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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxtree (version 2.1.0.) modeling tool was developed by IDEA Consult Ltd (Sofia, Bulgaria) and is approved and recommended by the EU Joint Research Center in Ispra (Italy) (LINK: http://ecb.jrc.ec.europa.eu/qsar/qsar-tools/index.php?c=TOXTREE).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Prediction by the Toxtree modelling tool
GLP compliance:
no

Test material

Constituent 1
Details on test material:
Chemical nonyl 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate evaluated by Toxtree modeling tool represent structure with C9 alkyl chain from isomeric mixture of Reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-trans-butyl-4-hydroxyphenyl) propionate.
Radiolabelling:
other: not applicable

Test animals

Species:
other: not applicable

Administration / exposure

Route of administration:
other: not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
not applicable
No. of animals per sex per dose / concentration:
not applicable

Results and discussion

Main ADME results
Type:
other: Prediction of metabolism by modeling
Results:
nonyl 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate is expected to be well metabolized by the Cytochrome P450 group of drugs metabolizing enzymes

Any other information on results incl. tables

Results of identification of sites in the molecule which are labile for enzymes from group of drug metabolizing Cytochrome P450 family:

Q1.Rank1:Yes; Class:SMARTCyp primary sites of metabolism: (cleavage at C5-C9 bond of propanoic acid moiety*)

Q2.Rank2:Yes; Class:SMARTCyp secondary sites of metabolism: (cleavage at C9-C15 bond of propanoic acid moiety and cleavage of benzene ring at C1 and C4 positions* (ortho and para positions))

Q3.Rank3:Yes; Class:SMARTCyp tertiary sites of metabolism: (cleavage of aliphatic chain (nonyl rest))

QRank>3.SMARTCyp:Yes;Class:SMARTCyp rank>3 sites of metabolism (further cleavage of benzene ring at tert-butyl rests)

* the numbering of carbon atoms is defined by modeling tool

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: well metabolized substance
Nonyl 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate is expected to be well metabolized by the Cytochrome P450 group of drugs metabolizing enzymes.
Executive summary:

Nonyl-3(3,5 -ditert-butyl-4 -hydroxyphenyl)propanoate is estimated to be well metabolized by the Cytochrome P450 group of metabolizing enzymes. The molecule possesses more than three sites of metabolism. Carbon atoms of the propanoic acid moiety are primary and secondary sites of metabolism. Secondary sites of metabolism are also parts of the benzene rings not hindered by halogens or comparable functional groups which can worsen the metabolism. The C9 alkyl-chain is regarded as tertiary site. Tert-butyl branches, which are present at benzene ring of the target chemical, will be metabolized at last.