By JOAN LOWY, Scripps Howard News Service
December 21, 2003
At Massachusetts General Hospital in Boston, Dr. Martha Herbert is seeing younger and younger children who have been prescribed powerful drugs because their behavior is "so extreme."
One 4-year-old was treated with Risperdol, an antipsychotic drug usually prescribed to adult schizophrenics, because she tried to kill a sibling. "I've had several cases like that," said Herbert, a pediatric neurologist. "It's scary because this kind of thing hardly ever used to happen."
Across the nation, evidence of a growing number of children diagnosed with attention, learning, behavioral and emotional disorders have perplexed doctors and researchers and worried teachers and parents.
The disturbing conclusion some experts are reaching is that a significant share of these conditions may be caused by environmental toxins that interfere with brain development in children beginning in the womb and which may be lowering the intelligence of the population at large.
There is no shortage of toxic suspects including lead, PCBs, mercury, pesticides, dioxins, flame-retardants and alcohol. Most children are exposed to some level of all these chemicals, raising the possibility of combined effects -- a question that scientists are only now beginning to research.
"You can almost think of the children who have been diagnosed with these clinical syndromes as the tip of the iceberg," said Deborah Rice, a toxicologist with the Maine Department of Environmental Protection.
"These are the kids that stand out, the ones that can actually go into a doctor's office and the doctor can say, 'Yes, this child has autism,' " Rice said. "But for every one of those children there may be many more children that don't reach the clinical criteria, but nonetheless may have been affected by the chemicals and other environmental milieu of a child's life."
Autism researcher George Lambert describes children as society's "canaries in the coal mine" because they are so much more sensitive than adults to poisons in the environment. They eat more food, breathe more air and drink more fluid per pound of body weight than adults -- and their brains and nervous systems are still developing. The most sensitive of all is the developing fetus.
In California, state health authorities have documented a 273 percent increase between 1987 and 1998 in diagnosed cases of autism, a neurodevelopmental disorder that usually appears before age 3 and can affect a child's ability to communicate, form relationships and respond to the world around them.
Reported autism cases in California doubled again over the last four years and the rate of increase appears to be accelerating, according to a follow-up study released earlier this year. In November, the U.S. Department of Health and Human Services held a two-day "autism summit" in Washington in response to demands from parents of autistic children for greater federal action to counter what they call a national "epidemic" of autism.
In North Port, Fla., kindergarten teacher Susan Owens said she has seen a dramatic increase in attention and learning disorders in children of all levels of intelligence and family income over the last 30 years.
Retarded students she taught in the late 1960s were better able to retain basic knowledge and skills such as the days of the week or simple addition and subtraction than many of today's kindergarteners of average intelligence, said Owens, 60.
"I can go over the days of the week with my children now the entire year, but if I say to them, 'Today is Friday. What will tomorrow be?' 50 percent of them will still not be able to tell me that tomorrow is Saturday," Owens said.
Epidemiologists caution that personal observations or even documented trends in diagnosis are not proof that any of these disorders is increasing in children. Only a national study that investigates and tracks tens of thousands of children -- something that has never been done in the United States -- would be able to determine the true prevalence of these problems and whether they are actually increasing.
"One can say there has been an increase in conduct disorders -- in violent and aggressive behaviors -- over the last 50 years in children, but the problem with saying the same thing about ADHD (attention deficit/hyperactivity disorder) or autism is that we simply don't have good enough data to draw conclusions," said Jane Costello, a psychiatric epidemiologist at Duke University Medical Center.
What is clear is that scientific understanding of the potential effects that toxins can have on the human brain has expanded markedly. Scientists now know that the timing of the exposure is just as critical as the amount -- or dose -- of the toxin. Very small amounts of chemicals at critical windows in fetal development or early childhood can have far more devastating effects than greater exposure later in life.
Scientists also know more about the relationship between genes and environment in the creation of disease. Even as researchers are linking individual genes to specific diseases, they are also discovering that particular substances in the environment can "turn off" or "turn on" these genes. The description often used by scientists is that "genetics loads the gun, but environment pulls the trigger."
Studies of identical twins show that 68 percent of the time when one twin has autism, the other twin will too, indicating that the disease probably has a genetic link. But 32 percent of the time one twin will not have autism. Since twins have identical genetic makeup, that means some environmental influence is involved in autism as well, Lambert said.
Scientists also are exploring the relationship between ADHD and toxins known to interfere with brain development. Rice found that monkeys exposed in early life to lead and PCBs in amounts similar to what children often encounter develop learning and behavioral problems that look remarkably like attention deficit disorder.
PCBs (polychlorinated biphenyls) were widely used to insulate electrical equipment until it was discovered that they were accumulating in the bodies of people and animals virtually everywhere in the world. Although PCBs were banned in 1972, children born three decades later still have small amounts of the chemical in their bodies.
"This is not to suggest that ADHD is caused exclusively by neurotoxic agents in the environment," Rice wrote in an article published in Environmental Health Perspectives. "However, it seems reasonable to postulate that environmental neurotoxicants contribute to the prevalence of ADHD currently being identified in children."
An Environmental Protection Agency report earlier this year identified ADHD as one of two "emerging issues" in children's environmental health. Children with ADHD are characterized by having chronic inattention, impulsive hyperactivity or both to an extent that daily functioning is impeded.
The second emerging issue identified by the EPA is mercury, a metal long known to be extremely toxic to the human nervous system. The term "mad hatter" described the severe effects of mercury used by 19th century hat makers in Danbury, Conn., to soften felt.
Most Americans have small amounts of mercury in their bodies, primarily from eating fish. Fish consumption in the United States has risen sharply since the 1980s, when doctors began urging patients to reduce beef in their diet to help prevent heart disease.
Tests by the Centers for Disease Control and Prevention show 8 percent of women of child bearing age have mercury levels in their blood that exceed the government's safety standard. That means about 320,000 children are born each year at risk for neurological damage from mercury.
Over the years, scientists have repeatedly lowered their estimates of how much mercury people can tolerate. The same is true for lead, which has been known for over a century to cause brain damage.
Two recent studies have concluded that there is no safe level for lead exposure. Although lead levels in children have dropped dramatically, government data show that about 90 percent of the nation's children have between 1 and 10 micrograms of lead in their blood, which means they are at risk for lowered intelligence.
While the dangers of lead, mercury and PCBs are established, scientists are also discovering that chemicals with less well understood effects are widespread in the environment and in people's bodies.
In 1999, researchers reported finding traces of a widely used group of flame-retardants known as PBDEs in the breast milk of Swedish women. In California, state toxicologists saw the Swedish study and decided to do their own studies. Not only did they find PBDEs in every woman tested, but the levels were significantly higher than those found in European women and they were increasing rapidly over time.
Laboratory studies show some PBDEs can alter brain development in mice during the important brain growth spurt. In humans, the growth spurt occurs from the last trimester of pregnancy to age 2. The concern is that PBDEs could have the same effect in children exposed through their mother's blood during pregnancy and through breast milk after birth.
Alarmed, the California General Assembly passed a law earlier this year phasing out the two PBDEs that showed the highest accumulation in women. Last month, Great Lakes Chemical Corp. of West Lafayette, Ind., agreed to cease production of the two chemicals by the end of 2004.
Industry officials contend children are not at risk from the flame-retardants because levels found in women are too low to pose harm. They also note that PBDEs are very effective flame-retardants, saving hundreds of lives every year.
Some scientists see PBDEs as a cautionary tale.
"We came across PBDEs really by chance because we looked for it, found a strange blip on screen and then it snowballed," said Tom McDonal, a toxicologist with the California Department of Environmental Protection.
"There are thousands of chemicals used in commerce and hundreds of new chemicals introduced each year, many of which we have very little information on their human toxicity and even less information on exposures."
© 2003 The E.W. Scripps Co
Scientists trying to unravel why childhood asthma has reached epidemic proportions have reported that a variety of chemical exposures during infancy - including pesticides and wood smoke - can substantially increase a child's risk of developing the disease.
Studying nearly 700 children in 12 communities in the Los Angeles region, a team at USC found that children exposed to household pesticides in their first year of life were more than twice as likely to develop asthma than those never exposed. Infants exposed to wood smoke, household cockroaches and farm animals also suffered considerably more asthma.
Asthma is the most prevalent disease affecting American children, causing more hospital stays and missed school days than any other chronic childhood illness. While medical officials today have a good understanding of how to treat breathing problems in asthmatics, they have struggled for years to figure out what makes so many children vulnerable to the disease.
About 20 million people in the United States suffer from asthma, including more than 3.5 million children under the age of 15. Nearly twice as many preschoolers and school-age children had asthma in 1999 than in 1980, according to a Centers for Disease Control and Prevention report. About 5,000 people die from asthma attacks in the country every year.
The USC study suggested that there was no single cause, but an array of factors in children's lives responsible for asthma. It also indicated that contaminants - indoors and outdoors - have particularly potent effects on infants, so that a baby's experiences might determine how healthy he or she is for the rest of his or her life.
"The main message is that early in life, the first year of life may be a very, very important time for respiratory health, and that children may be uniquely susceptible then," said Dr. Frank D. Gilliland, a professor of preventive medicine at USC's Keck School of Medicine. Gilliland was the lead author of the report, which was published in the online version of the scientific journal Environmental Health Perspectives.
The study, which was one of the largest worldwide to examine factors contributing to childhood asthma, confirmed many of the findings of other research. Of 691 children between the ages of 8 and 18 recruited for the study, 279 had asthma and 412 did not.
Eight factors included in parents' questionnaires were compared - day-care attendance, household pets, cockroaches, pesticides, smoke from burning wood and oil, exposure to farm animals or crops, number of siblings and breastfeeding. Only two categories - pets and breastfeeding - were not associated with a substantially higher risk of asthma, the report said.
In people with asthma, airways are inflamed and constricted as immune cells react to allergens, reducing the flow of air to and from the lungs and causing shortness of breath, wheezing and coughing.
Scientists have long theorized that exposure to irritants or chemicals could alter a child's developing immune and respiratory systems.
The USC scientists said "the widespread use of pesticides and herbicides in the home and farm environments, and the magnitude of the observed risks" warrant giving priority to investigating their link to asthma.
Dr. Deepak Jajou, a pediatrician who specializes in asthma at Mount Sinai Hospital in Chicago, said asthma is an "an interplay between genetics and environment" and "that the experience of a child in early life does influence whether he develops asthma or not."
"Clearly, wood smoke, pesticides, irritants cause problems in developing lungs. They really make things worse. Whether they cause asthma, I don't know, but they could clearly make it come to the surface," he said.
Jajou cautioned that the USC research and similar studies "give us some clues about causes, but they are not considered very conclusive" because they rely on parents' subjective memories about their children's past exposure.
Dr. Miles Weinberger, director of the Pediatric Allergy and the Pulmonary Division at University of Iowa College of Medicine, questioned the findings. He said genetics - whether parents have asthma or allergies - play the major role in determining which children develop asthma. Although soot, secondhand cigarette smoke and other environmental factors exacerbate symptoms and can lead to an asthma diagnosis for young children, Weinberger said he did not believe those factors caused the disease.
In the study, children exposed to smoke from burning wood or oil were 1.6 times more likely to have asthma than those never exposed.
The risk was slightly higher for those exposed during the first year of life.
Children were also twice as likely to have asthma if, as infants, they had cockroaches in their homes. Experts suspect that early exposure to the insects causes an allergic reaction. Exposure to farm animals increased the asthma rate by 60%, perhaps because of a bacteria on farms called endotoxin.
In the study, children attending day-care centers were more prone to temporary wheezing if they had colds - especially children who attended the centers before they were 4 months old. But children at day-care centers were not more likely to develop persistent asthma than the children who did not attend day-care centers.
The chances of a child developing asthma decreased by half if he or she had four or more siblings, the study found.
Some experts suspect that children who spend a lot of time around other children develop immunity to asthma because they are exposed early and often to respiratory infections, which prompt their immune cells to be geared toward fighting bacteria.
Gilliland said the findings are not definitive because they do not examine all relevant factors, offering just "one small part of the puzzle."
The study is part of the 10-year Children's Health Study that has examined the effects of air pollution on about 6,000 Southern California schoolchildren.
Copyright 2003 Los Angeles Times
(Beyond Pesticides, November 21, 2003) According to Science News, a new study has found chlorpyrifos, a neurotoxic organophosphate insecticide commonly sold as Dursban, was recently found to damage heart and liver cells, in addition to the affects it is already known to have on the brain. Although chlorpyrifos had many of its uses "phased-out" by an agreement between EPA and the pesticide industry in 2000, it may still be used on golf courses, in baits, in agriculture, for mosquito control and in food processing plants. Existing stocks purchased before 2002 may be used indefinitely.
To test for effects of the chemical outside the nervous system, researchers at Duke University in Durham, N.C., injected rats daily with 1, 2, or 5 milligrams of chlorpyrifos per kilogram of body weight for 4 consecutive days. Some animals received the injections while they were pregnant, and their offspring were then studied for possible effects. Other animals were exposed during the first or second week of life. The researchers looked for effects shortly after exposure and when the animals were juveniles and adults.
While the doses of chlorpyrifos were too low to cause immediate symptoms, rats exposed in utero or during the first week after birth later showed subtle biochemical abnormalities. Chlorpyrifos exposure in older animals seldom had an effect, suggesting that a "window of vulnerability" closes soon after birth, say Theodore Slotkin, PhD, and his colleagues at Duke.
The abnormalities affect adenylyl cyclase signaling, a process by which cells communicate, and in some experiments, effects were evident only in male rats. Because adenylyl cyclase signaling modifies insulin production, glucose metabolism, and heart rate, the findings imply that early exposure to chlorpyrifos and other organophosphates could increase risks for cardiovascular and metabolic disorders that typically arise later in life, Dr. Slotkin argues.
10-23-2003 -- Pacific Northwest National Laboratory
Home testing of saliva to measure personal hormone levels is gaining popularity, with dozens of companies offering do-it-yourself, mail-in test kits. Battelle scientists at the Department of Energy's Pacific Northwest National Laboratory envision a day when it may be nearly as easy to detect chemical exposure or even nerve gas poisoning - simply by analyzing a victim's saliva. And the results would be almost immediate.
Using sophisticated mass spectrometry equipment at PNNL, researchers have been able to identify breakdown products of a common pesticide in the saliva of rats exposed to known amounts of the pesticide. The researchers are working now to develop a simpler, portable microanalytical sensor system to quickly diagnose pesticide exposure in humans and a modeling method than can estimate the dose. Researchers say the technology could be adapted to test for a variety of contaminants, including chemical warfare agents.
The research project began with an Environmental Protection Agency grant to study pesticide exposure in adults and children working or living near farms. The research team exposed rats to a common agricultural chemical and found traces in the saliva shortly after exposure.
"The fact that we were able to find the chemical in very low concentrations confirms that saliva can be a reliable, non-invasive method to monitor farm or industrial workers who are exposed routinely to potentially harmful pesticides," said Jim Campbell, an analytical chemist working with mass spectrometers at PNNL.
Researchers believe saliva monitoring may be able to detect a broad range of chemical contaminants from ongoing occupational exposure, accidents or even acts of war and terrorism.
"The class of pesticides we are studying, organophosphates, are chemically similar and work on the same general principal as nerve gas," said Charles Timchalk, a Battelle toxicologist at PNNL. "Both pesticides and nerve gases inhibit an enzyme called acetylcholinesterase. Without acetylcholinesterase, nerves, including those responsible for breathing, stop functioning."
Chemical nerve agents also bind to and disrupt other enzymes, including one called butyrylcholnesterase. "Researchers at the laboratory have demonstrated that rat saliva contains a nearly pure population of this enzyme," said Campbell. "This data strongly suggests that it's possible to develop a portable device to yield immediate results from a small amount of saliva. Such a device might save lives in the event of a military or terrorist attack."
Real-time diagnosis is the key, as some treatments for nerve gas poisoning are effective, if initiated in time. Typically, however, testing for chemical exposure requires drawing blood or collecting urine samples, which must then be sent to a laboratory. Results may be days or weeks away.
"If expanded to identify chemical warfare agents, saliva analysis would not only identify those who need medical treatment, but might also offer up forensic evidence against the attackers," said Timchalk. "It might be possible to detect trace levels of the chemical agents in the saliva of a terrorist who handled the poisons before releasing them." The saliva monitoring technology under development at PNNL is being designed to provide immediate results and be simple enough to be operated in the field by technicians with little training.
"We have demonstrated that a biosensor linked to a hand-held electrochemical detector can identify the organophosphates in solution with a high degree of sensitivity," said Yuehe Lin, a Battelle analytical chemist at PNNL. "The biosensor consists of electrodes coated with carbon nanotubes. The carbon nantotubes hold the enzymes, which are targeted to the organophosphate chemicals, and electricity is applied. If organophophates are present, there is a decrease in the electrical current that can be correlated to the amount of chemical present. The hand-held biosensor detection system will facilitate the on-site saliva monitoring of exposures to these pesticides."
The Battelle team hopes to secure additional funding to study saliva testing and monitoring for nerve agents. Meanwhile they continue to develop the technology to assess exposure to agricultural pesticides.
Pacific Northwest National Laboratory is a Department of Energy Office of Science research facility that advances the fundamental understanding of complex systems, and provides science-based solutions to some of the nation's most pressing challenges in national security, energy and environmental quality. The laboratory employs more than 3,800 scientists, engineers, technicians and support staff, and has an annual budget of nearly $600 million. Battelle, based in Columbus, Ohio, has operated PNNL for the federal government since the laboratory's inception in 1965
By Kellyn Betts, Environmental Science & Technology, Sept. 22, 2003
The air and dust inside U.S. homes are likely to contain a wide variety of chemicals and pesticides that have been identified as endocrine-disrupting compounds, according to research posted to ES&T's Research ASAP website this week.The most comprehensive analysis conducted to date, it reveals that many people may be continually exposed to dangerous levels of toxic substances, including chemicals like DDT and PCBs, which have been banned for decades.
This study, together with other data, shows that U.S. families may have "very widespread exposures" to chemicals that could affect the health of everyone from infants to senior citizens, warns Mary Wolff, of Mount Sinai School of Medicine in New York City. Currently, the U.S. EPA has no regulatory authority over indoor air or endocrine- disrupting chemicals.
The study was led by Ruthann Rudel of the Silent Spring Institute, a nonprofit organization based in Boston, Mass., as part of its ongoing Cape Cod Breast Cancer and Environment Study. The group measured concentrations of 89 suspected endocrine disrupters in air and dust samples taken from 120 homes on Massachusetts' Cape Cod peninsula, where the state's Bureau of Environmental Health Assessment has documented elevated incidences of breast, colorectal, lung, and prostate cancers.
The researchers found bis(2-ethylhexyl) phthalate (DEHP), which is "reasonably anticipated to be a human carcinogen", according to the National Institutes of Health, in the dust of every home tested, at concentrations ranging from 16.7 to 7700 micrograms per gram (micrograms/g). DEHP is used in a wide variety of flexible poly(vinyl chloride) products, including children's toys, shower curtains, raincoats, shoes, and floor tiles. The concentrations of DEHP in the dust of most of the tested homes exceeded EPA's risk-based safety guidelines of 35 micrograms/g for residential soil, which are based on the compound's carcinogenicity. There is scientific debate over whether DEHP is a human carcinogen, but the levels in some households also exceeded EPA's guidelines of 1240 micrograms/g to protect against reproductive toxicity, Rudel says.
The study also contains the first reports of residential concentrations for 30 of the measured compounds, including 4- nonylphenol, an alkylphenol that can act like female estrogen hormones, and its ethyoxylates. Nonylphenol or nonylphenol ethoxylates are found in some laundry detergents, disinfecting cleaners, all- purpose cleaners, spot removers, hair-coloring and other hair-care products, and spermicides. The researchers found 4-nonylphenol to be one of the most abundant chemicals in the air of the sampled homes. It was discovered in every tested home at concentrations ranging from 21 to 420 nanograms per cubic meter of air (ng/m3).
The European Union (EU) Parliament has approved a directive that would restrict the use of 4-nonylphenol, but no EPA safety guidelines have been set for human exposure for it or any chemicals based on their endocrine activity.
"Finding the alkylphenols in air was a bit of a surprise because EPA and some documents from the manufacturers had suggested that you wouldn't expect it to volatilize at all," Rudel says. She adds that this is just one example raised by the study showing that reliance on using manufacturers' claims by EPA and the U.S. Food and Drug Administration can be problematic. Wolff points out that "air pollutants don't have to be volatile" because they can be adsorbed onto particles.
People have a limited exposure to nonylphenols through the use of products, and the daily intake is thought to be very low, according to the Alkylphenols and Ethoxylates Research Council, an industry group. Rudel says that the findings show that the compound's potential for inhalation toxicity merits further investigation.
The researchers also documented the presence of some long-banned substances in the tested samples, including PCBs and the pesticides dieldrin, chlordane, and DDT, at levels that exceed federal risk-based safety guidelines.
4-4' DDT was one of the most abundant pesticides in the tested household dust. The scientists detected it in 65% of the homes at concentrations of up to 9.61 micrograms/g. Although they also detected some of DDT's breakdown products, most of the chemical was in the form of DDT. "Since [DDT] really hasn't been used in 30 years, it means it's really not breaking down indoors," Rudel says.
The results could help explain why the Centers for Disease Control (CDC) has reported that DDT's breakdown product, DDE, is present in the bodies of youth aged 12-19 who were born after the United States banned the pesticide.
Another chemical measured for the first time in the study is 2,3- dibromo-1-propanol, a mutagenic and carcinogenic chemical that was found as an impurity in the TRIS flame retardant, which was banned in the late 1970s. Rudel is currently trying to solve the mystery of why the research team detected the chemical in the air of 9% and in the dust of 6% of the tested homes.
Other banned pesticides frequently detected in the homes included heptachlor (found in the air of 44% of the tested homes), pentachlorophenol (detected in the dust of 86% and the air of 58% of the homes), methoxychlor (in the dust of 54% of the homes), -chlordane (detected in 51% of the tested air in the homes), -chlordane (found in the air of 53% of the tested homes), and chlorpyrifos (found in the air of 38% and the dust of 18% of the homes). All of these banned pesticides were detected in some of the homes at levels that exceed EPA's risk-based safety guidelines.
The Silent Spring team's finding of high levels of the recently banned chlorpyrifos in some homes could also provide explanatory fodder for why CDC found that levels of this pesticide are higher in children aged 6-11 than in the rest of the population.
Although the presence of these compounds in the tested homes should set off alarm bells, Rudel stresses that the risk presented by exposure to the compounds could be much higher. EPA has developed toxicity guidelines for only 12 of the tested compounds, and the agency does not yet consider the impacts of exposure to mixtures of chemicals, she says. The agency does not regulate indoor air.
On average, the dust in the tested homes contained 26 different compounds and the air contained 19 different compounds. In a high proportion of the homes, the concentrations of at least one of compounds exceeded risk-based guidelines for safety developed by EPA, Rudel says.
Although the researchers took samples from the homes of breast cancer survivors and healthy women, they cannot make associations between cancer incidence and the levels of chemicals in the homes they studied because the sample size is too small and the samples were collected many years after the women were diagnosed. On the basis of values recorded in other U.S. studies, the researchers say that the levels they measured in Cape Cod are not significantly higher than elsewhere in the country.
Home contaminants are important contributors to people's overall exposure and health effects because studies show that people in the United States spend 65% of their time in their residences, according to John Spengler of the Harvard School of Public Health, a paper coauthor. This figure holds true for most other industrialized countries, he says.
The Silent Spring researchers focused their efforts on looking for chemicals that are produced in high volumes in the United States and have been identified as endocrine disrupters in either whole-animal or cell-based tests. The pesticides measured in the study are regulated by the federal government, as are some of the toxic compounds, while others are candidates.
The study contains what Rudel believes to be the first report of the levels of the polybrominated diphenyl ether (PBDE) flame retardants in U.S. household dust. It shows that the levels of PBDEs in household dust are 10% higher than the levels in Europe and higher than the levels of PCBs in dust in U.S. homes. "We know that levels of PCBs are going down, and the PBDE flame retardants are still being made and their levels of usage are increasing," Rudel says.
Linda Birnbaum, director of the Experimental Toxicology Division of EPA's National Health and Environmental Effects Research Laboratory, agrees that this finding is important. Three new animal studies show that BDE-99 - the PBDE congener found in most abundance in household dust, according to the study - can have neurotoxic effects and that embryonic exposures can impair sexual development in addition to causing thyroid toxicity, Birnbaum adds.
The presence of contaminants like PBDEs and phthalates in household dust has significant health implications, Spengler says. Many studies of dust have focused on what crawling babies and children are exposed to, but he argues that everyone comes into contact with household dust. "Carpets are very effective at re-suspending materials," he explains.
Spengler's lab has conducted tracer measurement studies showing that approximately 10 micrograms/m3 of dust is suspended back in air, on average, from the dust that has settled. In this manner, dust can be continually redistributed throughout a home, he says. Vacuuming also re-suspends contaminants, says Rob Hale of the Virginia Institute of Marine Science.
The movement of household dust takes on added significance given that some of the toxic compounds measured in the study - particularly the phthalates and alkylphenols, which were found in the air or dust of every tested home - are present in high concentrations.
The Silent Spring findings also imply that people who buy used homes can be unwittingly exposed to the pesticides and chemicals used by the prior owners, Spengler says. "The real concern is, How does an individual get informed about the concentrations in their own home? It's not easy for an individual consumer to get these measurements made - the laboratories that can make these measurements are few and far between, and they're expensive measurements to make," he explains.
In addition to measuring the carcinogenic and teratogenic DEHP, the Silent Spring researchers detected seven other phthalates, which are suspected of harming male reproductive systems by interfering with androgen function, in the homes they tested. As was the case with previous studies, the phthalate levels were very high - orders of magnitude higher than the levels of other contaminants (Environ. Sci. Technol. 2001, 35, 235A). For example, the researchers found a median value of 340 micrograms/g of DEHP in the dust they tested, while the median values for all of the other measured chemicals were less than 10 micrograms/g, if they were above the detection limits.
The new phthalate data also raise some new questions. In the past, most researchers doubted that inhalation was an important route of exposure for phthalates, but the new measurements suggest that inhalation may indeed be important, Rudel says. The phthalates that the researchers found in most abundance in the air of the tested homes - diethyl phthalate (DEP), which was present at a median level of 590 ng/m3, and di-n-butyl phthalate (DBP), which was present at levels ranging from 52 to 1100 ng/m3 - are the same ones determined to be most abundant in human urine by CDC for a cross-section of U.S. adults.
When CDC's results were first published, they were a surprise because they were not the phthalates that the National Toxicology Program had predicted that people would be most exposed to, Rudel explains. However, although DEP and DBP are not the phthalates used in greatest quantities, they are used in many personal care products like perfume and nail polish, she says. DBP is of particular concern because it is known to be a reproductive toxin. Although the risk-based safety guideline for DBP in air of 370 micrograms/m3 is significantly higher than the values the Silent Spring researchers recorded, Rudel says that the number is not based on the newest research.
"The phthalates and phenols are so widely used in commerce now that we've got to be concerned about this component of the body burden," Spengler says, noting that other studies have shown that food and water are also sources. Phthalates and alkylphenols are the chemicals most urgently in need of further toxicity testing, agree Rudel and Julie Brody, executive director of the Silent Spring Institute and a paper co-author.
The study also points out the importance of considering the mixtures of chemicals to which people are exposed in their homes, say Rudel, Spengler, and Brody. The science of evaluating mixture toxicity is in its infancy, but European studies have shown that endocrine-disrupting chemicals can be evaluated as mixtures. Compounds that target the estrogen receptor site share similar mechanisms of action, and experiments show that the activity of mixtures of such compounds is indeed additive, Wiebke Meyer of the University of Bremen in Germany told attendees at a Society of Environmental Toxicology and Chemistry meeting in his native country this past May.
However, Meyer's experiments, which are being conducted as part of the European Commission's ACE project charged with "analyzing combination effects of mixtures of estrogenic chemicals in marine and freshwater organisms," are based on evaluations of aquatic toxicity.
"The need to assess mixture toxicity is recognized by most environmental toxicologists, but the tools to do this, especially for complex mixtures, are lacking or poorly developed," adds Paul Sibley, an assistant professor at Canada's University of Guelph who is interested in aquatic mixture toxicology.
The mixtures of endocrine-disrupting chemicals to which people are exposed is likely to be more complex than what the Silent Spring study indicates, the researchers stress. "We just happened to look for 89 of these chemicals...but most chemicals that are actually in use haven't been screened yet, so probably the true number of endocrine-active chemicals that people are exposed to is much, much higher than the number we came up with," Rudel says.
The finding that a few homes had significantly higher levels of each chemical has significant implications for risk policy, Rudel says. For example, a few homes had concentrations of DBP and DEHP, which both have reproductive toxicity, that were far higher than in the other tested homes. "We typically go chemical by chemical and say we're protecting the 95th percentile person, and if you actually look at these kinds of exposure data, there are a lot of people in the top 1- 2% of the concentration distribution that you're really not protecting," Rudel says.
Rudel and Brody will consider themselves successful if their work provides impetus for rethinking such policies and conducting more toxicity tests. Although the reports on endocrine disruption by such influential organizations as EPA, the Endocrine Disruptor Screening and Testing Advisory Committee, and the National Academies, have identified the need for exposure information to help prioritize which substances should most urgently be evaluated, there are as yet very little exposure data, Rudel explains. This new data, says Birnbaum, give scientists a place to start.
Moreover, Brody adds, "Breast cancer research has really been hindered by lack of adequate measurements of the pollutants that women are exposed to that might be relevant to breast cancer, so this is really a necessary first step."
The researchers are currently analyzing the relationships between the levels of phthalates and pesticides in the air and dust of different homes, and the amount of phthalates in the urine of the women living in those homes. They are also trying to track down the sources of some of the compounds measured in the study.
* * *
Copyright 2003 American Chemical Society
Recent research found a new method to detect human exposure to organophosphate (OP) pesticides. Scientists from the Russian Academy of Sciences released a study, "Biosensor detection of neuropathy target esterase in whole blood as a biomarker of exposure to neuropathic organophosphorus compounds," which appeared in the April 11 2003 edition of the Journal of Toxicology and Environmental Health, that looked at the effectiveness of the newly developed biosensor of OP exposure.
Exposure to organophosphates inhibits a protein in the body called neuropathy target esterase (NTE). Historically, human exposure to OPs could be biomarked by looking at NTE activity in the brain hours after OP exposure. In addition, lymphocyte NTE can be used as a biomarker, although it is more limited. The new biosensor is highly sensitive and can be assayed from whole blood, unlike the other methods. To test its effectiveness, researchers dosed hens with O,O-di1-propyl O-2,2-dichlorvinyl phosphate (PrDChVP). After 24 hours, they measured NTE activity in the brain and lymphocytes, as well as the brain and blood. The NTE inhibition in lymphocyte and blood were both highly correlated to NTE inhibition in the brain, suggesting that "the biosensor NTE assay for whole blood could serve as a biomarker of exposure to neuropathic OP compounds."
The study suggests that the biomarker can predict the onset of OP compound-induced delayed neurotoxicity (OPCIDN), and serve as "an adjunct to its early diagnosis." Neuropathy is a common result of OP poisoning. Symptoms of neuropathy include imbalance, tingling sensations, weakness, and severe pain and/or numbness in the limbs. The disease is widespread. A report released in 2001 from The Neuropathy Association, "The Incidence, Characteristics and Costs of Medicare Beneficiaries with Neuropathy," shows that the disease impacts millions of Americans, costing billions of dollars. The report examined 1999 Medicare records and "revealed 3.4 million Medicare beneficiaries with neuropathy accounted for $3.5 billion in claims."
The problem is that many people who suffer from neuropathy are unaware they have the disease. Neuropathy "appears in many different forms and it is believed that certain toxins and chemicals are among its causes," said Dr. Norman Latov, director of The Neuropathy Center of Weill Cornell Medical College and medical and scientific director of The Neuropathy Association. "Neuropathy may be the most prevalent undiagnosed and often untreatable nerve disease known to medicine today."
Public knowledge of neuropathy, as well as its connection to organophosphate pesticide exposure, is limited. This is detrimental to public health protection, considering the widespread use of OP pesticides. In 1999, EPA's Office Pesticide Programs, Health Effects Division, reported that four OP pesticides, phosmet, proetamphos, chlorpyrifos, and dimethoate, had consistently high rankings in being responsible for symptoms, health care facility visits, hospitalizations, and fatal outcomes in adults and children. These four OP pesticides are responsible for 90% of pesticide exposures reported in children under six to the Poison Control Centers around the country from the 1993-1996. The report also stated that "children, under six exposed to organophosphates, were three times more likely to be hospitalized, five times more likely to be admitted for critical care, and four times more likely to have experienced a major medical outcome or death, than if exposed to some other, non organophosphate, pesticide."
ABSTRACT. Exposures to chemical mixtures have reportedly produced unexpected effects. Examination of new case studies, as well as those previously reported, shows that when the human body is exposed to mixtures of chemicals that include lipophilic and hydrophilic species, the lipophiles facilitate the absorption of the hydrophiles at enhanced levels and produce effects that are not expected from an individual chemical. These effects include enhanced acute and chronic responses, low-level concentration response, and unexpected target organ attack. Octanol:water partition coefficients are predictive of relative lipophilicity and hydrophilicity. The findings have implications for safe drinking water standards, air quality standards, safe industrial and environmental exposure levels, product formulation, product labeling, and protocols for toxicity testing of chemical products.
On June 18, 2003, The New York Times reported that scientists from the Environmental Protection Agency (EPA) say there is "sufficient evidence" to conclude that the country's most widely used pesticide, atrazine, causes sexual abnormality in frogs. They are recommending that the agency conduct more research to understand atrazine's mechanisms and its broader impact on frog populations.
The scientists noted that there had been six studies involving three species of frogs that show a variety of defects, including frogs with both multiple testes and multiple ovaries, when exposed to the chemical. "Over several studies and environmental conditions and species, atrazine exposure did appear to be having some impact on gonadal effects," Tom Steeger, a scientist with the environmental agency's pesticide office, said on Tuesday in a presentation to an independent scientific panel convened here to assess atrazine's impact on amphibians.
Scientists hired by Syngenta, a major manufacturer of atrazine, said they did not draw the same conclusions from available research. But EPA scientists said many of the industry-sponsored studies had a variety of problems, including testing conditions that led to high mortality in their frogs. The four-day hearing by the panel, which ends on Friday, is an extension of EPA's nine-year review of whether atrazine poses unacceptable risks to the environment and to public health. Later this year, the panel will make recommendations to the agency on how to proceed.
Atrazine is the most commonly used weed killer in North America and can be found in rainwater, snow runoff and ground water, according to Tyrone B. Hayes of the University of California at Berkeley, head of one of the research teams responsible for the studies cited by EPA. Atrazine has been banned in seven European countries.
Dr. Hayes' team found that frogs were affected by atrazine at doses as small as 0.1 parts per billion (ppb), though up to 3ppb is permitted in drinking water by EPA. As the amount of atrazine increased, up to 20 percent of frogs exposed during their early development produced multiple sex organs or had both male and female organs. Many also had small, feminized larynxes. When asked if atrazine is also a threat to people at low levels, Dr. Hayes said he did not know, adding that unlike frogs, we're not in water all the time. "I'm not saying its safe for humans. I'm not saying it's unsafe for humans. All I'm saying is it makes hermaphrodites of frogs," he said.
In another study, Pennsylvania State University researcher Joseph Kiesecker found that pesticides, including atrazine, play a role in frog leg deformities. His findings suggest that pesticides severely weaken the immune system, making frogs much more susceptible to parasitic infection and deformities such extra and missing legs. Dr. Keisecker's study not only linked atrazine with weakened immune systems in frogs, but slower development and smaller size. The levels of atrazine used by the researchers were below EPA-recommended levels for safe drinking water. Dr. Keisecker commented, "Amphibians have become an important model system. We have to consider that factors that influence infection rates in frogs may also play a role in human diseases."
Steve Tvedten
President
Get Set, Inc.
BLACKSBURG, Va., March 24, 2003 -- A grant from the U.S. Army has led Virginia Tech researchers to discover that exposure to some insecticides may cause a cascade of chemical events in the brain that could lead to Parkinson's Disease.
Jeffrey R. Bloomquist, a neurotoxicologist and associate professor in the university's Department of Entomology, described his findings as part of the International Award for Research in Agrochemicals, a symposium honoring Robert M. Hollingworth, at the annual meeting of the American Chemical Society in New Orleans this week.
"We found low-level exposures set in motion a process with an early onset that develops slowly and is persistent," Bloomquist said. "More surprising is that high-level exposures resulted in few immediate effects that we could observe, but in the longer term there was a delayed effect."
The Virginia Tech researchers studied the levels of dopamine, dopamine transporter protein expression, and the levels of a synaptic protein (alpha-synuclein) in mice exposed to various doses of the insecticide permethrin. The increase in dopamine uptake indicated the mouse's system was reacting to a neurochemical insult caused by the presence of the insecticide. The slow response to high levels of exposure to pesticides is caused, Bloomquist thinks, to the system being overloaded and only after a period of a few weeks is it capable of responding to the insult in the same way as low doses.
In some individuals, dopamine-producing neurons may be challenged by genetic factors or by previous exposure to other neurotoxins. For individuals with a genetic predisposition, exposure to permethrin may trigger chemical events in the brain that result in an increased risk for damage to the area of the brain that is selectively damaged in Parkinson's disease.
The loss of motor skills, resulting in symptoms such as muscle rigidity, shuffling gait, and a rhythmic tremor, has been linked to the loss of dopamine production in the brain. That loss of dopamine is the major neurochemical expression of Parkinson's Disease.
"Our studies have documented low-dose effects of permethrin, doses below one-one thousandth of a lethal dose for a mouse, with effects on those brain pathways involved in Parkinson's Disease," he said. "We have found effects consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism."
Bloomquist also found permethrin exposure resulted in an overproduction of the protein alpha-synuclein at low doses. The accumulation of the protein is a major component of the formation of the Lewy bodies, fibrous tangles observed in the brains of patients with Parkinson's Disease.
The studies so far have concentrated on two-week exposures in mice. Bloomquist hopes to continue the work, looking at longer-term exposure. He is also studying the effects of another widely used pesticide, chlorpyrifos.
Bloomquist and his co-investigator, Dr. Bradley Klein, are supported by a five year, $584,558 grant from the United States Army Medical Research and Materiel Command. One purpose of the Neurotoxin Exposure Treatment Research Program, under which the project was funded, is to determine if military operational and deployment exposures increase risks for neurodegenerative disease and, if so, determine means of protecting troops.
"Permethrin is used worldwide in agriculture and urban settings," Bloomquist said. "Widespread human exposure to this compound occurs, so its effects are not limited to soldiers."
FOR MORE INFORMATION: Jeffrey R. Bloomquist, (540) 231-6129, jbquist@vt.edu.
Research at the Salk Institute has identified a gene that may link certain pesticides and chemical weaponry to a number of neurological disoders, including the elusive Gulf War syndrome and attention deficit/hyperactivity disorder (ADHD). The finding, published in the March 17 online version of Nature Genetics, is the first to demonstrate a clear genetic link between neurological disorders and exposure to organophosphate chemicals; the gene is one that scientists had not studied in previous efforts to find connections between these chemicals and disease.
Dr. Carrolee Barlow, who led the work at the Salk Institute and is now at Merck and Co., Inc., and her team, headed by Christopher Winrow, found in mice that organophosphate exposure inhibited the activity of a genecalled neuropathy target esterase, or NTE. This inhibition either killed the mice before birth, or over time led to a range of behaviors very similar to ADHD. Some of the neurological problems also echoed many of the symptoms seen in Gulf War syndrome.
Barlow's group had originally
been looking at how environmental factors immediately affect the nervous system.
They found that mice bred to lack the NTE gene died before birth. But the group
also found that mice with only one copy of the NTE gene, when
exposed to experimental organophosphates and examined over a prolonged period,
exhibited behavior similar to ADHD. The mice with only one NTE copy had a 40
percent decrease in the NTE enzyme produced by the NTE gene. The mice with normal
NTE genes also showed ADHD-like behavior, though to a lesser degree, when exposed
to organophosphates. The gene is active in parts of the brain controlling movement,
including the hippocampus, the cerebellum and the spinal cord.
At the Salk, researcher
Matthew Hemming in Professor Stephen Heinemann's laboratory is continuing to
work on unlocking the secrets of NTE's activity. The Salk team is working to
detail how losing NTE function results in behavioral and neurological changes,
as well as focusing on what happens when the gene for NTE is turned off in one
part of the brain, but working in other areas ... The researchers are supported
by a $1.5 million grant from the U.S. Department of Defense ..." - The
Salk
Enviornmental Health Perspectives, 111-1, 2003, Science Selections
Studying Household Pesticide Exposures Traditionally, risk assessment of pesticide exposure has focused on agricultural and occupational use of pesticides. However, there is growing evidence that pesticide concentrations may be even higher in urban areas--especially within homes--than in rural areas. In this month's issue, a team of researchers led by Gertrud Berkowitz at the Mount Sinai School of Medicine report that pregnant women in New York City face considerable pesticide exposure [EHP 111:79-84]. The findings are part of Mount Sinai's prospective Children's Environmental Health Study, which is examining the effects of indoor pesticide exposure on fetal growth and development among these women's babies.
Among the pesticides studied
were chlorpyrifos and pentachlorophenol. Chlorpyrifos residues persist up to
two weeks after application, exposing people to levels far above those recommended
by the U.S. Environmental Protection Agency (EPA)--potential exposure to young
infants can reach levels 60-120 times greater than the EPA-recommended reference
levels. Although an agreement between the EPA and pesticide manufacturers ended
the sale of virtually all household-use products containing chlorpyrifos by
late 2001, at the time the study was being set up (1998), chlorpyrifos was the
most frequently used pesticide in Manhattan and Brooklyn, and the chemical may
still be stored in some homes. Pentachlorophenol is used as a fungicide and
herbicide, and was widely used as a wood preservative until the 1970s.
Other studies have quantitated urban use of household pesticides and measured
pesticide exposure in adults and children. This is the first, however, to look
at urinary pesticide metabolites in pregnant women as a marker of their exposure
to these chemicals.
For this part of the study, the cohort included 386 pregnant Hispanic, black,
white, and mixed-race women who went on to give birth at Mount Sinai Hospital
between May 1998 and July 2001. The researchers collected a urine specimen from
each woman during her third trimester and quantified the levels of urinary pesticide
metabolites. Each woman also filled out a questionnaire that assessed her exposure
to pesticides in her home and in common areas of her apartment building.
When considering reported pesticide use by someone living within the home, exposure
was higher among black and Hispanic women, younger women, and single and cohabiting
(versus married) women. However, when considering any reported pesticide use,
including that by an exterminator or building employee (such as a superintendant),
the sociodemographic differences disappeared. Only 46.4% of the women reported
that they or a family member had applied pesticides during the woman's pregnancy.
However, when pesticides applied by exterminators and building employees were
also considered, a total of 72.3% of this pregnant cohort were exposed, a number
close to the 80% previously reported for a different pregnant New York cohort.
However, the researchers found that pesticide metabolite levels were higher
in this population than in some previously described populations. For example,
the median metabolite concentration of 11.3 µg/g for chlorpyrifos was
similar to that found in another recent study of children but higher than the
median found in the National Health and Nutrition Examination Survey (NHANES)
III. Similarly, the median metabolite concentration of 7.3 µg/g for pentachlorophenol
was over six times that found in NHANES III but similar to levels among children
in a recently reported German study.
To explain the discrepancies
between questionnaire and metabolite data, the researchers point out that questionnaires
tend to yield only limited information on the specific type and amount of exposure,
and are also subject to over- and underreporting. On the other hand, metabolite
data reflect not only home-use pesticide exposures but also exposures through
food, the workplace, and other sources. While understandable, these limitations
point up the difficulty of accurately estimating pesticide exposure and should
be considered, the authors say, when interpreting the results of this and similar
studies.
Reuters Health, http://www.nlm.nih.gov/medlineplus/news/fullstory_11150.html
By Todd Zwillich
Wednesday, January
8, 2003
WASHINGTON (Reuters Health) - Scientists and environmental groups urged a federal advisory panel Wednesday to recommend a ban on chemical industry experiments that test the safety of pesticides and other potentially toxic chemicals in humans.
Labeling the experiments unethical and scientifically suspect, the groups asked experts on a National Academy of Sciences panel to condemn the studies and recommend that government regulators refuse to consider them when evaluating the safety of companies' chemical agents or pollutants.
But representatives of the
pesticide industry defended the experiments, saying that they are ethically
sound and essential to
accurately determining safe exposure levels for members of the public.
Manufacturers of pesticides or other chemicals sometimes give adult volunteers a dose of the product in order to determine what levels humans can tolerate without getting sick. Determining a safe level for humans is necessary before companies can gain Environmental Protection Agency (EPA) approval to market most pesticides and other chemicals.
Scientists attacked the studies Wednesday, calling them unethical because people can only be hurt, and not helped, by receiving doses of toxic chemicals.
Most ethical standards for human medical research, including the Nuremburg Code created after the trials of Nazi doctors conducting research on World War II Holocaust prisoners, require that study participants stand a chance of gaining from research conducted on them.
"There is no benefit
to the health of a subject nor to the health of anyone else," said Dr.
Lynn Goldman, a professor of environmental
health sciences at Johns Hopkins University and chair of the Children's Environmental
Health Network.
Eberhart told the panel that animal studies have often failed to accurately predict safe pesticide levels for humans.
"Only human data directly reflects human response," said Judith A. MacGregor, a researcher with Toxicology Consulting Services, a private research company.
Lawyers for the EPA and pesticide industry are set to argue the case before the Federal Appeals Court in Washington in March.
The NAS panel is due to
release its recommendations on human-based chemical testing in about one year,
officials said.
January 2003. Environmental Health Perspectives 111 (1): 79-84. Gertrud S., Josephine Obel, Elena Deych, Robert Lapinski, James Godbold, Zhisong Liu, Philip J. Landrigan, and Mary S. Wolff
Abstract: Evidence
is growing that indoor pesticide exposure is of considerable magnitude in the
United States and that pesticide concentrations may be especially high in urban
areas. Of particular concern is exposure of pregnant women because animal data
suggest that exposure to pesticides during pregnancy and early life may impair
neurodevelopment in the offspring. To investigate the relationship between prenatal
exposure to indoor pesticides and infant growth and development, we are conducting
a prospective, multiethnic cohort study of mothers and infants delivered at
Mount Sinai Hospital in New York City. This article provides data on
pesticide exposure based on questionnaire items and analysis of maternal urinary
metabolite levels among 386 women. Both the questionnaire and laboratory data
revealed that exposure to indoor pesticides was considerable. The proportion
of women estimated from questionnaire data as having been exposed during pregnancy
to indoor pesticides (approximately 70%) was somewhat lower than the 80-90%
of American households who reportedly used pesticides in previous surveys, but
some of the latter surveys included both indoor and outdoor pesticide use. Urinary
metabolite levels of 3,5,6_trichloro_2_pyridinol (TCPy; median = 11.3 µg/g
creatinine), phenoxybenzoic acid (PBA; median =19.3 µg/g creatinine),
and pentachlorophenol (PCP; median =7.3 µg/g creatinine)
were higher than those reported in other studies of adults in the United States.
Furthermore, no associations were evident between the pesticide questionnaire
data and the urinary metabolites.
Assessments of sociodemographic and building charactertics with questionnaire data and the metabolite levels revealed no consistent trends. Significant temporal variations were observed for urinary PBA but not TCPy or PCP. The temporal variations for PBA were consistent with seasonal spraying of pyrethroid pesticides. These data underscore the need to assess the potentially adverse effects of pesticide exposure on fetuses and infants and the importance of finding alternative methods for pest management to reduce pesticide exposures.