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Administrative data

Description of key information

Skin sensitisation: not sensitising (OECD 406; GLP)

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:
1992-08-28 to 1992-09-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Deviations from the OECD 406 (1992): positive control was missing,
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981-05-12
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1991-09-13
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The conduct of this study was prior to the establishment of the LLNA method (OECD 429).
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 272 to 337 g
- Housing: opaque PPL (Type IV) cages, two or three to a cage; bedding: softwood sawdust "Hahnflock H 3/4"
- Diet (ad libitum): pelleted diet, "3113 Altromin"
- Water (ad libitum): vitamin C enriched tap water acidified to pH 2.5 with HCI
- Acclimation period: four days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3°C,
- Relative humidity: 55 ± 15%.
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
5 % (w/w) of the test item
Day(s)/duration:
day 1
Route:
epicutaneous, occlusive
Vehicle:
other: diethylphathalate (DEP)
Concentration / amount:
50 % (w/w) of the test item
Day(s)/duration:
day 8 (duration: 48 hours)
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: diethylphathalate (DEP)
Concentration / amount:
50 % (w/w) of the test item
Day(s)/duration:
day 22 (duration: 24 hours)
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 guinea pigs
Details on study design:
RANGE FINDING TESTS:
On the basis of the preliminary investigations the doses for the main study were chosen.
The intradermal irritancy of the test article was investigated in order to find a slight to moderate irritant test concentration for the intradermal induction using intradermal injections as in the main study. The following test item concentrations were tested: 0.63 %, 1.25 %, 2.5 %, and 5 %

The topical irritancy of the test article was investigated in order to find a slight to moderate irritant concentration for the dermal induction and a non-irritating concentration for the challenge application using procedures similar to the main study. The following test item concentrations were tested: 25 % and 50 %.

Results:
intradermal injection: no skin reactions was observed for any test item concentration.
topical application: no skin reactions was observed for any test item concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection and dermal application)
- Site: area of dorsal skin 4 x 6 cm in the scapular region was clipped free of pair with an electric clipper.
- Frequency of applications: three pairs of intradermal injections were given once and 6 days later the same site was treated with approximately 0.5 g sodium lauryl sulphate (10% in petrolatum) to provoke a mild inflammatory reaction. 24 hours later 0.4 mL of the test item was topically applied to the skin using a patch.
- Exposure period: 48 hours (dermal application)
- Concentrations:
Test animals:
Intradermal:
i) 0.1 mL FCA diluted 1:1 with sterile distilled water
ii) 0.1 mL test article in groundnut oil (final concentration: 5 % (w/w))
iii) 0.1 mL test article and FCAin the ratio 1:1 (final concentration: 10 % (w/w))
Topical application:
50 % test material in diethylphathalate

Control animals:
Intradermal injection:
i) 0.1 mL FCA diluted 1:1 with sterile distilled water
ii) 0.1 mL groundnut oil
iii) 0.1 mL groundnut oil and FCA in the ratio 1:1 (w/w)
Topical application:
diethylphathalate

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (topical application three weeks after the intradermal induction)
- Exposure period: 24 hours
- Site: flanks (right flank: diethylphathalate; left flank: 50 % of the test item)
- Evaluation (hr after challenge): 24 and 48 hours after removal of the patch
Evaluation according to the Magnusson and Kligman grading scale.
Challenge controls:
20 guinea pigs were used as control animals
Challenge dose: 50 % of the test item
Positive control substance(s):
no
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 % (w/w) of test item
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 % (w/w) of test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No positive skin reactions were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 % (w/w) of test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No positive skin reactions were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 % (w/w) of test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No positive skin reactions were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.

Induction

Injections of FCA mixed with vehicle, test article and sterile distilled water elicted irritation. No skin reactions were seen following the topical induction.

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not a skin sensitiser.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin sensitiser.
Executive summary:

The skin sensitisation potential of the substance was investigated according to the guinea pig maximization test (OECD guideline 406 (1981)) using 20 Dunkin-Hartley guinea pigs. A control group of 20 animals were run concurrently.

The treatment regime involved an intradermal induction (5 % of the substance in groundnut oil) and a topical induction (50 % of the substance in diethylphathalate; occlusive dressing, exposure period: 48 hours). The day before topical induction the skin was treated with 10% sodium lauryl sulfate in petrolatum. The control animals were treated with groundnut oil during the intradermal induction and diethylphathalate during the topical induction.

Both control and test animals were subjected to a topical challenge exposure (test item concentration: 50 % of the substance in diethylphathalate, occlusive dressing, exposure period: 24 hours) three weeks after the intradermal induction. Administration sites were examined for erythema and oedema formation at 24 and 48 hours after removal of the test item application and scored according to the Magnusson and Kligman grading scale.

The sensitisation rate of the test item was 5 % and 0 % at 24 hours and 48 hours after patch removal, respectively.The test item is not considered to be a skin sensitiser.

According to the EC-Regulation 1272/2008 and subsequent regulations, the test substance is not classified as skin sensitiser.

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

Justification for classification or non-classification

Skin sensitisation

The substance does not possess a skin sensitisation potential and does not require classification as skin sensitiser according to Regulation (EC) No 1272/2008 and subsequent adaptations.