Dibenzyl ether

Endpoint summary

Description of key information

Two valid acute oral and an acute dermal toxicity study are available. An inhalation study is not required because a reliable oral and dermal study is on hand.

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:

1978-02 to 1978-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to OECD 401. No clear deviations observed and sufficiently described. Not GLP. Lack of individual results for gross pathology.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Remarks:

likely not due to testing date

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 84 - 119 g
- Fasting period before study: 12 hr prior (overnight)


No further data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.6 to 6.4 mL/Kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: range finding study LD 50 determined to be between 2.5 and 6.4 mL/Kg bw

No further data

Doses:

0.64, 1.6, 2.5, 4 and 6.4 mL /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: once a week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, diuresis
No further data

Statistics:

LD50 was established based on the method of Weil C.S.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3.7 mL/kg bw

Based on:

test mat.

95% CL:

>= 3.1 - <= 4.6

Remarks on result:

other: The density of dibenzylether is 1.0428 g/cm³ at 20°C. Therefore 3.7 ml/kg bw corresponds with 3.86 g/kg bw.

Mortality:

Death occured from withing twenty-two hours and forty-six hours of treatment.

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing included pilo-erection, abnormal body carriage(hunched posture) and abnormal gait (waddling). Pilo-erection was also observed in controls animals. Lowest dosed rats exhibited lethargy, increased

Gross pathology:

Autopsy revealed congestion and hemorrhage of the lungs, pallor of the liver, kidneys and spleen. Opacity of the eyes was observed.Terminal autopsies of sacrified animals returned normal.

Table 1: Number of animals dead and time range within which mortality occurred

Dose (mL/kg bw)	Mortality (# dead/total)			Time range of deaths (hours)
	Male	Female	Combined
Control	0/5	0/5	-	-
1.6	0/5	0/5	-	-
2.5	1/5	1/5	-	< 46
4	1/5	4/5	-	< 22
6.4	5/5	5/5	-	< 22

Interpretation of results:

GHS criteria not met

Conclusions:

In the test conditons the authors established the LD 50 for rats of dibenzyl oxide to 3.7 mL/Kg bw. In the test conditions, dibenzyl oxide should not be classified for acute oral toxicity.

Executive summary:

In this study, the authors tested the acute oral toxicity of dibenzyl oxide (CAS n° 103-50-4) on CFY rats in a methodology very similar to the OECD guideline 401. The authors monitored for two weeks after a single oral intubation of dibenzyl oxide alone, the behaviour, clinical signs, mortality and body weight gain of male and female treated. Each concentration tested (ranging from 1.6 to 6.4 mL/kg bw) was on five individuals of each sex.

In the test conditions, death occured from within twenty-two hours and fourty-six hours of treatment in both sexes. Signs of reaction to treatment observed shortly after dosing included pilo-erection, abnormal body carriage(hunched posture) and abnormal gait (waddling). Pilo-erection was also observed in controls animals. Lowest dosed rats exhibited lethargy, increased salivation and decreased respiratory rates increasing with test materials concentrations. Diuresis and diarrhoea was observed in high dosed rats. Ataxia, loss of righting reflex, fine body tremors and ptosis were observed amongst treated rats. Three rats appareared in a comatose like condition.

Bodyweight of rats treated at 4 mL/kg bw exhibited signs of depressed body weight gains during firts week but returned normal afterwards. All other surviving treated rats gained bodyweight similarly to controls rats.

Autopsy revealed congestion and hemorrhage of the lungs, pallor of the liver, kidneys and spleen. Opacity of the eyes was observed.Terminal autopsies of sacrified animals returned normal.

In the test conditons the authors established the LD 50 for rats of dibenzyl oxide to 3.7 mL/Kg bw (3.1-4.6). Thus, in the test conditions, dibenzyl oxide should not be classified for acute oral toxicity.

The study is well documented and very similar to a guideline. No obvious deviations to this guideline are observed. Thus this study is considered as relliable with restrictions, a Klimisch 2.b study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 860 mg/kg bw

Quality of whole database:

Scientifically acceptable and sufficiend documented for evaluation.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documentd

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

2 animals of each sex used, one tested dose

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

5.15 mL/Kg

No. of animals per sex per dose:

2

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5.15 mL/kg bw

Based on:

test mat.

Remarks on result:

other: The density of dibenzylether is 1.0428 g/cm³ at 20°C. Therefore 5.15 ml/kg bw corresponds with 5.37 g/kg bw.

In this study report, the authors calculated a LD 50 for rabbits higher than 5.15 mL/Kg in an acute test after an exposure of 24 hours under occlusive conditions to dibenzyl oxide.

Interpretation of results:

GHS criteria not met

Executive summary:

In this study report, the authors calculated a LD 50 for rabbits higher than 5.15 mL/Kg in an acute test after an exposure of 24 hours under occlusive conditions to dibenzyl oxide.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 397 mg/kg bw

Quality of whole database:

In this study report, the authors calculated a LD 50 for rabbits higher than 5.15 m/kg (equivalant to 5397 mg/kg bw) in an acute test after an exposure of 24 hours under occlusive conditions to dibenzyl oxide.

Additional information

In the key study for acute oral toxicity, male and female rats were administered by gavage 0.64, 1.6, 2.5, 4 and 6.4 ml/kg bw (= ca. 671, 1677, 2620, 4192, and 6707 mg/kg) of dibenzyl ether with a method similar to OECD guideline 401; in this study no vehicle was used and the undiluted compound was administered. A LD50 of ca. 3860 mg/kg bw was determined (Kynoch, 1978).

In a second experiment 10 male rats each received a single oral application per gavage of 0.5, 1.0, 2.0, 3.1, 3.5, 4.0, 5.0 ml test substance/kg bw (= equivalent to 1.04, 3.23, 4.17, 5.21, 5.73, or 6.57 g/kg bw). An LD50 = 4800 mg/kg bw was found (Loeser, 1976).

In the key study for acute dermal toxicity, 2 male and 2 female New Zealand White rabbits were treated occusively for 24 hours with 5.15 ml/g bw (equivalent to 5397 mg/kg bw) of undiluted dibenzyl ether. The LD50 was > 5397 mg/kg bw.

Several oral studies are available. The determined LD50 values of the studies with reliability 2 were 3860 mg/kg bw (Kynoch) and 4800 mg/kg bw (Loeser). In the Kynoch study male and female rats were treated with the test substance whereas in the study by Loeser only male rats were used. Therefore the Kynoch study was used as key study. All other studies had LD50 values > 2500 mg/kg bw.

Only one acute dermal toxicity study is study available.

Justification for classification or non-classification

LD50(oral) = 3860 mg/kg bw.

LD50(dermal) = 5397 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.