Registration Dossier

Administrative data

Description of key information

skin irritation (rabbit, occlusive, intact and abraded skin BASF 1979): not irritant 
eye irritation (rabbit, powder, BASF, 1979): classified as H318: causes serious eye damage

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.41
Principles of method if other than guideline:
The hair was removed from the lateral skin over an area of about 8 x 8 cm on both sides of the trunks of 6 rabbits with an average weight of 2.3 kg using electric clippers 24 hours before the beginning of the study. The skin on the right flank was also abraded by means of a scarifier at the site where the test patch was to be applied. Patches (2.5 x 2.5 cm) of double layers of surgical gauze were coated/impregnated with 500 mg of the test substance made into a paste with water and covered with indifferent impermeable PVC film (5 x 5 cm). The film with the patch underneath was attached to the two test sites by means of adhesive tape (Leukoflex R ) that does not irritate the skin. The whole trunk of the animals was then bandaged with an elastic fixed bandage (Elastoflex R ) for the duration of the exposure period of 24 h. The animals were restrained.Findings were reported immediately (about 30 min) after the removal of the patches (24-h value) and then 48 h and 72 h after the beginning of the study (48 h after the first reading).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Versuchstierzuchten W. Ostrop, Meerbusch, F.R.G.- Housing: animals were housed in single cages.- Diet: "muemmel z" feed (sniff, Soest F.R.G.) ad libitum- Water: ad libitum- Acclimation period: 4-6 days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 16-18 °C- Humidity (%): 40%
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount applied: 500 mg
Duration of treatment / exposure:
24 h
Observation period:
8 days
Number of animals:
6
Details on study design:
TEST SITE- Area of exposure: 2.5 x 2.5 cm- Type of wrap if used: Leukoflex, ElastoflexSCORING SYSTEM: Erythema and eschar formation: Value- No erythema: 0- Very slight erythema (barely perceptible): 1- Well-defined erythema: 2- Moderate to severe erythema: 3- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4Edema formation- No edema: 0- Very slight edema (barely perceptible): 1- Slight edema (edges of area weil defined by definite raising): 2- Moderate edema (raised approximately 1 mm): 3- Severe edema (raised more than 1 mm and extending beyond the area of exposure): 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Reading and exact calculation of the erythema index not possible because of staining of the skin caused by the test substance. Staining persisted until study end (8 days).
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: The 48-h value does not appear on the report sheet.

Reading and exact calculation of the erythema index not possible because of staining of the skin caused by the test.

Mean edema score:

   Animal No.  24h  72h  8 days  mean 24 -72 h  mean score all animals (24 - 72 h)        
 intact skin  1  0  0  0  0          
   2  1  1  2  1          
   3  0  0  0  0          
   4  0  3  0  1.5          
   5  1  2  2  1.5          
   6  0  0  1          
             0.83        
 abraded skin  1  1  0  0  0.5          
   2  1  2  2  1.5          
   3 1  1  0  1          
   4  1  3  1  2          
   5  1  2  2  1.5          
   6  0  0  0          
             1.083        
Interpretation of results:
other: Not classified under Regulation 1272/2008
Conclusions:
The analogue substance 1 was tested for skin irritation following Code of Federal Regulations, Title 16, Section 1500.41 . Under the experimental conditions the substance does not show any skin irritation potential.
Executive summary:

The analogue substance 1 was tested for skin irritation following Code of Federal Regulations, Title 16, Section 1500.41 . Under the experimental conditions the substance does not show any skin irritation potential.

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions performed on analogue substance 1
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
Principles of method if other than guideline:
The test was carried out by applying 100 µl bulk volume of the crystalline substance to the conjunctival sac of the lower right eyelid of rabbits that had been previously examined and had a mean weight of 2.3 kg. The lids were then gently held together for 1 sec. The eye was not washed after the application. The second, left eye of the rabbits always remained untreated as the control. The assessment was made with the aid of an ophthalmoscope.Cornea findings were verified after 8 days using the fluorescein test (instillation of 1 drop of fluorescein solution in an ophthalmological formulation directly onto the cornea. After washing with physiological saline solution corneal lesions appear yellow-green, UV light or cobalt blue-filter).Findings were obtained 24, 48 and 72 h and 8 days after the beginning of the study.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Versuchstierzuchten W. Ostrop, Meerbusch, FRG- Weight at study initiation: 2.3 kg- Housing: animais were housed in single cages- Diet: "muemmel z" feed (ssniff, Soest, FRG) ad libitum.- Water: ad libitum- Acclimation period: 4-6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 16-18 °C- Humidity (%): 40%
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as control.
Amount / concentration applied:
TEST MATERIAL- Amount applied: 100 µl
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6
Details on study design:
TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal:
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
conjunctivae score
Basis:
animal:
Time point:
24/48/72 h
Remarks on result:
not measured/tested

   24h                 48h                 72h                 8 days               
 Animal No.  1  2  3  4  5  6  1  2  3  4  6  1  4  6  1  2  3

Cornea

                                               
 A) Opacity  3  3  2  1  1  1  3  2  2  1  2  1  1  2  2  2  1  2  1  2  1  1  1
 B)Area  4  4  4  1  1  3  3  2  2  1  3  2  3  1  1  1  1  1  4  1  1  1  1  1
 a=A*B*5  60  60  40  5  5  15  45  20  20  5  30  10  15  10 10   10  10  5            
                                                 

 Iris

 2  2  1  1  2
 b=A*5  10  10  10  5  5  10  10  10  10  5  5  10  10  10  10  5  5 10             
                                                 

 Conjunctivae

                                               
 A) Redness  3  3  3  3  3  3  3  3  3  3  3  3  3  3  2  3  3  3  3 1  2  1  1  3
 B) Swelling  4  4  4  4  4  4  4  2  2  2  4  4  3  2  3  3  2  1  2  1  2
 C) Discharge  3  2  3  3  3  3  2  2  2  3  3  2  2  2  2  2  3  2  0  1  1  2
 c=(A+B+C)*2  20 20  18  20 20  20  20  14  14  14  20  20  16  14  14  14  16  16             
                                                 
total= a+b+c(max. 110) 90   90  68  30  30  45  75  44  44  24  55  40  41  34  34  29  31  31            
Interpretation of results:
other: classified under Regulation 1272/2008 H318, Eye Damage 1
Conclusions:
The analogue substance 1 was tested for eye irritation following Code of Federal Regulations, Title 16, Section 1500.42 . Under the experimental conditions and following critieria set by Regulation 1272/2008 the substance is classified as Eye Damage 1, H318: Causes serious eye damage (iris score > 1.5 for 4 animals out of 6).
Executive summary:

The analogue substance 1 was tested for eye irritation following Code of Federal Regulations, Title 16, Section 1500.42 . Based on the iris average indexes at 24, 48 and 72h, under the experimental conditions and following critieria set by Regulation 1272/2008 the substance is classified as Eye Damage 1, H318: Causes serious eye damage.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two in vivo studies are available for the assessment of irritation/corrosion potential of the analogue substance 1 to the skin and the eye.

The intact and abraded skin of New Zeakand rabbits were exposed to the substance in an occlusive way without showing any irritation effect (only oedema could be assessed and not erythema due to the staining of the skin by the dye substance).

The eye irritation potential was tested with powdered form of the substance on New Zealand rabbits showing a mean value (24,48 and 72h) of the iris score equal to 2 for 4 animals out of 6, which classifies the substance as H318: serious eye damage.

based on the read across considerations the same classification for eye irritation potential is applied to Basic Brown 1 acetate.


Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on provided data the substance is classified as H318: Causes serious eye damage, Eye Damage 1 under the Regulation 1272/2008.

Based on the provided data the substance is not classified for skin irritation