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Administrative data

Description of key information

Available information indicate that the Dibenzylbenzene, ar-methyl derivative is practically not toxic after single oral (LD50 > 10360 mg/kg), dermal (LD0 > 2000 mg/kg) or inhalative (LC0 > 0.24 mg/m³) exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

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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: Test procedure in accordance with national standard methods with acceptable restrictions.
Qualifier:
according to
Guideline:
other: AFNOR T03-021
Deviations:
yes
Remarks:
the age of the animals at study initiation or the individual results (bodyweight, clinical signs) were not reported.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: Charles River France (76410, Saint-Aubin-lès-Elbeuf)
- Age: 6 weeks
- Weight at study initiation: 184 g (males) and 153 g (females)
- Number of animals per dose group: 5 males + 5 females
- Controls: 5 males + 5 females received the same volume of sterile distilled water.
- Fasting period before study (with water): yes, 18 to 19 hours before treatment
- Housing: 5/polycarbonate cage (40.8 cm x 33.3 cm x 15 cm)
- Diet (e.g. ad libitum): rodent diet ad libitum
- Water (e. g. ad libitum): ad libitum in 500-800 mL feeding bottle
- Acclimatation 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

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Dosage-volume: 10 mL/kg
Doses:
10360 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
EXAMINATIONS:
- Post dose observation period: 14 days
- Clinical signs: examined at least once a day
- Mortality: recorded at least once a day
- Body weight: measured just before administration and then on days 6 and 14.
- Necropsy:
. macroscopic examination of the main organs such as digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities.
. microscopic examination: no


Statistics:
no
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 10 360 mg/kg bw
Mortality:
No deaths were recorded.
Clinical signs:
A piloerection was observed in all the treated animals approximately 4.5 hours after administration. However, it was no more observed the following day.
Body weight:
The body weight gain was similar in the treated and control groups.
Gross pathology:
No abnormalities were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU and CLP-GHS
Conclusions:
The LD0 was > 10360 mg/kg.
Executive summary:

The acute oral toxicity of Dibenzylbenzene, ar-methyl derivative was tested on male and female Sprague-dawley rats at the limit dose of 10360 mg/kg. No mortality was observed during the exposure and 14 days following the exposure. Piloerection was noted in all the treated animals, 4.5 hours after the administration of Dibenzylbenzene, ar-methyl derivative but was no more observed the following day. No differences in body weight gain or in macroscopic findings were observed.

Under these experimental conditions, the LD0 was consider to be > 10360 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions : analytical concentrations are lacking, two different batch numbers are reported.
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 26°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: 180-192 g (mean: 184,5g)
- Fasting period study: not reported
- Housing: 5/sex/cage
- Diet (e.g. ad libitum): sourifarrat 18%, ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimatation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- 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
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
- 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
- air changes (per hr): 10

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


VEHICLE: air
- Theoretical concentration of test material in vehicle (if applicable): 0.24 mg/L


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
0.24 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
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 0.24 mg/L air
Exp. duration:
4 h
Mortality:
No mortality was observed.
Clinical signs:
- During exposure: after an initial agitation, sedation occurred (10 minutes after the start of exposure). After 30 minutes, eyes were closed but reactivity to noise was normal. Afterwards, behaviours were normal.
- After exposure: normal behaviour was noted all along the observation period.
Body weight:
No effect was observed on the body weight.
Gross pathology:
No abnormalities were observed at the necropsy.
Interpretation of results:
other: the results do not allow a precise interpretation
Remarks:
Criteria used for interpretation of results: other: EU and CLP-GHS
Conclusions:
No mortality was found at the dose level of 0.24 mg/L. In the absence of data at higher concentrations, the substance should be classified as toxic,
however a supporting study with dibenzyltoluene heated at 700°C (Ineris, 1993) indicated that LC0 was higher than 15,8 mg/L and thus the
substance was not classified for acute inhalation.
Executive summary:

The acute inhalation toxicity of Dibenzylbenzene, ar-methyl derivativewas evaluated in a 4-hour, single-exposure study in rats at the concentration of 0.24 mg/L, according to a protocol study close to OECD Guideline 403 (May 12th1981) with acceptable restrictions. 

Mortality, clinical observations for clinical signs and body weight changes were evaluated over a 14-day observation period.All animals were subjected to a gross necropsy.

No mortality was observed. During the exposure, initial agitation was first observed before sedation occurred (10 minutes after the start of exposure). After 30 minutes, eyes were closed but reactivity to noise was normal. Afterwards and until the end of the observation period, behaviours were normal. No abnormalities were observed at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-08-17 to 1990-09-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
The purity of the material used for the test was lower than the purity of the actual material. It contained ca. 26% of isomers of dimethyl tribenzenes. However, based on comparable basic structure of the impurities and the assumption that any toxic effects would increase with higher molecular weight and lipophilicity, we regard that the studies conducted with the lower purity material being "worst case" and can be used for the evaluation of the actual product.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 196 - 209 g (male); 187 - 194 g (female)
- Fasting period before study: not mentioned
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet (e.g. ad libitum): Ssniff-R complete feed ad libitum, Ssniff Spezialdiäten GmbH, Soest, Germany
- Water (e.g. ad libitum):drinking water ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 85
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1990-08-08 To: 1990-09-03
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: roughly 5 x 10 cm on the back of each animal
- % coverage: not mentioned
- Type of wrap if used: porous gauze dressing and Elastoplast (Beiersdorf)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not mentioned
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,38 - 0,42 mL

Duration of exposure:
24 hours
Doses:
2000 mg/kg
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: Clinical observations: 10 min, 1 h, 2 h, 6 h, 24 h after patch removal, and thereafter once daily up to day 14; skin reactions: once daily for 14 days after patch removal; weighing: before treatment (day 0) and surviving animals were reweighed on days 7 and 14 (termination)
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical observations: In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwing-Screening procedure (Screening Methods in Pharmacology, R.A. Turner, 1965, p.26). Any changes from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed.
Skin reactions: After patch removal, dermal irritation was evaluated according to a scheme bazed on Draize
Statistics:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd edition, Cambridge, 1971
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths occurred in the course of the study
Clinical signs:
no abnormal clinical signs were observed, no signs of erythema and oedema were observed
Body weight:
all animals showed normal weight gains
Gross pathology:
no test substance related findings were observed
Other findings:
- Potential target organs: not identified
- Other observations: no sex-specific differences were found

Table: Number of animals dead [and with evident toxicity]

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

2000

0/5 

0/5

0/10 

n.a. 

0/5 

 0/5

0/10 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 after dermal application was found to be greater than 2000 mg/kg.
Executive summary:

The acute dermal toxicity of Dibenzylbenzene, ar-methyl derivative was tested in male and female Wistar rats at the limit dose of 2000 mg/kg. No mortality was observed during the exposure and 14 days following the exposure. Under the conditions of the study, the LD50 was considered to be > 2000 mg/kg.

Endpoint:
acute toxicity: dermal
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
Qualifier:
according to
Guideline:
other: AFNOR NF T 03-033
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 360x 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
- Photoperiod (hrs dark/hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 225 cm2 (15 x15 cm) on the back
- % coverage: not reported
- Type of wrap if used: adhesive

REMOVAL OF TEST SUBSTANCE
-Washing (if done): skin is wiped with a gauze pad, rinsed with tepid water and dried with paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1,98 ml/kg
- Concentration (if solution) : 1.01 g/mL
Duration of exposure:
24
Doses:
2000 mg/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 and weighing on Days 1, 4, 7, 11 and 14
- Necropsy of survivors performed: dermal reactions
Statistics:
Student's test
Preliminary study:
No mortality was observed at any dose level.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed.
Clinical signs:
No observed effects.
Body weight:
Normal body weight gain was noted in treated and control groups.
Gross pathology:
No abnormalities were revealed at necropsy.
Other findings:
CUTANEOUS FINDINGS:
In all the treated animals, a slight irritation was noted (grade 1 erythema). It disappeared on the second week. A slight cutaneous dryness was
observed between day 5 and day 10. A pelling occured between day 6 and day 11. No oedema was found at any moment.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU and CLP-GHS
Conclusions:
The dermal LD50 of the substance was found to be greater than 2000 mg/kg/bw. Therefore, no classification for acute dermal toxicity is required.
Executive summary:

The acute dermal toxicity of Dibenzylbenzene, ar-methyl derivative was determined in rabbits in a limit test (2000 mg/kg bw) performed according the French Guideline AFNOR NF T03 -333. The mortality and general behavior of the animals were observed for a period of 14 days after the administration of the 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.

The dermal LD50 of the substance was found to be greater than 2000 mg/kg bw; therefore, no classification for acute dermal toxicity should be required.

Additional information

The acute toxicity of Dibenzylbenzene, ar-methyl derivative was evaluated in various studies, using oral and dermal exposure, as well as exposure via inhalation. All data demonstrate that Dibenzylbenzene, ar-methyl derivative is of low toxicity after single administration. The LD50 values after oral and dermal application are above 2000 mg/kg bw. No mortality was observed after a single exposure of up to 15.6 mg/L for one hour.

Justification for classification or non-classification

No classification for acute toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (67/544 EEC) or the classification, labeling and packaging (CLP) regulation (EC 1272/2008).

However, hydrocarbons with viscosity below 20 mm²/s at 40 °C poses aspiration hazard.

DSD: R65

CLP: Asp. Tox. 1