N-(n-dodecyl)pyrrolidinone

Basic toxicokinetics

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:

bioaccessibility (or bioavailability)

metabolism

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 (or Bioavailability)

Bioaccessibility (or Bioavailability) 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.