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Description of key information

The test substance was found to be devoid of skin-sensitizing (contact allergenic) potential in albino guinea-pigs. Furthermore, in a human patch test the test substance was found to be not a skin sensitizer at concentrations of 0.5% and 1%.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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.
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
Route:
intradermal
Vehicle:
other: polyethyleneglycol : saline (70 : 30 parts)
Concentration / amount:
0.1 %
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
Positive control results:
Not applicable.
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.

 

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.

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin-sensitising potential of the test substance was investigated on groups of 10 male and 10 female guinea pigs (optimization test). During the induction period the animals received one injection every second day to a total of 10 intracutaneous injections of a freshly prepared 0.1 % suspension of the test substance in propylene glycol (70 %). One control group was treated with the vehicle alone. 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 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 the test substance in propylene glycol 70 % 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. Ten days after the intracutaneous challenge injection a subirritant dose of the test compound (30% in vaseline) was applied epicutaneously under occlusive dressings which were left in place for 24 hours. Under the experimental conditions employed, no differences between the test group and the vehicle-treated controls were seen. In the epidermal challenge, no animal showed a dermal reaction. The test substance was found to be devoid of skin-sensitizing (contact allergenic) potential in albino guinea-pigs.

 

In a supporting study, a patch test with humans was performed with the test substance. The test substance in 0.5 % and 1 % concentrations in paraffin was applied to the skin of a total of 102 people; a second or "challenge" application was made to all of these same people after an interval of two or three weeks. Out of all these test there were no positive reactions to suggest that the test substance were either primary an irritant or sensitizer, and it was concluded that the test substance is safe at these concentrations.

 

Another skin-sensitising study is available which was disregarded since no epidermal challenge was performed. Thus, the results were not considered relevant for the evaluation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP). As a result the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008.