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Description of key information

Two studies of skin irritation and two studies of eye irritation are available for the read-across substance ESBO

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
10 August 1981 to 17 August 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The experimental design is similar to that of OECD guideline 404 with enhanced exposure due to an extended exposure period - 24 hours - and inclusion of dermal abrasion prior to application of the test material.
Qualifier:
equivalent or similar to guideline
Guideline:
other: Proposed Guidelines of the United States Environmental Agency (EPA) S 163.81-5 "Primary dermal irritation study" Federal Register, Vol. 43, No. 163, August 22, 1978
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
The test was performed on 3 male and 3 female adult New Zealand White rabbits bred and raised on the laboratory premises. They weighed 2 - 3 Kgs.

They were housed individually in metal cages numbered by ear tags.
They were kept at constant room temperature of 22 ± 2 °C, at a relative humidity of 55 ± 10 % and on a 12-hours light cycle day.
The animals received ad libitum standard rabbit food - NAFAG, No. 814, Gossau SG - and water.
Prior to treatment they were adapted to the laboratory for a minimum of 4 days.
Type of coverage:
occlusive
Preparation of test site:
other: skin was shaved. One site abraded one left unabraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Gauze patches of 2.5 x 2.5 cm laden with 0.5 mL of the test material were applied to the prepared abraded and intact skin.

The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.
Duration of treatment / exposure:
The dressings were removed after a 24 hour application.
Observation period:
Reactions were appraised using standard Draize assessment, on removal of dressing and during an observation period of 7 days.
Number of animals:
3 male and 3 female adult New Zealand White rabbits
Details on study design:
Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaved skin on one side was lightly sacrified using a scalpel blade.

Gauze patches of 2.5 x 2.5 cm laden with 0.5 mL of the test material were applied to the prepared abraded and intact skin. The patches were covereed with an impermeable material and were fastened to the body of the rabbit with adhesive tape.

The skin reaction was appraised on ths basis of the following evaluation scheme:

Score for skin irritation in rabbits:

Erythema and eschar formation:
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) :......................................... 4

Total possible erythema score:...................................... 4

Oedema formation
No edema: .......................................................................0
Very sllght edema (barely perceptible): ..................... 1
Sllght edema (edges of area well defined by
definite raising):............................................................. 2
Moderate edema (raised approximately 1 mm): ...... 3
Severe edema {raised more than 1 mm and
extending beyond area of exposure): ........................4

Total possible oedema score: ........................................ 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 h post application
Score:
1.7
Max. score:
8
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Only limited information is provided relating to 24 and 72 scores. Reversibility is presented graphically
Irritant / corrosive response data:
The results of the primary skin irritation test are reported in Table 1.

Tha calculated primary irritation index was 2.6 - this includes results from abraded and non-abraded skin.
TK 11'278 was found to cause a moderate irritation when applied to intact and abraded rabbit skin, according to the interpretation of PII results

After 24 hours the surface of the erythema was greater than the site of application on all sites except No. 415 (intact) and No. 416 (abraded). This observation was made after 48 hours on both sites of animal No. 417 and after 72 hours on the abraded side of the same animal.

Results were revaluated to determine a possble classification in accordance with EU/GHS criteria.

In the absence of individual animal scores, taking into account the extended exposure period and assuming a linear response for ameliorating dermal responses between 24 and 72 hours, the mean results for non-abraded skin were averaged for 24 and 72 hour responses as an approximation of the Draize result. On this basis, the mean erythema score for non-abraded skin over 24-72 h was 1.5 and for oedema the mean result was 0.75.
Neiher of these values exceeds the EU classification threshold.
Other effects:
With the exception of the last day of the test, a slight sedation was observed.

Dermal reactions

Time after exposure (hours)

Mean Reaction Score

Erythema

Oedema

Intact Skin

Abraded Skin

Intact Skin

Abraded Skin

24

1.7

2.0

1.0

1.5

72

1.3

1.5

0.5

0.7

 

Total

3.0

3.5

1.5

2.2

Assessment of Irritation

0

0.1 - 1.0 = minimal

1.1 - 2.0 = slight

2.1 - 4.0 = moderate

4.1 - 6.0 = marked

6.1 - 8.0 = extreme

The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4. The primary irritation index was 2.6.

The abraded skin results are not appropriate for assessment under EU classification guidelines. The mean scores are 24 and 72 hours were used as approximations to the 24 -72h mean. Erythema and oedema mean scores were approximated to be 1.5 and 0.75 respectively. Neither results exceeds the EU classification threshold

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the condition of the present experiment TK 11'278 was found to cause a moderate irritation when applied to intact and abraded rabbit skin. The calculated primary irritation index was 2.6.
Individual values are not presented for each rabbit and so it is not possible to fully evaluate in accordance with EU criteria, however an approximation can be calculated that indicates the erythema score for intact skin was approximately 1 and slightly higher for the abraded sites, when averaged over the 24 and 72 hour assessments. On this basis the material would be considered to be only slightly or mildly irritating and would not warrant classification according to EU criteria.
Executive summary:

Under the condition of the present experiment TK 11'278 was found to cause a moderate irritation when applied to intact and abraded rabbit skin. The calculated primary irritation index was 2.6. The estimation of the mean score for irritation based on the 24 and 72 hour assessments was circa 1.0. According to Directive 67/548/EEC no classification is required for dermal irritation. According to Regulation (EC) No. 1272/2008, no classification is warranted.

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
Study period:
August 10, 1981 - August 24, 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study meets the criteria laid out in OECD Guideline 405.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Procedure used was that described in the Proposed Guideline of the United States Environmental Protection Agency (EPA) S 163.81 - 4 "Primary eye irritation study", Federal Register Vol. 43, No. 163, August 2, 1978 that were in draft at time of study conduct and subsequently adopted.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The test was performed on 3 male and 6 female New Zealand White rabbits bred and raised on the premises weighing 2 to 3 kgs. The animals were housed individually in metal cages, numbered by ear tags, were kept at constant room temperature of 22 ± 2°C, at a relative humidity of 55 ± 10% and on a 12 hour light cycle day. The animals had ad libitum access to standard rabbit food and water.

Prior to treatment they were adapted to the laboratory for a minimum of 4 days. Only rabbits with normal opthalmic findings were used for these tests.
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each rabbit served as the inherent control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
In three of the nine rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of physiological saline.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
9 - three rinsed and six not rinsed after installation
Details on study design:
0.1 mL of undiluted test material was instilled into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In three of the nine rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4, 7, 10 and 14 and was scored for each individual rabbit.

As the test compound is not soluble in water, an assessment of pH was not performed prior to dosing.
Irritation parameter:
other: PII
Remarks:
Primary Irritation Index
Basis:
mean
Remarks:
Kay and Callendra system
Time point:
other: 24 hours
Score:
4.7
Max. score:
20
Reversibility:
fully reversible within: 10 days
Irritation parameter:
other: PII
Remarks:
Primary Irritation Index
Basis:
mean
Remarks:
Kay and Callendra system
Time point:
other: 24 hours
Score:
3.3
Max. score:
20
Reversibility:
other: after 7 days only one of the three animals had slight conjunctival redness
Irritant / corrosive response data:
The ocular reactions were assessed by the Kay and Callendra system, from which a PII was derived. For classification purposes the results were re-calculated using a standard Draize score deriving a mean for the reactions over 24-72 hours.
On this basis the mean results for the rinsed eyes (scores for six rabbits) were -
corneal opacity = 0.0
Iris response = 0.0
Conjunctival redness = 1.06
Conjunctival swelling/chemosis = 0.61
and for the rinsed eyes the mean values for 24-72 hours were:
corneal opacity = 0.0
Iris response = 0.0
Conjunctival redness = 0.89
Conjunctival swelling/chemosis = 0.56.
No corneal or iridial changes were evident for any of the nine rabbits. Conjunctival irritation did not exceed diffuse crimson coloration and had resolved in all unrinsed rabbits by Day 10. reactions persisted for one of the rinsed eyes to Day 14. Conjunctival chemosis had largely resolved by Day 4 for all nine rabbits although slight reactions persisted for one, unrinsed, eye to Day 7.


Other effects:
No symptoms of systemic intoxication were observed throughout the whole test period.

Calculation of the primary eye irritation index

Time after exposure days

Mean reaction score

Unrinsed eyes (A)

Rinsed eyes (B)

Cornea

iris

conjunctiva

cornea

iris

conjunctiva

1

0

0

4.7

0

0

3.3

2

0

0

3.3

0

0

2.7

3

0

0

2

0

0

2.7

4

0

0

1.3

0

0

1.3

7

0

0

1

0

0

0.7

10

0

0

0

0

0

0.7

14

0

0

0

0

0

0.7

The ocular reactions were assessed by the Kay and Callendra system, from which a PII was derived. For classification purposes the results were re-calculated using a standard Draize score deriving a mean for the reactions over 24-72 hours. On this basis the mean results for the rinsed eyes (scores for six rabbits) were - corneal opacity = 0.0 Iris response = 0.0 Conjunctival redness = 1.06 Conjunctival swelling/chemosis = 0.61 and for the rinsed eyes the mean values for 24-72 hours were: corneal opacity = 0.0 Iris response = 0.0 Conjunctival redness = 0.89 Conjunctival swelling/chemosis = 0.56. No corneal or iridial changes were evident for any of the nine rabbits. Conjunctival irritation did not exceed diffuse crimson coloration and had resolved in all unrinsed rabbits by Day 10. reactions persisted for one of the rinsed eyes to Day 14. Conjunctival chemosis had largely resolved by Day 4 for all nine rabbits although slight reactions persisted for one, unrinsed, eye to Day 7.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The read-across substance ESBO was found to be a mild eye irritant under the conditions of this study.
Executive summary:

The eye irritation potential of the read-across substance ESBO was investigated in a test performed on three male and six female New Zealand White rabbits. In the unrinsed eyes no irritation of cornea and iris was observed at any reading. Irritation was seen only in the conjunctiva with a maximum mean acore of 4.7 after 24 hours. After 10 days all irritation had disappeared. In the rinsed eyes, no irritation of cornea and iris was observed at any reading. Irritation was seen only in the conjunctiva with a maximum mean score of 3.3 after 24 hours. After 7 days onwards only one of the three animals had a slight conjunctival redness. No symptoms of systemic intoxication were observed throughout the whole test period. Reactions reassessed using EU classification criteria confirm that values do not exceed the EU thresholds for triggering classification.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Two studies are available for the read-across substance ESBO and indicate a low level of skin irritation that does not warrant classification as a skin irritant.

Eye irritation

Two studies are available for the read-across substance ESBO and indicate a low level of skin irritation that does not warrant classification as an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Two studies are available for the read-across substance ESBO; this study has more detailed reporting

Justification for classification or non-classification

Studies of skin and eye irritation for the read-across substance ESBO and indicate a low level of irritation that does not trigger classification according to EU criteria.

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