Registration Dossier

Administrative data

Endpoint:
genetic toxicity in vitro
Remarks:
Type of genotoxicity: other: in silico prediction
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Series on Testing and Assessment No. 69
Principles of method if other than guideline:
GUIDANCE DOCUMENT ON THE VALIDATION OF (QUANTITATIVE) STRUCTURE-ACTIVITY RELATIONSHIP [(Q)SAR] MODELS
GLP compliance:
no
Type of assay:
other: QSAR

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
the endpoint information of the 1,1-cyclohexanediacetic acid monoamide (CAM) was used to predict the same endpoints for the target cyclohexanediacetic acid (CDA)

Results and discussion

Test results
Genotoxicity:
negative

Any other information on results incl. tables

Justification in terms of supporting information: physicochemical properties. Since read-across represents a limited and ad hoc approach to grouping, it is important to provide supporting information that strengthens the case for the read-across. Thus, in addition to the endpoint being read-across, it is considered also useful to show that the analog and the target are (qualitatively or quantitatively) similar with respect to additional properties, relevant to the endpoint. Mutagenicity is a rather complex endpoint and several properties are thought to strengthen the mutagenic response and are therefore useful in modelling mutagenicity, as mentioned in the report recently published and available on the EFSA (European Food Safety Authority) webpage (http://www.efsa.europa.eu/en/scdocs/scdoc/50e.htm) on the “Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment”. Therefore, CAM and CDA were compared in terms of several physicochemical properties, like hydrophobicity (log P), H bonding acceptor and H bonding donor, melting point and boiling point, polarizability and molar refractivity, solubility. The physicochemical profile of CAM and CDA is illustrated and compared in the table below.

Structure

MW

LogP

H bonding acceptors

H bonding donors

Molar volume (cm3)

PSA

Polariz.

(10-24cm3)

Solubility

in pure water (mg/ml)

Molar refractivity (cm3)

CAM

199

0.71

4

3

175

81

20.36

6.77 (pH 3.1)

51.36

CDA

200

1.27

4

2

169

74.6

20

10.18 (pH 2.86)

49.36

It can be concluded that the two structures are similar enough with respect to their physicochemical profile, which allows the use of the read-across approach.

Conclusions

The identified analog, i.e. 1,1-cyclohexanediacetic acid monoamide (CAM), can be considered structurally sufficient similar to the target, cyclohexanediacetic acid (CDA), to apply the read-across approach. In addition, the read-across between CAM and CDA is further supported by their similarity with respect to their physicochemical profile. Therefore, the experimental test result on the Ames test on Salmonella typhimurium of 1,1-cyclohexanediacetic acid monoamide (CAM) (Study IPL (Institute Pasteur de Lille)-R 0308009)) can be read-across to CDA, concluding that CDA is not mutagenic.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The CDA is not mutagenic.