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Description of key information

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:
Date of study initiation: September 13, 1988; Date of animal purchase: October 20, 1988; Date of administration: October 27, 1988; Date of autopsy: November 10, 1988; Date of Final report development: January 13, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crj:CD (SD) SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan Inc.
- Age at study initiation: 4 weeks old when were purchased. Subsequently, animals with good growth and general conditions were chosen at the age of 5 weeks to use in this study.
- Weight at study initiation: The mean body weight (the range of body weight) of males and females on administration was 126 g in male (122 - 129 g) and 103 g in female (100 - 106 g), respectively.
- Fasting period before study: Animals were fasted and given only water from 5pm thte day before administration to 3 hr after administration
- Housing: 2 or 3 animals were housed in a stainless metal cage (W 276 x D 426 x H 200 mm) separately by sex.
- Diet (e.g. ad libitum): Animals were fed ad libitum with pellet (Lab M R Stock, Nosan Corporation, Japan) and water (tapping water sterilized by filtration with 1-μ cartridge filter and UV irradiation).
- Water (e.g. ad libitum): Animals were fed ad libitum with pellet (Lab M R Stock, Nosan Corporation, Japan) and water (tapping water sterilized by filtration with 1-μ cartridge filter and UV irradiation).
- Acclimation period: habituated in the test conditions for 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2
- Humidity (%): 55±10
- Air changes (per hr): more than 10 times/hr (all fresh air) of ventilation
- Photoperiod (hrs dark / hrs light): 12-hr light and 12-hr dark cycle (light on: 6 AM, light off: 6 PM)
Route of administration:
oral: gavage
Vehicle:
other: methyl cellulose
Details on oral exposure:
Preparation and administration procedures of test substance: The test substance were prepared with solvent 1.0 w/v% solution of methylcellulose (100cP, lot No.: AWL 3082, Wako Pure Chemical Industries) using an agate mortar and centrifugal ball mill to make suspension at 25 w/v%, the highest concentration physically available. The volume of administration was 20 mL/kg.

The test substance was orally administered by gastric gavage. Animals were fasted and given only water from 5 PM the day before administration to 3 hr after administration.
Doses:
The volume of administration was 20 mL/kg (see above).
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
Observation items: The observation period was 14 days after administration and general symptoms and death/survival were confirmed at least three times from immediately after administration to 6 hr (Administration Day 0) and at least once a day from the next day to the completion of observation. Body weight was measured immediately before administration, and 1, 3, 7 and 14 days after administration. On the final day of observation period (14 days after administration), all animals were sacrificed by ether anesthesia and autopsied.
Statistics:
No details provided in report
Preliminary study:
Preliminary dose-finding study: Based on the results of a preliminary dose-finding study, no death was found in both male and female animals even at a dose of 5,000 mg/kg, which was almost the upper limit physically and technically available. Consequently, 1, 2-diphenoxyethane was considered to be extremely low toxic. Therefore, the dose for male and female animals was determined 5,000 mg/kg. Of each 12 male and female animals, 5 each with good general conditions after habituation were randomly chosen to use in the study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no effects at highest dose tested
Mortality:
Mortality and lethal dose: No death was observed in male and female animals for 14 days of observation period. Therefore, the minimum lethal dose for males and females was 5,000 mg/kg or more.

See Table 1 of attached report
Clinical signs:
General symptoms: No change in general conditions was found in both male and female animals from immediately after administration and no toxic symptom caused by the test substance was found.

See Table 2 and Appendices 1-2 of attached report
Body weight:
Changes in body weight: Both male and female animals gained body weight well throughout the observation period and no effect on body weight gain was found.

See Table 3 and Appendices 3-4 of attached report
Gross pathology:
Autopsy findings: No gross abnormal finding was observed in organs of male and female animals.

No death was observed in male and female animals and the minimum lethal dose was 5,000 mg/kg or more.

In addition, general symptoms, body weight gain and autopsy findings indicated no toxic effect of the test substance.

 

In conclusion, acute toxicity of 1, 2-diphenoxyethane to rats was considered to be minimal.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 1, 2-diphenoxyethane to rats was > 5000 mg/kg bw
Executive summary:

An acute oral toxicity study of 1, 2-diphenoxyethane was conducted in rats and the results are as follows.

 

1. Dose: Male and female: 5,000 mg/kg

 

2. Minimum lethal dose: Male: >5,000 mg/kg Female: >5,000 mg/kg

 

3. General symptoms: No toxic symptom was observed in male and female rats.

 

4. Changes in body weight: No effect on body weight gain was found in male and female rats.

 

5. Autopsy findings: No gross abnormal finding was observed in organs of male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral toxicity: No death was observed in male and female animals and the minimum lethal dose was 5,000 mg/kg or more. In conclusion, acute toxicity of 1, 2-diphenoxyethane to rats was considered to be minimal.


Justification for selection of acute toxicity – oral endpoint
Only available study

Justification for classification or non-classification