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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
publication
Title:
Distribution and metabolism of topically applied ethanolamine
Author:
Klain GJ, et al.
Year:
1985
Bibliographic source:
Fundam. Appl. Toxicol. 5, 127 -133

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The absorption, distribution and metabolism of topical [14C]-MEA was studied in vivo, using athymic nude mice and human skin grafted onto athymic nude mice.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ethanolamine
- Analytical purity: 97 %
- Radiochemical purity (if radiolabelling): >95%
- Specific activity (if radiolabelling): 4 µCi/mmol
- Locations of the label (if radiolabelling): [1,2-14C]ethanolamine-HCl
Radiolabelling:
yes
Remarks:
C14 ethanolamine

Test animals

Species:
mouse
Strain:
other: nude
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 30 g

Administration / exposure

Route of administration:
dermal
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: 1.45 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 µg

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 µl

USE OF RESTRAINERS FOR PREVENTING INGESTION: no
Duration and frequency of treatment / exposure:
24 hours, single exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
4 µg/animal (radioactive dose of 3.6 µCi to a 1.45-cm²)
No. of animals per sex per dose:
5 animals in total per treatment group
Control animals:
yes
Positive control:
Animals were injected intraperitoneally with the labelled test substance.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : exhaled air, urine, faeces, liver, kidney, lung, brain, heart, muscle

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The results indicated that topical applied 2-aminoethanol penetrates the skin and is widely distributed in the body, radioactivity being detected in all the tissues and organs examined. Percutaneous penetration of the skin appears however to be relatively slowly, demonstrated by a marked time lag in the initial appearance of labelled carbon dioxide between topical and intraperitoneal treatment. Radioactivity in expired CO2 was detected 5 min after an intraperitonealadministration of 2-aminoethanol, while no radioactivity in expired air was detected during the first 20 min post-topical application.
Details on distribution in tissues:
24% of the applied radioactive dose was recoved in the liver. Further recovery of the administered radioactive dose was at skin administration site (24.3%), as exhaled CO2(over 18%), in urine (4.6%), in kidneys (2.5%) and in feces (1.8%). Lungs, brain, and the heart contained 0.55, 0.27, and 0.15% of the dose, respectively.
Transfer into organs
Test no.:
#1
Transfer type:
blood/brain barrier
Observation:
distinct transfer
Details on excretion:
Over 18% of the topical radioactive dose was oxidized to [14]CO2 and 4.6% was excreted in the urine and 1.8% in feces over 24 hr .

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The substance is readily metabolized in the skin as well as in other organs and tissues in the mouse. Liver is a major site for metabolism of 2-aminoethanol. Extensive metabolization was indicated by appearance of labelled carbon dioxide in skin and hepatic amino acids, proteins and incorporation into phospholipids, and by recovery of over 18% of radioactive dose as [14]-CO2. Urea, glycine, serine, choline, and uric acid were the urinary metabolites of 2-aminoethanol.

Any other information on results incl. tables

Results summary:

Results details:

Distribution of radioactivity in grafted and ungrafted athymic nude mice 24 h after topical application of ethanolamine (n=5)

Organ/tissue

Human skin grafted nude mouse

ungrafted nude mouse

heart

0.15 ± 0.02

0.13 ± 0.01

brain

0.27 ± 0.07

0.25 ± 0.04

lungs

0.55 ± 0.09

0.63 ± 0.03

kidneys

2.53 ± 0.15

2.24 ± 0.19

liver

24.30 ± 3.82

25.80 ± 4.1

muscle gastroeneminus

398 ± 49*

427 ± 39*

skin application site

18.4 ± 2.7

12.1 ± 0.93

skin untreated

201 ± 34*

275 ± 24

urine

4.60 ± 0.57

5.20 ± 0.72

feces

1.82 ± 0.21

0.98 ± 0.64

cotton swabs

2.85 ± 0.36

3.28 ± 0.25

data represent means ± SE percentage of administered dose; * dpm/mg tissue

Radioactivity in proteins and amino acids isolated from the liver, human skin grafts and mouse skin after topical application

 

Liver*

Graft**

Mouse skin**

Protein (dpm/mg)

958, 983

241, 199

119, 157

Amino acids***

Glycine

47.1, 44.6

38.6, 39.4

40.2, 42.8

Serine

22.2, 18.3

traces only

traces only

Glutamic acid

10.2, 8.1

15.4,13.8

15.8, 14.5

Alanine

2.7, 1.9

6.3, 6.4

5.9, 6.5

Aspartic acid

1.4, 1.1

3.1, 4.1

3.8, 3.2

Proline

13.6, 14.9

34.2, 34.9

31.9, 33.1

* individual values from 2 grafted mice

** individual values from 2 grafted mice and two ungrafted mice

*** percentage of radioactivity applied to chromatographic columns

Applicant's summary and conclusion