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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)

Data source

Reference
Reference Type:
publication
Title:
Metabolism and pharmacokinetics of ethylenediamine in the rat following oral, endotracheal or intravenous administration.
Author:
Yang, R. S. H. and Tallant, M. J.
Year:
1982
Bibliographic source:
Fundam. Appl. Toxicol. 2:252-260

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
Oral, tracheal or intravenous administration. Fate of radiochemicals was followed for 24 or 48 hours.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Ethylenediammonium dihydrochloride
IUPAC Name:
Ethylenediammonium dihydrochloride
Constituent 2
Reference substance name:
Ethylenediammonium dichloride
EC Number:
206-369-6
EC Name:
Ethylenediammonium dichloride
Cas Number:
333-18-6
IUPAC Name:
ethane-1,2-diaminium dichloride
Details on test material:
- Radiochemical purity (if radiolabelling): >99%
- Specific activity (if radiolabelling): 8mCi/mmol
- Locations of the label (if radiolabelling): 1,2 14C-Ethylenediamine *2HCl
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
other: oral gavage, intravenous and endotracheal
Vehicle:
other: water, or 0,9% saline solution
Duration and frequency of treatment / exposure:
24 or 48 hours study of distribution following single dose.
Doses / concentrations
Remarks:
Doses / Concentrations:
5, 50 and 500 mg/kg bodyweight
No. of animals per sex per dose / concentration:
3 - 8 animals per dose, only male
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, plasma, tissues, cage washes
- Other: Air CO2 trapping

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Rapid absorption from gastrointestinal as well as from respiration tract.
Details on distribution in tissues:
Distributed in body, but liver, kidneys, thyroid and bone marrow contained highest concentrations.
Details on excretion:
Urine: 45-55%, Feces: 4-16%, CO2: 6-8%,

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
N-acetylethylenediamine is a major metabolite. It accounted for approximately half of the urinary radioactivity. The route of administration did not appear to change the metabolic profile.

Any other information on results incl. tables

Tissue distribution pattern in male Wistar rats was very similar following a single oral, intratracheal or intravenous. administration of [1,2-14C]ethylenediamine dihydrochloride. The radioactivity was distributed throughout the body although thyroid, bone marrow, liver and kidney contain relatively higher concentrations of radioactivity. Measurements of radioactivity in 26 tissues revealed a direct proportion to the dosage levels in all cases.

Material Balance study following single oral dose

 

 

 

 

 

 

 

 

% of administered dose

 

Experimental Period

5 mg/kg

50 mg/kg

500 mg/kg

Urine

0±24

55.8± 3.4

55.9± 3.0

45.7±3.3

24±48

1.4± 0.1

1.5± 0.2

2.5±0.4

Feces

0±24

4.5± 2.7

13.8± 1.0

16.2±2.5

24±48

0.6± 0.3

0.6± 0.1

1.1±0.2

14CO2

0±24

7.8± 1.6

4.8± 0.4

5.9±0.4

24±48

1.1± 0.03

0.8± 0.1

1.3±0.2

Cage Washing

0±24

3.8± 1.8

2.8± 1.2

3.0±0.8

24±48

<0.1

0.1± 0.01

0.4±0.1

Major organs

 

2.3± 0.4

1.7± 0.1

2.0±0.2

Carcass

 

12.2± 1.0

9.4± 0.1

10.8±0.3

Total Recovery

 

90.5±3.8

91.4± 2.3

90.4±2.2

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results