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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Maurer et al: The Optimization test in the guinea pig, Agents & Actions 5 (2), 174-179, 1975; Predictive evaluation in animals of the contact allergenic potential of medically important substances Contact Dermatitis 4, 321-333, 1978
Principles of method if other than guideline:
The optimization test was used, an intracutaneous sensitization procedure similar to 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
Remarks:
prior to GLP
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
An older guinea pig test was already available. No further testing is necessary.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)
EC Number:
230-426-4
EC Name:
2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)
Cas Number:
7128-64-5
Molecular formula:
C26H26N2O2S
IUPAC Name:
2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)
Details on test material:
- Physical appearance: yellow/greenish powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Pirbright white strain bred on own premises
- Age at study initiation: no data
- Weight at study initiation: 260 to 430 grams
- Housing: individually in Macrolon cages, type 3
- Diet: standard guinea pig pellets - NAFAG No. 830, Gossau SG; ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 55 +/-5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 10/14
- Experiment started: May 28, 1979

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: polyethyleneglycol : saline (70 : 30 parts)
Concentration / amount:
0.1 %
Challengeopen allclose all
No.:
#1
Route:
intradermal
Vehicle:
other: polyethyleneglycol : saline (70 : 30 parts)
Concentration / amount:
0.1%
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30%
No. of animals per dose:
20
Details on study design:
MAIN STUDY

A. INDUCTION EXPOSURE
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 % dilution in polyethylene glycol (PEG 400) + saline (70 : 30 parts). One control group was treated with the vehicle alone ("negative control").
On the first day, injections of 0.1 mL were administered into the shaven 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 the induction period the test substance were incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant [complete Freund, Difco, USA] (vehicle : adjuvant = 1: 1).

B. CHALLENGE EXPOSURE
Fourteen days after the last sensitizing injection, a challenge injection of 0.1 mL of a freshly prepared 0.1% dilution of freshly prepared test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts) 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 “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 allergic 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").

Ten days after the intracutaneous challenge injection a subirritant dose of the test compound was applied epicutaneously under occlusive dressings which were left in place for 24 hours.
Challenge controls:
One group treated with the vehicle alone.
Positive control substance(s):
no

Results and discussion

Positive control results:
Not applicable.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: after occlusive epicutaneous application
Hours after challenge:
24
Group:
test chemical
Dose level:
30 % in Vaseline
No. with + reactions:
0
Total no. in group:
20
Reading:
other: after occlusive epicutaneous application
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle control
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One female guinea pig died spontaneously 23 days after starting the experiment.
Reading:
other: after intradermal challenge injection
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1% dilution of the test substance
No. with + reactions:
10
Total no. in group:
20
Reading:
other: after intradermal challenge injection
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle control
No. with + reactions:
3
Total no. in group:
19
Clinical observations:
One female guinea pig died spontaneously 23 days after starting the experiment.

Any other information on results incl. tables

 

Mean Bodyweights / Standard Deviation (g)

 

Vehicle control

Test substance

 

male

female

male

female

pre test

484/18

459/26

418/54

419/29

end of test

577/60

565/37

467/44

471/38

Remark: One female guinea pig of the control group died spontaneously 23 days after starting the experiment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions employed, no differences between the test group and the vehicle-treated controls were seen, the test article was found to be devoid of skin-sensitizing (contact allergenic) potential in albino guinea-pigs.

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