Dioxin Cancer Potency Lower Than Once Thought

Determining New Dioxin Elimination Rate Leads To Change

March 31, 2005

Introduction

 

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.

An 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 to dioxins.

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 slow down.

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%"

Malisch 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 of menstruation.

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.

Conclusions

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 once thought.

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.

iU.S. Centers for Disease Control and Prevention (2003). Second National Report on Human Exposure to Environmental Chemicals. On-line. Available: http://www.cdc.gov/exposurereport/2nd/pdf/secondner.pdf

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 to Dioxin.

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.

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