4-chloro-2,6-diaminopyrimidine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

Remarks:

other: (Q)SAR prediction

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

November 2015

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: 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: REACH guidance on QSARs R.6 May/July 2008

Principles of method if other than guideline:

Model or submodel name: ACD/Percepta: Skin Irritation.
Model version: ACD labs/Percepta (2015 Release).

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: Nc1cc(Cl)nc(N)n1
InChI: InChI=1S/C4H5ClN4/c5-2-1-3(6)9-4(7)8-2/h1H,(H4,6,7,8,9)

Test animals

Species:

rabbit

Results and discussion

In vivo

Results

Irritation parameter:

other: predicted probability to cause severe/moderate skin irritation

Score:

0.36

Any other information on results incl. tables

Endpoint: Skin irritation/corrosion

Dependent variable: Skin irritation is modelled for study calls, where the positive calls are trained as binary 1 and negative calls as binary 0. The output of the probabilistic QSAR model consists of the probability for a chemical to cause moderate or severe irritation to skin of rabbit at a standard dose (500 mg).

Model or submodel name: ACD/Percepta: Skin Irritation

Model version: ACD labs/Percepta (2015 Release).

Domains: detailed structural and/or response limits of the applicability domain are not defined. However, for each prediction, a list of all the rules (alerts) applicable to the calculation of irritation potential of the analyzed molecule is provided, as well as the percentage of training set chemicals containing these alerts and exhibiting moderate or stronger skin irritation. In addition, the software displays up to five most similar structures from the training set along with experimental results. The information on analogues, together with information on alerts, can be used to assess the reliability of the prediction, since it illustrates how the test compound is represented in the training set. The model is suitable for the calculation of the irritational properties for the salts of common organic electrolytes.

i. descriptor domain: not applicable.

ii. structural fragment domain: not applicable.

iii. mechanism domain: No structural alerts for skin irritation are identified by ACD/Percepta.

Considerations on structural analogues: the three training set compounds exhibit moderate similarity with respect to 6-chloropyrimidine-2,4-diamine (similarity indices in the range 0.75-0.83), meaning that the target is moderately represented in the training set. Experimental Draize test results for these analogues are not consistent, being two not irritating and one slightly irritating.

The uncertainty of the prediction was evaluated based on the following criteria: i) predicted probability of skin irritation; ii) presence of structural alerts relevant for skin irritation; iii) analysis of structural analogues from the training set (structural similarity and consistency of experimental data). For the target 6-chloropyrimidine-2,4-diamine it was noted that: i) the target is predicted as not skin irritant, however the predicted probability is close to the threshold value for irritation/not irritation; ii) no structural alerts for skin irritation are identified by ACD/Percepta; iii) training set analogues exhibit moderate similarity with respect to the target, but their experimental data are not consistent, being two not irritating and one slightly irritating. Based on these information, ACD/Percepta prediction for 6-chloropyrimidine-2,4-diamine was assessed as moderate reliable.

6-chloropyrimidine-2,4-diamine is predicted negative for skin irritation in standard rabbit Draize test based on a predicted probability to cause severe/moderate skin irritation equal to 0.36.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

6-chloropyrimidine-2,4-diamine is predicted by ACD/Percepta as not skin irritant in standard rabbit Draize test based on a predicted probability to cause severe/moderate skin irritation equal to 0.36. The prediction is considered moderate reliable.

Executive summary:

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

Approach for regulatory interpretation of the model result: ACD/Percepta predicted 6-chloropyrimidine-2,4-diamine as not skin irritant. The prediction is considered of moderate reliability.