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Description of key information

The substance was found to be non sensitizing in a guinea pig maximization test and a guinea pig optimization test with intradermal induction concentrations of 0.1 or 1% and epidermal induction and challenge concentrations of 30%.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Sept. 20, 1982 to Dec. 30, 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Two intradermal and one epicutanous induction treatments; no sodium lauryl sulphate applied, no summary of the results of the reliability check provided.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Since valid in vivo data are available, no LLNA is necessary.
Species:
guinea pig
Strain:
other: Pribright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ivanovas Dermany
- Age at study initiation: 10 weeks old
- Weight at study initiation: 291 to 485 g
- Housing: individually in macrolon cages
- Diet: ad libitum standard guinea pig pellets NAFAG no. 830 supplemented with fresh carrots.
- Water: ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 50 +/- 10%
- Photoperiod (hrs dark / hrs light): 10 hrs dark/ 14 hrs light
Route:
intradermal
Vehicle:
other: sesame oil
Concentration / amount:
1%
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline PhH VI
Concentration / amount:
30%
Day(s)/duration:
48 h
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline PhH VI
Concentration / amount:
30%
Day(s)/duration:
24 h
No. of animals per dose:
10 male and 10 female per group
Details on study design:
RANGE FINDING TESTS:
The concentrations of the test compound for induction and challenge periods were determined on separate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two (intradermal and epicutaneous)
- Test groups: three pairs of intradermal injections (0.1 ml per injection) into the neck of the guinea-pigs with a mixture of adjuvant and saline, with the test compound in sesame oil and with the test compound in the adjuvant saline mixture. One week later the test article was incorporated in vaseline and applied on a filterpaper patch to the neck of the animals epicutaneously for 48 hours.
- Control group: treated with the vehicles alone
- Site: neck
- Concentrations: 1% for intradermal injection and 30% for epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Exposure period: 24 hours
- Test groups: Two weeks after the epidermal induction application the animals were tested on the flank with in vaseline
- Control group: treated with the vehicles alone
- Site: flank
- Concentrations: 30%
- Evaluation (hr after challenge): 24 and 48 hours after removing the dressings the challenge reactions were graded according the Draize scoring scale
Challenge controls:
Vehicle only
Positive control substance(s):
no
Positive control results:
The sensitivity of the strain is controlled every six months with p-phenylenediamine. No values given in the report.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30 % (epicutaneous)
No. with + reactions:
0
Total no. in group:
19
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 % (epicutaneous)
No. with + reactions:
0
Total no. in group:
19
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% (epicutanous)
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (epicutanous)
No. with + reactions:
0
Total no. in group:
20

One animal died during the performance of the test. The death of the animal can not related to the compound application.

Interpretation of results:
GHS criteria not met
Conclusions:
No animal was sensitized by the test item under the experimental conditions employed and the test item can, therefore, be classified to the lowest sensitization grade according to Magnusson and Kligman (Appendix 2)
Executive summary:

In order to investigate the sensitization potential of the test item a maximization test according to Magnusson and Kligman was peformed using 10 male and 10 female guinea-pigs. Two intradermal injections (0.1 ml per injection) were made into the neck of the guinea-pigs with a mixture of adjuvant and saline, with the test compound in sesame oil and with the test compound in the adjuvant saline mixture. One week later was incorporated in vaseline and applied on a filterpaper patch to the neck of the animals (occlusive administration for 48 hours). Two weeks after the epidermal induction application the animals were tested on the flank with in vaseline (24 h occlusive application). Twenty-four hours after removing the dressings the challenge reactions were graded according the Draize scoring scale. The application sites were chemically depilated 3 hours before examination (Veet, 5 minutes) per group. A control group was treated with the vehicles alone (negative control). One animal died during the performance of the test. The death of the animal can not related to the compound application. No animal reacted after the challenge application and the test itel can therefore be classified to the lowest sensitization grade of Magnusson and Kligman.

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

The skin sensitizing properties were investigated in two valid studies (Optimization test and Maximization test). Both studies are similar in design to OECD testing guideline 406 (1981). They were not performed under GLP, but are reported in sufficient detail as reasonably thorough description of authors, dates, design, results and interpretation is given. Both studies used a non-irritant dose for epidermal induction and therefore, a topical application of 0.5 mL of 10% sodium lauryl sulfate in vaseline should have been applied in order to create local irritation.

For the Maximization test, Pirbright White guinea pigs received two intradermal induction treatments with 1% in sesame oil and one epicutaneous induction treatment with 30% in vaseline. For each injection, three pairs (adjuvant/saline; test item in vehicle; test item in vehicle plus adjuvant/saline) were given. Epidermal challenge was performed by occlusive application for 24h two weeks later. No skin reactions were observed either for control or test group animals. The sensitivity of the strain was verified by treatment with p-phenylenediamine every six months.

For the Maurer Optimization tests, Pirbright White guinea pigs received ten intradermal induction treatments of 0.1% in olive oil. Of these, 6 injections also included Freund's adjuvant. Two challenge experiments were performed: First, intradermal challenge with either vehicle or with 0.1% test item in vehicle were used. Intradermal injection of the vehicle itself caused a reaction in 13 of 20 animals, whereas treatment with the test item caused reactions in 12 of 18 animals. Second, epidermal challenge was performed by occlusive application for 24h ten days later. No skin reactions were observed either for control or test group animals. The sensitivity of the strain was verified by treatment with p-phenylenediamine every six months.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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

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