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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Testing procedures do not follow an official European testing guideline, nevertheless the studies are well documented and the results scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf.
- Weight at study initiation: 2-3 kg.
- Housing: individually in metal cages.
- Diet: rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water: water ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ±3 °C
- Humidity: 55 ± 15 %
- Air changes: 15 air change/h.
- Photoperiod: 12/12 hrs dark / hrs light.
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skin.
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
- Application: gauze patches soaked with 0.5 ml of the test material were applied to the abraded and intact skin.
Duration of treatment / exposure:
The dressings were removed after 24 hours.
Observation period:
7 days
Number of animals:
6 (3 males and 3 females).
Details on study design:
TEST SITE
- Area of exposure: before treatment, the entire back and the flank of the rabbits were shaved with an electric clipper. Immediately before treatment, the skin on one side was slightly scarified.
- Type of wrap if used: the gauze patches with substance were covered with an impervious material and were fastened to the body of the rabbit with adhesive tape.

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
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
The calculated primary irritation index was 2.33.

INTACT skin reactions

Animal/sex Reaction 24 hrs 48 hrs 72 hrs 4 days 7 days Mean 24, 48 and 72 hrs
55 M Erythema 2 2 2 1 0 2.00
56 M Erythema 2 2 2 2 0 2.00
57 M Erythema 2 2 2 1 0 2.00
58 F Erythema 2 2 2 1 0 2.00
59 F Erythema 2 1 1 0 0 1.33
60 F Erythema 2 1 1 0 0 1.33
55 M Oedema 1 1 1 0 0 1.00
56 M Oedema 1 2 1 1 0 1.33
57 M Oedema 1 1 1 0 0 1.00
58 F Oedema 1 0 0 0 0 0.33
59 F Oedema 1 0 0 0 0 0.33
60 F Oedema 1 0 0 0 0 0.33

ABRADED skin reactions

Animal/sex Reaction 24 hrs 48 hrs 72 hrs 4 days 7 days Mean 24, 48 and 72 hrs
55 M Erythema 2 2 1 1 0 1.50
56 M Erythema 2 1 1 0 0 1.00
57 M Erythema 0 0 0 0 0 0.00
58 F Erythema 2 2 2 0 0 1.50
59 F Erythema 2 1 1 0 0 1.00
60 F Erythema 2 1 1 0 0 1.00
55 M Oedema 2 1 1 1 0 1.33
56 M Oedema 1 1 0 0 0 0.67
57 M Oedema 0 0 0 0 0 0.00
58 F Oedema 2 1 0 0 0 1.00
59 F Oedema 1 0 0 0 0 0.33
60 F Oedema 1 0 0 0 0 0.33
Interpretation of results:
not irritating
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not irritating.
Executive summary:

Method

The skin irritation potential was assessed with test procedure similar to those outlined in the EPA OPP 81-5 (Acute Dermal Irritation) guideline.

Results

Primary irritation index was estimated to be 2.33, therefore the substance resulted moderate irritating.

Discussion and conclusion

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

Mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema/eschar and oedema reactions.

In conclusion, the test item can be classified as NON irritating, according to the CLP (EC 1272/2008) 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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Testing procedures do not follow an official European testing guideline, nevertheless they are well documented and scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Principles of method if other than guideline:
The procedure used is based, but not in every part identical with the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study".
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf.
- Weight at study initiation: 2-3 kg.
- Housing: individually in metal cages.
- Diet: rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water: water ad libitum.
- Acclimation period: 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C.
- Humidity: 55 ± 15 %.
- Air changes: 15 air changes/h.
- Photoperiod: 12 hours light/day.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
- Concentration: undiluted.

Duration of treatment / exposure:
single exposure; in 3 of the 6 rabbits approximately 30 seconds after the treatment the treated eye was washed out.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 (3 male and 3 female).
Details on study design:
APPLICATION
The test material was inserted in the conjunctival sac of the left eye of the rabbits and the lids were gently closed for 15 seconds. The right eye was not treated and served as an untreated control.

REMOVAL OF TEST SUBSTANCE
- Washing: with 10 ml of sterile physiological saline.
- Time after start of exposure: in 3 of the 6 rabbits approximately 30 seconds after the treatment the treated eye was flushed.

TOOL USED TO ASSESS SCORE: hand-slit lamp.

SCORING SYSTEM
The eye irritation was assessed at 24, 48, 72 hours and 4 and 7 days after treatment.
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 #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.67
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible

Non-washed eye results

Exposure Cornea Iritis Conjunctival
redness chemosis

Animal no. 1 (eyes not washed out)
24 hrs 0 0 0 1
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

 0.00 0.00 0.00 0.33

Animal no. 2 (eyes not washed out)
24 hrs 0 0 1 0
48 hrs 0 0 1 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

 0.00 0.00 0.67 0.00

Animal no. 3 (eyes not washed out)
24 hrs 0 0 1 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

 0.00 0.00 0.33 0.00

Washed eye results

Exposure Cornea Iritis Conjunctival
redness chemosis

Animal no. 1 (eyes washed out)
24 hrs 0 0 1 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.33 0.00

Animal no. 2 (eyes washed out)
24 hrs 0 0 0 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.00 0.00

Animal no. 3 (eyes washed out)
24 hrs 0 0 0 1
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.00 0.33
Interpretation of results:
not irritating
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not irritating
Executive summary:

Method

The eye irritation potential was assessed on the basis of the procedures reported in the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study", Federal Register, Vol. 43 No. 163 August 22, 1978.

Results

Under the conditions the test substance was found to cause minimal irritation when applied to the rabbit eye mucosa.

The calculated primary irritation index were: 0.8 in unrinsed eyes and 0.3 in rinsed eyes.

Discussion and conclusion

The criteria for the evaluation of the eye irritation potential followed in the test are different from those reported into the OECD guideline. The scoring system used for the corea opacity and degree of density, for the iris and conjunctivae redness and chemosis is the same of that reported into the OECD, but the timing for the removal of the substance are very different (30 seconds in the current study and 1 hours in the OECD). Nevertheless, because the raw tables 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 for both rinsed and unrinsed eyes were lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals.

Therefore the substance does not meet the criteria to be classified as eye irritating.

In conclusion, the test item can be classified as NON irritating, according to the CLP (EC 1272/2008) Regulation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Eight in vivo studies are available assessing skin irritation for 16090-02-1. Some of them were performed on a substance of good purity. All results are reported following a scoring system different from the European one, but for some of them the original report reported the tables, making possible to calculate the irritation score according to CLP Regulation. All studies are consistent and indicate no irritant effects for any of the samples.

Seven in vivo studies are available assessing eye irritation. Some of them were performed on a substance of good purity. In some cases the results are reported following a scoring system different from the European one, but for some of them the original raw tables are included, making possible to calculate the irritation score according to CLP Regulation. All studies are consistent and indicate no irritant effects for any of the samples.

Justification for selection of skin irritation / corrosion endpoint:

Test procedures does not follow an official European testing guideline, nevertheless are well documented and scientifically acceptable. The substance testes has an active ingredient of 83 %.

Justification for selection of eye irritation endpoint:

Test procedures does not follow an official European testing guideline, nevertheless are well documented and scientifically acceptable. The substance testes has an active ingredient of 83 %.

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. Also in the cases in which the reaction scores at 48 hours was not reported, the mean values scored are in all cases 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.

According to the Regulation EC 1272/2008 (CLP) substances the 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.

In all the studies presented the criteria for the evaluation of the eye irritation potential followed in the test are different from those reported into the OECD guideline, nevertheless the scoring system used to record the effects are the same of that reported into the OECD. Because the raw tables are included into the studies, it is possible to re-evaluate the results according to the CLP Regulation (EC 1272/2008).

It has to be noted that there the timing for the removal of the substance in the studies reported is very different from that indicated into the OECD guideline (30 seconds in the current studies and 1 hours in the OECD); nevertheless, the mean values from gradings at 24, 48 and 72 hours for both rinsed and unrinsed eyes are lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals. Therefore the substance does not meet the criteria to be classified as eye irritating.

In conclusion, the available experimental data are adequate for classification and labelling.

The substance is not classified for the eye/skin irritation, according to the CLP Regulation (EC 1272/2008).