Associations between prenatal exposure to power plants and birth outcomes across the United States.

OBJECTIVES: Although there is growing evidence that in utero exposure to power plants increases the risk of adverse birth outcomes, studies have focused on coal-fired plants and single US locations, limiting generalizability. We used birth certificate data from 50 states and DC to examine the associations between prenatal exposure to power plants and birth outcomes overall and by race/ethnicity. METHODS: We linked 2009-2018 county-level microdata natality files on 34,674,911 singleton births from 50 states and DC with 9-month county-level averages of power plant fuel consumption based on month/year of birth. We estimated linear regression models for birth weight and gestational age and probit models for the dichotomous outcomes of low birth weight, small for gestational age (SGA), and preterm birth. We subsequently examined interactions between plant fuel consumption and race/ethnicity. RESULTS: Overall, 69.1% of counties had any power plant fuel consumption. Although we found no overall effects of prenatal exposure to power plants on birth weight or SGA, a significant interaction (both P < 0.01) revealed that a 10% increase in fuel consumption was associated with infants born to White women having slightly lower birth weights (1.76 g; 95% confidence interval = -2.87, -0.65) and higher risk of being born SGA (0.0002; 95% confidence interval = 0.0002, 0.0002). CONCLUSION: Power plants have negative effects on infant health, which exist independent of locality.

Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study.

BACKGROUND: Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders. METHOD: A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks. RESULTS: Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories. CONCLUSIONS: Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.

Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders.

BACKGROUND: Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations. METHOD: Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11. RESULTS: CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time. CONCLUSIONS: Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.

The World Trade Center health surveillance program: results of the first 10 years and implications for prevention.

BACKGROUND: The terrorist attacks on the World Trade Center (WTC) of September 11, 2001 resulted in the deaths of 2,823 persons. They also generated a long-lasting burden of multiple physical and mental health illnesses among the cohort of 50,000 rescue workers who responded to the attacks and in the 400,000 residents and workers in nearby areas of New York City. A comprehensive health surveillance program was developed from the first months after the accidents and was further developed in the subsequent ears. Individual exposure and health data were stored in ad hoc databases and produced epidemiological outcomes on the various exposure-related illnesses. METHODS: About 10 years of longitudinal assessment of this large cohort of WTC rescue and recovery workers, yielded data from participants in the WTC Screening, Monitoring, and Treatment Program. Police officers, firefighters, construction workers, and municipal workers were included in the cohort. Cumulative and annual incidence were estimated for various physical disorders including asthma, sinusitis, and gastroesophageal reflux disease, mental health disorders including depression, post-traumatic stress disorder [PTSD], and panic disorder. Respiratory functionality was also assessed. Exposure was characterized with qualitative parameter including working on the pile and being engulfed in the dust cloud, and quantitative parameters including the time of arrival on site and the exposure duration. RESULTS: Upper and lower respiratory conditions such as rhinosinusitis and asthma have been found in a significant number of people in WTC-exposed populations. A lack of appropriate respiratory protection may have contributed to these effects. Other commonly observed physical health conditions include gastro-esophageal reflux disease, obstructive sleep apnea and musculo-skeletal injuries. Many WTC-exposed individuals also suffer from mental health conditions, primarily post-traumatic stress disorder, depression, panic disorder, and substantial stress reaction. Recent studies suggest that WTC exposure may increase the risk of cancer and of mortality from cardiac disease. CONCLUSION: Ten years of systematic health surveillance after the 9/11 WTC attacks, show long lasting burden of physical and mental health problems. Continued monitoring and treatment of this population is needed for early diagnoses of initial clinical conditions that can be treated more effectively. The experience of September 11 offers also indications on how to approach the acute and delayed health effects of civilian catastrophes. Critical lessons are derived about the importance of having trained responders--medical and non-medical--in place in advance of disasters, and about the need to proceed with adequate exposure assessment in a timely manner.

Developmental neurotoxicity of industrial chemicals.

Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.

Occupational injury and illness in the United States. Estimates of costs, morbidity, and mortality.

OBJECTIVE: To estimate the annual incidence, the mortality and the direct and indirect costs associated with occupational injuries and illnesses in the United States in 1992. DESIGN: Aggregation and analysis of national and large regional data sets collected by the Bureau of Labor Statistics, the National Council on Compensation Insurance, the National Center for Health Statistics, the Health Care Financing Administration, and other governmental bureaus and private firms. METHODS: To assess incidence of and mortality from occupational injuries and illnesses, we reviewed data from national surveys and applied an attributable risk proportion method. To assess costs, we used the human capital method that decomposes costs into direct categories such as medical and insurance administration expenses as well as indirect categories such as lost earnings, lost home production, and lost fringe benefits. Some cost estimates were drawn from the literature while others were generated within this study. Total costs were calculated by multiplying average costs by the number of injuries and illnesses in each diagnostic category. RESULTS: Approximately 6500 job-related deaths from injury, 13.2 million nonfatal injuries, 60,300 deaths from disease, and 862,200 illnesses are estimated to occur annually in the civilian American workforce. The total direct ($65 billion) plus indirect ($106 billion) costs were estimated to be $171 billion. Injuries cost $145 billion and illnesses $26 billion. These estimates are likely to be low, because they ignore costs associated with pain and suffering as well as those of within-home care provided by family members, and because the numbers of occupational injuries and illnesses are likely to be undercounted. CONCLUSIONS: The costs of occupational injuries and illnesses are high, in sharp contrast to the limited public attention and societal resources devoted to their prevention and amelioration. Occupational injuries and illnesses are an insufficiently appreciated contributor to the total burden of health care costs in the United States.

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups. Similar changes were found in nonwhites; among nonwhites in the geriatric age range, increases of 22% to 553% were observed among women. Men generally had a 100% higher risk of death due to PD than did women. Whites were at three times the risk of nonwhites. The observed temporal changes appear to reflect improved treatment, better case ascertainment, and a true rise in the incidence of PD, particularly among the elderly. This rise may be due to preventable environmental causes and will require further investigation.

Strategies for epidemiologic studies of lead in bone in occupationally exposed populations.

Lead exposure is widespread among industrial populations in the United States. X-ray fluorescence (XRF) analysis of the lead content of bone offers a promising approach to acquisition of individualized data on chronic lead absorption in occupationally exposed populations. Dosimetric data obtained by XRF will permit accurate definition of dose-response relationships for such chronic consequences of lead exposure as central and peripheral neurologic impairment, renal disease. hypertension, and possibility reproductive dysfunction. Additionally, data on bone lead content obtained by XRF will permit validation of models describing the body lead burden and will allow direct assessment of the efficacy of therapeutic chelation. XRF data may also permit assessment of the possible role of genetic polymorphism of the enzyme delta-aminolevulinic dehydrase as a determinant of the pharmacokinetics and toxicity of lead. In both cross-sectional and prospective epidemiologic studies of body lead burden in occupationally exposed populations, the K-XRF instrument appears to be the technology of choice.

Critical assessment of epidemiologic studies on the human carcinogenicity of 1,3-butadiene.

1,3-Butadiene, a major ingredient of synthetic rubber, has been shown to be carcinogenic in two animal species. To assess the possible human carcinogenicity of 1,3-butadiene, a critical review was undertaken of the epidemiologic literature. An early retrospective study of 8017 males employed in tire manufacturing found excess mortality for lymphatic and hematopoietic neoplasms in production workers (standardized mortality ratio, SMR = 560); these workers were exposed to 1,3-butadiene as well as to styrene and possibly to benzene. A recently updated epidemiologic study of 2568 workers at a butadiene manufacturing plant in Texas reported low mortality overall (SMR = 84) but found excess deaths for lymphosarcoma and reticulum cell sarcoma (SMR = 229). A retrospective study of workers employed at two synthetic rubber plants in Texas found excess mortality for lymphatic and hematopoietic malignancies in the older of these facilities; the excesses for lymphosarcoma (SMR = 224) and leukemia (SMR = 278) were most significant in wartime workers. A large, recently updated retrospective study of 12,113 workers employed in eight synthetic rubber manufacturing plants in the United States and Canada found excess mortality for lymphatic and hematopoietic cancer in production workers; the SMR for other lymphatic cancers in white production workers was 230, and the SMR for all lymphatic malignancies in black production workers was 507. These updated epidemiologic results strongly suggest an etiologic association between occupational exposure to 1,3-butadiene and human cancer. It is reasonable, therefore, to conclude that there now exists at least limited evidence for the human carcinogenicity of 1,3-butadiene.

Prevention of toxic environmental illness in the twenty-first century.

Previous introductions of new technologies have frequently resulted in unanticipated occupational and environmental illness. Prevention of such illness in the twenty-first century requires stringent application of two fundamental principles of public health: evaluation of new technologies before their introduction, and surveillance of exposed persons after the introduction of new technologies. Failure to establish these basic preventive mechanisms in advance will inevitably result in the development of new toxic diseases in the twenty-first century.

Current issues in the epidemiology and toxicology of occupational exposure to lead.

Occupational exposure to lead is widespread in the United States. Clinically evident lead poisoning as well as subclinical toxicity occur in populations with occupational lead exposure. The focus of current research on lead toxicity in industrial populations is in the definition of dose-response relationships, particularly at low levels of exposure. Major interest surrounds the development of biochemical and physiologic markers of subclinical toxicity. Need exists to better delineate the toxicity of lead on the peripheral and central nervous system, the kidneys, the cardiovascular system, and the reproductive organs using newly developed markers. To obtain more accurate information on cumulative individual exposure to lead, future research on lead toxicity will increasingly use X-ray fluorescence analysis for determination of the lead content in home.

Epidemiologic approaches to persons with exposures to waste chemicals.

Evaluation of disease in populations exposed to hazardous waste dumps requires: documentation of the chemicals in a dump; assessment of the materials released from the dump into environmental media; tracing of the probable routes of human exposure (groundwater, air, direct contact, or occupational); development, when possible, of individual exposure estimates and/or direct biological assessment of absorption; precise definition of the subpopulations at highest risk of exposure; and the employment of specific and sensitive health outcome indicators. Demonstration of dose-response relationships between chemical exposure and disease provides the most compelling evidence for a chemical etiology of illness in exposed populations. Interpretation of apparently negative data must be cautious, given the small size of most high-risk populations and the usual brevity of exposures.

Quantitative assessment of lives lost due to delay in the regulation of occupational exposure to benzene.

Benzene exposure can cause leukemia, aplastic anemia, and possibly lymphoma. In 1978, on the basis of strong but incomplete data then available on the risk of benzene-induced leukemia, the U.S. Occupational Safety and Health Administration (OSHA) reduced the permissible occupational exposure standard for benzene from 10 ppm to 1 ppm. Shortly thereafter, the Fifth Circuit Court of Appeals stayed this ruling, and in 1980, the Supreme Court overturned the regulation, citing insufficient evidence of benefit. Thus, from 1978 until the standard was again lowered to 1 ppm in 1987, American workers were exposed to benzene at levels in excess of 1 ppm. An estimated 9600 were exposed to levels between 1 and 10 ppm, and an additional 370 were exposed at levels above 10 ppm. To assess the risk resulting from this delay in regulation, we have conducted an epidemiologic risk analysis. We merged data on numbers of persons (238,000) exposed to benzene in seven occupational categories with dose-response data from three epidemiologic studies. The range of risk in these studies indicates that 44 to 152 excess leukemia deaths will ultimately result from exposure to benzene at 10 ppm over a working lifetime (45 years) and that lower or briefer exposures will result in proportionately fewer deaths. On this basis, we calculated that between 30 and 490 excess leukemia deaths will ultimately result from occupational exposures to benzene greater than 1 ppm that occurred between 1978 and 1987. Deaths from aplastic anemia and lymphoma will likely add to this toll. These data confirm the risk of regulatory delay. They suggest that the courts, in reviewing public health regulations, must beware of facile cost-benefit arguments and be willing to accept strong evidence of health risk even when such evidence is incomplete.

The developing brain and the environment: an introduction.

mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester conference came from both public and private sources. The National Institute of Environmental Health Sciences (NIEHS), the National Institute of Child Health and Human Development, and the EPA represented the federal government. The conference also received grants from several foundations: the Jennifer Altman Foundation, the Heinz Family Foundation, the National Alliance for Autism Research, the Violence Research Foundation, the Wacker Foundation, and the Winslow Foundation. The second of these conferences helped launch a new Center for Children's Health and the Environment at the Mount Sinai School of Medicine. It was held in New York City on 24-25 May 1999, and was convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference title was Environmental Influences on Children: Brain, Development, and Behavior. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its (italic)Handbook of Pediatric Environmental Health (/italic)((italic)17(/italic)), the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline.

Environmental neurotoxic illness: research for prevention.

Recognition of the deleterious neurological effects of chemicals has evolved from anecdotal observation to studies of illness in persons exposed to high doses. Now, the more subtle effects of exposures to environmental neurotoxicants are being documented: reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alteration of behavior. Substances to which millions of persons are exposed occupationally and in the general environment that can result in such deficits include lead, organophosphorus pesticides, certain chlorinated hydrocarbons, carbon disulfide, solvents, and mercury. The first step in the prevention of neurological impairments due to environmental exposures is to assess the toxicity of chemicals. Fewer than 10% of the 70,000 chemicals in commercial use have been evaluated for neurotoxicity. This knowledge gap needs to be narrowed by building on existing systems of toxicity testing. Concurrent with assessment of chemicals will be tiers of in vivo screening tests to measure functional and structural changes following exposures in vitro. Epidemiologic surveillance of populations at high risk will continue to inform on the ranking of suspect or known neurotoxicants. Research and researchers must become more sophisticated in the development and application of refined biologic markers so the findings can be used to detect absorption of toxicants and early neurological or neurobehavioral dysfunction before disability occurs and to protect human health and the environment.

Chemical wastes, children's health, and the Superfund Basic Research Program.

Three to 4 million children and adolescents in the United States live within 1 mile of a federally designated Superfund hazardous waste disposal site and are at risk of exposure to chemical toxicants released from these sites into air, groundwater, surface water, and surrounding communities. Because of their patterns of exposure and their biological vulnerability, children are uniquely susceptible to health injury resulting from exposures to chemical toxicants in the environment. The Superfund Basic Research Program, funded by the U.S. Environmental Protection Agency and directed by the National Institute of Environmental Health Sciences, is extremely well positioned to organize multidisciplinary research that will assess patterns of children's exposures to hazardous chemicals from hazardous waste disposal sites; quantify children's vulnerability to environmental toxicants; assess causal associations between environmental exposures and pediatric disease; and elucidate the mechanisms of environmental disease in children at the cellular and molecular level.

Environmental health sciences education--a tool for achieving environmental equity and protecting children.

Children are highly susceptible to deleterious effects of environmental toxins. Those who live in underserved communities may be particularly at risk because environmental pollution has been found to be disproportionately distributed among communities. Mounting evidence suggests that asthma rates are rising and that this disease can be caused or aggravated by air pollution. Although ambient air quality has generally improved, these improvements have not reached minority communities in equal proportions. This and other data has fueled the concept of environmental justice or environmental equity, which has led to community activism and government actions. One possible example of environmental inequity and its consequences is the Hunt's Point community, in the South Bronx, New York. This community experiences a high pollution burden with the siting of facilities that emit hazardous wastes into the air. Our approach to this problem has been the formation of mechanisms for bidirectional communication between community residents, government entities, and academic institutions such as Mount Sinai Medical Center. As a result of this experience, we believe that the key to achieving environmental health, especially in communities of color where many children are at risk, is to empower residents to take charge of their environment by providing relevant educational opportunities. Strategies for environmental health education include multitiered training approaches that include community residents, parent education, direct children education, and community education through professional counselors and train-the-trainer approaches. We propose that academic researchers must use community residents not just as subjects of our studies, but to increase our mutual understanding of environmental health, resulting in active participation of community members in research design, data collection, analysis, and dissemination of results in order to make intervention strategies more effective.

A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)

Nine children and their mother were exposed to vapors of metallic mercury. The source of the exposure appears to have been a 6-oz vial of mercury taken from a neighbor's home. The neighbor reportedly operated a business preparing mercury-filled amulets for practitioners of the Afro-Caribbean religion Santeria. At diagnosis, urinary mercury levels in the children ranged from 61 to 1,213 microg/g creatinine, with a geometric mean of 214.3 microg/m creatinine. All of the children were asymptomatic. To prevent development of neurotoxicity, we treated the children with oral meso-2,3-dimercaptosuccinic acid (DMSA). During chelation, the geometric mean urine level rose initially by 268% to 573.2 microg mercury/g creatinine (p<0.0005). At the 6-week follow-up examination after treatment, the geometric mean urine mercury level had fallen to 102.1 microg/g creatinine, which was 17.8% of the geometric mean level observed during treatment (p<0.0005) and 47.6% of the original baseline level (p<0.001). Thus, oral chelation with DMSA produced a significant mercury diuresis in these children. We observed no adverse side effects of treatment. DMSA appears to be an effective and safe chelating agent for treatment of pediatric overexposure to metallic mercury.

Unraveling the chronic toxicity of lead: an essential priority for environmental health.

Although population exposure to lead has declined, chronic lead toxicity remains a major public health problem in the United States affecting millions of children and adults. Important gaps exist in knowledge of the pathophysiology of chronic lead intoxication. These gaps have impeded development of control strategies. To close current gaps in knowledge of chronic lead toxicity, we propose an integrated, multidisciplinary, marker-based research program. This program combines a) direct measurement of individual lead burden by 109Cd X-ray fluorescence analysis of lead in bone, b) determination of ALA-D phenotype, an index of individual susceptibility to lead, and c) assessments of subclinical injury produced by lead in the kidneys, nervous system and, reproductive organs. Data from this research will provide answers to questions of great public health importance: a) Are current environmental and occupational standards adequate to prevent chronic lead intoxication? b) is lead mobilized from the skeleton during pregnancy or lactation to cause fetal toxicity? c) Is lead mobilized from bone during menopause to cause neurotoxicity? d) What is the significance of genetic variation in determining susceptibility to lead? e) What is the contribution of lead to hypertension, renal disease, chronic neurodegenerative disease or declining sperm counts? f) Is chelation therapy effective in reducing body lead burden in persons with chronic overexposure to lead?

The U.S. EPA Conference on Preventable Causes of Cancer in Children: a research agenda.

On 15-16 September 1997, the U.S. Environmental Protection Agency sponsored the Conference on Preventable Causes of Cancer in Children. The conference was convened to examine rising trends in reported incidence of childhood cancer and the association of these trends with environmental exposures. This paper summarizes recommendations for future research offered by participants. These recommendations included more collaborative research integrating epidemiology, molecular biology, toxicology, and risk assessment; the development of better protocols for toxicologic testing including carcinogenicity using young animals; and research focused on specific periods of development during which susceptibility to environmental agents may be enhanced. Also recommended was enhanced use and development of molecular biomarkers for identification of susceptible populations, and documentation of exposures and effects in epidemiologic and toxicologic studies. Although toxicologic testing is considered essential to determine the effects of potential carcinogens on biological organisms, participants emphasized the need to link these findings with epidemiologic and exposure assessment research.