[Name confidential or not available]

Endpoint summary

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:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Certified by BAM according to DIN EN 45001.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Number: 3 animals,
- Average bodyweight: 3.0 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: undiluted (no vehicle) after warming the test material (temperature not specified in the report)

Controls:

not required

Amount / concentration applied:

0.5 mL test material (after warming it) per approx. 6 cm2 skin (2.5 cm x 2.5 cm) per animal

Duration of treatment / exposure:

4 hours

Observation period:

7 days post patch removal

Number of animals:

3

Details on study design:

TEST SITE PREPARATION

Samples of 0.5 mL of the warmed test material were applied to the shaved skin of albino rabbits and covered with gauze squares of the size 2.5 cm x 2.5 cm on the skin. Patches were fixed with adhesive plaster. Untreated shaved skin served as controls.

TREATMENT PERIOD AND REMOVAL OF TEST MATERIAL

Semi-occlusive treatment lasted 4 hours. Then the dressings were removed and residual test substance was dabbed off the skin with a wet towel.

Time points of skin evaluation:

The treated skin patches were evaluated at 1 hour post patch removal and at 24, 48 and 72 h and 7 days post patch removal. Only differences from controls were considered to be positive reactions. The scoring system for the grading of skin reactions is listed in Table 1 (next field below).

Irritation parameter:

erythema score

Remarks:

as defined in table 1

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

erythema score

Remarks:

as defined in table 1

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

erythema score

Remarks:

as defined in table 1

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Remarks:

as defined in table 1

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Remarks:

as defined in table 1

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Remarks:

as defined in table 1

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritant / corrosive response data:

In each animal, erythema, scab or edema formation was not evident at any observation time point of the study.

Other effects:

Mortality or behavioural changes indicative of an adverse effect were not evident. Weighing of the animals at 7 days post treatment revealed normal body weight gain.

Interpretation of results:

other: not irritating

Remarks:

not classified according to Regulation (EC) 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:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Certified by BAM according to DIN EN 45001.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Number: 3 animals,
- Average bodyweight: 3.2 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
Prior to dosing the animals were starved for 16 hours.
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Vehicle:

other: undiluted (no vehicle) after warming the test material to 37°C

Controls:

not required

Amount / concentration applied:

After warming undiluted test material (no vehicle) to 37°C, 0.1 ml of it was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

There was no mentioning in the report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 7 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.

Observation period (in vivo):

7 days post instillation

Number of animals or in vitro replicates:

3 adult rabbits

Details on study design:

Eyes were evaluated for occular lesions using ultraviolet light. The numerical scoring system listed in Table 1 in the field below was adopted. Time points of evaluation were: Pretest (prior to treatment), 1, 2, 4, 8, 24, 48, 72 and 96 hours after administration and daily thereafter until 7 days after administration. Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification or non-classification.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Irritation parameter:

other: lacrimation score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Chemosis was not evident during the study

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Chemosis was not evident during the study

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Chemosis was not evident during the study

Irritant / corrosive response data:

Corneal and iridic lesions and chemosis were not evident throughout the study. Conjunctival redness grade 1 and lacrimation usually grade 1, in one incidence grade 2, were seen in all treated eyes at 1, 2, 4 and/or 8 hours post instillation of the test substance. Conjunctival redness had completely disappeared in one of the animals by 8 hours post instillation and in the other two by 24 hours post instillation and lacrimation had completely disappeared in two of the animals by 8 hours post instillation and in the other one by 24 hours post instillation. Daily examination of the eyes from 24 hours until 7 days post instillation did not reveal any findings.

Other effects:

Daily determination of bodyweight did not reveal any test related changes. Bodyweight gain was normal.

Interpretation of results:

other: not irritating

Remarks:

not classified according to Regulation (EC) 1272/2008

Conclusions:

The outcome of the present study does not necessitate any classification or labelling regarding eye irritation according to REGULATION (EC) 1272/2008. The minor findings noted were fully reversible and within the category “not irritating to eyes”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In view of the absence of any effects during the skin irritation study and the absence of relevant effects during the eye irritation study, the attained results do not necessitate any classification and labelling regarding skin or eye irritation according to Regulation (EC) 1272/2008.