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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: experimnental result on similar substance
Adequacy of study:
key study
Study period:
May 11, 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:
equivalent or similar to
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
Deviations:
not specified
GLP compliance:
no
Remarks:
Study conducted before 1981
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA-skin sensitisation study does not need to be conducted because adequate data from an in vivo (non-LLNA) study are already available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin and Kingman Ltd. Grimston, Hull, England
- Weight at study initiation: 330 to 460 g
- Housing: individually in Macrolon cages
- Diet:standard guinea pig pellets - NAFAG, No. 830, Gossau SG ad libitum
- Water: ad libitum
- Randomisation: the animals were 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 ml of 0.1 % suspension
Day(s)/duration:
21 days
Challenge
No.:
#1
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
0.1 ml of 0.1 % suspension
Day(s)/duration:
Intradermal: 10 days, epicutaneous 24 hours
No. of animals per dose:
10 male and 10 female
Details on study design:
Testing procedure
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 the test substancein physiological saline. 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 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 the test substance in physiological saline 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.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Group:
test group
Dose level:
0.1 ml of 0.1 % of test substance
No. with + reactions:
13
Total no. in group:
20
Remarks on result:
other: Incidence of positive animals per group after intradermal challenge injection
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1 ml of 0.1 % of test substance
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Incidence of positive animals per group after occlusive epicutaneous application

Any other information on results incl. tables

One animal (male) of the test group died spontaneously 34 days after starting the experiment.

Applicant's summary and conclusion

Interpretation of results:
other: Category 1A (indication of significant skin sensitising potential) based on CLP criteria
Conclusions:
Sensitising
Executive summary:

Method:

To assess the allergenic potential of the test substance in albino guinea pigs the Maximization-Test was used according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).The test was performed on groups of 10 male and 10 female guinea pigs.

 

Observation

Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were only seen after intradermal challenge application of the test substance. No difference between the test and the control group was seen after epidermal challenge application. The negative results upon epidermal challenge demonstrate that, in artificially sensitized guinea-pigs, exposure of the intact skin to the test compound does not provoke contact dermatitis.

One animal (male) of the test group died spontaneously 34 days after starting the experiment.

 

Conclusion

The positive response during the test is ≥ 30 % responding at ≤ 0,1 % intradermal induction dose therefore the substance is considered as sensitising.