Oxirane, reaction products with ammonia, distn. residues

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: Basic data given acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Reference 2

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

Test material information

Constituent 1

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 / concentration:

4

Control animals:

no

Positive control reference chemical:

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:

0.7% of the dose remained in the tissues 72 hours after dosing.

Details on excretion:

26% of the dose was recovered in 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.

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. 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.