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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to international guidelines, e.g. OECD 404 (Acute Dermal Irritation / Corrosion) und GLP conditions. The study is reliable without restrictions and fully sufficient for endpoint evaluation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 404
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,7,11-trimethyldodecyn-3-ol, CAS: 1604-35-9
- Analytical purity: 98.8 area-% (for details see analytical report No.: 06L00128).
- Lot/batch No.: 05-0001
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Other: pH-value: ca. 5 (undiluted test substance)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rabbits / New Zealand white A 1077 INRA (SPF); Supplier: Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: 5 – 8 months
- Weight at study initiation: 3.62 kg – 3.85 kg
- Housing: Single housing, Stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: about 130 g/animal per day, Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland
- Water: Tap water ad libitum
- Acclimation period: Acclimatization for at least 5 days before application


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: At least 24 hours before the beginning of the study clipping of the dorsolateral part of the trunk of the animal(s).
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume): 0.5 ml undiluted test substance
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was removed at the end of the exposure period with Lutrol®** and Lutrol® / water (1 : 1); Lutrol® E 400 = Polyethylenglycol, BASF AG

SCORING SYSTEM:
The evaluation of skin reactions was performed according to the quoted guidelines.
- Erythema and eschar formation - Grading:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

- Edema formation - Grading:
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72h mean
Score:
2
Max. score:
2
Reversibility:
not fully reversible within:
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72h mean
Score:
0.1
Max. score:
1
Reversibility:
not fully reversible within:
Irritant / corrosive response data:
Individual data: Mean scores over 24, 48 and 72 hours for each animal were 2.0 for erythema and 0.3, 0.0 and 0.0 for edema.

Any other information on results incl. tables

    

Tabelle 1: Individual animal weight data at the beginning and the end of the study

 

Animal

Ear tattoo

Weight d0 (kg)

Weight d14 (kg)

Sex

01

365

3.62

3.63

male

02

380

3.85

3.88

female

03

342

3.79

3.77

male

Tabelle 2: Individual animal data at on erythema and edema (4h exposure)

Readings

Animal

Erythema

Edema

Additional Findings

0h

01

2

0

15

02

2

0

15

03

2

0

15

0h

01

2

0

15

02

2

0

15

03

2

0

15

1h

01

2

0

15

02

2

0

15

03

2

0

15

24h

01

2

1

15

02

2

0

15

03

2

0

15

48h

01

2

0

15

02

2

0

15

03

2

0

15

72h

01

2

0

15

02

2

0

15

03

2

0

15

7days

01

2

2

15, 16, 18

02

2

0

15, 18

03

3

2

15, 16, 25

14days

01

2

0

S

02

2

0

S

03

2

2

15, 16, 28

Mean 24-72h

01

2.0

0.3

02

2.0

0

03

2.0

0

Mean

2.0

0.1

15 = erythema extending beyond the area of exposure

16 = edema extending beyond the area of exposure

18 = severe scaling extending beyond the area of exposure

25 = eczematoid skin change

28 = detachment of superficially altered skin layers in the region of

eczematoid skin change with smooth and reddened skin underneath

S =scaling

REMARKS: Moderate or marked erythema (grade 2 or 3), partly extending beyond the area of exposure, was observed in all animals immediately after removal of the patch up to study termination on day 14. Slight edema (grade 1) was observed in a single animal at the 24-hour reading, only. Moderate edema (grade 2) extending beyond the area of exposure, noted in two animals on day 7, persisted in a single animal up to day 14. Additional findings like scaling, severe scaling extending beyond the area of exposure, eczematoid skin change and detachment of superficially altered skin layers in the region of eczematoid skin change with smooth and reddened skin underneath were observed in the animals during the observation period. The cutaneous reactions were not reversible in all animals within 14 days after removal of the patch. Moderate erythema as well as edema, both extending beyond the area of exposure, and detachment of superficially altered skin layers in the region of eczematoid skin change with smooth and reddened skin underneath were still observed in a single animal at study termination. The other two animals showed moderate erythema and scaling on day 14.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information
Conclusions:
Considering the described cutaneous reactions as well as the average score for irritation, 3,7,11-trimethyldodecyn-3-ol shows a skin irritation potential under the test conditions chosen.
Executive summary:

An in vitro study using the EpiDerm™ human skin model showed the non-corrosivity of 3,7,11-trimethyldodecyn-3-ol. In order to further assess the acute skin irritation potential of the test substance, a dermal irritation/corrosion test in White New Zealand rabbits was performed according to the method described in OECD guideline 404. An amount of 0.5 mL of the test substance was applied for 4 hours to the intact skin of three rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and then in weekly intervals until day 14.

Moderate or marked erythema and slight or moderate edema, both partly extending beyond the area of exposure, were observed in the animals during the course of the study. Additional findings like scaling, severe scaling extending beyond the area of exposure, eczematoid skin change and detachment of superficially altered skin layers in the region of eczematoid skin change with smooth and reddened skin underneath were observed in the animals during the observation period. The cutaneous reactions were not reversible in all animals within 14 days after removal of the patch. Moderate erythema as well as edema, both extending beyond the area of exposure, and detachment of superficially altered skin layers in the region of eczematoid skin change with smooth and reddened skin underneath were still observed in a single animal at study termination. The other two animals showed moderate erythema and scaling on day 14. The average score (24 to 72 hours) for irritation was calculated to be 2.0 for erythema and 0.1 for edema.

Considering the described cutaneous reactions as well as the average score for irritation, 3,7,11-trimethyldodecyn-3-ol shows a skin irritation potential under the test conditions chosen.