Human exposure assessment to environmental chemicals
using biomonitoring
Antonia M. Calafat, Xiaoyun Ye, Manori J. Silva, Zsuzsanna Kuklenyik and Larry L. Needham
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
Introduction
The probability of non-occupational human exposure to
chemicals present in commonly used products is high
given their high production volumes and extensive use.
For the most part, no information exists about the
extent of human exposure to these chemicals, and the
potential toxic health effects of these compounds in
humans are largely unknown. As information on risk to
human health from exposure to environmental chemi-
cals is limited, studies to investigate the prevalence of
these exposures are warranted. However, exposure
assessment is complex in epidemiological studies because
human exposure does not occur under controlled condi-
tions of dose–response evaluations associated with ani-
mal studies (exposure-health effect). Indirect measures
of exposure that combine environmental monitoring
and exposure history/questionnaire data have been used
to assess human exposure to environmental chemicals.
Advances in analytical chemistry have made measuring
trace levels of multiple environmental chemicals in bio-
logical tissues (i.e. biological monitoring or biomonitor-
ing) possible and have contributed to increased use of
biomonitoring in exposure assessment (Pirkle et al.,
1995). Although biomonitoring can also be used in risk
assessment, assessing potential health risks from bio-
monitoring exposure data will not be discussed in this
overview.
Biomonitoring programmes
Biomonitoring programmes are useful for investigating
human exposure to environmental chemicals. One of
these programmes, the National Health and Nutrition
Examination Survey (NHANES), conducted annually in
the United States by the Centers for Disease Control
and Prevention (CDC) is designed to collect data on the
health and nutritional status of the non-institutionalized,
civilian US population (CDC, 2003a). The survey
includes a physical examination, and collection of
detailed medical history and biological specimens from
participants. Although biological specimens are used
mostly for clinical and nutritional testing, some can be
used to assess exposure to environmental chemicals.
Beginning with NHANES 1999, levels of selected chemi-
cals in urine and blood of NHANES participants have
Keywords:
biological monitoring, emerging pollutants,
glucuronidation, matrix, NHANES, oxidative
metabolism, perfluorinated chemicals, phenol,
phthalates
Correspondence:
Antonia M. Calafat, Division of Laboratory
Sciences, National Center for Environmental
Health, Centers for Disease Control and
Prevention, 4770 Buford Hwy., NE, Mailstop
F17, Atlanta, GA 30341, USA.
E-mail: acalafat@cdc.gov
Received 3 June 2005; revised 5 July 2005;
accepted 11 July 2005
doi:10.1111/j.1365-2605.2005.00570.x
Summary
In modern societies, humans may be exposed to a wide spectrum of environ-
mental chemicals. Although the health significance of this exposure for many
chemicals is unknown, studies to investigate the prevalence of exposure are
warranted because of the chemicals’ potential harmful health effects, as often
indicated in animal studies. Three tools have been used to assess exposure:
exposure history/questionnaire information, environmental monitoring, and
biomonitoring (i.e. measuring concentrations of the chemicals, their metabo-
lites, or their adducts in human specimens). We present an overview on the
use of biomonitoring in exposure assessment using phthalates, bisphenol A and
other environmental phenols, and perfluorinated chemicals as examples. We
discuss some factors relevant for interpreting and understanding biomonitoring
data, including selection of both biomarkers of exposure and human matrices,
and toxicokinetic information. The use of biomonitoring in human risk assess-
ment is not discussed.
international journal of andrology ISSN 0105-6263
166 international journal of andrology 29 (2006) 166–171. ª 2005 Blackwell Publishing Ltd

been reported in the National Report on Human Expo-
sure to Environmental Chemicals (CDC, 2003b). These
reports provide the most comprehensive biomonitoring
assessment of the US population’s exposure to environ-
mental chemicals, and may help prioritize and foster
research on human health risks that result from expo-
sure, largely unknown for many of the chemicals inclu-
ded in the reports.
The NHANES data can be used to establish reference
ranges for selected chemicals, provide exposure data for
risk assessment (e.g. set intervention and research priorit-
ies, evaluate effectiveness of public health measures), and
monitor exposure trends. Reference ranges can be used to
assist epidemiological investigations, to correlate the levels
to other NHANES parameters/measurements (including
potential health effects), and to identify (i) populations
with the highest exposures, (ii) potential sources/routes of
exposure, and (iii) chemicals with highest prevalence/fre-
quency (Pirkle et al., 1995). However, even a comprehen-
sive programme such as NHANES has limitations:
persons under 1 year of age are not included, and no data
are collected on foetal exposures. Furthermore, NHANES
by design does not intentionally include population
groups that might be highly exposed to various point
sources and could be examined to evaluate possible asso-
ciations between high exposures and adverse health
effects.
Analytical considerations for biomonitoring
Blood (or its components) and urine are the most com-
mon matrices for biomonitoring; many alternative matri-
ces can also be used (Needham et al., 2005a). Some are
particularly useful for assessing exposure during foetal
and early childhood life, when humans are most suscept-
ible to potential adverse health effects of environmental
chemicals. Amniotic fluid, cord blood and meconium are
promising matrices for monitoring prenatal exposures
(Burse et al., 2000; Foster et al., 2000; Whyatt & Barr,
2001). Breast milk can be used to monitor neonatal expo-
sures and its analysis also can provide an estimate of foe-
tal exposures to some chemicals (Landrigan et al., 2002;
LaKind et al., 2004). Biological matrices are complex, can
be difficult to obtain, and may be available only in small
amounts. Furthermore, although environmental chemicals
are normally present in the matrix at trace levels, other
matrix components occur at higher concentrations.
Therefore, highly sensitive, specific and selective multiana-
lyte methods for the extraction, separation and quantifi-
cation of these chemicals must be developed (Needham
et al., 2005b).
Phthalates are widely used as plasticizers, in consumer
goods, and in personal care products. Prenatal exposure
to some phthalates produced developmental and repro-
ductive toxicity in experimental animals, particularly in
male offspring (Gray et al., 2000; Mylchreest et al., 2000;
Ema et al., 2003). Currently, evidence on the association
between exposure to phthalates and human health effects
is limited. Phthalates are non-persistent compounds that
are rapidly metabolized and excreted (Fig. 1) (ATSDR,
1995, 1997, 2001, 2002). Many are ubiquitous, and their
direct measurements in biological specimens are subject
to error because of contamination that can occur during
sample collection, storage and throughout the analytical
measurement process. To minimize contamination, the
preferred biomonitoring approach is to measure urinary
levels of phthalate monoester metabolites (Blount et al.,
2000).
Phthalates can be hydrolysed to their hydrolytic mono-
esters by esterases present in milk (Calafat et al., 2004)
and serum (Kato et al., 2003); other matrices such as
amniotic fluid and meconium may also contain esterases.
If the concentration of hydrolytic monoesters in matrices
other than urine is used to estimate exposure, care must
be taken to minimize contamination with phthalates dur-
ing sampling, storage and analysis. Otherwise, measured
concentrations may include an unknown contribution
from hydrolysis of contaminant phthalates by endogenous
esterases. Therefore, not only the chemical properties of
the compounds of interest, but also the composition of
the matrix and its potential effects on concentrations
of selected analytes must be considered when developing
sampling, storage and analysis protocols for biomonitor-
ing studies.
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Figure 1 Phthalates metabolize to hydrolytic monoesters and may be
further metabolized to oxidative products. Oxidative metabolism is
prevalent for high molecular weight phthalates. Phthalate metabolites
can be excreted unchanged or as conjugated species after undergoing
phase II biotransformation.
A. M. Calafat et al. Biomonitoring in human exposure to environmental chemicals1
international journal of andrology 29 (2006) 166–171. ª 2005 Blackwell Publishing Ltd 167