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Toxicological information

Skin irritation / corrosion

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
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

Test material

Constituent 1
Reference substance name:
TK 11'278
IUPAC Name:
TK 11'278
Constituent 2
Reference substance name:
ESBO
IUPAC Name:
ESBO
Constituent 3
Reference substance name:
Epoxidised Soybean Oil
IUPAC Name:
Epoxidised Soybean Oil
Constituent 4
Reference substance name:
Soybean oil, epoxidized
EC Number:
232-391-0
EC Name:
Soybean oil, epoxidized
IUPAC Name:
232-391-0
Constituent 5
Reference substance name:
8013-07-8
Cas Number:
8013-07-8
IUPAC Name:
8013-07-8
Details on test material:
- Name of test material (as cited in study report): TK 11'278
- Physical state: Yellow liquid
- Lot/batch No.: Prod. Oct. 80
- Storage condition of test material: not stated
- Other:
- Solubility in water: insoluble

Test animals

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.

Test system

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

Results and discussion

In vivo

Results
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.

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