2,4-Pyrimidinediamine, 6-chloro-, 3-oxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Other: read across from a SAR prediction

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

November 2015

Reliability:

3 (not reliable)

Justification for type of information:

Read across from a (Q)SAR prediction for the substance 6-chloropyrimidine-2,4-diamine CAS 156-83-2: SAR migrated from IUCLID 5.6

Data source

Reference

Reference 1

Reference Type:

other: QMRF

Title:

Unnamed

Year:

2015

Report date:

2015

Reference 2

Reference Type:

other: QPRF

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Guideline:

other: guideline REACH guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

Model or submodel name: Skin sensitisation reactivity domains.
Model version: Decision tree implemented in Toxtree (version 2.6.13).

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-2,6-diaminopyrimidine

EC Number:

205-863-9

EC Name:

4-chloro-2,6-diaminopyrimidine

Cas Number:

156-83-2

Molecular formula:

C4H5ClN4

IUPAC Name:

6-chloropyrimidine-2,4-diamine

Details on test material:

SMILES: Clc1cc(N)nc(N)n1
InChI: InChI=1S/C4H5ClN4/c5-2-1-3(6)9-4(7)8-2/h1H,(H4,6,7,8,9)

In vivo test system

Test animals

Species:

mouse

Results and discussion

Any other information on results incl. tables

Endpoint: Skin sensitisation

Dependent variable: Skin sensitization reactivity domain (i.e., mechanism of action). Compounds are classified into 6 possible reactivity domains using a SMARTS pattern based approach: i) aromatic nucleophilic substitution (SNAr), ii) Schiff base formation (SB),iii) Michael-type addition (MA), iv) aliphatic nucleophilic substitution (SN2), v) acylation (Ac), vi) No skin sensitization reactivity domain. The capability of chemicals to act via one of these mechanisms after undergoing either oxidative or metabolic transformations is also considered.

Model or submodel name: Skin sensitisation reactivity domains.

Model version: Decision tree implemented in Toxtree (version 2.6.13).

Domains: Toxtree is not supported by a procedure to assess the applicability domain of the skin sensitisation reactivity domains decision tree.

i. descriptor domain: not applicable.

ii. structural fragment domain: not applicable.

b. mechanism domain: A structural alert for nucleophilic aromatic substitution (SNAr) was identified.

The uncertainty of the prediction: Toxtree does not provide any explicit methodology for evaluating the uncertainty of model prediction.

Applicant's summary and conclusion

Interpretation of results:

other: One structural alert for skin sensitisation reactivity domains ( nucleophilic aromaticsubstitution)

Remarks:

Criteria used for interpretation of results: other: Decision tree implemented in Toxtree (version 2.6.13)

Conclusions:

One structural alert for skin sensitisation reactivity domains was identified in 6-chloropyrimidine-2,4-diamine, namely an alert for nucleophilic aromatic substitution.
Thus the target compound is predicted potential positive for skin sensitisation. However, a detailed assessment of the reliability is not available.
Read across from 6-chloropyrimidine-2,4-diamine predicted that the substance 2,4-Diamino-6-chloropyrimidine-3-oxide is potential positive for skin sensitisation.

Executive summary:

Regulatory purpose: This study was designed to generate estimated in silico (nontesting) data for skin sensitisation for 6-chloropyrimidine-2,4-diamine to be used in the regulatory framework of REACH.

Approach for regulatory interpretation of the model result: Toxtree decision tree for skin sensitisation reactivity domains identified one skin sensitization reactivity domain alert, namely an alert for nucleophilic aromatic substitution, leading to a potential positive prediction for skin sensitization. A detailed assessment of the reliability is not available.

A Read across from 6-chloropyrimidine-2,4-diamine as supporting substance (structural analogue or surrogate) of the substance 4-Diamino-6-chloropyrimidine-3-oxide is done.