To counter all the recent
misinformation being feed the local community, the following is a summary of dioxins
effects on human health as presented on the Coming Clean sites Body Burden Dioxin Case study page.
Exposure to dioxin can lead
to a wide array of adverse health effects including cancer, birth defects, diabetes,
learning and developmental delays, endometriosis, and immune system abnormalities.
Dioxin is a known
carcinogen. IARC, the International Agency for Research on Cancer, which is part of the
World Health Organization, classified it as a known human carcinogen in 1997. In January
2001, the Department of Health and Human Services' National Toxicology Program classified
dioxin as a known human carcinogen. The September 2000 draft of the U.S. EPA's Health
Assessment document on dioxin also classifies dioxin as a known human carcinogen. In that
same report, the U.S. EPA projected an excess cancer risk of one in 100 for the most
sensitive people who consume a diet high in animal fats. In other words, the risk of
getting cancer from dioxin--over and above the risk of cancer from other sourcesis
one in 100 for some people. This is a worst-case scenario. It's for the most sensitive
people among the five percent of the population who consume the most dioxin. For the
average person, EPA estimates a risk level of one in 1,000, which is also a serious risk
level. The EPAs generally "acceptable" risk level is one-in-one-million.
Dioxin also causes a wide
range of non-cancer effects including reproductive, developmental, immunological, and
endocrine effects in both animals and humans. Animal studies show that dioxin exposure is
associated with endometriosis, decreased fertility, inability to carry pregnancies to
term, lowered testosterone levels, decreased sperm counts, birth defects, and learning
disabilities. In children, dioxin exposure has been associated with IQ deficits, delays in
psychomotor and neurodevelopment, and altered behavior including hyperactivity. Studies in
workers have found lowered testosterone levels, decreased testes size, and birth defects
in offspring of Vietnam veterans exposed to Agent Orange.
Effects on the immune
system appear to be among the most sensitive endpoints studied. Animal studies show that
dioxin decreased immune response and increased susceptibility to infectious disease. In
human studies, dioxin was associated with immune system depression and alterations in
immune status leading to increased infections. Dioxin can also disrupt the normal function
of hormoneschemical messengers that the body uses for growth and regulation. Dioxin
interferes with thyroid levels in infants and adults, alters glucose tolerance, and has
been linked to diabetes.
2005 study of humans finds epidemiological
evidence of an association between increased PCDD/PCDF and PCB body burden and
10/24/09 VA adds three more diseases
associated with Agent Orange
New to the list:
B Cell Leukemia's, such as “Hairy Cell Leukemia”
Ischemic Heart Disease: Any condition in which heart muscle is damaged
or works inefficiently because of an absence or relative deficiency of its
blood supply; most often caused by atherosclerosis, it includes angina
pectoris, acute myocardial infarction, chronic ischemic heart disease, and
Acute and Subacute Transient Peripheral Neuropathy: A nervous system
condition that causes numbness, tingling and motor weakness.
AL Amyloidosis: A rare disease caused when an abnormal protein, amyloid,
enters tissues or organs.
Chloracne: A skin condition that occurs soon after dioxin exposure and
looks like common forms of acne seen in teenagers.
Chronic Lymphocytic Leukemia: A disease that progresses slowly with
increasing production of excessive numbers of white blood cells.
Diabetes Mellitus (Type 2): A disease characterized by high blood sugar
levels from the body’s inability to respond properly to the hormone insulin.
Hodgkin’s Disease: A malignant lymphoma (cancer) characterized by
progressive enlargement of the lymph nodes, liver and spleen, and by
Multiple Myeloma: A cancer of specific bone marrow cells that is
characterized by bone marrow tumors in various bones of the body.
Non-Hodgkin’s Lymphoma: A group of cancers that affect the lymph glands
and other lymphatic tissue.
Porphyria Cutanea Tarda: A disorder characterized by liver dysfunction
and by thinning and blistering of the skin in sun-exposed areas.
Prostate cancer: Cancer of the prostate, one of the most common cancers
Respiratory cancers: Cancers of the lung, larynx, trachea and bronchus.
Soft tissue Sarcoma: A group of different types of cancers in body
tissues such as muscle, fat, blood and lymph vessels and connective tissues.
concerns me, the more I read about it, the more concerned I become. Why am I
here? I can sum it up in three words - for the children." Dr. Suzanne White,
M.D., Medical director for Children's Hospital of Michigan Regional Poison Control Center
Whites comments where made during her presentation at the Freeland High School public
meeting hosted by the MDCH August 20, 2003.
Dr. White went on to say:
that dioxin especially can interfere with childhood development and have lifelong
consequences. There is even a hazard to a child playing the the back yard if the
soil has high dioxin content.
isolated studies suggest dioxin can increase a person's chances of getting cancer by 40
to 100 percent.
data shows a higher than expected incidence of cancer near Midland.
many studies show a link between the substance and cancer and birth defects in humans as
well as a host of other ailments.
Her recommendations to limit exposure: do not eat fish caught in river, washing and
peeling produce grown near river, and discouraging children from placing toys or dirty
items in their mouths. For additional precautions recommended by the Michigan
Department of Agriculture, click
It should also be noted that the head of the ATSDR, Dr. Henry Falk, M.D. attended
the meeting to make a presentation and to meet with local residents to hear their
concerns. The following day he made a tour to the entire flood plain as well as Dow
Chemicals Midland plant. During his presentation, Dr. Falk said his agency receives
400-500 new cases each year. He went on to say that he personally could not visit
every site and therefore limited visits to those sites with the greatest potential for
exposing the public to harm.
State MDEQ warns schools to limit
children's exposure to
park soils In a letter
dated 12/3/03, the MDEQ notified schools in the area to plan activities so that students
are not in direct contact with dioxin laden soils. The soils of frequently flood
parks located in the Tittabawassee River flood plain have been found by the MDEQ to
contain dioxin contamination with levles almost 38 times the states
Residential Direct Contact Criteria of 90 ppt.
Click here for levels discovered in Phase 2 sampling.
Effects of prenatal exposure (before birth while in
The health effects most likely to be associated with low level exposures relate to the
Dioxin possible cause of Attention Deficit Hyperactivity Disorders (ADD or ADHD)
In the January 1998 issue of the scientific journal Toxicology and Industrial
Health, Dr. Peter Hauser and colleagues summarize recent studies that suggest links
between perinatal exposure to dioxin-like substances and developmental
learning and attention. They propose that the genetic condition known as resistance to
thyroid hormone (RTH) may be a useful model for further study of the disruptive effects of
dioxin and PCBs on brain development.
Hauser is professor of psychiatry at the UM School of Medicine and chief
of psychiatry at the Baltimore Veterans Affairs Medical Center. Co-authors are Drs. J.
Michael McMillin and Vinod S. Bhatara of the University of South Dakota School of
Thyroid hormone plays an essential role in prenatal brain growth and
development, as well as in normal behavioral and intellectual development. Even moderate
impairment of thyroid hormone function has been associated with various problems in
behavioral and intellectual development, and certain thyroid diseases such as RTH are
associated with attention deficit hyperactivity disorder (ADD or ADHD) and language
here for details.
Effects of prenatal PCB and dioxin background exposure on cognitive and motor
abilities in Dutch children at school age. Click
here for copy of article as published in January 2002 Journal of Pediatrics,
Volume 140 number 1
Neurotoxic effects of prenatal PCB and dioxin exposure may persist into school
age, resulting in subtle cognitive and motor developmental delays. More optimal
intellectual stimulation provided by a more advantageous parental and home environment may
counteract these effects of prenatal exposure to PCBs and dioxins on cognitive and motor
abilities. (J Pediatr 2002;140:48-56)
Perhaps the most important, and most disturbing, new evidence about dioxin's toxicity is
the neurodevelopmental and reproductive effects observed in children. Read the
entire report Dioxin:
Children are most vulnerable
child's chemical exposures are greater
pound-for-pound than those of adults.
porous blood-brain barrier allows greater
chemical exposures to the developing brain.
lower levels of some chemical-binding proteins,
allowing more of a chemical to reach "target
A baby's organs
and systems are rapidly developing, and thus are
often more vulnerable to damage from chemical
detoxify and excrete industrial chemicals are
not fully developed.
The longer future
life span of a child compared to an adult allows
more time for adverse effects to arise.
Milk: "When a woman becomes pregnant, the dioxins in her body can
cause irreversible changes in the development of the central nervous system, immune
system, reproductive system and endocrine system of the fetus. The dioxins in a
womans body are also passed to her nursing infant in her milk"
Listen to the EPA's Dr. Linda Birnbaum's comments on this topic, click here
The above are excerpts from Green Peace's report on the global
effort to eliminate the sources of dioxin worldwide. Chapter 8 (page 30) focuses on
Dioxin and it's effect on human health. Read the entire report Dioxin Elimination
Tooth Development in children.
In the Jan. 16 1999 Lancet, Alaluusua's team reports that children who had
encountered the most dioxin in their mother's milk had the highest rate of these tooth
defects. Breast-milk exposure to polychlorinated biphenyls, another group of dioxin-like
chemicals, played little if any role. Article published in Science News Online
In addition to being carcinogenic, dioxin disrupts the way
human hormones and chromosomes work. Because of its
endocrine-disrupting qualities, dioxin also causes a host of other illnesses and problems,
including reproductive, neurotoxic, immune system, other hormonal and developmental
effects. Remember that most literature on dioxin's health effect is based on
exposure levels of the "General Population" via the food chain. Would you
consider yourself the "General Population" when levels in the vicinity of your
back yard have been recorded as the HIGHEST ever found in Michigan & up to 80 times
the level for which the MDEQ recommends cleanup? Many opinions exist on whether the
health effects are demonstrated in High or Low levels of exposure or somewhere
in-between. Which ones are correct?
properly conducted Health Study may provide insight into the answer. Then again,
it may find it's conclusion "Indeterminate". Until then, follow
recommended guidelines to reduce your exposure in the
MDCH Dioxin Fact Sheet.pdf,
Information about dioxin and
the Tittabawassee river flood plain, and
Food and gardening dioxin guide brochures.
"The appropriate way to view dioxin is as a modulator
of growth and development. Dioxin appears to perturb normal
homeostasis and hormonal balance leading to alterations in proliferation and
differentiation. In the adult, such changes may lead to cancer,
immunosuppression, chloracne, and endometriosis."
DO THESE DIOXIN-LIKE
COMPOUNDS CAUSE CANCER IN HUMANS?
08/03/11 New dioxin cancer risk study of women in the Seveso
Italy supports report of Breast Cancer increase in Midland and Tittabawassee
"Individual serum TCDD is significantly positively related with all
cancer incidence in the SWHS cohort, more than 30 years later. This
all-female study adds to the epidemiologic evidence that TCDD is a
multi-site carcinogen. "
study seems to reinforce the conclusion of another peer reviewed study
published in April 2011 (see TRW Current News 4/2/11) which identified
higher breast cancer rates in women living in the city of Midland and in the
vicinity of the Tittabawassee River:
"These findings suggest that increased breast cancer incidences are spatially
associated with soil dioxin contamination. Aging is a substantial factor in
the development of breast cancer. Findings can be used for heightened
surveillance and education, as well as formulating new study hypotheses for
(TCDD), a widespread environmental contaminant, disrupts
multiple endocrine pathways. The International Agency
for Research on Cancer classified TCDD as a known human
carcinogen, based upon predominantly male occupational
studies of increased mortality from all cancers
Objectives: After a chemical explosion on July 10, 1976,
in Seveso, Italy, residents experienced some of the
highest levels of TCDD exposure in a human population.
In 1996, we initiated the Seveso Women’s Health Study (SWHS),
a retrospective cohort study of the reproductive health
of the women. We previously reported a significant
increased risk for breast cancer and a non-significant
increased risk for all cancers combined with individual
serum TCDD, but the cohort averaged only 40 years old in
1996. Herein we report results for risk of cancer from a
subsequent follow-up of the cohort in 2008.
Methods: In 1996, we enrolled 981 women who were 0 to 40
years in 1976, lived in the most contaminated areas, and
had archived sera collected near the explosion.
Individual TCDD concentration was measured in archived
serum by high-resolution mass spectrometry. A total of
833 women participated in the 2008 follow-up study. We
examined the relation of serum TCDD with cancer
incidence using Cox proportional hazards models.
Results: In total, 66 (6.7%) women had been diagnosed
with cancer. The adjusted hazard ratio (adj-HR)
associated with a ten-fold increase in serum TCDD for
all cancers combined was significantly increased (adj-HR=1.80
(95% CI 1.29, 2.52)). For breast cancer, the HR was
increased, but not significantly ((adj-HR=1.44 (95% CI
Conclusions: Individual serum TCDD is significantly
positively related with all cancer incidence in the SWHS
cohort, more than 30 years later. This all-female study
adds to the epidemiologic evidence that TCDD is a
Citation: Warner M, Mocarelli P, Samuels S,
Needham LL, Brambilla P, Eskenazi B 2011. Dioxin
Exposure and Cancer Risk in the Seveso Women’s Health
Study. Environ Health Perspect :-.
March 2011; Accepted: 02 August 2011;
Online: 02 August 2011
Local breast cancer rates
elevated, study finds statistical relationship to elevated dioxin levels
variations in the incidence of breast cancer and
potential risks associated with soil dioxin
contamination in Midland, Saginaw, and Bay
Counties, Michigan, USA
and Tonny J
Health 2008, 7:49doi:10.1186/1476-069X-7-49
21 October 2008
High levels of dioxins
in soil and higher-than-average body burdens of
dioxins in local residents have been found in the
city of Midland and the Tittabawassee River
floodplain in Michigan. The objective of this study
is threefold: (1) to evaluate dioxin levels in
soils; (2) to evaluate the spatial variations in
breast cancer incidence in Midland, Saginaw, and Bay
Counties in Michigan; (3) to evaluate whether breast
cancer rates are spatially associated with the
dioxin contamination areas.
We acquired 532
published soil dioxin data samples collected from
1995 to 2003 and data pertaining to female breast
cancer cases (n = 4,604) at ZIP code level in
Midland, Saginaw, and Bay Counties for years 1985
through 2002. Descriptive statistics and
self-organizing map algorithm were used to evaluate
dioxin levels in soils. Geographic information
systems techniques, the Kulldorff's spatial and
space-time scan statistics, and genetic algorithms
were used to explore the variation in the incidence
of breast cancer in space and space-time. Odds ratio
and their corresponding 95% confidence intervals,
with adjustment for age, were used to investigate a
spatial association between breast cancer incidence
and soil dioxin contamination.
High levels of dioxin
in soils were observed in the city of Midland and
the Tittabawassee River 100-year floodplain. After
adjusting for age, we observed high breast cancer
incidence rates and detected the presence of spatial
clusters in the city of Midland, the confluence area
of the Tittabawassee, and Saginaw Rivers. After
accounting for spatiotemporal variations, we
observed a spatial cluster of breast cancer
incidence in Midland between 1985 and 1993. The odds
ratio further suggests a statistically significant
(alpha = 0.05) increased breast cancer rate as women
get older, and a higher disease burden in Midland
and the surrounding areas in close proximity to the
dioxin contaminated areas.
These findings suggest
that increased breast cancer incidences are
spatially associated with soil dioxin contamination.
Aging is a substantial factor in the development of
breast cancer. Findings can be used for heightened
surveillance and education, as well as formulating
new study hypotheses for further research.
EPA research on three high-profile pollutants -- dioxin, atrazine and
perfluorooctanoic acid (PFOA) -- suggests a link to the trend of early puberty
among U.S. girls, and one agency scientist involved in the studies says the
findings may also shed light on breast cancer risk factors.
The findings could result in the compounds being given a high priority in the
agency’s Endocrine Disruptor Screening Program (EDSP), for which the agency is
still developing a research strategy. In the studies, carried out by the Office
of Research and Development (ORD), female mice subjected to prenatal exposure to
each of the substances demonstrated an effect on mammary gland development, said
ORD researcher Suzanne Fenton in a presentation of the findings at the Society
of Toxicology’s annual meeting March 7.
Source: Superfund Report via
InsideEPA.com Date: March 28, 2005 Issue: Vol. 19, No. 7 Inside Washington Publishers
New evidence supports IARC classification as Class I carcinogen
Steenland, K., Bertazzi, P., Baccarelli, A., Kogevinas, M.,
2004. Dioxin revisited: developments since the 1997 IARC classification of dioxin as a
human carcinogen. Environ. Health Perspect. In Press. doi:10.1289/ehp.7219 (available at
In 1997 the International Agency for Research on Cancer (IARC) classified 2,3,7,8-TCDD
(tetrachlorodibenzo-para-dioxin, the most potent dioxin congener, hereafter
referred to as simply TCDD) as a Group 1 carcinogen based on limited evidence in humans,
sufficient evidence in experimental animals, and extensive mechanistic information
indicating that TCDD acts through a mechanism involving the Ah receptor which is present
in both humans and animals. The judgment of limited evidence in humans was based primarily
on an elevation of all cancers combined in four industrial cohorts. The Class 1
classification has been somewhat controversial, and has been challenged in the literature
in recent years. Here we review the epidemiologic and mechanistic evidence which has
emerged since 1997. New epidemiologic evidence consists primarily of positive
exposure-response analyses is several of the industrial cohorts, as well as evidence of
excesses from several specific cancers in the Seveso accident cohort. There are also new
data regarding how the Ah receptor functions in mediating the carcinogenic response to
TCDD. We conclude that the new evidence generally supports the 1997 IARC
Cancer Risk; Re-analysis of data finds no evidence of dioxin cancer
Recently published paper (Oct 2003) found no threshold for dioxin's cancer causing
effects, in other words, there is no level below which one can say dioxin is safe.
Click here for
The researchers concluded: "We have reexamined the threshold analysis and found
that the data have been incorrectly weighted by cohort size. In our reanalysis, without
the incorrect weighting, the threshold effect disappears."
Risk of soft tissue sarcomas and
residence in the neighbourhood of an incinerator of industrial wastes.
Environ Med (Occupational and environmental medicine.) 2003 Sep; 60(9): 680-3 Additional Info: England
Standard No: ISSN: 1351-0711;
Unique Journal Identifier: 9422759
investigate the association between occurrence of soft tissue sarcomas (STS) in Mantua and
residence near an incinerator of industrial wastes. METHODS: Cases were subjects with
histologically confirmed primary malignant STS diagnosed 1989-98 in the population
resident in Mantua and in the three neighbouring municipalities. Controls were randomly
extracted from population registries, matched for age and sex. Residential history was
reconstructed for all study subjects since 1960. Main residence was geographically
positioned according to GPS standards. RESULTS: The study included 37 STS cases (17 men
and 20 women) and 171 controls. The incidence of STS in the area of study was estimated as
8.8 per 100 000 in men and 5.6 per 100 000 in women. The odds ratio associated with
residence within 2 km, standardised by age and sex, was 31.4 (95% CI 5.6 to 176.1), based
on five exposed cases. At greater distances, risk rapidly decreased, showing a fluctuation
around the null value of 1.
CONCLUSION: The study shows a significant increase in risk of STS associated with
residence within 2 km of an industrial waste incinerator; an aetiological role of
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be hypothesised.
June 2003: National Toxicology Program Lists Dioxin As a Known Human Carcinogen
This past January, the National Toxicology Program announced an addendum to
the Ninth Report on Carcinogens adding dioxin to the list of substances it
considers "known to be human carcinogens." The NTP had planned to reclassify
dioxin as a known human carcinogen when the original report was released in
May 2000 but was prevented from doing so by a lawsuit filed by Jim Tozzi,
former OMB staffer and frequent industry consultant. The lawsuit was
dismissed by the U.S. Court of Appeals for the District of Columbia. The NTP
is the second major international scientific body, following the World
Health Organization's International Agency for Research on Cancer (IARC), to
declare that dioxin is a human carcinogen. The U.S. EPA has come to the same
conclusion in its draft reassessment report on dioxin. Click here for all the
details (pdf file)
June 2003: Cancer Rates in Seveso Are Up
The latest update on the health of residents of Seveso, Italy, who were
exposed to dioxin from an explosion at a pesticide manufacturing plant in
1976, was released in June. The study shows that people who lived in the
areas of highest exposure died more often from cancer than an unexposed
population and that there was an excess of leukemia and Non-Hodgkins
lymphoma. The incidence of diabetes was also higher, as was chronic
circulatory and respiratory disease. These cancer findings further support
the EPA's decision to classify dioxin as a human carcinogen. See Bertazzi,
P.A.,et al., "Health effects of dioxin exposure: A 20-year mortality study,"
American Journal of Epidemiology, 153 (11): 1031-1044, June 1, 2001.
Follow-up study in Seveso indicates breast cancer risks increased significantly.
Warner et al. found that a 10-fold increase in dioxin levels was
associated with a 2.1 increase in risk for breast cancer. Despite the small
number of cases, the increase was statistically significant.
Previous work in the aftermath of the 1976 Seveso, Italy, pesticide factory accident
failed to establish links between dioxin exposure and breast cancer incidence. This new
study of Seveso residents by Warner et al. finds that breast cancer risk
increases significantly with higher dioxin exposures. The authors suggest that an
earlier study, covering only the first decade after the accident, had not allowed
sufficient time to pass since exposure for dioxin's impacts to be manifest.
The EPA estimated body burden for the general
population in the USA ranges from 10 - 40 ppt TEQ. Research in the
EPA and the CHEJ
American Dioxin Report indicates people who live near dioxin release sites, children,
nursing infants, and people who eat fish as a main staple of their diet are likely to be
exposed to at least 3 - 10 times as much dioxin as the general populaiton. Simple
extrapolation of these numbers indicate serum TCDD levels of some floodplain residents
will be in the range of 30-400 ppt TEQ. While it's true the Seveso event exposed
people to very high levels of dioxin, the low end of the studies TCDD serum range suggests
breast cancer risks at contamination levels found in the Tittabawasse flood plain and the
city of Midland.
Short- and long-term morbidity and
mortality in the population exposed to dioxin after the "Seveso accident".
Source: Ind Health (Industrial
health.) 2003 Jul; 41(3): 127-38 Additional Info: Japan
Standard No: ISSN:
0019-8366; NLM Unique Journal Identifier: 2985065R
Abstract: The early
effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population
involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies.
Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The
possible long-term consequences were investigated with mortality and cancer incidence
studies. Mortality and morbidity findings during the 20-year period following the accident
showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in
males, and biliary tract among females, in particular) and respiratory system cancer
(lung, among males). In the incidence analyses, also thyroid gland and pleura cancer
appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest,
yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects
with dioxin exposure were corroborated by findings in the Seveso population: this was the
case with cardiovascular effects (possibly linked to both chemical exposure and stressful
disaster experience), endocrine effects (diabetes among females) and reproductive effects:
exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring.
The results of many Seveso studies point to possible gender effects, in accordance with
animal models. Notwithstanding the acknowledged study limitations (lack of individual
exposure markers, short latency, and small population size for certain cancer types),
results of previous experimental and epidemiological studies, along with mechanistic
knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be
associated with dioxin exposure. The mortality and cancer incidence follow-up of the
Seveso cohort are continuing
Cancer and Developmental Exposure to Endocrine Disruptors
Linda S. Birnbaum1 and Suzanne E. Fenton2
Experimental Toxicology and 2Reproductive Toxicology
Divisions, National Health and Environmental Effects Research Laboratory, Office of
Research and Development, U.S. Environmental Protection Agency, Research Triangle Park,
North Carolina, USAAbstract Developing organisms have increased susceptibility to cancer if they are exposed
to environmental toxicants during rapid growth and differentiation. Human studies have
demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and
there is suggestive evidence that brain tumors and leukemia are associated with parental
exposures to chemicals. Animal experiments have demonstrated increased tumor formation
induced by prenatal or neonatal exposure to a variety of chemicals, including
direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as
known human carcinogens. Prenatal exposure to natural and synthetic estrogens is
associated with increases in breast and vaginal tumors in humans as well as uterine tumors
in animals. Synthetic halogenated chemicals increase liver tumors after early
life-stage exposure. Recently, a prototypical endocrine-disrupting compound,
2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant
of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects
on the developing breast involve delayed proliferation and differentiation of the mammary
gland, as well as an elongation of the window of sensitivity to potential carcinogens.
Implications of these new findings suggest that causes of endocrine-related cancers or
susceptibility to cancer may be a result of developmental exposures rather than exposures
existing at or near the time of tumor detection. Key words: animal models,
atrazine, carcinogenesis, childhood cancers, development, dioxin, endocrine disrupters.
In February 1997, the International Agency for Cancer Research
confirmed 2,3,7,8 TCDD Dioxin as a Class 1 carcinogen. A 1996 study by the
National Research Council estimates dioxin to be 300,000 times more carcinogenic than DDT.
Many cancers are associated with these organochlorines, especially soft tissue and
hormone-related cancers. A 1999 German study concluded that dioxin may be
responsible for 12% of all human cancers in industrialized countries.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits growth factor withdrawal-induced
apoptosis in the human mammary epithelial cell linDavis JW 2nd, Melendez K, Salas VM,
Lauer FT, Burchiel SW. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits growth factor
withdrawal-induced apoptosis in the human mammary epithelial cell line, MCF-10A.
Carcinogenesis 2000 May;21(5):881-6 Toxicology Program, The University of New Mexico
College of Pharmacy, Albuquerque, NM 87131
Death comes to Midland?
While corporations crank up the PR and politicians ponder and labor over
their next steps, and
we fight our daily environmental battles, we often forget that real people with
families and children
are the victims of the chemical trespass we are all forced to live in. My hope
is that Dave will continue
to share these stories with all of us. Dave Linhardt is author of
Michelle Hurd Riddick
Lone Tree Council
Dow's mortality studies provide ample evidence that employee death rates from
certain cancers are elevated,
some being statistically significant. Due to a lack of data, we do not know if a
similar increase in mortality
has been experienced by persons living in Midland and riverside
neighborhoods which have high levels of
Statistics have definite value but they do not provide any information about
the persons that died prematurely
or the pain and loss suffered by their family and friends. In fact, "medical
privacy" laws prohibit the release of
personal information. Perhaps, if a name and a history was associated with each
premature death, the long
overdue correct action would have been already implemented.
In the spring, I placed an ad in the Midland Daily News requesting contact
with anyone that believes his/her
illness or a death is related to dioxin exposure. The response was far
greater than expected.
From time to time, I would like to share what I know about a person whose
death may have been related
to dioxin exposure and whose death came too early.
Study finds dioxin increases liver tumors and lung metaplasia
Epidemiological studies indicated that people exposed to dioxins were
prone to the development of lung diseases including lung cancer. Animal
studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
increased liver tumors and promoted lung metaplasia in females.
WHAT ABOUT DISRUPTION OF
THE ENDOCRINE SYSTEM?
Disruption of endocrine function (the bodies chemical messenger system)
appears to occur at body levels approximately 100 times lower than those associated with
cancer. International peer-approved research demonstrates that dioxin-like compounds
can have transgenerational effects in wildlife and humans. Included are:
reproductive illnesses such as endometriosis, fertility problems and impotence; birth
defects; developmental and immune system disorders and more.
to visit an excellent web site devoted to the topic of Hormone
The development and functioning of the human -
and animal - body depends on a complex interaction of chemicals, in
which everything must happen at the right time.
Three crucial parts of the human body are the
immune system, the hormonal system and the nervous system. It is easy to
detect abnormalities in many other parts of the body - if you break your
leg, or are bleeding, it is pretty obvious. Detecting changes in these
systems is far harder. This is one of the reasons that providing proof
of harm to any of these systems is difficult, unless the harm is very
substantial - e.g. the damage to the immune system due to HIV. These
three systems also affect each other, particularly during the
development of the body.
Many of the interactions within and between these
systems depend on fairly simple chemicals - all potential targets for
imitation by man - made chemicals. The pharmaceutical industry
deliberately produces chemicals that affect these systems - the chemical
industry does it accidentally - Every chemical is potentially a
New research shows that the environment is more important to health than
anyone had imagined. Recent information indicates that toxic effects on
health can be inherited by children and grandchildren even when there
are no genetic mutations involved. These inherited changes are caused by
subtle chemical influences, and this new field of scientific inquiry is
called "epigenetics." RACHEL'S ENVIRONMENT & HEALTH NEWS #819, June
Click here for 9 articles about epigenetics from the Wall Street
Journal, New York Times, New Scientist, Washington State
University News Service, Forbes, Times Magazine, and the Seattle Post -
Excerpt from Skinner Study:
"The transient exposure of a pregnant female at the time of embryonic
sex determination to an environmental toxin (endocrine disruptor) can
induce an epigenetic transgenerational disease phenotype in all
subsequent generations. This has a significant impact on our
understanding of factors that influence human disease and the basic
concepts of evolutionary biology." Matthew D. Anway, Andrea S. Cupp,
Mehmet Uzumcu, and Michael K. Skinner, Science 3 June 2005; 308:
1466-1469 [DOI: 10.1126/science.1108190
years later, study finds Serveso babies 6x likely to suffer thyroid
As the authors conclude, these findings suggest that maternal exposure to
dioxins such as TCCD in the environment produces damaging effects on the
thyroid function of their babies "far apart in time from the initial
Long-lasting effects of the Seveso disaster on thyroid function in babies
Three decades after an accident at a chemical factory in Seveso, Italy
in 1976, which resulted in exposure of a residential population to the
most dangerous type of dioxin, newborn babies born to mothers living in
the contaminated area at the time of the accident are over six times
more likely to have altered thyroid function than those born to mothers
in a non-contaminated area. The study finding these results is published
in the open access journal PLoS Medicine this week by Andrea
Baccarelli (of the University of Milan) and colleagues from the United
States and Italy.
High dioxin levels linked to reduced thyroid hormone FT4 ?
Chronic exposure to dioxin-like compounds and thyroid function among
New York anglers.
Experimental studies suggest that dioxin-like compounds influence
although human studies have presented equivocal results. Great Lakes
sportfish consumers represent a population with greater potential for
exposure to dioxin-like compounds than non-consumers. Thirty-eight licensed
anglers participating in a dioxin exposure study, consumers and
non-consumers, conducted as part of the New York Angler Cohort Study,
donated blood and completed questionnaires regarding demographic, clinical,
and sportfish consumption data. ....
The results of this study are preliminary but suggest an inverse
association between dioxin-like compounds and fT4.
Source: Bloom, M., Vena, J., Olson, J., Moysich, K., 2006. Chronic exposure
to dioxin-like compounds and thyroid function among New York anglers.
Environ. Toxicol. Pharmacol. 21: 260-267.
Large Effects from Small Exposures. I. Mechanisms for Endocrine-Disrupting
with Estrogenic Activity.
Information concerning the fundamental mechanisms of action of both natural and
environmental hormones, combined with information concerning endogenous hormone
concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity
(EEDCs) can be active at concentrations far below those currently being tested in
toxicological studies. Using only very high doses in toxicological studies of EEDCs thus
can dramatically underestimate bioactivity. Specifically: a) The hormonal action
mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose
ranges of biological activity, which have been missed by traditional toxicological
testing. b) Toxicology assumes that it is valid to extrapolate linearly from high
doses over a very wide dose range to predict responses at doses within the physiological
range of receptor occupancy for an EEDC; however, because receptor-mediated responses
saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses
can first increase and then decrease as dose increases, contradicting the assumption that
dose-response relationships are monotonic. d) Exogenous estrogens modulate a system
thatis physiologically active and thus is already above threshold, contradicting the
traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These
four fundamental issues are problematic for risk assessment methods used by regulatory
agencies, because they challenge the traditional use of extrapolation from high-dose
testing to predict responses at the much lower environmentally relevant doses. These doses
are within the range of current exposures to numerous chemicals in wildlife and humans.
These problems are exacerbated by the fact that the type of positive and negative controls
appropriate to the study of endocrine responses are not part of traditional toxicological
testing and are frequently omitted, or when present, have been misinterpreted. Key
words: dose response, endocrine disruptors, estrogen action, estrogen receptors, fetal
development, inverted U, MCF-7 cells. Environ Health Perspect 111:994-1006 (2003).
doi:10.1289/ehp.5494 available via http://dx.doi.org/[Online 2 February 2003] .
Wade V. Welshons,1 Kristina A. Thayer,2
Barbara M. Judy,1 Julia A. Taylor,1 Edward M. Curran,1
and Frederick S. vom Saal2
Dioxin body burden significantly affects
This is the first report on the
association of human body burdens of PCDDs/PCDFs and PCBs with estrogen
metabolites. The information presented is crucial to understand their
hormonally related health effects in women, such as the risk for breast
Dioxins (PCDDs), furans (PCDFs), and biphenyls (PCBs) are environmental
endocrine disruptors that have half-lives of 7–10 years in the human body
and have toxicities that probably include carcinogenesis. ... In this
cohort study of maternal–fetal pairs, we examined the relationship of PCDD/PCDF
and PCB exposure to levels of estrogen metabolites in the sera of 50
pregnant women 25–34 years of age from central Taiwan. ... We measured 17
dioxin congeners, 12 dioxin-like PCBs, and 6 indicator PCBs in placenta ...
Altered estrogen catabolism might be associated with body burdens of PCDDs/PCDFs.
Our study suggests that exposure to PCDDs/PCDFs significantly affects
estrogen metabolism. Therefore, PCDD/PCDF exposure must be considered when
using the OH-E2 ratio as a breast cancer marker.
Dioxin Exposure, from Infancy through Puberty, Produces
and Affects Human Semen Quality
This study on men from Seveso published in January 2008
of a permanent disruptive effect of TCDD on the human male reproductive
depending on the age at exposure.
TCDD in infancy reduces sperm concentration and motility, and an
opposite effect is seen with exposure during puberty. Exposure in either
period leads to
permanent reduction of estradiol and increased FSH. These effects are
occur at TCDD concentrations < 68 ppt, which is within one order of
magnitude of those
in the industrialized world in the 1970s and 1980s and may be responsible at
least in part
for the reported decrease in sperm quality, especially in younger men.
Paolo Mocarelli,1,2 Pier Mario Gerthoux,1 Donald G.
Patterson Jr.,3 Silvano Milani,4 Giuseppe Limonta,1 Maria Bertona,1 Stefano
1 Pierluigi Tramacere,1 Laura Colombo,1 Carla Crespi,1 Paolo Brambilla,1
Cecilia Sarto,1 Vittorio Carreri,5 Eric J. Sampson,3 Wayman E. Turner,3
and Larry L. Needham3
Department of Laboratory Medicine, Hospital of Desio, Milano, Italy;
2School of Medicine, University Milano- Bicocca, Milano, Italy; 3National
Center for Environmental Health, Centers for Disease Control and
Prevention, Atlanta, Georgia, USA; 4Institute of Medical Statistics and
Biometrics, University of Milano, Milano, Italy; 5Department for Preventive
Medicine, Ministry of Health of Regione Lombardia, Milano, Italy
It is a question posed by a new 2007 study that has found the proportion of
boys born over
the past three decades has unexpectedly dropped in both the
United States and Japan. I
n all, more than a quarter of a million boys are
missing, compared to what would have been
expected had the sex ratio
existing in 1970 remained unchanged.
The study also says the world's most skewed sex ratio is in Canada, in a
surrounded by petrochemical plants in Sarnia, Ont., where
the number of boys born has
plunged since the mid-1990s at a rate never
THE RESPIRATORY SYSTEM
Respiratory disease in relation to patient residence near to hazardous waste
Kudyakov, R., Baibergenova, A., Zdeb, M., Carpenter,
D., 2004. Environ. Toxicol. Pharmacol. 18: 249-257
Abstract We have examined rates of hospitalization for respiratory diseases in relation
to residences in zip codes with hazardous waste sites, as well as socio-economic
status. Chronic bronchitis and chronic airway obstruction were elevated in
persons who live in zip codes containing persistent organic pollutants (POPs)
(PCBs and persistent pesticides) as compared to "clean" zip codes without
hazardous waste sites or zip codes with hazardous waste sites containing other
kinds of wastes, but the differences could be due to socio-economic status and
behavioral risk factors since these are also important risk factors for
respiratory diseases. Therefore, we investigated rates of hospitalization for
individuals living in zip codes along the Hudson River, because here the average
per capita income is higher than in the rest of the state, and there is less
smoking, better diet and more exercise. We found a similar elevation of chronic
bronchitis and chronic airway obstruction along the Hudson.
These observations are consistent with the possibility that living near a POPs-contaminated
site poses a risk of exposure and increased risk of chronic respiratory disease,
probably secondary to suppression of the immune system.
One of the primary toxic effects of dioxin in laboratory animals is immune suppression,
which results in decreased resistance to infectious agents and some cancers. The mechanisms and relationship between altered host resistance and immune
dysfunction is complex, poorly defined, but extremely important to understanding health
effects. NIEHS researchers are examining the mechanisms of immune suppression. Other
studies are examining alterations in immune cell function in several human populations
exposed to dioxin at both high levels and at low levels similar to that seen in the
general US population.
dioxin does to our immune system. The immune system is a complex set of
specialized cells and organs that defends the body against attack. When it functions
properly, the immune system fights off diseases caused by bacteria, viruses, fungi,
parasites and cancer cells. "When it malfunctions, however, it can unleash a torrent
of diseases, from allergy to arthritis to cancer to AIDS", according to the US
National Institutes of Health (NIH).
A study by scientists at Johns Hopkins University concludes that
at least ten million Americans are affected by one of 80 known autoimmune diseases
conditions such as type 1 (insulin-dependent) diabetes, lupus, multiple sclerosis and even
Takayasu's arteritis, which attacks the aorta and its branches. These conditions result
when a person's immune system mounts an attack against one's own tissues.
Immunotoxic effects that result from prenatal exposure to environmental
chemicals may be more dramatic or persistent than those from exposure during adult life.
For example, prenatal exposure to the insecticide chlordane, or the aromatic hydrocarbon
benzopyrene, produces what appears to be lifelong immunosuppression in mice. Furthermore,
when mice genetically predisposed to develop autoimmune disease were treated with the
environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) before birth, their postnatal
autoimmunity was increased.
Dioxin affects ability to fight Flu infections
Hogaboam, J, A Moore and BP Lawrence. 2008. The aryl hydrocarbon receptor affects distinct tissue
compartments during ontogeny of the immune system. Toxicological Sciences 102(1):160-170.
Researchers find for the first time that mice exposed to the contaminant
dioxin during development or while nursing have a diminished capacity to
fight a flu infection later in life. Mouse pups born to pregnant mice that
were exposed to a small amount of the ubiquitous and persistent pollutants
had fewer white blood cells that normally kill the flu virus and more of a
different kind that increases lung inflammation. The increased inflammation
can make the disease more severe and recovery more difficult. ...
This study looked at the long term immune effects of dioxin when exposure
occurs during development. The authors tried to identify the critical
windows of exposure where fetuses are most sensitive to dioxin's harmful
The number of specialized white blood cells -- referred to as CD8+
T-cells specifically recognize and kill the flu virus, were significantly
reduced in the pups but not their moms, who had been exposed to dioxin. ...
Dioxin exposure in the womb, and/or during nursing, impacts the
development of the immune system in mouse pups. Ultimately, the immune
system of the pups is permanently changed such that their response to an
infection later in life is seriously impaired. These results demonstrate the
importance of the critical windows of exposure for dioxin induced immune
suppression: there are periods in life where individuals are especially
sensitive to exposure to harmful chemicals potentially resulting in
Immune system toxins
In 1987, about 45% of Americans were living with one or more
chronic conditions (a term that includes chronic diseases and
impairments). In 1935, the proportion was 22%, so chronic
conditions have approximately doubled during the last 60 years.
The majority of people with chronic conditions are not disabled,
nor are they elderly. In fact, one out of every four children in
the U.S. (25%) now lives with a chronic condition.
Dioxins and PCBs are carcinogenic and powerfully immunotoxic in many animals, including humans.
Strength of Evidence in
Epidemiologic Studies Based on material presented in the papers and reports reviewed
here, as well as the cumulative findings of research reviewed in Veterans and Agent
Orange (1994), Veterans and Agent Orange: Update 1996, and Veterans and
Agent Orange:Update 1998, the committee finds that there is limited/suggestive
evidence of an association between exposure to the herbicides used in Vietnam or the
contaminant dioxinand Type 2 diabetes. No one paper or study was determinative in
reaching this decision. Instead, the committee found that the information accumulated over
years of research now meets the definition established for limited/suggestive
evidencethat is, evidence is suggestive of an association between herbicides and
the outcome, but limited because chance, bias, and confounding could not be ruled out with
June 2003: Dioxin Linked To Diabetes
The Department of Veterans Affairs (VA) has proposed adding type 2 diabetes
to the list of diseases positively associated with exposure to Agent Orange
and other herbicides used in Vietnam during the war. Dioxin is found in
Agent Orange and other similar herbicides. If approved by the VA, veterans
who served in Vietnam who develop adult-onset diabetes will be able to file
claims for compensation without having to prove that their diabetes was
specifically caused by exposure to herbicides sprayed in Vietnam. The
proposal follows a review by the Institute of Medicine of the National
Academy of Sciences that evaluated mounting evidence supporting the
possibility of a link between Agent Orange/dioxin and type 2 diabetes. The
review found new "limited or suggestive" evidence of an association, though
this evidence was not conclusive. For more information see Veterans and
Agent Orange: Herbicide/Dioxin Exposure and Diabetes, available from the
National Academy Press, Washington, DC for $18. Call 202-334- 3313 or
Diabetes is increasing The finding
that an endocrine-disrupting chemical like dioxin may be able to promote diabetes opens up
new avenues for thought about this rapidly-increasing disease. Perhaps it isn't fat itself
that causes diabetes --perhaps it is the toxic chemicals stored in our fat that cause
disease. It has been known for a long time that human fat accumulates toxic chemicals. For
example, the U.S. Public Health Service has been collecting samples of fat from humans for
20 years and analyzing them for halogenated hydrocarbons, including dioxin,
beta-hexachlorocyclohexane, heptachlor, DDT, DDD, DDE, PCBs, trichloroethylene,
perchloroethylene, 2,4-D, methyl chloride, vinyl chloride, polyvinyl chloride (PVC), and
chloroform, among others. We each carry literally hundreds of exotic toxic chemicals in
our body fat. For any particular chemical, our fat often has a concentration 100 times as
high as the concentration in our blood serum. It is also known that chemicals can be
released from fat to re-circulate in the blood stream during times of pregnancy, stress,
illness or fasting. Many fat-stored organohalogens are known to interfere with our
endocrine systems by mimicking or blocking natural hormones.
Cranmer M, Louie S, Kennedy RH, Kern PA, Fonseca VA. Exposure to
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin
resistance. Toxicol Sci 2000 Aug;56(2):431-6. The Department of Pharmacology and
Toxicology, the University of Arkansas for Medical Sciences, Little Rock, USA.
DIOXIN and ENDOMETRIOSIS
New 2005 study: 1st epidemiological evidence of dioxin body burden &
endometriosis in humans
The results provide the first epidemiological
evidence of an association between increased PCDD/PCDF and PCB body
burden and endometriosis.
Fertil Steril. 2005 Aug;84(2):305-12.
Heilier JF, Nackers F, Verougstraete V, Tonglet R, Lison D, Donnez J.
Industrial Toxicology and Occupational Medicine Unit, Universite
Catholique de Louvain, Brussels, Belgium.
investigate the possible association between the body burden of
dioxin-like compounds and endometriotic disease.
SETTING: Gynecology ward
in a university hospital.
women with peritoneal endometriosis (n = 25) or deep endometriotic (adenomyotic)
nodules (n = 25) and controls (n = 21).
INTERVENTION(S): Collection of
200 mL of blood (fasted) and face-to-face interview.
MAIN OUTCOME MEASURE(S):
Assessment of dioxin (PCDD), furan (PCDF), and dioxin-like PCB serum
concentrations (picograms toxic equivalent [TEQ]/g lipids).
RESULT(S): Age and body
mass index were traced by linear multiple regression as determinants of
total TEQ levels. After standardization for these variables (30 years
and 22.5 kg/m2), the mean TEQ levels were 24.21 (controls), 30.62
(peritoneal endometriosis), and 37.60 (deep endometriotic [adenomyotic]
nodules) pg TEQ/g lipids. Logistic regressionanalysis indicated a
significantly increased risk of deep endometriotic (adenomyotic) nodules
(odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-7.6) for an
increment of 10 pg in total TEQ levels/g lipids. An increased risk was
also found for peritoneal endometriosis (OR, 1.9; 95% CI, 0.9-3.8) for
total TEQ levels and for dioxins alone (OR, 3.2; 95% CI, 1.0-9.9).
CONCLUSION(S): The results provide the first
epidemiological evidence of an association between increased PCDD/PCDF
and PCB body burden and endometriosis.
Endometriosis is a disease in which tissue similar
to the lining of the uterus, the endometrium, implants and grows outside of the uterus,
often in the abdominal cavity, frequently causing pain, infertility, pain with sex, and
bowel or bladder problems. Endometriosis requires involvement of hormones and immune
system malfunction in order to develop, and is associated with increased risk of other
immune system disorders and certain cancers. Although genetic factors may contribute to
the risk of endometriosis in some women, human and animal studies indicate a potentially
important role for environmental factors as well, including exposure to dioxins, furans,
PCBs, chemicals that mimic estrogen, and radiation. It is important to consider that
combinations of chemical and radiation exposures may add up to increase the risk more than
would be expected from any one alone. Ted Schettler, MD, Science Director and Chair, Science Work Group, CHE Science and Environmental Health Network
Increased levels of polychlorobiphenyls
in Italian women with endometriosis.
NOTE: SOME PCB'S ARE
DIOXIN-LIKE IN THEIR TOXICITY
The results obtained clearly
show an increase of PCB congeners most abundant in human tissues in
women with endometriosis.
Porpora, M., Igelido, A., de
Dominico, A., Ferro, A., Crobu, M., Pallante, D., Cardelli, M., Cosmi,
E., De Felip, E., 2006. Chemosphere. In Press.
Abstract Endometriosis has been hypothesised to be linked to persistent
and toxic organochlorinated chemicals. Dioxins and dioxin-like compounds
have in particular been associated with the disease, mainly on the basis
of experimental studies. Data in women are conflicting. A case-control
study on 80 Italian nulliparous women of reproductive age was carried
out to assess whether there is a correlation between the presence of
endometriosis and blood levels of polychlorobiphenyls (PCBs), a family
of ubiquitary environmental pollutants which comprises congeners with
dioxin-like activity. Higher levels of PCBs were found in women with
endometriosis. A mean cumulative value of 410 ng g -1, lipid base, was
found in cases versus the value of 250 ng g- 1 observed in the control
group (odds ratio for upper tertile 4.0, CI 95% 1.3-13; p = 0.0003). PCB
increase involved both dioxin-like (PCBs 105, 118, 156, and 167) and
non-dioxin-like congeners (PCBs 101, 138, 153, 170, 180). Š The results
obtained clearly show an increase of PCB congeners most abundant in
human tissues in women with endometriosis. The interpretation of these
results is made particularly difficult by the fact that the observed
increase involves congeners of both dioxin-like and non-dioxin-like
type, this making necessary to considerate the broad range of different
and not fully elucidated mechanisms of action pertinent to both groups
of congeners. Further studies are ongoing aimed to understand the
complex network of factors and the mechanisms that may be thought to be
responsible of the association we observed, with a particular attention
to polymorphism in genes encoding enzymes involved in PCB detoxification
Effect of dioxins on regulation of tyrosine hydroxylase gene
expression by aryl hydrocarbon receptor: a neurotoxicology study
Dioxins and related compounds are suspected of causing neurological
disruption. Epidemiological studies indicated that exposure to these
compounds caused neurodevelopmental disturbances such as learning
disability and attention deficit hyperactivity disorder, which are
thought to be closely related to dopaminergic dysfunction.
Although the molecular mechanism of their actions has not been fully
investigated, a major participant in the process is aryl hydrocarbon
receptor (AhR). This study focused on the effect of 2, 3, 7,
8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the regulation of TH, a
rate-limiting enzyme of dopamine synthesis, gene expression by AhR.
Methods: N2a-R beta cells were established by transfecting murine
neuroblastoma Neuro2a with the rat AhR cDNA.
TH expression induced by TCDD was assessed by RT-PCR and Western
blotting. Participation of AhR in TCDD-induced TH gene expression was
confirmed by suppressing AhR expression using the siRNA method.
Catecholamines including dopamine were measured by high-performance
liquid chromatography. A reporter gene assay was used to identify
regulatory motifs in the promoter region of TH gene.
Binding of AhR with the regulatory motif was confirmed by an
electrophoretic mobility shift assay (EMSA).
Results: Induction of TH by TCDD through AhR activation was detected at
mRNA and protein levels. Induced TH protein was functional and its
expression increased dopamine synthesis.
The reporter gene assay and EMSA indicated that AhR directly regulated
TH gene expression. Regulatory sequence called aryl hydrocarbon receptor
responsive element (AHRE-) was identified upstream of the TH gene from
285 bp to 167 bp.
Under TCDD exposure, an AhR complex was bound to AHRE-as well as the
xenobiotic response element (XRE), though AHRE-was not identical to XRE,
the conventional AhR-binding motif.
Conclusions: Our results suggest TCDD directly regulate the dopamine
system by TH gene transactivation via an AhR- AHRE--mediated pathway.
The AhR- mediated pathway could have a particular AhR-mediated genomic
control pathway transmitting the effects of TCDD action to target cells
in the development of dopaminergic disabilities.
WHAT ARE THE BIOLOGICAL
MECHANISMS OF DIOXIN'S TOXICITY?
The way in which dioxin affects cells is similar in some way to the
way in which hormones such as estrogen work. Dioxin enters a cell and binds to a protein
present in cells known as the Ah receptor. The receptor when bound to dioxin can then bind
to DNA and alter the expression of some genes. This can lead to alterations in the level
of specific proteins and enzymes in the cell. While it is not known exactly how changes in
the levels of these different proteins cause the toxicity of dioxin, it is believed by
most scientists that the initial binding of dioxin the Ah receptor is the first step.
The highly toxic group of dioxins and dioxin-like chemicals (also called
ligands) enter the cell and bind to a protein in the cytoplasm called Ah receptor (AhR).
This ligand-AhR complex, after further exchange of some smaller proteins (e.g., AhR
translocator, ARNT) to become 'transformed', enters the nucleus to bind to a specific
'dioxin receptor element' (or enhancer) (DRE) of DNA. This DNA interaction occurs
'upstream' of genes which then are activated to produce certain enzymes, some of which are
highly correlated with the subsequent toxicity events.
ARE SOME PEOPLE AT EVEN HIGHER RISK?
Scientists are most concerned about exposures to fetuses, nursing infants
and children, due to the delicate balance in the developing body. Children in the
U.S. are believed to receive up to 12% of their lifetime exposure to dioxin in their first
year of life. People of color suffer disproportionate exposure to these chemicals,
as do others who live or work near incinerators, paper mills, chemical plants and toxic
Dioxin Levels In Food Are NOT Going Down
A newly published report shows that the amount of dioxin in food has
remained at the same dangerous level it was more than a decade ago. This
finding directly contradicts the assurances of the U.S. EPA that dioxin
levels in food are not a public health concern because dioxin levels in food
are down from what they were a few years ago. The EPA's strategy of not
having to reduce levels in meat and dairy, the primary sources of dioxin in
food, now needs to be re-evaluated. See "Schecter, A., et al., "Intake of
dioxins and related compounds from food in the U.S. population," Journal of
Toxicology and Environmental Health, Part A, 63: 101-118, 2001.
..for any particular community, understanding the potential health threats that could
result from toxic releases is a nearly impossible task. Public health officials often lack
sufficient understanding of how citizens have been exposed to toxic substances, how those
substances work within the body, and how many people have contracted chronic disease
within a community to render conclusive judgments as to whether particular toxic exposures
have ledor can leadto increases in disease" The above is an excerpt of a report mentioned in a 1/22/02 USPIRG
Press Release. The report (a very large PDF file), is titled "Toxic Releases and
Health: A Review of Pollution Data and Current Knowledge on the Health Effects of Toxic
Chemicals". A section specific to dioxin starts on page 25.
The EPA and WHO (World Health Organization) have been investigating Dioxin for years.
DRAFT Reassessment of Dioxin April 2002 (pdf). Interesting comparisons
between EPA and WHO findings can be found starting on page 43. The EPA's final
report is due out late 2002 or early 2003. Note that most of document focuses on
exposures to the "general population" via the food chain. Citizens living
in highly contaminated Tittabawassee flood plain probably have a much higher exposure.
The point is, we are expected to sit in the middle of the most dioxin contaminated
land found in Michigan until they figure it out.
Body Burden studies indicate dioxin/furan pollution maybe present in almost
EVERYONE. Low dose exposure produces health problems. See Body Burden: The Pollution in People (very
large pdf file)
Division of Environmental Health and Occupational Medicine, National
Health Research Institute, 35 Keyan Road, Zhunan Town, Miaoli County
350, Taiwan Institute of Occupational Safety and Health, Kaohsiung
Medical University, Kaohsiung, Taiwan Department of Environmental and
Occupational Health, College of Medicine, National Cheng Kung
University, 138 Sheng-Li Road, Tainai 704, Taiwan
Received 24 September 2005; revised 11 February 2006; accepted 13
February 2006. Available online 4 April 2006.
A large pentachlorophenol (PCP)-manufacturing plant located in
southwestern Taiwan operated between 1965 and 1982. The present study
was conducted to ascertain whether an increased body burden of dioxins
existed in pregnant women living in an area of Tainan city contaminated
by chemicals from this plant. Twenty-eight pregnant subjects, 21ö39
years of age and residing in the study area between March and December
of 2004 with a mean dwelling time of 6.07 ± 6.11 years, were recruited.
Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs),
and dioxin-like polychlorinated biphenyls (PCBs) in serum of recruited
residents were determined. Pregnant women residing in the study area >3
years had significantly higher PCDD (7.48 versus 5.13 pg-toxic
equivalents [TEQ]/g-lipid) and dioxin-like PCB (6.70 versus 3.74 pg-TEQ/g-lipid)
values as compared to those residing 3 years. Furthermore, dioxin
concentrations increased with increasing dwelling time. Statistical
analyses performed according to demographic characteristics and
socioeconomic and dietary habits revealed that total TEQ values were
significantly associated with fish consumption and smoking status.
Dioxin congeners with greater degrees of chlorine substitution (e.g.,
HpCDD/F and OCDD/F) partitioned to greater degrees in the subjects of
this study as compared to subjects in the general Taiwanese population.
The findings of this study strongly implicate the activity of the PCP
manufacturing plant in the observed increase in dioxin body burden.
Investigation of the health consequences of this increased body burden
The most clearly established health effect of dioxin in humans is a skin eruption called
The Seveso incident in 1976 contaminated the vicinity with dioxin and caused many cases of
Viktor Yushchenko (Before and After dioxin poisoning )
In 1996 the Environmental Protection Agency (EPA) relocated some
members of the Pensacola community in Florida whose dioxin soil levels reached or exceeded
200 ppt TEQ.
In the spring of 2002, the MDEQ took 36 samples from downriver
areas lying withinthe Tittabawassee River floodplain. The sampling in Phase 1 found dioxin levels ranging from 35 ppt to
7,261 pptTEQ, with anaverage
level of 998 ppt. That summer, Phase 2, with over 150 samples,
averaged 799 ppt with a max of 3,400 ppt in
soils downstream of Dow and actually in the floodplain. A floodplain residents yard
averaged 529 ppt with a high of 1,400 ppt. Eggs from
freerange chickens on this residents property had dioxin levels of 16 - 48 ppt
in each egg! According to the Michigan Department of Community Health, the EPA
draft dioxin reassessment reportwill require MDEQ to revise its
residential direct contact criteria for dioxin downward, not upward, from
90 ppt to somewhere between 12 and 53 ppt.
"At higher risk of exposure to dioxin are children, nursing
infants, some workers and farmers, people who eat fish as a main staple of their diet such
as some indigenous peoples and fishermen, and people who live near dioxin
release sites. These groups of people are likely exposed to at least 10 times as much
dioxin as the general population. "