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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:
other: Basic data given acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004
Reference Type:
secondary source
Title:
Unnamed
Year:
2004

Materials and methods

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
Details on test material:
- Name of test material (as cited in study report): Triethanolamine
- no further data
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female

Administration / exposure

Route of administration:
intravenous
Vehicle:
acetone
Details on exposure:
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.
Duration and frequency of treatment / exposure:
72 hrs
Doses / concentrations
Remarks:
Doses / Concentrations:
3 mg/kg bw
No. of animals per sex per dose:
4
Control animals:
no
Positive control:
not done
Details on dosing and sampling:
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

Details on metabolites:
Urine collected 6 to 24 hours after intravenous dosing contained more than 95% radiolabeled components that coeluted with unchanged triethanolamine, with minor components eluting the same fractions in mice as those in rats.

Any other information on results incl. tables

With only 40% of the dose excreted within 24 hours, mice appeared to excrete intravenously administered triethanolamine much slower than did rats. Considerably more of the dose was recovered in the feces of mice (28 %) than in rats (0.6 %). However, it is common for mice to shred and powder their food pellets, and the feces collections are often contaminated with urine-soaked solids and their associated radiochemical equivalents. Less than 0.5 % of the dose was recovered in carbon dioxide traps, and less than 0.1 % was recovered in volatiles traps. The distribution of radioactivity present in tissue samples from female mice showed that, as with rats, the heart, kidney, liver, lung, and spleen contained higher concentrations of triethanolamine equivalent relative to blood.

Applicant's summary and conclusion