Quaternary ammonium compounds, C12-18-alkyltrimethyl, chlorides

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 February, 1988 to 8 March, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

EC Number:

263-038-9

EC Name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

Cas Number:

61789-18-2

Molecular formula:

C(n+3) H(2n+10) N Cl (n=8-18)

IUPAC Name:

Quaternary ammonium compounds, cocoalkyl trimethyl, chloride

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mohican Valley Rabbitry; Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,736 to 3,450 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 85023.
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 71-74 °F
- Humidity (%): 50-74%
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

IN-LIFE DATES: From: 23 February, 1988 to 8 March, 1988

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL/site

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
0.5 mL dose was applied under secured 1 x 1 inch2 guaze patches that were overwrapped with a gauze binder secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: At the end of 4 h, the collars and bandages were removed and the sites wiped with wet disposable paper towels.

SCORING SYSTEM: Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

5.6

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: severely irritating (due to not completely reversible reactions (moderate irritation was still present in one rabbit); in addition desquamation was noted on all sites late in the study period and fissuring was present on two sites

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.8

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 7

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 9

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 10

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 3.6

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Results 11

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of mild irritation

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 13

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 14

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 3.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Results 15

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 2.3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Average erythema score for all animals at 24h: 3; 48h: 3; 72h: 2.8
Average edema score for all animals at 24h: 3.2; 48h: 2.8; 72h: 2.2
Reversibility: Yes, the highest levels of irritation occurred two to three days after dosing and irritation subsequently decreased although moderate reactions still persisted in one animal after study Day 12.
The test substance induced moderate erythema and moderate to severe oedema on all sites. Irritation decreased as the study progressed, however, moderate irritation was present in one rabbit (score: erythema:2; edema:1) through study Day 11.

Other effects:

Desquamation was noted on all sites late in the study period and fissuring was present on two sites.

Any other information on results incl. tables

Mortality: One rabbit was sacrificed in extremis on Day 3 due to broken back.

Body weight: No remarkable changes occurred.

Result details

Table 1:                           Table for skin irritation study
score (average animals investigated)		time	Erythema	Edema
average score Draize scores (0 to maximum 4)	< 1 hr After exposure		2.6	1.5
	24 h		3	3.2
	48 h		3	2.8
	72 h		2.8	2.2
other times	State time
average score	24h, 48h, 72h		3.0	2.7
reversibility: *			n.c	n.c
Average time for reversibility
*    c :    completely reversible   n c :    not completely reversible      n :    not reversible

Applicant's summary and conclusion

Interpretation of results:

other: Category 1C (corrosive) based on CLP criteria

Conclusions:

Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive.

Executive summary:

A study was conducted to determine the skin irritation potential of the test substance, Coco TMAC (33% active in water), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted test substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and test substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The test substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the test substance is considered to be severely irritating. Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive (Naas, 1988).