Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: Not irritating. 
Eye irritation: Not irritating.

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:
12 to 28 November 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD test guideline in compliance with GLP and reported with a valid GLP certificate.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: Albino, not specified
Details on test animals and environmental conditions:
Species: Albino rabbitSource: VŰŽV Nitra, SlovakiaNumber and sex: Four healthy young adult animals (males), weighing from 3,63kg to 4,62kgIdentification: The animals were housed individually in cages. The animals were marked by serial numbers 1 – 4. These numbers were placed in the cage and on the auricle. Husbandry:Housing: Animals were housed in cages individually. Diet: A standard certified laboratory diet (supplier Top Dovo Dobrá Voda) was served. The diet is routinely analysed by the manufacturer for nutritional components and environmental contaminants. Water: Ad libitum.Environment: Environmental control for the animal room was set to maintain 18 ± 3°C, a relative humidity of 40 – 70% a minimu of 10 air changes/hour, and a natural light regime. Acclimation: According SOP No 001/53204/07 Quarantine of animals.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Olivae oleum raffinatum
Controls:
no
Amount / concentration applied:
A dose of 0.5 g of Dusantox 86 was pulverised, moistened with the vehicle. Vehicle Article: Olivae oleum raffinatum, Certificate of analysis No 625/539/64/2007, Lot Number: L706203
Duration of treatment / exposure:
exposure period 4 hours.
Observation period:
72 hours.
Number of animals:
4 male rabbits.
Details on study design:
Preparation of dosesThe test article was pulverised and moistened sufficiently with olivae oleum shortly prior to administration. Test ProcedurePreparation of Test Area: Approximately 24h before the test, fur was removed from the test area by clipping from the dorsal area of the trunk of the animals. Only animal with healthy intact skin were used. Exposure of Animals: The study was begun with an initial test using one animal. The test article was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch. The patch was loosely held in contact with the skin by means of a suitable semi-occlusive dressing for the duration of the exposure period (4h). At the end of the exposure period, residual test preparation was removed using olivae oleum. Because a corrosive effect was not observed in initial test, the irritant response was confirmed using up to three additional animals simultaneously.Application of Test Article: The test article (0.5 g) was moistened sufficiently with olivae oleum and was applied to the skin and to the gauze patch.Observation of Animals: The appearance of skin reactions was observed and recorded at 1h, 24h, 48h and 72 h following removal of the patches. The skin reactions for erythema and oedema were described and graded according to the classification system for the application site at each time interval.
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Irritation score: 0.33
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Irritation score: 0.5
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Irritation score: 0.17
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #4
Time point:
other: 24, 48 & 72 hours
Score:
0 - 2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Irritation score: 0.67
Irritant / corrosive response data:
Because a corrosive effect was not observed in initial test, the irritant response was confirmed using up to three additional animals simultaneously.
Other effects:
The well-defined erythema classified as grad 2 was observed as the worst skin reaction on the Dusantox 86 only in one animal. Skin reactions on other animals were determined as grad 1 – very slight erythema. No observation of erythema or oedema was noted on the vehicle application site. During 7 days after removal of patches erythema had disappeared in all animals. No oedema was occurred in the course of study.

Table 3. Score of reaction – numerical grading for skin reaction

Animal No.

Weight (kg)

Date of application

Time observation after removal patches

Irritation scores Dusantox 86

Irritation Scores of each animalΣErythema + oedema : 6

Primary irritation index (PII)

h.

date

Erythema

Oedema

1

4.33

13.11.07

1

13.11.07

1

0

0.33

0.4

24

14.11.07

1

0

48

15.11.07

1

0

72

16.11.07

0

0

2

3.65

14.11.07

1

14.11.07

1

0

0.5

24

15.11.07

1

0

48

16.11.07

1

0

72

17.11.07

1

0

3

3.63

14.11.07

1

14.11.07

1

0

0.17

24

15.11.07

1

0

48

16.11.07

0

0

72

17.11.07

0

0

4

4.62

14.11.07

1

14.11.07

1-2

0

0.67

24

15.11.07

2

0

48

16.11.07

1

0

72

17.11.07

1

0

Response category

Negligible

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Primary Irritation Index of Dusantox 86 for single exposure determined in this study was PII = 0.4. According to this value the test article belongs to response category “negligible”.
Executive summary:

The skin irritation potential of Dusantox 86 was tested in four albino rabbits. The test article was applied in a single dose to the clipped skin of experimental animals, each animal serving as its own control. A dose of 0.5 g of Dusantox 86 was pulverised, moistened with olivae oleum and applied to the intact skin of rabbits for 4 h under semi-occlusive dressings. The degree of irritation was read and scored at specified intervals (1 h, 24h, 48 h and 72h following removal of the patches) and was described to provide a complete evaluation of the effects. The Primary Irritation Index of Dusantox 86 for single exposure determined in this study was PII = 0.4. According to this value the test article belongs to response category “Negligible”.

No classification and labelling is applicable.

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:
16 November 2007 to 07 December 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OCED test guidelines in compliance with GLP and reported with a valid GLP certificate.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
NZW (albino) rabbits from SCPV Nitra, SRNumber: 3Initial weight: > 3kgSource: VŰŽV Nitra, SlovakiaHousing conditions: Animals were housed individually in metallic cages. Environment: Environmental control for the animal room was set to maintain 18 ± 3°C, a relative humidity of 55 ± 10% a minimum of 10 air changes/hour. Lighting was artificial, the sequence being 12h light, 12h dark. Acclimation: 20 days.Diet: A standard certified laboratory diet (supplier Top Dovo Dobrá Voda) was served. The diet is routinely analysed by the manufacturer for nutritional components and environmental contaminants. Water: Ad libitum.Identification of animals: The animals were marked by serial numbers 1 – 3. These numbers were placed on cages.
Vehicle:
other: olivae oleum raffinatum
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Dusantox 86 (100 mg) was pulverized, moistened sufficiently with olivae oleum raffinatum and apply to right eye. Vehicle Article: Olivae oleum raffinatum, Certificate of analysis No 625/539/64/2007 Lot Number: L706203
Duration of treatment / exposure:
Not specified
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 rabbits (sex not specified).
Details on study design:
TEST PERFORMANCEBefore the study animals were quarantined for 20 days in the conditions identical to the conditions during the experiment. Both eyes of the rabbits were examined within 24 hours before beginning of the test. Test material was placed in amount of 100 mg of Dusantox 86 in the conjunctival sac of rabbit’s right eye. The left eye was served as control. The eyes in all rabbits were examined and score for signs of irritation in the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours after test substance application. Examination of reactions were facilitated by used of hand lamp and magnifying glass. Application of the test articleDusantox 86 (100 mg) was pulverized, moistened sufficiently with olivae oleum raffinatum and apply to right eye. EvaluationChanges of rabbits’ eyes were described and graded according to OECD No 405: Grading of ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Some blood vessels were hyperacmic (injected) in conjunctivae of all rabbits 1 hour after Dusantox 86 application. This change had continued in one rabbit (No.2) 24 hours after application and lids of rabbits No.1 and 3 had swollen above normal in the same time. All changes had value of 1 grad. Eye of all rabbits were normal 48 hours after application of test article.

Protocol 1 – Examination of rabbits 24 hours before beginning of the test

Date

Rabbit No

Results of examination

19.11.2007

1

No clinical changes, Eyes : No ocular lesions

19.11.2007

2

No clinical changes, Eyes : No ocular lesions

19.11.2007

3

No clinical changes, Eyes : No ocular lesions

 

Protocol 2 – Body weight of animals

Rabbit No

Date

Initial body weight (kg)

Date

Body weight at the end of the test (kg)

1

19.11.2007

4.13

23.11.2007

4.17

2

19.11.2007

3.84

23.11.2007

3.85

3

19.11.2007

3.40

23.11.2007

3.42

 

Protocol 3 – Results of eyes examination

Rabbit No

Time after application (hours)

Grading of ocular lesion

Date

Cornea

Iris

Conjunctivae

Lids (swelling)

Issue

1

1

0

0

1

0

0

20.11.2007

24

0

0

0

1

0

21.11.2007

48

0

0

0

0

0

22.11.2007

72

0

0

0

0

0

23.11.2007

2

1

0

0

1

0

0

20.11.2007

24

0

0

1

0

0

21.11.2007

48

0

0

0

0

0

22.11.2007

72

0

0

0

0

0

23.11.2007

3

1

0

0

1

0

0

20.11.2007

24

0

0

0

1

0

21.11.2007

48

0

0

0

0

0

22.11.2007

72

0

0

0

0

0

23.11.2007

Interpretation of results:
not irritating
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Dusantox 86 had not apparent irritant or corrosive effects on eyes of NZW rabbits.
Executive summary:

Test article was applied in a single does to right eye of the rabbits. The left eye was used as the control. The degree of eye irritation was evaluated scoring lesions of conjunctiva, cornea, iris and lids at 1, 24, 48 and 72 hours after application. Dusantox 86 had not apparent corrosive or irritation effect on rabbits eyes. No classification and labelling is applicable.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

The skin irritation potential of Dusantox 86 was tested in four albino rabbits. The test article was applied in a single dose to the clipped skin of experimental animals, each animal serving as its own control. A dose of 0.5 g of Dusantox 86 was pulverised, moistened with olivae oleum and applied to the intact skin of rabbits for 4 h under semi-occlusive dressings. The degree of irritation was read and scored at specified intervals (1 h, 24h, 48 h and 72h following removal of the patches) and was described to provide a complete evaluation of the effects. The Primary Irritation Index of Dusantox 86 for single exposure determined in this study was PII = 0.4. According to this value the test article belongs to response category “Negligible”.

No classification and labelling is applicable.

 

Eye Irritation

The test article was applied in a single does to right eye of the rabbits. The left eye was used as the control. The degree of eye irritation was evaluated scoring lesions of conjunctiva, cornea, iris and lids at 1, 24, 48 and 72 hours after application. Dusantox 86 had not apparent corrosive or irritation effect on rabbits eyes. No classification and labelling is applicable.


Justification for selection of skin irritation / corrosion endpoint:
Study performed to OECD guideline 404.

Justification for selection of eye irritation endpoint:
Study performed to OECD guideline 405.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP and in accordance with appropriate OECD Guideline. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.