Dibenzyl ether

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Dibenzyl ether

EC Number:

203-118-2

EC Name:

Dibenzyl ether

Cas Number:

103-50-4

Molecular formula:

C14H14O

IUPAC Name:

[(benzyloxy)methyl]benzene

Details on test material:

- Name of test material (as cited in study report): oxyde de dibenzyle, benzyl ether
- Physical state: liquid
No further data

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.