Registration Dossier

Administrative data

Description of key information

Eye irritation: Not irritating

Skin irritation: Not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From May 31 to June 03, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 1. Further information was attached at section 13
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH Chemisch-pharmazeutische Fabrik D-88397 Biberach
- Weight at study initiation: between 2190 to 2310 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet - Nafag No. 814, Gossau, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: A gauze patch (approx. 12-16 cm2) bearing 0.5 g of test substance


Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: gauze patch
Irritation parameter:
erythema score
Basis:
animal: 071/M, 197/M, 187/M
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal: 071/M, 197/M, 187/M
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No deremal effects observed
Interpretation of results:
other: Not classified according to Regulation 1272/2008
Conclusions:
Not irritating.
Executive summary:

Method:

The Skin irritation was determined in an irritation test on rabbits according to the OECD Guideline 404 and the EU Method B.4.

Result:

Not irritating

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From June 7 to July 5, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 1. Further information was attached at section 13
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH Chemisch-pharmazeutische Fabrik D-88397 Biberach
- Weight at study initiation: between 2040 to 2340 g
- Housing: housed individually in metal cages
- Diet: standard rabbit pellet - Nafag No. 814, Gossau, Switzerland ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 ° C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day.
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 mg was placed into the conjunctival sac of the left eye
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
animal: 277/M, 570/F, 468/F
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No ocular effects observed
Irritation parameter:
iris score
Basis:
animal: 277/M, 468/F
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No ocular effects observed
Irritation parameter:
iris score
Basis:
animal: 570/F
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
REDNESS
Basis:
animal: 277/M
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
REDNESS
Basis:
animal: 570/F
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
REDNESS
Basis:
animal: 468/F
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: 277/M, 468/F
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 570/F
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Interpretation of results:
other: Not classified under Regulation 1272/2008
Conclusions:
Not irritating
Executive summary:

Method:

The eye irritation was determined in an irritation test on rabbits according to OECD Guideline 405 and EU Method B.5.

Observation:

Under the experimental conditions employed the test substance induced reactions of the iris and conjunctiva when instilled into the conjunctival sac of albino rabbit eyes. These effects are fully reversible within 7 days and the mean value of the readings 24 to 72 hours after instillation are below the threshold of significance.

 

Result:

Not irritating

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

No studies on the "Irritation" are available for the substance in itself.

Nevertheless studies have been conducted with an analogue molecule (Similar Substance 01). Further information are reported in the Read Across justification attached to section 13.

Different available tests may be considered, that gives information on Skin and Eye Irritation.

Skin Irritation

The test substance was evaluated in the key study for its skin irritation potential according to the OECD Guideline 404 and the EU Method B.4..

The mean score of observed values of irritation/corrosion , calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the substance is considered as not irritant.

The same result was achieved with the Supporting test conducted according to EPA OPP 81-5 (Acute Dermal Irritation), conducted with six rabbits. One animal showed erythema and edema not fully reversible within the 7 days observation period, but as the observation period was shorter than 21 days, it was not possible to determine the real reversibility of the symptoms.

Further confirmation on the result obtained with the two tests described above, is given by a test conducted according to the Food and Drug Administration of the U.S.A. in The , Federal Register (17 September 1964 § 191.11), with six rabbits, which showed no irritation after application of 0.5 g of test substance ( 40% of dye).

 

Eye Irritation

The test substance was evaluated in the key study for its eye irritation potential according to the OECD Guideline 405 and EU Method B.5.

The mean score of observed values of irritation/corrosion , calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the test item does not show any eye irritation potential.

The same result was achieved with the Supporting test conducted according to the Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study", Federal Register, Vol. 43 No. 163 August 22, 1978. 100 mg of the test substance was instilled in the in the conjunctival sac of the left eye of six the rabbits. The mean score value calculated for each rabbit, after 24, 48, 72 hours, was, as above , under the limit of classification.

Justification for classification or non-classification

SKIN IRRITATION/CORROSION

According to the CLP Regulation (EC n. 1272/2008) a substance shall be classified as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2,3 - ≤ 4,0.

Category 2:

- Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

- Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

- In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical eposure in a single animal but less than the criteria above.

The substance is not classified as skin irritant because in the performed tests it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.

 

EYE IRRITATION

According to the CLP Regulation (EC n. 1272/2008), a susbtance shall be classified as Irritating to eyes (Category 2) when applied to the eye of an animal, produces:

- at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

The test substance does not meet the requirements to be classified in Category 2, therefore it is not classified.