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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:
March-May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This in vivo study on skin sensitization according to Magnusson & Kligman and OECD test guidelines (OECD TG 406) was conducted in 1998, which was prior to the adoption of the initial OECD guideline on the Local Lymph Node Assay in 2002. By that time, the method according to Magnusson & Kligman was one of two preferred test protocols for studying a skin sensitisation potential and is still considered adequate and sufficient for the assessment of that endpoint.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan S.r.l., Correzzana (MI), Italy
- Age at study initiation: about 6 weeks
- Acclimation period: at least 5 days

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: corn oil (pilot study and intradermal and topical induction in the main study) or petrolatum (challenge)
Concentration / amount:
Pilot study:
- intradermal injection: 0.1, 0.5, 1, 2, 5, and 10 % (vehicle: corn oil); the 0.5 % concentration led to very slight erythema in 1 of 2 animals and was chosen for the main study
- topical application: 1, 5, 10, 20, and 50 % (vehicle: corn oil); none of the concentrations induced signs of skin irritation; the 50 % concentration was chosen for the main study

Main Study:
- intradermal injection: 0.5 % in corn oil
- topical application: 50 % in corn oil
- challenge (topical application): 20 % in petrolatum
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: corn oil (pilot study and intradermal and topical induction in the main study) or petrolatum (challenge)
Concentration / amount:
Pilot study:
- intradermal injection: 0.1, 0.5, 1, 2, 5, and 10 % (vehicle: corn oil); the 0.5 % concentration led to very slight erythema in 1 of 2 animals and was chosen for the main study
- topical application: 1, 5, 10, 20, and 50 % (vehicle: corn oil); none of the concentrations induced signs of skin irritation; the 50 % concentration was chosen for the main study

Main Study:
- intradermal injection: 0.5 % in corn oil
- topical application: 50 % in corn oil
- challenge (topical application): 20 % in petrolatum
No. of animals per dose:
10 in control group, 20 in test group
Details on study design:
1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 20 % occlusive epicutaneous
Challenge controls:
yes

Results and discussion

Positive control results:
The most recent reliability checks were performed in 1999 (Study number 5246-010) and 2000 (Study number 5246-011) with the reference Substance Mercaptobenzothiazole and showed the sensitivity and validity of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group treated with test substance at challenge
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group treated with test substance at challenge. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group treated with the test substance at challenge
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: control group treated with the test substance at challenge. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle alone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle alone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Mercaptobenzothiazole
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
no data
Remarks on result:
positive indication of skin sensitisation
Remarks:
RTC Study Number 5246-011
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Mercaptobenzothiazole
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
RTC Study Number 5246-011

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

In a delayed dermal sensitization test in the Guinea pig (Magnusson and Kligman Test) performed according to OECD TG 406 the test item was intradermally injected in a concentration of 5 % and topically applied in a concentration of 50 % for induction (in corn oil). The challenge was performed with a 20 % concentration in petrolatum. After challenge no response to the test item was apparent in any animal of either test or control group. These results indicate that the test item does not elicit a skin sensitization response in the Guinea pig.