Dibenzylbenzene, ar-methyl derivative

Endpoint summary

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

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:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

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 or test system 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:

other: A piloerection was observed in all the treated animals approximately 4.5 hours after administration. However, it was no more observed the following day.

Gross pathology:

No abnormalities were observed.

Interpretation of results:

GHS criteria not met

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

Dose descriptor:

LD0

Value:

> 10 360 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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Analytical concentrations are lacking, two different batch numbers are reported.

Qualifier:

equivalent or similar to guideline

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 or test system 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:

other: - 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

Body weight:

No effect was observed on the body weight.

Gross pathology:

No abnormalities were observed at the necropsy.

Interpretation of results:

study cannot be used for classification

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

Dose descriptor:

LC0

Value:

> 0.24 mg/m³ air

Physical form:

inhalation: vapour

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990-08-17 to 1990-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

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 or test system 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:

other: no abnormal clinical signs were observed, no signs of erythema and oedema were observed

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:

GHS criteria not met

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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

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 or test system 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:

other: No observed effects.

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:

GHS criteria not met

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 2 000 mg/kg bw

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 to the registered substance at up to 0.24 mg/L for four hours and to its combustion products at up to 15.6 mg/L for one hour.

Oral acute toxicity

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.

Inhalation acute toxicity

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.

Dermal acute toxicity

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.

 

Justification for classification or non-classification

No classification for acute toxicity is indicated according to the classification, labeling and packaging (CLP) regulation (EC 1272/2008).

However, hydrocarbons with viscosity below 20 mm²/s at 40 °C poses aspiration hazard : Asp. Tox. 1 (H304).