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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
An iodinated heparin derivative was injected with carrier heparin into healthy volunteers. The iodinated material was of similar molecular weight to the underivatised heparin, highly sulphated, and biologically active. It bound to plasma proteins including antithrombin III in vivo, and more than 85% was firmly bound to platelet factor 4 or protamine in vitro.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate
EC Number:
700-834-1
Cas Number:
9041-08-1
Molecular formula:
not applicable (UVCB substance)
IUPAC Name:
nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate
Details on test material:
Batch No.: 79B-1510
Purity: not specified
Radiolabelling:
yes

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
None stated

Administration / exposure

Route of administration:
intravenous
Vehicle:
not specified
Details on exposure:
None stated
Control animals:
not specified
Positive control reference chemical:
None stated
Details on study design:
None stated
Details on dosing and sampling:
None stated
Statistics:
None stated

Results and discussion

Main ADME results
Type:
metabolism
Results:
It was not bound to antithrombin III in vivo, or to platelet factor 4 and protamine in vitro, and it was markedly desulphated. Except at doses greater than 1,000 units, the labelled material was degraded to small fragments before excretion in the urine.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
In conclusion, after intravenous injection in man heparin is first totally desulphated by the reticuloendothelial system - mainly in the liver and spleen. The desulphated metabolite is then degraded to low molecular weight saccharides by an unknown glycosidase which is probably located in the kidney. Both systems are readily saturated at higher doses.