Fatty acids, C16-18 (even numbered), reaction products with tetraethylenepentamine, acetates (salts)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Objective of study:

absorption

excretion

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Principles of method if other than guideline:

The radioactively labelled compound was applied as a single oral dose (appr. 10 mg/kg body weight) to three female rats. The intestinal absorption was studied for 96 hours after application.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Imidazolium compounds, 2-(C15-17(odd numbered), C17-unsatd. alkyl)-1-[2-(C16-18(even numbered), C18-unsatd. amido)ethyl]-4,5-dihydro-N-methyl, Me sulfates)

IUPAC Name:

Imidazolium compounds, 2-(C15-17(odd numbered), C17-unsatd. alkyl)-1-[2-(C16-18(even numbered), C18-unsatd. amido)ethyl]-4,5-dihydro-N-methyl, Me sulfates)

Radiolabelling:

yes

Remarks:

labelled at the C-atom in the N-methyl-group of the imidazolinium-ring, specific activity 2.55 mCi/mMol

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa. Winkelmann, Borchen
- Weight at study initiation: 220 g - 235 g
- Housing: individually in metabolism cages
- Diet (e.g. ad libitum): Altromin 1324, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C
- Fasting period: 24 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
444.7 mg test item (50% solution) was dissolved in 99.114 g bidestilled water, resulting in 2.23 mg test item/g solution
approx. 1 g of this solution was administered to the animals, corresponding to 9.115±0.39 mg/kg bw

Doses / concentrations

Dose / conc.:

10 mg/kg bw/day

No. of animals per sex per dose / concentration:

3

Control animals:

no

Details on dosing and sampling:

TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired air, cage washes, gastro intestinal tract, carcass
- Time and frequency of sampling:
Urine: 0 - 8 h; 8 - 24 h; 24 - 48 h; 48 - 72 h; 72 - 96 h
faeces: 0 - 24 h; 24 - 48 h; 48 - 72 h; 72 - 96 h
expired air: 0 - 8 h; 8 - 24 h; 24 - 48 h; 48 - 72 h; 72 - 96 h
cage wash: after 96 h

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

at least 0.792%

Main ADME results 2

Type:

excretion

Results:

urine: 0.524
faeces: 78.7%

Main ADME results 3

Type:

distribution

Results:

gastrointestinal tract: 0.077%
carcass: below detection limit

Toxicokinetic / pharmacokinetic studies

Details on absorption:

An intestinal absorption of at least 0.792 % of the administered dose was found.

Details on excretion:

0.407% of the applied dose was excreted in the urine within 24 hrs after application, 0.221% within the first 8 hrs.
In the faeces 78.7% of the adminstered radioactivity was eliminated within 96 hrs, 54.9% of the adminstered radioactivity within the first 24 hours. Hence it follows that either a great part of the applied substance was not absorbed intestinally or a part was eliminated by biliary excretion after intestinal absorption.

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Executive summary:

(N-methyl-14C)-imidazoliniumquat-methosulfate was used for this study. The compound was labelled at the C-atom in the N-methyl-group of the imidazolinium-
ring. The radioactive compound was applied as a single oral dose (appr. 10 mg/kg body weight). Three female rats (SPF-Cpb) were used as a test group (mean body weight: 227 ± 7 g). The intestinal absorption was studied for 96 hours after application.
An intestinal absorption of at least 0.792 % of the administered dose was found.
0.407% of the applied dose was excreted in the urine within 24 hrs after application, 0.221% within the first 8 hrs.
In the faeces 78.7% of the adminstered radioactivity was eliminated within 96 hrs, 54.9% of the adminstered radioactivity within the first 24 hours. Hence it follows that either a great part of the applied substance was not absorbed intestinally or a part was eliminated by biliary excretion after intestinal absorption.
The radioactivity found in the expired air (measured with all rats) was below the detection limit.
Also, the radioactivity found in the carcass 96 hours after application was below the detection limit (except one animal).