Docosyltrimethylammonium methyl sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18.03.2008-22.04.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 404, EU B.4). For justification for read-across see chapter 1 of the chemical safety report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000) including the most recent partial revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides

EC Number:

271-756-9

EC Name:

Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides

Cas Number:

68607-24-9

IUPAC Name:

68607-24-9

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 7 - 13 weeks old
- Weight at study initiation: 1492-2366 g
- Housing: Individually in labelled cages with perforated floors (dimensions 56x44x37.5 cm)
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 - 21.4
- Humidity (%): 44 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: moistened with water

Controls:

not required

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- % coverage: 100
- Type of wrap if used: mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 hrs

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 hrs

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 hrs

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 hrs

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: on day 7 reached score 4

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 hrs

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 hrs

Score:

2

Max. score:

4

Reversibility:

fully reversible within: within 14 days

Remarks on result:

other: on day 7 reached score 4

Irritant / corrosive response data:

Four hours exposure to 0.5 g of the test substance resulted in moderate to severe or severe erythema and very slight or slight oedema in the treated skin-areas of the three rabbits. In all animals, the observed erythema was scattered at 48 and/or 72 hours after exposure. Fissuring of the skin was noted at 7 days after exposure in two animals and these animals showed scaliness at 7 and 14 days after exposure and bald skin at 14 days after exposure. The other animal showed scaliness at 7 days after exposure.
The skin irritation had resolved within 14 days after exposure, except for scaliness and bald skin in two animals.

There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Animal		778^1				757				803
Time after exposure		Erythema	Oedema	comments		Erythema	Oedema	comments		Erythema	Oedema	comments
1 hour		2	1			1	1			2	1
24 hours		3	1			2	2			2	1
48 hours		3	1	v		2	2			2	1	v
72 hours		3	1	v		3	1	v		2	0	l,v
7 days		4	-	g,l		1	1	l		4	-	g,l
14 days		0	0	h,l		0	0			0	0	h,l

¹Sentinel.

 

Comments:

-.      No scoring possible due to fissuring of the skin

g.     Fissuring of the skin.

h.     Bald skin.

l.      Scaliness.

v.     Scattered erythema.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline-compliant primary skin irritation/corrosion test in rabbits, a supporting substance caused moderate-to-severe or severe erythema and very slight or slight oedema. No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of the test substance to the intact rabbit skin. The supporting substance was irritating to rabbit skin.

Executive summary:

A primary skin irritation/corrosion study with a supporting substance in the rabbit (4-hour semi-occlusive application) was carried out based on the following guidelines:

OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, An.V, B.4 (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

USEPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

JMAFF Guidelines (2000) including the most recent partial revisions.

Three rabbits were exposed to 0.5 grams of the test substance, moistened with water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

Exposure to the supporting substance resulted in moderate to severe or severe erythema and very slight or slight oedema in the treated skin-areas of the three rabbits. In all animals, the observed erythema was scattered at 48 and/or 72 hours after exposure. Fissuring of the skin was noted at 7 days after exposure in two animals and these animals showed scaliness at 7 and 14 days after exposure and bald skin at 14 days after exposure. The other animal showed scaliness at 7 days after exposure.  The skin irritation had resolved within 14 days after exposure, except for scaliness and bald skin in two animals.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of the supporting substance to the intact rabbit skin.