3,7-dihydropurin-6-one;sodium

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

See attached QPRF and QMRF documents.

Data source

Reference

Reference 1

Reference Type:

other: computer model

Title:

ECOSAR v1.11

Author:

US Environmental Protection Agency's Office of Chemical Safety and Pollution Prevention

Year:

2017

Bibliographic source:

https://www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-ecosar-predictive-model

Reference 2

Reference Type:

other: Estimation software

Title:

Estimation Programs Interface Suite for Microsoft Windows, v4.11

Author:

US EPA

Year:

2012

Bibliographic source:

United States Environmental Protection Agency, Washington DC, USA; November 2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

May 2008

Principles of method if other than guideline:

QSAR prediction using ECOSAR v1.11.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,7-dihydropurin-6-one;sodium

Cas Number:

45738-97-4

Molecular formula:

C5H3N4NaO

IUPAC Name:

3,7-dihydropurin-6-one;sodium

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: White powder
- Purity / Composition: 98%
- Test item storage: Room temperature

Specific details on test material used for the study:

SMILES : O([Na])c1ncnc2ncnc12

Sampling and analysis

Analytical monitoring:

no

Test organisms

Test organisms (species):

Daphnia sp.

Study design

Total exposure duration:

48 h

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

26.93 mg/L

Nominal / measured:

estimated

Conc. based on:

other: QSAR

Remarks:

Imidazoles

Basis for effect:

other: predicted

Effect concentrations 2

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

ca. 37 242.51 mg/L

Nominal / measured:

estimated

Conc. based on:

other: QSAR

Remarks:

Amides

Basis for effect:

other: predicted

Remarks on result:

other: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

Details on results:

see QPRF/QMRF

Any other information on results incl. tables

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that LC50 estimates are less accurate for compounds outside the MW range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.

Interpreting QSAR Class Reference Documents:

ECOSAR is currently programmed to identify over 120 chemical classes and allows access to over 600 QSARs for numerous endpoints and organisms. The Class Definition Documents and QSAR Class Reference Documents (Technical Reference Sheets) are provided for each class in the ECOSAR Help Menu to establish model transparency as outlined by the OECD in the document below. These documents are provided to assist users in understanding the model and interpreting the results. OECD (Organization for Economic Cooperation and Development). (2004a) The Principles for Establishing the Status of Development and Validation of (Quantitative) Structure-Activity Relationships [(Q)SARs]. Organization for Economic Cooperation and Development, Paris; ENV/JM/TG(2004)27.

Class Definition Document:

These documents outline the structural definitions for each ECOSAR class, including “exceptions” to the rules. These “fragment definitions” comprise the expert decision tree component of ECOSAR used to identify the appropriate chemical class or classes for a particular molecule.

QSAR Equation Document (Technical Reference Sheet):

Data Tables for Training Set Chemicals: The QSARs in ECOSAR for both neutral organics (baseline toxicity) and classes with excess toxicity are based on linear mathematical relationships between the predicted log Kow values and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest. The studies collected for the training set chemicals in ECOSAR are provided in the QSAR Equation Documents, expect in the case where data used was considered confidential business information (CBI). The data used for ECOSAR development undergo an extensive data validation step to ensure appropriateness for inclusion in the model. ECOSAR study criteria articulate that the toxicity should be measured at pH levels between 6 and 8 (replicating environmental conditions), the total organic carbon content should not exceed 2 mg/L, the water hardness should be less than 150 mg/L CaCO3, results should be adjusted to, or measured at, 100% active ingredient, and measured test concentrations maintained at greater than 80% of nominal concentrations. When collecting studies for inclusion in the training sets, standard test species were preferred as identified in OPPTS guidelines for aquatic toxicity testing.

http://www.epa.gov/opptsfrs/publications/OPPTS_Harmonized/850_Ecological_Effects_Test_Guidelines/Drafts).

Therefore, Sodium Hypoxanthine is considered to be in the applicability domain of the model.

Applicant's summary and conclusion

Conclusions:

ECOSAR v1.11 predicted 48-hr LC50 for Daphnids = 26.93 mg/L for (Imidazoles).
ECOSAR v1.11 predicted 48-hr LC50 for Daphnids = 37242.51 mg/L (Amides), however, Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

Executive summary:

ECOSAR v1.11 predicted 48-hr LC50 for Daphnids = 26.93 mg/L for (Imidazoles).

ECOSAR v1.11 predicted 48-hr LC50 for Daphnids = 37242.51 mg/L (Amides), however, Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.