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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 November 2012 - 24 January 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2013

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:
yes

Test material

Constituent 1
Reference substance name:
N-(2-Hydroxypropyl) Oleamide
IUPAC Name:
N-(2-Hydroxypropyl) Oleamide
Test material form:
other: waxy solid
Details on test material:
- Name of test material: N-(2-hydroxypropyl) Oleamide
- Physical state: waxy solid beige
- Lot/batch No.: T22221 without solvent
- Analytical purity: 100% dry matter
- Expiry date: 29 May 2014
- Storage condition: at room temperature.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: 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: 201 g (range: 191 g to 208 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed by three from the same group in polycarbonate cages with stainless steel lids (Techniplast 2154, 940 cm2)
- 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 days before the beginning of the study.

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

IN-LIFE DATES: 04 December 2012 to 26 December 2012.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/kg
- Maximum dose-volume applied: 10 mL/kg.

DOSAGE PREPARATION (if unusual): The test item was administered as a homogenous suspension in the vehicle. Although the test item was a wax, it 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 in agreement with the Sponsor, based on available test item toxicity data, no morbidity or mortality was expected to occur at the dose level of 2000 mg/kg. This was therefore chosen as the starting dose-level.
After treatment at the starting dose-level, the next dose-level was administered in a sequential manner, under the same conditions to different animals, based on the dose-levels indicated in the flow charts of OECD Guideline No. 423, 17th December 2001, which are equivalent to those of Commission Regulation (EC) No. 440/2008, B.1tris (30 May 2008).
Based on the results obtained for groups 1 and 2, a third group was not tested.
Doses:
2000 mg/kg.
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 days
- Clinical observations: frequently during the hours following treatment; then once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Results and discussion

Effect levels
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:
other: No clinical signs were observed in any animals.
Gross pathology:
There were no macroscopic post-mortem observations.

Any other information on results incl. tables

see Executive summary

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
The oral LD50 of the test item was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as toxic by oral route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

 

Methods

The test item was administered once by oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

Based on available test item toxicity data, the starting dose-level of 2000 mg/kg was chosen. After the first assay, as no toxicity was observed, the results were confirmed in three other females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on the day of allocation of the animals into groups, then on days 1, 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.

 

Results

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

When compared to CiToxLAB France historical control data and taking into account the initial body weight values, a lower body weight gain was noted in 1/6 females between days 1 and 8 and in 2/6 females between days 8 and 15. In addition, an overall lower body weight gain was observed in 1/6 females between days 1 and 15. The test item had no effect on the body weight evolution, as these lower body weight gains were considered to be minimal and of fortuitous occurrence.

There were no macroscopic post-mortem observations.

 

Conclusion

The oral LD50of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified as toxic by oral route according to the criteria of CLP Regulation.