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Description of key information

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
Reliability:
1 (reliable without restriction)
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Magnusson and Kligman
Deviations:
not specified
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This Magnusson and Kligman test had been published in 2000 and performed before the OECD 429 guideline (LLNA)
Test material information:
Composition 1
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Nippon Bio Supp. Center, Tokyo, Japan - Age at study initiation: 4 weeks- Weight at study initiation: 300 - 350 g- Housing: in groups of 3 in stainless steel wire-mesh cages- Diet (e.g. ad libitum): solid diet ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): 23 +/- 2 °C- Humidity (%): 55 +/- 5 %- Air changes (per hr): 15 per h- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: no data
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
1.0 % test item concentration
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1.0 % test item concentration
No. of animals per dose:
6
Details on study design:
RANGE FINDING TESTS: no dataMAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 2- Exposure period, frequency of applications, and sites:On day 0, a row of 3 injections was given. 81) 0.1 mL emulsified mixture of Freund's Complete Adjuvant (FCA) and saline 1:1; (2) 0.1 mL of 0.1% PTD dissolved in saline, (3) 0.1 mL of 0.1% PTD in FCA and saline 1:1.In order to enhance the sinsitisation, sodium lauryl sulphate 10% in petrolatum was applied on introduction area for 24 h before the topical application. On day 7, 0.5 g of 0.1% test item in petrolatum were occlusively applied for 48 h. The samples were covred with lint pads which were lining with Blenderm tape. The region patched was then bandaged with fixing tape.- Duration: 20 d- Concentrations: 0.1 % test item concentrationB. CHALLENGE EXPOSURE- No. of exposures: 1- Day(s) of challenge: day 21- Exposure period: 24 h- Test groups: treated with test item- Control group: no treat,emt- Site: flank- Concentrations: 0.1%, 0.01%, 0.001%- Evaluation (hr after challenge): 24, 48, and 72 hOTHER:Draize's scoring system was applied. The summation of numerical scoring more than 2 was judged as a positive reaction.Scoring system for erythema and eschar formation: 0 (no observation) to 4 (most severe reactions)Scoring system for edema formation: 0 (no observation) to 4 (most severe reactions)Whole number steps for inbetween scores
Challenge controls:
no data
Positive control substance(s):
not specified
Positive control results:
No positive control reported as such, however a whole group of para-substituted benzenes were being test in this study. The known sensitiser p-phenylenediamine gave strong skin sensitising responses at challenge concentrations of 0.15 and 0.01%, which can be considered as equvalent to positive control data.
Reading:
other: Either reading at 24, 48, or 72 h after challenge. Since not specified, an average reading time of 48 h is given.
Hours after challenge:
48
Group:
test group
Dose level:
0.1%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: see Remark
Remarks:
Reading: other: Either reading at 24, 48, or 72 h after challenge. Since not specified, an average reading time of 48 h is given.. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Reading:
other: Either reading at 24, 48, or 72 h after challenge. Since not specified, an average reading time of 48 h is given.
Hours after challenge:
48
Group:
test group
Dose level:
0.01%
No. with + reactions:
5
Total no. in group:
6
Remarks on result:
other: see Remark
Remarks:
Reading: other: Either reading at 24, 48, or 72 h after challenge. Since not specified, an average reading time of 48 h is given.. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01%. No with. + reactions: 5.0. Total no. in groups: 6.0.

The study indicated that the grade of skin sensitisation potencies of the chemicals tested is p-phenylendiamine (PPT) = p-toluene-diamine x 2 HCl (PTD, source chemical for read across to target chemical p-toluene-diamine, free base) = p-aminoazobenzene > p-aminophenol >> Sudan III. Concerning cross-reactivities, the PPT-sensitised group was most susceptible to elicit positive reactions in th cross challenges among the chemicals tested, followed by the PTD-sensitised group.

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
In this study, test item p-toluene-diamine x 2 HCl, source chemical for read across to target chemical p-toluene-diamine (free base) was considered a strong sensitiser.
Executive summary:

The data presented have been taken from a scientific publication from the year 2002. The purpose of this study was to evaluate the skin sensitising potential of five hair-dye-related chemicals. One of the test items was p-toluenediamine x 2 HCl, which is being used in a read across approach as source chemical for target chemical toluene-2,5 -diamine (free base) CAS 95 -70 -5.

Applicability of read-across approach is given, as test item toluene-2,5-diamine x 2 HCl, once inside the cell systemically available, is dissociating into target chemical toluene-2,5-diamine (free base) and chlorides, due to buffering capacity of the cell fluids.

The procedure of Magnusson and Kligman was followed for induction. Open applications were used for the challenge. As test animals guinea pigs were used, with groups of 6 animals per test item concentration.

The test item was applied during the induction exposure in a concentration of 0.1%, for challenge exposure concentrations of 0.1%, 0.01% a,d 0.001% were being applied. After challenge exposure readings were taken at 24, 48, and 72 hours. The Draize's scoring system was applied. The summation of numerical scoring of (1) erythema/eschar formation and (2) edema formation more than 2 was judged as a positive reaction.

Challenge exposure with 0.1% of the test item p-toluenediamine x 2 HCl gave sensitising reactions in 6 of 6 test animals.

Challenge exposure with 0.01% of the test item p-toluenediamine x 2 HCl gave sensitising reactions in 5 of 6 test animals.

No sensitising reactions when 0.001% test item was being applied.

Based on these results, source chemical p-toluenediamine x 2 HCl is to be considered a strong skin sensitiser. Referring to the applicability of the proposed read across approach, the same assesssment is likely to apply to target chemical toluene-2,5 -diamine (CAS 95 -70 -5).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The study of Xie (2000; OECD Guideline 406, Magnussen & Kligman) was conducted with test item p-toluenediamine x 2 HCl.

Studies on similar compound Toluene 2,5 -diamine sulphate confirm the skin sensistisation effect.

Furthermore a consolidated summary report is given on nine occupational health reports and human patch tests, all uniformly supporting the skin sensitising effect of the test item for hairdressers and their clients. Reports usually lacking detailed information, thus Klimisch 4 rating was assigned.


Migrated from Short description of key information:
Data taken from two scientific publications indicate that target chemical toluene-2,5-diamine (CAS 95-70-5) is a strong skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

For target chemical toluene-2,5 -diamine, the following classification is applicable (in accordance to the harmonised classification as given in CLP Annex VI, Index # 612 -125 -00 -3):

CLP: Sens. Skin 1, H317, may cause allergenic skin reaction.

DSD: Xi; R43, may cause sensitisation by skin contact