Reaction mass of pentadecylamine and tridecylamine and 2-Methyldodecylamine and 2-Methyltetradecylamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Secondary literature, review

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

various alkyl amines

Results and discussion

Any other information on results incl. tables

A.   Excerpt from Cavender et al. 2000:

"In animals, the lower aliphatic amines are mainly metabolized to the 
corresponding carboxylic acid and urea; the intermediate compounds have 
been shown by in vitro experiments to be the corresponding aldehyde and ammonia.
MAOs oxidatively deaminate primary, secondary, and tertiary amines. 
However, compounds that have a substituted methyl group on the alpha carbon are
not metabolized by MAOs (14).

To serve as a substrate, the amine group must be attached to an unsubstituted 
methylene group (alpha-carbon hydrogen prerequisite).  For example, MAO cannot 
catalyze the oxidation of aniline, amphetamine, or methylamine. 
Ethylamine and propylamine have also been demonstrated to be 
poor substrates for MAO. The rate of enzyme oxidation activity increases with 
an increase in aliphatic chain length to an optimum of C5 or C6, 
followed by a decline in activity to a maximum at 13 methylene groups (14a). 

For example, butyl-, amyl-, isoamyl-, and heptylamines are readily 
metabolized to aldehyde and ammonia (15, 16), but compounds of longer chain 
lengths, for example, octadecylamine, may inhibit the enzyme. 
Deamination rate also diminishes with secondary and tertiary amines (51a)."
   ------------------

B.   Excerpt from Cavender et al. 2000:

"MAO is involved only to a limited extent in the metabolism of aliphatic 
amines (16), whereas microsomal enzymes can be responsible for multiple 
amine biotransformations. Microsomal versus mitochrondrial substrate affinity 
depends not only upon structural characteristics, but also upon the degree of 
lipophilicity. Microsomal enzyme-catalyzed aliphatic and alicyclic amine 
biotransformation reactions can include deamination, methylation, 
N-dealkylation, N-oxidation, N-acetylation, cyclization, N-hydroxylation, 
and nitrosation (19 - 21)." 


C.   Excerpt from Cavender et al. 2000:

"In summary, the principal routes of biotransformation of aliphatic and 
alicyclic amines are N-dealkylation or oxidative deamination and
N-oxidation (30a-30b).
Primary aliphatic amines are susceptible to N-oxidation only if the 
alpha-carbon is subtituted. This prevents the formation of a carbinolamine
intermediate,and N-oxidation occurs,resulting in formation of primary 
hydroxylamines, which can then undergo further oxidation to nitroso and 
oxime metabolites."