1,3-Propanediaminium, N1-[3-[[2-[dimethyl[3-[(2-methyl-1-oxo-2-propen-1-yl)amino]propyl]ammonio]acetyl]amino]propyl]-2-hydroxy-N1,N1,N3,N3,N3-pentamethyl-, chloride (1:3)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From the 01-Jul-2009 to 05-Oct-2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study has been performed according to OECD guidelines and EC methods in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]. These principles are compatible with Good Laboratory Practice regulations specified by regulatory authorities throughout the European Community, the United States (EPA and FDA), and Japan (MHLW, MAFF and METI). The study was conducted in compliance with agreed protocols, with no deviations from standard test guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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)

Test material

Test material information

Constituent 1

Reference substance name:

[3-(2-{dimethyl[3-(2-methylprop-2-enamido)propyl]azaniumyl}acetamido)propyl][(2R)-2-hydroxy-3-(trimethylazaniumyl)propyl]dimethylazanium [3-(2-{dimethyl[3-(2-methylprop-2-enamido)propyl]azaniumyl}acetamido)propyl][(2S)-2-hydroxy-3-(trimethylazaniumyl)propyl]dimethylazanium hexachloride

EC Number:

700-055-7

Cas Number:

630113-05-2

Molecular formula:

C22 H48 N5 O3.3Cl

IUPAC Name:

[3-(2-{dimethyl[3-(2-methylprop-2-enamido)propyl]azaniumyl}acetamido)propyl][(2R)-2-hydroxy-3-(trimethylazaniumyl)propyl]dimethylazanium [3-(2-{dimethyl[3-(2-methylprop-2-enamido)propyl]azaniumyl}acetamido)propyl][(2S)-2-hydroxy-3-(trimethylazaniumyl)propyl]dimethylazanium hexachloride

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan France ZI Le Malcourlet 03800 Gannat / France
- Age at study initiation: males: 15 weeks, females 15 weeks
- Weight at study initiation: male: 2245 g, females 2393 g and 2546 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (Harlan Laboratories Ltd., Füllinsdorf) and haysticks 4642 (batch no. 69/08, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 27/09) provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland.
- Water (e.g. ad libitum):Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 01-Jul-2009 to 05-Jul-2009


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 06-Jul-2009 To: 10-Jul-2009

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped with an electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/animal

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

1 male, 2 females

Details on study design:

TEST SITE
- Area of exposure: approx. 6.25 cm2
- % coverage: approximately 0.4% of the surface area
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the dressing was removed the skin was flushed with lukewarm tap water to clean the application site
- Time after start of exposure: 4hours


SCORING SYSTEM: according to the numerical scoring system listed in the Commission Regulation (EC) No. 440/2008, B.4, at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).
Data were summarized in tabular form, showing for each individual animal the irritation scores for erythema and oedema at all measurement intervals. Any lesions were described, including the degree and nature of irritation, corrosion or any other toxic effects observed, and their reversibility.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Other effects:

No staining produced by the test item of the treated skin was observed.
Neither were alterations of the treated skin observed nor were corrosive effects evident on the skin.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, TRIQUAT Monomer is considered to be “not irritating” to rabbit skin.

Executive summary:

The primary skin irritation potential of TRIQUAT Monomer was investigated according to OECD test guideline No. 404, Commission Regulation (EC) No. 440/2008, B.4. and Regulation (EC) No 1272/2008. The test item was applied by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

The test item did not cause any staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.