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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 October 2015 - 13 April 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Octadec-2-enylsuccinic acid
EC Number:
268-159-0
EC Name:
Octadec-2-enylsuccinic acid
Cas Number:
68015-93-0
Molecular formula:
C22H40O4
IUPAC Name:
2-octadec-2-en-1-ylsuccinic acid
Test material form:
solid
Specific details on test material used for the study:
Identification: EXP1505385
Label Lot No.: E00350-288
Batch No: E00974-38D&F
Re-test Date: 22 June 2018*
Physical Description: Pale amber waxy solid
Purity: 100 %
Storage Conditions: Ambient temperature/ Dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD (SD) (
Sex:
female
Details on test animals or test system and environmental conditions:
Twelve female Sprague-Dawley Crl:CD (SD) (nulliparous and non-pregnant) rats were supplied by Charles River, Margate, UK and arrived at the Test Facility on 27 Oct2015. Nine rats were used on this study and the remaining 3 animals (scheduled for treatment in Group 4) were not used and returned to stock after completion of the study. Animals were approximately 7 to 8 week old on despatch and weighed between 176 and 200 g. On the day of dosing animals were approximately 8 to 11 weeks old and weighed between 180 and 229 g. All animals weighed within +/- 20% of the mean body weight of the previously dosed groups.

The animals were allowed to acclimatise to the Test Facility rodent toxicology accommodation for a period of at least 8 days before dosing.

Animals were housed in groups of 3 in appropriately sized solid-bottomed polycarbonate cages with stainless steel mesh tops. Wood shavings were used as bedding.
Husbandry practices and environmental enrichment were in accordance with Test Facility SOPs and the protocol. SDS Rat and Mouse (modified) No. 1 Diet SQC Expanded was available ad libitum. Food was withdrawn overnight before dosing, and returned as soon as practicable after administration of the test item. Water from the public supply was available ad libitum.

Certificates of analysis for significant contaminants in diet, water, bedding and environmental enrichment materials are retained at the Test Facility. There were no contaminants present in significant quantities that would have interfered with the objectives of the study.
The environmental conditions were continually monitored and recorded every 15 min. Target ranges were 19¿C to 23°C for temperature and 40% to 70% for relative humidity. From animal arrival, the temperature was between approximately 19¿C and 23¿C and the relative humidity was approximately 31% to 74%. On occasions where the target environmental conditions were not mentioned the change was transient and did not trigger the internal alarm and notification procedure at the Test Facility. The health of the animals was unaffected in any occasion, and these events were considered not to have had an impact on the outcome or integrity of the study.

A 12 h light/dark cycle was in operation (light hours 0700-1900 h) with a minimum of 10 air changes per hour.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The animals received a single oral dose via a gavage tube after being deprived of food overnight. The doses were calculated on the basis of each animal’s body weight on the day of dosing.
Doses:
Dose level of 300 mg/kg and 2000 mg/kg were used
No. of animals per sex per dose:
3 animals were tested at 300 mg/kg
6 animals were tested at 2000 mg/kg
Control animals:
no
Details on study design:
A dose of 300 mg/kg was selected as a suitable starting dose level for administration to Group 1 animals. There were no adverse signs in these animals so 2000 mg/kg was chosen as dosage level for Group 2, and as there were no unscheduled deaths, the third group of rats was treated at the same dose level to complete the study.

All animals were for checked for mortality early each morning and as late as possible each day for viability. All animals were examined for clinical signs to treatment for up to 5 hours post dosing on the day of dosing and once daily thereafter, until Day 15. The body weight of each individual animal was recorded before dosing on Day 1 and on Days 8 and 15.

Animals were euthanised on Day 15 by exposure to a rising concentration of carbon dioxide followed by exsanguination. Gross necropsy was performed on all animals. The necropsy consisted of an examination of the cranial, thoracic and abdominal organs and tissues in situ.
Statistics:
No formal statistical analysis was conducted.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no unscheduled deaths.
Clinical signs:
other: There were no adverse signs noted at 300 mg/kg. After treatment at 2000 mg/kg adverse clinical signs were noted from 15 minutes after dosing up to 3 days after dosing (Day 4). The majority of adverse signs were recorded 30 minutes to 2 hours after dosin
Gross pathology:
There were no macroscopic abnormalities in any animal.
Other findings:
Not Applicable

Any other information on results incl. tables

See attached background document

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose level (LD50) of Substance was considered to be > 2000 mg/kg.
Executive summary:

The objective of this study was to assess the adverse effects which can follow within a short period of time after a single oral (gavage) administration of the test item, Substnace to rats.

The test item was administered to 3 groups of female Sprague- Dawley rats. The study design was as follows:

Text Table1
Experimental Design

Group
Numbers

Number of Animals

Dose Level
(mg/kg)

Dose Volume
(mL/kg)

Dose
Concentration (mg/mL)

1

3

300

10

30

2

3

2000

10

200

3

3

2000

10

200

The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and on Day 15, gross necropsy findings.

There were no unscheduled deaths. There were no adverse signs noted at 300 mg/kg. After treatment at 2000 mg/kg adverse clinical signs were noted from 15 minutes after dosing up to 3 days after dosing (Day 4). The majority of adverse signs were recorded 30 minutes to 2 hours after dosing, and included decreased activity, eyes partly closed, piloerection (fur erect), a hunched appearance and abnormal gait. There were wet muciod feaces between 3-4 hours after dosing. The animals gradually recovered and 3 days after dosing only one animal still had a hunched appearance. There were no adverse signs from Day 5. Slight body weight loss of approximately 2% in 3 of the animals that received 2000 mg/kg, when body weights recorded on Day 8 were compared with those on Day 15. The body weight gains of animals at 300 or 2000 mg/kg were generally considered to be acceptable for rats of this age and strain. There were no macroscopic abnormalities in any animal.

Under the conditions of the study the median lethal dose level (LD50) of test Substance in Sprague-Dawley rats was considered to exceed 2000 mg/kg.

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