Dioxin Cancer Potency Lower
Than Once Thought
Determining New Dioxin Elimination Rate
Leads To Change
March 31, 2005
What is a half-life of elimination?
A half-life describes the rate at
which something diminishes. In the case of dioxin elimination
from the human body, the half-life is the time it takes
the human body to eliminate one-half of all of the dioxin
it contains. Scientists used to think that the half-life
of dioxin elimination was about 7 years. Now they are
realizing the half-life changes, based on an individual's
dioxin level. It probably ranges from as rapid as about
1 year to approximately 10 years.
Government and industry efforts to lower dioxin levels in the
U.S. environment and population are paying off. Whether considering
dioxins in industrial emissions, soils, sediments, foods or
human tissue, the trends are consistent: levels have decreased
substantially, are low, and will continue to decline. Because
people are exposed to dioxins mainly through the diet, human
tissue levels are diminishing as levels in foods are falling.
Researchers who study the declining presence of dioxins in
the general population are eager to understand the timetable
of its elimination from the human body. To this end, valuable
information is being gathered by monitoring those who have
been exposed to higher-than-average levels of dioxin, including
occupationally-exposed workers, persons exposed in Seveso,
Italy after a chemical plant accident, Vietnam veterans who
handled Agent Orange, and a few cases of intentional dioxin
poisoning, such as that of Ukrainian President Viktor Yushchenko.
Besides supplying important data to the dioxin elimination
timetable, this research is challenging old views of the
cancer potency of dioxin.
Cup Overflow: Eliminating Dioxin at High Body Levels
Scientists used to assume that dioxin is eliminated from
the human body at a constant half-life rate (see sidebar discussion
of half-life). New research shows a much different equation
applies: The half-life of dioxin elimination depends on the
amount of dioxin in the body. The more dioxin in one's
body, the shorter the half-life, and the greater the rate
of elimination. The reason for this pattern stems
from the complex way in which dioxin is absorbed by and released
from the human liver and fat tissue.
apt analogy for human elimination of TCDD, the most potent
of the dioxin family compounds, is a one-cup-volume measuring
cup with a leaky base. As long as the level of liquid in the
cup remains below the rim, liquid will leak out at a rate
that depends upon the amount of liquid in the cup. The higher
the level of liquid in the cup, the faster the leak. If significantly
more than one cup of liquid is poured into the cup, elimination
will occur more rapidly--the liquid will overflow the measuring
cup, spilling out over the rim in addition to slowly leaking
from the cup base. Similarly, people with high levels of dioxin
expel the substance rapidly, while those with low levels experience
only the "slow leak" of dioxin.
Learning from Rare Cases of High Exposure to Dioxin
The highest dioxin level ever recorded in a human being resulted
from the 1998 poisoning of an Austrian woman who, along with
a friend, ingested TCDD. The woman had a blood TCDD level
of 144,000 parts per trillion (ppt). Mr. Yushchenko, the victim
of an alleged political crime, registered a blood TCDD level
high of 100,000 ppt, the second highest level ever recorded.
Through their misfortune, Viktor Yushchenko and two Austrian
women have become unwitting subjects in the scientific study
of the health effects of dioxins in humans. All three have
suffered severe cases of acne--known as chloracne--the most
clearly manifested health effect resulting from high exposures
From monitoring the TCDD blood levels of the Austrian women
and others exposed to high levels of dioxins, scientist have
learned that dioxin is lost from the body most quickly at
the highest body levels. It is likely that Mr. Yushchenko
is eliminating dioxin rapidly at this early stage, while his
level is still very high. Later, his elimination rate will
In contrast to the few rare cases of high dioxin exposure,
most people have very low levels of dioxin in their bodies.
The CDC reported that the TCDD level of the average U.S. resident
is quite low--below the level of detection of 4.8 ppti.
Current, undetected levels represent a decline from an estimated
blood level of 20 ppt in 1970ii.
The elimination of dioxin from the Austrian women who
were poisoned is occurring much faster than predicted
by the conventional seven-year half-life assumption
(brown line above). Based on data from these women and
persons exposed at Seveso, the half-life for elimination
after high exposures can be as short as about 1 year.
From Aylward (2005)iii
Dioxin Cancer Risk May Be Much Lower than Previously Thought
The new finding that dioxin elimination rates depend on exposure
levels tells us that occupationally-exposed individuals, whose
dioxin levels have been measured many years since their exposure,
may have been exposed initially to much greater levels of
dioxins than previously thought. Had their elimination half-lives
remained unchanged since their first exposure, the red arrow
in the graph below would apply. Knowing, however, that their
actual initial exposures were probably much higher leads us
to the conclusion that cancer risk increases more slowly with
dioxin exposure. Therefore, the green TCDD cancer slope factor
is flatter than previously thought, indicating that it, and
other similar dioxin compounds, may present a much lower cancer
risk at low exposures than previously thought.
Good News for Breast-feeding Moms
Average dioxin levels in the breast milk of American mothers
are relatively low compared to those of mothers around the
world. The chart illustrates the levels of dioxins (PCDDs/Fs-yellow
bar) and dioxin-like PCBs (blue bar) in mothers' milk from
26 countries around the world. These values represent about
a 40 percent decline in contaminant levels over the span of
approximately a decade.
This news is encouraging because new research indicates that
breast-feeding may be related to the prevention of diabetes,
heart disease and other diseases that appear in adulthoodiv.
Scientists, pediatricians and public health officials overwhelmingly
endorse and encourage breast-feeding because of the many benefits
it provides to the health and development of infants1.
"On average, the decline
between the levels found in... 1993 and the levels found
in the current study is about 40%"
and van Leeuwen. Organohalogen Compounds 60-65, Dioxin
2003, Boston MA
Women of Child-bearing Age Have Very Low Dioxin Levels
Preliminary data from the CDCv show that women
of child-bearing age who live in America have some of the
lowest dioxin levels in the population, regardless of their
race or ethnicity. Low levels of dioxins were measured in
the blood of Mexican-Americans, non-Hispanic black Americans
and non-Hispanic white Americans.
According to a study by the WHO, in utero exposure
to PCBs, while low, is more significant than post-natal exposure
via breast-feedingvi. The CDC's preliminary data
demonstrate low levels of PCBs in the blood of women of child-bearing
age in all three categories of race and ethnicity--again,
good news for mothers and babies.
The graph below illustrates total "TEQ" levels of American
females of four age groups. Total TEQ denotes total "toxic
equivalent," a quantitative measure of the combined toxicity
of a mixture of dioxins and dioxin-like PCBs.
TCDD Levels and Age of Onset of Menstruation
On July 10, 1976, a chemical explosion in Seveso, Italy
exposed the nearby population to high levels of dioxins.
In 1996, a team of researchers initiated the Seveso
Women's Health Study to investigate whether the female
residents of Seveso are at higher risk for reproductive
disease as a result of their exposure.
Recently, the researchers compared the TCDD blood levels
(taken soon after the explosion) of 282 Seveso females
who were pre-pubescent at the time of the exposure,
with their reported age of onset of menstruation. The
researchers found no relationship between this population's
elevated TCDD exposures and their reported ages of onset
When they were children, the women in this study experienced
TCDD blood levels that averaged more than 25 times higher
than current typical exposure levels. The researchers
are continuing to study this population. vi
Current total TEQ levels in U.S. residents, female and male,
increase with age, as shown in the graph. This is due to the
fact that environmental levels of dioxins and dioxin-like
compounds peaked around the early 1970s, and older residents
had time to bioaccumulate more TEQ when environmental levels
were high. With declines in environmental levels since the
early 1970s, younger people, born post-1970, have been exposed
to progressively lower levels of these compounds. For that
reason, the children of today will never attain the body levels
of total TEQ of their grandparents. The graph below demonstrates
the continual decline in dioxin TEQ levels, projecting significant
"flattening" of levels across age groups by 2030.
Dioxins are declining in the environment and in people.
New studies inform us that the rate at which TCDD is eliminated
from the human body depends upon the amount of dioxin in the
body. People who experience rare, high exposures eliminate
dioxin more rapidly than those who have typical, low levels
in their bodies.
Dioxin elimination science sheds new light on the cancer
potency of TCDD. The cancer rate in populations accidentally
or occupationally exposed to dioxin has been miscalculated,
based on old ideas of steady half-lives of elimination. Re-calculation,
based on more accurate models of TCDD elimination, demonstrates
that dioxin is probably not as potent a carcinogen as was
As dioxins decline in the environment and in people, levels
in breast milk are also diminishing, good news for mothers
and infants. Similarly, dioxin-like PCBs are declining, lowering
in utero exposures.
Regardless of race or ethnicity, American women of child-bearing
age have some of the lowest levels in the U.S. population
of dioxins and dioxin-like PCBs in their bodies. Most children
of today will never attain the dioxin body levels of their
grandparents as environmental exposures have declined drastically.
1Groups endorsing breast-feeding
include the World Health Organization, the American Academy
of Pediatrics and LaLeche League International.
for Disease Control and Prevention (2003). Second National
Report on Human Exposure to Environmental Chemicals. On-line.
iiAylward, L., Hayes, S. (2002).
Temporal trends in human TCDD body burden: Decreases over
three decades and implications for exposure levels. Journal
of Exposure Analysis and Environmental Epidemiology 12, 319-328.
iii Aylward, L., (2005, Feb. 1).
Concentration-dependent elimination kinetics in humans?Impact
on human cancer risk assessment. Presentation to the NAS Committee
to Review EPA's Assessment of the Health Implications of Exposure
ivPronczuk, J., Moy, G. and Vallenas,
C. (Sept., 2004). Guest editorial: Breast milk: An optimal
food, Environmental Health Perspectives, v. 112, p. A722-3.
vParaphrased from presentation
of Dr. L. Needham, Centers for Disease Control and Prevention,
to the NAS Review Panel for EPA's Exposure & Human Health
Reassessment of TCDD & Related Compounds, February 1, 2005.
viWHO (2002). Safety evaluation
of certain food additives and contaminants. WHO Food Additives
Series 48. Genera: World Health Organization, 311-16.
vii Warner, M., Samuels, S., Mocarelli,
P., Gerthoux, P.M., Needham, L., Patterson, D.G., Eskenazi,
B. (2004). Serum dioxin concentrations and age at menarche.
Environmental Health Perspectives, v. 112, 1289-92.