Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 November - 7 December, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Ditetrahydrofurylpropane
- Lot/batch No.: 6-7B09
- Analytical purity: 99.7%
- Substance type: Clear colourless liquid
- Physical state: liquid
- Purity test date: 09 February 2007
- Expiration date of the lot/batch: 09 February 2010
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, The Netherlands (animals 607 and 611); Harlan, Gannat, France (animal 596)
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): ad libitum 100 grams per day
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 – 22.4°C
- Humidity (%): 42 - 61%
- Air changes (per hr): 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:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL


Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test substance.

Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2x3 cm
- % coverage: not indicated
- Type of wrap if used: A metalline patch was mounted on Micropore tape#, which was wrapped around the abdomen and secured with Coban elastic bandage#.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
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
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is 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 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Four hours exposure to 0.5 mL of Ditetrahydrofurylpropane resulted in well-defined erythema and slight oedema in the treated skin-areas of the three rabbits. Scaliness was seen 24 hours, 48 hours, 72 hours and/or 7 days after exposure. The skin irritation had completely resolved within 14 days after exposure in all 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

Table 1: Individual skin irritation scores

Animal

5961

607

611

Time after exposure

Erythema

Oedema

comments

Erythema

Oedema

comments

Erythema

Oedema

comments

1 hour

1

1

-

2

2

-

2

2

-

24 hours

2

2

l

2

1

-

2

1

-

48 hours

2

2

l

2

2

-

2

2

-

72 hours

1

2

l

2

2

l

2

2

l

7 days

0

0

l

0

0

l

1

0

l

14 days

0

0

-

0

0

-

0

0

-

1Sentinel.

Comments:l.Scaliness.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An in vivo skin irritation tudy was performed according to OECD/EC guidelines and GLP prinicples. The average score at 24, 48 and 72 hours is for erythema and edema a 2 and 1.7, respectively, in two out of three animals and a 1.7 and 2, respectively in one animal. According to the CLP Regulation (EC) 1272/2008, no classification for skin irritation is required.
Executive summary:

In a study performed according to OECD 404 test guideline, three rabbits were exposed to the substance by application onto clipped skin using semi-occlusive dressing. Skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test substance. Four hours exposure to 0.5 mL of Ditetrahydrofurylpropane resulted in well-defined erythema and slight oedema in the treated skin-areas of the three rabbits. Scaliness was seen 24 hours, 48 hours, 72 hours and/or 7 days after exposure. The skin irritation had completely resolved within 14 days after exposure in all animals. There was no evidence of a corrosive effect on the skin. 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.  Based on these results it is concluded that the test substance is not corrosive and not irritant to the skin.