Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 25 July 2012 to 21 September 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine
IUPAC Name:
Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine
Constituent 2
Reference substance name:
100545-48-0
Cas Number:
100545-48-0
IUPAC Name:
100545-48-0
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: Approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 207 g (range: 191 g to 225 g)
- Fasting period before study: Yes, fasted overnight before treatment. Food was given approximately 4 h after administration of the test substance.
- Housing: The animals were housed by three from the same group in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: Tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: At least 5 or 8 d before the treatment.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 07 August 2012 to 05 September 2012.

DEVIATION: The temperature recorded in the animal room was sometimes outside of the target ranges specified in the study plan. However, this deviation was considered not to have compromised the validity or integrity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methylcellulose aqueous
Details on oral exposure:
VEHICLE
The solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis.
As heterogeneous suspension at 200 mg/mL was obtained with drinking water treated by reverse osmosis, the test substance was tested with 0.5% methylcellulose aqueous solution.
A homogenous suspension was obtained at the concentration of 200 mg/mL in 0.5% methylcellulose aqueous solution.

DOSAGE PREPARATION (if unusual): The test substance was administered as a homogeneous suspension in the vehicle. The test substance was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle.
Dose formulations preparations were prepared by the CiToxLAB France Pharmacy extemporaneously on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in brown flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose:
The starting dose-level was selected since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose level was 300 mg/kg for ethical reasons.
After treatment at the starting dose-level, the next higher dose-level of 2,000 mg/kg was tested.

ADMINISTRATION:
The dose formulations were administered once by gavage, using a plastic syringe fitted with a plastic gavage tube. The quantity of dose formulation administered to each animal was adjusted according to the body weight recorded on the day of dose administration.
A constant dosage-volume of 10 mL/kg was used. The dose formulations will be stirred continuously throughout the dosing procedure.
Doses:
300 and 2000 mg/kg bw.
No. of animals per sex per dose:
3 females per treatment step.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Clinical observations: At least once during the first 30 minutes, periodically during the first 4 h, then once a day, at approximately same time.
- Morbidity and mortality: Frequently during the hours following administration, then at least once a day until the end of the observation period, including weekends and public holidays.
- Body weight: Just before treatment on Day 1; then on Days 8 and 15.
- Necropsy of survivors performed: Yes (macroscopic). The main organs included digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities. All gross observations were recorded individually for each animal.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs were observed in any animals.
Body weight:
A trend to a slightly lower mean body weight gain was noted in females given the test substance at 2,000 mg/kg bw between Days 1 and 15: -14% when compared to CiToxLAB France historical control data. This resulted from a lower mean body weight gain of 25% and 45% recorded between Days 8 and 15 for the first and the confirmatory assays, respectively, when compared to historical control data.
A lower mean body weight gain (25%) was observed in females treated at 300 mg/kg between Days 8 and 15 when compared to historical control data, but no difference was observed between Days 1 and 15.
Gross pathology:
There were no macroscopic post-mortem findings.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the study conditions, the oral LD50 of the test substance was considered to be >2,000 mg/kg bw in rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).
Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance in rats according to the OECD Guideline 436 and EU Method B.1 tris, in compliance with GLP.

The test substance was administered at 300 and 2,000 mg/kg bw once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test substance was prepared in a 0.5% solution of methylcellulose. Each animal was observed at least once a day for mortality and clinical signs for 15 d. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

 

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. A trend to a slightly lower mean body weight gain was noted in females given the test substance at 2,000 mg/kg, when compared to historical control data. There were no macroscopic post-mortem findings.

 

Under the study conditions, the oral LD50of the test substance was considered to be >2,000 mg/kg bw in rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).