Cyclohexanediacetic acid

Genetic toxicity: in vitro

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

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

Test material information

Constituent 1

Reference substance name:

Cyclohexanediacetic acid

EC Number:

224-427-9

EC Name:

Cyclohexanediacetic acid

Cas Number:

4355-11-7

Molecular formula:

C10H16O4

IUPAC Name:

2-[1-(carboxymethyl)cyclohexyl]acetic acid

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.