Registration Dossier

Administrative data

Description of key information

1-Vinyl-imidazole was found not to be irritating to the rabbit skin under semi-occlusive conditions, although it was tested to be corrosive to the skin in vitro.

The test substance was found to be corrosive to the rabbit eye and a single application of 10% 1-vinyl-imidazole to the chorionallantoic membrane of eggs caused intravascular coagulation and haemorrhages.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A. (01540 Vonnas, France)
- Age at study initiation: 7-8 months
- Weight at study initiation: 3.91-4.35 kg
- Housing: individually in stainless steel wire mesh cages with grating, floor area : 3000 cm2
- Diet: Kliba-Labordiät, Kaninchen & Meerschweinchenhaltung "GLP" (Provimi Kliba SA, Kaiseraugst, Basel, Switzerland), ca. 130 g/animal per day
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
14 days but study was discontinued after 7 days because all animals were free of findings
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsolateral part of the trunk
- % coverage: 2.5 x 2.5 cm
- Type of wrap: semiocclusive (test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: with Lutrol and Lutrol/water 1:1
- Time after start of exposure: after 4 hours of exposure

SCORING SYSTEM: as described in OECD guideline 404
Irritation parameter:
erythema score
Remarks:
1 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Remarks:
1 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: no edema observed
Irritation parameter:
erythema score
Remarks:
4 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
4 h exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
4 h exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
4 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: no edema observed
Irritation parameter:
edema score
Remarks:
4 h exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: no edema observed
Irritation parameter:
edema score
Remarks:
4 h exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: no edema observed
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Method: BASF test: 50 µl of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed up to 24 days after treatment. Findings were recoded daily.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Vehicle:
water
Controls:
other: untreated eyes of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.05-0.1 mL
- Concentration (if solution): undiluted and 10, 5, 1 and 0.1% aqueous solution
Duration of treatment / exposure:
single application
Observation period (in vivo):
up to 24 days
Number of animals or in vitro replicates:
2 for undiluted test substance, 1 per aqeous solution (10, 5, 1 and 0.1%)
Irritation parameter:
other: severe redness of the conjunctivae, secretion of pus, bleeding of the conjunctivae, ciliary injection and severe oedema
Basis:
animal: 2 animals
Reversibility:
other: Corneal cloudiness was still reported at the end of the observation period (d24).
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
The pure substance caused severe redness of the conjunctivae, secretion of pus, bleeding of the conjunctivae, ciliary injection and severe oedema. Cloudiness of the cornea was still reported at the end of the observation period (day 24).
The 10 and 5% solutions caused redness and swelling of the conjunctivae, which had disappeared 2 to 3 days after exposure.
The 1 and 0.1% solutions caused slight redness of the conjunctivae, which had disappeared 1 day after exposure.
Interpretation of results:
corrosive
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
HET-CAM in vitro corrosion test (alternative method to study the potential of serious damage to the eyes/mucous membranes in incubated hen eggs). The study was performed according to the methods described in the following publications:
- Lüpke N.P. (1985): Hen's Egg Chorio allantoic Membrane Test for Irritation Potential. Fd. Chem. Toxic. 23, pp. 287 - 291.
- Spielmann, H. (1995): HET-CAM Test. In: Methods in Molecular Biology, 43 (eds.: O'Hare, S. and Atterwill, C. K.) pp. 199 - 204.
- Spielmann, H. et al. (1996): Results of a Validation Study in Germany on Two In Vitro Alternatives to the Draize Eye Irritation Test the HET-CAM Test and the 3T3 NRU Cytotoxicity Test. ATLA 24, pp. 741 - 858.
GLP compliance:
yes (incl. certificate)
Species:
other: chorionallantoic membrane of fertilized hen eggs
Strain:
other: White Leghorn
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH (Exertal, Germany)
- Age at study initiation: fresh, fertilized hen eggs
- Weight at study initiation: 53.7 - 59.9 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 37.5 (± 0.5), breeding in an incubator
- Humidity (%): 62.5 (± 7.5)
Vehicle:
water
Remarks:
doubly distilled
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amounts applied: 0.3 mL unchanged solution or 0.3 mL of a 10% solution in water
Duration of treatment / exposure:
Single application
Observation period (in vivo):
Up to 3.5 minutes
Number of animals or in vitro replicates:
3 eggs per dose
Details on study design:
SCORING SYSTEM:
After application of the test substance the chorionallantoic membrane was observed by means of a stereomicroscope until unambiguous irritation reactions were detected or up to a maximum time period of 3.5 minutes, respectively. The time of appearance (in seconds after application) of intravascular resp. extravascular coagulation and, if applicable, other reactions (haemorrhagia, vessel lysis) were determined.
The evaluation of the reactions was performed according to the following grading:
0 = no visible change
1 = slight reaction
2 = moderate reaction
3 = severe reaction

EVALUATION CRITERIA:
The evaluation depends on the solubility of the test substance, the tested concentrations and the time until appearance of unambiguous intravascula coagulation of middle-sized vessels or extravascular coagulation of the treated CAM, respectively. The mean time until appearance of reaction over the eggs of a treatment group was calculated (mean time to coagulation = mtc in seconds).
mtc(10%) = mean time to coagulation of a 10% solution in seconds
mtc(100%) = mean time to coagulation of the unchanged test substance in seconds

Water-soluble test substances
mtc(10%) < 90; risk of serious damage to the eyes
mtc(10%) ≥ 90; no risk of serious damage to the eyes
Usually the result of a 10% aqueous solution is used for evaluation. If the unchanged test substance (mtc100%) is considerable more reactive than the 10% solution, further information on the properties of the test substance or results from structurally related compounds will be taken into account for evaluation.

TOOL USED TO ASSESS SCORE: stereomicroscope
Irritation parameter:
other: mtc(10%) in sec
Value:
> 30 - < 62
Remarks on result:
other: moderate intravascular coagulation in all eggs
Irritation parameter:
other: mth(10%) in sec
Value:
> 25 - < 30
Remarks on result:
other: moderate haemorrhagia
Irritation parameter:
other: mtc(100%) in sec
Value:
> 6 - < 11
Remarks on result:
other: moderate intravascular coagulation in all eggs
Irritation parameter:
other: mth(100%) in sec
Value:
> 3 - < 6
Remarks on result:
other: moderate haemorrhagia
Other effects / acceptance of results:
mtc(10%) - mean time of coagulation of a 10% test solution
mth(10%) - mean time of haemorrhagia of a 10% test solution
mtc(100%) - mean time of coagulation of a 100% test solution
mth(100%) - mean time of haemorrhagia of a 100% test solution

With a mtc(10%) < 90, a risk of serious damage to the eyes is concluded to be possible.

Interpretation of results:
other: severe eye damage in the HET-CAM test
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

1-Vinyl-imidazole was applied to the skin of New Zealand White rabbits for 4 hours (using 2 animals at all exposure durations) under semi-occlusive conditions and observed for 14 days in a GLP compliant OECD404 study (2005; RL2). The exposure period of 4 hours caused moderate erythema in all animals immediately and 1 hour after removal of the patch. Moderate erythema persisted in one animal up to 24 hours and decreased to slight after 48 and 72 hours. In two animals moderate erythema decreased to slight after 24 hours and persisted up to 48 hours. No other cutaneous reactions were observed during the study. The cutaneous reactions were reversible in two animals within 72 hours and in one animal within 7 days after removal of the patch. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.7 and 1.3 for erythema and 0.0 for edema. The study was discontinued after 7 days because all animals were free of findings. 1-Vinyl-imidazole was judged not irritating to the skin.

In a pre-GLP and pre-guidline study in vivo (1953; RL2), 2 rabbits were exposed occlusively for 20 h to the test substance; undiluted, 50, 10 and 5 % aqueous solution, inducing slight irritation. The study was not taken into account for classification due to the worse conditions compared to the OECD404 study above.

In an in vitro corrosivity test (EpiDerm, 2005; RL2) the viability of the test substance treated tissue determined after an exposure of 3 min was 56 % and 12 % after 1 h exposure. This is near the threshold for the evaluation criteria (corrosive / non-corrosive) of 50 % viablilty after 3 min exposure and 20 % after 1 h exposure. The study was not taken into account for classification due to the OECD404 study above.

In conclusion, 1 -vinyl-imidazole is considered to be not irritating to the skin because of the results of the OECD404 study above.

 

Eye irritation

1-Vinyl-imidazole was tested in a HET-CAM in vitro corrosion test under GLP-compliant conditions (2005; RL2). The chorionallantoic membrane of the eggs treated with a 10 % test substance solution in double distilled water showed moderate (grade 2) intravascular coagulation in all eggs after 30 - 62 seconds (mean: 51 seconds). Moderate haemorrhages (grade 2) were observed in all eggs after 25 - 30 seconds (mean: 28 seconds). The unchanged test substance caused moderate (grade 2) intravascular coagulation in all eggs after 6 - 11 seconds (mean: 9 seconds). Moderate (grade 2) haemorrhages were observed in all eggs after 3 - 6 seconds (mean: 4 seconds).

Supportingly, in a pre-GLP and pre-guideline in vivo study (1953, RL2) the single application of the undiluted test substance to two rabbit eyes induced severe redness of the conjunctivae, secretion of pus, bleeding of the conjunctivae, ciliary injection and severe oedema. Cloudiness of the cornea was still reported at the end of the observation period (day 24). Application of an aqueous solution of the test substance (10, 5, 1 or 0.1%; one animal each) induced redness and swelling for 2 to 3 days or only slight redness for 1 day.

Based on the results of the in vitro study and its evaluation criteria and the supporting effects of the undiluted substance in the in vivo study, 1-vinyl-imidazole is considered to cause severe eye damage.

Justification for classification or non-classification

Based on the available data, 1-vinyl-imidazole needs to be classified for risk of serious damage to the eyes according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 (Eye Damage 1, H318).