Tetradonium bromide

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:

data from handbook or collection of data

Justification for type of information:

Read-across to tetradonium bromide from data on dodecyltrimethylammonium bromide.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

Route and rate of excretion of radiolabelled dodecyltrimethylammonium bromide given by parenteral injection in rats.

GLP compliance:

not specified

Remarks:

Test performed before GLP guideline

Test material

Test material information

Constituent 1

Reference substance name:

Dodecyltrimethylammonium bromide

EC Number:

214-290-3

EC Name:

Dodecyltrimethylammonium bromide

Cas Number:

1119-94-4

Molecular formula:

C15H34N.Br

IUPAC Name:

N,N,N-trimethyldodecan-1-aminium bromide

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): [14C] Dodecyltrimethylammonium bromide (DTB)
- Specific activity (if radiolabelling): 7.6 mCi/mmol; 24.7 µCi/mg
- Locations of the label (if radiolabelling): [1-14C] dodecyl
- Obtained from Farbwerke Hoechst AG, Frankfurt, Germany.

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-230 g
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

other: intravenous and subcutaneous

Vehicle:

other: 0.9% (w/v) aqueous NaCl

Details on exposure:

Intravenous: A 0.023% solution of dodecyltrimethylammonium bromide (500 µl) was injected into the tail vein of each of two rats (0.822 mg and 0.767 mg/kg bw). Rats were kept in metabolism cages for 24 hours. To three further rats, 0.135-0.174% solution of dodecyltrimethylammonium bromide (50 µl) was administered via a jugular cannula.
Subcutaneous: 1 ml containing 0.29 mg dodecyltrimethylammonium bromide was administered subcutaneous in the dorsal region of 3 rats. Rats were kept individually in metabolism cages for 48 hours.

Duration and frequency of treatment / exposure:

Intravenous: Animals were killed 24 hours after injection. When administered via a jugular cannula, two animals were killed after 15 minutes and one animal after 300 minutes.
Subcutaneous: 48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
Intravenous: 0.822 mg and 0.767 mg/kg bw
To three further rats, 0.135-0.174% solution of dodecyltrimethylammonium bromide (50 µl) was administered via a jugular cannula.
Subcutaneous: 1 mg/kg bw

No. of animals per sex per dose / concentration:

Intravenous: 2
Via jugular cannula 3
Subcutaneous: 3

Details on dosing and sampling:

Intravenous administration: Radioactivity was measured in urine, faeces and organs after 24 hours. Urine and faeces were checked for metabolites by thin-layer chromatography.
Administration via a jugular cannula: Radioactivity was measured in organs after 15 minutes and 24 hours. Radioactivity was measured in blood samples withdrawn 3, 9, 15, 30, 60, 120 and 300 minutes after administration.
Subcutaneous: Radioactivity was measured in urine and faeces for every 24 hours and in tissue and carcass after 48 hours.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The concentrations af radioactivity in organs expressed as % of the applied dose were after 15 min: 24.8 in liver, 5.54 in kidneys, 0.48 in heart, 0.15 in spleen and 0.83 in lungs. After 24 hours: 2.08 in liver, 0.36 in kidneys, 0.11 in heart, 0.029 in spleen, 0.14 in lungs, 0.18 in stomach and 1.41 in intestinal tract. No detectable level of radioactivity was found in stomach and intestinal tract after 15 minutes.
The blood levels at 3, 9, 15, 30, 60, 120 and 300 minutes after injection were 0.50, 0.10, 0.04, 0.03, 0.04, 0.02 and 0.009 µg/ml blood, respectively.

Details on excretion:

24 hours after iv injection, 58.9±1.06% of radioactivity was excreted in urine and 11.6±0.42% in faeces.
48 hours after sc administration, 68.1±13.1% of radioactivity was excreted in urine and 14.1±3.56% in faeces.

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

Only unchanged surfactant was found in the faeces. Several unidentified metabolites were detected in the urine after iv injection.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
After either intravenous or subcutaneous administration more than 70% of the applied radioactivity was eliminated within the first 24 hours. The distribution of radioactivity in organs 24 hours after intravenous administration did not demonstrate any significant affinity of dodecyltrimethylammonium bromide for any organ or tissue. The measured levels of radioactivity in all organs were decreasing during the 24 hours period. Radioactivity levels in blood samples showed a rapid fall in less than 30 minutes. There was no sign of accumulation of the test substance in any organs.

Executive summary:

The reported study examines the excretion and distribution of radiolabelled dodecyltrimethylammonium bromide administered either intravenous or subcutaneous. After either intravenous or subcutaneous administration more than 70% of the applied radioactivity was eliminated within the first 24 hours. The distribution of radioactivity in organs 24 hours after intravenous administration did not demonstrate any significant affinity of dodecyltrimethylammonium bromide for any organ or tissue. The measured levels of radioactivity in all organs were decreasing during the 24 hours period. Radioactivity levels in blood samples showed a rapid fall in less than 30 minutes. There was no sign of accumulation of the test substance in any organs.