Registration Dossier

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
based on QSAR simulation
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
1. SOFTWARE: QSAR Toolbox

2. MODEL (incl. version number) 3.4.0.17

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CCCCCCCCCCCCN1CCCC1=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Profiling:
- Protein binding by OASIS v.1.4; OECD; potency
- Mutagenicity
- Protein binding for Chromosomal aberration
- Protein binding for Skin sensitization
- Toxic hazard classification by Cramer
- Bioaccumulation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Objective of study:
metabolism
bioaccessibility
Principles of method if other than guideline:
- Principle of test: Simulation of rat metabolism and specific profiling of metabolites.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.2%
Batch No.: 14

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not specified
Details on distribution in tissues:
Not specified
Details on excretion:
Not specified

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
CCC(O)CCCCCCCCCN1CCCC1=O
CCCC(O)CCCCCCCCN1CCCC1=O
CCCCCCCCCCCCN1C(=O)CCC1=O
CCCCCCCCCCCCN1CCC(O)C1=O
CCC(=O)CCCCCCCCCN1CCCC1=O
CCC(O)CCCCCCCCCN1C(=O)CCC1=O
CCCC(=O)CCCCCCCCN1CCCC1=O
CCCC(O)CCCCCCCCN1C(=O)CCC1=O
CC(O)CCCCCCCCCCN1C(=O)CCC1=O
CC(O)CC(O)CCCCCCCCN1C(=O)CCC1=O
CCCC(=O)CCCCCCCCN1C(=O)CCC1=O
CCCCCCCCCCCCN1C(O)CCC1=O
CCCCCCCCCCCCN1CCC(O)C1=O
CCCC(=O)CCCCCCCCNC(=O)CCC(O)=O
CCCCCCCCCCCCN
CCCCCCCCCCCC=O
NCCCCCCCCCCCC(O)=O
CCCCCCCCCCCC(O)=O
CCCCCCCCCC(O)=O
OC(=O)CCC(O)=O
CC(O)=O

Bioaccessibility

Bioaccessibility testing results:
Evaluation of the profiles of the different metabolites using QSAR Toolbox gave the following alerts for some but not all molecules:
- Mechanism of protein binding potency by OECD: An acylation mechanism has been suggested for chemicals of this type. Necessary conditions for eliciting direct or indirect Protein interaction, described in this general mechanistic profile, are met. However, the specific structural boundaries providing sufficiency for interaction to proteins may not be identified. These specific structural boundaries are examined in the corresponding endpoint-specific profile.
- In-vivo mutagenicity (Micronucleus test) alerts by ISS: This alert explores the possibility that a chemical interacts with DNA and/or proteins via non-covalent binding, such as DNA intercalation or groove-binding (Snyder et al. 2006). Among the descriptors potentially accounting for non-covalent interactions, the present molecular framework representing two bonded atoms connecting two H bond acceptors (calculated with software Leadscope Enteprise 2.4.15-6) resulted in an increased sensitivity/specificity for what concerns the Micronucleus training set (source: QSAR Toolbox).
- There are no alerts for protein binding for Chromosomal aberration or for Skin sensitization.
- Toxic hazard classification by Cramer: High Class III for the highlighted molecules.
- Potential for Bioaccumulation: Bioaccumulation of parent molecule and its metabolites is considered to be very low as their metabolism half lives are fast to very fast.

Applicant's summary and conclusion

Conclusions:
Bioaccumulation of parent molecule and its metabolites is considered to be very low as their metabolism half lives are fast to very fast.