Registration Dossier

Administrative data

Description of key information

The test item cyclohexylvinylether was tested for skin irritation/corrosion properties in a non-GLP study equivalent or similar to OECD 404 with rabbits. The test item was classified irritating to the skin. These findings were confirmed by an in vitro skin corrosion/irritation study (GLP study).
The test item cyclohexylvinylether was tested for eye irritation properties in a GLP study according to OECD 405 with rabbits. Cyclohexylvinylether was found to be not irritating to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1964-07-06 to 1964-08-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP. Equivalent or similar to OECD 404
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
No data
Duration of treatment / exposure:
The test item was applied to the dorsal skin and the ear of the test animals.
Times of exposure were as follows:
Dorsal skin: 1 min, 5 min, 15 min, 20 h;
Ear: 20 h;
Observation period:
8 days
Number of animals:
2 animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap: occlusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing : No


SCORING SYSTEM:
ER = erythema
ED = edema
e = extending beyond the area of exposure
SC = scaling
+ = slight
++ = severe
+++ = very severe
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Reversibility:
other: reversible within 8 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
2.33
Max. score:
4
Reversibility:
other: reversible within 8 d
Irritant / corrosive response data:
The test substance caused slight to severe erythema and edema which were extending beyond the area of exposure after 24 hours observation. After the 8 days observation, the animals showed slight erythema and severe scaling on the dorsal exposure sites.
Other effects:
Severe erythema and skin hemorrhages were detected on the ears of the test animals after 24 hours. After 8 days observation, severe scaling was detetctable on the ears of the test animals.
Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-08-18 to 2011-12-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Commission Regulation (EC) No 440/2008 of 30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 405
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Stolzenseeweg 32 – 36, 88353 Kisslegg
- Age at study initiation: ca. 9 weeks
- Weight at study initiation: 2.0 kg – 2.3 kg
- Housing: Single housing, Terulan cages, Ehret GmbH, A-3430 Tulln, 65 cm x 65 cm bottom area, 50 cm height.
- Diet: Ssniff K-H maintenance diet for rabbits (item V-2333-000), ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany.
- Water: Tap water from an automatic watering system ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C +/- 3 °C
- Humidity: 30 – 70 %
- Air changes: 12 per hour
- Photoperiod: 12 h dark/ 12 h light (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

IN-LIFE DATES: From: 2011-08-30 To: 2011-09-16
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: About 24 hours after application of the test item the treated eye of the animal(s) was rinsed with 3 to 6 mL of warm tap water for 1 to 2 minutes using a syringe with a blunt probe.

SCORING SYSTEM: according to the quoted guidelines.

TOOL USED TO ASSESS SCORE: eyes were examined using an otoscope lamp. Additional eye examination was performed 24 h after application with the instillation of a fluorescein solution.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
The ocular reactions were assessed at approximately 1, 24, 48 and 72 hours after application.
The cornea and the iris were not affected in any animal at any examination timepoint.
Slight conjunctival redness (grade 1) was noted in all animals from 1 hour after application until 48 hours p.a. at the latest.
Slight conjunctival chemosis (grade 1) was noted in all animals only 1 hour after application and in one animal 1 h and 24 hours p.a.
Slight discharge (grade 1) was noted in all animals only 1 hour after application.
The ocular reactions were reversible in all animals within 72 hours after application.
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity, 0.0, 0.0 and 0.0 for iris lesions, 0.0, 0.7 and 0.3 fo redness of the conjunctiva and 0.0, 0.3 and 0.0 for chemosis, respectively.
Considering the described ocular reactions as well as the average score for irritation, the test itemis not irritating to eyes under the conditions of this test.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

The test item cyclohexylvinylether was tested for skin irritation/corrosion properties in a non-GLP study equivalent or similar to OECD 404 with rabbits. The test item was applied undiluted in a dose of 5 mL per animal to the dorsal skin and ear of two albino Vienna white rabbits. Exposure duration was 1 min, 5 min, 15 min, 20 hours. The test substance caused slight to severe erythema and edema which were extending beyond the area of exposure after 24 hours observation. After the 8 days observation, the animals showed slight erythema and severe scaling on the dorsal exposure sites.

The test item was classified irritating to the skin (BASF, 1964).

The test item cyclohexylvinylether was tested for skin corrosion/irritation potential in an in vitro GLP study according to OECD 431 /439 in the EpiDermTM Skin Corrosion / Irritation Test by a single topical application of 50 μL (corrosion test) or 30 μL (irritation test) of the test substance to a reconstructed three dimensional human epidermis model (EpiDerm™). Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability.

The EpiDerm™ skin corrosivity/irritation test showed the following results:

The test substance is not able to reduce MTT directly.

Corrosion test: The mean viability of the test-substance treated tissues determined after an exposure period of 3 minutes was 98%, and it was 72% after an exposure period of 1 hour.

Irritation test: The mean viability of the test-substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 7%.

Based on the observed results it was concluded, that Cyclohexylvinylether shows a skin irritation potential in the EpiDerm™ skin corrosion/irritation test under the test conditions chosen (BASF, 2012).

Eye:

The test item cyclohexylvinylether was tested for eye irritation properties in a GLP study according to OECD 405 with rabbits. The test item was applied undiluted in a dose of 100 mm³ to the right eye of albino Vienna white rabbits. The untreated left eye was used as control. The cornea and the iris were not affected in any animal at any examination timepoint. Slight conjunctival redness (grade 1) was noted in all animals from 1 hour after application until 48 hours p.a. at the latest. Slight conjunctival chemosis (grade 1) was noted in all animals only 1 hour after application and in one animal 1 h and 24 hours p.a. Slight discharge (grade 1) was noted in all animals only 1 hour after application. The ocular reactions were reversible in all animals within 72 hours after application (Seibersdorf, 2011).

In an older supporting study the test item cyclohexylvinylether was tested for eye irritation properties in a non-GLP study equivalent or similar to OECD 405 with rabbits. The test item was applied undiluted in a dose of 50 mm³ to the right eye of albino Vienna white rabbits. The untreated left eye was treated with the same amount used as control. After 1 and 24 hours slight conjunctiva redness was observed. This finding was found to be reversible within 48 h. The test item was not classified for eye irritation (BASF, 1964).


Justification for selection of skin irritation / corrosion endpoint:
Older in vivo study available, which was confirmed by a new GLP and guideline in vitro irritation/corrosion study.

Justification for selection of eye irritation endpoint:
GLP and guideline key study available.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Cyclohexylvinylether was tested for skin and eye irritation. The test item was found irritating to the skin and not irritating to the eye of rabbits. Cyclohexylvinylether was classified Xi - R38, Irritating to the skin - and not irritating to the eye according to Directive 67/548/EEC (DSD) criteria.

Cyclohexylvinylether was classified irritating to skin, cat. 2 - H315: Causes skin irritation - and not irritating to the eye according to Regulation (EC) No 1272/2008 (CLP, GHS) criteria.