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Description of key information

A modern acute oral toxicity study performed with the submission substance is supported by an older study with the read-across substance ESBO  Dermal toxicity data are available for ESBO.

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:
December 20th, 2013 to January 24th, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried according to OECD guideline 420. A minor deviation (one animal was not observed on day 8) was reported and it is not deemed to affect the scientific validity of the study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
One animal was not examined on day 8 however since no clinical signs were reported prior and after day 8, this deviation is not deemed to affect the scientific validity of the study.
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
One animal was not examined on day 8 however since no clinical signs were reported prior and after day 8, this deviation is not deemed to affect the scientific validity of the study
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd.
- Age at study initiation: 8-12 weeks of age
- Weight at study initiation: 168-201 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: Groups of up to 4 animals in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Food (2014C Teklad Global Rodent diet) ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: From: December 20th, 2012 To: January 24th, 2013
Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
Arachis oil BP was used because the test item did not dissolve in water.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Justification for choice of vehicle: The test substance did not dissolve/suspend in water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding toxicity, one animal was administered 300 mg/kg of test substance. In the absense of toxicity at the 300 mg/kg dose level, an additional animal was treated at 2000 mg/kg. Since no toxicity was reported at 2000 mg/kg, 4 additional animals were treated at a dose level of 2000 mg/kg,
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg: 1 animal
2000 mg/kg: 5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: clinical observations were made at 30 minutes, 1, 2 and 4 hours after dosing and once daily therafter until study termination. Morbidity and mortality were checked twice daily. Body weights were recorded on the day of administration and on days 7 and 14.
- Necropsy of survivors performed: yes, necropsy was performed at the end of the 14-day observation period.
- Other examinations performed: At necropsy, external examination and opening of the abdominal and thoracic cavities were carried out. The appearance of any macroscopic abnormalities was recorded and no tissues were retained.
Statistics:
Not applicable
Preliminary study:
No mortality was reported at 300 mg/kg bw in one animal. No mortality was recorded in animals treated with a dose level of 2000 mg/kg bw.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality at the Limit Dose
Mortality:
There was no mortality at 300 and 2000 mg/kg bw.
Clinical signs:
other: No signs of toxicity were reported during the course of the study.
Gross pathology:
No abnormalities were reported at necrospy
Other findings:
Not applicable

No additional results or findings were reported.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute oral median lethal dose (LD50) for female rats is greater than 2000 mg/kg bw.
Executive summary:

This study was conducted to determine the acute oral toxicity of soybean, epoxydised, ether with ethylene glycol when administered by gavage to female Wistar rats at the limit dose level 2000 mg/kg bw. The test substance was administered as a solution in arachis oil. In the absence of toxicity data, a preliminary test was performed at 300 mg/kg bw and 2000 mg/kg bw. No effect was reported at these dose levels and 4 additional animals were treated at 2000 mg/kg bw. The animals were fasted overnight prior to dosing. The rats were observed for 14 days following administration. No mortalities were observed; no abnormal clinical findings were reported and all animals gained weight throughout the course of the study. Gross pathology performed at the end of the 14-day observation period did not show abnormal findings. Based on these results under the conditions of this study, the acute oral LD50 was found to exceed 2000 mg/kg bw.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
A modern study performed with the submission substance is supported by an older study with the read-across substance ESBO

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted prior to introduction of test guidelines or adoption of GLP, however he testin laboratory is reputable and the study design appears to follow methods similar to those adopted subsequently as international standards
Qualifier:
no guideline available
Principles of method if other than guideline:
Similar to OECD Guideline 402 or EC Method 403 but as a rangefinding test fewer rabbits used than recommended in formal guidelines adopted many years after study conduct.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: 3-5 months old
- Weight at study initiation: mean weight 2.5 kg
- Fasting period before study: No
- Housing: No data
- Diet (e.g. ad libitum): Rockland rabbit ration
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From:No details provided To: No details provided
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: Impervious 'Vinylite' sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: Exposure period was 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 ml/kg bw applied undiluted
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hour occluded exposure
Doses:
20 ml/kg bw
No. of animals per sex per dose:
NOt stated, but report wording suggests only four rabbits were treated
Control animals:
not specified
Details on study design:
No further details available
Statistics:
Thompson's method for calculating median lethal doses, used where appropriate
Preliminary study:
No data
Sex:
male
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality
Mortality:
Four rabbits survived treatment at 20 ml/kg bw. It appears that only four rabbits were treated and therefore there were no mortalities.
Clinical signs:
other: No data
Gross pathology:
No data
Other findings:
Topical application of 20 ml/kg bw to rabbit skin under fully occluded conditions for 24 hours, resulted in no deaths. All four treated rabbits survived 24 h treatment and the 13 day observation period
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
24 hour exposure to undiluted ESBO under fully occluded conditions did not result in signs of reaction to treatment, mortality or evidence of dermal toxicity in the four rabbits tested.
Executive summary:

The acute dermal LD50 of the read-across substance ESBO (epoxidised soybean oil) was reported to be >20 mL/kg bw in the rabbit.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
20 000 mg/kg bw
Quality of whole database:
An older study with the read-across substance ESBO is reported as the original study report and in a published summary

Additional information

Acute oral toxicity

In a range-finding study, the acute oral LD50 of the read-across substance ESBO (epoxidised soybean oil) was found to be >22.5 mL/kg bw in the rat.

In a study performed with the submission substance, no mortalities were observed; no abnormal clinical findings were reported and all animals gained weight throughout the course of the study. Gross pathology performed at the end of the 14-day observation period did not show abnormal findings. Based on these results under the conditions of this study, the acute oral LD50 was found to exceed 2000 mg/kg bw. 

Acute inhalation toxicity

A waiver is proposed for this endpoint in line with Column 2 of Annex VII of the REACH Regulation, based on the physicochemical properties of the substance and the availability of data by the oral and dermal routes.

Acute dermal toxicity study

In a range-finding study, the acute dermal LD50 of the read-across substance ESBO (epoxidised soybean oil) was reported to be >20 mL/kg bw in the rabbit. Based on read-across and in the predicted absence of dermal absorption, very low acute dermal toxicity is predicted.


Justification for selection of acute toxicity – oral endpoint
Modern study performed with the submission substance

Justification for selection of acute toxicity – dermal endpoint
Only one study is available; this reference is the original study report.

Justification for classification or non-classification

The acute oral LD50 of the submission substance was found to be greater than 2000 mg/kg bw. According to Directive 67/548/EEC and Regulation (EC) No 1272/2008, no classification is warranted. According to Regulation (EC) No. 1272/2008, no classification is warranted for acute oral toxicity.