Risk Assessment - Toxicology of Metals - page 278

and urine samples as an indicator of exposure and
for risk estimations. Such biological monitoring takes
into consideration interindividual and intraindividual
variations in uptake because of variations in, for exam-
ple, metabolism and physical activity. Biological moni-
toring measures total exposure and not only exposure
through, for example, inhalation. Much information
of importance for occupational health criteria and
standards comes, for example, from studies in which
humans have been exposed to metals through contam-
inated food, even though occupational exposure limit
values mostly are set for air concentration. Biological
monitoring approaches and practices for a number
of substances, including metals, have been recently
reviewed by the NRC (2006).
For metals, such as lead and cadmium, exposure
through food usually constitutes the major exposure
route for the general population. For cadmium, smok-
ing is an additional important source, giving rise
to considerable increases in blood cadmium. When
exposure through food is low, smoking may contrib-
ute to approximately half the body burden of cad-
mium. Exposure within industry may not necessarily
be through inhalation only. Secondary contamination
of hands, clothing, and of cigarettes, snuff, and pipe
tobacco carried in pockets may be an important expo-
sure source (Chen et al ., 2006; Piscator et al ., 1976). For a
few metals it is possible to determine the concentration
in the critical organ by direct in vivo measurements.
An example is in vivo cadmium measurements of the
amount of cadmium in the kidney (Chapter 23).
The rationale for the use of biological monitoring to
estimate internal dose and critical concentration in crit-
ical organ as a proxy to critical target dose is discussed
in Chapter 4. Emphasis is given to the importance of
adequate use of chemical speciation, quality assurance
of sampling, and chemical determinations. A prereq-
uisite for successful use of concentrations in indicator
media for estimation of exposure, accumulation of the
metal in critical organs, and risks of adverse effects is
knowledge of the toxicokinetics and metabolism of
the metal, including data on the relationship between
external exposure, internal dose, concentration in criti-
cal organ, and concentrations in indicator media. For
risk estimation, data are also required on mechanism
for elicitation of adverse effects and relationships
between critical organ concentration (a proxy of criti-
cal target dose) and the appearance of adverse effects.

effects of the metal or metal compound are evaluated.
The weight of evidence is considered whether specifi c
adverse effects can be caused under exposure condi-
tions existing for humans. The primary consideration
is what specifi c chemical species of the metal humans
are exposed to. Subsequently, hazard assessment is per-
formed based on information concerning relationships
between such exposures and adverse health effects.

3.1 Speciation
The fundamental importance of speciation in risk
assessment has recently been highlighted in “Elemen-
tal Speciation in Human Health Risk Assessment”
(WHO/IPCS, 2007).
The need to consider different metal compounds
(species) separately when evaluating metabolism and
effects is well recognized for some metals and has
recently been reviewed by Yokel et al . (2006) (see also
Chapters 18, 19, 24, 31, 33, and 38). Mercury is a classic
example. Not only is it necessary to separate organic
from inorganic mercury compounds, but also metal-
lic mercury has a different metabolism from both its
organic and inorganic compounds, and, for example,
methylmercury is much more toxic than phenyl mer-
cury. Arsenic occurs as inorganic, as well as organic,
compounds. Man is exposed primarily to certain
stable organic arsenic compounds in fi sh and crusta-
ceans. The toxicity of such compounds is considered to
be low, although detailed data on possible long-term
effects are lacking. Usually, trivalent inorganic arsenic
compounds are considered more toxic than pentava-
lent ones. Evidence for carcinogenicity is mostly avail-
able for the trivalent form or a mixture of trivalent and
pentavalent forms, because they occur in groundwater
used as drinking water (IARC, 2004). Arsenic concen-
trations in urine are used as an indicator of exposure
and risk, but it may be that a small, poorly soluble frac-
tion of arsenic is of importance in the causation of lung
cancer in inhalation exposures, and the relationship
between lung cancer risk and urinary arsenic may be
different than the one for oral exposures.
In all risk assessment, it is fundamentally impor-
tant to recognize the different kinetics, metabolism,
and toxicity of different species of metals. It, therefore,
becomes more and more important to analyze not
only the metals as such but also the different forms
they occur in. Reliable methods are available (e.g., for
analysis of different compounds of arsenic and mer-
cury) (see WHO/IPCS, 2007, and Chapters 2, 19, and
33). The issue of speciation has not been a part of haz-
ard and risk assessment of metals except for mercury.
The role of elemental speciation and speciation analy-
sis in human health hazard and risk assessment is also

3 HAZARD IDENTIFICATION

On the basis of all available evidence in humans,
experimental animals, and in vitro , possible adverse