(2-hydroxyethyl)ammonium nitrate

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:

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

Test material information

Constituent 1

Reference substance name:

2-aminoethanol

EC Number:

205-483-3

EC Name:

2-aminoethanol

Cas Number:

141-43-5

IUPAC Name:

2-aminoethanol

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 or test system 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 / concentration:

5 animals in total per treatment group

Control animals:

yes

Positive control reference chemical:

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