/dose were given the substance at 0 to 3.5 mL/kg by gavage. The mortality and general behavior of the animals were observed  for a period of 14 days after the administration. The mortality rate was 10%, 60%, 70% and 100% at the dose levels of 3, 3.1, 3.2, 3.5 ml/kg, respectively. Prostration and sedation were observed after treatment. The bodyweight of the animals were not influenced by the treatment. The LD50 was found to be 3.105 ml/kg bw, equivalent to 3015 (2962-3068 mg/kg) mg/kg bw, based on the density of the substance of 0.971 mL/g.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 015 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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods (AFNOR norm).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The temperature measured at the end of the experiment was 27°C, above the recommended limit of 25°C; only one concentration was tested; there was no monitoring of the test atmosphere: test concentration, particle size and oxygen level not measured
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO, France
- Age at study initiation: not reported
- Weight at study initiation: 188 - 200 g (mean: 193.5 g)
- Fasting period before study: not reported
- Housing: 5 per cage
- Diet (e.g. ad libitum): Sourifarrat 18%, ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: not reported
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: pure air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel cage
- Exposure chamber volume: 350 x 240 x 200 mm (100 L)
- Method of holding animals in test chamber: 5/sex/cage
- Source and rate of air: pure air passed through a debimeter; the rate was 1000 L/h
- Air changes (per hr): 10
- Method of conditioning air: not indicated
- System of generating particulates/aerosols: pure air passed through a debimeter, then in a 500-mL erlenmeyer containg 350 mL of the substance, heated at 70°C by thermo-shaking, and then delivered to the exposure chamber
- Method of particle size determination: particle size not determined
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber:
beginning: 22°C and 45% humidity
end: 27°C and 53% humidity


TEST ATMOSPHERE
- Brief description of analytical method used: Theoretical nominal concentration calculated by the ratio between the weight of substance per time unit (determined by the difference in the weight of the erlenmeyer) and air volume that passed into the exposure chamber during this time unit.
- Samples taken from breathing zone: no
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined


VEHICLE: air
- Concentration of test material in vehicle (if applicable): 1.88 mg/L
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
1.88 mg/l
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 observation and weighing on days 1, 2, 4, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
Not applicable
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 1.88 mg/L air
Exp. duration:
4 h
Mortality:
No mortality was observed
Clinical signs:
Slight sialorrhea observed only during the 2 first hours of treatment.
No other clinical signs were observed during the exposure and post-exposure periods.
Body weight:
A slight decrease in the bodyweight of females was observed at day 1, then the observed bodyweight gain was normal during the study reminder.
The bodyweight of males was normal throughout the study period.
Gross pathology:
No effects were observed
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC0 in rats by inhalation was found to be > 1.88 mg/L.
Executive summary:

The acute toxicity of benzyl toluenes vapors generated at 70°C was tested in a group of 10 Sprague-Dawley rats (5 males and 5 females). Exposure duration were 4 hours and the maximum concentration reached was 1.88 mg/l. The mortality and general behavior of the animals were observed for a period of 14 days after the administration of the test substance. Under these experimental conditions, benzyl toluenes did not induce any mortality, toxic effects and decrease of the body-weight gain.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
1 880 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 14 to 28 October 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: AFNOR NF T 03-333
Deviations:
yes
Remarks:
The following parameters were missing: the age of animals at study start, the temperature, humidity and air changes during acclimation period.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: GWEN MEUR, France
- Age at study initiation: not reported
- Weight at study initiation: 2.5 +/- 0.1 kg
- Fasting period before study: not reported
- Housing: individually in cage of 540 x 360 x 315 mm
- Diet (e.g. ad libitum): 150 g of commercial granules given daily
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 14 October To: 28 October 1981
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 225 cm2 (15 x 15 cm)
- % coverage: not reported
- Type of wrap if used: adhesive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gauze, then water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): 0.99 g/mL



VEHICLE: No
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily observation and weighing on Days 1, 4, 7, 11 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions
Statistics:
Student's t test
Preliminary study:
No mortality was observed at any dose level.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed.
Clinical signs:
No treatment related clinical signs were observed. Diarrhea have been observed in 3 test substance treated animals, but also in 3 control animals.
Body weight:
No treatment related change has been observed.
Gross pathology:
No treatment related effect was elicited.
Other findings:
- Other observations:
Cutaneous reactions: In all treated animals, an moderate erythema (score = 2) was noted 24 hours after treatment, with oedema slight or moderate (score: 1 to 3). Oedema was reversible but not erythema.
Dryness of the skin from day 3 and skin desquamation from day 7 were also noted in most of treated animals. Those later findings persisted up to the end of experiment.
Interpretation of results:
GHS criteria not met
Executive summary:

The possible acute dermal toxicity of benzyl toluenes was evaluated in New-Zealand albinos rabbits. Benzyl toluenes was administered as such under occlusive binders at the dose level of 2000 mg/kg in groups of 10 rabbits (5 males and 5 females). The mortality and general behavior of the animals were observed for a period of 14 days after the administration of the test substance. No mortality was observed at the dose-level of 2000 mg/kg. The general behavior and the bodyweight of the animals were not influenced by the treatment. Under these experimental conditions, the LD0 of benzyl toluenes administered by dermal route in the rabbits was higher than 2000 mg/kg.

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

Additional information

Justification for classification or non-classification

According to test results for acute toxicity by different routes of exposure (oral, dermal, inhalation), no classification should be applied to the substance according to EU Regulation (EC) N0. 1272/2008 (CLP).