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Description of key information

Non skin irritating

Non 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
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
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: all animals were housed in single cages.
- Diet: a standard laboratory diet was provided ad libitum. The batch of the diet used for the study was analysed for chemical and microbiological contaminants.
- Water: ad libitum.
- Acclimation period: all animals were acclimatized to the environment for a period of five days prior to the start of the study.
- Health check: prior to the test, the eyes of each rabbit were examined for pre~existing casual injury.

ENVIRONMENTAL CONDITIONS
- Temperature: the room temperature was maintained within a median of 23 ± 2°C recorded by a maximum-minimum thermometer.
- Humidity: 50 ± 10 % was measured by a hygrometer.
- Air changes: the rate of air exchange was maintained at approximately 15 changes/hour.
- Photoperiod: the light/dark cycle was 12 hours.
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded skin
Vehicle:
other: dimethylsulphoxide
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amout: 1.0 ml
- Vehicle: test item was diluted in DMSO to a 50 % suspension.
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
Three males and three females
Details on study design:
TEST SITE
- Area of exposure: 24 hours prior to the test, the skin on the back of the animals was clipped by means of an electric clipper and the skin was investigated for pre-existing injuries. Test item was introduced under a square patch of surgical gauze measuring 6.5 cm2.
- Type of wrap if used: the animals were immobilized with patches secured in place by a plastic patch and the entire trunk was wrapped with a plasic sIeeve for the 24 hour exposure.

SCORING SYSTEM:
The irritation was measured by patch test technique on the intact and abraded skin.
After 24 hours, the patches were removed and the resulting reactions were evaluated on the basis of the code of Federal Regulations, Title 16, Section 1500.41.
Irritation parameter:
erythema score
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The irritation score was 0.0
The substance can be considered as non irritating, according to the ETAD-Subcommittee for Toxicology.
Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
Non irritating
Executive summary:

Six rabbits (three males and three females) were used to test the skin irritation potential of the substance. The abraded and intact skin of rabbits was treated with 1.0 ml of test item, which was used diluted in 50 % DMSO. The irritation was measured by patch test technique on the intact skin. After 4 hours, the patches were removed and the resulting reactions were evaluated on the basis of the code of Federal Regulations, Title 16, Section 1500.41.

None of the animals showed any observable response to treatment throughout the 72 hours observation period.

The irritation score was 0.0 and the substance has been judged to be non irritating, according to the ETAD-Subcommittee for Toxicology.

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 in accordance with the CLP Regulation (EC) No 1272/2008.

None of the animals showed any observable response to treatment throughout the 72 hours observation period, thus it can be concluded that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.

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
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
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: all animals were housed in single cages.
- Diet: a standard laboratory diet was provided ad libitum. The batch of the diet used for the study was analysed for chemical and microbiological contaminants.
- Water: ad libitum.
- Acclimation period: all animals were acclimatized to the environment for a period of five days prior to the start of the study.
- Health check: prior to the test, the eyes of each rabbit were examined for pre~existing casual injury.

ENVIRONMENTAL CONDITIONS
- Temperature: the room temperature was maintained within a median of 23 ± 2°C recorded by a maximum-minimum thermometer.
- Humidity: 50 ± 10 % was measured by a hygrometer.
- Air changes: the rate of air exchange was maintained at approximately 15 changes/hour.
- Photoperiod: the light/dark cycle was 12 hours.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg of the test material was placed into the conjunctival sac of the right eyes of the animals.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Nine rabbits: three males and females unwashed eyes and three males whose eyes were washed.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: in three animals, the treated eye was rinsed with 20 ml lukewarm water.
- Time after start of exposure: after half a minute.

SCORING SYSTEM:
The eyes were inspected after 24, 48 and 72 hours. Reading score for ocular lesions were made according to the recommendations of the USA Food and Drug officials, published in 1959 (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics).

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Irritation parameter:
cornea opacity score
Remarks:
unwashed eyes
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
< 1
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
unwashed eyes
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
< 1
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
unwashed eyes
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
< 2
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Remarks:
unwashed eyes
Basis:
animal: 6/6
Time point:
24/48/72 h
Score:
< 2
Reversibility:
fully reversible within: 72 hrs
Irritant / corrosive response data:
The irritation score resulted to be 0.67.
The substance can be considered as non irritating, according to the ETAD-Subcommittee for Toxicology.

Summary of eyes unwashed

Animal N. Reaction 24 hrs 48 hrs 72 hrs Mean 24/48/72 hrs
Male 201 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 0 0 0 0
Conjunctival redness 0 0 0 0
Male 202 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 0 0 0 0
Conjunctival redness 0 0 0 0
Male 203 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 1 0 0 0.33
Conjunctival redness 1 1 0 0.67
Male 204 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 0 0 0 0
Conjunctival redness 0 0 0 0
Male 205 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 0 0 0 0
Conjunctival redness 1 0 0 0.33
Male 206 Cornea opacity 0 0 0 0
Iris 0 0 0 0
Conjunctival swelling 0 0 0 0
Conjunctival redness 1 0 0 0.33

Eye unwashed

Animal N. Reaction 24 hrs 48 hrs 72 hrs
Male 201 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Male 202 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Male 203 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 1 0 0
(E) swelling 1 0 0
(F) redness 1 1 0
(D+E+F)x2 6 2 0
Male 204 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Male 205 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 1 0 0
(D+E+F)x2 2 0 0
Male 206 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 1 0 0
(D+E+F)x2 2 0 0

Eye washed

Animal N. Reaction 24 hrs 48 hrs 72 hrs
Male 207 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Male 208 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Male 209 Cornea (A) density 0 0 0
(B) area 0 0 0
AxBx5 0 0 0
Iris (C) 0 0 0
Cx5 0 0 0
Conjunctival (D) secretion 0 0 0
(E) swelling 0 0 0
(F) redness 0 0 0
(D+E+F)x2 0 0 0
Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
Non irritating
Executive summary:

Nine rabbits were used to test the eye irritation potential of the substance. 100 mg of the undiluted test material were placed into the conjunctival sac. The eyes were inspected after 30 minutes, 24, 48 and 72 hours. Reading scores for ocular lesions were made according to the recommendations of the USA Food and Drug officials, published in 1959 (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics).

The irritation score resulted to be 0.67. The substance can be considered as non irritating, according to the ETAD-Subcommittee for Toxicology.

Conclusion

Although 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 is the same. Because the raw tables are included into the study report, it is possible to re-evaluate the results according to the CLP Regulation (EC) No 1272/2008.

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis, lower than 2 for both conjunctival redness and chemosis, in all the tested animals, thus the substance does not meet the criteria to be classified as eye irritating, according to the CLP Regulation (EC) No 1272/2008.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN IRRITATION

Three male and three female rabbits were used to test the skin irritation potential of the substance. The abraded and intact skin of rabbits was treated with 1.0 ml of test item, which was used diluted in 50 % DMSO. The irritation was measured by patch test technique on the intact skin and the resulting reactions were evaluated on the basis of the code of Federal Regulations, Title 16, Section 1500.41. None of the animals showed any observable response to treatment throughout the 72 hours observation period. The irritation score was 0.0 and the substance has been judged to be non irritating, according to the ETAD-Subcommittee for Toxicology.

EYE IRRITATION

Nine rabbits were used to test the eye irritation potential of the substance. 100 mg of the undiluted test material were placed into the conjunctival sac. Reading scores for ocular lesions were made according to the recommendations of the USA Food and Drug officials, published in 1959 (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics). The irritation score resulted to be 0.67. The substance can be considered as non irritating, according to the ETAD-Subcommittee for Toxicology.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 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 the available experiment, the 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.

According to the CLP Regulation (EC) No 1272/2008, serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance, which is not fully reversible within 21 days of application.

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis, lower than 2 for both conjunctival redness and oedema, in at least two of three tested animals.

In conclusion, the substance does not meet the criteria to be classified for the eye/skin irritation, according to the CLP Regulation (EC) No 1272/2008.

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