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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer-reviewed journal

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparison of the local lymph node assay with the guinea pig maximization test for the detection of a range of contact allergens
Author:
D.A. Basketter and E.W. Scholes
Year:
1992
Bibliographic source:
Fd. Chem. Toxic .Vol. 30, No 1, pp.65-69,1992
Reference Type:
publication
Title:
Compilation of Historical local Lymph Node Data for Evaluation of skin Sensitization Alternative method
Author:
G. Frank Gerberick, Cindy A. Ryan, Petra S. Kern, Harald Schlatter, Rebecca J. Dearman, Ian Kimber, Grace Y. Patlewicz, and David A. Basketter
Year:
2005
Bibliographic source:
Dermatitis, Vol 16, No 4, pp 157-202, 2005

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Skin sensitization study of N-methyl-p-aminophenol sulphate was performed in mouse by LLNA method
GLP compliance:
not specified
Type of study:
mouse local lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)
Specific details on test material used for the study:
- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animalTEST ANIMALS- Source: No data available- Age at study initiation:8-12 weeks - Weight at study initiation: No data available- Housing: No data available- Diet (e.g. ad libitum): No data available- Water (e.g. ad libitum): No data available- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%):No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data available

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
0.5, 1, 2.5, %
No. of animals per dose:
Total:160.5%: 41% : 42.5%: 4Vehicle control:4
Details on study design:
Details on study designPRE-SCREEN TESTS:- Compound solubility: Test material soluble in DMF- Irritation: No data available- Systemic toxicity:- Ear thickness measurements: 4-5 days after the first application, all mice injected intravenously through the tail vein with 250 μl of phosphate buffered saline (PBS) containing 20 μCi of tritiated thymidine (³H-TdR). After approximately 5 hours, they were killed by CO2 asphyxiation and the auricular lymph nodes excised. The nodes from each group were pooled, a suspension of auricular lymph node cells prepared, and proliferation of these cells measured using β-scintillation counting. The results were used to calculate the Stimulation Index (SI) for proliferation. The EC3 value (the theoretical concentration resulting in an SI value of 3) was subsequently determined.- Erythema scores: No data available MAIN STUDYANIMAL ASSIGNMENT AND TREATMENT- Name of test method: LLNA- Criteria used to consider a positive response: A chemical was regarded as a sensitizer in the LLNA if at least one concentration of the chemical resulted in a threefold or greater increase in HTdR incorporation compared with control value.TREATMENT PREPARATION AND ADMINISTRATION: The dose volume of 25 μl was applied to the dorsal surface of both ears at concentrations of 0.5%, 1%, 2.5% once daily for 3 consecutive days. Control animals received Vehicle alone.
Positive control substance(s):
not specified
Statistics:
No data available

Results and discussion

Positive control results:
No data available

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
2.5
Test group / Remarks:
0.5% test group
Remarks on result:
other: positive effect was observed
Parameter:
SI
Value:
3.4
Test group / Remarks:
1% test group
Remarks on result:
other: positive effect was observed
Parameter:
SI
Value:
6.7
Test group / Remarks:
2.5% test group
Remarks on result:
other: positive effect was observed
Cellular proliferation data / Observations:
The ratio of test to control lymphocyte proliferation (T/C) was determined as 2.5, 3.4 and 6.7 indcated positive effect for skin sensitization.

Applicant's summary and conclusion

Interpretation of results:
other: sensitizing
Conclusions:
The N-methyl p-aminophenol sulphate (55-55-0) was considered to be sensitizing in mice by LLNA method
Executive summary:

The skin sensitization studyN-methyl p-aminophenol sulphate(55-55-0)was performed on 16CBA/Ca male or female mice of age 8-12 weeks .The test material soluble in DMF.The dose volume of 25 μl was applied to the dorsal surface of both ears at concentrations of 0.5%, 1%, and 2.5% once daily for 3 consecutive days. Control animals received Vehicle alone.4-5 days after the first application, all mice injected intravenously through the tail vein with 250 μl of phosphate buffered saline (PBS) containing 20 μCi of tritiated thymidine (³H-TdR). After approximately 5 hours, they were killed by CO2 asphyxiation and the auricular lymph nodes excised. The nodes from each group were pooled, a suspension of auricular lymph node cells prepared, and proliferation of these cells measured using β-scintillation counting. The results were used to calculate the Stimulation Index (SI) for proliferation. The EC3 value (the theoretical concentration resulting in an SI value of 3) was subsequently determined.A chemical was regarded as a sensitizer in the LLNA if at least one concentration of the chemical resulted in a threefold or greater increase in HTdR incorporation compared with control value. The ratio of test to control lymphocyte proliferation (T/C) was determined as 2.5, 3.4 and 6.7 HenceN-methyl p-aminophenol sulphate(55-55-0) was considered to be sensitizing in mice by LLNA method.