Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
QSAR Toolbox estimation
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
Remarks:
Data predicted by OECD Toolbox v4.1. OECD Toolbox uses a valid estimation method; the substance was found to fall in the applicability domain of this method and results are considered relevant for risk assessment
Justification for type of information:
1. SOFTWARE
QSAR Toolbox

2. MODEL (incl. version number)
QSAR Toolbox 4.1
Database version: 4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS#: 68296-59-3
SMILES: COc1ccc2NC3N(C(=O)c4cccc5cccc3c54)c2c1
SMILES: COc1cccc2NC3N(C(=O)c4cccc5cccc3c54)c21

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
see attached report

5. APPLICABILITY DOMAIN
see attached report

6. ADEQUACY OF THE RESULT
see attached report

Data source

Reference
Reference Type:
other: Prediction of gene mutation
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Results and discussion

Test results
Key result
Species / strain:
not specified
Metabolic activation:
with and without
Genotoxicity:
negative
Additional information on results:
Predicted endpoint: gene mutation, Gene mutation; No effect specified; No species specified; No duration specified; No guideline specified
Predicted value: Negative
Unit/scale: Gene mutation I
Data gap filling method: Read-across analysis

Prediction details (I)
Predicted value: Negative
Predicted endpoint (OECD Principle 1 - Defined endpoint): Human Health Hazards -> Genetic Toxicity -> Gene mutation
Calculation approach (OECD principle 2 - Unambiguous algorithm): takes the highest mode value from the nearest 5 neighbours
Active descriptor: log Kow (calculated)
Data usage: All values (When multiple values are available for the same chemical, all of them are taken individually in prediction calculations)

Prediction details (II)
Uncertainty of the prediction (OECD principle 4 - Uncertainty of the prediction):
The prediction is based on 18 values, 14 of them (77.8%) equal to predicted value
Prediction confidence is measured by the p-value: 0.000145

Target profiles
(OECD principle 5 - Chemical and biological mechanisms)
Profiles used for grouping/subcategorization
DNA binding by OECD (primary grouping) SN1; SN1 >> Nitrenium Ion formation; SN1 >> Nitrenium Ion formation >> Secondary aromatic amine
log Kow (calculated): 2.68

Analogue(s) selection
(OECD principle 3 - Applicability domain)
Database(s) used:
- Bacterial mutagenicity ISSSTY
- Genotoxicity OASIS
Category boundaries (applicability domain):
- Active descriptor(s) range:
- log Kow: from 2.58 to 2.81 target chemical is in domain
- Response range:
- Gene mutation: from Negative to Positive
Profilers:
- DNA binding by OECD (primary grouping) target chemical is in domain
Additional data pruning:
Data inconsistency filter 191 value(s) from 34 chemical(s)
Manually eliminated data points:
none
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

Applicant's summary and conclusion

Conclusions:
Based on the QSAR prediction results, the test substance has no mutagenic properties
Executive summary:

Predicted endpoint: gene mutation, Gene mutation; No effect specified; No species specified; No duration specified; No guideline specified

Predicted value: Negative

Unit/scale: Gene mutation I

Data gap filling method: Read-across analysis

Prediction details (I)

Predicted value: Negative

Predicted endpoint (OECD Principle 1 - Defined endpoint): Human Health Hazards -> Genetic Toxicity -> Gene mutation

Calculation approach (OECD principle 2 - Unambiguous algorithm): takes the highest mode value from the nearest 5 neighbours

Active descriptor: log Kow (calculated)

Data usage: All values (When multiple values are available for the same chemical, all of them are taken individually in prediction calculations)

Prediction details (II)

Uncertainty of the prediction (OECD principle 4 - Uncertainty of the prediction):

The prediction is based on 18 values, 14 of them (77.8%) equal to predicted value

Prediction confidence is measured by the p-value: 0.000145

Target profiles

(OECD principle 5 - Chemical and biological mechanisms)

Profiles used for grouping/subcategorization

DNA binding by OECD (primary grouping) SN1; SN1 >> Nitrenium Ion formation; SN1 >> Nitrenium Ion formation >> Secondary aromatic amine

log Kow (calculated): 2.68

Analogue(s) selection

(OECD principle 3 - Applicability domain)

Database(s) used:

  - Bacterial mutagenicity ISSSTY

  - Genotoxicity OASIS

Category boundaries (applicability domain):

- Active descriptor(s) range:

  - log Kow: from 2.58 to 2.81 target chemical is in domain

- Response range:

  - Gene mutation: from Negative to Positive

Profilers:

  - DNA binding by OECD (primary grouping) target chemical is in domain

Additional data pruning:

  Data inconsistency filter 191 value(s) from 34 chemical(s)

Manually eliminated data points:

  none