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 | DL50 (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 |
DL50
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 essential while Cr(VI)
is cancerogen
- Inorganic
As(III) compounds are cancerogen while
Arsenobetaine is essential non-toxic
- Inorganic
tin compounds are discussed asbeing
essential for plants and some animals but
tributyltin (TBT) is an endocrine discuptor
The chemical species of a metal can effect its toxicokinetics by influencing its
- absorption
- distribution
- biotransformation
- elimination.
It is
therefore essential that toxicological studies should always consider the species
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 evaluationg 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 Resources
The Metal Speciation Toxicokinetics Database EVISA Link Database: Toxicity of Elemental Species
Further Reading
H.E. Allen, R.H. Hall, T.D. Brisbin, Metal speciation. Effect on aquatic toxicity, Environ. Sci. Technol., 14/4 (1980) 441-443. DOI: 10.1021/es60164a002
M.L. Freedman, P.M. Cunningham, J.E. Schindler, M.J. Zimmerman, Effect of lead speciation on toxicity, Bull. Environ. Contam. Toxicol., 25/1 (1980) 389-393. DOI: 10.1007/BF01985543
G.M.P. Morrison, G.E. Batley, T.M. Florence, Metal speciation and toxicity, Chem. Br., 25 (1989) 91-96.
K.A. Biedermann, J.R. Landolph, Role of valency state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroplasts, Cancer Res., 50/24 (1990) 7835-7842.
E. Luedke, E. Lucero, G. Eng,
Molecular volume as a predictor of organotin biotoxicity, Main Group Metal Chemistry, 14 (1991) 59
T. Kaise, S. Fukui,
The chemical form and acute toxicity of arsenic compounds in marine organisms, Appl. Organomet. Chem., 6/2 (1992) 155-160.
doi: 10.1002/aoc.590060208 S.B. Jonnalagadda, P.V. Rao,
Toxicity, bioavailability and metal speciation, Comp. Biochem. Physiol. C, 106/3 (1993) 585-595.
doi: 10.1016/0742-8413(93)90215-7 Guy Berthon,
Chemical speciation studies in relation to aluminium metabolism and toxicity, Coord. Chem. Rev., 149 (1996) 241-280.
doi: 10.1016/S0010-8545(96)90030-2
D.M. Templeton,
Trace element speciation in toxicology and clinical sciences, Analusis, 26/6 (1998) M68-M71.
doi: 10.1051/analusis:1998151 S.D. Kim, H. Ma, H.E. Allen, D.K. Cha,
Influence of dissolved organic matter on the toxicity of copper to Ceriodaphnia dubia: effect of complexation kinetics, Environ. Toxicol. Chem., 18 (1999) 2433-2437.
DOI: 10.1897/1551-5028(1999)018<2433:IODOMO>2.3.CO;2 Evert Nieboer, Glenn G. Fletcher, Yngvar Thomassen,
Relevance of reactivity determinants to exposure assessment and biological monitoring of the elements, J. Environ. Monit., 1 (1999) 1–14.
DOI: 10.1039/a808849g D. Bagchi, S.J. Stohs, B.W. Downs, M. Bagchi, H.G. Preuss,
Cytotoxicity and oxidative mechanisms of different forms of chromium, Toxicol., 180/1 (2003) 5-22.
doi: 10.1016/S0300-483X(02)00378-4
J.H. Duffus,
Chemical speciation terminology: chromium chemistry and cancer, Mineral. Mag. (London), 69/5 (2005) 557-562.
doi: 10.1180/0026461056950270 K.F. Akter, G. Owens, D.E. Davey, R. Naidu,
Arsenic speciation and toxicity in biological systems, Rev. Environ. Contam. Toxicol., 184 (2005) 97-149.
doi: 10.1007/0-387-27565-7_3 P. Apostoli, R. Cornelis, J. Duffus, P. Hoet, D. Lison, D. Templeton,
Elemental Speciation in Human Health Risk Assessment, WHO,
Environmental Health Criteria #234 (2006) Richard J. Reeder, Martin A. A. Schoonen, Antonio Lanzirotti,
Metal Speciation and Its Role in Bioaccessibility and Bioavailability, Rev. Mineral. Geochem., 64/1 (2006) 59-113.
DOI: 10.2138/rmg.2006.64.3 B. Michalke, S. Halbach, V. Nischwitz,
Metal speciation related to neurotoxicity in humans, J. Environ. Monit., 11 (2009) 939-954.
doi: 10.1039/b817817h L. Lévesque, C.A. Mizzen, D.R. McLachlan, P.E. Fraser,
Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes, Brain Res., 877 (2009) 191-202.
doi: 10.1016/S0006-8993(00)02637-8
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