Ethylenediamine

Basic toxicokinetics

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:

Age-dependent pharmacokinetic changes of ethylenediamine in Fischer 344 rats parallel to a two-year chronic toxicity study.

Author:

Yang, R. S. H., Tallant, M. J. and McKelvey, J. A.

Year:

1984

Bibliographic source:

Fundam. Appl. Toxicol. 4:663-670

Materials and methods

Objective of study:

distribution

Principles of method if other than guideline:

As part of a chronic study, plasma kinetics was followed 24 h after a single oral dose.

GLP compliance:

not specified

Test material

Test material information

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

Radiolabelling:

yes

Remarks:

1,2 14C ethylene diamine dihydrochloride

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
50 mg EDA*2HCl per kg bodyweight

No. of animals per sex per dose / concentration:

Four animals

Results and discussion

Any other information on results incl. tables

Following a single or repeated oral administration (up to 18 month) to Fischer 344 rats there were no age-, sex-, and/or chronic dosing-related differences in absorption rate constant or terminal half-life for plasma elimination. However, significant age-related changes in area under the curve (AUC) were evident: The older rats had approximately two- to threefold higher AUC values than the younger ones (Table 1); the volume of distribution in the older rats was between a fourth and a half of the value in the younger rat (Table 2). There was much more EDA present in the systemic circulation in the older rats than the younger rats. Similarly, the older rats had much smaller volumes of distribution on the basis of liters/kg body weight. This indicates that EDA is distributed through a proportionally smaller circulatory and tissue volume in the older rats.

 

Table 1 Comparison of Area under the Curve
	AUC (ug/ml hr)
	Control	High level
Zero-day (male)	13.1+ 2.6	-
Zero-day (female)	16.9+ 2.6	-
6-month (male)	37.4+ 7.7	34.0+ 6.5
6-month (female)	41.0+11.2	41.2+15.0
18-month (male)	50.0+ 9.0	80.9+72.2
18-month (female)	41.3+ 6.4	48.5+12.9
Table 2 Comparison of Volume of Distribution
	Vd (liters/kg)
	Control	High level
Zero-day (male)	14.0+10.3	-
Zero-day (female)	12.6+ 3.1	-
6-month (male)	6.1+ 1.2	6.2+ 1.0
6-month (female)	6.8+ 2.5	5.9+ 0.8
18-month (male)	3.8+ 1.1	4.4+ 0.4
18-month (female)	6.4+ 0.6	4.5+ 1.2

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results