Biomonitoring Studies Confirm
Human Exposure to Bisphenol A is Very Low - Low Exposure
Supports Low Risk to Human Health
May 4, 2005
Human biomonitoring data on bisphenol A (BPA) have been reported
in a number of studies worldwide. These studies consistently
indicate that human daily intake of bisphenol A is very
low and likely to be in the range of 20-30 nanograms/kg-body
weight/day for adults. These levels are about 1,000,000
times below the levels where no adverse effects on reproduction
and development were observed in multi-generation animal
studies. Similarly, these levels are about 400-2,000
times below lifetime daily intake levels set by government
bodies in the US and Europe. Exposures below the lifetime
daily intake levels are expected to have no adverse
effect on health. Both comparisons indicate a substantial
margin of safety between actual and safe exposure levels.
Overall, the available biomonitoring data on bisphenol
A supports the conclusion that exposure to bisphenol
A from all sources poses no known risk to human health.
What is Biomonitoring?
Biomonitoring is a scientific technique for directly
measuring human exposure to natural or synthetic substances.
The technique involves analysis of human tissues or
fluids such as blood or urine for the substance itself
or for a biomarker that indicates exposure to the substance.
(1) An important aspect of biomonitoring
is that it can directly measure the amount of a substance
in the body from all sources of exposure at a certain
point in time. However, biomonitoring by itself does
not provide information on the source, timing or health
effects of the exposure.
Biomonitoring is not new. It was applied more than
100 years ago to monitor occupational exposure to chemicals
such as lead or uptake of pharmaceutical compounds.
In recent years biomonitoring has become more common
due to lower laboratory costs and advances in analytical
techniques that allow detection of very low levels of
substances. A notable example is the biannual biomonitoring
study on the US population conducted by the US Centers
for Disease Control and Prevention (CDC), which currently
includes more than 100 substances. (2)
How is Biomonitoring Data Used?
Public health scientists use biomonitoring data to
establish reference ranges for exposure within a population,
understand differences in exposure between different
groups, and evaluate trends in exposure over time.
An important caution is that detecting a substance
in a person's body does not by itself indicate that
the exposure causes harm, only that the substance is
present at that point in time. Sensitive analytical
techniques increasingly allow detection of very low
levels of many substances, but those same techniques
do not provide any indication whether the detected substances
have caused or could cause a health effect. (3)
However, when combined with toxicity information, direct
measurements of exposure, such as biomonitoring data,
are of particular value for assessing potential health
risks from exposure to a substance. Information on exposure
levels is a critical requirement for risk assessment,
since health risks are a function of exposure level
(i.e., "the dose makes the poison").
How is Biomonitoring for Bisphenol A Conducted?
Biomonitoring is most commonly conducted by analysis
of blood or urine but, in principle, many other human
tissues and fluids can be analyzed. For any substance,
the most appropriate tissue or fluid is selected based
on the chemical and physical properties of the substance
and, in particular, the basic mechanisms by which the
substance is processed in the body (i.e., absorption,
distribution, metabolism and excretion). In general,
substances that do not persist or accumulate in the
body are most commonly measured in urine.
The mechanisms by which bisphenol A is processed in
the body have been very well characterized by a variety
of studies on laboratory animals and, most importantly,
in human volunteer studies. (4) After
ingestion, which is the most probable route of exposure
for people, bisphenol A is readily absorbed and efficiently
converted to a glucuronide metabolite as it passes through
the intestinal wall and the liver. The metabolite, in
which bisphenol A is chemically linked to a sugar molecule,
is water soluble and is entirely excreted into urine
The lifetime of the glucuronide metabolite in the human
body is quite short with a half-life less than 6 hours,
which means that any bisphenol A exposure will be eliminated
from the body within a day. Neither bisphenol A nor
the metabolite accumulate or persist in the body. Because
of the efficiency of the metabolic process, essentially
all bisphenol A in the body is in the form of the glucuronide
metabolite, which has been shown to be non-estrogenic
and has no known biological activity. (5)
Based on the characteristics of bisphenol A in the
body, biomonitoring studies are most appropriately conducted
by analysis of urine, where bisphenol A is present in
the form of the glucuronide metabolite. Because it is
easier to measure bisphenol A itself, the glucuronide
metabolite is usually hydrolyzed back to bisphenol A
by treatment of urine samples with an enzyme before
What Does Biomonitoring Data Tell Us About Human
Exposure to Bisphenol A?
Recently published studies in which human urine samples
were analyzed for bisphenol A indicate that exposure
to bisphenol A is extremely low, in the range of 20-30
nanograms/kg-body weight/day. Included are two studies
in which urine samples were collected over 24-hour periods.
In one of these studies, the median level of bisphenol
A excreted by 36 Japanese adult males was estimated
as 1.2 micrograms/day. (6)This study
also examined day-to-day variation by collecting 24-hour
urine samples for 5 consecutive days for 4 males and
1 female. Although the median value was essentially
the same at 1.3 micrograms/day, the study demonstrated
variation between days and between individuals. A second
study reported the average level of bisphenol A excreted
by 11 Japanese males and 11 females, all adults, to
be 1.68 micrograms/day. (7)
The amount of bisphenol A excreted in a 24-hour period
is a good estimate of bisphenol A daily intake because
of the short half-life of bisphenol A in the body. For
an adult body weight of 60 kg, the typical bisphenol
A daily intake estimated from 24-hour urine data is
in the range of 20-30 nanograms/kg-body weight/day.
Although single day intakes may be somewhat higher or
lower than this range, the day-to-day variation demonstrated
in one study suggests that this range is a reasonable
estimate of average long-term daily intake for individuals
and groups. Average long-term daily intake is the most
appropriate intake value for risk assessment purposes.
A number of other studies have also analyzed spot samples
of human urine for bisphenol A. Daily intakes can be
estimated by multiplying bisphenol A concentration values
(i.e., reported as micrograms BPA/liter urine or micrograms
BPA/gram creatinine) by either a typical daily urinary
volume (2 liters/day) or a typical daily creatinine
excretion rate (1.2 grams/day). Using this technique,
three recent Japanese studies indicate median daily
intakes of 1.2 micrograms/day for 42 males, (8)
0.92 micrograms/day for 48 females, (9)and
less than 2.0 micrograms/day for 56 pregnant women,
(10), (11) each of which
are very similar to the daily intakes directly measured
from 24-hour urine samples.
Most recently, the CDC reported bisphenol A concentrations
in spot urine samples from 394 adults in the US. (12)
Based on a median concentration of 1.32 micrograms BPA/gram
creatinine, the median daily bisphenol A intake can
be estimated as approximately 1.6 micrograms/person/day,
which indicates that human exposures to bisphenol A
in the US and Japan are very similar.
Overall, the studies conducted in Japan and the US
consistently indicate that typical long-term human exposure
to bisphenol A is very low and likely to be in the range
of 20-30 nanograms/kg-body weight/day.
What Does the Bisphenol A Biomonitoring Data Mean?
To put the biomonitoring data into perspective, it
is helpful to compare typical daily intakes to acceptable
daily intakes set by government bodies. These acceptable
daily intakes are derived from toxicity studies to which
conservative safety factors are applied to estimate
lifetime exposure levels that are expected to be without
adverse effects. Typical daily intake values can also
be compared directly to doses that have been shown to
cause no adverse effects in toxicity studies.
A typical daily intake of 25 nanograms/kg-body weight/day
is about 1,000,000 times lower than levels where no
adverse effects on reproduction or
development were observed in multi-generation animal
studies, which indicates a very large margin of safety.
By application of safety factors, the US Environmental
Protection Agency has set a Reference Dose of 50 micrograms/kg-body
weight/day (14) and the European Commission's
Scientific Committee on Food has set a Tolerable Daily
Intake of 10 micrograms/kg-body weight/day. (15)
In comparison, a typical daily bisphenol A intake of
25 nanograms/kg-body weight/day is 400-2,000 times lower,
which also indicates a substantial margin of safety
between actual and safe exposure levels.
Overall, the available biomonitoring data on bisphenol
A indicates that actual human exposure to bisphenol
A is far below levels that could cause adverse health
effects and supports the conclusion that exposure to
bisphenol A from all sources poses no known risk to
1. For general information on biomonitoring,
2. Information on the CDC biomonitoring
program is available at http://www.cdc.gov/biomonitoring/.
3 For a general discussion on the significance
of trace chemicals in the body, see "Traces of
Environmental Chemicals in the Human Body: Are They
a Risk to Health?" from the American Council on
Science and Health at http://www.acsh.org/publications/pubID.195/pub_detail.asp.
4 "Metabolism and kinetics of bisphenol
A in humans at low doses following oral administration",
W. Völkel, T. Colnot, G. A. Csanady, et al., Chemical
Research in Toxicology (2002), 15:1281-1287.
5 "In vitro and in vivo interactions
of bisphenol A and its metabolite, bisphenol A glucuronide,
with estrogen receptors alpha and beta", J. B.
Matthews, K. Twomey, and T. R. Zacharewski, Chemical
Research in Toxicology (2001), 14:149-157.
6 "Daily urinary excretion of bisphenol
A", C. Arakawa, K. Fujimaki, J. Yoshinaga, et al.,
Environmental Health and Preventive Medicine (2004),
7 "Development of analytical method
for determining trace amounts of BPA in urine samples
and estimation of exposure to BPA", T. Tsukioka,
J. Terasawa, S. Sato, et al., Journal of Environmental
Chemistry (2004), 14:57-63.
8 "Urinary bisphenol A and plasma
hormone concentrations in male workers exposed to bisphenol
A diglycidyl ether and mixed organic solvents",
T. Hanaoka, N. Kawamura, K. Hara, and S. Tsugane, Occupational
and Environmental Medicine (2002), 59:625-628.
9 "Measurement of bisphenol A in
human urine using liquid chromatography with multi-channel
coulometric electrochemical detection", K. Ouchi
and S. Watanabe, Journal of Chromatography B (2002),
10 A more accurate median value could
not be estimated since BPA was below the detection limit
for 39 of 56 samples. Consequently, the reported median
of <2 micrograms/day overestimates actual exposure,
which is likely to be comparable to or below the levels
reported in other studies.
11 "Estimation of intake level
of bisphenol A in Japanese pregnant women based on measurement
of urinary excretion levels of the metabolite",
K. Fujimaki, C. Arakawa, J. Yoshinaga, et al., Japanese
Journal of Hygiene (2004), 59:403-408.
12 "Urinary concentrations of
bisphenol A and 4-nonyl phenol in a human reference
population", A. M. Calafat, Z, Kuklenyik, J. A.
Reidy, et al., Environmental Health Perspectives (2005),
13 "Three-generation reproductive
toxicity study of dietary bisphenol A in CD Sprague-Dawley
rats", R. W. Tyl, C. B. Myers, M. C. Marr, et al.,
Toxicological Sciences (2002), 68:121-146.
14 See http://www.epa.gov/iris.
15 See http://europa.eu.int/comm/food/fs/sc/scf/out128_en.pdf.