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Description of key information

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:
other: Study Conducted in accordance with OECD test guideline but no details of whether this study was conducted in accordance with OECD
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals were acclimatised to laboratory conditions for at least 5-days. The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20+3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day. The rabbits received ad libitum standard rabbit pellet and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.

The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschütz ) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by
the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
The patches were loosely covered with an aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape.
Observation period:
The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after
removing the gauze patches according to the OECD scoring system
Number of animals:
3 male rabbits
Details on study design:
An area of at least 36 cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2)
bearing 0.5 ml of the test material was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank.

The patches were loosely covered with aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system

The irritant/corrosive potency of TK 10406 was classified according to the EEC Council Directive 83/467
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
429/M
Time point:
24/48/72 h
Score:
2.67
Reversibility:
fully reversible within: 14-days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
527/M
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
401/M
Time point:
24/48/72 h
Score:
0.167
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
429/M
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
527F/M
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
401/M
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
The reactions were observed within 72 hours after removing the bandages, the observation period was extended to 14 days to determine
the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the
bandages, the test material must be classified as irritant in albino rabbits.

The erythema and edema reactions observed were reversible until the end of the observation period on day 14.
In one animal the treated skin showed a yellowish discoloration 72 hours after patch removal, and on experimental day 7 a white crust was formed
within a small area of the exposed skin. Scaling was observed in this animal from day 7 until the final reading on day 14, and in another animal on
days 7 and 10 of the test.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Executive summary:

An acute Dermal Irritation/Corrosion Study in the Rabbit was conducted in accordance with the OECD 404 test guideline. An area of at least 36 cm was shaved on both flanks of the animals (3 males) approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2) bearing 0.5 ml of the test material was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank. The patches were loosely covered with aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system and the irritant/corrosive potency of the test material was classified according to the EEC Council Directive 83/467. The reactions were observed within 72 hours after removing the bandages, the observation period was extended to 14 days to determine the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the bandages, the test material must be classified as irritant in albino rabbits. After 72 -hours, the mean irritation parameters for erythema and edema were 2.11 and 1.0 respectively. Because the mean values of the readings 24 to 72 hours after application are above the threshold of significance (score 2 for erythema or edema) the substance must be classified as irritant according to the EEC Council Directive 83/467. The erythema and edema reactions observed were reversible until the end of the observation period on day 14.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with guidance but not GLP
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO).
Deviations:
not applicable
GLP compliance:
no
Species:
rabbit
Strain:
other: English Silver
Details on test animals or tissues and environmental conditions:
Rabbits were kept separately in V2A wire cages and fed on NAFAG, Gossau SG, rabbit food and water ad libitum.
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Amounts of 0.1 g. of the test material was introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml. lukewarm water about 30
seconds after treatment.
Duration of treatment / exposure:
7 days
Observation period (in vivo):
Days 1,2,3,4 and 7
Number of animals or in vitro replicates:
Total of six rabbits (3 male and 3 female)
Details on study design:
The procedure adopted was the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO). The substance was tested on 6 rabbits (3 males/3 females) of the English Silver strain, which were kept separately in V2A wire cages and fed on NAFAG, Gossau SG, rabbit food and water ad libitum. Only rabbits showing normal ophthalmic findings were
included in the test.

Amounts of 0.1 g. of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml. lukewarm water about 30 seconds after treatment.

The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
25.5
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
Eyes not rinsed
Basis:
mean
Remarks:
Rabbits 1, 2, and 3 (M)
Time point:
24/48/72 h
Score:
40
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
Eyes rinsed
Basis:
mean
Remarks:
Rabbit 4, 5, 6 (F)
Time point:
24/48/72 h
Score:
20
Max. score:
80
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0.5
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
Eyes not rinsed
Basis:
mean
Remarks:
Rabbit 1, 2 and 3 (M)
Time point:
24/48/72 h
Score:
0.16
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
Eyes rinsed
Basis:
mean
Remarks:
Rabbit 4, 5 and 6 (F)
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
14.3
Max. score:
20
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Eyes not rinsed
Basis:
mean
Remarks:
Rabbit 1, 2 and 3 (M)
Time point:
24/48/72 h
Score:
18
Max. score:
20
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Eyes rinsed
Basis:
mean
Remarks:
Rabbit 4, 5 and 6 (F)
Time point:
24/48/72 h
Score:
14
Max. score:
20
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
The results of the eye irritation test are summarized in table above. The total maximum is 80 for the cornea, 10 for the iris and 20 for the conjunctivae.
The irritation index was found to be 25.5 for the cornea. 0.5 for the iris and 14.3 for the conjunctivae
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test material was considered to be a severe irritant to the eyes of rabbits
Executive summary:

Irritation of the test material to the rabbit eye was assessed following the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO).

The substance was tested on 6 rabbits (3 males/3 females) of the English Silver strain, which were kept separately in V2A wire cages and fed on NAFAG, Gossau SG, rabbit food and water ad libitum. Only rabbits showing normal ophthalmic findings were included in the test. Amounts of 0.1 g. of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml. lukewarm water about 30 seconds after treatment. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety

The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 25-5 for the cornea, 0.5 for the iris and 14.3 for the conjunctivae. Thus, the test material is to be considered as a severe irritant (GHS Cat 2a) to the eye of rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In-vivo skin irritation/corrosion test

An acute Dermal Irritation/Corrosion Study in the Rabbit was conducted in accordance with the OECD 404 test guideline. An area of at least 36 cm was shaved on both flanks of the animals (3 males) approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2) bearing 0.5 ml of the test material was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank. The patches were loosely covered with aluminium foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system and the irritant/corrosive potency of the test material was classified according to the EEC Council Directive 83/467. The reactions were observed within 72 hours after removing the bandages, the observation period was extended to 14 days to determine the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the bandages must be classified as irritant in albino rabbits. After 72 -hour the mean irritation parameters for erythema and edema were 2.11 and 1.0 respectively. Because the mean values of the readings 24 to 72 hours after application are above the threshold of significance (score 2 for erythema or edema) the substance must be classified as irritant according to the EEC Council Directive 83/467. The erythema and edema reactions observed were reversible until the end of the observation period on day 14.

In-vivo eye irritation test

Irritation of the test material to the rabbit eye was assessed following the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO).

The substance was tested on 6 rabbits (3 males/3 females) of the English Silver strain, which were kept separately in V2A wire cages and fed on NAFAG, Gossau SG, rabbit food and water ad libitum. Only rabbits showing normal ophthalmic findings were included in the test. Amounts of 0.1 g. of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml. lukewarm water about 30 seconds after treatment. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety

The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 25.5 for the cornea, 0.5 for the iris and 14.3 for the conjunctivae. Thus TK-10406 is to be considered as a severe irritant (GHS Cat 2a) to the eye of rabbits.


Justification for selection of skin irritation / corrosion endpoint:
One in vivo study available with klimisch score 1.

Justification for selection of eye irritation endpoint:
One in vivo study available with klimisch score 1.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the above results, the test material has obligatory labelling requirement of irritant for skin and severe eye irritation (GHS Cat 2 and Cat 2a respectively) according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.