Fatty acids, C16-18 and C18-unsatd., reaction products with diethylenetriamine, di-Me sulfate-quaternized

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-10-31 to 2007-11-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C16-18 (even numbered) and C18 unsatd., reaction products with diethylene triamine, di-Me sulfate quaternized

Cas Number:

1370006-50-0

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Fatty acids, C16-18 (even numbered) and C18 unsatd., reaction products with diethylene triamine, di-Me sulfate quaternized

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Weight at study initiation:
- 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. 08/07, Provimi Kliba AG / Switzerland) were provided for gnawing.
- Diet: ad libitum, pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 52/07) provided by Provimi Kliba AG, 4303 Kaiseraugst /
Switzerland.
- Water: ad libitum, municipal water
- Acclimation period: 4-6 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

purified

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL test substance was weighed as delivered by the Sponsor and then moistened with approximately 0.5 mL of purified water
before application.
- pH: 6.44 (1 % solution)

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3 animals, 1 male, 2 females

Details on study design:

PRE-EXPERIMENTAL PROCEDURE
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin
of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.

ADMINISTRATION OF THE TEST ARTICLE
On the day of treatment, 0.5 mL of test substance was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.
The application sites were observed for erythema, edema and other dermal findings approximately 1, 24, 48 and 72 hours after patch removal and on study days 7, 10 and 14.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours
Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
Grading of skin reaction

Erythema and Eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) or eschar formation
(injuries in depth preventing erythema reading) 4

Oedema formation
No oedema 0
Vera slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1mm) 3
Severe oedema (raised more then 1mm and
extending beyond the are of exposure) 4

Mortality / Viability: the rabbits were observed daily from acclimatization of the animals to the termination of test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: scaling present

Results 2

Irritation parameter:

erythema score

Basis:

animal: #2, #3

Time point:

other: mean 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: scaling present

Results 3

Irritation parameter:

edema score

Basis:

animal: #1, #2

Time point:

other: mean 24, 48 and 72 hours

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: scaling present

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: scaling present

Irritant / corrosive response data:

CLINICAL SKIN OBSERVATIONS
One hour after removal of the dressing a well-defined erythema was observed in all animals which progressed into moderate to severe and persisted as very slight up to 10 or 14 days after treatment. A very slight to moderate oedema was recorded in all animals from the 1-hour up to the 72-hour reading or up to 10 days after treatment. Scaling was present in all animals 7 to 14 days after removal of the application patch.
No alterations and no corrosive effects were observed on the treated skin.
REVERSIBILITY
With the exception of scaling in all three animals and a very slight erythema in the male, these effects were reversible and were no longer evident 14 days after treatment.

Other effects:

TOXIC EFFECTS OTHER THAN SKIN IRRITATION
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- Body weights: the body weights of all rabbits were considered to be within the normal range of variability.
- No necropsy was performed on the animals sacrificed at termination of observation.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time

Score at time point	Erythema	Edema
	Max. score: 4	Max. score: 4
1 hour	2/2/2	3/2/2
24 hours	3/3/3	3/3/2
48 hours	3/3/3	2/2/2
72 hours	3/3/3	2/2/2
7 days	1/1/1	1/0/1 *
10 days	1/1/1	1/0/1 *
14 days	1/0/0	0/0/0 *

* = scaling present

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

Judgment is based on erythema/eschar and edema calculated as mean scores for each animal following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility. The following mean scores were calculated for partially unsaturated IQAC, DMS quaternised (no solvent): erythema 3 and edema 2.33/2.33/2. Edema was fully reversible within 14 days in all animals, whereas scaling was still present in all animals at study termination (day 14). Erythema was not fully reversible at study day 14 in one animal.

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 (Apr. 24, 2002), three young adult New Zealand White rabbits were dermally exposed to 0.5 mL of partially unsaturated IQAC, DMS quaternised (100 % a.i.) moistened with 0.5 mL purified water for 4 hours under semi-occlusive dressing. Animals then were observed for 14 days. The skin reaction was scored according to OECD Guideline 404.

One hour after removal of the dressing a well-defined erythema was observed in all animals which progressed into moderate to severe and persisted as very slight up to 10 or 14 days after treatment. A very slight to moderate oedema was recorded in all animals from the 1-hour up to the 72-hour reading or up to 10 days after treatment. Scaling was present in all animals 7 to 14 days after removal of the application patch. No alterations and no corrosive effects were observed on the treated skin.

In this study, partially unsaturated IQAC, DMS quaternised is a dermal irritant. The test substance is irritating to the skin based on results of the topical semi-occlusive application in rabbits.