Carbonic acid, compound with 2-aminoethanol (1:2)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

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; Reifenrath, WG; Black, KE.

Year:

1985

Bibliographic source:

Fundamental and Applied Toxicology 5, S127-S133

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]-ethanolamine 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

Molecular formula:

C2H7NO

IUPAC Name:

2-aminoethanol

Details on test material:

Name if test material: ethanolamine
Analytical purity: 97%
Radiochemical purity: >95%
Specific activity: 4 µCi/mmol
Location of the label: [1,2-14C]ethanolamine HCl

Radiolabelling:

no

Remarks:

[14C]-ethanolamine

Test animals

Species:

mouse

Strain:

other: nude

Sex:

male

Details on test animals or test system and environmental conditions:

Source: Harlan Industries (IND, US)
Weight at initiation: 30 g

Mice were grafted with human skin (0.5mm thickness), obtained by dermatome from consenting volunteers following breast surgery.
Grafting was performed using procedure described in Black and Jederberg (Athymic nude mice and human skin grafting. In Models in Dermatology
(L. Maibach, ed.), Vol 1, pp. 228-239. Karger, Basel.1985).

Administration / exposure

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

Ethanolamine was applied with a microliter syringe at a chemical dose of 4.0 µg and a radioactive dose of 3.6 µCi to a 1.45-cm2 graft area, using ethanol (10 µl) as a vehicle.

The same dose was applied to a similar circular area outlined on the flank skin of nongrafted mice or administered intraperitoneally to another group of nongrafted mice. The mice were immediately placed in all-glass metabolism cages, and expired 14CO2 was collected for 24 hr in 2% aqueous NaOH. Radioactivity in the NaOH solution was periodically determined. Urine was collected for 24 hr in 0.5% HCl.

Duration and frequency of treatment / exposure:

24 h, single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
chemical dose of 4.0 µg and a radioactive dose of 3.6 µCi to a 1.45-cm2 graft area, using ethanol (10 µl) as a vehicle

No. of animals per sex per dose / concentration:

5 animals in total per treatment group

Control animals:

yes

Positive control reference chemical:

(1) same dose applied to a similar circular area outlined on the flank skin of non-grafted mice
(2) same dose administered intraperitoneally to another group of non-grafted mice.

Details on study design:

Pharmacokinetic study (Adsorption, 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 oxidised to [14C]CO2 and 4.6% was excreted in the urine and 1.8% in faeces over 24h.

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 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

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Topical administration of ethanolamine penetrates the skin (to similar extents in mice and human sin grafted mice),and is readily metabolised in the skin as well as in other organs and tissues of the mouse. Percutaneous penetration is relatively slow.
Metabolism is most extensive in the liver, where ethanolamine is converted into amino acids serine and choline.