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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:
1 (reliable without restriction)

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:
FUNDAMENTAL AND APPLIED TOXICOLOGY 2:252-260 (1982)

Materials and methods

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Ethylenediamine dihydrochloride (EDA-2HCI)-1,2-MC (specific activity 8.0 mCi/mmol) was purchased from New England Nuclear, Boston, Massachusetts 02118. The radiochemical purity was established to be greater than 99% by paper chromatography.
The chemical identity was reconfirmed by mass spectrometry.
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Hilltop-Wistar male rats were supplied by Hilltop Laboratory Animals, Inc., Scottdale, Pennsylvania 15683.
Routinely, 3-8 animals with similar body weights were used for each experiment.
The body weight of the'rats used in this study ranged from 154 to 266 g.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
5, 50, 500 mg/kg oral exposure, endotracheal and intravenous exposure.
Doses / concentrations
Remarks:
Doses / Concentrations:
5, 50, 500 mg/kg oral exposure.
No. of animals per sex per dose:
3-8 male animals

Results and discussion

Metabolite characterisation studies

Details on metabolites:
N-acetylation is a major metabolic pathway for EDA in the rat. In the urine, AcEDA accounts for approximately half of the radioactivity. The data on the ion-exchange chromatography of aqueous fecal extract also revealed the presence of AcEDA as a major metabolite. In addition to acetylation, the enzymatic formation of aminoacetaldehyde from EDA as suggested by Hoshika (1967) is highly probable in the rat. If this reaction happens in vivo, it is conceivable that CO2 might be generated from ethanolamine, a probable metabolite of aminoacetaldehyde, through a series of reactions as discussed by Taylor and Richardson (1967).

Any other information on results incl. tables

The primary route of excretion of EDA and its metabolites is via urine. This is understandable because EDA and its known and probable metabolites are all relatively small, watersoluble molecules.

In all three routes of excretion (urinary, fecal, respiratory), the major portion was eliminated in the first 24 hours. However, at 500 mg/kg, higher rates of excretion during the 24-48 hour period are evident; this is particularly true in the case of intravenous administration . These observations are indicative of the involvement of capacity-limited processes at the dosage level of 500 mg/kg.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Primary route: urine (42-65%)
fecal excretion: 5-32%
CO2 expired: 6-9%
in body: 11-21 % (thyroid, bone marrow, liver, kidney).
Major metabolite: N-acetyl ethyldiamine.