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Toxicological information

Basic toxicokinetics

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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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
according to
Guideline:
other: See explanations
Principles of method if other than guideline:
Groups of four female mice received a single intravenous dose of 3 mg/kg [14C]-triethanolamine. Expired radioactivity was trapped and quantitated and urine and feces were collected from all B6C3F1 mice dosed intravenously up to 72 hours after dosing. Tissue samples at 72 hours after dosing were also examined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female
Details on test animals and environmental conditions:
Single intravenous doses contained approximately 6 μCi radiolabel for mice, an appropriate amount of nonradiolabeled triethanolamine, and isotonic saline as a vehicle that delivered a total dosing volume of 2 mL/kg to mice. Intravenous doses were drawn into a syringe equipped with a Teflon®-tipped plunger (Hamilton) and a 30 gauge hypodermic needle. Excess dose formulation was wiped off the needle before weighing the filled dosing syringe. Intravenous doses were injected into one lateral tail vein. After dosing, the needle was wiped clean with a Kimwipe®, and the empty syringe was reweighed. The Kimwipe® was placed into a vial containing 2 mL ethanol and analyzed by liquid scintillation spectrometry. Each dose was calculated as the difference between the weights of the filled and empty dosing apparatus less the amount found in the Kimwipe®. To determine the concentration of [14C]-triethanolamine in the dose formulation, two weighed aliquots were taken before, two after, and one during dosing.

Administration / exposure

Route of administration:
intravenous
Vehicle:
acetone
Duration and frequency of treatment / exposure:
72 hr
Doses / concentrations
Dose / conc.:
3 mg/kg bw/day (nominal)
No. of animals per sex per dose:
4
Control animals:
no
Positive control:
no
Details on study design:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, tissues, cage washes, CO2
- Time and frequency of sampling: 24, 48, 72 hrs

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
The distribution of radioactivity present in tissue samples from female mice showed that the heart, kidney, liver, lung, and spleen contained higher concentrations of triethanolamine equivalent relative to blood.
Details on excretion:
26% of the dose was recovered in the urine within 24 hours.
An average of 62% of the dose was recovered in the urine within 72 hours after dosing, and 27.6% was recovered in the feces during this time.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Intravenously administered triethanolamine was rapidly excreted by female rats and mice, primarily in the urine.
Less than 1% of the dose was present in tissues sampled 72 hours after dosing. In both species, the heart, kidney, liver, lung, and spleen contained higher concentrations of triethanolamine equivalents than did blood.

After intravenous and dermal dosing in female rats and mice, triethanolamine was excreted, for the most part, unchanged in urine. Two additional polar peaks, each less than or equal to 5% of the total, were present in the urine. At least one of these polar peaks may have originated from impurities in the [14C]-triethanolamine stock, which were better resolved from the test article peak during development of HPLC onditions for metabolite analysis.
Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.