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Great Fear of Small Amounts of ElementsЧThe Significance of Analytical Chemistry in our Modern Industrialized Community as Exemplified by Trace Element Analysis.

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1301 1. Weissbuch, L. Addadi, 2. Berkovitch-Yellin, E. Gati, S . Weinstein, M.
Lahav, L. Leiserowitz, J . Am. Chem. Soc. 105 (1983) 6615; 1. Weissbuch,
Ph. D. Thesis, to be submitted to the Feinberg Graduate School, Rehovot (Israel).
[31] S. Weinstein, M. H. Engel, P. E. Hare, Anal. Biochem. I 2 1 (1982) 370; S .
Weinstein, Anyen,. Chem. 94 (1982) 221: Angew. Chem. I n t . Ed. Engl. 21
(1982) 218: Angeiv. Chem. Suppl. 1982, 425.
[32] 1. Weissbuch, L. S h ~ m o nL.
, Addadi. Z. Berkovitch-Yellin, M. Lahav, L.
Leiserowitz, I v . J . Chem. Special Isrue. in press.
1331 1. Weissbuch, L. Addadi, Z. Berkovitch-Yellin, E. Gati, M . Lahav, L.
Leiserowitz, Nature /London)310 (1984) 16.
.I341 L. Shimon, M. Lahav, L. Leiserowitz, unpublished; L. Shimon, M. Sc.
Thesis, Feinberg Graduate School, Rehovot (Israel) 1982.
1351 W. G. Johnsteon, Prugr. Cemm. Sci. 2 (1962) 175; J. J. Gilrnan, W. G.
Johnsteon, C . W. Sears, J. Appl. Phys. 29 (1958) 749.
[36] P. Hartman, W. G. Perdok, Acta Cr.vstal1ngr. 8 (1955) 49.
[37] P. Hartman, J. Cryst. G?YJW~/I
49 (1980) 157, 166.
1381 Z. Berkovitch-Yellin, J . Am. Chem. Sor. 107 (1985) 3375.
[39] A. F. Wells, Discuss. Faraday Soc. 5 (1949) 197.
[40] R. .I. Davey, J . Cryrt. Growfh 34 (1976) 109; R. J. Davey in E. Kaldis:
Current Topics in Malerial Science, Yo/. 8 , North Holland Publishing
Co., Amsterdam 1982, Chapter 6.
1411 B. S. Milisavljevic, Dissertation, ETH Zurich 1982 (Dissertation No.
6898).
1421 F. Wireko, M. Sc. Thesis, Feinberg Graduate School, Rehovot (Israel);
F. Wireko, Z. Berkovitch-Yellin, F. Frolow, M . Lahav, L. Leiserowitz,
unpublished.
1431 Z. Berkovitch-Yellin, L. Leiserowitz, Acta Crystallogr. 8 4 0 (1984) 159.
[44] S. Weiner, W. Traub, H. A. Lowenstarn in P. Westbroek, E. W. de Johng:
Biomrneralizatron and Biological Metal Accumulation, Reidel, Dordrecht
1983. p. 205.
[45] L. Addadi, S. Weiner, Proc. Nut. Arad. Sci.. i n press.
[46] A. L. d e Vries in R. Gilles: Animals and Enoironmental Fitness, Pergarnon Press, Oxford 1980, p. 583.
[47] W. F. Berg, J . Photogr Sci. 31 (1983) 62.
Great Fear of Small Amounts of ElementsThe Significance of Analytical Chemistry in our Modern
Industrialized Community as Exemplified by Trace Element Analysis
By Giinther Tolg" and Rainer P. H. Garten
Dedicated to Professor Rudolf Bock on the occasion of his 70th birthday
Analytical chemistry is consolidating an important position within the framework of our
modern industrial community; the frontiers of trace (and ultra-trace) analysis have expanded into new territories, thus demanding a constant change in our mode of thinking in a
substance-related manner in analytical chemistry. An outline of the development of analytical chemistry during this century reveals a period of underdeveloped research and education followed by a current phase of impetuous advancement. However, as a result of increasingly antagonistic sectional convictions in the public mind concerning reservations
against, as well as efforts towards, efficient technological progress, this advancement evokes
new existential risks for analytical chemistry-viz. either to be used in an uncritical way or
to fall into discredit following slogans like 'high-performance analytical chemistry is to
blame for it all!' A much more constructive consideration says that risks can be estimated
and evaluated solely by means of a highly efficient analytical chemistry, when used with a
sense of responsibility. Analysts may help to clarify and to cope with the increasing fear of
decreasingly smaller amounts of trace elements-in both adverse groups in our community.
Strategies necessary to gain this end are outlined with regard to a methodological as well as
a political platform.
1. The Role of Analytical Chemistry in our Modern
Industrial Society
The chemical, biological, and physical properties of materials and-what is of interest to us in connection with
our environment-of complex systems of substances are
[+I, Dr. R. P. H. Garten
Laboratorium fur Reinststoffanalytik des Max-Planck-Instituts fur
Metaliforschung Stuttgart
Bunsen-Kirchhoff-Strasse 13, D-4600 Dortmund 1 (FRG)
[*] Prof. Dr. G. Tdlg
['I
Other address:
lnstitut fur Spektrochemie und angewandte Spektroskopie
Runsen-Kirchhoff-Strasse 1 I , D-4600 Dortmund 1 (FRG)
Angew Chem. In/. Ed. Enyl. 24 (1985) 485-4414
often dependent upon very small alterations in composition. This dependence forms the basis of many fields of research, e.g. in the life sciences, in the earth sciences, and in
materials science; but, as we are learning more and more
each day, it also has direct serious consequences for man
and his environment in terms of health, working conditions, and other factors determining the quality of his life.
Thus, this research and public policy are entering progressively into closer relationships with which not only every
responsible, forward-looking scientist and politician, but
also every individual citizen must come to an understanding.
In an effort to comprehend these very complicated interrelationships, it is very easy to come to false conclusions
0 V C H Vrrlagsgesell.rchaJt mbH. 0-6940 Weinheini. 1985
0570-0833/85/0606-0485 $ 02.50/0
485
concerning the function of scientific disciplines for the
common good, such as is the case, for example, in analytical chemistry. Even many scientists are scarcely aware of
the importance of analytical chemistry for the future development of our quality of life.
All the natural events in our biosphere occur in a multitude of extremely complicated regulated cycles, which in
turn are interdependent on very sensitive equilibria. We
are increasingly realizing the difficulty, not only of understanding their interactions in detail, and of affecting them
only so that the human race can survive intact, but also of
assuring the disturbances of these equilibria are limited as
much as possible. Very often we d o not even recognize the
consequences on the affected ecosystem^.^'-^]
Our trust in technical progress, built up slowly and with
difficulty over the centuries, is shaken nowadays by fastreacting, alarming reports, which are very often sensationally, but inaccurately presented by the media. The human
need for security then motivates some to defend themselves against that which is incomprehensible and even
sinister. The anxiety arising from such uncertainty is another only too natural response. The widespread aversion
to chemistry (“Modern Inquisition”), will unfortunately
not promote the solution of pressing problems. What we
need is an accelerated elucidation of the role of chemistry
in order to learn factually and circumspectly its advantages
and disadvantages (see, e.g., [41). This, however, presupposes reliable information and data concerning complex
processes in the material field. In other words, whenever
synthetic or anthropogenically mobilized substances impinge on our lives, both in a positive and in a negative
sense, analytical chemistry faces the challenge to make
available reliable data for a critical evaluation of changes
in material systems. Only in this way, will we make any
possible risks calculable. This is also indispensable if we
wish to terminate some absurd endeavors either to turn
back the wheel of progress or to ignore the fear-provoking
consequences of our progress by burying our heads in the
sand. Only this will help to lessen the conflict between
these two extreme schools of thought, a conflict which is
continually becoming more threatening. Thus, analytical
chemistry is today taking on an interdisciplinary and society-relevant
this requires for the future-particulady in teaching-an accelerated change of attitude concerning its standing, which has been stagnating for decades
(cf. [’.*I). However, an unsatisfactory system can only be
improved if its weaknesses are known.
2. Changes in the Catalogue of Functions
As the oldest branch of chemistry, the first functions of
analytical chemistry were concerned with the composition
of terrestrial materials for the sake of a basic understanding of nature. Its intrinsic value was at first undisputed
(cf. ‘‘.’.‘O1) and led to an extraordinarily successful development in the classical-chemical age. In more recent times,
its standing has gradually diminished, in particular as a result of the following development~?”’~
1. In the chemical industries it took over more and more
of a quality control function whereby routine tasks had
486
the upper hand and scarcely any capacity remained for
further methodological developments.
2. Chemical analytical methods had to endure more and
more competition from physical methods. This led to
further uncoordinated parallel development on both
sides, i.e. chemical and physical. But since the teaching
of analytical chemistry was mainly in the hands of
chemists, the new blood that was recruited was mainly
chemically orientated (cf. [8.1’1), whereby the synopsis of
chemical and physical methods was increasingly lost.
The triumphal incursion of physical methods, which
proved themselves to be more economical for routine
work, into industrial laboratories dominantly in the
hands of the self-taught, occurred largely outside the
framework of analytical chemistry. It was subsequently
sought to replace the fine art of analysis, by instruments
o r tools, more and more of which were becoming available on the burgeoning instrument market.
The original unity of methodological development
and strategic application of these methods to the solving of problems has been increasingly lost. Physically or
technically oriented method specialists and highly
specialized instrument manufacturers established themselves, on the one hand, while, on the other, there were
more and more “measurement slaves” who tackled
problems with “black boxes”. From an economical
point of view this process could even be justified in the
short term because the difficulty of the analyses remained practically the same for a long period of time.
3. The fact that the solution to analytical problems could
be, as it were, bought, released research policy makers
from the necessity of educating analysts in sufficient
numbers and reinforced the view that analytical chemistry was no longer topical as an independent scientific
discipline. This opinion is unfortunately still so widely
held today that, in spite of the superfluity of constantly
perfected methods, the solution of difficult analytical
problems has become more and more intractable, because the challenge imposed by the degree of difficulty
and scope has risen dramatically.
The very first environmental problems indicated that
it was not just the major and minor components of a
synthetic product that were of interest, but the anthropogenically mobilized trace components too.
3. Ambivalent Thinking as a Requirement for the
Increasing Employment of Trace-Analytical
Information
Our usual, very successful, reductionistic, linear causeand-effect thinking based on Newton and Descartes, that at
first had only to be extended by dualistic models in quantum mechanics, is revealing itself over a wide area to be
too one-~ided.‘~.~.’’.’~.’~’
Here is not the place to lay down
why it is necessary to learn to think cybernetically or in
cross-linked dynamic systems, but some simple examples
will show that the chemistry of trace components encounters the boundaries of all too one-sided thought processes,
both with respect to the production of analytical information and to its interpretation.
Angew. Chem. Int. Ed. Engl. 24 /19HS) 485-494
At least 26 of the naturally occurring elements are now
regarded as necessary for life (Fig. 1). Of these, 15 are present in the organism at concentrations of <0.01%. These
are collectively categorized under the heading “trace elements” in the biochemical sense. All other elements are
ubiquitous in biogenic systems below certain concentration levels, which are laid down within a certain range of
scatter by nature; it has not yet been possible to establish
physiological effects at these natural concentrations. However, if given concentration thresholds are exceeded,
usually because of anthropogenic activities, then, with only
a few exceptions, negative effects can be detected on the
living conditions of individuals or ecosystems (see, for example, 13 15-17] ).
0constituent elements
0essential trace elements
oncogenic or mutagenic
‘”.,
anticarcinogenic
possibly oncogenic o r mutagenic
0 oncogenic, mutagenic.and
possibly essential
radioactive
others: insufficient
tig I . P e r i o d i c table vI t h e r l r r n r i i t b with esaential, oncogenic, and inutagenic trace elements (after [61]).
Each essential trace element only exerts its vital function
over a certain concentration range (Fig. 2);[’’] too little
leads to just as serious a biological problem as too muchunder certain conditions either state can lead to mortality.
In other words, a natural equilibrium of element concentrations has been set u p during the course of evolution between animate and inanimate matter and this setting is restricted in each case to a very narrow range of trace element concentrations for optimal living conditions.
disease :deficiency;
fatality Iconditions
health
)toxic
idisease ’
Iconditioq fatality I
E l e m e n t a l c o n c e n t r a t i o n ---c
Fig. 2. Ambibalent physiological dose-effect relationship of an essential trace
element (after [IS]).
This poses the question as to whether the lower limits,
below which symptoms of deficiency occur, ought to be
defined more closely in future, in order to avoid not only
man-made overdosage but also to allow for natural and
man-made d e f i c i e n c i e ~ . [ ’ ~ ~ ~ ~ ~
Anqew. Chem. Inr. Ed. Engl. 24 (1985) 485-494
Probably the most impressive example at present for
demonstrating the ambivalent effects of a trace element, is
selenium, the concentration limits of which in the physiologically optimal range differ only by about one order of
magnitude.l2‘I There have also been found distinct indications of such ambivalent behavior for As, Cd, and Pb.’”] It
is highly likely that further elements will follow, as analytical techniques improve. Already under discussion is a protective effect of selenium (cf. [”]) against the heavy metals
Hg, Cd, or Pb via the formation of physiologically less active compounds. Thus, in order to evaluate the toxicity of
heavy metals, which react with selenium yielding extremely stable compounds, it is not only necessary to have
a detailed knowledge of the various types of toxic bonding
(cf., e.g., [23,241)
of metals, but also of their concentration in
relation to that of selenium, just as, vice versa, the concentration of heavy metals in the system must be taken into
account for the evaluation of a selenium deficiency. By
analogy, corresponding protective effects by “detoxification”, i.e. immobilization of toxic substances, are to be expected for a range of other trace substances, whose damaging effect on living organisms is known at higher dosages if
they are observed in isolation.
If it is assumed that all naturally occurring elements
have acquired physiological activity during the course of
evolution, which is by no means impossible, then there is a
considerable degree of obscurity concerning all those elements whose natural concentrations in living systems are
too low for their ambivalent function to be demonstrated,
because they cannot be determined analytically or because
the analysis is very unreliable.
At the moment we can only observe the toxic upper concentration levels of these elements, since these are generally
analytically controllable. An exception here is found in the
concept of homeopathy, which postulates a positive physiological effect for the smallest possible concentrations of
an element and employs these therapeutically. Without
wishing here to question the success of such treatments,
this one-sided point of view is irrelevant for the trace analyst, at least as far as higher degrees of dilution are concerned (powers> D lo). This has nothing to d o with the
controversy between conventional medicine and homeopathy, as to whether such low element concentrations can
possibly exert any effect. This dispute is pointless, since
even the most uncommon elements in the earth’s crust,
such as for instance Hg, Ag, Au, are present in every organism and every preparation in concentrations that are
many orders of magnitude greater than the reported concentrations. For instance, a commercially available preparation purporting to contain silver at a dilution of D 19
(lo-”%) actually contained Ag in a concentration of ca.
i.e. equivalent to the natural concentration of
silver in blood serum. The ubiquitous concentration of
gold is about one order of magnitude lower. We are on the
verge of greatly increasing the ubiquitous concentration of
the even less common platinum in the environment
(cf. [25,261), without being able to predict the consequences.
The next example has deliberately been chosen from the
bordering fields of contention between conventional and
alternative thinking in chemistry. It ought to demonstrate
that not everything is as “healthy” as ideologists assume.
4x7
As early as 1967 Weinig and Zink“” observed that the concentration of thallium in the urine of vegetarians and
smokers is significantly higher than that in control samples
from “normally” nourished subjects; it is up to one order
of magnitude higher in vegetarian smokers. TI(1) accompanies potassium, whose atomic radius is very similar. It is
therefore preferentially enriched in plants. This finding is
of analytical relevance, because the authors determined
the concentration of TI by the very reliable technique of
isotope dilution analysis using mass spectrometry, and
checked their results by a second independent method. Accordingly, vegetarian smokers are at greater risk than “normal consumers” so far as chronic TI intoxication is concerned, at least until we know the concentration interval
for TI provided by nature. In the case of selenium, and
possibly beryllium,12x1this range most likely lies within
only one order of magnitude.
Beryllium provides a further example which illustrates
the inadequacies of our conventional way of thinking. A
large-scale systematic study of the distribution of beryllium in the environment led certain authors, who shall remain anonymous here, based on their one-sided way of
thinking, to the conclusion that beryllium did not constitute a risk for smokers. Their chain of arguments was completely logical. They found that tabacco ash contained very
little beryllium. According to the textbooks B e 0 cannot be
volatilized in the combustion process. The analytical methods employed were impeccable; in spite of this the authors
made a grave error of judgement.
Had they investigated the urine o r the blood of smokers
they would have discovered a significant enrichment of
volatilized beryllium (cf. Fig. 3), which can on no account
be neglected as a risk factor, at least until the toxicology of
beryllium and the chemical behavior of Be traces have
been fully explored.[28.2”1
-cn
.
m
I
I
’
d
t
d u e
0
5
-
-
10
tlhl
.,
Fig. 3. Time course of Be concenlralron in the urine of active ( 0 ,
A, V)
and passive (0) smokers after each hour’s inhalation of dense cigarette
smoke [29].
4. Criteria of Analytical Quality- Aims and Limits
This section is devoted to a discussion of some significant factors arising from different viewpoints regarding the
environmentally related tasks of the trace analyst. The uni488
versal analytical method that is ultimately sought for is one
that ensures an economical optimal combination of sample
preparation, decomposition, separation, and detection, and
yields reliable results for all trace elements in all samples;
a method with such a degree of universality has not, as yet,
been discovered and is unlikely to be so, even in the future.
Thus, the major task of the trace analyst is to focus his attention on improving the methodological criteria of quality, that is power of detection, sensitivity,
and e ~ o n o m y , l “in
- ~ ~to~ provide efficient solutions
.~ ~order
for the innumerable, interdisciplinary problems that exist.
He should also recognize today what complicated analytical problems will emerge tomorrow in all fields in which
materials are investigated, so as to be able to develop suitable methods in advance. It is only in this way that he will
be able to establish himself as a partner of many colleagues in a very wide interdisciplinary field who are dependent on analytical progress, but who are out of their
depth in the development of ever more demanding analytical methods.
While the problem of detection power and sensitivity is
inherent in the analytical problem, the other two quality
criteria, namely reliability and economy, are parameters
that depend on the power of detection. Basically the improvement of the detection power and sensitivity of analytical determination has to be looked at from several points
of view.
Increasingly sensitive methods of determination also
lead to the danger of their misuse. Those who would like
to turn back the wheel of history, employ sophisticated
analytical procedures to hunt for more pollutants, often in
a very uncritical manner. The main effect is to create uncertainty and anxiety and this provokes many of the antagonistically thinking group to believe, in accord with the
motto “analytical chemistry is to blame for it all”, that
there is no sense in developing analytical methods offering
higher power of detection. It is to be hoped that those will
succeed, both in general and in research policies in particular, who will look at the problem as as whole and will realize that unbiased, efficient analytical chemistry is an indispensable prerequisite for evaluating risks and making
them calculable.
But many analysts who honestly try to employ analytical
progress as a driving force in the quest for new knowledge,
better products, and a healthier life, are also in danger of
slowing down necessary progress by false attitudes. Because of their training, many analysts are inclined to oversimplify, to standardize, to generalize, or to fall into the
trap of extrapolating data. We should therefore make ourselves more conscious of the fact that it is just these useful,
even indispensable human facilities which can be the more
dangerous the lower the concentration of the elements to
be determined. Obviously, we are constrained to standardize our analytical methods and to make them as simple as
possible for economic reasons, in order to guarantee broad
compatibility in routine application. But it must be ensured that these methods already function reliably and that
each user, who follows the standardized instructions, can
also guarantee the accuracy of his results in all the envisaged areas of application. The results obtained in many interlaboratory comparisons (round robin analyses) carried
Anyew. Chem. Inr. Ed. Enyl. 24 I L Y R S ) 485-494
out in the last few years reveal very impressive interrelationships between the power of detection and the reliability of the results.
The lower the concentration of the elements to be determined in an actual sample, the greater the systematic error
~ , ~ ~ ~ the good agreement sometimes
that O C C U ~ S . ' ~ .Despite
found for results obtained by one particular method for a
particular sample, normally statistically distributed about
the true value, results can be obtained that are very different from the true concentration, as has been shown by
round robin analyses comparing various methods and/or
various laboratories' results on analyzing the same sample.
A further problem resulting from these systematic errors
in the determination of very small traces of an element is
illustrated in Figure 4. A large number of determinations
have been made of the normal concentration of trace elements in the matrix "human serum", so that the results can
be evaluated statistically. The mean concentrations recorded for some essential trace elements by various authors over periods up to 1976 and after 1976 reveal two
groups of trace elements:
1. Elements, for which values were obtained which were
practically in agreement with each other over both periods. These are the elements Cu, Zn, and also Se, whose
determination is unproblematical nowadays. With slight
reservations, this also holds for their determination in
other biotic matrices. Thus, it is meaningful in these instances to develop standard procedures for their routine
analysis.
2. Elements, whose measured normal concentration in the
blood serum has been tending to drop to ever lower values up to the present time. They are real problem elements which demand continual attention by the experienced trace analyst.
As long as the systematic errors involved in the determination of these elements prevail over the statistical errors,
standard procedures may only be designed with the employment of extreme analytical expert knowledge and critical understanding.
-
1030
1500
c
m
I
100
50
10
5
1
05
01
A1
I 1g 4 c
V
Cr
Mn
Co
N8
~ ) I I I ~ ~ I I(11I ~111s
~ I i~i i Ic i l i i r 111
Cu
Zn
Se
Mo
w i n s c I c i i i s i i t r i l wncentrations in serum,
determined in the period before 1976 and after 1976 (according to data assembled by Verc-ieck et al. [62]); 0 before 1976, kZ4 after 1976, L Z realistic.
Annew Cheni lnr. E d . Enqf. 24 (1985) 485-494
5. Pathways to Accuracy in Trace Analysis
Long years of experience and thought concerning the
causes and the avoidance of systematic errors in ultratrace
analysis can be summarized in one sentence: "Systematic
errors of combined procedures are minimized if only absolutely essential unit steps are carried out in closest combination in reaction spaces with the smallest surface areas at
the lowest temperatures possible, all apparatus materials
are as inert as possible and only a minimum of easily
highly purified reagents and additives are employed, all
contamination by laboratory air is avoided. and each unit
step of such a procedure is carefully investigated for its
analytical yield-using radioactive tracers if possible."
This fundamental sentence summarizes our methodological strategy;'351 it therefore requires some comment. The
largest systematic errors are expected to arise from impurities, which are introduced into the analytical system from
components of the apparatus, from the reagents, and from
the atmosphere in the laboratory. They are the greater the
more common an element is in the environment (ubiquitous concentration). Irreversible adsorption of trace elements occurs on the vessel walls and losses due to evaporation occur during the whole analytical procedure, which
begins with sampling. Some of these errors are in opposite
directions and can sometimes compensate each other.
Since it is primarily the blank value that limits the power
of detection, it must be remembered that it is the ratio of
the concentration of the element to be determined in the
sample to its concentration in the environment of the analytical system which is decisive rather than the sensitivity
of the detector system itself. Thus, in present day ultratrace
analysis, it is more meaningful to keep the blank concentration as low as possible than to search for new and more
sensitive detector^.^'^-^^]
Basically, it is only possible to achieve an optimal power
of detection for each analytical method when the element
to be determined has been isolated. We do not, as yet, possess any methods of determination where the excitation of
an analytical signal for the element is not affected in a positive or negative sense by other accompanying elements
above a certain threshold concentration. All economical
direct instrumental methods (cf., e.g., [3'.3y1), in which the
sample itself is analyzed directly, not only fail to yield optimal detection power, but, under certain circumstances,
are also subject to considerable interference by other elements. It is possible to compensate for such interferences,
however, but only if reliably investigated standard reference samples are available for calibrating the m e t h ~ d " ~ . ~ " ~
which are as similar as possible to the analytical samples.
In ultratrace analysis, however, this applies in only very
few cases (cf. c4'1). Consequently, one must resort to less
economical and more complicated combined procedures,
in which the element of interest is separated as far as possible from other accompanying elements before being determined.[r-371In contrast to routine methods where systematic errors have already been removed, in ultratrace analysis, only complex combined procedures lead to reliable
results, and, in end effect, are more economical than direct
instrumental methods yielding inadequate or even false results and their consequences. Systematic errors naturally
489
behaves biologically very differently in the various comoccur also in these procedures; they may have different
pounds in which it appears (see Fig. 5).
origins which are distributed with different importance
over the various individual steps of the p r ~ c e d u r e . ' ~ . ~ ~ . ~ ' '
This catalogue of tasks in modern trace analysis can be
extended by some specific examples from our own investigations. They are considerably complex examples involving complicated interdisciplinary problems. We were
therefore only able to make modest contributions towards
obtaining reliable analytical information and optimal solutions to individual problems. For a scientific interpretation
of the data we always seek the cooperation of other suitably qualified colleagues who may not be in a position to
develop the analytical part by themselves, while we for our
part often feel overtaxed with the scientific interpretation
of our results.
Fig. 5. The circulation of mercury
5.1. Example: Species and Distribution Analysis of
Mercury
Along with Cd, Pb, TI, and As, mercury, in particular,
counts among the most important problem elements which
pollute the environment as a result of anthropogenic activities-apart from the not inconsiderable basic emissions
caused by volcanism and the weathering of
In certain industrial areas relatively large amounts of
mercury are emitted into the atmosphere during the production and use of its compounds. Much more mercury is
emitted, however, by its release from all materials removed
by mankind from the earth's crust, during combustion and
heating processes (Table I). Its ubiquitous concentration
in these materials is in the middle ng/g range. The growth
in industrialization has led to a cumulative increase in
these emissions, so that it is not possible with our present
state of knowledge to say unequivocally how this increasing Hg-emission, which is unavoidable in our industrial society, will affect the health of living individuals in the next
generations; this also applies, but not to such a serious degree, for all other relatively volatile elements. The risks involved are probably more difficult to calculate than the
risk which is involved in the peaceful use of nuclear energy. The main reason for this is that the ecological circulation of mercury is exceedingly complex and that mercury
Table 1. Comparison of global mercury emissions of natural and anthropogenic origin [43j (based on data from 1970 and 1974).
Globally released
mercury [tlyear]
Natural origin:
Volcanism and weathering in the
hydrosphere
500-
SO00
Gaseous form from the earth's crust into
the atmosphere
25 000-1 SO000
Hg-reserve in the oceans: 2 x 10' t
Evaporation from sea water
Rivers and glaciers
23 000
3 800
Anthropogenic origin:
Hg-processing industry
6000- 10000
Preparation of ores and minerals
1500- 20000
Combustion of fossil fuels
490
100-
in
[he en\ironmeni (according lo (631);
u.a. = and other gases.
8000
The route by which organomercury compounds in particular enter the human nutritional chain via water is relatively well understood as a result of the impetus given by
the catastrophe in Minimata Bay in Japan in 1954. The methylmercury compounds are greatly enriched by fish ,in
particular (cf. [43.441). On the other hand, we understand
very little about the mobility of mercury and its compounds in soils, which take the mercury up again from the
atmosphere. It is only known that there is a high degree of
enrichment in the upper horizons of all soils (cf. Fig. 6).f451
The question as to whether and in what form Hg can be
transported into the human nutritional chain via water, has
not been investigated sufficiently enough for it to be possible to estimate future risks.
CI
A!
BI
BC
C
1 ig. 0. lypic'i \erticdl prulileb 01 mercury conwiitrriiioii 111 \ m o w huiI\. a )
arable; b) forest; c) high bog (broken line: humus content in g/kg) soil horizons: A,: ploughed top soil: A,: humus-containing mineral soil; A , : leached
para brown soil; B,: mean soil horizon with argillaceous illution; Bv: mean
soil horizon of mineral weathering; BC: transition horizon; C : living rock
"W.
The first, very crude step in our analytical strategy was
to learn how to determine as reliably as possible the total
Hg-content of all environmentally relevant matrices, i.e. in
rocks, soils, water, air, plants, animal organs, tissues, and
even in the individual serum protein fractions. It was necessary to strive for a detection power down to the lower
pg/g range, at least for the organic matrices, in order to
distinguish natural concentrations from anthropogenically
originating concentrations. The aforementioned problems
of systematic errors due to contamination, adsorption and
evaporation were encountered during the solution of this
Angew. Chem. Inr. Ed. Engt. 24 (798.5)48.5-494
supposedly relatively simple task. In order to overcome
them i t was necessary to adhere strictly to our strategy for
the ultratrace analysis of elements; combination procedures were designed that were as compact as possible, and
performed in a closed system.
As starting point for the combined procedure several decomposition methods were investigated which had been
specially developed for ultratrace analysis and which were
considered to be practically free from systematic err o r s , [ 46
~ ~471 Combustion or heating the sample in an oxygen plasma excited by microwaves proved almost ideal.
The mercury vapor produced during decomposition of the
sample (cf. Fig. 7, left) is quantitatively absorbed on a gold
absorber (Fig. 7, center) before it is transferred for the actual determination (Fig. 7, right) by pulse heating the Auabsorber. This compact combination of decomposition, enrichment, and actual determination methods in a closed
system provides the basis for a very universal, extremely
sensitive and reliable determination of the mercury isolated from the sample by a newly developed spectroscopic
detector (microwave-induced plasma optical emission
spectrometry, MIP-OES), which makes it possible to detect
absolute quantities of less than 1 pg Hg.12.481
With the experience gained so far (several man years) it was possible
to commence the following briefly reviewed investigations
on the mobility of mercury in soils.
Using radioactively labeled Hg it was possible to demonstrate that ca. 15% of the mercury taken u p by the high
bog was released again in the form of metal vapor or methylmercury. It was more difficult to answer the question
as to how the mercury behaved that was retained by the
peat bog soil. Was it completely fixed in an insoluble form,
or did stable soluble complexes form, with humic acids for
instance, which could be transported away by drainage
water and thus gain access to the water circulation?
It proved possible to isolate the mercury compounds
formed in the peat bog soil by employing a complicated
separation system (cf. Fig. 8) using HPLC with MIP-OES
caustic extraction With
NaOH
and acid prenp.w,th HCI
extraction with H 2 0
Y a l l O u 5 poiar oiganlc
and
5OiYellt5
ia'?
7
15
Fig. 7. Combined procedure for mercury determination in biological material
and rocks by \ample decomposition in microwave induced oxygen plasma
( 3 ) , enrichment of Hg o n an Au absorber (6) and excitation of the optical Hg
emission spectrum in a microwave induced argon plasma (Kaiser et al. [48]):
I rotameter, 2 gas purification, 3 decomposition chamber (quartz), 4 sample
container support, 5 quartz wool, 6 Au absorber, 7 heating spiral, 8 three-way
cock. 9 quartz capillary, 10 hollow resonator, 1 I microwave generator, 12 manometer, 13 vacuum pump, 14 spectrometer, 15 cooling water).
Since soil is exceedingly complex from a chemical point
of view we searched, in collaboration with a soil scientist,
for a suitable model soil which woutd be relatively simple
to understand, particularly with respect to transport mechanisms.
In the case of upland high bogs, mercury can only be
taken up from the atmosphere. Analysis of samples from
various depths always gave similar profiles for the distribution of Hg-concentration, which made it possible to recognize the natural background, the anthropogenic portion, and an equilibrium between input from the atmosphere and return of Hg from the upper soil layers into the
atmosphere (Fig. 6c).14']
Angeu,. Chrm. Inr. Ed. Engl. 24 (1985) 485-494
Soil+Mixture
O f Hg-humins
rHgi(203Hg!
Separation:
extraction
separatl;n (HPLCI
enrichment
OES-MI~~-deteCliOn
separation I H P L C I
I
fraction COlleCtlOn
Isolated humins
Identification
.n g 1 w
Isolated Hg-humins
Hg!
-m-
5peCtrOSCOpY
Fig. 8. Isolation and identil'icauon 01' Hg specie, i n
1
I
flllrallO"
mil5
(after [h4])
as detector. The real breakthrough was the element-specific MIP-OES detector system, which enabled a differentiation between the Hg-containing and the remaining fractions separated chromatographically (Fig. 9).1491
Furthermore, it was possible to identify the most common mobile Hg-compound occurring in the peat bog soils.
According to ultramicro elemental analysis, UV, 1R and
'H-NMR spectroscopy it is unequivocally Hg h ~ m a t e . [ ~ ~ ]
The other four Hg-containing substances detected are
present in such minute quantities that their identification
will only be possible after further very expensive enrichment processes.
ii
5
-
0 2 ' L 6 8 1 0 l Z l i 16<820222L
to
t fminl
Fig. 9. Chromatographic separation of Hg-specie\ aCter rxiractioii 0 1 H g - ~ o n taminated high peat bog with ethanol. a) MIP-OES detection: Hg(I),
A=253.6 nm; b) UV/VIS detection, absorption at A=250 nm. reference
wavelength A =430 nm. Details: [49].
49 1
About 15% of the total Hg taken u p by the peat bog soil
is returned to the atmosphere by evaporation within a very
short time of residence; ca. 10% is transported away by water as soluble species, mainly humates, and, according to
our present knowledge, ca. 75% remains fixed in the peat
bog soil. Thus, profile analysis of peat bog soils with suitable corrections can significantly differentiate and make a
balance of the anthropogenic input of the Hg in comparison with the natural background.
In spite of these analytical improvements this Hg-problem will be with us for some time until it will be possible to
make a realistic estimate of the risks involved, since other
relationships are as yet incompletely clarified. One important point is that until now the evaluation of the toxicity of
heavy metals has always been focussed on the consideration of a single element, without taking into account its interaction with other elements. But many antagonistic or synergistic effects occur in this field, and they always ought
to be taken into account.'"] Hg reacts, in particular, with
selenium and sulfur to form selenides or sulfides with virtually no solubility. It is of utmost importance concerning
the biological activity of mercury at the site of its action to
know the ratio of uptake of antagonistic elements and their
species transported in the organism.
5.2. Example: Traces of Selenium between Toxic and
Essential
Concentrations of selenium of more than 1 pg/g taken
u p in the daily nutrition lead to selenosis.
On the other hand, Se-deficiency in the food intake
(probably < 0.2 ug/g) also causes severe damage to health,
since not only does selenium fulfill important enzymatic
functions, but, as described previously, it can also bind
mercury and render it biologically inactive.Ic' 50,511
In the case of selenium the analyst must be in a position
to be able to make an unequivocal distinction as to
whether the very narrow selenium concentration limits,
laid down by nature for optimal biological effect, are
maintained, exceeded, or not reached. Above all, the remaining uncertainties in the analytical data for the very
low relevant concentration range make it difficult to evaluate the risks involved in selenium deficiency. Even the normal natural concentration range is difficult to determine
satisfactorily, as has been confirmed by recent round robin
Consequently, an analytical procedure has been sought
which is economically acceptable for routine work and
which enables the determination of selenium in a wide
spectrum of matrices, in the ng/g range and below, as reliably as possible. Many methods promised success here because selenium can be detected very sensitively using any
of the common analytical techniques (Fig. lo). The real
difficulty lies in the employment of a critical comparison
to find the starting point for a method which is as sensitive
and reliable as possible while at the same time economical
and universally applicable to all matrices of interest in an
ecological survey, from geological to biological materials,
so as to yield results that are as comparable as possible.
492
-
Se-concentratlon (g m ~ - ' j
HG -AAS
HG-MIP-OES
HG-ICP-OES
HG -FA F S
Photometry
IJ
Fluorimetry
0 4h
ECD - GC
0 4 8 P 0 2 1 e eno.
[ htlo-pl
,PI
DP- Polarogr
XRFA
PIXE
Pellet
NAA
INAA
Enrich
IOMEV-P
RN44
Fig. 10. Concentrdtioti rangca 01 rhc I I I U ~ L~ C I I ? I I I I \ C inelhod\ for t h e ti-dce determination of selenium (according to Tolg [SO]): STAT: slotted tube atomic
trapping: HC-AAS: Hydride generation atomic absorption spectrometry;
HGC: Hydride generation and condensation; HG-MIP-OES: HG-microwave induced plasma-optical emission spectrometry; HG-ICP-OES: HG inductively coupled plasma-OES: HC-FAFS: HG flame atomic fluorescence
spectrometry; DAB: 3,3'-diaminobenzidine: DAN: 2,3-diaminonaphthalene;
ECD-GC: electron capture detector gas chromatography: DPP: differential
pulse polarography: DPCSV: differential pulse cathodic stripping voltammetry; XRFA: X-ray fluorescence analysis; TRXRF; total reflection XRFA;
SRXRF: synchrotron radiation XRFA; PIXE: proton induced X-ray emission spectrometry: INAA: instrumental neutron activation analysis:
IOMEV-P: proton activation analysis ( E , = 10 MeV): RNAA: radiochemical
neutron activation analysis.
Just as in our experiences with the determination of Hg
and many other elements, we found confirmation of the
principle that the most sensitive and reliable analysis can
only be achieved after prior isolation of the selenium. The
strategy followed for selenium determination is comparable with that for the determination of mercury, since selenium is easily separated by evaporation during the decomposition of the sample.
Once again it is a matter of an optimal combination of
decomposition, separation, and determination methods.
This combination has been achieved in many different
ways. Only one of them will be described briefly here
which possesses the optimal quality criteria for determin-
I
Fig. 1 I . HGC-AAS apparatus for the determination ot s d e t i i u m i n thc
p g ' m L - ' range (according to J . Piwonka 1521): 1. Quartz flask, 2. heating
block, 3. reducing solution, 4. peristaltic pump, 5. quartz U tube, 6. Dewar
flask, 7. cold trap (-7O"C), 8. quartz adsorption tube, 9. heater, 10. adsorption trap Chromosorb W30/60, 1 I . cold block (Al, - 196°C). 12. insulation,
13. liquid Nz,14. quartz cuvette, 15. furnace, 16. EDL-lamp, 17. atomic absorption spectrometer, 18. recorder.
Angew. Chem. In!. Ed. Engl. 24 (IY85J 485-494
ing selenium reliably in all biotic matrices in the lower pgrange. The high detection power of the AAS method,
which is only exceeded by the gas-chromatographic determination of selenium as piazselenol using the electron capture detector, is based on a simple preconcentration step.
As a supplement to conventional hydride AAS, after a special decomposition of the sample in oxygen, hydrogen selenide is released and collected in an absorber tube by
freezing onto Chromosorb (HGC-AAS). The hydrogen selenide collected can then be transferred in a pulse-like
fashion to the atomization cuvette by simply heating u p
the absorber tube (Fig. I
It is now possible to determine selenium in blood serum
protein fractions by a complicated combined analytical
procedure (cf. Scheme
Thus, very sensitive procedures are available for the determination of Hg and Se,
and their antagonistic effects can be investigated even in
the serum protein fractions.
that the selenium had diffused into the hair. However, the
detection power of PIXE does not suffice for the determination of selenium in the interior of the hair strand.
Se-distribution
Zn-distribution
1
LO
80
120
LO
80
120
Position [prnl
Fig. 12. Concentration distribution of Zn and Se across the cross-section of
hair segments (distances in pm) after various periods of treatment with a selenium-containing shampoo. X-ray emission analysis with a proton microprobe PIXE (after [55]).
Whole blood
I
I
Serum
Hydrophobic
interaction
chromatography
6. Future Challenges
I
Concentration by
ultrafiltration and
freeze drying
I
Preparative isotachophoresis
F yI t i o n a t i o n
Immunoelectrophoresis
I
Protein
identification
I
Sample preparation
freeze drying and
acid treatment
I
Selenium determination
by HGC-AAS
I
I
Result
F eeze drying
and
acid treatment
I
Determination of
total selenium
I
Balance
Correlation of
trace element and protein
Scheme I.Flow diagram for the separation and determination of selenium in
the protein fractions of blood serum (after [53)).
The procedure is even suitable for the micro-distribution
analysis of selenium in sections of a single hair or in finger
nails. Very good reproducibility was obtained in the investigation of different hairs from a single subject, but when
the selenium content of hairs from various subjects was determined surprisingly large variations were found. The
cause of this could be traced to selenium contaminatiod5''
(cf. f541), which could only be incompletely removed by
even the most careful cleansing process. Other authors["]
revealed in a gradient analysis, scanning a proton microprobe (PIXE) across the hair's cross section that selenium
was strongly enriched at the surface of the hair, and definitely originated from selenium-containing shampoos (cf.
Fig. 13). It was concluded from the thickness of the layer
Angew Chem. In{. Ed. Enyl. 24 (1985) 485-494
The problems discussed here as examples are similarly
imposed in other fields of analysis also, for example in
the analysis of semi-conductors, metals, ceramics and
plastics; here also, the positive and negative effects caused
by previously ignored impurities are recognized.[561 In all
these fields, interest centers not only on ever decreasingly
lower concentration ranges of a total impurity but also on
its distribution in samples and on sample s ~ r f a c e s . ~ ~ ~ ~
The decisive question is often the mode of bonding of a n
element,f23.6"1
the formation of the compound, or the metabolism of active agents in very complex systems, which
can only be elucidated by including analyses of microstructures, surfaces, and bonding properties. There is danger arising, whenever a single-minded course is followed
without observing critically the sum total. This also applies
to the interpretation of analytical data: and here, in particular, it can be said that the whole is more than the sum of
its parts. Once again, an appeal must be made for closer
partnership between specialized analysts and scientists of
all spheres who need reliable data. Only such cooperation
will lead to the urgently required progress which can repair
the currently disturbed relationship between man and his
environment.
The inter-methodological approach in basic analytical
research itself urgently needs intensification. This presupposes, apart from an improvement in research capacity, a
high degree of critical and creative thought concerning
analytical strategies, which can only be worked out by
highly qualified analysts-both chemically and physically
orientated-with the necessary background knowledge
(see ["I). The primary task is the furtherance of junior analytical scientists. However, this will only succeed, if a concerted effort is made to promote efficient analytical chemistry; and this will call on those responsible for research
policies as well as those interested in reliable analytical
493
data, viz. all users of such data, expert colleagues in universities, in civil authorities, in industry, and in scientific
and medical institutes.
Received: February 13, 1985 [A 535 IE]
German version: Angew. Chem. 97 (1985) 439
Translated by Dr. F. Hampson. Saarhriicken
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Angew. Chem. Inr. Ed. Engl. 24 119851 485-494
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