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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles; but as read-across from supporting substance maximum reliability is 2. Read-across hypothesis: for details please see read-across report in IUCLID section 13.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1976
Report date:
1976
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1996

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
no guideline required
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Octylammonium chloride
EC Number:
205-574-8
EC Name:
Octylammonium chloride
Constituent 2
Reference substance name:
205-74-8
IUPAC Name:
205-74-8
Details on test material:
Name of test material (as cited in study report): [11C]-octylamine
- Molecular formula (if other than submission substance): octylamine-HCl
- Molecular weight (if other than submission substance): 165.7
- Specific activity (if radiolabelling): 2,000 Ci/mmole
- Locations of the label (if radiolabelling): C1
Radiolabelling:
yes
Remarks:
[11C]-n-octylamine - HCl

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals or test system and environmental conditions:
no detail information given

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: 0.9% saline
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1-1 mCi of [11C]-octylamine-HCl per animal (i.e. 0.05 to 0.5 nmole/mouse; equivalent to 0.008 to 0.08 µg/mouse)
No. of animals per sex per dose / concentration:
Total: approx. 15 to 20 mice
Control animals:
no
Positive control reference chemical:
not required
Details on study design:
Following i.v. injection, the following was determined:

1) tissue distribution (blood, brain, herat, lungs, spleen, kidneys, liver) at 1,5, and 15 minutes after injection
2) determination of non-amine metabolites in blood and lungs
3) MAO inhibition: determination of 11CO2-excretion with and without administration of iproniazid
4) MAO activity: influence of chain length
5) Lung uptake: influence of amino-group and log P
Details on dosing and sampling:

1) tissue distribution (blood, brain, herat, lungs, spleen, kidneys, liver): at 1,5, and 15 minutes after injection
2) determination of non-amine metabolites in blood and lungs: at 1,5, and 15 minutes after injection
3) MAO inhibition: determination of 11CO2-excretion with and without administration of iproniazid: at 1-minute intervals for 20 minutes, starting immediately after dosing
4) MAO activity: influence of chain length: at 5, 10, 15, and 20 minutes
Statistics:
calculation of means +/- standard deviation

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
[11]CO2

Any other information on results incl. tables

Read-across hypothesis: for details please see read-across report in IUCLID section 13

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Octylamine was rapidly metabolized by MAO and subsequently to CO2 via ß-oxidation. Octylamine and higher homologues show an affinity for the lung after injection. At low dose levels, the concentration in the lung declines to blood levels within 15 minutes after dosing. As to the metabolism by MAO it should be noted that the Vmax for octylamine is extremely small compared to other enzyme reactions, i.e. in the range 120 -180 nmole/hr. This is not reflected in the present publication because metabolism rates and concentrations are expressed as percentage of an extremely small dose.
Executive summary:

The distribution and metabolism of octylamine (and several other linear alkylamines with chain lengths from C4 to C13) was examined in mice after intravenous injection of radiolabelled 11C-octylamine hydrochloride. The radiolabel was positioned at the a.C atom. The specific activity was extremely high (2000 Ci/mmol) compared to 14C-labelled chemicals, an allowed to administer extremely low doses (0.1-1 mCi of [11C]-octylamine-HCl  per animal; i.e. 0.05 to 0.5 nmole/mouse; equivalent to 0.008 to 0.08 µg/mouse). The examinations included tissue distribution following injection, and metabolism and excretion.

Tissue distribution: at 1 min after dosing, high octylamine levels were seen in kidneys (11% of dose/organ), liver (8%)  and lung (7.1% of dose/organ). At 15 minutes, values remained elevated in kidneys (9.2%) and liver (4.8%), but returned to blood levels in the lungs (1.9% vs. 1.44% in the lungs) 

Initially high levels in the lung followed by a substantial decrease was seen for all primary alkylamines with chain lengths of C8 to C13. It was demonstrated that uptake of alkylamine is dependent on two factors, i.e. the presence of an amino group, and an relatively lipophilic alkyl group. Octylamine, and the higher analogs, provide both factors.

Metabolism:  extractable non-amine metabolites appeared rapidly in blood and lungs, accounting for 58% (blood) and 28% (lungs) of the extractable radioactivity at 0.5 minutes after injection, and for 97% (blood) and 73% (lungs) at 15 minutes. 11CO2 accounted for 12% of the radioactivity extractable from blood at 1 minute after injection, and for 25% at 5 and 15 minutes after injection. These findings suggested that octylamine was rapidly deaminated by Monoamine oxidase (MAO) and further metabolized by aldehyde dehydrogenase the utilization in the ß-oxidation reactions. This was in good agreement with the finding that up to 50% of the octylamine dose was expired as 11CO2 at 20 min after injection, whereas the excretion was significantly decreased to (7% of the dose at 20 min) in mice that had been pre-treated with an MAO-inhibitor, iproniazid.

As to the substrate specificity of MAO, the excretion rate of 11CO2 varied with chain lengths (cf. reference, Fig 7). The maximum rate was seen with hexylamine (C6), and the rates of the other amines were in the order:

C4 C5 C6 >C7 >C8 > C9 > C10 > C13  

Overall, octylamine was rapidly metabolized by MAO and subsequently to CO2via aldehyde dehydrogenase and ß-oxidation. Octylamine and higher homologues show an affinity for the lung after intravenous injection. At low dose levels, the concentration in the lung declines to blood levels within 15 minutes after dosing.

It should, however, be noted that the Vmax of MAO for octylamine is extremely small compared to other enzyme reactions, i.e. in the range 120 -180 nmole/hr (cf. quotation in teh reference, page 144). This is not properly reflected in the present publication because metabolism rates and tissue concentrations are expressed as the percentage of an extremely small dose. Distribution and clearance from the lung and excretion as CO2 are expected to show a different pattern at dose levels in the range 10 to 1000 mg/kg bw that are commonly used in laboratory animal testing, because MAO is then expected to be by far saturated (Fowler, 1976a).