Registration Dossier

Administrative data

Description of key information

- Skin: The substance did not cause skin irritation in the rabbit skin. Neither erythema nor oedema was evident within 7 days following a 24 hour exposure duration. 

- Eye: Conjunctival reactions were seen in 2 of 6 animals. The effects on the conjunctivae were fully reversible in all affected animals within 7 days after instillation. Very slight corneal opacity which was seen in only 2 of 6 animals was fully reversible by day 4 following instillation.

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: Comparable to guideline standards with acceptable restrictions - analytical purity of the test substance not indicated
Qualifier:
equivalent or similar to
Guideline:
other: Federal Register, 38, No.187 §1500.41
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(14/10 hour dark/light rhythm, treatment on intact and abraded skin, occlusive treatment, 24 hour long treatment)
Principles of method if other than guideline:
Draize test
GLP compliance:
no
Specific details on test material used for the study:
- Analytical purity: no data
- Batch No.: A 16-234/5
- pH: 6
Species:
rabbit
Strain:
other: Himalayan breed
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA Versuchstierzuchtanstalt, 8741 Sulzfeld, Germany
- Weight at study initiation: 1.5 - 2 kg.
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit food (NAFAG Gossau SG)
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14/10
Type of coverage:
occlusive
Preparation of test site:
other: shaved (unabraded and abraded)
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated parts of the same rabbit
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
7 days
- Scoring of skin irritation was performed 24 and 72 hours after initiation of treatment.
Number of animals:
6
Details on study design:
TEST SITE
- Before treatment the entire back, and the flank of the rabbits were shaved and immediately before treatment, the shaven skin of the left side was slightly scarified. The right side was not scarified.
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The patches were covered with an impermeable material and fastened with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure: 24 hours

SCORING SYSTEM: draize system
Irritation parameter:
erythema score
Remarks:
(unabraded skin)
Basis:
mean
Remarks:
(of all 6 animals)
Time point:
other: mean over 24, 48 and 72 hours after start of treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Remarks:
(unabraded skin)
Basis:
mean
Remarks:
(of all 6 animals)
Time point:
other: mean over 24, 48 and 72 hours after start of treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Other effects:
Effects on scarified skin 24 hours after start of exposure (6 animals)
- Erythema: 1 (animals # 1, 3, 5 and 6), 0 (animals # 2 and 4)
- Oedema: 0 (all animals)

Effects on scarified skin 48 hours after start of exposure (6 animals)
- Erythema: 1 (animal # 6), 0 (animals # 1 - 5)
- Oedema: 0 (all animals)

Effects on scarified skin 72 hours after start of exposure (6 animals)
- Erythema: 0 (all animals)
- Oedema: 0 (all animals)

In accordance with conventional practice, only results of the non scarified skin sections are adopted in the final assessment for skin irritation.

Interpretation of results:
GHS criteria not met
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:
other: see 'Remark'
Remarks:
Comparable to guideline standards with acceptable restrictions - analytical purity of the test substance not indicated - reporting deficiencies: individual animal scores not provided (only average scores were provided). As a consequence, effects on unwashed eyes could be only partly evaluated.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(14/10 hour dark/light rhythm, 6 test animals, result reporting deficiencies)
Qualifier:
equivalent or similar to
Guideline:
other: Federal Register, 38, No.187 §1500.42
Principles of method if other than guideline:
Draize method
GLP compliance:
no
Specific details on test material used for the study:
- Analytical purity: no data
- Batch No.: A 16-234/5
- pH: 6
Species:
rabbit
Strain:
other: Himalayan breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: WIGA Versuchstierzuchtanstalt, 8741 Sulzfeld, Germany
- Weight at study initiation: 1.5 - 2 kg.
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit food (NAFAG Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days. Only rabbits with normal opthalmic findings were used in the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14/10

Vehicle:
unchanged (no vehicle)
Controls:
other: other eye (not treated)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
After instillation, eyes were not washed
Observation period (in vivo):
Eye irritation was scored on day 1, 2, 3, 4, and 7
Number of animals or in vitro replicates:
6
- animals 1 - 3 (eyes were not washed)
- animals 4 - 6 (eyes were washed)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes (in 3 of 6 animals); with luke warm water (10 mL)
- Time after start of exposure: 30 sec. after instillation

SCORING SYSTEM: draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Remarks:
(unwashed eyes)
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Remarks:
(unwashed eye)
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Remarks:
(unwashed eye)
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Remarks:
(washed eye)
Basis:
mean
Remarks:
of animal # 4, 5 and 6
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Remarks:
(washed and unwashed eye)
Basis:
mean
Remarks:
(of all 6 animals)
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
(unwashed eye)
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
(unwashed eye)
Basis:
animal #2
Time point:
other: mean over 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Due to reporting style, draize scores at 24 hours could not be deciphered. However, effect that occurred at 24 hours was reversible within 48 hours.
Irritation parameter:
conjunctivae score
Remarks:
(unwashed eye)
Basis:
animal #3
Remarks on result:
other: Due to reporting style, draize scores could not be deciphered. However, effect that occurred was reversible within 7 days.
Irritation parameter:
conjunctivae score
Remarks:
(washed eye)
Basis:
mean
Remarks:
of animal # 4, 5 and 6
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Remarks:
(unwashed eye)
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Remarks:
(unwashed eye)
Basis:
animal #2
Time point:
other: mean over 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48
Remarks on result:
other: Due to reporting style, draize scores at 24 hours could not be deciphered. However, effect that occurred at 24 hours was reversible within 48 hours.
Irritation parameter:
chemosis score
Remarks:
(unwashed eye)
Basis:
animal #3
Remarks on result:
other: Due to reporting style, draize scores could not be deciphered. However, effect that occurred was reversible within 7 days.
Irritation parameter:
chemosis score
Remarks:
(washed eyes)
Basis:
mean
Remarks:
mean of animal # 4, 5 and 6
Time point:
other: mean over 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: not applicable

As a consequence of the poor documentation of the results (only average scores but not individual animal scores were provided), the parameters conjunctivae redness and swelling could not be assessed fully for unwashed eyes. Nevertheless, from the documented results, it is evident that conjunctival effects were totally absent in one animal over the observation period (score = 0), fully reversible in the second animal within 48 hours after start of treatment and fully reversible in the third animal by day 7.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

In a primary dermal irritation study, performed using a method identical to that described in the Federal Register, 38, No.187 §1500.41. 0.5 g of the test substance (no data on analytical purity) was applied under occlusive cover to the intact and abraded skin (2.5 x 2.5 cm) of 6 rabbits of Himalayan breed. Treatment was terminated (skins were not washed) 24 hours following application and the animals were observed for up to 7 day in which time irritation was scored according to the Draize method 24, 48 and 72 hours after begin of treatment. Average scores per animal - computed from the individual scores on intact skin at the 24, 48 and 72 hour post start of treatment – were 0 for erythema (maximal attainable score = 4), and 0 for edema (maximal attainable score = 4). No signs of skin irritation were evident by the end of the observation period (day 7).

Because of its lack of scientific justification and gross deviation from today's acceptable standardized procedures for the appraisal of skin irritation, results from the abraded skins are not included in the final judgment for skin irritation of the test substance.

Eye irritation

The eye irritation potential of the test substance was determined in a procedure identical to the procedure described in the Federal Register 38, No.187 §1500.42. 0.1 g of the substance was applied to the conjunctival sac of the left eye of each of 6 rabbits (Himalayan breed). After application the eye lids were closed for ca. one second. The right eye remained untreated and served as control. Thirty seconds after instillation, treated eyes of 3 of 6 animals were rinsed with water (10 mL). Irritation was appraised after 24, 48, 72, 96 and 168 hours. Appraisal of eye irritation was according to the method of draize. Average draize scores after 24, 48 and 72 hours were calculated per animal for corneal opacity, iritis, conjunctivae redness and chemosis.

No indication of eye irritation was seen in those animals whose eyes were washed. All scored parameters (redness, corneal opacity, chemosis, iritis) in the 3 animals whose eyes were washed produced a draize score of 0 (over the entire observation period). 

As a consequence of the poor documentation of the results - only average scores and no individual animal scores were provided, - the parameters conjunctivae redness and swelling could not be fully assessed for unwashed eyes (In this study conjunctivae was appraised as a combination of effects resulting from redness, swelling and discharge). Nevertheless, from the documented results, it is evident that conjunctival effects were totally absent in one animal (score = 0) over the observation period and fully reversible within 48 hours and day 7 in the second and third animal, respectively. Taken together, this indicates a low irritation potential of the test substance.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No.1272/2008, as amended for the fifth time in Directive EC 944/2013, classification for skin and eye irritation is not warranted.