earlier "new developments about endocrine disruption"
see archives: 1999, 2000,
Also see the Scientific Epilogue in the paperback
on endocrine disruption has exploded since Our Stolen Future
was published. New results, new syntheses, new policy recommendations
and debates appear, it would seem, almost weekly. Below is a discussion
of important new developments in the field. For a broad overview
of the scientific trends since OSF was published,
see Broad Trends. And
for pointers to a
host of important new research results, organized by topic,
visit Recent Important Studies.
Note that beginning in 2003, press coverage of endocrine disruption was placed in archives at:
FDA: A small step for BPA... and a huge leap for the FDA. Investigative reporting by the Milwaukee Sentinel Journal reveals that a commentator on bisphenol Afor the 'non-profit, non-partisan' organization STATS is part of a unit that has worked for the tobacco industry and is now participating in a large-scale effort to prevent regulations on BPA.
Trevor Butterworth: BPA poseur unmasked. Investigative reporting by the Milwaukee Sentinel Journal reveals that a commentator on bisphenol Afor the 'non-profit, non-partisan' organization STATS is part of a unit that has worked for the tobacco industry and is now participating in a large-scale effort to prevent regulations on BPA.
Losing on science, BPA lobbyists plan to play fear card. Leaked to the press, minutes of a BPA planning session provide insight into tactics that industry is preparing to use to regain the upper hand in its effort to protect BPA from bans.
A timeline of BPA research and FDA's decisions. For the last decade, FDA's decision-making on BPA has consistently given undue weight to flawed industry studies while repeatedly ignoring data published in the scientific literature by academic and government scientists.
Controversy swirls around a key paper used by the US FDA to reach the conclusion that BPA is safe. The FDA's draft decision on BPA relied largely upon one industry funded study that found no adverse reproductive effects caused by low-dose exposure to BPA. But controversy is building swiftly about the scientific validity of this paper, as important flaws are identified and as the lead author contradicts herself and her published paper at two federal hearings. Reports of a bisphenol A fire in her laboratory add to the questionable validity of the work, according to investigative reporting by the Milwaukee Journal Sentinel.
A review of scientific literature published on bisphenol A is flawed by errors of omission, commission, misreprentation and misinterpretation. The review, carried out by a scientist at the California Dept. of Toxic Substance Control 'working on his own time' and thus not representing the agency's position, ignores a large body of literature on low-dose effects of BPA, uses criteria that would, if accepted, invalidate 30 years of well-established research on diethylstilbestrol (DES) and employs a statistical method that violates basic statistical principles.
A new analysis by the CDC indicates that many Americans are exposed to bisphenol A at levels above the current safety threshold set by the EPA based upon decades-old data. These levels are significantly higher than those sufficient to cause a wide array of health effects in animals following exposure in the womb. Exposure to another industrial chemical, 4-tertiary-octylphenol, is also widespread. The CDC data also reveal that children are more exposed to BPA than adolescents, who in turn had higher concentrations than adults. Families with high household incomes had the lowest levels.
Thirty-eight of the world's leading scientific experts on bisphenol A have warned policymakers of potential adverse health effects of exposure to the widespread molecule used to make plastic and food can lining. They conclude that average levels in people are above those that cause harm to animals in laboratory experiments. And they calculate that average serum levels in people can only be explained by assuming that exposures today are already above the level that EPA considers safe.
A new study with mice is the first to link low level neonatal exposure to bisphenol A to uterine diseases that women develop as they age, including fibroids, adenomysois and cystic ovaries. Some of the adverse conditions induced by BPA in mice have been previously described in daughters of mothers who took the drug diethylstilbestrol, a synthetic estrogen which is structurally and functionally similar to BPA. These uterine defects, which often require severe medical intervention, are common and appear to be increasing in women but remain poorly understood.
In a unique, new study, scientists report that women exposed to relatively high levels of DDT prior to mid-adolescence are 5 times more likely to develop breast cancer later in life than women with lower exposures. In contrast, exposure after adolescence is not associated with increased risk. This new approach-- taking age of exposure into account-- may help explain why studies that depend upon exposure measurements after breast cancer develops often report no association.
A substantial body of scientific evidence published in the peer-reviewed literature challenges the central tenet of regulatory toxicology, which assumes 'the dose makes the poison.' Experimental data now conclusively show that some endocrine-disrupting contaminants can cause adverse effects at low levels that are qualitatively different from those caused by high level exposures. Regulatory toxicology has assumed that high dose experiments can be used to predict low-dose results. These findings invalidate that assumption. As a result, it is highly likely that health standards established using standard toxicological procedures are too weak.
Experiments with mice show that exposure during pregnancy to very low doses of bisphenol A scrambles the chromosomes of their daughters' fertilized embryos, ie., the pregnant female's grandchildren. This third-generation effect is possible because the eggs of a female mammal, including human, are formed while the female is still in the womb. Exposure to BPA at comparable levels appears widespread among people in the United States, because of its use in common consumer products, including polycarbonate plastic and food cans.
A common plastic molecule to which virtually all Americans are exposed may interfere with the standard medical treatment for prostate cancer, according to new experiments with human prostate tumors implanted into mice. The doses of the plastic molecule, bisphenol A, were chosen specifically to be within the range of common human exposures. Tumor size and PSA levels were significantly greater in exposed animals just one month after treatment.
Testosterone levels have declined on average 1.2% per year in Massachusetts men, or 17% overall, since the late 1980's. The pattern is consistent with other long-term trends in male reproductive health, including decreases in sperm count and increases in testicular cancer, hypospadias and cryptorchidism. The study controlled for the normal decline in testosterone levels that takes place as men age, as well as potential confounding variables like smoking and obesity.
Experiments with rats demonstrate that low level exposure to bisphenol A during fetal growth causes breast cancer in adults. At all levels tested down to 2.5 parts per billion, BPA induced formation of aberrant cell growth patterns associated in rodents and people with breast cancer. Levels only 5 times higher than EPA's current safe level caused carcinoma in situ. Using these results to set safety standards would radically reduce use of BPA in plastics and resins.
Data gathered by the US CDC reveal strong associations between exposures to persistent contaminants and risk of type 2 diabetes. In a sample of 2,016 Americans, diabetes risk rose significantly with exposure to five of 6 studied contaminants (a PCB, two dioxins and three pesticides). Using an index reflecting simultaneous exposure to the mix of contaminants, the study found that people in the highest exposure category were almost 38 times more likely to have diabetes than those in the lowest.
A large study of men in the Boston area finds that increases in a metabolite of the phthalate DBP are associated with impaired sperm quality, at exposure levels within the range experienced by the general population. Both sperm concentration and sperm motility were more likely to be beneath WHO reference levels at higher exposure levels to MBP, the metabolite. Metabolites of DEHP, DMB and BbZP were not associated with lowered sperm quality.
An analysis of published research in peer-reviewed journals reveals important examples of scientists failing to disclose links to industry, including by one of epidemiology's biggest names. According to Swedish researchers, Sir Richard Doll, co-author of a famous paper minimizing the role of chemicals in causing cancer, failed to disclose funding from Monsanto, Dow, ICI and the American Chemistry Council for work on vinyl chloride, dioxin and phenoxy herbicides.
The risk of adult-onset asthma is more than double for workers employed in offices with plastic wall-lining. This conclusion emerged from a case-control study in southern Finland examining the work and home environment of 521 asthmatics and 932 controls. The researchers suggest that the association is a result of increased exposure to the phthalate DEHP in work environments that have used materials containing polyvinyl chloride, which can be as much as 40% by weight DEHP.
Environmentally-relevant levels of the phthalate DEHP suppress aromatase activity in the brain of young male rats following perinatal exposure, while higher doses stimulate aromatase. This enzyme is crucial for masculinization of the male brain. The effects differed between males and females, and also differed depending upon when after birth aromatase was measured. Impacts on females were seen at the lowest dose tested, which was calculated to be similar to the median daily intake of German citizens.
The phthalate DEHP increases allergic reaction to a mite allergen in mice at levels within the range deemed safe by current EPA standards. The dose-response relationship followed an inverted-U pattern, with an intermediate dose causing larger effects than the highest dose use. This is the first report of non-monotonic response for a phthalate. The results implicate DEHP as a possible causal agent in increasing prevalence of allergic reactions in developed countries.
High dose experiments fail to accurately predict low dose responses to endocrine-disrupting compounds, but this doesn't support the idea, called hormesis, that low dose stimulation is beneficial. Standard toxicology tests at levels that are overtly toxic, and looks for a 'safe level' at which no toxic response can be detected. The problem is that some compounds, like bisphenol A, turn on genes at levels a million or more times lower in concentration than the levels required to be overtly toxic. Hence the standard tests used by toxicologists to set safety thresholds may have missed many adverse impacts.
Industry research on the safety of bisphenol A is beset by problems in experimental design and execution. One central flaw is their failure to use positive controls, which are used in experiments to demonstrate that the research methods and materials are capable of detecting adverse effects when they occur. They also use animal strains known to be insensitive to any estrogen, not just BPA, and they misrepresent analyses in their publications, even calling positive results negative.
Advances in environmental health sciences are opening up possibility that we may be able to prevent many of today's chonic diseases. As this science advances, and as people, government, and companies act upon these developments, it is possible to envision a transformation in public health just as radical, and positive, as that achieved when society cleaned its water of infectious-disease agents.
Prenatal exposure to bisphenol A, a ubiquitous endocrine-disrupting contaminant, causes long-lasting changes in female rat breast tissue that increase the risk of cancer and also make the animals more sensitive to cancer-causing chemicals as adults. The study strengthens support for a link between increasing rates of breast cancer in recent decades and increasing exposure to chemicals like BPA. It also indicates that human epidemiological studies that fail to incorporate developmental exposures can't be trusted to identify cancer-causing agents.
An endocrine-disrupting fungicide, vinclozolin, causes chronic diseases of ageing in rats following exposure in the womb, and these disease states are inherited epigenetically across multiple generations without changes in DNA sequence. Adverse effects included increased incidence of tumors, diseases of the kidney and prostate, testis abnormalities and impaired immune function. Observations also indicated very early onset of ageing, although it was not possible to distinguish this with certainty from other diseases.
Early life exposure to bisphenol A at environmentally-relevant levels causes precancerous lesions in the prostate of adult rats, linking BPA to prostate cancer. Animals exposed perinatally to BPA and estradiol develop a prostate lesion in adulthood, high-grade PIN, that is generally accepted as a precursor to prostate cancer in humans. For BPA, the effect requires changes in adult hormone levels that mirror estrogen changes in ageing men. The effects are associated with failures in a key gene to undergo hypermethylation, following perinatal exposure.
Experiments with eel embryos indicate the collapse of Atlantic eel populations is likely to be the result of the acute sensitivity of eel embryos to PCB and dioxin contamination. Most eels from European locations carry contaminant levels well within the range that, based on these experiments, would severly impair eel embryo survival. Damage seen in the embryos is typical for dioxin-induced impacts in a number of fish species.
An analysis of public records and court documents reveals an industry campaign to undermine steps taken by the US occupational health agency to develop safety standards for exposure to hexavalent chromium. By splitting a study into two parts and publishing them separately, industry scientists made a significant elevation in risk of lung cancer go away. This study was never submitted by industry in its entirety to OSHA, but only became available when it was discovered in bankruptcy legal filings.
EPA's current 'reference doses' for exposure to several phthalates may be far too high, perhaps by a factor of 100-fold or more. The reference dose is the level thought low enough to cause no adverse effects. This conclusion is based upon calculations, using pharmokinetic models, of the maternal exposures that would have been required to cause urinary phthalate metabolite levels associated with altered genital tract development in boys.
An environmentally-relevant mixture of pesticides unexpectedly weakens tadpole immune function, resulting in fatal infections. A study of pesticide effects on frog tadpoles finds unexpectedly that a mixture of 9 pesticides, each at environmentally-relevant levels (0.1 ppb), undermines the tadpoles' defenses against a bacterial infection. 35% of animals exposed to the mixture died compared to 4% of those treated with pesticides one at a time. Of those that survived, 70% of the animals exposed to the mixture developed bacterial infections whereas none of the controls or animals exposed to one pesticide at a time showed similar symptoms.
Industry depends upon flawed science to argue for the safety of bisphenol A. Human exposure to bisphenol A is widespread because of its use in polycarbonate plastic and epoxy resins used to line food cans. Current US safety standards are based upon data from the 1980s, even though over 100 recent studies show it has effects at levels thousands of times lower than today's standard. While chemical manufacturers claim in public statements that "high-quality repeat studies in independent laboratories have not been able to replicate" claims that bisphenol A causes adverse effects at low levels, a careful analysis of the 'high quality' studies they reference reveals deep flaws, and that industry-financed research on the health effects of bisphenol A is strongly biased against finding adverse effects.
Industry mounts coalition effort to defeat California legislation on bisphenol A and phthalates. They argue that bisphenol A is millions of times lower than levels required to harm animals. But to make their case they must ignore over 90% of the recent scientific literature on bisphenol A and depend upon a small number of flawed studies funded and conducted by industry.
Industry spokesman has history of fraud and perjury. An investigative story in Mother Jones magazine reveals that Gilbert Ross, Executive/Medical director of the American Council on Science and Health, was convicted of medical fraud and perjury, and that he served time in jail in 1996. He was subsequently hired by ACSH, an organization that has close ties to industry and regularly misrepresents scientific results on links between contamination and health. Earlier this year, Ross wrote an essay for the ACSH website containing blatant misrepresentations of research into the health effects of bisphenol A.
Common plastic molecule causes insulin resistance in mice at low exposure levels. Experiments with mice show that exposure to bisphenol A within the range that people commonly experience causes insulin resistance. The results indicate that exposure to low levels of BPA may be involved
in 'metabolic syndrome,' including type II diabetes. Human exposure to
BPA has become almost universal in the last 2 decades, because of its
use in polycarbonate plastic, epoxy linings for food cans, and cavity
prevention tools for children.
Decline in sex ratio in First Nation community, Canada. The sex ratio in a First Nation community near Sarnia, Ontario, has dropped to fewer than 35% boys, far below normal. Prior to 1993, the sex ratio appeared to be normal and stable. Since that time, it has declined significantly, with the strongest decline in the last 5 years. The community lives in close proximity to a large petrochemical complex. Researchers propose that chemical exposures may be causing the decline. This would be consistent with some but not all prior studies.
Scientists criticize hormesis. In a peer-reviewed commentary published in the scientific journal of the US National Institute of Environmental Health Sciences, 5 scientists from government, academic and independent laboratories raise strong challenges to proposals that 'hormesis' be used to justify weakening public health standards. They conclude that it is irresponsible for proponents of hormesis to portray chemicals with numerous adverse effects as having "benefits" while ignoring their hazards.
Scientists call for action on endocrine disruption. In June 2005, over 100 research scientists with active research programs studying endocrine disruption from 15 countries issued a joint, signed statement concluding that scientific uncertainty should not delay precautionary action on reducing the exposures to and the risks from endocrine disrupters. According to their assessment, current safety standards are ill-equipped to deal with risks caused by endocrine disrupters and that current testing procedures may lead to serious underestimations of risk.
Bisphenol A linked to miscarriage in people. In a small prospective study, researchers in Japan report that bisphenol A levels are higher in women with a history of repeated spontaneous miscarriages. This research was based on proof that BPA causes meiotic aneuploidy in mice. Meiotic aneuploidy is the commonest cause of miscarriage in people. The researchers also followed the pregnancies of the women to completion, and found evidence of aneuploidy in several of the miscarried fetuses. Bisphenol A is widely used in consumer product, including polycarbonate water bottles, epoxy linings for food cans and coatings for papers. Almost all Americans carry measureable levels of BPA, at levels within the range known to cause changes in cellular responses.
Infants contaminated by phthalates used in hospitals. Infants in a hospital that has continued use of phthalate-containing plastics in equipment used in neonatal intensive care units have higher phthalate metabolites in their urine than one that switched to other materials. Infants most exposed to DEHP had five times the level of a metabolite as those least exposed.
New research with rodents suggests that your infertility could be the result of an environmental exposure that your great-grandmother experienced while she was in her mother's womb. In laboratory experiments, exposure to two endocrine disrupting compounds at a key time in fetal development seriously impaired sperm count in almost all males in 4 subsequent generations, even though the exposure occurred only once. The changes appear not to be mediated by DNA mutation, but instead through epigenetic changes in DNA methylation. More...
In mice, exposure to bisphenol A in the womb at extremely low levels alters mammary gland development around puberty. The changes, which involved increased numbers of terminal buds and an increased sensitivity to estrogen, are consistent with an increased risk to breast cancer. The levels of exposure are within the range that many people experience More...
For the first time, researchers have identified an association between pregnant women’s exposure to phthalates and adverse effects on genital development in their male children. The pattern of genital changes seen in these baby boys is consistent with the "phthalate syndrome" previously observed in rodents prenatally exposed to phthalates. It is also suggestive of "testicular dysgenesis syndrome," a human health condition proposed to be linked to exposure to endocrine-disrupting compounds. The adverse effects are seen at phthalate levels below those found in one-quarter of women in the United States, based on a nation-wide survey by the Centers for Disease Control. More...
for audio files of an international teleconference with the scientists about these results
Two estrogenic contaminants cause adverse effects in prostate development in mice at levels to which millions of Americans are exposed each year. The results raises questions about the possible contributions of these compounds, the birth control agent ethinylestradiol and the plastic monomer bisphenol A, in human prostate diseases, including prostate cancer. The study also shows the futility of predicting the developmental consequences of low-dose exposures based on high-dose experiments. More...
Industry responses to new science and policy initiatives on bisphenol A, an endocrine-disrupting molecule that leaches from polycarbonate plastic, are based on highly flawed misrepresentations of current scientific knowledge. The compound is now linked by animal experiments to a wide array of health effects following exposure to extremely low doses. Public comments from the American Council on Science and Health and junkscience.com contain blatant errors that reveal either a lack of scientific understanding. More...
A flood of new information about bisphenol A revealing both widespread human exposure and effects at extremely low doses sparks a call for a new risk assessment of the ubiquitous compound.
Bisphenol A, the basic building block of polycarbonate plastic, alters
development of the reproductive tract, the immune system, increases
prostate tumor proliferation, changes brain chemistry and structure and
affects an array of behaviors, including hyperactivity. Of 11 studies
of the compound's effects at low doses, none funded by industry
reported impacts. In contrast, 94 out of 104 government-funded studies
found effects. This summary includes audio files of an international teleconference about bisphenol A. More...
Research in Denmark finds that low sperm counts in an earlier study was not the result of sexual immaturity in the study population. In 2000, a Danish study of young military recruits reported that many of them had low sperm counts, lower than earlier Danish measurements from prior decades. One explanation offered for this observation was the possibility that they were not yet sexually mature. This new study finds that sperm count of a subset of these young men did not increase as they were tracked over the next four years. Hence the low sperm counts are unlikely to be due to sexual immaturity. More...
Several 'weakly' estrogenic compounds including bisphenol A and endosulfan are as powerful as estrogen at increasing calcium influx into cells and stimulating prolactin secretion. The effects are mediated by a cell membrane surface receptor instead of nuclear hormone receptors, the focus of most studies to date. Changes in calcium and prolactin occur at extremely low doses, well within the range of human exposures. More...
Traces of bisphenol A were detected in 95% of samples examined in a survey of the chemical's presence in Americans. The study also detected a metabolite of nonylphenol in 51% of samples examined. The concentrations were similar to those observed in other human studies. The levels of BPA observed in this survey are within the range shown in laboratory studies to cause adverse effects, but are thousands of times lower than the level EPA currently considers safe. That 'reference dose' was established in 1988, long before low dose studies of bisphenol A were initiated. More...