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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Acceptable, reasonably well documented publication Deviations: - none of the reference substances recommended in the guideline were used as positive control. - the induction procedure and schedule differed from that specified in the guideline for the Guinea pig maximisation test. Instead of giving the test animals three sets of different intra-dermal injections (1. mixture FCA/water or physiological saline; 2. test substance with vehicle; 3. test substance-vehicle in FCA/water or physiological saline mixture) at the initiation and a topical induction application on day 6 for 48 hours under occlusion, each animal was treated three times a week with only one intra-dermal injection (test substance in physiological saline, and in the second and third week test substance in FCA and physiological saline) for three weeks. The challenge occurred 14 days after the last induction, but as an injection instead of topical administration.
Justification for type of information:
The extrapolation from sorbic acid to potassium sorbate is considered not to be restricted in any way, since the determinant of potential toxicity is the sorbate anion.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
, 1996
Deviations:
yes
Remarks:
, please refer to "rationale for reliability incl. deficiencies" above
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A test guideline for a local lymphnode assay was not available at the time the study was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Sorbid acid
- Purity: "purum"
- Expiration date of the lot/batch: the test substance was considered to be stable for the duration of this study.

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: Research Department of the Pharmaceuticals Dividsion, Ciba-Geigy Ltd., Basel, Switzerland.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: physiological saline (induction and intra-dermal challenge), soft white petrolatum (epidermal challenge)
Concentration / amount:
Induction 0.1 % intracutaneous
First challenge 0.1 % intracutaneous
Second challenge 1 % occlusive epicutaneous
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: physiological saline (induction and intra-dermal challenge), soft white petrolatum (epidermal challenge)
Concentration / amount:
Induction 0.1 % intracutaneous
First challenge 0.1 % intracutaneous
Second challenge 1 % occlusive epicutaneous
No. of animals per dose:
Number of animals per group: 10 males and 10 females
Details on study design:
PREPARATION OF TEST SUBSTANCE FOR APPLICATION:
- Induction period (first week) and first challenge: 0.1 % test substance in physiological saline
- Induction period (second and third week): 0.1 % test substance in physiological saline and adjuvant
- Second challenge: 1 % test substance in soft white petrolatum.
- Concentration Freund's Complete Adjuvant (FCA): test material in 1:1 adjuvant/saline

MAIN STUDY
A. INDUCTION EXPOSURE
- Induction schedule: intracutaneous, 3 days/week for 3 weeks
- Way of induction: intra-dermal: first week in flank and/or back, second and third week into nuchal skin.
- Amount applied: 0.1 mL per application

B. CHALLENGE EXPOSURE
- Challenge schedule: 14 days after last induction dose
- Concentrations used for challenge: 0.1 %, intracutaneous; flank
- Rechallenge: yes, 14 days after first challenge; topical
- Concentrations used for rechallenge: 1 %, occlusive for 24h

EXAMINATIONS: erythema, skinfold thickness
Challenge controls:
Controls: yes, physiological saline (10 males / 10 females)
Positive control substance(s):
yes
Remarks:
0.1 % (intra-dermal challenge) and 1 % ethylene diamine in physiological saline (epidermal challenge)

Study design: in vivo (LLNA)

Statistics:
Fisher's exact test

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: First challenge
Group:
test group
Dose level:
0.1 % test substance in physiological saline (intra-dermal challenge)
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading:
Reading:
rechallenge
Group:
test group
Dose level:
1 % test substance in physiological saline (epidermal challenge)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No incidences were observed following epidermal challenge.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. Group: test group. Dose level: 1 % test substance in physiological saline (epidermal challenge). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No incidences were observed following epidermal challenge..
Reading:
other: First challenge
Group:
negative control
Dose level:
physiological saline (intra-dermal challenge)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading:
Reading:
rechallenge
Group:
negative control
Dose level:
physiological saline (epidermal challenge)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. Group: negative control. Dose level: physiological saline (epidermal challenge). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
other: First challenge
Group:
positive control
Dose level:
0.1 % ethylene diamine in physiological saline (intra-dermal challenge)
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading:
Reading:
rechallenge
Group:
positive control
Dose level:
1 % ethylene diamine in physiological saline (epidermal challenge)
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. Group: positive control. Dose level: 1 % ethylene diamine in physiological saline (epidermal challenge). No with. + reactions: 4.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification: not sensitizing
The observed challenge incidence for sorbic acid after intradermal injection was 4 of 20 animals. No incidences were observed following epidermal challenge.