1-Propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 August 2007 to 5 September 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 30 August 2005 Date of Signature: 21 November 2005

Test material

Test material information

Constituent 1

Reference substance name:

trimethyl[3-(octadecyloxy)propyl]azanium chloride

EC Number:

700-414-8

Cas Number:

23328-71-4

Molecular formula:

C24H52ClNO

IUPAC Name:

trimethyl[3-(octadecyloxy)propyl]azanium chloride

Details on test material:

- Name of test material (as cited in study report): 3-Octadecyloxypropyl-N,N,N-trimethylammonium chloride
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not applicable
- InChl (if other than submission substance): Not applicable
- Structural formula attached as image file (if other than submission substance): Not applicable
- Substance type: white solid
- Physical state: solid
- Analytical purity: Not reported
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Isomers composition: Not reported
- Purity test date: Not reported
- Lot/batch No.: Exp. I-070518
- Expiration date of the lot/batch: Not reported
- Radiochemical purity (if radiolabelling): Not applicable
- Specific activity (if radiolabelling): Not applicable
- Locations of the label (if radiolabelling): Not applicable
- Expiration date of radiochemical substance (if radiolabelling): Not applicable
- Stability under test conditions: Not reported.
- Storage condition of test material: room temperature in the dark
- Other: Not reported.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12 to 20 weeks old.
- Weight at study initiation: In the weight range of 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended cages. The animals were returned to their cages for the duration of the exposure period.
- Diet (e.g. ad libitum): Certified Rabbit Diet ad libitum throughout the study.
- Water (e.g. ad libitum): Mains drinking water ad libitum throughout the study.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: distilled water to moisture the test substance.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5g of test material was moistened with 0.5 ml of distilled water.

Duration of treatment / exposure:

4 hours

Observation period:

7 days (1 h, 24 h, 48 h, 72 h and 7 days).

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: back (dorsal/flank).
- Type of wrap if used: Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours.

SCORING SYSTEM: Approximately 1 hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the grading in the test guideline. An additional observation was made on Day 7 to assess the reversibility of skin reactions. The results were interpreted under EU classification system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 66520 Male

Time point:

other: Mean score at 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks on result:

other: Max score observed at 24, 48 and 72 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal: 66521 Male

Time point:

other: Mean at 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks on result:

other: Max score observed at 24, 48 and 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal: 66522 Male

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max score observed at 24 hour

Results 4

Irritation parameter:

edema score

Basis:

animal: 66520 Male

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effects

Results 5

Irritation parameter:

edema score

Basis:

animal: 66521 Male

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effects

Results 6

Irritation parameter:

edema score

Basis:

animal: 66522 Male

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema are given in the table below.
Very slight erythema was noted at all treated skin sites one hour after patch removal and at the 24 hour observation and at two treated skin sites at the 48 and 72 hour observations.
One treated skin site appeared normal at the 48-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation.

Other effects:

Not reported.

Any other information on results incl. tables

Table Individual Skin Reactions

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		66520 Male	66521 Male	66522 Male
Erythema/Eschar Formation	1 Hour	1	1	1	(3 )
	24 Hours	1	1	1	3
	48 Hours	1	1	0	( 2 )
	72 Hours	1	1	0	2
	7 Days	0	0	0	( 0 )
Oedema Formation	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	0	0
	48 Hours	0	0	0	( 0 )
	72 Hours	0	0	0	0
	7 Days	0	0	0	( 0 )
Sum of 24 and 72-hour Readings (S):              5

(   ) = Total values not used for calculation of primary irritation index

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008). No corrosive effects were noted.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted)

§        Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Initial considerations. In the absence of data suggesting that the test material was unlikely to produce severe irritation/corrosion, an ex vivo pre‑screen test, the Transcutaneous Electrical Resistance (TER) Assay, was performed. The results of the pre‑screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo test was performed. 

Results. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. One treated skin site appeared normal at the 48-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation.

Conclusion. The test material does not meet the criteria for classification according to EU classification system. No corrosive effects were noted.