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Toxicological information

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:
from August 29, 1983 to October 21, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
guideline test, well performed and detailed information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
The study was performed long before availability of the LLNA protocol.

Test material

Constituent 1
Chemical structure
Reference substance name:
[[(2-ethylhexyl)oxy]methyl]oxirane
EC Number:
219-553-6
EC Name:
[[(2-ethylhexyl)oxy]methyl]oxirane
Cas Number:
2461-15-6
Molecular formula:
C11H22O2
IUPAC Name:
2-{[(2-ethylhexyl)oxy]methyl}oxirane
Test material form:
other: colourless liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Auxiliary compounds: Bacto Adjuvant, Complete Freund
Test system
Guinea pigs are the animals of choice for sensitization studies.
The test was performed on 10 male and 10 female guinea pigs of the Pirbright white strain (Tif:DHP) weighing between 259 g to 447 g (~10 weeks old).
Animals received: 19.08.1983, Acclimatisation period: 11 days
The animals were housed individually in Macrolon cages type 3, assigned to the different groups by means of random numbers generated by the random number generator incorporated in the Hewlett-Packard desk computer, identified with individual ear tags, kept at a constant room temperature of 21 ±2 °C, at a relative humidity of 50 ±10% and on a 14 hours light cycle day. A 14 hours light cycle day is necessary to eliminate seasonal variation because the animal rooms are not totally protected from natural sunlight.
The animals received ad libitum standard guinea pig pellets - NAFAG No. 84 6, Gossau SG - and water, supplemented with fresh carrots.
The sensitivity of the strain is controlled every six month with p-phenylenediamine.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal,20% propylene glycol/ 80% physiological saline;epidermal,vaseline
Concentration / amount:
0.1 % for intradermal application
30 % for epidermal application
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal,20% propylene glycol/ 80% physiological saline;epidermal,vaseline
Concentration / amount:
0.1 % for intradermal application
30 % for epidermal application
No. of animals per dose:
20
Details on study design:
During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1% suspension of TK 10529 in 20% propylene glycol/80% saline, homogenized with ultrasound. One control group was treated with the vehicle alone ("negative control").
On the first day, injections of 0.1 mL were administered into the shaved skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back.
During the second and third week of induction the test material was incorporated in a mixture of the normal vehicle with complete Bacto adjuvant (vehicle: adjuvant = 1 : 1).
Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1% suspension of TK 10529 in 20% propyleneglycol/80% saline, homogenized with ultrasound, was administered into the skin of the left flank.
Twenty-four hours after each injection during the first week of induction 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 a "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 of the induction period was graded as an allergic reaction and the animal termed "positive". The number of positive animals in the test group was compared with the number of positive animals in the control group (treated with the vehicle alone) that showed non-specific reactions of at least the same magnitude ("negative control").
Ten days after the intracutaneous challenge injection a sub-irritant dose of the test compound (30% TK 10529) in vaseline and vaseline alone was applied epicutaneously under, occlusive dressings which were left in place for 24 hours. The reactions were evaluated 24 and 48 hours after removing of the bandages according to the Draize scoring scale. The control group was treated with vaseline and, in at least 10 animals, with TK 10529 in vaseline to check the sub-irritant concentration of the test compound in adjuvant treated animals.

Challenge controls:
0.1 mL vaseline, 20 animals
Positive control substance(s):
yes
Remarks:
p-phenylenediamine

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
rechallenge
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
The guinea pig strain is tested every six month with p-phenelendiamine as positive control substance for sensitivity. Sensitivity of the test system was confirmed in the report.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20% propylene glycol/80% saline,
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading 24 hours after challenge: Group: negative control. Dose level: 20% propylene glycol/80% saline,. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 % suspension of TK 10529 in 20% prop,ylene glycol/80% saline,
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading 24 hours after challenge: Group: test group. Dose level: 0.1% suspension of TK 10529 in 20% propylene glycol/80% saline,. No with. + reactions: 18.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 mL vaseline
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 24 hours after challenge: Group: negative control. Dose level: 0.1 mL vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: control group: test article treated
Dose level:
30% TK 10529
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge 24 hours after challenge: Group: other: control group: test article treated. Dose level: 30% TK 10529. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
30% TK 10529
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 24 hours after challenge: Group: test group. Dose level: 30% TK 10529. No with. + reactions: 19.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: test group: vehicle treated
Dose level:
0.1 mL vaseline
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 24 hours after challenge: Group: other: test group: vehicle treated. Dose level: 0.1 mL vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.1 mL vaseline
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 48 hours after challenge: Group: negative control. Dose level: 0.1 mL vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: control group: test article treated
Dose level:
30% TK 10529
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge 48 hours after challenge: Group: other: control group: test article treated. Dose level: 30% TK 10529. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
30% TK 10529
No. with + reactions:
17
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 48 hours after challenge: Group: test group. Dose level: 30% TK 10529. No with. + reactions: 17.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: test group: vehicle
Dose level:
0.1 mL vaseline
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge 48 Hours after challenge: Group: other: test group: vehicle. Dose level: 0.1 mL vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

A)   Incidence of positive animals per group of intradermal challenge injection.

  No. of positive animals/

No. of treated animals               P

Control group, vehicle control                                             2/2 0

TK 10529                                                                         18/2 0                       <0.01

 

B)    Incidence of positive animals per group after occlusive epicutaneous application.

  No. of positive animals/

No. of treated animals               P

After 24 hours

Control group, vehicle control                                             0/2 0

TK, 10529                       0/1 0

Test group,        TK 10529                                              19/ 20                         <0.01

Vehicle control                                       0/2 0

After 48 hours

Control group,    vehicle control                                          0/2 0

TK 10529                                           0/1 0

Test group,          TK 10529                                            17/2 0                        < 0.01

Vehicle control                                      0/2 0

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Test substance is considered to possess skin-sensitizing (contact allergenic) potency in albino guinea-pigs.
Executive summary:

This key study was conducted to assess the allergenic potential of the test article when administered to the skin of guinea pigs using the optimization test.


The intradermal induction of sensitization was carried out with a 0.1% suspension of the test article in 20% propylene glycol/80% saline. The epicutaneous induction of sensitization was conducted under occlusion with the test article at the same concentration above. Two weeks after the epicutaneous induction application the first challenge was completed by epicutaneous application of the test article at 0.1% in 20% propylene glycol/80% saline under occlusive dressing. The animals of the control group were induced with 20% propylene glycol/80% saline and challenged similarly as those of the test group. Ten days after the intracutaneous challenge injection a sub-irritant dose of the test compound (30% TK 10529) in vaseline and vaseline alone was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The control group was treated with vaseline and, in at least 10 animals, with TK 10529 in vaseline to check the sub-irritant concentration of the test compound in adjuvant treated animals. Cutaneous reactions, i.e erythema and oedema formation were evaluated at 24 and 48 hours after removal of the dressing.


90% of the animals of the test group were observed with positive skin reactions after the first challenge treatment with test substance concentration of 0.1% in 20% propylene glycol/80% saline. No positive reactions were observed in the control group. And in the second challenge assay, positive skin reaction of erythema was observed in 19 of 20 animals after 24 hrs of administration, and 17 of 20 animals showed positive reaction after 48 hrs of application.


Under the experimental conditions employed, significant differences between the test group and the vehicle-treated controls were seen after both intradermal and epidermal challenge application of test substance. Therefore, the test substance is considered to possess skin-sensitising (contact allergenic) potency in albino guinea-pigs. The test substance can be classified as skin sensitisation sub-category 1A according to the CLP regulation (Regulation EC No. 1272/2008).