21 février, 2007 17:41

Body Burden — The Pollution in Newborns

Chemicals and pollutants detected in human umbilical cord blood

Babies are vulnerable to chemical harm

Parents know intuitively that babies in the womb are more vulnerable to the effects of industrial chemicals than adults. A pregnant woman may avoid using hair dye and nail polish, pumping gas, or painting the nursery, for example, to protect her baby. This intuition is backed by science that has unfolded primarily over the past two decades. In 1993 the National Academy of Sciences enumerated, in a Congressionally mandated study, the primary factors that contribute to children's unique vulnerability to the harmful effects of chemicals (NAS 1993):

• A developing child's chemical exposures are greater pound-for-pound than those of adults.
• An immature, porous blood-brain barrier allows greater chemical exposures to the developing brain.
• Children have lower levels of some chemical-binding proteins, allowing more of a chemical to reach "target organs."
• A baby's organs and systems are rapidly developing, and thus are often more vulnerable to damage from chemical exposure.
• Systems that 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.

The pace and complexity of growth and development in the womb are unmatched later in life. Three weeks after conception, an embryo, still only 1/100th the size of a water droplet, has nevertheless grown at such an explosive rate that were it not to slow down, it would be born literally the size of a million Earths. Over the next five weeks the baby constructs the beginnings of elbows, knees, eyelids, nipples, hair follicles on chin and upper lip, external genitals, primitive internal organs, a four-chambered heart, working fingers and toes, and even a footprint (Greene 2004). At no other time in life does a person create so much from so little in so short a time. Industrial chemicals that interrupt this intricate process can, at high levels, wreak havoc in the form of severe birth defects, or at lower levels cause subtle but important changes in development that surface later in childhood as learning or behavioral problems, or in adulthood in the form of certain cancers or perhaps neurodegenerative disease.

A recent review by government scientists of the "critical windows" of vulnerability reveals an urgent need for public health policies that recognize childhood sensitivity (Selevan et al. 2000). Many of these windows of vulnerability are found in the early months of human pregnancies, when cells are multiplying and differentiating into specific tissues and organs. Exposures during these times can lead to permanent damage. But a child's vulnerability continues long beyond early pregnancy: the central nervous system, immune, reproductive and endocrine systems, for example, continue to mature even after birth (NAS 1993, Makri et al. 2004). As a whole, these windows facilitate more pronounced risks and effects for chemical exposures in childhood than adulthood. For example, a mother's exposure to dioxins, mercury, or certain pesticides during pregnancy could measurably harm her baby, while affecting her own health perhaps not at all.

In a decades-long mercury poisoning disaster in Minamata, Japan that began in the 1950s, some babies born to women who ate mercury-polluted seafood died within days of birth, while their mothers were free of symptoms. Autopsies revealed that in adults, mercury induced lesions that were concentrated in a few areas of the brain. In the fetus, however, mercury spawned lesions over nearly the entire brain cortex.

In the decades following Minamata, scientists have developed a much fuller understanding of children's vulnerability to chemicals, discovering links between a host of health problems — including asthma, childhood cancer, and brain damage — and such common contaminants as solvents, pesticides, PCBs, and lead (Trasande and Landrigan, 2004). A recent National Academy of Sciences study suggests that environmental factors contribute to at least 28 percent of childhood developmental disabilities (NAS 2000a).

The latest research investigates not only relationships between disease and exposures, but the root causes of chemically-induced disease with in utero origins. This research pinpoints traits of a fetus that contribute to vulnerability: low levels of some chemical-binding proteins in the blood, immature excretion pathways, and an immature blood brain barrier, for instance, which combine to increase the transfer of chemicals from the blood to the aptly named "target organs" that may ultimately bear the harm.

The risks to a baby derive not only from his or her physical makeup, but also from the very behaviors and events that prepare the baby for life outside the womb. Beginning in the fifth month of pregnancy, babies regularly swallow and breathe, building muscles essential for survival after birth. Through these actions, the lungs and the gut are filled, again and again, with the same amniotic fluid that collects the baby's urine. Pollutants like plasticizers and pesticides excreted in urine accumulate in this fluid and are cycled right back into the baby's body through the mouth and nose. And in the third trimester the mother's body dissolves stored, maternal fat, shunting it to the baby through the blood, but with this fat the child also receives the persistent pollutants clinging to it, like PCB's, flame retardants, and dioxins. Faced with such diverse exposures and armed with a body ill-equipped to rid itself of chemicals, it is small wonder that a developing baby so often proves vulnerable to chemical exposures (Makri et al. 2004).

Some studies are beginning to measure the sensitivity of a child relative to an adult for suffering impacts from chemical exposures. For instance, studies of mutagens called polyaromatic hydrocarbons (PAHs) — target chemicals examined in this study and waste products from burning gasoline and garbage — found that even though levels of PAHs are thought to be lower in the fetus than the mother (Srivastava et al. 1986), the fetus bears more cancer-inducing DNA damage from the exposures (Whyatt et al. 2001).

But health and environmental officials have been slow to act on the wealth of studies on childhood vulnerability produced in the past 20 years. After nearly a decade of review, the Environmental Protection Agency updated its cancer risk guidelines in 2003 to explicitly acknowledge the importance of childhood exposures. The agency concluded, after a review of 23 studies of early life exposures to cancer-causing chemicals, that carcinogens average 10 times the potency for babies than adults, and that some chemicals are up to 65 times more powerful (EPA 2005a).

EPA's new policy, though, targets only cancer. It leaves EPA with no formal policy regarding childrens' vulnerability to chemicals that damage the immune system, the brain, or the hormone system, kidney, liver, lungs, thyroid or a host of other potential targets, even though plenty of evidence says that children face higher risks for harm.

Human health problems on the rise

Over the past 50 years, as infectious childhood diseases like polio, smallpox, rheumatic fever, and diphtheria have largely been controlled, chronic conditions of less obvious origins have taken their place. Asthma, autism, attention deficit and hyperactivity disorders (ADD and ADHD), childhood brain cancer and acute lymphocytic leukemia have all increased over the past 30 years. Five to ten percent of American couples are infertile. Up to half of all pregnancies end in miscarriage. Three to five percent of babies are born with birth defects (CDC 2004, Jahnke et al. 2005, Trasande and Landrigan 2004). Scientists cannot fully explain these increases, but early life exposure to environmental pollutants is a leading suspect.

Fetal exposures lead to adult disease. Some chemicals are directly toxic to an exposed child — lead and mercury, for example, which harm a developing brain — while other chemicals induce a chain of events that may culminate in a diagnosed health problem later in life. Hormone-mimicing chemicals like dioxins and furans, for example, could induce delayed cancers in hormone-sensitive tissues like the breast, testicle, or prostate gland. Chemicals like PCBs or DDT can reduce growth rates in the womb, initiating in low birthweight babies lasting, internal survival mechanisms that cascade into cardiovascular disease or diabetes later in life.

The fact is, a child can bear a lifelong imprint of risks from the countless molecules of industrial pollutants that find their way through the placenta, down the umbilical cord, and into the baby's body. The consequences — health disorders, subtle or serious — can surface not only in childhood but also in adulthood. Studies now support origins in early life exposures for a startling array of adult diseases, including Alzheimers, mental disorders, heart disease, and diabetes.

Laboratory studies show increased deposits of the Alzheimer-related protein amyloid in the brains of older animals exposed to lead as newborns, but not in animals that were exposed to an equal amount of lead as adults (Basha et al. 2005). And over the past two decades numerous studies have linked low birth weight with adult onset of coronary heart disease, diabetes, stroke, hypertension, depression and other conditions (Barker 1995, Wahlbeck et al. 2001, Thompson et al. 2001, Hales et al. 1991). Low birth weight can arise not only from poor maternal nutrition but also from a host of industrial pollutants, including arsenic, mercury, lead, organic solvents, PCBs, and pesticides, including DDT.

Recent studies shed new light on how early life chemical exposures set adult disease in motion. In laboratory studies scientists from the University of Texas found that fetal exposures to the synthetic hormone (and now-banned drug) DES permanently "reprogrammed" body tissues, dramatically raising rates of uterine cancer, in this case, in later life (Cook et al. 2005). With an estimated 75,000 chemicals registered for use in the U.S., and an average of seven new chemicals approved each day, many not tested for safety and certaintly not tested for their ability to "reprogram" body tissues, the ramifications of this study are enormous.

Fetal exposures cause disease in future generations. Remarkably, it appears that early life exposures can lead to health problems not only in adulthood, but also down through subsequent generations. For instance, adult diseases linked to newborns' low birth weight, enumerated above, cause adverse effects not only in those babies born small, but also in their children of any birth size, through heritable changes in gene expression that result in a phenomenon known as "epigenetic inheritance." Very different from genetic mutations, which are physical changes in gene structure, epigenetic inheritance is instead characterized by certain genes being turned on or off, but near permanently in ways that can be inherited.

If a genetic mutation is like changing a light fixture, the comparable epigenitic change would involve taping the light switch on or off. Since genes are responsible for making the chemicals that build and repair the body, this unnatural forcing to a permanent on or off position can have far-reaching consequences. In humans, both kinds of genetic changes, mutations as well as epigenetic changes in gene expression, can be passed down to a baby in the womb.

Scientists have recently found heritable epigenetic changes linked to the fungicide vinclozolin and pesticide methoxychlor, which impaired sperm counts and sperm motility not only among animals exposed in utero, but also in three subsequent generations (Anway et al. 2005). In other words, what each of us was exposed to in our mother's womb might affect the health of our great-grandchildren.

Notably, both of these pesticides were recently banned under a federal law that requires pesticides to be safe for newborns and children. The government gives children no explicit protection under the federal law meant to ensure the safety of other commercial chemicals (the Toxic Substances Control Act), even though risks from childhood exposures to industrial chemicals are no lower than those from pesticides.

Cord blood pollutants in this study, linked to health problems. Scientific studies implicate some of the chemicals we detected in cord blood with serious, ongoing human health problems:

• Dioxin exposures during fetal development have been implicated in endocrine-related cancers in women (breast and uterine, for example) by altering hormone levels, increasing the sensitivity of children and adolescents to other carcinogens (Birnbaum and Fenton 2003). In men, tiny levels of dioxin in the range of 0.02 to 10 parts per billion alter testosterone levels and are linked with diabetes (EPA 2004a). Dioxin at 80 parts per trillion in paternal — but not maternal — serum causes a significant change in the sex ratio of children (Mocarelli, et al. 1996, Mocarelli, et al. 2000). At this tiny dose, men father nearly twice as many girls as boys. As body burdens increase within and above these ranges, the likelihood, severity, and potential spectrum of non-cancer effects increases (EPA 2004a). Fetal dioxin exposure can harm the immune system, thyroid, and brain (Van Loveren et al. 2003, Faroon et al. 2001, ten Tusscher and Koppe 2004). Dioxin from garbage incinerators is associated with increased incidence of infant death and birth defects (Tango et al. 2004).
• Methylmercury exposure in the womb causes measurable declines in brain function in children exposed to levels corresponding to 58 parts per billion in maternal blood (NAS 2000b). Researchers in the Netherlands found a doubling in the risk of heart attacks and death from coronary heart disease at methylmercury hair levels of 2 mg/kg, which corresponds to about one fifth the assumed safe maternal blood level (Salonen, et al. 1995). Increased diastolic and systolic blood pressure and decreased heart rate variability in developmentally exposed children have also been observed at doses below what the EPA considers a safe maternal blood level (NAS 2000b, Sorensen et al. 1999).
• PCBs at 9.7 ppb in maternal serum during fetal development can impair brain development, with resultant attention and IQ deficits that appear to be permanent (Jacobson and Jacobson 1996). Notably, IQ deficits are linked to the mother's PCB levels, not the PCB levels in children at 4 and 11 years of age (by which time the children's PCB levels had decreased substantially compared to levels at birth), underscoring the limitations of studies that look for correlations between current body burdens and health effects in the absence of data on in utero exposures. Levels of PCBs in the general population are also associated with abnormal menstrual cycles (Cooper et al. 2005).
• DDE above 15 ppb in maternal blood is associated with preterm birth and low birth weight, with weight corrected for gestational age (Longnecker et al. 2001). DDE is a metabolite of the banned, persistent pesticide DDT. Using the associations derived from tests of archived blood samples from a pool of 42,000 women, researchers estimated that DDT exposures in the U.S. population could have accounted for up to 15 percent of infant deaths during the 1960s. Low birth weight is recognized as a risk factor for type II diabetes, high blood pressure, and cardiovascular disease later in life (Prentice and Moore 2005, Godfrey and Barker 2001, Hales and Barker 2001). Even if these lower birth weight babies "catch up" later, the damage may have already been done. A substantial number of studies have found that low birth weight followed by an accelerated growth rate during childhood is a significant risk factor for high blood pressure, stroke, insulin resistance and glucose intolerance (Eriksson, et al. 2000a, Eriksson, et al. 2002, Eriksson et al. 2000b, Eriksson et al. 1999, Eriksson and Forsen 2002, Forsen et al. 2000, Ong and Dunger 2002, Stettler et al. 2002).

Cancer. Cancer incidence has steadily increased over the decades for many forms of the disease, including breast, prostate, and testicular (NCI 2005). The incidence of childhood cancer increased by 27.1 percent between 1975 and 2002, with the sharpest rise estimated for brain and other nervous system cancers (56.5 percent increase) and acute lymphocytic leukemia (68.7 percent increase). The incidence of testicular cancer also steadily rose 66 percent between 1975 and 2002 (NCI 2005). The probability that a U.S. resident will develop cancer at some point in his or her lifetime is 1 in 2 for men and 1 in 3 for women (ACS 2004). A broad array of environmental factors plays a pivotal role in the initiation and promotion of cancer. Just 5 to 10 percent of all cancers are directly linked to inherited, genetic factors (ACS 2001).

• Breast cancer. Among girls born today, one in seven is expected to get breast cancer and one in 30 is expected to die from it. Invasive female breast cancer increased an average of 1.5 percent per year between 1973 and 1996, for a total increase of 25.3 percent. Among those 65 and younger, breast cancer incidence rose 1.2 percent per year, corresponding to a doubling every two generations (58 years). If trends continue, the granddaughters of today's young women could face a one in four chance of developing breast cancer (NCI 1996, NCI 1997).
• Testicular cancer. At its current pace, the incidence of testicular cancer is doubling about every one and a half generations (39 years). In the U.S. the incidence of testicular cancer rose 41.5 percent between 1973 and 1996, an average of 1.8 percent per year (NCI 1996, NCI 1997). Testicular cancer is now the most common cancer in men age 15 to 35 (NCI 2005).
• Prostate cancer. Prostate cancer rates rose 4.4 percent a year between 1973 and 1992, or more than a doubling of risk in a generation. Since 1992, the incidence has declined, but it is still 2.5 times its 1973 rate. Part of this increase can be explained by better detection, but increased incidence has also been accompanied by an increase in mortality - which better detection cannot explain. Prostate cancer is now the most common cancer among U.S. men, and the second most lethal, killing an estimated 31,900 men in the year 2000 alone (NCI 1996, NCI 1997).

Major nervous system disorders. Several recent studies have determined that the reported incidence of autism is increasing, and is now almost 10 times higher than in the mid-1980's (Byrd 2002, Chakrabarti and Fombonne 2001). The number of children being diagnosed and treated for attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) has also increased dramatically in the past decade (Robison et al. 1999, Robison et al. 2002, Zito et al. 2000). The causes are largely unexplained, but environmental factors, including chemical exposures, are considered a likely contributor. Environmental factors have also been increasingly linked with Parkinson's disease (Checkoway and Nelson 1999, Engel et al. 2001).

Preterm births and low birth weights. Preterm births have increased 23 percent over the past 2 decades; low-weight births have become more common (Ananth et al 2001, Branum and Schoendorf 2002). The causes are largely unknown, but environmental factors such as chemical pollutants and nutrition are thought to play a role. Low birth weight has been linked to adult obesity, diabetes, cardiovascular disease, schizophrenia, and other conditions (Barker 1995, Wahlbeck et al. 2001, Thompson et al. 2001, Hales and Ozanne 2003). It has also been linked to lower academic performance, neurosensory impairment, and lower rates of pregnancy in the offspring (Hack et al. 2002).

Defects of the reproductive system. Studies show that sperm counts in certain parts of the world are decreasing (Swan, et al. 2000, Toppari, et al. 1996). Scientists have measured significant regional differences in sperm count that cannot be explained by differences in genetic factors (Swan et al. 2003). Girls may be reaching puberty earlier, based on comparing current appearance of breast development and pubic hair growth with historical data (Herman-Giddens, et al. 1997). Rates of hypospadias, a physical deformity of the penis, have risen in recent years (Paulozzi et al. 1997). The incidence of undescended testicles (cryptorchidism) and testicular cancer also appear to be rising in certain parts of the world (Bergstrom et al. 1996, McKiernan et al. 1999, Toppari et al. 1996, Paulozzi 1999). Several studies have suggested links between developmental exposure to environmental contaminants and cryptorchidism or testicular cancer (Hardell, et al. 2003, Hosie, et al. 2000, Toppari, et al. 1996, Weidner, et al. 1998).

• Declining sperm count. An analysis of 101 studies (1934-1996) by Dr. Shanna Swan of the University of Missouri confirms results of previous studies: average sperm counts in industrialized countries appear to be declining at a rate of about one percent each year (Swan et al. 2000).
• Hypospadias. Incidence of hypospadias, a birth defect of the penis, doubled in the United States between 1970 and 1993, and is estimated to affect one of every 125 male babies born (Paulozzi et al. 1997). Data from the Centers for Disease Control and Prevention show that rates in the U.S. began climbing in about 1970, and continued this increase through the 1980s. This condition is a physical deformity of the penis in which the opening of the urethra occurs on the bottom of the penis instead of the tip.
• Undescended testicles. This birth defect, where testicles fail to completely descend into the scrotum during pregnancy, occurs in two to five percent of full-term boys in Western countries. Rates of the defect increased greatly in the U.S. in the 1970s and 1980s. Men born with this defect are at higher risk for testicular cancer and breast cancer (Paulozzi 1999).

Together with 287 industrial pollutants in 10 newborn babies, this body of science and the litany of serious, continuing human health concerns reveals the critical need for reform of our system of public health protections, which fails to require proof that chemicals are safe for children.

Recommendations

U.S. industries manufacture and import approximately 75,000 chemicals, 3,000 of them at over a million pounds per year. Studies show that hundreds of industrial chemicals circulate in the blood of a baby in the womb, interacting in ways that are not fully understood. Many more pollutants are likely present in the womb, but test methods have yet to be developed that would allow health officials to comprehensively assess prenatal exposure to chemicals, or to ensure that these exposures are safe. From a regulatory perspective, fetal exposure to industrial chemicals is quite literally out of control.

The reason: the Toxic Substances Control Act (TSCA), the nation's notoriously weak chemical safety law. TSCA deprives the EPA of the most basic regulatory tools. The vast majority of chemicals in use today do not have anywhere near sufficient data needed to assess their safety, particularly their safety for the unborn baby or young child. Under TSCA, however, the EPA cannot require this data as a condition of continued chemical use. Instead, the EPA must negotiate with industry or complete a formal "test rule" for every study that it needs, for every chemical on the market. Consequently, very few high quality toxicity tests are conducted.

When industry submits results of voluntary testing to the agency, huge portions, including key health and safety findings, are routinely redacted as confidential business information, meaning that even state regulatory agencies are not allowed to review them. If risks are identified and action is contemplated, minimizing "unreasonable" costs to industry is the TSCA mandate, no matter how serious the risks and no matter the population that bears them — even unborn babies. And if there is any scientific uncertainty, as there often is, TSCA prohibits precautionary action and requires certainty of harm before actions can be taken to protect the public health. TSCA has not been improved for nearly 30 years — longer than any other major environmental or public health statute.

This study and a strong body of supporting science suggest that fetal exposure to industrial chemicals is contributing to adverse health effects in the human population. This is cause for concern.

But experience also shows us that it is never too late to take action. Blood levels of PCBs and pesticides like DDT are lower today than 30 years ago when they were banned. Since these watershed actions in the 1970s, however, few industrial chemicals have been regulated to any significant degree. The various reasons for this stagnation — the need for data on chemical toxicity and exposure, lack of ambition at the EPA, and chemical industry intransigence — all come back to one central cause: the absence of a strong federal chemical safety law that provides the EPA with unambiguous statutory authority to take the actions needed to ensure that chemicals are safe.

Because TSCA does not mandate safety studies and makes it difficult for EPA to demand them, a number of voluntary initiatives to gather more information about chemicals have been attempted, most notably the high production volume (HPV) chemical screening program. These efforts, however, have been largely ineffective at reducing exposure and are no substitute for a clear statutory requirement to protect children from the toxic effects of chemical exposure.

Federal law must be reformed to ensure that children are protected from chemical exposures, and that to the maximum extent possible exposure to industrial chemicals before birth be eliminated entirely. The nation's pesticide law was amended nearly a decade ago to require explicit protection of infants and children from pesticides. Actions taken under the 1996 Food Quality Protection Act (FQPA) have reduced or eliminated children's exposures to a number of highly hazardous pesticides, with no discernable adverse impact on the availability or price of a wholesome food supply, and without adverse impact on the agricultural or pesticide industry. We recommend a similar standard be applied to commercial chemicals.

This would mean transforming TSCA into a true public health and environmental law, with the following core provisions. A new TSCA would:

• Require chemical manufacturers to demonstrate affirmatively that the chemicals they sell are safe for the entire population exposed, including children in the womb. In the absence of information on the risks of pre-natal exposure, chemicals must be assumed to present greater risk to the developing baby in utero, and extra protections must be required at least as strict as the 10 fold children's safety factor in FQPA.
• Require that the safety of closely related chemicals, such as the perfluorochemicals used to make Teflon and other stain-resistant and water repellant products, be assessed as a group. The presumption would be that these chemicals have additive toxicity unless manufacturers clearly prove otherwise.
• Grant the EPA clear and unencumbered authority to demand all studies needed to make a finding of safety and to enforce clear deadlines for study completion.
• Remove from the market chemicals for which tests demonstrating safety are not conducted.
• Eliminate confidential business protection for all health, safety, and environmental information.
• Require that material safety data sheets provided to workers contain the results of studies conducted under these provisions.
• Provide strong incentives for green, safer chemicals in consumer products and industrial processes.

Detailed Findings

In a study spearheaded by the Environmental Working Group (EWG), researchers at two major laboratories found an average of 200 industrial compounds, pollutants, and other chemicals in 10 newborn babies, with a total of 287 chemicals found in the group. To our knowledge this work represents the first reported cord blood tests for 261 of the targeted chemicals, and the first reported detections of at least 209 chemicals. Scientists refer to this contamination as a person's body burden.

The study found a broad array of pollutants that collectively are known to present potential risks to nearly every organ and system in the body:

• Of the 287 chemicals found in newborn umbilical cord blood, 180 cause cancer in humans or animals, 217 are toxic to the brain and nervous system, and 208 cause developmental problems. The dangers of exposure to these chemicals in combination has never been studied.
• We detected 287 chemicals of 413 tested (69 percent) in umbilical cord blood samples from 10 newborn babies, with a range of between 154 and 231 for each child. We found 101 chemicals in all babies tested.
• Our tests targeted nine chemical classes; we detected at least half of the analyzed chemicals in each class.

The chemicals we found span organochlorine pesticides (DDT and dieldrin, for example), chemicals currently or formerly used in a wide range of consumer products (perfluorochemicals, brominated fire retardants, PCBs), and chemical pollutants from waste incineration and fossil fuel combustion (polyaromatic hydrocarbons, polychlorinated and polybrominated dioxins and furans, polychlorinated naphthalenes, mercury).

Fetal exposures to mixtures. The few published biomonitoring studies that measure fetal and newborn exposures among the general population confirm work that the pharmaceutical industry conducted more than 40 years ago establishing that the placenta is permeable not just with respect to oxygen, nutrients and fetal waste materials, but also with respect to xenobiotic chemicals. These chemicals move through the placenta via passive diffusion and, less frequently, active transport mechanisms from maternal to fetal blood (Syme et al. 2004).

The few published cord blood biomonitoring studies of the North American general population target a range of chemical classes, including polybrominated biphenyl ethers, or PBDEs (Mazdai et al. 2003); polychlorinated biphenyls, or PCBs (Stewart 1999,2000; Schecter 1998); organochlorine pesticides (Walker et al. 2003, Rhainds et al. 1999, Lagueux et al. 1999): polyaromatic hydrocarbons, or PAHs (PAH—DNA adducts were analyzed in Bocskay et al. 2005); methylmercury (Rhainds et al. 1999, Belles-Isles et al. 2002, and Bilrha et al. 2003); and polychlorinated dioxins and furans, or PCDD/PCDFs (Schecter 1998). Although these studies each target a fairly limited number of contaminants, collectively they confirm the findings of the current study: babies are exposed to hundreds of industrial chemicals even before birth.

The mixtures comprising a typical baby's body burden create an environment in the body that is drastically different from what is produced in toxicology studies, nearly all of which focus on single chemicals. Studies that target mixtures most often investigate simple mixtures at high doses encompassing only a handful of chemicals, rarely outside the same chemical class. In a few cases, scientists have investigated the toxicity of mixtures designed to mimic chemical combinations found in the environment. The Agency for Toxic Substances and Disease Registry (ATSDR), for instance, has begun to develop "interaction profiles" — assessments of the evidence on joint toxic actions of mixtures — for some common chemical combinations found in the environment (de Rosa et al. 2004, ATSDR 2004). But as a rule, toxicologists have not investigated mixtures that are considered representative of those found in people, much less in sensitive subpopulations such as developing children.

The results of our investigation raise questions with respect to the role of exposures in utero both in a range of children's health problems and in diseases developed in adulthood that may have their origins in early life exposures; the study also reinforces the importance of explicit consideration of fetal and childhood exposures in developing public health policies.

Source: Chemical analyses of 10 umbilical cord blood samples conducted by AXYS Analytical Services (Sydney, BC) and Flett Research Ltd. (Winnipeg, MB).

Source: Chemical analyses of 10 umbilical cord blood samples conducted by AXYS Analytical Services (Sydney, BC) and Flett Research Ltd. (Winnipeg, MB).

The chemicals found in 10 newborns are linked to a number of health problems

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* Some chemicals are associated with multiple health impacts, and appear in multiple categories in this table.

Guide to the chemical families tested in umbilical cord blood

Polychlorinated biphenyls (PCBs). PCBs are toxic, persistent, bioaccumulative, and lipophilic ("fat-loving"). This means that PCBs build up and are stored in fatty tissues and fluids, such as breast milk, and can be passed on to fetuses and infants during pregnancy and lactation. In humans PCBs are linked to increased rates of a number of cancers, including malignant melanoma; non-Hodgkin's lymphoma; and brain, liver, and lung cancer. PCB poisonings in humans have caused fetal and infant death, birth defects, and brain damage in children exposed in the womb. PCBs are known to interfere with hormonal processes. In 1976, the manufacture of PCBs was banned in the United States because of concern for human health impacts, but PCBs are still widely found in the general population of the U.S.

In humans, PCBs are associated with skin lesions, thyroid disruption, and altered menstrual cycling, as well as damage to the nervous, immune, and cardiovascular systems. PCB exposure in the womb or during lactation is also associated with decreased IQ and impaired psychomotor development, decreased immune function and skin disease (chloracne) (ATSDR 2000a). The National Toxicology Program considers several PCB mixtures to be "reasonably anticipated" human carcinogens (NTP 2004). Likewise, EPA considers PCBs to be "probable" human carcinogens (EPA 2000a).

In laboratory animals, PCBs are known to cause cancer and damage to the reproductive, endocrine, immune, and nervous systems. In addition, PCBs damage the kidney and gastrointestinal tract, and cause birth defects.

PCBs do not occur naturally. Through their manufacture, use and disposal PCBs were released into the air, water, and soil. They were used primarily in transformers and other electrical equipment. Some consumer products still in use today may contain electrical components containing PCBs. PCBs continue to enter the environment through leaks at hazardous waste sites, during trash incineration, and through illegal dumping. People are exposed primarily through eating high fat meat and dairy products and PCB-contaminated seafood (ATSDR 2004).

Organochlorine Pesticides (OCs). As a class, the organochlorine (OC) pesticides are toxic, persistent, bioaccumulative, and lipophilic ("fat-loving"). They build up in the body, are stored in fatty tissues and fluids, such as breast milk, and can be passed on to fetuses and infants during pregnancy and lactation. OC pesticides can harm the brain of humans and laboratory animals, which is not surprising since they were designed to attack the nervous system of insects. In addition, many OC pesticides disrupt the hormone system. This family of chemicals includes many pesticides banned in the U.S., including DDT and dieldrin.

Polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs, or chlorinated dioxins and furans). Chlorinated dioxins and furans are unwanted byproducts of the manufacture and burning of products that contain chlorine. They cause cancer in humans, and they are generally considered to be among the most toxic environmental contaminants known to man. As a class, these chemicals are extremely toxic, persistent, bioaccumulative, and lipophilic ("fat-loving"). They build up in the body, are stored in fatty tissues and fluids, such as breast milk, and can be passed on to fetuses and infants during pregnancy and lactation. Most people are exposed to dioxin through the food they eat, primarily from meat, dairy, fish and eggs.

In humans, chlorinated dioxins and furans are associated with cancer, skin lesions, damage to the nervous system and immune system, altered carbohydrate and lipid metabolism, thyroid disruption, altered menstrual cycling, and cardiovascular effects.

In laboratory animals, the chemicals are known to cause a variety of effects including cancer and impaired reproductive, endocrine, cardiovascular, immune, respiratory, neurological and metabolic function. In addition, dioxins cause skin disease and birth defects (ATSDR 1994, 1998).

Methylmercury. Methylmercury is toxic to the developing fetal brain, and exposure in the womb can cause learning deficiencies and can delay mental development in children. The U.S. Centers for Disease Control (CDC) recently reported data showing that one of every six American women of childbearing age already has mercury in her blood at levels that the National Academy of Sciences considers potentially unsafe for the developing fetus. Most women are exposed to methylmercury through seafood, which accumulates the metal, much of which is released to the environment from the burning of coal at coal fired power plants.

High dose methylmercury poisoning during development causes severe neurotoxicity, including mental retardation in humans (NAS 2000b). Methylmercury also causes developmental malformations and altered immune, reproductive, cardiovascular and kidney function (NAS 2000b).

Polynuclear aromatic hydrocarbons (PAHs). PAHs are a group of chemicals formed during the incomplete burning of coal, oil, gas, wood, garbage, or other organic substances, such as tobacco and charbroiled meat. Other sources of PAHs include asphalt and roofing tar. PAHs are found throughout the environment in air, water, and soil. There are more than 100 PAH compounds, and although the toxicity of individual PAHs is not identical, there are some similarities.

PAHs are linked to cancer in both animals and humans. In humans, PAH exposure by inhalation or skin contact has been linked to cancer. Laboratory studies show that PAHs cause tumors in laboratory animals when inhaled, ingested, or in contact with the skin. PAHs cause birth defects, are toxic to the skin, blood, reproductive and immune systems in animals. Although robust information exists for only some of the PAHs investigated in this study, studies show that toxicity profiles are likely similar across all chemicals in this family. EPA has determined that seven PAH chemicals are "probable" human carcinogens: benz[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, dibenz[a,h]anthracene, and indeno[ 1,2,3-c,d]pyrene. (ATSDR 1995).

Polybrominated dibenzodioxins and dibenzofurans (PBDD/Fs, or brominated dioxins and furans). Brominated dioxins and furans are toxic, persistent, bioaccumulative and lipophilic ('fat-loving'). They build up in human tissues, are stored in fatty tissues and fluid, such as breast milk, and can be passed on to fetuses and infants during pregnancy and lactation. Brominated dioxins and furans are formed unintentionally, either from incineration of wastes that include consumer products infused with brominated flame retardants like PBDEs, or as trace contaminants in mixtures of bromine-containing chemicals.

Brominated dioxins and furans have dioxin-like activity, meaning that they cause birth defects in animals and otherwise disrupt the reproductive development, immune and hormone systems. They add to the total dioxin body burden, which are near levels where effects may be occurring in the general population (Birnbaum 2003, EPA 2000a, WHO 1998).

Perfluorochemicals (PFCs). PFCs are industrial chemicals widely used as water, stain and grease repellants for food wrap, carpet, furniture, and clothing. The family includes such well known name brands as Scotchgard and Teflon. PFCs are also released to the environment in air and water emissions at numerous manufacturing and processing facilities worldwide, including primary production sites such as DuPont's Washington Works facility, WV; 3M's Cottage Grove, MN site, and Daikin's Decatur, AL plant. PFCs are likely also released to the environment at countless secondary manufacturing facilities, including sites where consumer products are coated for water, stain, and grease repellency.

But the dominant source of PFCs to the environment are likely fluorotelomer chemicals, the active ingredients in coatings of furniture, clothing, food packacking, and other products. Fluorotelomers break down in the environment and in the body to PFCs differing only in the carbon chain length and end group (Dinglasan et al. 2004; Ellis et al. 2004; Hagen et al. 1981). Most PFCs are fairly mobile in water, but due to low volatility of the persistent carboxy acids and sulfonates many do not have the potential to migrate in air far from locations of its release as a manufacturing pollutant. In contrast, studies indicate that PFC telomers are relatively volatile and could migrate long distances through the atmosphere (Ellis et al. 2004; Martin et al. 2004). Fluorotelomers are a likely source of the persistent perfluorochemicals found in newborns in this study, and in wildlife and water in areas remote from manufacturing sites and human populations.

Available scientific findings to date show that PFCs widely contaminate human blood (Kannan et al. 2004; Olsen 2002a; Olsen 2002b; Olsen 2002c), that they persist in the body for decades (Burris et al. 2002), that they act through a broad range of toxic mechanisms of action to present potential harm to a wide range of organs (ovaries, liver, kidney, spleen, thymus, thyroid, pituitary, testis), and that they persist indefinitely in the environment with no known biological or environmental breakdown mechanism (3M 2000, 3M 2001a, 3M 2001b, NAS 1972). The U.S. Environmental Protection Agency has described PFCs as combining "persistence, bioaccumulation, and toxicity properties to an extraordinary degree" (Auer 2000). Two individual PFCs that are associated with Teflon and Scotchard products are described below.

• Perfluorooctanoic acid (PFOA). PFOA is a synthetically produced chemical used in the manufacture of Teflon and other non-stick cookware. It is also used to make fluorinated chemicals used as fire retardants and for oil, stain, grease and water repellency for furniture, carpet, clothing, food packaging, and countless other applications (Kissa 2001). Importantly, PFOA is also a breakdown product and metabolite of many of these chemicals (Dinglasan et al. 2004, Ellis et al. 2004). PFOA causes testicular, breast, and pancreatic tumors in animals. PFOA has been linked with increased cholesterol, stroke, and prostate cancer in exposed workers. PFOA also suppresses the immune system, and affects the pituitary, spleen, ovaries, thymus, thyroid, testicles, liver, kidney, and reproductive system in laboratory animals.
• Recently, the human health implications of widespread PFOA exposures has become a concern (EPA 2002a, 2003b), and in 2003 the Environmental Protection Agency (EPA) launched a major review of PFOA that Agency's Assistant Administrator called "the most extensive scientific assessment ever undertaken on this type of chemical" (EPA 2003d). Currently there is considerable data on PFOA that is not yet publicly available. Court documents from a lawsuit filed by EPA over DuPont's alleged suppression of PFOA health studies (EPA 2004b) indicate that the Agency has recently received at least 15 boxes of additional data from DuPont, and potentially in excess of one million pages, comprising company studies and other documents relevant to human health and exposure (EPA 2004c). EPA is only now processing these documents.
• Perfluorooctane sulfonate (PFOS). PFOS is a synthetically-produced chemical used for grease and water repellency for furniture, carpet, clothing and other applications. For decades it was the active ingredient in 3M's Scotchgard. 3M removed PFOS from the US market in 2001 under pressure from the EPA due its widespread pollution of people and the environment combined with its toxicity. In humans, PFOS has been linked with bladder, digestive tract, and male reproductive organ cancers. Other effects in humans have not been adequately studied. In animals, PFOS causes cancer, birth defects and other reproductive effects in animals (OECD 2002).

Polybrominated diphenyl ethers (PBDEs). PBDEs are brominated fire retardants, intentionally added to computers, TVs, foam furniture, and hundreds of other consumer products. They are toxic, persistent, bioaccumulative and lipophilic ('fat-loving'). They build up in the body, are stored in fatty tissues and fluid, such as breast milk, and can be passed on to fetuses and infants during pregnancy and lactation. People are exposed through the food they eat, primarily meat, dairy, fish and eggs. They are also exposed through PBDE-containing products in their homes, offices and cars. Commercial uses and human exposure sources for three commercial mixtures of PBDEs are described below.

• Penta commercial PBDE mixture. Penta is the common name for one of the three commercial PBDE mixtures. Penta was commonly added to foam products (mattresses, upholstered furniture, automobile seats, and carpet padding) manufactured before 2005. It was voluntarily phased out of production by 2005 in the wake of concerns over its toxicity and ubiquity in human breast milk, but will persist in the environment and people for decades to come. Single exposures to Penta in laboratory animals cause permanent impacts to learning, memory and behavior. These effects appear to grow worse with age. The period of greatest sensitivity in laboratory animals correlates with the third trimester of human pregnancy. Penta PBDEs are also know to cause hearing deficits, delayed puberty, decreased sperm count, fetal malformations, and possibly cancer (NIEHS 2001, deWit 2002).
• Octa Commercial PBDE mixture. Octa is the common name for one of the three commercial PBDE mixtures. The vast majority of all Octa production was added to ABS plastics to slow the spread of fire. Octa made up about 15 percent of the weight of computer casings, until it was phased-out by 2005 due to concerns about its accumulation in people and the environment. People may be exposed to Octa through their diet or when the chemical is slowly released from products in their home, office or vehicle. Octa PBDEs have not been subject to the same level of scientific scrutiny as other PBDEs. Decades old studies have found reduced increased enzyme activity, fetal weights and fetal malformation at relatively high doses (NIEHS 2001, deWit 2002).
• Deca Commercial PBDE mixture. Deca is the common name for one of the three commercial PBDE mixtures. Deca is the most widely used brominated fire retardant in the world. It is added to plastics in electronic products and sprayed on industrial fabrics to slow the spread of fire. Computer monitors, televisions, copiers and home appliances often contain Deca. People are exposed to Deca in foods and through Deca-containing products in their homes and workplace. Single exposures to Deca in laboratory animals cause permanent impacts to learning, memory and behavior. These effects appear to grow worse with age. The period of greatest sensitivity in laboratory animals correlates with the third trimester of human pregnancy. Deca is also know to cause hearing deficits, delayed puberty, decreased sperm count, fetal malformations, and possibly cancer (Viberg et al. 2003, de Wit 2002). Recent studies indicate that Deca breaks down into other forms of PBDEs, and may contribute to levels of penta and octa PBDE compounds in human tissues.

Polychlorinated Naphthalenes (PCNs). There are 75 possible chemical variations of PCNs. They have been used as cable insulation, wood preservatives, engine oil additives, electroplating masking compounds, capacitors, and in dye production (EPA 1983). Products are generally mixtures of several different PCNs. The largest source of PCNs believed to be waste incineration and disposal of items containing PCNs, although other potential sources of PCNs to the environment include sewage discharge from municipal and industrial sites, leaching from hazardous waste sites. PCNs are also unwanted byproducts formed after the chlorination of drinking water (Kuehl et al. 1984b, Vogelgesang 1986, Furlong et al. 1988, Lin et al. 1984, Shiraishi et al. 1985). They have not been used commercially in significant quantities since the 1980s.

PCNs are toxic and persistent. They bioaccumulate in people and are stored in fatty tissues. PCNs have not been tested for their ability to induce cancer. The toxic effects of many PCNs are thought to be similar to dioxin. In humans, severe skin reactions (chloracne) and liver disease have both been reported after occupational exposure to PCNs. Other symptoms found in workers include cirrhosis of the liver, irritation of the eyes, fatigue, headache, anaemia, haematuria, impotentia, anorexia, and nausea. At least 10 deaths were reported from liver toxicity. Workers exposed to PCNs also have a slightly higher risk of all cancers combined. (WHO 2001).

FOOTNOTES - HEALTH EFFECTS SUMMARY

Study methodology

Introduction. For 10 children born in U.S. hospitals between August 11th and September 8th, 2004, the moment of birth was marked not only by a first cradling in parents' arms, but also by a blood draw integral to a benchmark study of industrial pollutants in newborns. In the most comprehensive tests yet conducted on human umbilical cord blood, we analyzed each child's cord blood for a broad battery of industrial chemicals, pollutants, and pesticides — 413 chemicals in total, from nine chemical classes. To our knowledge this work includes the first reported cord blood tests for 261 of the targeted chemicals. Information below describes the components of this new study, detailing the blood collection procedures, sample preparation and analysis methods, and the quality assurance and quality control provisions included in the study design.

Cord blood sample acquisition and storage. The American National Red Cross obtained ten umbilical cord blood samples from live births in U.S. hospitals in August and September 2004. Besides each child's birthday, the Environmental Working Group obtained no identifying information, either personal or geographic, regarding the samples. Samples consisted of between 79 and 121 milliliters (mL) of umbilical cord blood and 35 mL citrate-phosphate-dextrose (CPD) anticoagulant in a 250 mL Baxter Fenwal Blood-Pack unit (Baxter Healthcare Corporation, Deerfield, IL). The 35 mL of CPD anticoagulant consisted of 921 mg sodium citrate, 893 mg dextrose, 105 mg citric acid, 78 mg monobasic sodium phosphate. Samples were shipped to AXYS Analytical Services (Sydney, BC) within 24 hrs of collection in coolers with gel ice packs. Samples were stored at 4 degrees C for up to four weeks until the entire set of 10 samples was received.

Sample preparation. Cord blood samples were transferred from the blood collection bags into measuring cylinders to determine the total sample volume. About 5 mL of the sample was then transferred into a polypropylene tube for perfluorochemical analysis. The remainder was transferred to a glass container. Both portions were stored at -20 degrees C. Concentrations of chemicals in blood samples were computed based on the total sample weight less the weight of the anticoagulant.

Analysis of PCDD/PCDFs, PBDD/PBDFs, PCBs, PBDEs, PCNs. Analyses for the following groups of compounds were achieved on a single 50 gram portion of the blood-anticoagulant mixture: polychlorinated dioxins and furans (PCDD/PCDFs), polybrominated dibenzodioxins and dibenzofurans (PBDD/PBDFs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated naphthalenes (PCNs). The sample was first spiked with an extensive suite of 13C labeled surrogate standards including compounds from all of the target analyte groups. The sample was extracted by shaking with 40 mL of ethanol and 40 mL of saturated ammonium sulfate solution followed by liquid-liquid extraction into 150 mL of hexane. The extract was cleaned up and fractionated by a series of adsorption chromatographic columns (silica, alumina, florisil and carbon) and analyzed by gas chromatography with high resolution mass spectrometric detection (GC/HRMS). Five separate analyses were conducted: PCBs following the protocols of EPA Method 1668A; PBDEs following the protocols for EPA Method 1614; PCDD/PCDFs following the protocols for EPA Method 1613B; and, separately, PCNs and PBDD/PBDFs following in-house methods patterned after the EPA 1600 series methods.

GC/HRMS analyses were performed using a Micromass Autospec Ultima magnetic sector high resolution mass spectrometer equipped with a Hewlett-Packard 6890 gas chromatograph. Quantification of target analytes was achieved by isotope dilution quantification using the 13C labeled surrogate standards.

Analysis of organochlorine pesticides. Another 40 gram aliquot of blood-anticoagulant mixture was used for analysis of organochlorine pesticides. The sample was first spiked with multiple 13C labeled surrogate pesticide standards. The sample was extracted by the procedure described above, cleaned up by gel permeation chromatography on BioBeads SX-3 and split into 2 fractions on Florisil. Each fraction (non-polar compounds and polar compounds) was analyzed by GC/HRMS for pesticides. Organochlorine pesticides were analyzed on a Micromass VG70 magnetic sector high resolution mass spectrometer equipped with a Hewlett-Packard 5890 gas chromatograph.

Analysis of Polyaromatic Hydrocarbons (PAHs). PAH analysis was conducted on a 20-gram aliquot of blood anticoagulant mixture. A suite of 2D labeled surrogate standards was added to the sample which was then extracted as described above. The extract was cleaned up by gel permeation chromatography on BioBeads SX-3 and adsorption chromatography on silica. It was then analyzed by gas chromatography with a mass selective detector (GC/MSD) using an Agilent 6890 gas chromatograph coupled to an Agilent 5973N mass selective detector operated at unit resolution in the electron impact ionization mode using multiple ion detection. Quantification of target analytes was achieved by isotope dilution quantification using the 2D labeled surrogate standards.

Analysis of Perfluorochemicals (PFCs). Analysis for perfluorochemicals was conducted on a 2 gram aliquot of sample. The sample was first spiked with two 13C labeled perfluorochemical surrogate standards, extracted with acetonitrile and cleaned up on a C-18 solid phase extraction cartridge. The extract was analyzed by LC/MS/MS using a Micromass Quattro Ultima MS/MS coupled with a Waters 2690 liquid chromatographic system. Quantification of target analytes was achieved by isotope dilution quantification using the 13C labeled surrogate standards.

Analysis for Methylmercury. Analysis for methylmercury was conducted by Flett Research Ltd. (Winnipeg, MB). Approximately 0.3 g of blood-anticoagulant mixture was analyzed by KBr extraction, followed by ethylation, purge and trap and cold vapor atomic fluorescence spectroscopy (CVAFS). The analysis batch included a procedural blank and a reference sample (DORM-2, National Research Council of Canada).

Procedures for quality assurance and quality control (QA/QC). All organic analyses were conducted in accordance with AXYS' accredited QA/QC program. Regular participation in international inter-laboratory calibration programs is a component of this program. Each analysis batch also included a procedural blank, a laboratory blank, blood bag blanks (extractions from ethanol and from q water-corn oil water mixture added to the standardized cord blood container), and an analysis duplicate. The sample results were reviewed and evaluated in relation to the QA/QC samples worked up at the same time. The sample surrogate standard recoveries and detection limits, procedural blank data and the laboratory control sample data were evaluated against method criteria to ensure data quality. A positive finding was determined as three times the minimum quantifiable area. Subsequently, to correct for possible procedural or equipment contamination, the blank sample analyses were subtracted from the respective determined analyte values.

FINAL DRAFT

Embargoed until 12:01 a.m. EDT July 14, 2005

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