(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in chemico

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Justification for type of information:

The prediction of the skin sensitising potential of 1574 Acide Crist ( IUPAC: 7-({6-chloro-10-methyl-9,9-dioxo-9λ⁶-thia-10-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}amino)heptanoic acid, CAS:72797-41-2, EC:276-851-9) was performed with, VEGA NIC 1.1.4 (CAESAR), OECD QSAR Toolbox 4.1, and DEREK Nexus 5.0.2. In addition, results from the Danish QSAR Database and Toxtree 2.6.13 were also checked but not used in consideration in this assessment.
The prediction results for 1574 Acide Crist are detailed in the (Q)SAR prediction reporting formats (QPRFs). Reliability indices are assigned to each prediction, and are based on considerations of similar structures in the training set, prediction statistics and the applicability domain. Further details are available in the QPRFs below. The OECD QSAR Toolbox reports results via its own reporting format and this is attached directly. Toxtree is based on classification trees and does not provide such information and thus no reliability index is assigned. No QPRFs were prepared for the predictions taken from the Danish QSAR database. The results are presented in the software printout section together with the printouts of all other models applied.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The prediction of the skin sensitising potential of 1574 Acide Crist ( IUPAC: 7-({6-chloro-10-methyl-9,9-dioxo-9λ⁶-thia-10-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}amino)heptanoic acid, CAS:72797-41-2, EC:276-851-9) was performed with, VEGA NIC 1.1.4 (CAESAR), OECD QSAR Toolbox 4.1, and DEREK Nexus 5.0.2. In addition, results from the Danish QSAR Database and Toxtree 2.6.13 were also checked but not used in consideration in this assessment.
The prediction results for 1574 Acide Crist are detailed in the (Q)SAR prediction reporting formats (QPRFs). Reliability indices are assigned to each prediction, and are based on considerations of similar structures in the training set, prediction statistics and the applicability domain. Further details are available in the QPRFs below. The OECD QSAR Toolbox reports results via its own reporting format and this is attached directly. Toxtree is based on classification trees and does not provide such information and thus no reliability index is assigned. No QPRFs were prepared for the predictions taken from the Danish QSAR database. The results are presented in the software printout section together with the printouts of all other models applied.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

EC Number:

276-851-9

EC Name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Cas Number:

72797-41-2

Molecular formula:

C21H25ClN2O4S

IUPAC Name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Test material form:

solid: crystalline

Details on test material:

White powder

In chemico test system

Details on the study design:

The prediction of the skin sensitising potential of 1574 Acide Crist ( IUPAC: 7-({6-chloro-10-methyl-9,9-dioxo-9λ⁶-thia-10-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}amino)heptanoic acid, CAS:72797-41-2, EC:276-851-9) was performed with, VEGA NIC 1.1.4 (CAESAR), OECD QSAR Toolbox 4.1, and DEREK Nexus 5.0.2. In addition, results from the Danish QSAR Database and Toxtree 2.6.13 were also checked but not used in consideration in this assessment.
The prediction results for 1574 Acide Crist are detailed in the (Q)SAR prediction reporting formats (QPRFs). Reliability indices are assigned to each prediction, and are based on considerations of similar structures in the training set, prediction statistics and the applicability domain. Further details are available in the QPRFs below. The OECD QSAR Toolbox reports results via its own reporting format and this is attached directly. Toxtree is based on classification trees and does not provide such information and thus no reliability index is assigned. No QPRFs were prepared for the predictions taken from the Danish QSAR database. The results are presented in the software printout section together with the printouts of all other models applied.

Results and discussion

In vitro / in chemico

Results

Key result

Remarks on result:

other: Therefore as no conclusion on a prediction is proposed from the available information, further testing is recommended.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

There is conflicting evidence for the skin sensitisation potential of 1574 Acide Crist.
The results gathered were deemed to be of poor to moderate reliability. A potential mechanism of action was identified via the toolbox but this was not supported by other predictions.
Toolbox identified no alerts for the query structure, but identified issues with potential metabolites. Derek was unable to identify any alerts for the substance, Toxtree also failed to identify any alerts. The CAESAR model showed a positive result but was out of domain and also the substances did not seem to behave similarly to the target compound according to the profilers in the Toolbox. In addition, the Danish QSAR database also provides inconclusive results.
Therefore as no conclusion on a prediction is proposed from the available information, further testing is recommended.

Test OECD 422C (Direct Peptide Reactivity Assay) planned - Expected results in June 2018