N-(2-hydroxypropyl)oleamide

Endpoint summary

Description of key information

Two acute oral and dermal toxicity studies are available (OECD 423 and OECD 402).

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:

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.

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

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.

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).

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.

see Executive summary

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

experimental study

Adequacy of study:

key study

Study period:

05 February 2013 - 22 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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: for the males 351 g (range: 345 g to 357 g) and the females 225 g (range: 218 g to 231 g).
- Housing: the animals were housed by five from the same sex and group in polycarbonate cages.
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: the animals were acclimated to the study conditions for a period of 5 days (females) or 8 days (males) before treatment.

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: 26 February 2013 to 15 March 2013

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ----
- Constant volume: no
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Sex:

male/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 indicative of systemic toxicity were observed in any animals. In females: Moderate to severe erythemas were noted at the application site in 3/5 females on day 2. Then, well defined erythemas were observed in 5/5 females from day 2 or

Gross pathology:

There were no test item treatment-related macroscopic findings.
The few macroscopic finding were those commonly observed in this species and strain.

 

Sex	Female		Male
Group	CiToxLAB France historical control data	1	CiToxLABFrancehistorical control data	2
Dose-level (mg/kg)	0	2000	0	2000
Body weight (mean (± SD))
. Day 1	236 (± 8.9)	225 (± 6.4)	332 (± 6.6)	351 (± 4.6)
. Day 8	253 (± 12.0)	250 (± 4.6)	377 (± 7.4)	382 (± 8.1)
. Day 15	273 (± 16.3)	269 (± 11.5)	422 (± 11.3)	430 (± 8.0)
Body weight change (mean (± SD))
. Days 1-8	+17 (± 11.0)	+25 (± 7.1)	+45 (± 4.0)	+31 (± 6.4)
. Days 8-15	+20 (± 7.1)	+19 (± 8.1)	+45 (± 6.2)	+48 (± 2.0)
. Days 1-15	+37 (± 16.3)	+44 (± 12.0)	+90 (± 8.2)	+78 (± 6.8)

SD: standard deviations.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 of the test item was higher than 2000 mg/kg in rats

Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats.

 

Methods

 

The test item was applied in its original form to the skin of five female then five male Sprague‑Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi‑occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. 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 macroscopicpost-mortemexamination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study reportas no microscopic examination was performed.

 

Results

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

In fermales, moderate to severe erythemas were noted at the application site in 3/5 females on day 2. Then, well‑defined erythemas were observed in 5/5 females from day 2 or 3 until day 5, which turned into very slight erythemas from day 6 until day slight dryness of the skin was noted at the application site in 5/5 females from day 3 until day 6 or 7.

In males, well-defined or very slight erythemas were noted at the application site of all males, from day 2 up to day 6.

When compared toCiToxLAB Francehistorical control data, a lower mean body weight gain was noted in males between day 1 and day 8. Mean body weight gain returned to normal values thereafter.

There were no test item treatment-related macroscopic findings.

Conclusion

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

 

Therefore, the test item is not classified as toxic by dermal route according to the criteria of CLP Regulation.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study

Justification for classification or non-classification

The registered substance is not classified for acute toxicity hazard