1,2-diphenoxyethane

Endpoint summary

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 for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

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 or test system 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:

other: 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

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

Value:

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