Carbamic acid,N,N'-[1,3-phenylenebis[methyleneiminocarbonylimino(methyl-3,1-phenylene)]]bis-di-C11-14-isoalkylesters, C13-rich

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

does not affect the validity of the study

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

bis(11-methyldodecyl) ((((1,3-phenylenebis(methylene)bis(azanediyl))bis(carbonyl) bis(azanediyl))bis(4-methyl-3,1-phenylene) dicarbamate

Cas Number:

865536-03-4

Molecular formula:

C52H80N6O6

IUPAC Name:

bis(11-methyldodecyl) ((((1,3-phenylenebis(methylene)bis(azanediyl))bis(carbonyl) bis(azanediyl))bis(4-methyl-3,1-phenylene) dicarbamate

Constituent 2

Reference substance name:

bis(11-methyldodecyl)(4-methyl-1,3-phenylene)dicarbamate

Molecular formula:

C35H62N2O4

IUPAC Name:

bis(11-methyldodecyl)(4-methyl-1,3-phenylene)dicarbamate

Constituent 3

Reference substance name:

11-methyldodecyl (3-(3-(3-(aminomethyl)benzyl)ureido)-4-methylphenyl)carbamate

Molecular formula:

C30H46N4O3

IUPAC Name:

11-methyldodecyl (3-(3-(3-(aminomethyl)benzyl)ureido)-4-methylphenyl)carbamate

Constituent 4

Reference substance name:

1,1'-(4-methyl-1,3-phenylene)bis(3-(3-(aminomethyl)benzyl)urea)

Molecular formula:

C25H30N6O2

IUPAC Name:

1,1'-(4-methyl-1,3-phenylene)bis(3-(3-(aminomethyl)benzyl)urea)

Test material form:

solid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

5%, 10%, 25%

No. of animals per dose:

4

Details on study design:

In order to study a possible allergenic potential of THIX Additiv VP-E 1724/02, three groups each of four female mice were treated with different concentrations of the test item by topical application at the dorsum of each ear (left and right) on three consecutive days. A control group of four mice was treated with the vehicle only. Five days after the first topical application, the mice were intravenously injected into a tail vein with radio-labelled thymidine (3H-methyI thymidine). Approximately five hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a -scintillation counter.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

EC3= 8.5%

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

ca. 1.4

Test group / Remarks:

5%

Remarks on result:

other:

Remarks:

The EC3 value could not be calculated, since all obtained Sl's were below 3.

Results 2

Key result

Parameter:

SI

Value:

ca. 2.64

Test group / Remarks:

10%

Remarks on result:

other:

Remarks:

The EC3 value could not be calculated, since all obtained Sl's were below 3.

Results 3

Key result

Parameter:

SI

Value:

ca. 2.8

Test group / Remarks:

25%

Remarks on result:

other:

Remarks:

The EC3 value could not be calculated, since all obtained Sl's were below 3.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In order to study a possible contact allergenic potential of THIX Additiv VP-E 1724/02, three groups each of four female mice were treated daily with the test item at concentrations of 5, 10, and 25% (w/v) in dimethylsulfoxide by topical application to the dorsum of each ear (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (dimethylsulfoxide) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3 H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of H-methyl thymidine measured in a ß-scintillation counter. All treated animals survived the scheduled study period and no signs of toxicity were observed. A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration resulted in 3-fold or greater increase in incorporation of 3 HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.) The estimated concentration of test item required to produce a S.l. of 3 is referred to as the EC3 value. In this study Stimulation Indices of 1.40, 2.64, and 2.80 were determined with the test item at concentrations of 5, 10, and 25% in dimethylsulfoxide. The EC3 value could not be calculated, since all obtained Sl's were below 3. The test item THIX Additiv VP-E 1724/02 was not a skin sensitiser under the described conditions.

Executive summary:

In the study the test item THIX Additiv VP-E 1724/02 formulated in dimethylsulfoxide was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations 5, 10, and 25%. The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. In this study Stimulation Indices (S.l.) of 1.40, 2.64, and 2.80 were determined with the test item at concentrations of 5, 10, and 25% in dimethylsulfoxide, respectively. The test item THIX Additiv VP-E 1724/02 was not a skin sensitiser.