N,N'-ethylenebis[N-acetylacetamide]

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Rationale for reliability incl. deficiencies:

other: There is only a summary of the study available.

Data source

Reference

Reference Type:

grey literature

Title:

HERA-draft: Tetraacetylethylenediamine (TAED)

Author:

HERA members

Year:

2002

Bibliographic source:

http://www.heraproject.com/RiskAssessment.cfm?SUBID=2

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The fates of tetra acetyl [14C]ethylene diamine (TA[14C]ED) and [1-14C]tetra acetyl ethylene diamine ([14C]TAED) were followed in groups in rats after oral intubation. The nature of the radio-labelled compounds in urine and feces was studied and 14C levels were monitored in tissues, carcass remains, urine and feces. A further group of rats was intubated with [14C]TAED and killed at 1, 2, 4, 7 and 24 hours to monitor the rate of absorption from the intestine and uptake by the liver, adrenal and kidney tissues.

GLP compliance:

no

Remarks:

, study was conducted prior to the implementation of GLP

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-ethylenebis[N-acetylacetamide]

EC Number:

234-123-8

EC Name:

N,N'-ethylenebis[N-acetylacetamide]

Cas Number:

10543-57-4

Molecular formula:

C10H16N2O4

IUPAC Name:

N,N'-ethylenebis[N-acetylacetamide]

Details on test material:

- Other: tetra acetyl [14C]ethylene diamine (TA[14C]ED) and [1-14C]tetra acetyl ethylene diamine ([14C]TAED) were used

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

not given

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: dietary slurry

Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml dietary slurry containing 5 mg TA[14C]ED or 4.6 mg [14C]TAED per animal

no further information given

Duration and frequency of treatment / exposure:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
5 mg TA[14C]ED or 4.6 mg [14C]TAED per rat

No. of animals per sex per dose / concentration:

3

Control animals:

not specified

Positive control reference chemical:

none

Details on study design:

The fates of tetra acetyl [14C]ethylene diamine (TA[14C]ED) and [1-14C]tetra acetyl ethylene diamine ([14C]TAED) were followed in groups of 3 male and 3 female Wistar rats after oral intubation with 0.5 ml dietary slurry containing 5 mg TA[14C]ED or 4.6 mg [14C]TAED. The nature of the radio-labelled compounds in urine and feces was studied and 14C levels were monitored in tissues, carcass remains, urine and feces. A further group of rats was intubated with [14C]TAED and killed at 1, 2, 4, 7 and 24 hours to monitor the rate of absorption from the intestine and uptake by the liver, adrenal and kidney tissues.

Details on dosing and sampling:

see above (details on study design)

Statistics:

none

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Rapidly and quantitatively absorbed form the intestine (already > 50% at one hour after dosing).

Main ADME results 2

Type:

distribution

Results:

Tissue levels of 14C were at their highest at 2 hours after dosing. Subsequently levels fell rapidly except in the adrenal gland where 14C levels rose during the 7 hours after dosing and declined thereafter.

Main ADME results 3

Type:

excretion

Results:

Rapidly excreted predominately via urine. More than 90% of the urinary 14C was excreted within 24 hours of dosing.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Chromatographic analysis showed only traces of TAED in the urine. Most of the 14C was excreted as triacetyl ethylene diamine (TriAED) and diacetyl ethylene diamine (DAED). Mono acetyl ethylene diamine (MAED) and ethylene diamine were not found.

Any other information on results incl. tables

There was no sex difference in the absorption, metabolism and excretion of TA[14C]ED and [14C]TAED. Monitored 14C levels:
2 days after [14C]TAED administration: 67.3% (urine), 2.8% (feces), 17.9% (expired air), 3.1% (carcass); total: 91.1%
4 days after TA[14C]ED administration: 97.7% (urine), 3.4% (feces), 0.4% (expired air), 1.0% (carcass); total: 102.5%

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
There was no sex difference in the absorption, metabolism and excretion of TA[14C]ED and [14C]TAED.
The results show that TAED was rapidly absorbed from the rat intestine and was largely metabolized and excreted in the urine within 24 hours. Differences in the levels of 14C recovered as expired CO2 reflect the different metabolic fates of the acetyl and ethylene diamine moieties. The 14C compounds identified in the urine, TirAED and DAED, indicate that deacetylation was the main metabolic route for TAED in the rat.