Cyclohexanediacetic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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

Test type:

other: in silico prediction

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

Any other information on results incl. tables

Since read-across represents a limited andad hocapproach 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. Therefore, CAM and CDA were compared in terms of hydrophobicity (log P), H bonding acceptor and H bonding donor, melting point and boiling point, polarizability and molar refractivity, which are physicochemical properties considered to play an important role on the acute toxicity by oral route as stated in I. Tsakovskaet al. (I. Tsakovskaet al.,QSAR Comb.Sci., 27, 2008,1, 41 – 48) and mentioned also 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”. The physicochemical profile of CAM and CDA is illustrated and compared in the table below.

Structure	MW	LogP ± error	H bonding acceptors	H bonding donors	Melting point (°C)*	Boiling point (°C)	Polariz. (10-24cm3)	Molar refractivity (cm3)
CAM	199.25	0.71 ± 0.26	4	3	160.33	443.63	20.36	51.36
CDA	200.23	1.27 ± 0.24	4	2	133.17	405.74	19.57	49.36

 * Melting point values were calculated with EPISUITE.

It can be concluded that the two structures are similar enough with respect to the physicochemical properties relevant to the acute toxicity by oral route on rat to support the read-across.

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 supported by their similarity with respect to the physicochemical properties relevant to the acute toxicity by oral route on rat. Therefore, the experimental test result on the acute toxicity by oral route on rat of 1,1-cyclohexanediacetic acid monoamide (CAM) (CERB study n.20010448 ST/RBM study n. R13730) can be read-across to CDA, concluding that CDA is not toxic by oral route on rat.

Applicant's summary and conclusion

Interpretation of results:

other: not toxic

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

CDA is not toxic by oral route on rat.