Alcohols, C12-14, ethoxylated, sulfates, sodium salts

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 Jun - 19 Jul 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certifying authority: Central Veterinary Public Health Inspectorate, Rijswijk, NL

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C12-14, ethoxylated, sulfates, sodium salts

EC Number:

500-234-8

EC Name:

Alcohols, C12-14, ethoxylated, sulfates, sodium salts

Cas Number:

68891-38-3

Molecular formula:

not applicable, UVCB

IUPAC Name:

Alcohols, C12-14(even numbered), ethoxylated < 2.5 EO, sulfates, sodium salts

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF-Quality

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, NL
- Age at study initiation: 13 - 15 weeks
- Weight at study initiation: 2382 - 2833 g
- Housing: individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, NL).
- Diet: standard rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, NL); approximately 100 g per day. In addition, hay (BMI, Helmond, NL) provided once per week.
- Water: tap water diluted with decalcified water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

3 x 0.5 g

Duration of treatment / exposure:

3 min, 1 h and 4 h

Observation period:

21 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 h prior to treatment, the dorsal fur was shaved with electric clippers, exposing an area of approximately 150 sqcm (10 x 15 cm^2).
- Type of wrap if used: Scotchpak-Non-Woven patches of 2 x 3 cm each mounted on separate Micropore tapes. Each dressing was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test substance was removed using firstly a tissue moistened with tap water and subseuqently a dry tissue.
- Time after start of exposure: 3 min, 1 h or 4 h.

OBSERVATION TIME POINTS
In the first animal: 24, 48 and 72 h and 7, 14 and 21 days.
In the two other animals: 1, 24, 48 and 72 h and 7, 14 and 21 days.


SCORING SYSTEM:
- Method of calculation:
Erythema and eschar formation
No erythema = 0
Very slight erythema (barely perceptible) = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beet redness)* = 4

* In case of signs of necrosis or corrosion (injuries in depth) preventing erythema reading, the maximum grade was given

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.2

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Very slight erythema was observed in the treated skin area immediately after the 3 min exposure. A gradual increase of the irritation was observed during the course of the study, resulting in severe erythema, moderate oedema and reduced flexibility of the skin after 72 h. After 7 days, the irritation had decreased and moderate to severe erythema, slight oedema and scaliness were observed in the bald skin area. The irrigation had completely resolved at termination (21 days after exposure)

Exposure for 1 h resulted in well -defined erythema immediately after exposure. The skin irration increased form day 2 onwards and after 72 h the maximum degree of irritation was observed, consisting of severe erythema and oedema and reduced flexibility of the skin. After 7 days moderate to severe erythema, slight oedema and scaliness were observe din a bald skin area. The bald skin persisted until 14 days after exposure. The irritation had completely resolved at termination.

Exposure for 4 h resulted in moderate to severe erythema and very slight oedema immediately after exposure. Fissuring of the skin, indicating superficial necrosis, reduced flexibility of the skin and severe erythema and oedema were noted after 72 h. after 7 days moderate to severe erythema, slight oedema and scaliness were observed in a bald skin area. The irritation had completely resolved within 21 days after exposure, however, the bald skin persisted at termination.

Exposure of two additional animals to the test substance for 4 h resulted in comparable irritation to the that observed in the first animal, when exposes for 4 h. Well – defined erythema without oedema and moderate to severe erythema and very slight oedema were observed in the two animals on day 1. After 72 h reduced flexibility, fissuring of the skin and severe erythema and oedema were apparent. The degree of irritation decreased thereafter and the irritation had completely resolved within 21 days after exposure. A bald skin was apparent from 14 days after exposure onwards and persisted at termination in the two animals.


PRIMARY IRRITATION INDEX
A primary irritation index of 6.7 (severely irritating) was calculated, using the scores of three animals, when the test substance was applied to the intact rabbit skin for 4 hours.

Other effects:

No symptoms of systemic toxicity were observed and no mortality occurred.

Any other information on results incl. tables

Table 1: Results of the skin irritation study

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	3	2	2	0	3	1
24 h	3	2	2	3	3	3
48 h	3	3	3	3	3	3
72 h	4	4	4	4	4	4
7 d	3	2	3	3	2	3
14 d	1	0	1	0	1	0
21 d	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	2.80	3.00	3.00	3.33	3.00	3.33

Applicant's summary and conclusion

Interpretation of results:

other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).

Conclusions:

In the present in vivo skin irritation study, the test substance induced erythema and oedema in the rabbits tested when exposed to 0.5 g test substance under semiocclusive conditions. For both erythema and oedema, the scores for all three animals were above the cut-off value of 2.3. However, erythema was fully reversible within 21 days and oedema within 14 days. Based on the obtained erythema and oedema scores, the test substance is concluded to be irritant to the skin.