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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1976-04
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
no details about the test substance; no pilot-/range-finding study was conducted to find appropriate test concentrations
Justification for type of information:
Justification for Read Across is given in Section 13 of IUCLID

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), of the US Association of Food and Drug Officials (AFDO)
Deviations:
not applicable
Principles of method if other than guideline:
Maurer optimisation test
GLP compliance:
no
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (different from LLNA test) is available.

Test material

Constituent 1
Chemical structure
Reference substance name:
Didodecyl 3,3'-thiodipropionate
EC Number:
204-614-1
EC Name:
Didodecyl 3,3'-thiodipropionate
Cas Number:
123-28-4
Molecular formula:
C30H58O4S
IUPAC Name:
Didodecyl 3,3'-sulfanediyldipropanoate

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: bred on the premises
- Weight at study initiation: 400 - 450 grams
- Housing: individually in Macrolon cages, type 3
- Diet: standard guinea pig pellets - NAFAG, Gossau SG, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Humidity: 55 ± 5 %
- Photoperiod: 10 hrs dark /14 hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: polyethylene glycol: saline (70:30)
Concentration / amount:
0.1 %
Route:
intradermal
Vehicle:
other: adjuvant
Concentration / amount:
0.1 %. When adjuvant was present, the test substance was mixed with adjuvant in a 1:1 ratio.
Challenge
Route:
intradermal
Vehicle:
other: polyethylene glycol : saline (70:30)
Concentration / amount:
0.1 % in polyethylene glycol / saline (70:30) without adjuvant
No. of animals per dose:
10 males and 10 females
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9 (3 in the first week, 3 in the second week, and 3 in the third week)
- Exposure period: intradermal injections
- Test groups: test substance + vehicle + saline the first week; test substance + adjuvant (Bacto Adjuvant) in the second and third week
- Control group: vehicle + saline (negative control) and DNCB + vehicle + saline (positive control) in the first week; vehicle + adjuvant (negative control) and DNCB + FCA (positive control) the second and third week
- Site: flank and back (first injection); back (2nd and 3rd injection); neck (4th-9th injection)
- Frequency of applications: Monday, Wednesday, and Friday
- Duration: 0 - 19 d
- Concentrations: 0.1 ml of 0.1 % test substance solution

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 33
- Exposure period: intradermal injection
- Test groups: test substance + vehicle + saline
- Control group: vehicle + saline (negative control) and DNCB + vehicle + saline (positive control)
- Site:previously untreated flank
- Concentrations: 0.1 ml of 0.1 % test substance solution
- Evaluation (hr after challenge): 24

OTHER:
Assessment
During the 1st week volumes of 0.1 ml of the test substance (0.1 %) in polyethylene glycol / saline (70:30) without adjuvant were injected intradermally on Monday at two sites (flank and back). Twenty-one hours after administration, the animals were chemically depilated with Butoquick® and three hours later the skin reaction was assessed under artificial lighting (Luxram E 27, "Daylight"). The two largest diameters of the erythematous reaction in vertical alignment were measured (mm) and the skin-fold thickness was determined with a skin-fold gauge (mm). The individual "reaction volume" (μl) was calculated from these values for each reaction from each animal. 24 hours after challenge, the reaction site was evaluated in the same manner as during the first testing week.
For each animal the mean value + one standard deviation was calculated for the reaction volumes of the intracutaneous injections from the first testing week. Skin sensitization was defined to occur of the challenge reaction whenever the reaction volume exceeded the mean value + one SD of the pre-sensitization responses.
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
Dinitrochlorobenzene (DNCB)

Study design: in vivo (LLNA)

Statistics:
The number of positive animals in each group was counted with significant differences between treated and control groups assessed by the Fisher test.

Results and discussion

Positive control results:
20/20 animals showed a positive reaction (significant difference to control group: p < 0.001)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
None reported
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
None reported
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 %
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
None reported

Applicant's summary and conclusion

Interpretation of results:
other: the substance is not classified for skin sensitisation according to the CLP Regulation (EC) No.1272/2008
Conclusions:
The substance is not considered as a skin sensitiser.
Executive summary:

The skin sensitisation potential of the substance was evaluated in the Maurer optimisation test according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), of the US Association of Food and Drug Officials (AFDO). During the induction period (days 0 -19) ten male and ten female guinea pigs were subjected to intradermal injections with 0.1 % of substance in polyethylene glycol:saline (70:30). After one week the animals were subjected to intradermal injections with 0.1 % of substance with adjuvant (ratio 1:1) for two weeks. The animals were later challenged with intradermal injections of 0.1 % of substance in polyethylene glycol:saline (70:30). After 24 hrs the skin reactions were assessed and the skin-fold thickness of the erythemateous reaction and the individual "reaction volume was determined.

Skin sensitization was defined to occur of the challenge reaction whenever the reaction volume exceeded the mean value + one SD of the pre-sensitization responses.

Only two out of 20 test group animals presented skin reactions while one out of 20 animals in the negative control group had a positive reaction.

The substance is not considered as a skin sensitiser.