Environmental Health Perspectives • volume 117 | number 10 | October 2009
Biomonitoring Data: Do
Collection Protocols Matter?
Biomonitoring (i.e., measurement of
environmental chemicals, their metabolites,
or specific reaction products in human bio-
logical specimens) to assess internal exposure
(i.e., body burden) has increased consider-
ably in the last two decades (Needham et al.
2007). Biological matrices are complex; some
may be difficult to obtain and available only
in small amounts. Moreover, environmen-
tal chemicals are normally present in the
biological matrix at trace levels. Therefore,
highly sensitive, specific, and selective mul-
tianalyte methods for the extraction, separa-
tion, and quantification of these chemicals
must be developed (Needham et al. 2005).
Undoubtedly, the adequacy of biomonitoring
data depends strongly on reliable analytical
measurements (Angerer et al. 2007). Even
when the best techniques are used, they guar-
antee accurate and precise measures of the
biomarkers levels only in any given specimen.
However, if the integrity of the specimen was
compromised before its analysis, the analytical
measures, although valid, could lead to erro-
neous interpretations. Sampling, storage, and
processing conditions have long been appreci-
ated as potential sources of contamination in
trace analyses for metals and volatile organic
compounds (Ashley et al. 1992; Bolann et al.
2007; Pineau et al. 1993). Unfortunately,
adequacy of sampling and processing meth-
ods, albeit critical for the evaluation of all
biomonitoring data, has not received as much
attention as the analytical techniques, espe-
cially for semivolatile organic chemicals.
Strict collection, handling, and storage
protocols are particularly important if the
chemicals monitored as exposure biomarkers
are ubiquitous environmental contaminants
or environmental degradates. Some of these
chemicals [e.g., phthalates, polybrominated
diphenyl ethers, polyfluoroalkyl chemicals,
bisphenol A (BPA)] have been detected in
indoor air and dust (Fromme et al. 2009;
Hwang et al. 2008; Rudel and Perovich 2009;
Volkel et al. 2008; Weschler 2009; Wilson
et al. 2003). Therefore, care must be taken
when collecting and processing specimens to
be analyzed for these chemicals to ensure that
sampling materials do not contain detectable
levels of the target chemicals, but also that
these materials are dust-free. Further contami-
nation with such chemicals during the analysis
is possible. However, laboratory contamina-
tion, should it occur, would be identified and
eliminated, provided that the laboratory per-
forming the analysis adheres to good labora-
tory practices and includes analytical/reagent
blank samples (Taylor 1987). Therefore, the
resulting biomarker concentrations should
never include a contribution from contamina-
tion during laboratory analyses.
Just as reagent blanks are needed for
assessing contamination during the analyti-
cal steps, field blanks can be used to assess
potential contamination during sample col-
lection, storage, processing, and/or transport
[National Institute for Occupational Safety
and Health (NIOSH) 1994]. However,
to further complicate matters, even if field
blanks are used, additional information may
be needed to determine the utility of the
biomonitoring findings. In this article, we
present examples that highlight the relevance
of unforeseen and unintended contamina-
tion before laboratory analysis and its impact
on the interpretation of biomonitoring data
of organic chemicals. We also discuss the
representativeness of specimens to be used
for biomonitoring purposes. Other factors
important for ensuring the adequate interpre-
tation of biomonitoring results, including the
selection of the most relevant biomarkers—
based on available toxicokinetic data—for
the chemical and population of interest; the
potential effects of the biological matrix on
the biomarkers’ concentrations (e.g., matrix
enzymes and levels of some phthalate metab-
olites); and adequate storage and shipment of
specimens (Angerer et al. 2007; Calafat and
Needham 2008; National Research Council
2006) are not discussed.
during Sampling or Handling
of Biological Specimens
For chemicals that are ubiquitous in the
environ ment, such as certain phthalates, care
is needed to avoid contaminating the sam-
ples. For example, contamination of biologi-
cal specimens with di(2-ethylhexyl) phthalate
(DEHP), a common plasticizer of polyvinyl
chloride (PVC) and other polymers (David
et al. 2001) used in many products, is difficult
to avoid. In humans, DEHP metabolizes into
its hydrolytic monoacid (commonly referred as
“monoester”), mono(2-ethylhexyl) phthalate
(MEHP), and then into oxidative metabo lites
(Figure 1) (Koch et al. 2004, 2005b, 2006;
Silva et al. 2006). MEHP and the oxidative
metabolites are primarily excreted in the urine
Address correspondence to A.M. Calafat, Division
of Laboratory Sciences, National Center for
Environmental Health, Centers for Disease Control
and Prevention, 4770 Buford Hwy., NE, Mailstop
F53, Atlanta, GA 30341 USA. Telephone: (770) 488-
7891. Fax: (770) 488-4371. E-mail: Acalafat@cdc.gov
The findings and conclusions in this report are
those of the authors and do not necessarily repre-
sent the views of Centers for Disease Control and
The authors declare they have no competing
Received 17 April 2009; accepted 24 June 2009.
What Additional Factors Beyond State-of-the-Art Analytical Methods Are
Needed for Optimal Generation and Interpretation of Biomonitoring Data?
Antonia M. Calafat and Larry L. Needham
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia, USA
Background: The routine use of biomonitoring (i.e., measurement of environmental chemicals,
their metabolites, or specific reaction products in human biological specimens) to assess internal
exposure (i.e., body burden) has gained importance in exposure assessment.
oBjectives: Selection and validation of biomarkers of exposure are critical factors in interpreting
biomonitoring data. Moreover, the strong relation between quality of the analytical methods used
for biomonitoring and quality of the resulting data is well understood. However, the relevance of
collecting, storing, processing, and transporting the samples to the laboratory to the overall biomon-
itoring process has received limited attention, especially for organic chemicals.
discussion: We present examples to illustrate potential sources of unintended contamination of
the biological specimen during collection or processing procedures. The examples also highlight the
importance of ensuring that the biological specimen analyzed both represents the sample collected
for biomonitoring purposes and reflects the exposure of interest.
conclusions: Besides using high-quality analytical methods and good laboratory practices
for biomonitoring, evaluation of the collection and handling of biological samples should be
emphasized, because these procedures can affect the samples integrity and representativeness.
Biomonitoring programs would be strengthened with the inclusion of field blanks.
key words: BPA, contamination, DEHP, extraction efficiency, field blank, phthalates. Environ
Health Perspect 117:1481–1485 (2009). doi:10.1289/ehp.0901108 available via http://dx.doi.org/
[Online 24 June 2009]
Calafat and Needham
volume 117 | number 10 | October 2009 • Environmental Health Perspectives
as phase II conjugates and much less so as the
unchanged or free species (Dirven et al. 1993;
Peck and Albro 1982). Measuring the urinary
concentrations of the total (conjugated plus
free) species of these metabolites is the most
common biomonitoring approach for assess-
ing human exposure to DEHP (Barr et al.
2003; Koch et al. 2003).
To evaluate the exposure to several con-
taminants, including the metabolites of DEHP
and other phthalates, among participants of
the Avon Longitudinal Study of Parents and
Children (ALSPAC) (Golding et al. 2001), we
analyzed one pooled urine sample, prepared
from 20 individual specimens, for these con-
taminants (Holmes et al., in press). Although
in a given urine specimen, the concentra-
tions of the total species of DEHP oxidative
metabolites are normally higher than the total
MEHP concentrations (Barr et al. 2003; Koch
et al. 2003), in the ALSPAC pooled sample,
the total urinary concentration of MEHP
(100 µg/L) was one order of magnitude higher
than the total concentrations of DEHP oxida-
tive metabolites mono(2-ethyl-5-hydroxyhexyl)
phthalate (MEHHP; 13.8 µg/L) and mono(2-
ethyl-5-oxohexyl) phthalate (MEOHP;
12.7 µg/L). Furthermore, the MEHP concen-
trations were about 25 times higher than the
median concentrations reported for the general
population of the U.S. National Health and
Nutrition Examination Survey (NHANES)
conducted during 2001–2002, but the con-
centrations of MEHHP and MEOHP were
very similar to the concentrations reported
for the same NHANES participants [Centers
for Disease Control and Prevention (CDC)
2005]. Moreover, although the DEHP
metabolites are excreted in the urine mainly
as glucuronides (Dirven et al. 1993; Peck and
Albro 1982), in the ALSPAC pooled sample
the urinary concentrations of free and total
species of MEHP were essentially equal; for
MEHHP and MEOHP, the fractions excreted
as a free species were within the expected
ranges (Kato et al. 2004). Of note, MEHP
can also be formed from DEHP by both
biotic and abiotic processes (Koch et al. 2006;
Nakamiya et al. 2005; Staples et al. 1997);
therefore, MEHP is itself an environmental
contaminant. By contrast, no environmental
sources of DEHP oxidative metabolites are
known (Koch et al. 2006). These results sug-
gest that the MEHP concentrations measured
in this pooled sample were likely the result
of contamination with DEHP or MEHP
during or after collection (Holmes et al., in
press). Therefore, this MEHP concentration,
although analytically valid, should not be used
for exposure or risk assessment purposes. In
addition to the higher potential for external
contamination of MEHP compared with the
oxidative metabolites, MEHP has a shorter
elimination half-life and represents a smaller
fraction of the DEHP urinary metabolites.
Together, these results suggest that MEHP
is a weaker biomarker of exposure to DEHP
than the DEHP oxidative metabolites (Koch
et al. 2006). Therefore, using only MEHP
for exposure or risk assessment—particularly
in archived biological samples, where external
DEHP or MEHP contamination cannot be
excluded—should be avoided.
Biomonitoring and Field Blanks
Sophisticated analytical chemistry techniques,
highly trained laboratory personnel, and strict
quality control/quality assurance laboratory
practices define high-quality biomonitoring
data (Angerer et al. 2007; Caudill et al. 2008;
National Research Council 2006; Needham
et al. 2007). Other factors, such as the integ-
rity of the specimen, are important to ensure
the validity of biomonitoring results (National
Research Council 2006).
In recent decades, biomonitoring initia-
tives have been implemented worldwide,
either in support of epidemiologic investi-
gations or as part of national health surveys
(CDC 2003; National Children’s Study 2009;
Viso et al. 2009). Combining environmen-
tal monitoring (e.g., air, water) and exposure
history/questionnaire data may also be used
to assess human exposure to environmental
chemicals and is common in occupational set-
tings (NIOSH 1994). In these scenarios, the
collection and storage of the environmental
specimens follow strict protocols to guarantee
the validity and comparability of the results.
In addition to collecting field blank and rep-
licate samples, these protocols often require
screening of collection materials to ensure
that they do not contain detectable levels of
the target chemical (NIOSH 1994).
Environmental chemicals are present in
human biological tissues at concentrations
considerably lower than in the environment.
Because some of these chemicals are rather
ubiquitous in the environment, the potential
for contamination of the biological specimen
during sampling exists. Biomonitoring sam-
pling protocols generally include screening
of the collection materials for potential con-
tamination, but they do not routinely include
other provisions required for environmental
sampling (e.g., field blanks). Commercially
available high-purity solvents (e.g., water,
methanol) placed in a sample container and
processed as a specimen could serve as field
blanks. Therefore, incorporating field blanks
into biomonitoring programs should not be
difficult. In addition to providing a control
for evaluating contamination during process-
ing and storage before analysis, field blanks
would be useful in determining whether
archived specimens could be analyzed for a
given chemical, even though the sampling
materials may have not been prescreened for
the presence of such a chemical. Therefore, we
strongly advocate including field blanks in all
ongoing and future biomonitoring initiatives.
Nonetheless, although having field blanks
Figure 1. DEHP metabolizes into its hydrolytic monoacid (“monoester”) MEHP and, after enzymatic oxi-
dation of the alkyl chain (R), to various oxidative metabolites. MEHP and the oxidative metabolites can
be excreted in the urine unchanged or as phase II glucuronide conjugates [R = CH2CH(C2H5)(CH2)3CH3
(MEHP); CH2CH(C2H5)(CH2)2CH(OH)CH3 (MEHHP); CH2CH(C2H5)(CH2)2COCH3 (MEOHP); CH2CH(C2H5)
(CH2)3COOH [mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)].
Sampling and interpretation of biomonitoring data
Environmental Health Perspectives • volume 117 | number 10 | October 2009
would strengthen all biomonitoring programs,
the absence of field blanks does not necessar-
ily invalidate these programs’ results.
Collection of Biological
Specimens in Medical Settings
or after Medical Interventions
For several chemicals (e.g., mercury, DEHP,
BPA), acute exposure can occur as a result of
medical interventions [Barregard et al. 1995;
Calafat et al. 2004, 2009; Food and Drug
Administration (FDA) 2001; Koch et al.
2005a]. However, many sources of exposure
to such chemicals, especially those that are
not considered “active” in a given product, are
unknown. The following example illustrates
the potential impact on interpreting biomoni-
toring results when the biological specimens
are collected in medical settings. More impor-
tant, this example highlights the need for
additional research to identify all sources and
pathways of human exposure to these chemi-
cals, particularly for those used extensively and
suspected to affect human health.
One hundred fifty pregnant women
partici pating in a prospective study of pes-
ticides and other endocrine disruptors in
maternal and fetal compartments were put
on intra venous injection for glucose, water,
and electrolyte balance support upon arrival
at a hospital for a scheduled cesarean birth.
Maternal urine specimens, collected before
delivery but after a Foley tube and the intra-
venous line were placed, were analyzed for
phthalate metabolites (Yan et al. 2009).
Among these women, the urinary concentra-
tions of most metabolites were similar to or
lower than those among the U.S. general pop-
ulation from NHANES 2001–2002 (CDC
2005). However, the median urinary con-
centrations of the DEHP oxidative metabo-
lites MEHHP (108.9 µg/L) and MEOHP
(95.1 µg/L) were more than 5 times their
corresponding NHANES concentrations; for
MEHP, the median (114.7 µg/L) was more
than 20 times higher. DEHP, approved by
the FDA for medical uses (FDA 2001), is a
plasticizer in PVC plastics, which can be used
in medical tubing and blood storage bags.
Therefore, the higher-than-population-based
urinary concentrations of DEHP metabolites
among these women likely reflect their expo-
sures to DEHP in the hospital. This example
further illustrates the limitations of MEHP
as exposure biomarker because the collection
of the urine (directly in a cup or through the
Foley tube into a bag) could affect the MEHP
urinary concentrations, because DEHP/
MEHP may leach from some of these mate-
rials, as well as from the intravenous line. In
contrast, the concentrations of the oxidative
metabolites, which cannot be formed except
through enzymatic processes, would reflect
these women’s acute DEHP exposure, thus
confirming the validity of the DEHP oxida-
tive metabolites as exposure biomarkers (Koch
et al. 2006).
This example also emphasizes that
biomonitoring for chemicals that are widely
used in consumer and personal care prod-
ucts (e.g., phthalates, BPA, parabens) requires
additional considerations beyond choosing
optimal exposure biomarkers and analytical
methods. Even if sampling materials are pre-
screened and known to be contaminant-free,
and field blanks are collected, the study design
itself, specifically the timing and mode of col-
lecting the biological samples, may involve
the use of materials or products that contain
the target compounds (or their precursors)
(National Toxicology Program 2008). In
the example above, the concentrations of the
DEHP metabolites, although accurate and
reflective of a real exposure to DEHP at the
time of delivery, cannot be used as surrogates
for DEHP exposure throughout gestation or
even for exposures of the general population.
Representativeness of the
Biological samples are complex in nature.
Because some may be difficult to obtain and
may be available only in small amounts, rig-
orous protocols for collecting these samples
are needed. In addition, it is crucial that
the specimens used for biomonitoring truly
reflect the composition of the original sample.
Maintaining a sample’s representativeness starts
when separating samples into specimens, gen-
erally performed to reduce repeated thaw/freeze
cycles, thus minimizing potential contami-
nation and degradation (National Research
Council 2006). The sample must be fully
thawed (if frozen before) and mixed before
making aliquots, and care must be taken to
ensure the correct labeling of each specimen.
Further, the concept of representativeness
may be of particular interest in the case of
samples collected from infants, young chil-
dren, and pregnant women and in situations
where cross-contamination of the specimen
with other tissues/fluids can occur. For exam-
ple, urine collected from a woman during
her period could be tainted with blood, and
contamination of seminal fluid with urine
cannot be ruled out. In these situations, we
recommend that the potential for contamina-
tion be noted. Furthermore, guidance for the
collection of samples to minimize potential
cross-matrix contamination in such situations
is needed. Amniotic fluid, cord blood, and
meconium are promising matrices for assessing
prenatal exposures, a period when humans are
highly susceptible to potential adverse health
effects from exposure to certain chemicals. If
cross-contamination of the specimen occurs,
biomarkers measured in meconium and in
amniotic fluid would reflect exposure not only
during gestation but also during the neo natal
period or during delivery, particularly for
ubiquitous chemicals or those commonly pres-
ent in medical settings. Therefore, it is critical
that the personnel responsible for collecting
the samples appropriately document all events
related to the collection and communicate
them to the study principal investigator and
the analytical laboratory personnel.
Cross-contamination of amniotic fluid
with the mother’s blood during delivery might
affect primarily the amniotic fluid concentra-
tions of persistent chemicals that are normally
measured in blood or serum/plasma. By con-
trast, cross-contamination of meconium or
another matrix with urine would likely have
a bigger impact for nonpersistent chemicals,
which are metabolized and eliminated primar-
ily in the urine, than for persistent chemicals
that undergo rather limited urinary excretion.
To minimize the potential impact of cross-
contamination of meconium/feces with urine,
additional measures for standardizing the col-
lection procedures, such as avoiding the use of
diapers containing meconium/feces that also
appear to be wet, can be implemented (Calafat
and Needham 2008). Although measuring
chemicals in complex biological matrices is
analytically possible (Needham et al. 2005),
because of potential uncertainties during col-
lection, interpreting the concentrations of
biomarkers in matrices with relatively high
potential for cross-contamination should be
One other consideration that may affect
the representativeness of a given sample relates
to the collection of urine by using absorbent
materials (e.g., diapers). First, one must ensure
that these materials do not contain the tar-
get chemical. Second, unlike urine collected
directly in a urine cup, bag, or similar con-
tainer, these specimens need to be extracted
from the absorbent material before their analy-
ses (Lee and Arbuckle 2009). As expected,
the urine, other urinary biomolecules or sol-
utes, and both conjugated and free urinary
species of the target chemicals will be only
partially recovered, and the composition of
the extracted urine will change. The extraction
efficiency of a given compound relates to its
aqueous solubility, which strongly depends on
its chemical structure—which determines its
physicochemical properties (e.g., lipophilic-
ity, ionizability)—and on the nature of the
solution (i.e., urine), which is affected by pH,
ionic strength, temperature, and other solutes
(Kerns et al. 2008).
In general, the recovery from absorbent
materials of the urinary conjugates of a chem-
ical will be higher than that of the less hydro-
philic free species. Because organic chemicals
are excreted mostly as urinary conjugates,
interpretation of biomonitoring results should
not be affected considerably provided an
Calafat and Needham
volume 117 | number 10 | October 2009 • Environmental Health Perspectives
adequate extraction of the conjugates exists.
Nonetheless, because of the differential extrac-
tion losses, exposures to organic chemicals,
if estimated from the concentrations of free
and conjugated (i.e., total) species in urine
collected from absorbent materials, may
be somewhat underestimated, whereas the
fraction of the chemicals excreted as conju-
gates may be overestimated. Therefore, urine
sampling methods from infants and young
children (Lee and Arbuckle 2009) should be
examined for their potential impact in the
exposure assessment process. Other methods
that do not require using absorbent materials
should be evaluated.
Recommendations for Best
Adequate generation of biomonitoring data
requires validated and high-quality analyti-
cal methods, qualified laboratory personnel,
and strict quality control/quality assurance
laboratory practices. Other important aspects
include the selection of the most relevant bio-
markers and understanding of the potential
effects of the biological matrix on the bio-
markers’ concentrations. Furthermore, other
factors, including adequate collection, han-
dling, shipping, and storage procedures to
preserve the integrity of the specimen and the
target analytes, must be considered to guar-
antee the valid interpretation of the biomoni-
toring data, particularly for chemicals with
widespread commercial and industrial use.
Recommendations for sampling and pro-
cessing approaches applicable to ongoing and
future biomonitoring initiatives include the
purity solvent(s) placed in a sample container
and processed as a biological specimen) in
the protocols for the collection and/or
processing of biological specimens for all
programs/ studies with a current or potential
a priori of the potential impact of the col-
lection setting on the biomonitoring con-
centrations (especially of chemicals that may
be present in commonly used products).
Available data suggest that the main issues
relate to collecting biological samples from
pregnant women at the time of delivery (e.g.,
use of intra venous line) or from persons
undergoing intensive care and/or outpatient
medical treatment (e.g., platelet donation,
dialysis). Therefore, additional research is
needed to identify all sources and pathways
of human exposure to these widely used
chemicals, many of which are not considered
“active” ingredients in commercial products.
lecting and processing of samples. This
includes information on the sampling time
and location (e.g., home, hospital, work-
place), whether sampling was embedded into
prescheduled or ad hoc health visits (e.g.,
child well-being, prenatal care appointments,
amniocentesis, delivery), and detailed descrip-
tion of collection procedures (e.g., urine
collected in a cup or diaper, or through a
catheter) and of the processing (e.g., making
aliquots, storage and shipping conditions) of
the samples before arrival to the laboratory
cols to identify the potential for cross-matrix
contamination (e.g., urine or amniotic fluid
with blood, meconium/feces, or seminal
fluid with urine).
of urinary species of chemicals from diapers
when interpreting biomonitoring data from
infants and young children. It is possible
that the conjugation capability, assessed
from the percentage of conjugated species,
would be somewhat overestimated. By con-
trast, exposure, categorized from the urinary
concentrations of the total (free plus conju-
gated) species, would be underestimated.
ing urine from infants and young children
for their potential impact on the exposure
assessment process (e.g., changes in the com-
position of urine extracted from a diaper),
and evaluation of collection methods not
relying on the use of absorbent materials for
their applicability in biomonitoring studies.
Biomonitoring requires a team approach.
Therefore, it is critical to facilitate constructive
dialog and partnership among laboratory and
field researchers and study participants from
the onset of the study to ensure its success.
Angerer J, Ewers U, Wilhelm M. 2007. Human biomonitoring:
state of the art. Int J Hyg Environ Health 210:201–228.
Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Holler JS,
Needham LL, et al. 1992. Determining volatile organic
compounds in human blood from a large sample popula-
tion by using purge and trap gas chromatography/mass
spectrometry. Anal Chem 64:1021–1029.
Barr DB, Silva MJ, Kato K, Reidy JA, Malek NA, Hurtz D, et al.
2003. Assessing human exposure to phthalates using
monoesters and their oxidized metabolites as biomarkers.
Environ Health Perspect 111:1148–1151.
Barregard L, Sallsten G, Jarvholm B. 1995. People with high
mercury uptake from their own dental amalgam fillings.
Occup Environ Med 52:124–128.
Bolann BJ, Rahil-Khazen R, Henriksen H, Isrenn R, Ulvik RJ.
2007. Evaluation of methods for trace-element determina-
tion with emphasis on their usability in the clinical routine
laboratory. Scand J Clin Lab Invest 67:353–366.
Calafat AM, Needham LL. 2008. Factors affecting the evaluation
of biomonitoring data for human exposure assessment. Int
J Androl 31:139–143.
Calafat AM, Needham LL, Silva MJ, Lambert G. 2004. Exposure
to di-(2-ethylhexyl) phthalate among premature neonates
in a neonatal intensive care unit. Pediatrics 113:e429–e434.
Calafat AM, Weuve J, Ye XY, Jia LT, Hu H, Ringer S, et al.
2009. Exposure to bisphenol A and other phenols in neo-
natal intensive care unit premature infants. Environ Health
Caudill SP, Schleicher RL, Pirkle JL. 2008. Multi-rule quality
control for the age-related eye disease study. Stat Med
CDC (Centers for Disease Control and Prevention). 2003.
National Health and Nutrition Examination Survey. National
Center for Health Statistics. Available: http://www.cdc.
gov/nchs/nhanes.htm [accessed 11 August 2008].
CDC. 2005. Third National Report on Human Exposure to
Environmental Chemicals. Atlanta, GA:Centers for Disease
Control and Prevention; National Center for Environmental
Health; Division of Laboratory Sciences. Available: http://
www.cdc.gov/exposurereport/ [accessed 11 April 2009].
David RM, McKee RH, Butala JH, Barter RA, Kayser M. 2001.
Esters of aromatic mono-, di-, and tricarboxylic acids,
aromatic diacids, and di-, tri-, or polyalcohols. In: Patty’s
Toxicology, Vol 6 (Bingham E, Cohrssen B, Powell CH,
eds). 5th ed. New York:John Wiley and Sons, 635–932.
Dirven HAAM, VandenBroek PHH, Jongeneelen FJ. 1993.
Determination of 4 metabolites of the plasticizer di(2-ethyl-
hexyl)phthalate in human urine samples. Int Arch Occup
Environ Health 64:555–560.
FDA. 2001. Safety assessment of di(2-ethylhexyl)phthalate
(DEHP) released from PVC medical devices. Rockville,
MD:Center for Devices and Radiological Health, U.S. Food
and Drug Administration. Available: http://www.fda.gov/
cdrh/ost/dehp-pvc.pdf [accessed 12 February 2009].
Fromme H, Tittlemier SA, Volkel W, Wilhelm M, Twardella D.
2009. Perfluorinated compounds—exposure assessment
for the general population in western countries. Int J Hyg
Environ Health 212:239–270.
Golding J, Pembrey M, Jones R, Alspac Study Team. 2001.
ALSPAC—the Avon Longitudinal Study of Parents
and Children—I. Study methodology. Paediatr Perinat
Holmes AK, Maisonet M, Rubin C, Kieszak S, Barr DB, Calafat AM,
et al. In press. A pilot study of exposures to endocrine-
disrupting compounds in pregnant women and children from
the United Kingdom. Int J Child Adolesc Health.
Hwang HM, Park EK, Young TM, Hammock BD. 2008.
Occurrence of endocrine-disrupting chemicals in indoor
dust. Sci Total Environ 404:26–35.
Kato K, Silva MJ, Reidy JA, Hurtz D, Malek NA, Needham LL,
et al. 2004. Mono(2-ethyl-5-hydroxyhexyl) phthalate and
mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for
human exposure assessment to di-(2-ethylhexyl) phthalate.
Environ Health Perspect 112:327–330.
Kerns EH, Di L, Carter GT. 2008. In vitro solubility assays in drug
discovery. Curr Drug Metabol 9:879–885.
Koch HM, Angerer J, Drexler H, Eckstein R, Weisbach V. 2005a.
Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary
plasma and platelet donors. Int J Hyg Environ Health
Koch HM, Bolt HM, Angerer J. 2004. Di(2-ethylhexyl)phthalate
(DEHP) metabolites in human urine and serum after a
single oral dose of deuterium-labelled DEHP. Arch Toxicol
Koch HM, Bolt HM, Preuss R, Angerer J. 2005b. New metabo-
lites of di(2-ethylhexyl)phthalate (DEHP) in human urine
and serum after single oral doses of deuterium-labelled
DEHP. Arch Toxicol 79:367–376.
Koch HM, Preuss R, Angerer J. 2006. Di(2-ethylhexyl)phthalate
(DEHP): human metabolism and internal exposure—an
update and latest results. Int J Androl 29:155–165.
Koch HM, Rossbach B, Drexler H, Angerer J. 2003. Internal
exposure of the general population to DEHP and other
phthalates—determination of secondary and primary
phthalate monoester metabolites in urine. Environ Res
Lee EJ, Arbuckle TE. 2009. Urine sampling methods for environ-
mental chemicals in infants and young children. J Expos
Sci Environ Epidemiol; doi:10.1038/jes.2009.36 [Online
24 June 2009].
Nakamiya K, Takagi H, Nakayama T, Ito H, Tsuruga H, Edmonds
JS, et al. 2005. Microbial production and vaporization
of mono-(2-ethylhexyl) phthalate from di-(2-ethylhexyl)
phthalate by microorganisms inside houses. Arch Environ
Occup Health 60:321–325.
National Children’s Study. 2009. National Children’s Study.
[accessed 23 February 2009].
National Research Council. 2006. Human Biomonitoring for
Environmental Chemicals. Washington, DC:National
National Toxicology Program. 2008. NTP-CERHR Monograph
on the Potential Human Reproductive and Developmental
Sampling and interpretation of biomonitoring data
Environmental Health Perspectives • volume 117 | number 10 | October 2009
Effects of Bisphenol A. Available: http://cerhr.niehs.
3 September 2008].
Needham LL, Calafat AM, Barr DB. 2007. Uses and issues of
biomonitoring. Int J Hyg Environ Health 210:229–238.
Needham LL, Patterson DG, Barr DB, Grainger J, Calafat AM.
2005. Uses of speciation techniques in biomonitoring for
assessing human exposure to organic environmental
chemicals. Anal Bioanal Chem 381:397–404.
NIOSH (National Institute for Occupational Safety and Health).
1994. NIOSH Manual of Analytical Methods. 4th ed.
[accessed 23 November 2008].
Peck CC, Albro PW. 1982. Toxic potential of the plasticizer di(2-
ethylhexyl) phthalate in the context of its disposition and
metabolism in primates and man. Environ Health Perspect
Pineau A, Guillard O, Chappuis P, Arnaud J, Zawislak R. 1993.
Sampling conditions for biological fluids for trace elements
monitoring in hospital patients: a critical approach. Crit Rev
Clin Lab Sci 30:203–222.
Rudel RA, Perovich LJ. 2009. Endocrine disrupting chemicals in
indoor and outdoor air. Atmos Environ 43:170–181.
Silva MJ, Reidy A, Preau JL, Samandar E, Needham LL,
Calafat AM. 2006. Measurement of eight urinary metabo-
lites of di(2-ethylhexyl) phthalate as biomarkers for human
exposure assessment. Biomarkers 11:1–13.
Staples CA, Peterson DR, Parkerton TF, Adams WJ. 1997. The
environmental fate of phthalate esters: a literature review.
Taylor JK. 1987. Quality Assurance of Chemical Measurements.
Chelsea, MI:Lewis Publishers.
Viso A-C, Eilstein D, Medeiros H, eds. 2009. Human biomonitor-
ing and environmental health. In: Bulletin Épidémiologique
Hebdomadaire, spec ed. Saint-Maurice, France:Institute
de Veille Sanitaire, 1–27.
Volkel W, Kiranoglu M, Fromme H. 2008. Determination of
free and total bisphenol A in human urine to assess daily
uptake as a basis for a valid risk assessment. Toxicol Lett
Weschler CJ. 2009. Changes in indoor pollutants since the
1950s. Atmos Environ 43:153–169.
Wilson NK, Chuang JC, Lyu C, Menton R, Morgan MK. 2003.
Aggregate exposures of nine preschool children to persis-
tent organic pollutants at day care and at home. J Expos
Anal Environ Epidemiol 13:187–202.
Yan X, Calafat A, Lashley S, Smulian J, Ananth C, Barr D, et al.
2009. Phthalates biomarker identification and exposure
estimates in a population of pregnant women. Hum Ecol
Risk Assess 15:565–578.