N-(2-hydroxypropyl)oleamide

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxypropyl)oleamide

EC Number:

203-828-2

EC Name:

N-(2-hydroxypropyl)oleamide

Cas Number:

111-05-7

Molecular formula:

C21H41NO2

IUPAC Name:

N-(2-hydroxypropyl)oleamide

Test material form:

other: beige waxy solid

Details on test material:

- Name of test material: N-(2-hydroxypropyl) Oleamide
- Physical state: beige waxy solid
- 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:

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

Administration / exposure

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).

Results and discussion

Effect levels

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.

Any other information on results incl. tables

 

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.

Applicant's summary and conclusion

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.