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Administrative data

Description of key information

Not a skin irritant
Not an eye irritant

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:
March 12, 1997 through March 20, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D-88397 Biberach/Riss
- Age at study initiation: 15 weeks
- Weight at study initiation: Male: 2971 g; Females: 2966 - 3150 g
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet ad libitum (batch no. 75/97).
- Water (e.g. ad libitum): Community tap water· from Itingen, ad libitum, in water bowls
- Acclimation period: Four days under test conditions after health examination. Only animals without any visual signs of illness wree used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
bi-distilled water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per animal
Duration of treatment / exposure:
4 hours
Observation period:
72 hours following treatment
Number of animals:
1 male, 2 females
Details on study design:
TEST SITE
- Area of exposure: 6 cm2 of the intact skin of the clipped area
- Type of wrap if used: A 2.5 cm x 2.5 cm patch of surgical gauze covered with a semi-occlusive dressing. The dressing was wrapped around the
abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to EEC Commission Directive 92/691EEC, July 31, 1992
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hour
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hour
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
Reversible light yellow staining by the test article of the treated skin was observed.

Table 1. Body weight (g) of test animals.

Animal No.

Sex

First Day of Acclimatisation

First Day of Treatment

Last Day of Treatment

16

Male

2900

2971

2999

17

Female

2983

3150

3351

18

Female

2823

2966

3041

Table 2. Skin irritation scores - individual values.

Animal No.

Sex

Evaluation Interval

Erythema

Edema

Cumulative

Score

Mean

16

M

1 hour

0

0

0.00

0.00

17

F

0

0

0.00

18

F

0

0

0.00

16

M

24 hours

0

0

0.00

0.00

17

F

0

0

0.00

18

F

0

0

0.00

16

M

48 hours

0

0

0.00

0.00

17

F

0

0

0.00

18

F

0

0

0.00

16

M

72 hours

0

0

0.00

0.00

17

F

0

0

0.00

18

F

0

0

0.00

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on these observations and on the referred classification criteria, CGP-C-1607 is considered to be "not irritating" to rabbit skin.
Executive summary:

The primary skin irritation potential of the test article was investigated by topical application of 0.5 g to 6 cm2 intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of figures. The primary irritation score was 0.00 (max. 8.0). Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused reversible light yellow staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Based upon the referred classification criteria (EEC Commission Directive 93/21IEEC of April 27, 1993), the test article is considered to be "not irritating" to rabbit skin.

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:
March 19, 1997 through March 27, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D-88397 BiberachlRiss
- Age at study initiation: 15 weeks
- Weight at study initiation: male: 3106 g; females: 3191 - 3422 g
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls and wood for gnawing
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet ad libitum (batch no. 75/97).
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum, in water bowls
- Acclimation period: Four days under test conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10 -15
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Vehicle:
unchanged (no vehicle)
Controls:
other: right eye used as reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g per animal

Duration of treatment / exposure:
Test article applied once then animals observed for 72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
SCORING SYSTEM: according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (A. Riegger, Basel/Switzerland)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24 - 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24 - 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24 - 72 hours
Score:
0.44
Max. score:
4
Remarks on result:
other: no score of 2 or greater
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24 - 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.44.
Slight to moderate reddening and slight swelling of the conjunctivae were noted in all animals, as well as hyperemia of the scleral blood vessels and slight to moderate watery discharge. All findings were reversible after 48 hours.
No corrosion of the cornea was observed at any of the reading times.
Other effects:
No staining of the cornea, sclera or conjunctivae by the test article was observed.

Table 1. Body weight (g) of test animals.

Animal No.

Sex

First Day of Acclimatisation

First Day of Treatment

Last Day of Observation

31

Male

3059

3106

3150

32

Female

2982

3191

3137

33

Female

3194

3422

3613

Table 2. Eye irritation scores - individual values.

Animal No.

Sex

Evaluation interval

Corneal Opacity

Iris

Conjunctivae

Cumulative

Redness

Chemosis

Score

Mean

31

M

1 hour

0

0

2

1

3.00

3.00

32

F

0

0

2

1

3.00

33

F

0

0

2

1

3.00

31

M

24 hours

0

0

1

0

1.00

1.00

32

F

0

0

1

0

1.00

33

F

0

0

1

0

1.00

31

M

48 hours

0

0

0

0

0.00

0.33

32

F

0

0

0

0

0.00

33

F

0

0

1

0

1.00

31

M

72 hours

0

0

0

0

0.00

0.00

32

F

0

0

0

0

0.00

33

F

0

0

0

0

0.00

Table 3. Eye irritation scores - mean values of 24, 48, and 72 hours.

Animal No.

Sex

Corneal Opacity

N

Iris

N

Conjunctivae

Primary Irritation Score

Redness

N

Chemosis

N

31

M

0.00

3

0.00

3

0.33

3

0.00

3

0.44

32

F

0.00

3

0.00

3

0.33

3

0.00

3

33

F

0.00

3

0.00

3

0.67

3

0.00

3

Table 4. Eye irritation scores - mean values over time.

Evaluation Interval

Corneal Opacity

Iris

Conjunctivae

Redness

Chemosis

1 hour

0.00

0.00

2.00

1.00

24 hours

0.00

0.00

1.00

0.00

48 hours

0.00

0.00

0.33

0.00

72 hours

0.00

0.00

0.00

0.00

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based upon the referred classification criteria, CGF-C-1607 IS considered to be "not irritating" to the rabbit eye.
Executive summary:

The primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of figures. The primary irritation score was 0.44 (max. 13). No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals. Based upon the referred classification criteria (EEC Commission Directive 93/211EEC of April 27, 1993), CGF-C-1607 is considered to be "not irritating" to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Bemotrizinol has been adequately tested for its potential to cause irritation and has been determined not to be a skin or eye irritant (RCC, 1997). According to OECD Guideline 404 (for skin irritation) the test substance received the primary irritation score of 0.00 (Max. 8.0), local signs consisted of grade 0.00 erythema, and grade 0.00 edema throughout a 72 hour period. There were no corrosive effects at any intervals. Based on these results Bemotrizinol is not irritating to rabbit skin. According to OECD Guideline 405 (for eye irritation) Bemotrizinol received the primary irritation score of 0.44 (Max. 13) throughout a 72 hour period. Based on these results Bemotrizinol is not irritating to rabbit eyes.


Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Key study

Justification for classification or non-classification

Skin irritation

Based on the results study (Primary irritation score 0.00 at 72 hours), Bemotrizinol would not be rated a primary dermal irritant under the EU DSD criteria (EU Directive 67/548/EEC) or under the EU CLP criteria (EU Regulation 1272/2008).

Eye irritation

Based on the results of the study (Primary irritation score 0.44 at 72 hours), Bemotrizinol would not be classified as eye irritant under the EU DSD criteria (EU Directive 67/548/EEC) or under the EU CLP criteria (EU Regulation 1272/2008).