Chemistry Reference
In-Depth Information
urine, and other biological materials), such errors have
been identifi ed, and methods for their control have
been developed. The errors include errors in design
and sampling, such as poorly defi ned criteria, and
biased selection of individuals for sampling. A number
of errors can be grouped as physiological and kinetic,
such as timing of specimen collection (in relation to
the exposure), diurnal, meal- and exercise-induced
variation, other variations in distribution (e.g., those
induced by changes in body posture and by application
of tourniquet). A further fundamental aspect impor-
tant in the exposure biomonitoring of metals is con-
tamination (and sometimes losses) during blood and
urine specimen collection, storage, pretreatment, and
analysis (Aitio, 1981; Aitio and Järvisalo, 1984; WHO,
1996). The importance of contamination depends on
the level of interest so, for example, contamination is
a much more important problem for the determination
of plasma lead, where only a small fraction of whole
blood lead is found, than with determination of lead
in blood cells or whole blood. Vials used for collec-
tion and storage of samples should not contribute any
signifi cant amounts of the metal being analyzed. For
example, glass tubes should not be used for aluminum
analyses, Cd-softened plastic tubes should not be used
for Cd analyses, etc. For metals constituting compo-
nents of steel (e.g., Cr, Mo, Ni, Mn, V), considerable
contamination can occur from steel needles during
blood sampling, and special precautions are necessary
to obtain meaningful results (see Chapter 2, Section 8).
Smoking chemists performing the analyses can some-
times contaminate samples from metals present on
their skin (e.g., cadmium). Improper calibration and
standardization of instruments used for analyses can
introduce analytical errors. Errors have been consider-
able in the past, as seen, for example, in the develop-
ment of what is considered to be the reference values
for several trace elements in blood or urine. Appropri-
ate sampling, quality control, and descriptions fulfi ll-
ing the recommendations by IUPAC (Cornelis
et al.
,
1995) have been provided in some articles, and such
information has allowed the defi nition of reference
values for some metals (Nordberg, 1996), but a contin-
uous need exists for critical evaluation and continuous
emphasis on quality control aspects for biomonitoring
programs to generate good and useful information.
For biomarkers of target dose (e.g., metal-enzyme
complexes, DNA and protein adducts) similar qual-
ity control aspects are warranted, but such biomark-
ers are still mainly a research tool at present, and very
few, if any, have been validated, and quality control
conditions have usually not been specifi ed in detail.
Some biomarkers of effects have been validated
according to principles developed in clinical chemistry.
Further validation activities are warranted (Albertini
et al.
, 2000; IPCS, 2001).
3 QUALITY ASSURANCE;
REFERENCE MATERIALS
The International Standardization Organization
Guide ISO 17025 (ISO, 2000) general requirements for
the competence of analytical laboratories and instructs
on the main components of quality management, that
is, quality system, audit, and review. Quality manage-
ment has been proposed as a prerequisite for laboratory
accreditation. An integral part of quality management
is continuous assessment and control of quality; this
can be divided into internal quality control and exter-
nal quality assessment. A guideline has been published
for the internal quality control for clinical chemistry
laboratories (Büttner
et al.
, 1983). The IUPAC guideline
for external quality assessment (profi ciency testing)
(Thompson and Wood, 1993) is being updated, with
special emphasis on analyses for which the number
of laboratories is small, which is the case for most
biomonitoring analyses.
Internal quality control comprises the set of proce-
dures undertaken by the laboratory for the continuous
monitoring of operations and results to decide whether
the results are reliable enough to be released. Internal
quality control mostly depends on repetitive analysis
of the same, homogeneous control specimens (refer-
ence materials). Together with replicate analyses of all
samples, an estimate of the imprecision and changes
in the systemic error, bias, may be obtained. By use of
certifi ed reference materials, accuracy may be ascer-
tained (see Chapter 2, Section 12). Although the avail-
ability of reference materials, and notably of certifi ed
reference materials, has improved recently, for many
elements certifi ed reference materials (i.e., blood and
urine) and concentration ranges relevant for biomoni-
toring are not available in matrices. At present, refer-
ence materials with specifi ed concentrations of metals
are presently available from the Institute for Reference
Materials and Measurements, Reference materials
unit, Geel, Belgium, web page:
www.irmm.jrc.be
; Inter-
national Atomic Energy Agency, Vienna, Austria, web
page:
www.iaea.org
; or National Institute of Standards
and Technology, Gaithersburg, MD, USA web page:
www.nist.gov
External quality assurance: The other main pro-
cedure to assist in achieving good quality in metals
analyses are programs providing comparison among
results from different laboratories. Such comparisons
can be organized ad hoc by interested laboratories or
more effi ciently by joining an available external quality
