4-chloro-2,6-diaminopyrimidine

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

November 2015

Reliability:

3 (not reliable)

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: ECOSAR (Anilines (unhindered) model for acute
aquatic toxicity in algae.
Model version: ECOSAR (Ecological Structure Activity Relationships
system) (version 1.11).

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)

Results and discussion

Effect concentrations

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

6.1 mg/L

Any other information on results incl. tables

Endpoint: Short-term toxicity to algae (96h)

Dependent variable: Acute toxicity as EC50, i.e. median effective

concentration, where the measured effect is the inhibition of growth rate after 96h.

Model or submodel name: ECOSAR (Anilines (unhindered) model for acute aquatic toxicity in algae.

Model version: ECOSAR (Ecological Structure Activity Relationships system) (version 1.11).

Descriptor values: LogKow = -0.39 (LogKow value estimated by EPI Suite/KOWWIN estimation model).

Domains: ECOSAR predictions are not supported by a specific parameter for the assessment of their reliability and models applicability domain. However, it is assumed that the prediction is less accurate for compounds outside the descriptor (i.e., LogKow) range and molecular weight (MW) range of the training set compounds (training set LogKow range= -0.9 / 3.2; training set MW range = 107/498). Additionally, a LogKow cut-off of 4.0 and a maximum MW of 1000 are defined for the applicability of the ECOSAR predicting acute effects in fish.

Above the LogKow cut-off, data generally indicate that the hydrophobicity of the molecules leads to “no effects at saturation”.

i. descriptor domain: The target compound 6-chloropyrimidine-2,4 - diamine is included in the MW and LogKow ranges, being characterised by a MW equal to 144.5 and a predicted LogKow equal to -0.39.

ii. structural fragment domain: not applicable.

iii. mechanism domain: not applicable.

iv. metabolic domain, if relevant: not applicable.

Structural analogues: No structural analogues are provided by the estimation tool.

The uncertainty of the prediction: ECOSAR predictions are not supported by a specific parameter for the assessment of their uncertainty. However, it is assumed that the prediction is less accurate for compounds outside the descriptor (i.e., LogKow) range and molecular weight (MW) range of the training set compounds (training set LogKow range= -0.9 / 3.2; training set MW range = 107 / 498). Additionally, a LogKow cut-off of 4.0 and a maximum MW of 1000 are defined for the applicability of the ECOSAR predicting acute effects in fish. Above the LogKow cut-off, data generally indicate that the hydrophobicity of the molecules leads to “no effects at saturation”. The target compound 6-chloropyrimidine-2,4-diamine is included in the MW and LogKow range, thus falling within the applicability domain of the QSAR model. However, some concerns related to the scientific validity of the Aniline (unhindered) QSAR equation are highlighted (limited number of training set chemicals). Thus, the prediction was assessed as

borderline reliable.

Applicant's summary and conclusion

Conclusions:

ECOSAR predicted for 6-chloropyrimidine-2,4-diamine an acute 96h EC50 to algae equal to 6.1 mg/L.
The prediction is considered borderline reliable.

Executive summary:

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

Approach for regulatory interpretation of the model result: ECOSAR predicted for 6-chloropyrimidine-2,4-diamine an acute 96h EC50 to algae equal to 6.1 mg/L. The prediction is considered borderline reliable.