Registration Dossier

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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: GLP and guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab.

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrahydro-4-methylene-2-(2-methyl-1-propenyl)-2H-pyran
EC Number:
262-475-2
EC Name:
Tetrahydro-4-methylene-2-(2-methyl-1-propenyl)-2H-pyran
Cas Number:
60857-05-8
Molecular formula:
C10H16O
IUPAC Name:
4-methylidene-2-(2-methylprop-1-en-1-yl)oxane

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Age of the animals at day 0: 6 - 7 months
Acclimatization for at least 5 days before application.
Animal identification: via ear tattoo
Body weight(s) on day 0: 3.73 - 3.88 kg
The animals were housed in fully air-conditioned rooms with a room temperature of 20 - 24°C and a relative humidity between 30 - 70%. The day/night rhythm was 12 h dark and 12 h light.
The animals were housed singly in stainless steel wire mesh cages with grating (floor area: 3000 cm2).
The rabbits were offered a standardized animal laboratory diet (ca. 130 g/animal/day) as well as tap water ad libitum.
- Source: Centre Lago S. A., France

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipping of the fur
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin site of same animal
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3
Details on study design:
Before study start, the application area was investigated for signs of pre-existing skin irritaiton of dense patches of hair. Only animals with intact healthy skin were used.
At least 24 h before application clipping of the fur of the dorsolateral part of the trunk of the animals.
Body weights were determined just before application and after the last reading.
The test article was applied in a single dose to the intact untreated skin. The test substance was removed at the end of the exposure period with Lutrol and Lutrol / water (1:1).
The test patches (2.5 x 2.5 cm) were moistened with 0.5 ml of the undiluted test substance.
Application site: flank
Readings: Immediately after removal of the patches, aprox. 1, 24, 48 and 72 h after removal of the patches and then in weekly intervals maximally up to day 14. A check for dead or moribund animal was made twice each working day and once daily at weekends and on public holidays.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritant / corrosive response data:
Slight to severe erythema and slight to moderate edema, both partly extended beyond the area of exposure, were observed in all animals during the course of the study. Additional findings like scaling, severe scaling partly extended beyond the area of exposure and petechiae were noted in all animals during the observation period.
The cutaneous reactions were not reversible in all animals within 14 days after removal of the patch. Slight erythema and scaling or severe scaling were still present in all animals at study termination (day 14).

Any other information on results incl. tables

 The present data fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and a classification "irritating to skin" (R38) and "skin irritant" (category 2) is warranted (based on mean erythema scores >=2.3).

Applicant's summary and conclusion

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