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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:
24 June- 25 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
see below
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
In the preliminary study for the determination of the maximum concentration causing a slight to moderate irritation by cutaneous application: by mistake, the filter paper saturated with the formulated test substance was held in place for 48 hrs using Elastplaste semi-occlusive dressing instead of Blenderm 3M (5 cm width) occlusive dressing made up of surgical tape.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The GPMT test was performed in 2003 before the LLNA test was performed in 2005.

Test material

Constituent 1
Reference substance name:
Hexadecanoic acid, 2-sulfo-,1-methylester, sodium salt
IUPAC Name:
Hexadecanoic acid, 2-sulfo-,1-methylester, sodium salt
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: white powder
- Storage condition of test material: at 4 ºC

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France
- Age at study initiation: no data
- Weight at study initiation: 392.7 +/- 8.6 g for the control males and 393.4 +/- 4.1 g for the treated males.
- Housing: five males per treatment group in a cage of standard size
- Diet (e.g. ad libitum): daily at fixed times
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days before the preliminary study and 6 days before the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% and 5%
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
2% and 5%
No. of animals per dose:
10
Details on study design:
PRELIMINARY TESTS:
- determination of the maximum concentration causing a slight to moderate irritation by intradermal injection of 0.1 mL in the retro-scapular region at 6 sites.
- Determination of the maximum concentration causing a slight to moderate irritation by cutaneous application of 0.2 mL over an area of 8 cm^2, using one concentration on each flank (5 w/v% and 2 w/v%).
- Determination of the Maximum Non-irritant Concentration by cutaneous application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal induction on Day 1 and topical induction on Day 8
- Exposure period: Day 1 and Day 8
- Test groups: 10 males
- Control group: 10 males
- Site:
Site 1: 2 injections of 0.1 ML of complete Freund's adjuvant diluted 50% in sterile and pyrogenfree isotonic sodium chloride solution.
Site 2: 2 injections of 0.1 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 0.1 w/v%
Site 3: 2 injections of 0.1 mL of an emulsion of equal volume of complete Freund's adjuvant diluted 50% in sterile and pyrogenfree isotonic sodium chloride solution and of fomulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt. The final concentration of fomulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt injected was the same as used for site 2.
- Frequency of applications: second induction with 0.2 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 5 w/v% by cutaneous application on a piece of filter paper, held in place for 48 hrs using an occlusive dressing.

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: on Day 22
- Exposure period: 24 hrs
- Test groups: 10 males/treatment
- Control group: 10 males
- Site: the right flank region over 2 areas of approx. 4 cm^2
- Concentrations: 0.1 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 5 w/v% and 2 w/v% on an occlusive dressing.
- Evaluation (hr after challenge): approx 24 hrs and 48 hrs after removal of the dressing

Challenge controls:
Negative control animals received 0.1 mL of formulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt at MNIC (2 w/v%) and the lower concentration chosen by the sponsor.
The positive control animals received 0.1mL of 1% DNCB solution.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB, 1% in alcoholic solution)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
not specified
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
not specified
No. with + reactions:
10
Total no. in group:
10

Any other information on results incl. tables

- No mortallity occurred throughout the study

- Behaviour of the animals treated with the test substance was normal and was not different from that of the control group.

- Mean body weight gain in animals treated with the test substance did not differ significantly from that of animals of the negative control group.

- Skin reactions: evaluation of local irritation: no irritation reaction was noted at times 24 and 48 hrs in animals of the negative control group and in animals treated during the challange phase with the test substance at the MNIC and at the lower concentration.

- the maximum slight to moderate irritant concentration by intradermal administration was 0.1 w/v% of formulated test substance

- The maximum non-irritant concentration (MNIC) determined by epicutaneous application was 2 w/v% of formulated test substance.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions adopted, the test substance showed no allergenicity at 24 and 48 hours. It is thus considered that the test substance is free of any sensitising capacity in the male guinea pig.