4-chloro-2,6-diaminopyrimidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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: Acute toxicity (LD50) – Rat/Oral.
Model version: ACD labs/Percepta (2015 Release).

Test type:

other: (Q)SAR predictions

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)

Test animals

Species:

rat

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

740 mg/kg bw

Any other information on results incl. tables

Domains: ACD/Percepta provides an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain. In particular: RI < 0.3 (Not Reliable), RI in range 0.3 -0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75 (High Reliability). Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. In this case the prediction is considered as borderline reliable since RI is equal to 0.39.

i. descriptor domain: not applicable.

ii. structural fragment domain: not applicable.

iii. mechanism domain: not applicable.

iv. metabolic domain, if relevant: not applicable.

Considerations on structural analogues: The five mostly similar compounds from the training set exhibit moderate similarity with respect to 6-chloropyrimidine-2,4-diamine (similarity index ranging from 0.55 to 0.57), and experimental LD50 values ranging from 670 mg/kg to 3800 mg/kg.

The uncertainty of the prediction is evaluated by ACD/Percepta by means of the reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the model applicability domain. In particular: RI < 0.3 (Not Reliable), RI in range 0.3-0.5 (Borderline Reliability), RI in range 0.5-0.75 (Moderate Reliability), RI >= 0.75 (High Reliability).

Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. In this case the prediction is considered as moderately reliable since RI is equal to 0.39. ACD/Percepta predicted for 6-chloropyrimidine-2,4-diamine an acute oral LD50 to rat equal to 740 mg/kg. The prediction is considered of borderline reliability.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

ACD/Percepta predicted for 6-chloropyrimidine-2,4-diamine an acute
oral LD50 to rat equal to 740 mg/kg. The prediction is considered of borderline
reliability.

Executive summary:

Regulatory purpose: This study was designed to generate estimated in silico (nontesting) data for acute oral toxicity in rat 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 for 6-chloropyrimidine-2,4-diamine an acute oral LD50 to rat equal to 740 mg/kg. The prediction is considered of borderline reliability.