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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 July 1981 to 4 September 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
There is no indication of the number of animals in the control group. There is no indication in the report that the concentration of the test substance used was the highest to cause mild-to-moderate skin irritation. Or that the concentration used for the challenge exposure was the highest non-irritant dose.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

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:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
The optimisation test was used, an intracutaneous sensitisatopn procedure exceeding the sensitivity of the method recommended in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA was adopted 2010 by OECD / current study is from 1981

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
Chemical structure
Reference substance name:
Soybean oil, epoxidized
EC Number:
232-391-0
EC Name:
Soybean oil, epoxidized
Cas Number:
8013-07-8
Molecular formula:
Not necessary, substance is a UVCB.
IUPAC Name:
Soybean oil, epoxidized
Details on test material:
- Name of test material (as cited in study report): TK 11'278
- Physical state: Liquid
- Lot/batch No.: prod. Oct. 80
- Expiration date of the lot/batch: January 1982

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
The test was performed on groups of 10 male and 10 female guinea pigs of the Pirbright White Strain, bred on the premise,s and weighing between 400 to 540 grams.
The animals were housed individually in type 3 Macrolon cages, kept at a constant room temperature of 22 ± 2 °C, at a relative humidity of 55 ± 10 % and in a 12 hour light cycle per day.
The animals were fed standard guinea pig pellets - NAFAG, No. 830, Gossau SG, SWitzerland - ad libitum and had ad libitum access to water.
Bodyweights were recorded immediately before initiation of dosing in the inductin phase and at termination of the study.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: propylenglycol 50 % / saline 50 %
Concentration / amount:
0.1 mL of 0.1 % solution of TK 11'278
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: propylenglycol 50 % / saline 50 %
Concentration / amount:
0.1 mL of 0.1 % solution of TK 11'278
No. of animals per dose:
10 male and 10 female
Details on study design:
The optimisation test was used, an intracutaneous sensitisation procedure exceeding the sensitivity of the method recommended in the "Appraisal of the Safety of Chemical in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).

During the induction period the animals received injections every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % solution of TK 11'278 in propylenglycol 50 % / saline 50 %. One control group was treated with the vehicle alone ("negative control").

On the first day of week 1, two injections of 0.1 mL were administered into the shaven skin of the right flank and on the following days a single intracutaneous injection was given into the flank.

During the second and third week of the induction period the test material was incroporated in a mixture of saline with complete Bacto Adjuvant. (saline : adjuvant = 1:1)

During week 6 a challenge injection of 0.1 mL of a freshly prepared 0.1 % solution of TK 11'278 in propylenglycol 50 % /saline 50 % was administered into the skin of the left flank.

Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded.

The two largest perpendicular diameters (in mm) and the increase in the skin-fold thickness (in mm) were measured and by multiplication of these values the "reaction volume" was obtained (in µL) for each reading from each animal. The mean volume plus one standard deviation of the induction reactions observed in the individual animal in the first week was taken as representing the skin irritation "threshold" for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergenic reaction and the animal termed "positive". The number of "positive" animals in the test group was compared with the number of animals in the control group (treated with the vehicle alone) that showed a non-specific reaction of at least the same magnitude ("negative control").

During week 8 a subirritant dose (30 % TK 11'278 in vaseline) of the test compound was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The skin irritation was recorded according to Draize (described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" 1959 of the US Association of Food and Drug Officials (AFD0) 24 hours after removal of the dressings. For irritation score see table below:

Score for Skin Irritation

Erythema and eschar formation
No erythema........................................................ 0
Very slight erythema (barely perceptible) ...... 1
Well defined erythema ....................................... 2
Moderate to severe erythema .......................... 3
Severe erythema (beed redness) to slight
eschar formation (injuries in depth) ...............4
Total Possible Erythema Score .........................4
Challenge controls:
No data
Positive control substance(s):
no

Results and discussion

Positive control results:
No data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: after intradermal challenge injection
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: other: after intradermal challenge injection. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
other: after occlusive epicutanous application
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: after occlusive epicutanous application. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Challenge reactions after occlusive epicutaneous administration of the test material:

Erythema scoer (Draize Score) 24 hours after removal of the dressing: 0

Neither the male or female guinea pigs displayed erythema.

Table 1        Incidence of positive animals per group after intradermal challenge injection

  No. of positive animals  
  No. of treated animals  
Vehicle alone  2/20 
TK 11'278  2/20   

Table 2        Incidence of positive animals per group after occlusive epicutaneous application

  No. of positve animals    
  No. of treated animals  
Vehicle alone  0/20 
TK 11'278  0/20   

Table 3        Meand Bodywieghts and Standard Deviation (g)

 

Vehicle control

TK 11’278

Male

Female

Male

Female

Pre-test

502/28

450/23

493/21

472/25

End of test

682/46

576/39

685/39

626/33

Mean body weight gain

180

136

187

154

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions employed, no differences between the test group and the vehicle-treated controls were seen. after either intradermal or epidermal challenge application of TK 11'278. According to Directive 67/548/EEC, no classification is warranted. According to Regulation (EC) No. 1272/2008, no classification is warranted.

TK 11'278 was found to be deviod of skin-sensitising (contact allergenic) potential in albino guinea pigs.
Executive summary:

Under the experimental conditions employed, no differences between the test group and the vehicle-treated controls were seen. after either intradermal or epidermal challenge application of TK 11'278.

TK 11'278 was found to be deviod of skin-sensitising (contact allergenic) potential in albino guinea pigs. According to Directive 67/548/EEC, no classification is warranted. According to Regulation (EC) No. 1272/2008, no classification is warranted.

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