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Administrative data

Description of key information

Not skin irritating
Not eye irritating

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:
August, 1975.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test procedure cannot be subsumed under a testing guideline, nevertheless are scientifically acceptable.
Principles of method if other than guideline:
Consumer Product Safety Commission of the U.S.A. in The Code of Federal Regulations, Title 16, Section 1500.41.
GLP compliance:
not specified
Remarks:
Pre GLP.
Species:
rabbit
Preparation of test site:
other: Intact and abraded skin
Vehicle:
water
Amount / concentration applied:
0.5 g mixed with 0.5 ml of distilled water.
Observation period:
72 hours.
Details on study design:
SCORING SYSTEM
Skin reactions were assessed on removal and after 48 and 72 hours and 4 and 7 days.

Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth): 4
Maximum possible: 4

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 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4
Maximum possible: 4
Irritant / corrosive response data:
Very slight to well-defined erythema with very slight to slight oedema was observed in two intact and one abraded site at the 24 hours reading.
Very slight oedema only was observed in one intact and three abraded sites.
Very slight erythema with and without very slight oedema was observed in three intact and four abraded sites at the 72 hours reading.
Discolouration of the skin consisting of blanching and subsequent scab formation was observed in the intact and abraded sites of one animal, and slight hyperkeratinization in the abraded site of one other animal at the 72 hours reading .
One animal did not show any observable response to treatment throughout the 72 hours observation period.

Reaction - Intact skin

Animal/sex Reaction 24 hrs 72 hrs
1 Erythema 0 0
2 Erythema 0 1
3 Erythema 0 0
4 Erythema 1 1
5 Erythema 0 0
6 Erythema 2 1
1 Oedema 1 0
2 Oedema 0 1
3 Oedema 0 0
4 Oedema 2 0
5 Oedema 0 0
6 Oedema 1 1

Reaction - Abraded skin

Animal/sex Reaction 24 hrs 72 hrs
1 Erythema 0 1
2 Erythema 0 1
3 Erythema 0 0
4 Erythema 0 0
5 Erythema 0 1
6 Erythema 2 1
1 Oedema 1 1
2 Oedema 1 1
3 Oedema 0 0
4 Oedema 0 0
5 Oedema 1 1
6 Oedema 1 1
Interpretation of results:
not irritating
Remarks:
Migrated information According to the CLP Regulation. Criteria used for interpretation of results: EU
Conclusions:
Non irritating.
Executive summary:

Method

The skin irritation potential was assessed with test procedure indicated in the Consumer Product Safety Commission of the U.S.A., Code of Federal Regulations, Title 16, Section 1500.41.

Results

Primary irritation index was estimated to be 1.1, therefore, according to the ETAD subcommittee for Toxicology classification, the substance resulted slightly irritant.

Discussion and conclusion

The scoring system criteria used to record the skin reactions followed in the current test is the same of the OECD scoring system, therefore it is possible to re-evaluate the results according to the CLP Regulation (EC 1272/2008), because the raw tables of skin reactions are included into the study report.

Despite the reaction scores at 48 hours were not reported, the mean value scored is reasonably expected to be less than 2.3 for erythema/eschar and for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal.

In conclusion, the test item can be classified as NON irritating, according to the CLP (EC 1278/2008) Regulation.

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:
experimental study
Adequacy of study:
key study
Study period:
August, 1975.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test procedures cannot be subsumed under a testing guideline, nevertheless are scientifically acceptable.
Principles of method if other than guideline:
Consumer Product Safety Commission of the U.S.A. in The Code of Federal Regulations, Title 16, Section 1500.42.
GLP compliance:
no
Remarks:
Pre GLP.
Species:
rabbit
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
44 mg.
Duration of treatment / exposure:
Single instillation.
Observation period (in vivo):
7 days.
Number of animals or in vitro replicates:
6.
Details on study design:
SCORING SYSTEM
Mean J.H. Draize score, for Cornea, Iris and Conjunctivae.

CORNEA:
A Opacity and degree of density (most dense area scored) .
No opacity: 0
Scattered or diffuse area, details of iris clearly visible: 1
Easily discernible translucent areas, details of iris slightly obscured: 2
Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
Opaque, iris invisible: 4

B Area of cornea involved
One quarter (or less) but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4
A x B x 5; Maximum possible score = 80

IRIS:
A Values
Normal: 0
Folds above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive: 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2
A x 5; Maximum possible score = 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal: 0
Vessels definitely injected above normal: 1
More diffuse, deeper crimson red, individual vessels not easily discernible: 2
Diffuse beefy red: 3

B Chemosis
No swelling: 0
Any swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids about half closed to completely closed: 4

C Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs, and considerable area around the eye: 3
(A + B + C) x 2; Maximum possible score = 20
Irritation parameter:
cornea opacity score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 1
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 6/6
Time point:
other: mean 24, 48 and 72 hours
Score:
< 2
Reversibility:
fully reversible
Irritant / corrosive response data:
A corneal opacity was observed in two animals 24 hors after instillation only.
Temporary mild conjunctival inflammation was seen in three animals.
One animal did not show any observable response to treatment throughout the 7 day observation period.
Main Draize score: 1.1.
See table 1 for further details.

Results on rabbit eye

Animal 24 hrs 48 hrs 72 hrs 7 days Mean 24, 48, 72 hrs

Cornea

1 0 0 0 0 0.00
2 0 0 0 0 0.00
3 1 0 0 0 0.33
4 0 0 0 0 0.00
5 0 0 0 0 0.00
6 1 0 0 0 0.33

Irirs

1 0 0 0 0 0.00
2 0 0 0 0 0.00
3 0 0 0 0 0.00
4 0 0 0 0 0.00
5 0 0 0 0 0.00
6 0 0 0 0 0.00

Conjunctivae - Redness

1 0 0 0 0 0.00
2 1 0 0 0 0.33
3 0 0 0 0 0.00
4 1 0 0 0 0.33
5 1 1 1 0 1.00
6 0 0 0 0 0.00

Conjunctivae - Chemosis

1 0 0 0 0 0.00
2 0 0 0 0 0.00
3 0 0 0 0 0.00
4 0 0 0 0 0.00
5 0 0 0 0 0.00
6 0 0 0 0 0.00
Interpretation of results:
not irritating
Remarks:
Migrated information According to the CLP Regulation. Criteria used for interpretation of results: EU
Conclusions:
Non irritating.
Executive summary:

Method

The eye irritation potential was assessed with test procedure indicated in the Consumer Product Safety Commission of the U.S.A., Code of Federal Regulations, Title 16, Section 1500.42.

Results

Main Draize score was 1.1, therefore, according to the ETAD subcommittee for Toxicology classification, the substance resulted non irritant.

Discussion and conclusion

The calculation of results for the evaluation of the eye irritation potential followed in the test is different from that reported into the OECD guideline. Nevertheless the scoring system criteria used to record the eye reactions followed in the current test is the analouge of the OECD scoring system. Since the raw tables of skin reactions are included into the study report, it is possible to re-evaluate the results according to the CLP Regulation (EC 1272/2008).

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals.

In conclusion, the test item can be classified as NON irritating, according to the CLP (EC 1278/2008) Regulation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN IRRITATION

The skin irritation potential was assessed following the test procedure indicated in the Consumer Product Safety Commission of the U. S. A., Code of Federal Regulations, Title 16, Section 1500.41. The primary irritation index was estimated to be 1.1, therefore, according to the ETAD subcommittee for Toxicology classification, the substance resulted slightly irritant.

The scoring system criteria used to record the skin reactions followed in the test is the same of the OECD scoring system, therefore it is possible to re-evaluate the results according to the CLP Regulation (EC 1272/2008) because the raw tables of skin reactions are included into the study report. Despite the reaction scores at 48 hours were not reported, the mean value scored is reasonably expected to be less than 2.3 for erythema/eschar and for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal.

In conclusion, the substance can be considered as non skin irritant (Kynoch R., Ligget P., 1975).

A second study is available; it was performed according to OECD 404 and confirms the outcomes of the key study. Nevertheless, in this case the substance was tested in diluted solution, with a concentration of 34 %.

EYE IRRITATION

The eye irritation potential was assessed following the test procedure indicated in the Consumer Product Safety Commission of the U. S. A., Code of Federal Regulations, Title 16, Section 1500.42. Main Draize score was 1.1, therefore, according to the ETAD subcommittee for Toxicology classification, the substance resulted non irritant. The calculation of results for the evaluation of the eye irritation potential followed in the test is different from that reported into the OECD guideline, nevertheless the scoring system criteria used to record the eye reactions are the analogue to that of the OECD. Since the raw tables of skin reactions are included into the study report, it is possible to re-evaluate the results according to the CLP Regulation (EC 1272/2008). The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals. In conclusion, the test item can be classified as non irritating, according to the CLP (EC 1278/2008) Regulation.

Even though the test substance concentration was low, further two studies are available and support the conclusion of the key study. The first one was performed according to OECD 405 and confirms the outcomes of the key study; in this case the substance was tested in diluted solution, with a concentration of 34 % (Zapatero et al, 1992). In the case of the second one, only a summary of the test with limited details is available. In this case the substance concentration was only of the 33 % (Benz et al, 1972).


Justification for selection of skin irritation / corrosion endpoint:
The test procedure cannot be subsumed under a testing guideline, nevertheless are scientifically acceptable.

Justification for selection of eye irritation endpoint:
The test procedure cannot be subsumed under a testing guideline, nevertheless are scientifically acceptable.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.2 Skin corrosion/irritation section, skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

In all the studies available, the mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in at least 2 of 3 animals for both erythema/eschar and oedema reactions.

According to the CLP Regulation (EC 1272/2008) substances that have the potential to induce reversible eye irritation are classified in Category 2 (irritating to eyes) if, when applied to the eye of an animal, a substance 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 mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals.

In conclusion, the available experimental data are adequate for classification and labelling and the substance is not classified for the eye and skin irritation, according to the CLP Regulation (EC 1272/2008).