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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: limited data available, not related to specific test guidelines, for a general overview of toxicokinetics

Data source

Reference
Reference Type:
publication
Title:
Metals and the Skin.
Author:
Hostynek J J, Hinz R S, Lorence C R, Price M & Guy R H
Year:
1993
Bibliographic source:
Critical Reviews in Toxicology 23(2): 171-235

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
No specific test design information
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
No additonal information
Radiolabelling:
no

Test animals

Species:
other: no information
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
other: various administrations
Details on exposure:
no further data
Duration and frequency of treatment / exposure:
no specific information
Doses / concentrations
Remarks:
Doses / Concentrations:
no details
No. of animals per sex per dose:
no data
Positive control:
no data
Details on study design:
A review of data on the skin permeability of metals includes some information on iron. Iron is essential in a number of metabolic processes including 
DNA and RNA synthesis, electron transport and oxygen metabolism in cells of plants, animals, most microorganisms and animals. The review reports  that absorption, storage, mobilisation and excretion are regulated at the cell surface by a homeostatic mechanism. Percutaneous absorption of iron 
has been reported only for chelated forms administered in ointments in mice.
Details on dosing and sampling:
A review of data on the skin permeability of metals includes some information on iron. Iron is essential in a number of metabolic processes including 
DNA and RNA synthesis, electron transport and oxygen metabolism in cells of plants, animals, most microorganisms and animals. The review reports  that absorption, storage, mobilisation and excretion are regulated at the cell surface by a homeostatic mechanism. Percutaneous absorption of iron 
has been reported only for chelated forms administered in ointments in mice.
Statistics:
no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
A review of data on the skin permeability of metals includes some information on iron. Iron is essential in a number of metabolic processes including 
DNA and RNA synthesis, electron transport and oxygen metabolism in cells of plants, animals, most microorganisms and animals. The review reports  that absorption, storage, mobilisation and excretion are regulated at the cell surface by a homeostatic mechanism. Percutaneous absorption of iron 
has been reported only for chelated forms administered in ointments in mice.
Details on distribution in tissues:
The average adult stores about 1 to 3 grams of iron in his or her body. Iron is almost never found in the free ionic state in living cells in appreciable concentrations; it is chaperoned in the form of protein complexes immediately it is absorbed from the diet. In the blood plasma it is transported (as FeII) by the protein transferrin, which passes it on to dividing cells, particularly the cells in the bone marrow that are the precursors of the red blood cells. This is mediated by the transferrin receptor. Transferrin, which binds iron with high affinity is only 20-35% saturated, thus the concentration of unbound iron is very low (0.5–1.5 mg/L (9–27 μmol/L). Iron is stored principally in the liver in the large proteins haemosiderin and ferretin, although these are also found in all cells and in the blood in lower concentrations. Ferritin exists as hollow spheres of 24 protein subunits and iron is taken up in the FeII state but stored as FeIII. As with transferrin, it is stored in a redox-inactive (and therefore non-toxic) form. Ferritin is also important in recycling iron within the body and is an important biological indicator of iron balance. One consequence of the parsimonious conservation of iron is that if there is an excess of the element within the body, there is no biochemical mechanism for its excretion and this may result in both severe and chronic symptoms if large amounts are ingested
Details on excretion:
One consequence of the parsimonious conservation of iron is that if there is an excess of the element within the body, there is no biochemical mechanism for its excretion and this may result in both severe and chronic symptoms if large amounts are ingested. The daily losses of iron from the human body correspond to a biological half-time of iron of 10 to 20 years.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
not applicable, water soluble inorganic iron salts do not undergo metabolism per se. Iron is bound to transferrin for transport to the bone marrow or contained within storage forms.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
A review of data on the skin permeability of metals includes some information on iron. Iron is essential in a number of metabolic processes including 
DNA and RNA synthesis, electron transport and oxygen metabolism in cells of plants, animals, most microorganisms and animals. The review reports  that absorption, storage, mobilisation and excretion are regulated at the cell surface by a homeostatic mechanism. Percutaneous absorption of iron 
has been reported only for chelated forms administered in ointments in mice.
Executive summary:

A review of data on the skin permeability of metals includes some information on iron. Iron is essential in a number of metabolic processes including 

DNA and RNA synthesis, electron transport and oxygen metabolism in cells of plants, animals, most microorganisms and animals. The review reports  that absorption, storage, mobilisation and excretion are regulated at the cell surface by a homeostatic mechanism. Percutaneous absorption of iron 

has been reported only for chelated forms administered in ointments in mice.