In classical toxicology, speciation of carbon is taken for granted and the carbon compounds responsible for toxicity are always described with the appropriate chemical nomenclature. By contrast, speciation of other elements is largely ignored and elements other than carbon are often condemned as toxic because of evidence relating toxicity to only a few of the chemical species in which they occur.
As an
example, the element arsenic is often taken as a synonym for poison, while the
arsenic compounds present in fish and other seafood are actually as harmless as
table salt:
| CHEMICAL
SPECIES | LD50 (mg/kg)
|
Arsenite
(As(III))
| 14
|
Arsenate
(As(V))
| 20
|
| Arsine
(AsH3) | 3 |
| Monomethylarsonic
Acid (MMA) | 700 - 1800 |
Dimethylarsinic
Acid (DMA)
| 700 - 2600 |
Arsenocholine
| > 10000 |
| Arsenobetaine | > 10000 |
LD50
rat: concentration leading to the death of 50 % of a rat population
Since the
physical, chemical and biological characteristics of a chemical substance
depend primarily on its molecular structure and not on one of its elemental
constituents, so does its toxicity.
As an
example let us discuss the toxicity of organotin compounds:
As has been
shown by Luedke et al., 1991, the toxicity of di- and
tri-organotin compounds (chlorides) depends on the target organism and is a
function of the molecular volume of the compound (and not of the inclusion of a "toxic element" tin in the compound !).
The
toxicity of often called “toxic trace
elements” depends on their speciation and concentration not only in a quantitative
way but also in a qualitative way.
Some examples:
- Cr(III) is
considered to be beneficial for the glucose metabolism while Cr(VI)
is cancerogen
- Inorganic
As(III) compounds are cancerogen while
Arsenobetaine is essential non-toxic
- Inorganic
tin compounds are discussed as being
essential for plants and some animals but
tributyltin (TBT) is an endocrine discuptor
The chemical species of a metal can effect its toxicity by influencing its
- absorption (or the physical availability for exposure - if the metal is tightly bound to in-absorbable material, it cannot be readily taken up, e.g. into the blood stream of the organism)
- distribution (the internal transport inside the organism to the tissue on which it has toxic effects - for example the crossing of the intestinal membrane or the blood-brain barrier)
- biotransformation (its accumulation, bio-modification, detoxification in – and excretion from – the tissues)
It is
therefore essential that toxicological studies should always consider the species
present rather than the elemental constituent in order to create meaningful data. With
respect to risk assessment and legislation it becomes more and more clear that failure to consider properly
chemical speciation of elements other than carbon can lead to poor use of our
resources. Laws and regulations based on simple elemental analysis may wrongly
condemn environmental media or products as toxic and prevent the use of
important resources.
When evaluating the toxicity of a target compound (species), the possibility of species conversion during the test period must be considered. Such conversion might be produced by reactions of the target compound with components of the studied system (e.g. cell culture media) such as redox reactions, hydrolysis, adduct formation or complexation, leading to declining concentrations of the target compound and appearance of new species. For such reasons, toxicity test should be accompanied by analytical testing verifying that the species present is the target compound and the concentration level being present during the exposure time is the target exposure level. If that is not the case, time weighted exposure levels can be used instead of concentration levels.
Related EVISA Resources
Brief summary: Toxicity of arsenic species
Link Database: Toxicity of Elemental Species
Further Reading
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