Dimantine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication/study report which meets basic scientific principles. Justification for read-across see chemical safety report chapter 1.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

A comparison of the elimination and biotransformation of dodecyldimethylamine oxide (DDAO) by rats, rabbits, and man

Author:

Turan T.S. and Gibson W.B.

Year:

1981

Bibliographic source:

Xenobiotica 11, 447-458

Reference 2

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report

Author:

OECD

Year:

2006

Bibliographic source:

OECD Existing Chemicals Database

Materials and methods

Objective of study:

excretion

metabolism

Principles of method if other than guideline:

Excretion and metabolism study in rats after oral application of test substance.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dodecyldimethylamine oxide

EC Number:

216-700-6

EC Name:

Dodecyldimethylamine oxide

Cas Number:

1643-20-5

Molecular formula:

C14H31NO

IUPAC Name:

dodecyl(dimethyl)amine oxide

Radiolabelling:

yes

Remarks:

C14

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 180 - 230 g
- Fasting period before study: overnight
- Housing: stainless stell cages
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
1 and 100 mg/kg

No. of animals per sex per dose / concentration:

1 mg/kg: 5 males
100 mg/kg: 2 males, 2 females

Control animals:

no

Positive control reference chemical:

No

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, feces, CO2
- Time and frequency of sampling: 24 h intervals for 72 h

Results and discussion

Preliminary studies:

no preliminary study

Main ADME results

Main ADME results 1

Type:

excretion

Results:

After 72 h 90 and 98 % of the administered dose were excreted mainly in the urine (54 and 66%).

Main ADME results 2

Type:

metabolism

Results:

No unmetabolized amine oxide was excreted in urine

Toxicokinetic / pharmacokinetic studies

Details on excretion:

After 72 h 90 and 98 % of the administered dose were recovered mainly in the urine (54 and 66%). See table below for details.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The metabolites identified in this study indicate various metabolizing ways for DDAOs. Urinary metabolites suggest omega-, and beta-oxidation, amine oxide reduction and aliphatic mid-chain hydroxylation.

Any other information on results incl. tables

Percentage of applied radioactivity in excretion products:

Animal	rat(72 h)
dose(mg/kg)	1	100
urine	66	54
feces	7	9
CO2	26	23
carcass	-	4
total	98	90

No unmetabolized amine oxide was excreted in urine

Percentage of applied radioactivity in urine

Species		rat
metabolite	Metabolic pathway
II	omega-, beta-oxidation	28

metabolite II = carboxylic acid intermediates ofw,B-oxidation, still carrying the amine oxide functional group.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Under the conditions of the test between 90 and 98 % of the dose administerd orally to rats were excreted within 72 h, mainy by urine. Only a metabolized product of the test substance was observed in urine.

Executive summary:

Male and female rats were exposed to 1 and 100 mg/kg test substance orally by gavage. Within 72 h 90 and 98 % of radioactivity was excreted mainly via urine (54 and 66%). No unmetabolized amine oxide was excreted in urine.