Trientine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was not performed accoding to guideline or GLP. Information on substance composition/purity is lacking. The study investigates the copper and zinc levels in rat fetal liver to elucidate the different teratogenic expression of DPA, TETA, and dietary copper deficiency.

Data source

Reference

Reference Type:

publication

Title:

Molecular Localization of Copper and Zinc in Rat Fetal Liver in Dietary and Drug-induced Copper Deficiency

Author:

Keen, C.L., Cohen, N.L., Hurley, L.S., Lonnerdal, B.

Year:

1984

Bibliographic source:

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Vol. 118, No. 3 Pages 697-703

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

3,6-diazaoctane-1,8-diamine tetrahydrochloride

EC Number:

225-604-3

EC Name:

3,6-diazaoctane-1,8-diamine tetrahydrochloride

Cas Number:

4961-40-4

Molecular formula:

C6H18N4.4ClH

IUPAC Name:

N,N'-bis(2-aminoethyl)ethane-1,2-diamine tetrahydrochloride

Results and discussion

Any other information on results incl. tables

There were no gross abnormalities in the fetuses of the control or copper deficient groups. For both DPA and TETA-fed groups, the frequency of abnormal fetuses increased with higher levels of drugs, but the pattern of abnormalities was quite different between the two drug groups.

Applicant's summary and conclusion

Executive summary:

The teratogenicity of copper deficiency is well known, but underlying mechanisms have not been delineated. One method of studying the biochemical

lesions of copper deficiency is the use of chelating drugs with different chemical characteristics. The teratogenicity of a copper deficient diet and of diets containing either D-penicillamine or triethylenetetramine is quite different, although all three diets result in decreased fetal liver copper levels. Feeding D-penicillamine can result in decreased fetal liver zinc, while feeding triethylenetetramine can result in increased fetal liver zinc. The effect of

these three diets on fetal liver copper and zinc molecular localization was determined. Gel filtration showed that fetal liver copper and zinc in controls was localized in 3 fractions with MWs of > 50,000 (H), 30,000 ( I ) and 8 -10,000 (L) . Independent of dietary treatment, as liver copper diminished, copper was missing first from the L peak, then the I peak and with severe deficiency, from the H peak. Drug induced increases and decreases in fetal liver zinc were reflected in the L peak. These data suggest that the absolute levels of copper in the liver of the term fetus determines the distribution of the element among its binding ligands.