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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2012-10-31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented and validated QSAR model (OECD QSAR toolbox)

Data source

Referenceopen allclose all

Reference Type:
other: software
Title:
Unnamed
Year:
2012
Reference Type:
publication
Title:
Identification of the structural requirements for mutagenicity by incorporating molecular flexibility and metabolic activation of chemicals
Author:
Mekenyan, O., Dimitrov, S., Serafimova, R., Thompson, E., Kotov, S., Dimitrova, N., and Walker, J.
Year:
2004
Bibliographic source:
Chem. Res. Toxicol. 17, 753-766.
Reference Type:
publication
Title:
Identification of the structural requirements for mutagencitiy, by incorporating molecular flexibility and metabolic activation of chemicals. II. General Ames mutagenicity model
Author:
Serafimova, R., Todorov, M., Pavlov, T., Kotov, S., Jacob, E., Aptula, A., and Mekenyan, O.
Year:
2007
Bibliographic source:
Chem Res. Toxicol. 20, 662-676
Reference Type:
publication
Title:
Unnamed
Year:
2010
Reference Type:
publication
Title:
GUIDANCE DOCUMENT ON THE VALIDATION OF (QUANTITATIVE)STRUCTURE-ACTIVITY RELATIONSHIPS [(Q)SAR] MODELS
Author:
Environment Directorate ORGANISATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT
Year:
2007
Bibliographic source:
ENV/JM/MONO(2007)2

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals, May 2008
Deviations:
no
Principles of method if other than guideline:
The data are taken from the: -ISSSTY database on Salmonella typhimurium (Ames test) bacterial mutagenicity. The experimental
results were retrieved from the Chemical Carcinogenesis Research Information System (CCRIS) database, in the Toxnet databases
cluster (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?CCRIS ); -Toxicity Japan MHLW: Japan Existing Chemical Database
http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPageENG.jsp.
general model Carcinogenicity & Mutagenicity ISSCAN:
The present database was developed by Italy’s Istituto Superiore di Sanita. It contains information on chemical compounds tested with the long-term carcinogenicity bioassay on rodents (rat, mouse). Donators: Istituto Superiore di Sanità (ISS), Rome, Italy; Federal Office of Public Health (FOPH), Switzerland)
GLP compliance:
no
Type of assay:
other: QSAR/ read across modeled data

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on test system and experimental conditions:
DEFINING THE ENDPOINTS
- endpoint variabel: gene mutation
- species: Salmonella typhimurium
DEFINING THE ALGORITHM
- unambiguous algorithm
- prediction approach: Read-across among category members; experimental values for the target substance (if any) were not used in prediction calculations
- calculation approach: Taking highest mode value from the 5 nearest neighbours
DESCRIPTION OF APPLICABILITY DOMAIN
- The target substance FALLS within applicability domain
REFERENTIAL BOUNDARY
- The target chemical should be classified as No alert found by DNA binding by OECD
PARAMETRIC BOUNDARY
- The target chemical should have a value of log Kow which is >= 2.18
- The target chemical should have a value of log Kow which is <= 6.21

Results and discussion

Test results
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
not applicable
Genotoxicity:
negative
Additional information on results:
-prediction approach: read across among category members Experimental values for the target substance (if
any) were not used in prediction calculations
- calculation approach: Taking highest mode value from the 5 nearest neighbours
- descriptor: log Kow bis(2-butoxyethyl)adipate: 3.78
-Prediction confidence: 100.0%; 20 of 20 neighbours' data points have experimental value equal to prediction "Negative"
- predicted value "gene mutation= negative" corresponds to "low" on the scale of "negative, equivocal and
positive".
- Profiling results for the target substance: DNA binding by OASIS, DNA binding by OECD, Estrogen Receptor Binding, OECD HPV Chemical Categories, Protein binding by OASIS, Protein binding by OECD, Protein Binding Potency, Superfragments, Toxic hazard classification by Cramer (original), Toxic hazard classification by Cramer (with extension), US-EPA New Chemical Categories
Remarks on result:
mutagenic potential (based on QSAR/QSPR prediction)

Any other information on results incl. tables

 Results
   Descriptor(s)  Endpoint(s)
   log Kow  "Gene mutation"
 Target chemical  3.78
 chemical No 1 CAS n° 105-99-7  4.33  Negative (x 4)
 chemical No 2 CAS n° 78-51-3  3.00  Negative (x 4)
 chemical No 3 CAS n° 683-10-3  2.18  Negative (x 4)
 chemical No 4 CAS n° 1338-41-6  6.10  Negative (x 4)
 chemical No 5 CAS n° 4016-24-4  6.21  Negative (x 4)
 chemical No 6 CAS n° 111-03-5  6.40  Negative (x 4)
 chemical No 7 CAS n° 1843-05-6  6.96  Negative (x 4)
 chemical No 8 CAS n° 3648-21-3  7.56  Negative (x 4)
 chemical No 9 CAS n° 103-24-2  9.59  Negative (x 4)
 chemical No 10 CAS n° 1806-54-8  9.71  Negative (x 4)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The predicted value for bis(2-butoxyethylene)adipate for the gene mutation test, using Salmonella typhimurium, is negative.
Executive summary:

For the determination of the bacterial reverse mutation (Salmonella typhimurium) potential of bis(2-butoxyethylene)adipate, OECD QSAR toolbox was used. For the prediction read-across among category members was applied and 5 nearest neighbours (compounds with CAS n° 105 -99 -7, 78 -51 -3, 683 -10 -3, 1338 -41 -6, 4016 -24 -4) were taken. Log Kow was taken into account as descriptor. For the target compound, log Kow is 3.78 and the 5 neighbours were within the log Kow range of 2.18 -6.21.