Cetrimonium bromide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: published study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The published study is well described. The study was not performed according to GLP and no guideline was given.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1975

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

The absorption, distribution and excretion of orally administrered radiolabelled cetyltrimethylammonium bromide in rats.

GLP compliance:

not specified

Remarks:

Performed before GLP guideline

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecyltrimethylammonium bromide

Cas Number:

57-09-0

IUPAC Name:

Hexadecyltrimethylammonium bromide

Test material form:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): [14C] CTAB, Cetyltrimethylammonium bromide
- Radiochemical purity (if radiolabelling): 99%
- Specific activity (if radiolabelling): 17.6 µCi/mg
- Locations of the label (if radiolabelling): [1-14C]cetyl

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 210-240 g
- Fasting period before study: 24 hours
- Individual metabolism cages: For excretion study
- Diet (e.g. ad libitum): After 8 hours for experiments lasting more than 24 hours
- Water (e.g. ad libitum): After 8 hours for experiments lasting more than 24 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

An aqueous solution of 0.8 mg/kg radiolabelled CTAB was given by gastric intubation in volumes of 4.0 ml/kg body weight.

Duration and frequency of treatment / exposure:

The animals were killed 2, 4, 8, 25, 48, 72 and 96 hours after intubation.

Doses / concentrations

Remarks:

Doses / Concentrations:
4.0 ml/kg bw of an aqueous solution of radiolabelled CTAB (0.8 mg/kg): 3.2 µg/kg bw

Details on dosing and sampling:

Distribution study: Blood samples were withdrawn from the tail before the animals were killed. The animals were killed 2, 4, 8, 25, 48, 72 and 96 hours after intubation. Tissue samples of liver, kidney, spleen, heart, lungs and hind leg were taken from the killed animal. In animals killed 8 hours after intubation, the gastro-intestinal tract was removed and divided into stomach, proximal and distal halves of the small intestine and the caecum and colon together.
Excretion study: Animals were kept in metabolism cages in order to collect urine and faeces in 4 hours interval for 3 days. Expired CO2 was trapped in NaOH at 4 hours interval during day 1 after intubation. Bile was collected for 12 hours at 2 hours interval

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

A total of about 80% of the administered radioactivity was found in the gastro-intestinal tract mostly being in the gastro-intestinal contents. About 90% of the dose had left the stomach within 8 hours. Only small amounts of the radioactivity were found in tissues of other organs indicating that the CTAB is not preferentially distributed to any single target organ. Liver and kidneys showed highest level of radioactivity with a peak level in liver of 0.8% of the administered dosae occurring 8 hours after dosing. The tissue radioactivity declined rapidly and only traces were found 4 days after dosing.

Details on excretion:

About 2% of the administered dose was excreted in the bile during the first 12 hours after administration. This indicated together with low levels in the serum poor intestinal absorption of CTAB. After 3 days of the oral administration, the excretion in faeces was 92% and in urine 1% of the administered dose. Most of the radioactivity excreted in the faeces is suggeted to be unabsorbed material. No radioactivity was found in the expired CO2 collected during day 1.

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
A total of about 80% of the administered radioactivity was found in the gastro-intestinal tract 8 hours of oral administration. The findings together with low levels of radioactivity in the serum and bile indicated that CTAB is poorly absorbed in the gastro-intestinal tract. After 3 days of the oral administration, the excretion in faeces was 92% and in urine 1% of the administered dose. Most of the radioactivity excreted in the faeces is suggested to be unabsorbed material. Only small amounts of radioactivity were found in the blood and in tissues of organs other than the gastro-intestinal tract indicating that the CTAB is not preferentially distributed to any single target organ.
These data indicate that at least 3% of the oral dose have been systimally absorbed as this was the amount that had been found to be excreted through bile + urine. As further 6% of the radioactivity could not be accounted for a maximum absorption rate of 9% can be assumed. Thus for further risk assessment pupose an average oral absorption rate of 6% is used.

Executive summary:

The reported study examines the excretion and distribution of radiolabelled cetyltrimethylammonium bromide orally administered in female rats.

About 80% of the administered radioactivity was found in the gastro-intestinal tract 8 hours after oral administration. Only small amounts were found in the blood and plasma and about 2% of the administered radioactivity was excreted in the bile during the first 12 hgours. After 3 days the total excretion in faeces was 92% and in urine 1% of the administered dose. The findings together with low levels of radioactivity in the serum and bile indicated that CTAB is poorly absorbed in the gastro-intestinal tract. Most of the radioactivity excreted in the faeces is suggested to be unabsorbed material. Only small amounts of radioactivity were found in the blood and in tissues of organs other than the gastro-intestinal tract indicating that the CTAB is not preferentially distributed to any single target organ. These data indicate that approximately 3% of the oral dose have been systimally absorbed as this was the amount that had been found to be excreted through bile + urine.