Registration Dossier

Administrative data

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:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): 1, 2-diphenoxyethane
- Molecular formula (if other than submission substance): C14H1402
- Molecular weight (if other than submission substance): 214.25
- Physical state: colorless crystal
- Analytical purity: 100%
- Lot/batch No.: 80402
- Storage condition of test material: stored in a dark room (at room temperature)
- Other:
- Supplier: Kanzaki Paper Co., Ltd.
- Responsible person of supplier: Makoto Kondo
- Date of receipt: July 4, 1988
- Amount: 90 g
- Melting point: 96°C
- Solubility: water - apx. 1.4ppm, DMSO - 5% or more
- Handling conditions: workers wore gloves and mask in handling the test substance

Test animals

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)

Administration / exposure

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

Results and discussion

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.
Effect levels
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.