Presented to the Senate Committee on Environment and Public Works, Hearing on the Government Accountability Office’s Investigation of EPA’s Efforts to Protect Children’s Health, March 2010

By Ted Schettler MD, MPH

(A fully referenced version of this testimony can be found here.)

Thank you for the opportunity to submit testimony to this Committee. My name is Ted Schettler and I am Science Director of the Science and Environmental Health Network (SEHN). SEHN is a not-for-profit organization working in collaboration with environmental and public health groups, health professionals, legal scholars, ethicists, government officials, legislators, and others seeking to protect public health and the environment for this and future generations.

I am a physician and also have training in public health and environmental medicine. I served on the U. S. Environmental Protection Agency’s (EPA) Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) from 1996-1998 and the Endocrine Disruptor Methods Validation Subcommittee from 2001-2003.

It is now 13 years since President Clinton issued executive order 13045, establishing an interagency Task Force on Environmental Health Risks and Safety Risks to Children and requiring every agency proposing regulatory action to consider its impacts on children. The new report from the Government Accounting Office contains recommendations intended to reinvigorate EPA’s early emphasis on children. I have been asked to comment on the US Environmental Protection Agency’s efforts to protect children’s health from my perspective.

The Vulnerability of Developing Children

Compared to adults, developing children are uniquely susceptible to hazardous environmental exposures. Windows of vulnerability during in utero development, infancy, and childhood increase risks of some adverse health outcomes resulting from exposures, often with lifelong consequences. Among the better known examples, lead exposures that have minimal or no discernable impacts in adults can permanently alter brain development and function in a child. Similarly, fetal alcohol exposures can have lifelong impacts in children, while the same exposure in adults has only mild, transient effects.

Many of the reasons for this vulnerability are well understood. During fetal, infant, and child development, cells rapidly divide, tissues and organs are formed, and signaling mechanisms, hormone levels, feedback loops, and their set points are established. Exposures to hazardous chemicals as well as other environmental influences may perturb these events through various mechanisms, with long-term consequences.

It is also important to recognize that environmental exposures during development can increase the risk of chronic, degenerative diseases much later in life. For example, life-long cumulative exposures to lead, including developmental exposures, increase the risk of cognitive decline and Parkinson’s disease in people decades later. Animal studies show that early life exposure to certain pesticides seem to prime the brain, making it more susceptible to further exposures in adulthood, resulting in neurodegeneration in areas responsible for Parkinson’s disease. Indeed, epidemiologic studies show an increased risk of Parkinson’s disease in agricultural communities where pesticides are heavily used. Thus, while protecting children, we are also lowering the risk of various diseases and disabilities much later in life.

During the 1990s it appeared that EPA was taking steps to address many unique aspects of children’s environmental health. But since then many of these efforts have fallen short. Two examples from my own experience are illustrative.

Endocrine disruptors

The first example has to do with the potential for some commonly encountered chemicals to disrupt the function of hormones and other chemical messengers that are vital to normal human development and function. These chemicals are known as endocrine disruptors.

An endocrine disruptor is “an exogenous agent or mixture of agents that interferes with or alters the synthesis, secretion, transport, metabolism, binding action, or elimination of hormones that are present in the body and are responsible for homeostasis, growth, neurological signaling, reproduction and developmental processes.” Endocrine disruptors interfere with the body’s key signaling pathways and can cause harm, especially during fetal and early life development.

Endocrine disruptors gained increased public and scientific attention during the 1990s, although the capacity for certain industrial chemicals to mimic or otherwise interfere with hormone function was known at least as long ago as the 1930s. For example, in 1938, scientists showed that bisphenol A, a chemical used to make many consumer products today, has estrogen-like properties, although its molecular structure is quite different from naturally-occurring estrogen. The use of this chemical is now so widespread that, according to the Centers for Disease Control and Prevention, 93% of all Americans have residues of bisphenol A in their urine. Recent studies link bisphenol A levels to altered brain development, heart disease, and diabetes.

In the 1950s, 1960s, and early 1970s the potent synthetic estrogen diethylstilbestrol was purposely given to many pregnant women with the unfounded promise that it would help to prevent miscarriages and promote healthier pregnancies. Tragically, fetal exposure to DES resulted in abnormalities of reproductive tract development in females and males and a sharply increased risk of reproductive tract cancers in women decades later. Thus, we learned through uncontrolled human experimentation that certain chemicals could profoundly alter development, with consequences that were often not apparent at birth and might only become manifest decades later.

During the 1980s and 1990s exposures of wildlife to industrial chemicals and their health effects were increasingly reported in the scientific literature. Reproduction and development of birds, amphibians, reptiles, and mammals have been affected by exposure to endocrine-disrupting chemicals. Fish in numerous rivers, including the Potomac, have disrupted sexual development—specifically, feminized male fish. When this finding was first noted in England in the 1990s, it was considered unusual. It is now recognized as a widespread, pervasive phenomenon.

Based on findings in wildlife and laboratory animal studies, many scientists are concerned that the increasing incidence of cancer of the testis, prostate, and breast; birth defects of the male reproductive tract; lower sperm counts; behavioral disorders; diabetes; and a wide range of other abnormalities in humans may result, at least in part, from exposures to endocrine-disrupting chemicals.

A recent report shedding new light on a puzzling observation that has baffled scientists for years is illustrative. Many studies find a higher incidence of testicular cancer and male reproductive tract abnormalities in Danish men than in nearby Finland. Finnish boys have larger testes and higher sperm counts than Danish boys. Reasons for these differences have been unclear. Recently, scientists analyzed the breast milk of 68 women from the two countries for 121 different chemicals and found significantly higher levels in the milk of the Danish women. The chemicals tested for included flame retardants, pesticides, phthalates, polychlorinated biphenyls, dioxins, and furans. These chemicals are commonly identified in biomonitoring studies around the world, including in the US. Their concentration in breast milk is a good indicator of fetal exposures during pregnancy. This kind of study cannot definitively establish a causal relationship between the different levels of these industrial chemicals in mothers in Denmark and Finland and the patterns of male reproductive tract abnormalities in the two countries. But a causal relationship is plausible, based on what we know about the effects of many of these chemicals in laboratory animal studies. Current environmental exposures also include hundreds if not thousands of chemicals that were not tested for in this study that may also be part of the problem.

Because of growing concern about endocrine-disrupting chemicals, in 1996 the EPA created the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) in response to a Congressional mandate in the Food Quality Protection Act and authorization in the Safe Drinking Water Act Amendments of 1996.

These laws specified that EPA:

“…develop a screening program, using appropriate validated test systems and other scientifically relevant information, to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate.”

The laws required EPA to develop a screening program by August 1998, to implement the program by August 1999, and to report on the program’s progress by August 2000. Unfortunately, EPA is now about a decade behind.

I served on the EDSTAC. The committee included representatives from industry, government, environmental and public health groups, and academia. We were charged with developing consensus-based recommendations for a screening program that would provide EPA the necessary information to make regulatory decisions about endocrine effects of chemicals.

The committee delivered a final report by the statutory deadline of August 1998. It included a groundbreaking priority-setting, screening, and testing approach that encompasses the universe of chemicals in use today, evaluates a range of human health and ecological effects, and recommends a feasible, health-protective approach. The committee:

• recognized that problems with endocrine disruption go beyond estrogen, and also called for screening of chemicals for interference with male androgens and thyroid hormone.

• recommended the use of new technologies to rapidly pre-screen numerous chemicals to see if they interact with hormone receptors in vitro (in the “test-tube”). The committee recommended that this technology be used to rapidly evaluate the ten thousand most widely used chemicals within one year.

• recommended a computer-based tracking system allowing information about health effects and exposure to be collected in one place to facilitate prioritization. That database didn’t exist then, and it doesn’t exist today.

• urged EPA to accept nominations from the public of chemicals or chemical mixtures for expedited testing. This would allow workers or impacted communities to press for more information about chemicals to which they are exposed.

Unfortunately, EPA missed deadline after deadline and became bogged down in an endless set of validation exercises that remain unfinished. Many of the recommendations were discarded. Finally, a decade late, EPA implemented an extremely scaled-down version of the program when it issued the first test orders in October 2009. Only 67 chemicals are on the list for this first round of screening – mostly pesticides, including a number of chemicals that are already well-known endocrine disruptors. Meanwhile tens of thousands of chemicals in consumer products, food, water, and air have not been tested for endocrine-disrupting properties.

In 2009 the Endocrine Society evaluated the science on endocrine disruptors and concluded:

“The evidence for adverse reproductive outcomes (infertility, cancers, malformations) from exposure to endocrine-disrupting chemicals is strong, and there is mounting evidence for effects on other endocrine systems, including thyroid, neuroendocrine, obesity and metabolism, and insulin and glucose homeostasis.”

The Endocrine Society is comprised of over 14,000 research scientists and physicians from over 100 countries. This statement has since been endorsed by the American Medical Association, which is joining the Endocrine Society in calling for decreased public exposure to endocrine-disrupting chemicals. The American Chemical Society just issued a similar statement with additional recommendations for: “More rapid advancement of the congressionally mandated effort by the EPA, called the Endocrine Disruptor Screening Program (EDSP).”

As a result of EPA’s failure to implement a strong endocrine disruptor screening program, the Endocrine Disruption Prevention Act was introduced in Congress in 2009. This act would authorize a new research program at the National Institute of Environmental Health Sciences (NIEHS) to identify endocrine-disrupting chemicals, using the most current science. It would establish an independent panel of scientists to oversee research and develop a prioritized list of chemicals for investigation. If the panel determined that a chemical presented endocrine-disrupting concerns, it would compel the federal agencies with established regulatory authority to report to Congress and propose next steps within six months. NIEHS has the capacity to carry out such a research program if provided with appropriate resources. But EPA remains the regulatory authority responsible for protecting children from environmental threats.

I have focused here on endocrine-disrupting chemicals, but my concerns about human exposures to industrial chemicals are not limited to those with endocrine-disrupting properties. Well-known flaws in the Toxic Substances Control Act (TSCA) have allowed tens of thousands of untested industrial chemicals to stay on the market and new ones to be brought to market with limited or no toxicity information. These include chemicals to which workers and people in the general population, including pregnant women and children, are regularly exposed.

The EPA Office of the Inspector General’s (OIG) report, released in February 2010, and previous GAO reports clearly describe these problems. Not only are basic safety data lacking, but whatever limited information is submitted to the agency is frequently accompanied by requests to protect it from public disclosure. The OIG report concludes that the agency’s process is “predisposed to protect industry information rather than to provide public access to health and safety studies.” Physicians and other healthcare professionals do not have access to the data they need in order to appropriately advise patients, and workers and communities remain ignorant of the potential hazards of the chemicals to which they may be exposed.

Meaningful TSCA reform is essential in order to protect developing children and people of all ages from the impacts of exposure to hazardous chemicals in consumer products, food, water, and air.

The impacts of industrial chemicals, including pesticides, on brain development and function

Another area of concern to bring to your attention is the failure of EPA to require adequate evaluation of the impacts of industrial chemicals, including pesticides, on brain development and function in children. Ample scientific evidence confirms the unique susceptibility of the developing brain to chemical exposures that can disrupt one or more of a number of biologic processes that must proceed in an orderly fashion as brain architecture and chemistry are established throughout pregnancy, infancy, and childhood.

Lead, mercury, polychlorinated biphenyls (PCBs), arsenic, ethyl alcohol, and toluene are recognized causes of neurodevelopmental disorders. A large body of experimental and human epidemiologic evidence shows diverse, long-lasting impacts of these substances on the ability of children to learn, remember, pay attention, and behave appropriately. The effects can occur after relatively low-level exposures that have no discernable effects in adults.

Policies that reduce exposures to these substances have been successful. For example, the removal of lead from gasoline resulted in a sharp decline in average blood levels in children throughout the US. Even so, the economic consequences of lower IQ resulting from lead levels in children in the US today are conservatively estimated to be in excess of $40 billion annually. That figure does not take into account costs to society incurred by responding to special educational needs and disruptive or criminal behavior.

Unfortunately, these well-studied substances are the exception. The large majority of industrial chemicals have never been evaluated for their potential impact on the developing brain of children. This is true even for those chemicals known to be toxic to the nervous system more generally.

Pesticides and organophosphates

Under the Federal Insecticide, Fungicide, and Rodenticide Act, the EPA has the authority to require pesticide registrants to provide data about the impacts of their chemicals on the developing brain. But these data are not part of the core requirement, and the agency may decide on a case-by-case basis whether to require their submission. Historically, the EPA has always been reluctant to exercise this authority, even when a food-use pesticide was known to have nervous system toxicity as the mechanism whereby it killed pests.

Organophosphates are a group of pesticides that are notorious nervous system toxicants. They disrupt nerve impulse transmission and can cause a plethora of symptoms. In the 1990s and early 2000s after EPA issued a data call-in, registrants slowly delivered developmental neurotoxicity data on various organophosphates. These data finally led to some restrictions, including a phaseout of chlorpyrifos-containing products for home and garden use. Chlorpyrifos is among the organophosphate pesticides known to adversely impact the developing brain of children as well as laboratory animals. But chlorpyrifos remains in widespread agricultural use in the US today. About 8 million pounds are applied to US crops annually. Children in farming communities are regularly exposed to this and other organophosphate neurotoxins. It is difficult to imagine the justification for continued use of chlorpyrifos in agriculture.

Methyl iodide

If we thought that we were finally going to see more regular requirements for neurodevelopmental testing of neurotoxic pesticides, we were sadly disappointed in 2007 when EPA registered the fumigant methyl iodide (MeI) for agricultural use without knowing what it might do to the developing brain of a fetus, infant, or child.

MeI was proposed as a substitute for methyl bromide, a fumigant that is supposed to be phased out under the Montreal Protocol because it depletes stratospheric ozone. MeI is an extremely toxic chemical that must be handled with extraordinary care in the laboratory setting. It is damaging to DNA, causing mutations, and is listed on the California Proposition 65 list as “known to the State of California to cause cancer.” But here I want to consider impacts of MeI on the developing brain.

Methyl iodide is highly likely to be a developmental neurotoxicant, with long-lasting impacts on the brain of fetuses, infants, and young children at levels of exposure lower than those that cause damage to the adult brain. This concern is based on several lines of evidence.

According to scientific reports, adults who have been accidentally exposed to MeI may develop “symptoms of irritability, headache diplopia, nystagmus, lethargy, somnolence, slurred speech, ataxia, dysmetria, and visual disturbances. . . . These symptoms may progress to paralysis, convulsions, coma, and death. If recovery occurs, the acute neurologic symptoms may . . . give way to late neuropsychiatric sequelae such as behavioral disturbances, and cognitive deficits, psychoses, and emotional lability.”

The mechanism(s) by which MeI exerts its neurotoxic effects are not completely understood. However, it is clear that glutathione (GSH) depletion is an important contributor in the causal pathway leading to neurotoxicity. Glutathione is a naturally occurring antioxidant that enables the body to cope with toxic substances that cause oxidative stress. Several studies conclude that glutathione depletion alone leads to neurotoxicity.

Fetuses and infants normally have lower levels of glutathione in their tissues than young adults. (Glutathione levels also decline in older people.) Lower baseline levels of glutathione would be anticipated to increase susceptibility to a neurotoxicant like MeI whose mechanism of action depends, at least in part, on glutathione depletion. For that reason alone, it can be predicted that the developing brain is more vulnerable to MeI neurotoxicity than the fully developed adult brain. Beyond that, however, impacts of oxidative stress differ in the developing brain because of unique developmental events without counterparts in the adult.

EPA’s rationale for not requesting developmental neurotoxicity testing was based on the assumption that protecting against exposures sufficient to cause thyroid effects would also protect against impacts in the developing brain. That is, they assumed that the only mechanism by which MeI could adversely impact the developing brain was through decreasing thyroid hormone levels or, alternatively, that other mechanisms would have a higher exposure threshold than that necessary to cause thyroid impacts. These are untested hypotheses for which there is no evidence.

Recently, the California Department of Pesticide Regulation carried out its own risk assessment of MeI and sent it out for external review by a Scientific Review Committee (SRC). In its final report, the SRC said: “The lacunae in our knowledge about methyl iodide are particularly wide and deep in relation to key aspects of its potential toxicity such as neuro- and other developmental effects, neuro-toxicity beyond the development stage (in particular, following chronic exposure), and mechanisms of carcinogenicity.”

This is a description of the existing data gaps pertaining to this dangerous, highly toxic chemical. EPA had the authority to require neurodevelopmental testing before registration but didn’t, despite concerns voiced by numerous scientists.

Recommendations:

EPA should:

1. Move more quickly to implement the Endocrine Disruptor Screening Program for chemicals in consumer products, air, food, and water, using current, up-to-date scientific methods. Evaluation should include commonly encountered mixtures as identified in environmental media (air, water, food) and biomonitoring studies. If NIEHS becomes the institution in which the endocrine-disrupting properties of chemicals are evaluated, EPA must then promptly respond to the findings with health protective interventions.

2. Require developmental neurotoxicity testing of MeI and suspend its registration until data gaps are filled and risks have been re-evaluated.

3. Routinely require neurodevelopmental toxicity testing of pesticides proposed for registration or continued use when they are known or suspected to be toxic to the nervous system.

Congress should pass comprehensive chemical regulatory policy reform. Effective reform should:

• Immediately Initiate Action on the Worst Chemicals: Persistent, bioaccumulative toxicants (PBTs) are uniquely hazardous. Any such chemical to which people could be exposed should be phased out of commerce.

• Require Basic Information for All Chemicals: Manufacturers should be required to provide basic information on the health hazards associated with their chemicals, how they are used, and the ways that the public or workers could be exposed.

• Protect the Most Vulnerable: Chemicals should be assessed against a health standard that explicitly requires protection of the most vulnerable subpopulations. That population is likely to include children, but it could also be workers, pregnant women, or another vulnerable group.

• Use the Best Science and Methods: The National Academy of Sciences’ recommendations for reframing risk assessment at the EPA should be adopted. Regulators should expand development and use of information gleaned from “biomonitoring” for setting priorities.

• Hold Industry Responsible for Demonstrating Chemical Safety: Chemical manufacturers should be responsible for evaluating and demonstrating the safety of their products.

• Ensure Environmental Justice: Effective reform should contribute substantially to reducing the disproportionate burden of toxic chemical exposure placed on people of color, low-income people, and indigenous communities.

• Enhance Government Coordination: The EPA should work effectively with other agencies such as the Food and Drug Administration that have jurisdiction over some chemical exposures. The ability of the states to enact stricter chemical policies should be maintained and state/federal cooperation on chemical safety encouraged.

• Promote Safer Alternatives: There should be national support for basic and applied research into green chemistry and engineering, and policies should favor chemicals and products that are benign over those that are hazardous.

• Ensure the Right to Know: The public, workers, and the marketplace should have full access to chemical safety data and information about the way in which government safety decisions are made.

Congress should also adopt legislation establishing the Endocrine Disruption Prevention Program so that 1) environmental chemicals can be screened for endocrine-disrupting properties using the most current science in a timely manner and 2) regulatory agencies are obligated to take action to protect public health based on the best available science.