Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication that meets generally accepted scientific standards, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Ethylenimine: Studies of the Distribution and Metabolism in the Rat Using Carbon-14
Author:
Wright, G.J. and Rowe, V.K.
Year:
1967
Bibliographic source:
Toxicol. Appl. Pharmacol. 11, 575-584

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Rats were dosed intraperitoneally with ethylenimine-14C. After administration of the radioactive compound the rats were placed in all-glass metabolism cages equipped for separate collection of urine, feces, and expired air. At the end of the experiment the rats were killed by decapitation, and the blood and tissues were saved for analysis of residual activity.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Ethyleneimine-14C. Special activity of the materials was 1.47 mc/mmole.
The ethylenimine was shipped as a benzene solution over a pellet of anhydrous potassium hydroxide.
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
other: Dow-Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 191-270 g
- Fasting period before study: no data
- Housing: individually in an all-glas metabolism cage
- Individual metabolism cages: yes
- Diet: ad libitum for the first 6 hours
- Water: ad libitum for the first 6 hours
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS - no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Details on exposure:
The ethylenimine was extracted from 0.2 ml of the benzene solution by 1.0 ml of water. Extraction into the water was essentially quantitative. Half a milliliter of the aqueous ethylenimine solution was injected intraperitoneally into a rat, and the remainder was retained for analysis of radioactivity and purity.
Duration and frequency of treatment / exposure:
Animals received 1 dose and were sacrificed 24 or 96 hours thereafter.
Doses / concentrations
Remarks:
Doses / Concentrations:
Male rats (191-270 g) of the Dow-Wistar strain were injected intraperitoneally with 2.7 µc contained in 80 µg of ethylenimine. With the exception of the doses used to detect urinary excretion of ethylenimine, the total dose amounted to 0.30-0.42 mg/kg.
No. of animals per sex per dose:
5-6
Control animals:
no
Positive control:
no data
Statistics:
no data

Results and discussion

Preliminary studies:
None

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
The data obtained in this study indicated that ethylenimine was generally distributed throughout the rat before reaction with tissue components took place. Even though the liver accumulated the label from ethylenimine to some extent, all tissues with the exception of the fat, were labeled to a relatively high degree.
Details on excretion:
Both after 24 and 96 hours, ca. 50% of the admininistered dose was excreted in the urine; small amounts were present in feces and expired air (3-5%). A small amount of the test substance itself was detected in urine, the major part of the radioactivity was due to unknown metabolites.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Metabolites have been detected and partially isolated, but have not been identified.

Applicant's summary and conclusion