Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-06-07 to 2001-06-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Guideline 11 Nousan No. 6283 (October 1, 1999); First Revision: 12 Nousan 8628 (December 6, 2000)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

oleic-acid based IQAC, DMS quaternised

IUPAC Name:

oleic-acid based IQAC, DMS quaternised

Constituent 2

Reference substance name:

Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

EC Number:

931-745-8

Cas Number:

1335203-21-8

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 3329 to 3867 grams
- Housing: individual housing in suspended wire mesh cages
- Diet: 150 g/day, standard laboratory rabbit diet PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322
- Water: ad libitum, municipal water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-71
- Humidity (%): 50-75
- Air changes (per hr): no data
- Photoperiod: 12 hour light/dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Each animal served as its one control with adjacent area of untreated skin.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3

Details on study design:

PRE-EXPERIMENTAL PROCEDURE
On the day prior to dosing, the hair was removed from the backs and flanks of the rabbits using an electric clipper.

ADMINISTRATION OF THE TEST ARTICLE
Prior to use, the original container of the test article was agitated to insure a homogeneous mixture. A sufficient amount of test article was dispensed into a labeled storage vessel and a stir bar was added. The test article was stirred continuously throughout the dosing procedure. Each 0.5-ml was applied to an area of skin approximately 2.5 x 2.5 cm under a two-ply gauze patch secured in place with Micropore™ tape. The patches were overwrapped with a gauze binder and secured with Dermiform® tape. Plastic restraint collars were applied to the animals to prevent ingestion of the test article and/or bandages. The application sites were observed for erythema, edema and other dermal findings approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and on study days 4, 7, 10 and 14.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours
At the end of four hours, the collars and bandages were removed and the sites wiped with disposable paper towels moistened with deionized water.

SCORING SYSTEM: Dermal irritation was graded in accordance with the method of Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Very slight erythema (score 1) in all animals at day 14

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

CLINICAL SKIN OBSERVATIONS
- All animals were noted with moderate to severe erythema and very slight to slight edema. Focal eschar was noted for two animals on study day 7, and desquamation was noted for all animals on study days 7 through 14.

REVERSIBILITY
- Very slight erythema was still present for all animals at study termination (study day 14).

Other effects:

TOXIC EFFECTS OTHER THAN SKIN IRRITATION
- There were no deaths during the study.
- Body weights: No remarkable body weight changes were noted during the study.

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
0.5-1 hour	3/2/2	1/1/1
24 hours	3/3/3	1/2/2
48 hours	3/3/3	1/1/2
72 hours	3/3/3	1/1/1
4 days	3/3/3	1/1/1
7 days	2d/2dg/3dg	1/1/1
10 days	2d/2d/2d	0/0/1
14 days	1d/1d/1d	0/0/0

d=desquamation; g = focal eschar

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Interpretation 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 oleic-acid based IQAC, DMS quaternised: erythema 3/3/3 and edema 1/1.33/1.67. Edema were fully reversible within 14 days in all animals, whereas very slight erythema (score 1) was still present in all animals at study termination (day 14).

Executive summary:

In a primary skin irritation study according to US Guideline EPA OPPTS 870.2500 (1998), OECD Guideline 404 (1992), EU Guideline B.4 (1992) and Japanese Guideline Nousan No. 6283 (1999), revised Nousan 8628 (2000), three White New Zealand rabbits were semi-occlusive dermally exposed to 0.5 ml of oleic-acid based IQAC, DMS quaternised (according to sponsor information: 80 % of CAS No. 72749-55-4, 15 % of CAS No. 9004-96-0 (Oleic acid, ethoxylated) and 5 % of CAS No. 25322-68-3 (Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated)) for 4 hours. Animals then were observed for 14 days. Irritation was scored by the method of Draize.

 

The oleic-acid based IQAC, DMS quaternised induced in all animals moderate to severe erythema and very slight to slight edema. Focal eschar was noted for two animals on study day 7, and desquamation was noted for all animals on study days 7 through 14. Very slight to slight erythema was still present for all animals at study termination (study day 14). Mean scores from gradings at 24, 48 and 72 hours after removal of the test material for erythema were for all animals >/=2.3 but < 4. Edema were less severe. Inflammation persisted to the end of the observation period (14 days) in all three animals.