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Background Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. Objective Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. Methods This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004–2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). Results Geometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = –0.045 (g/cm3) × 100 (95% CI: –0.084, –0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: –0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = –0.15, 95% CI: –0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: –0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = –0.37, 95% CI: –0.63, –0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was –16.8 g (95% CI: –75.0, 41.3) versus –29.7 (95% CI: –93.9, 34.6) with all covariates. Corresponding values for ponderal index were –0.030 (g/cm3) × 100 (95% CI: –0.065, 0.005) and –0.045 (95% CI: –0.084, –0005). Conclusion We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies. Citation Wells EM, Herbstman JB, Lin YH, Jarrett J, Verdon CP, Ward C, Caldwell KL, Hibbeln JR, Witter FR, Halden RU, Goldman LR. 2016. Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: potential confounding and effect modification by omega-3 fatty acids, selenium, and sex. Environ Health Perspect 124:373–379; http://dx.doi.org/10.1289/ehp.1408596

Background: A database for studies used for U.S. Environmental Protection Agency (EPA) pesticide and chemical reviews would be an excellent resource for increasing transparency and improving systematic assessments of pesticides and chemicals. There is increased demand for disclosure of raw data from studies used by the U.S. EPA in these reviews. Objectives: Because the Information Quality Act (IQA) of 2001 provides an avenue for request of raw data, we reviewed all IQA requests to the U.S. EPA in 2002–2012 and the U.S. EPA’s responses. We identified other mechanisms to access such data: public access databases, the Freedom of Information Act (FOIA), and reanalysis by a third party. Discussion: Only two IQA requests to the U.S. EPA were for raw data. Both of these were fulfilled under FOIA, not the IQA. Barriers to the U.S. EPA’s proactive collection of all such data include costs to the U.S. EPA and researchers, significant time burdens for researchers, and major regulatory delays. The U.S. EPA regulatory authority in this area is weak, especially for research conducted in the past, not funded by the U.S. government, and/or conducted abroad. The U.S. EPA is also constrained by industry confidential business information (CBI) claims for regulatory testing data under U.S. chemical and pesticide laws. The National Institutes of Health Clinical Trials database systematically collects statistical data about clinical trials but not raw data; this database may be a model for data from studies of chemicals and pesticides. Conclusions: A database that registers studies and obtains systematic sets of parameters and results would be more feasible than a system that attempts to make all raw data available proactively. Such a proposal would not obviate rights under the IQA to obtain raw data at a later point.

We appreciate the opportunity to respond to the letter from Stahlhut et al. regarding our Brief Communication. We stressed the importance of biospecimen integrity and the potential danger of unrecognized contamination of convenience samples, particularly with ubiquitous environmental chemicals such as bisphenol A (BPA) and phthalates. We did not discuss the important area of experimental research and specifically pharmacokinetic studies, although we based our argument partly on knowledge of concentration changes in various compartments postexposure. We agree that information from pharmacokinetic models is quite valuable and note that experimental studies that use isotope-labeled materials are not susceptible to extraneous contamination. Such experimental studies do not support using polar metabolites, such as unmetabolized BPA, as biomarkers in epidemiologic studies (Thayer et al. 2015). For example, even in situations that may result in exposures higher than background levels, such as handling cash register receipts, BPA serum concentrations are below or near the detection limit and much lower than urinary concentrations (Thayer et al. 2016). The figure in our Brief Communication revealed the sharp increase in the number of publications using blood-based polar biomarkers over the past 15 years, especially etiologic studies. Our main point was that urine is the most dependable biomonitoring matrix for population research, a position that Stahlhut et al. also support in their letter. Target-organ dose may inform biological models, but measuring this dose is not always possible, although it can be inferred from pharmacokinetic studies. For environmental epidemiology, reliable measurements in urine can be used to quantify exposures. A suitable exposure biomarker involves more than detecting the analyte with precise and accurate methods. For pervasive chemicals and particularly for archived samples, specimen integrity must be confirmed. This is true for any matrix, including urine (Guidry et al. 2015; Koch et al. 2012), to ensure valid results.

In a recent Brief Communication, Calafat et al. expressed concern that epidemiological studies inappropriately assess exposure to nonpersistent chemicals such as bisphenol A (BPA) and phthalates by measuring chemical concentrations in serum and tissues. They assert that urine is the most scientifically valid matrix and that accurate measurement of other matrices is difficult due to contamination of samples and assays. We believe their assertions require clarification. The scientifically appropriate matrix is determined by the study objectives. For population studies, we agree urine is an appropriate matrix to initially probe whether exposure to a nonpersistent chemical is associated with a disease or risk factor. However, Calafat et al. appear to target more than population studies. They illustrate the purportedly growing problem of non-urine measurement in epidemiology with a list of 80 studies, cited by PubMed identification numbers (PMIDs), which surprisingly includes pharmacokinetic and experimental studies. Of these 80 studies, 35 arguably required non-urine matrices to achieve study objectives. For example, in five studies (PMIDs 10716589, 10964036, 11604266, 17661831, 23145999) the subjects were dialysis patients—i.e., people without normal capacity to produce urine. One study used a placenta perfusion system to examine phthalate distribution between maternal and fetal circulation (PMID 17049806). A dog study (PMID 23761051) found unmetabolized BPA was rapidly absorbed into circulation following sublingual administration. A human study (PMID 25337790) exposed participants to BPA-containing thermal receipt paper and found a substantial increase of unmetabolized BPA in serum. It seems inconceivable to us that Calafat et al. would consider such studies inherently flawed. For chemicals excreted in urine, the urinary concentration provides an estimate of exposure. However, the bioactive form in serum and tissue is what alters physiology. When a nonpersistent chemical is absorbed via the gut, first-pass metabolism by the liver can dramatically reduce the amount of unmetabolized compound reaching the bloodstream as compared with other routes (Soeborg et al. 2014). Therefore, for chemicals in widespread undocumented use—where route-of-exposure information is unavoidably incomplete—one cannot accurately predict the internal concentrations of the unmetabolized compounds with urine measurements and a model that includes only gut absorption. Such models may grossly underestimate internal bioactive dose from non-gut exposures and incorrectly suggest that measurement of higher-than-predicted serum concentrations is due to contamination. In our view, Calafat et al. suggest that non-urine measurements are invariably contaminated. However, contamination cannot explain the results of the studies by Gayrard et al. (2013) and Hormann et al. (2014), which demonstrated classic pharmacokinetic curves with logical interrelationships between the parent compound and metabolites. Furthermore, the proposition that contamination is unavoidable is contradicted by numerous studies spanning 15 years (vom Saal and Welshons 2014). For example, in a paper coauthored by Calafat (Ye et al. 2013), the authors reported accurately measuring BPA in human serum after identifying and eliminating contamination. Subsequently, Vandenberg et al. (2014) reported a blinded study directed by the National Institutes of Health (NIH) in which several U.S. laboratories accurately measured BPA in human serum spiked by NIH personnel. Arguing that chemical X cannot be measured in tissue Y because of contamination is an odd position to take, given that eliminating sources of contamination is a normal part of the development and validation of any assay—as was clearly described by Ye et al. (2013). In summary, without further clarification, the Brief Communication by Calafat et al. could easily be interpreted as proposing that human environmental studies of any kind must measure nonpersistent chemicals and metabolites only in urine if they are to be funded and published. Such an interpretation would greatly restrict our ability to move from surface-level exposure measures to internal dose, pharmacokinetics, and in vivo pathophysiology. Given the prominence of the authors in environmental health research, this issue needs to be clarified.

Background: Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped. Objectives: Our goal was to accelerate biomarker research on UCB by exploring its detectable protein content and providing a priority list of potential biomarkers based on known proteins involved in disease pathways. Methods: We explored cord blood serum proteins by profiling a UCB pool of 12 neonates with different backgrounds using a combination of isoelectric focusing and liquid chromatography coupled with matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) and by comparing results with information contained in metabolic and disease databases available for adult blood. Results: A total of 1,210 UCB proteins were identified with a protein-level false discovery rate of ~ 5% as estimated by naive target-decoy and MAYU approaches, signifying a 6-fold increase in the number of UCB proteins described to date. Identified proteins correspond to 138 different metabolic and disease pathways and provide a platform of mechanistically linked biomarker candidates for tracking disruptions in cellular processes. Moreover, among the identified proteins, 38 were found to be approved biomarkers for adult blood. Conclusions: The results of this study advance current knowledge of the human cord blood serum proteome. They showcase the potential of UCB as a diagnostic medium for assessing infant health by detection and identification of candidate biomarkers for known disease pathways using a global, nontargeted approach. These biomarkers may inform about mechanisms of exposure–disease relationships. Furthermore, biomarkers approved by the U.S. Food and Drug Administration for screening in adult blood were detected in UCB and represent high-priority targets for immediate validation.

Background Lead exposure is associated with elevated blood pressure during pregnancy; however, the magnitude of this relationship at low exposure levels is unclear. Objectives Our goal was to determine the association between low-level lead exposure and blood pressure during late pregnancy. Methods We collected admission and maximum (based on systolic) blood pressures during labor and delivery among 285 women in Baltimore, Maryland. We measured umbilical cord blood lead using inductively coupled plasma mass spectrometry. Multivariable models were adjusted for age, race, median household income, parity, smoking during pregnancy, prepregnancy body mass index, and anemia. These models were used to calculate benchmark dose values. Results Geometric mean cord blood lead was 0.66 μg/dL (95% confidence interval, 0.61–0.70). Comparing blood pressure measurements between those in the highest and those in the lowest quartile of lead exposure, we observed a 6.87-mmHg (1.51–12.21 mmHg) increase in admission systolic blood pressure and a 4.40-mmHg (0.21–8.59 mmHg) increase in admission diastolic blood pressure after adjustment for confounders. Corresponding values for maximum blood pressure increase were 7.72 (1.83–13.60) and 8.33 (1.14–15.53) mmHg. Benchmark dose lower limit values for a 1-SD increase in blood pressure were < 2 μg/dL blood lead for all blood pressure end points. Conclusions A significant association between low-level lead exposures and elevations in maternal blood pressure during labor and delivery can be observed at umbilical blood lead levels < 2 μg/dL.

Background: Metals can interfere with hormonal functioning by binding at the receptor site and through indirect mechanisms; thus, they may be associated with hormonal changes in premenopausal women. Objectives: We examined the associations between cadmium, lead, and mercury, and anovulation and patterns of reproductive hormones [estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone] among 252 premenopausal women 18–44 years of age who were enrolled in the BioCycle Study in Buffalo, New York. Methods: Women were followed for up to two menstrual cycles, with serum samples collected up to eight times per cycle. Metal concentrations were determined at baseline in whole blood by inductively coupled mass spectroscopy. Marginal structural models with stabilized inverse probability weights and nonlinear mixed models with harmonic terms were used to estimate the effects of cadmium, lead, and mercury on reproductive hormone levels during the menstrual cycle and anovulation. Results: Geometric mean (interquartile range) cadmium, lead, and mercury levels were 0.29 (0.19–0.43) μg/L, 0.93 (0.68–1.20) μg/dL, and 1.03 (0.58–2.10) μg/L, respectively. We observed decreases in mean FSH with increasing cadmium [second vs. first tertile: –10.0%; 95% confidence interval (CI), –17.3% to –2.5%; third vs. first tertile: –8.3%; 95% CI, –16.0% to 0.1%] and increases in mean progesterone with increasing lead level (second vs. first tertile: 7.5%; 95% CI, 0.1–15.4%; third vs. first tertile: 6.8%; 95% CI, –0.8% to 14.9%). Metals were not significantly associated with anovulation. Conclusions: Our findings support the hypothesis that environmentally relevant levels of metals are associated with modest changes in reproductive hormone levels in healthy, premenopausal women.

Background Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects. In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Therefore, an understanding of fetal responses to environmental exposures is essential. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared with that of adults. Objectives Our goal was an initial global assessment of the fetal serum proteome and for the identification of protein biomarkers indicative of toxic in utero exposures related to maternal cigarette smoking. Methods Drawing from a repository of 300 samples, we selected umbilical cord blood sera from 12 babies born to six smokers and six nonsmokers and analyzed both sample pools by tandem mass spectrometry in conjunction with isobaric tags (iTRAQ) for protein quantification. Results We identified 203 proteins, 17 of which were differentially expressed between the cigarette smoke–exposed and control populations. Most of the identified candidate biomarkers were biologically plausible, thereby underscoring the feasibility of screening neonates with global proteomic techniques for biomarkers of exposure and early biological effects triggered by in utero chemical exposures. Conclusions This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns’ health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p

Use of polybrominated diphenyl ethers (PBDEs) as flame retardants (FRs) in plastics, including electronic enclosures and poly-urethane used in upholstery cushioning and carpet pads, has increased steadily in the past 30 years (Alaee et al. 2003; de Wit 2002; Hardy 2002b). PBDEs used as additive FRs are more likely to leach over time than reactive FRs, which are chemically bonded to the plastic polymer (Alaee and Wenning 2002; Eriksson et al. 2001; Sjodin et al. 2001a). PBDEs are similar to polychlorinated biphenyls (PCBs) in structure, lipophilicity, persistence, and ability to bioaccumulate (Hardy 2002a; McDonald 2002). Since the 1970s, environmental concentrations of PCBs and other persistent organic pollutants (POPs) have fallen whereas levels of PBDEs have increased exponentially (Alaee and Wenning 2002; Eriksson et al. 2001; Meironyte et al. 1999; Sjodin et al. 2001b). Currently, human PBDE levels are of a magnitude similar to PCB concentrations in some regions (Hites 2004; Petreas et al. 2004). Human levels of PBDEs are higher in North America than in Europe and within a given population, a small fraction (5–10%) of individuals have concentrations far exceeding average levels (Betts 2003; Hites 2004; Schecter et al. 2005; Sjodin et al. 2003; Wilford et al. 2005). Although there have been no studies investigating the health effects associated with PBDEs in humans, there are reports of human exposure levels that may be on par with levels eliciting harmful effects in laboratory animals (McDonald 2005). Animal studies have shown evidence of the disruption of normal endocrine function and neurodevelopmental, hepatic, and reproductive toxicity (Betts 2004, 2005; Johnson-Restrepo et al. 2005). Currently, there is an incomplete understanding of how humans are exposed to PBDEs. It is reasonable to posit that among those with high concentrations, occupational exposures may be involved in some cases (Sjodin et al. 1999; Thuresson et al. 2005). In the general population, several potential routes of PBDE exposure have been identified: a) direct contact with treated products; b) dietary, as these lipophilic compounds are stored in the fat of meats, fish, and dairy products (Harrad et al. 2004; Schecter et al. 2004, 2006; Wilford et al. 2005); and c) ingestion and to a lesser degree inhalation of PBDE-containing house dust (Jones-Otazo et al. 2005; Stapleton et al. 2005; Wilford et al. 2005; Wu et al. 2007) Only a few studies have been able to explore individual determinants of PBDE body burdens in much detail (Morland et al. 2005; Wu et al. 2007). Levels of PBDEs (as well as PCBs and organochlorine pesticides) measured in adipose tissue, blood, or milk can be used to assess exposures (Sjodin et al. 2003). Infants and fetuses are sensitive subpopulations to consider, because these stages of development may be especially susceptible to effects of chemical exposures (Howdeshell 2002). Toxicologic models have indicated that immature animals have slower metabolism and excretion of PBDEs; approximately 50% of the administered 2,2′,4,4′-tetraBDE (BDE-47) dose is excreted in the first 24 hr in adult animals compared with 31% and 41% in animals dosed at 10 and 22 days after birth (Staskal et al. 2006). Measuring PBDEs in cord blood serum is noninvasive, using a blood sample that is otherwise usually discarded, and is a direct measure of prenatal exposure. The estimated half-lives of these compounds in humans are long enough—BDE-47 1.8–3.0 years, 2,2′,4,4′,5-pentaBDE (BDE-99) 2.9–5.4 years, and 2,2′,4,4′,5,5′-hexaBDE (BDE-153) 6.5–11.7 years (Geyer et al. 2004)—that cord blood concentrations reflect exposure through the course of pregnancy. Such levels also provide a reasonable estimate of maternal serum concentrations (Mazdai et al. 2003). The principal objective of this investigation was to characterize fetal exposure to PBDEs and selected PCBs among newborns from Baltimore, Maryland, via the assessment of concentrations in umbilical cord serum. We explored demographic characteristics and attributes to identify determinants and to explain variations in exposure levels and patterns within this largely urban and African-American population.

Polyfluoroalkyl compounds (PFCs) comprise a class of man-made, fluorinated organic compounds that have been used in a variety of consumer and industrial applications. Although these have been produced for many years, only recently have reports surfaced suggesting widespread exposure in wildlife and humans (Butenhoff et al. 2006; Calafat et al. 2007; Giesy and Kannan 2001; Houde et al. 2006; Kannan et al. 2004). Two of the most widely detected and studied compounds in this class are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). PFOS and related compounds (polyfluorinated sulfonamides) are surfactants used in applications ranging from oil and water repellents for fabrics, apparel, carpets, and paper coatings to specialty chemical applications such as insecticides and fire fighting foams (3M Company 1999). PFOA and its salts are used as chemical intermediates and processing aids in the production of fluoropolymers and fluoroelastomers. Both PFOS and PFOA have shown the potential for developmental toxicity in animal studies. PFOS has been shown, in rats and mice, to induce developmental and reproductive effects, such as reduced birth weight, decreased gestational length, structural defects, developmental delays, and increased neonatal mortality (Fuentes et al. 2006; Grasty et al. 2003; Lau et al. 2003; Luebker et al. 2005a, 2005b; Thibodeaux et al. 2003). Recent studies have also reported developmental toxicity from PFOA in rodents, including pregnancy loss, reduced fetal weight, reduced postnatal survival, and delays in postnatal growth and development in offspring (Butenhoff et al. 2004; Lau et al. 2004, 2006). However, such studies of PFOS and PFOA have been conducted using doses that produce serum concentrations much higher than general population human exposures. There are limited epidemiologic data on the potential impacts of PFC exposure on fetal growth and development. However, one recent occupational study found no association between employment in jobs with high exposure to PFOS before the end of pregnancy and maternally reported birth weight (Grice et al. 2007). PFOS and PFOA have also been shown to cause reductions in serum cholesterol and/or triglycerides in several animal species (Haughom and Spydevold 1992; Seacat et al. 2002, 2003; Thibodeaux et al. 2003). Conversely, a few cross-sectional occupational studies conducted among fluorochemical production employees have reported positive relationships between PFOS and/or PFOA concentrations and serum lipid levels (Gilliland and Mandel 1996; Olsen et al. 1999, 2003). The fetus is likely to be sensitive to the availability of cholesterol and triglycerides, which support cellular growth, differentiation, and adipose accumulation (Woollett 2001). Disruptions to normal fetal growth and development have been associated with effects across the lifespan, including adverse neonatal and childhood outcomes (Hofman et al. 1997; Kramer et al. 1990) and metabolic diseases in adulthood (Barker 2006). In a previous report, we documented factors associated with cord serum concentrations of PFOS and PFOA in a population of newborn deliveries known as the Baltimore THREE study (Apelberg et al. 2007). In this study, we examined the relationship between these concentrations and gestational age, birth weight, and measures of birth size, including head circumference, length, and ponderal index (a measure of body mass at birth).

Pesticide manufacturers have tested pesticides increasingly in human volunteers over the past decade. The apparent goal of these human studies is to establish threshold levels for symptoms, termed "no observed effect levels." Data from these studies have been submitted to the U.S. Environmental Protection Agency (EPA) for consideration in standard setting. There are no required ethical guidelines for studies of pesticides toxicity conducted in humans, no governmental oversight is exercised, and no procedures have been put in place for the protection of human subjects. To examine ethical and policy issues involved in the testing of pesticides in humans and the use of human data in standard setting, in February 2002 the Center for Children's Health and the Environment of the Mount Sinai School of Medicine convened an expert workshop for ethicists, physicians, toxicologists, and policy analysts. After a peer consensus process, participants developed a number of ethical and public policy recommendations regarding the testing of pesticides in humans. Participants also strongly encouraged active biomonitoring of every pesticide currently in use to track human exposure, particularly in vulnerable populations, and to assess adverse effects on health.

The risk assessment process as spelled out in the National Research Council's (NRC's) report Risk Assessment in the Federal Government: Managing the Process, called the “Red Book,” has created a framework for incorporation of toxicology into environmental decision-making that has withstood the test of time. However, the time has come for a reassessment of this framework. Risk assessment is often unsuccessful as a public health tool when data are limited and it does not, in itself, provide an incentive for the generation of new data. The risk assessment framework did not envision the need to develop formal methods for the incorporation of precautionary approaches into the formal regulatory/analytical process. This needs to be addressed, as we see a widening gulf in approaches between the U.S. and Europe. Likewise, the process has not provided a clear road map for the utilization of epidemiology and health tracking information to guide environmental regulation. Finally, the concept of separating the intelle...

Technology has improved the food supply since the first cultivation of crops. Genetic engineering facilitates the transfer of genes among organisms. Generally, only minute amounts of a specific protein need to be expressed to obtain the desired trait. Food allergy affects only individuals with an abnormal immunologic response to food--6% of children and 1.5-2% of adults in the United States. Not all diseases caused by food allergy are mediated by IgE. A number of expert committees have advised the U.S. government and international organizations on risk assessment for allergenicity of food proteins. These committees have created decision trees largely based on assessment of IgE-mediated food allergenicity. Difficulties include the limited availability of allergen-specific IgE antisera from allergic persons as validated source material, the utility of specific IgE assays, limited characterization of food proteins, cross-reactivity between food and other allergens, and modifications of food proteins by processing. StarLink was a corn variety modified to produce a (Italic)Bacillus thuringiensis(/Italic) (Bt) endotoxin, Cry9C. The Centers for Disease Control and Prevention investigated 51 reports of possible adverse reactions to corn that occurred after the announcement that StarLink, allowed for animal feed, was found in the human food supply. Allergic reactions were not confirmed, but tools for postmarket assessment were limited. Workers in agricultural and food preparation facilities have potential inhalation exposure to plant dusts and flours. In 1999, researchers found that migrant health workers can become sensitized to certain Bt spore extracts after exposure to Bt spraying.

On the final afternoon of the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods," held 10-12 December 2001 in Chapel Hill, North Carolina, USA, speakers and participants met in breakout groups to discuss specific questions in the areas of use of human clinical data, animal models to assess food allergy, biomarkers of exposure and effect, sensitive populations, dose-response assessment, and postmarket surveillance. Each group addressed general questions regarding allergenicity of genetically modified foods and specific questions for each subject area. This article is a brief summary of the discussions of each of the six breakout groups regarding our current state of knowledge and what information is needed to advance the field.

Modern biotechnology has dramatically increased our ability to alter the agronomic traits of plants. Among the novel traits that biotechnology has made available, an important group includes Bacillus thuringiensis-derived insect resistance. This technology has been applied to potatoes, cotton, and corn. Benefits of Bt crops, and biotechnology generally, can be realized only if risks are assessed and managed properly. The case of Starlink corn, a plant modified with a gene that encodes the Bt protein Cry9c, was a severe test of U.S. regulatory agencies. The U.S. Environmental Protection Agency had restricted its use to animal feed due to concern about the potential for allergenicity. However, Starlink corn was later found throughout the human food supply, resulting in food recalls by the Food and Drug Administration and significant disruption of the food supply. Here we examine the regulatory history of Starlink, the assessment framework employed by the U.S. government, assumptions and information gaps, and the key elements of government efforts to manage the product. We explore the impacts on regulations, science, and society and conclude that only significant advances in our understanding of food allergies and improvements in monitoring and enforcement will avoid similar events in the future. Specifically, we need to develop a stronger fundamental basis for predicting allergic sensitization and reactions if novel proteins are to be introduced in this fashion. Mechanisms are needed to assure that worker and community aeroallergen risks are considered. Requirements are needed for the development of valid assays so that enforcement and post market surveillance activities can be conducted.

The environmental health literature is rife with controversial papers that evoke criticism, support, and, most importantly, a desire to better understand the findings put forth by the authors. A research article by Seralini and colleagues (Seralini et al. 2012), published in the journal Food and Chemical Toxicology (FCT), is one such article resulting in considerable discourse (Arjo et al. 2013; Barale-Thomas 2013; Grunewald and Bury 2013; Ollivier 2013; Wagner et al. 2013; Sanders et al. 2013; Schorsch 2013; Seralini et al. 2013) and a call for new research (European Commission 2013). This is all part of the scientific process in a modern research environment. However, the retraction of the article by Seralini et al. from FCT sets a new precedent in the management of peer-reviewed publications that we believe has serious implications for environmental public health. The retraction announcement by the Editor-in-Chief specifically states, “Ultimately, the results presented (while not incorrect) are inconclusive, and therefore do not reach the threshold of publication for Food and Chemical Toxicology” (FCT 2013). The Editor-in-Chief also was very clear that he “found no evidence of fraud or intentional misrepresentation of the data.” This article (Seralini et al. 2012) has been controversial from its initial publication. We do not wish to discuss the merits of the authors’ conclusions or their implications for the commercial products in question. Those issues have been debated in the open scientific literature since the publication of the paper, and we agree with many of the critiques. However, the retraction of any paper because it is “inconclusive” has adverse implications on the integrity of the concept of the peer-review process as the critical foundation of unbiased scientific inquiry. The paper was peer reviewed by scientists on behalf of the FCT and published accordingly. Hence, it initially met the threshold for publication. In our opinion, there must be a different threshold for forced retraction of the paper, and we believe that this paper did not reach that threshold. The COPE guidelines for retracting articles (Committee on Publication Ethics 2009) provide four reasons for retraction: scientific misconduct/honest error, prior publication, plagiarism, or unethical research. None of these reasons apply to this particular article, and yet Elsevier, a member of COPE, chose to retract the paper. The nature of science is such that individual studies are rarely, if ever, conclusive. Numerous published studies have later been found to be deeply flawed through further scientific investigation, as may well be the study by Seralini et al. To our knowledge, there is no precedent for “inconclusive data” being a reason for retraction for Elsevier or other publishers, or elsewhere in the scientific literature. To single out this one study for retraction is almost certainly due to the controversy following its publication. The repercussions of this directed action extend well beyond this single publication and raise several larger scientific questions. Will these data, which could well have been accepted by another journal, now be tainted beyond possibility for inclusion in usual weight-of-evidence reviews of the body of peer-reviewed science? Will the response to new science by interested parties now be focused on dueling attempts to have the paper retracted rather than on performing additional studies to replicate or refute the findings? Does this retraction strengthen the scientific process, or does it confuse scientific discourse with public relations? Efforts to suppress scientific findings, or the appearance of such, erode the scientific integrity upon which the public trust relies. The retraction by the FCT marks a significant and destructive shift in management of the publication of controversial scientific research. Equally troublesome is that this retraction does not really impact how the science will be viewed by scientists, but only how it is viewed by others outside of the scientific community. We feel the decision to retract a published scientific work by an editor, against the desires of the authors, because it is “inconclusive” based on a post hoc analysis represents a dangerous erosion of the underpinnings of the peer-review process, and Elsevier should carefully reconsider this decision.

Although we know that certain types of childhood cancers are increasing, we do not know why. With few exceptions, we know little about the role of environmental carcinogens in childhood cancer. Generally, we have adequate information to screen chemicals for potential hazard for only certain categories of chemicals--drugs, food additives, and pesticides. The U.S. Environmental Protection Agency (U.S. EPA) is implementing the 1996 Food Quality Protection Act, which provides added protections against pesticide risks, especially for children. But the situation is quite different for many industrial chemicals. We lack even basic toxicity data for a majority of the U.S. EPA's list of approximately 3000 nonpolymeric high-production-volume industrial chemicals being produced in the United States each year that are found in consumer products and the workplace. We know even less about the remaining 70,000 chemicals on the U.S. EPA inventory. The U.S. EPA has initiatives underway to address the risks posed by some of these commercial chemicals, including efforts to reduce risks posed by indoor air pollutants and household products. These initiatives specifically address children's risks. We are supporting toxicity screening of high-volume industrial chemicals on a cooperative international basis through the Organisation for Economic Co-operation and Development. Until more information is available, it is difficult to assess the possible role of these chemicals in childhood cancer and to take steps to reduce exposure to children.

To assess the impact of elevated levels of inorganic mercury in soil and dust and organic mercury in fish, biological monitoring was conducted among Native Americans living next to an inactive mercury mine in Clear Lake, California. Of resident tribal members, 46% (n = 56) participated in biomonitoring. Urine mercury levels are equivalent to background, indicating that soil and dust exposures among study participants are not substantial. The average blood organic mercury level among study participants is 15.6 +/- 8.8 micrograms/l (n = 44), which is higher than levels reported by others among those who do not consume fish (2 micrograms/l). Consistent with results from other studies, a correlation between fish consumption and blood organic mercury is observed (p = 0.03). The margin between observed and established adverse effect levels for adults is examined for blood organic mercury and found to be less than 10-fold for 20% of the study population. Protective public health efforts for the study population and other similarly exposed populations, notably those who consume commercial fish products, are considered. Images Figure 1.

Human tissue banking could provide a tool to address a number of public health concerns. We can potentially use it to monitor trends in human exposures, serve as an early warning system for new environmental exposures, assess low-level exposures around hazardous waste and other point sources of pollutants, evaluate the effectiveness of regulatory programs, and study etiologies of diseases (e.g., childhood cancer and birth defects) that are likely to be related to the environment. This article discusses opportunities to establish human tissue banks in connection with pre-existing public health surveillance programs for cancer and adverse reproductive outcomes. This is a cost-effective way to conduct surveillance and enhances the ability to carry out epidemiologic studies. The article also discusses ethical issues that are particularly important for public health practice. One is the issue of risk communication and the need to explain risks in a way that provides people with the information they need to determine appropriate action on the individual and community levels. Second is the issue of environmental justice. We recommend early involvement of communities that are likely to be involved in tissue-banking projects and full explanation of individual and group social risks from their participation.

Children’s environmental health issues are inherently multidisciplinary, often requiring integration of the skills of epidemiologists, analytical chemists, toxicologists, social scientists, clinicians, public health practitioners, policy makers, specialists in living and learning environments (e.g., housing, schools), and community leaders, among others. The diverse group of professionals whose primary interests concern children’s environmental health research and policy has lacked a professional home that facilitates interdisciplinary collaborations. Many scientific and medical societies include children or the environment among the topics on which members focus, but rarely have the two been combined in a way that provides an international forum dedicated to discovering ways to protect children from environmental hazards. To address the need for a professional society that provides such a forum, a new organization was recently formed and incorporated, the International Society for Children’s Health and the Environment, or ISCHE (http://www.ische.ca). The first election of officers was held in April 2010. The goals of ISCHE reflect the broad array of issues germane, worldwide, to children’s environmental health and safety: To translate research into policies that protect children’s health by enhancing the quality of their environments To catalyze the development of multidisciplinary research aimed at protecting children from environmental hazards To enhance the training of professionals in children’s environmental health To promote the delivery of services to create healthy environments for children To enhance surveillance of childhood exposures and environmentally induced diseases or disabilities To enhance clinical care of children with environmentally induced disease or disability. Because of its multidisciplinary membership, ISCHE is well positioned to make current scientific findings more accessible to the health care, public health, and policy communities via position papers, technical reports, and testimony. We envision this happening in several ways, including the following: ISCHE will foster interdisciplinary collaborations, providing an environment in which individuals from the many disciplines involved in children’s health and environments can come together to share information and to combine forces to work on topics of common interest. ISCHE will connect individuals or organizations seeking expertise on children’s health and the environment with members who might be able to serve as speakers, reviewers, or consultants. ISCHE committees will review and translate research to promote evidence-based policies, standards, and educational initiatives that protect children from adverse environmental influences and promote healthier environments. These committees will also propose critically needed children’s health research and facilitate pooled analyses. The committees will be composed of a standing group of scientists drawn from the ISCHE membership, as well as invited scientists who bring expertise on a specific issue. The conclusions and policy recommendations of these committees will be published in the scientific and medical literature. On occasion, committees might also produce op-ed pieces for the lay press on topical issues. ISCHE will help to establish children’s environmental health as an essential part of the curricula in various health training programs internationally and assist in the creation and advancement of appropriate research and policy initiatives for developing as well as developed nations. “International” is the first word in the title of ISCHE because we believe that children’s environmental health and safety must be viewed from a global perspective. Some recent incidents involving children’s harm from environmental chemical exposures have occurred in developing countries (e.g., the recent epidemic of severe childhood lead poisoning in Nigeria) and countries in transition (e.g., melamine in infant formula in China), but others have occurred in highly industrialized countries (e.g., the Fukushima Daiichi nuclear disaster in Japan). To contribute to capacity building worldwide, membership dues are reduced for individuals from developing countries (and waived for students from these countries). Eventually ISCHE plans to hold an annual membership meeting and research conference. However, during this formative time, we are coordinating our meetings with those of other societies. For example, in September 2011, ISCHE met at the International Society for Environmental Epidemiology (ISEE) meeting in Barcelona, Spain. In addition to holding meetings for its officers and members, ISCHE sponsored a pre-meeting Workshop on Assessment of Neurobehavioral Effects of Environmental Exposures on Children. This workshop was intended to inform attendees of the methodologic issues pertinent to the design, conduct, and analysis of studies on associations between children’s environmental exposures and their neurodevelopment. In future years, at meetings of ISEE and/or other societies, ISCHE will organize additional workshops, focusing on specific exposures (e.g., pesticides, bisphenol A), target organ systems (e.g., the lung), methods (e.g., genome-wide association studies), and policies. ISCHE is dedicated to providing a professional home for those with scientific, policy analysis, educational, and clinical interests in children’s environmental health. ISCHE plans to work with other organizations with related missions, both in the United States and internationally, to ensure complementarity of our efforts rather than duplication.

PCDD and PCDF measurements were made on selected retail milk products, including paper packaged milk samples, covering all known paper carton suppliers in the state of California during 1989. Significant levels of 2,3,7,8 tetrachlorodibenzofuran (TCDF) and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) were found in the paper packaged milk in all brands investigated except one. All other 2,3,7,8 substituted PCDFs and PCDDs were either not detected or detected at very low levels. Two non 2,3,7,8 substituted TCDFs were consistently detected in the contaminated milk samples. Using the mean concentration of 2,3,7,8 TCDF and TCDD detected and assuming a 480 ml daily consumption of milk for an adult, we estimated that the milk represented an additional 2.3 pg/kg/day of TCDD equivalent exposure based on the California toxic equivalence (CA TE), but only a 0.56 pg/kg/day increase using the International TE (ITE). The lifetime cancer risk was calculated to be 470 10 6 (CA TE) and 80 10 6 (ITE). Monitoring of retail milk products continued during 1990 but 2,3,7,8 TCDD and 2,3,7,8 TCDF were either not detected or detected at very low levels in all products investigated.

Controlled exposure studies under laboratory and field conditions have been initiated to investigate the biotransfer and bioaccumulation of PCDD/Fs in soil, at low concentrations, to animals which have contact with soil. The chicken was chosen as a model for grazing animals. The accumulation over time of specific isomers is being tracked in eggs, blood, feces, liver, adipose, and edible flesh. Measurable increases of PCDD/F concentration in eggs of exposed chickens, as compared to controls, were seen after 30 days of exposure. The exposure characterization, as well as data on isomer specific biotransfer and bioaccumulation rates in eggs are discussed.

We thank Scialli for his interest in our study (Apelberg et al. 2007). As he notes, we recognize that several factors could be responsible for the relationships observed between cord serum concentrations of perfluorooctane sulfonate/perfluorooctanoate (PFOS/PFOA) and birth weight, head circumference, and ponderal index in our study. Although diet may be a source of exposure (including consumption of polyfluoroalkyl compounds used in fast-food packaging), we are not aware of any evidence that such diets are associated with smaller size at birth. In fact, they may be related to obesity, which is associated with larger birth size (Surkan et al. 2004). Despite existing knowledge gaps on exposure pathways and the role of dietary intake, we do know that in our study, adjusting for body mass index of the mother had little impact on the associations observed.

Background Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Objective We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots. Methods We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T4) and free T4 (FT4) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004–2005. We abstracted results of total T4 (TT4) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones. Results In the full study population, no compounds were associated with a change in average TSH, FT4, or TT4. BDE-100 was associated with increased odds of low cord TT4, BDE-153 with increased odds of low cord TT4 and FT4, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT4 and FT4 and lower TT4 measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT4 and FT4 measurements. Conclusions Prenatal PCB and PBDE exposures were associated with reduced TT4 and FT4 levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.

Additional data have been obtained which relate the bioaccumulation of polychlorodibenzodioxins and polychlorodibenzofurans (PCDDs and PCDFs) in foraging chickens to the ingestion of soil contaminated at the low part per trillion (ppt) level. These new data indicate that both the concentration and congener profiles of PCDDs and PCDFs in eggs and body tissues, are correlated with the PCDD and PCDF concentration and congener profile seen in soil on which these chickens were grazing. Additionally, a cow grazing in these areas of low soil PCDD/PCDF contamination showed characteristic PCDD and PCDF profiles in milk. Breast milk from women living in the area did not show the characteristic PCDD/PCDF contamination. Controlled feeding studies of chickens have been initiated which are designed to demonstrate the transfer of PCDDs and PCDFs from soil to tissue and eggs and to establish the kinetics and equilibrium concentrations of the bioaccumulation. Levels and patterns of PCDDs and PCDFs in tissues and eggs from foraging animals appear to be closely related to the levels and patterns in the soils to which they are exposed. This suggests the possibility of animals functioning as sensitive biomonitors for low level soil contamination. In addition, if such animals are used for food, the possibility of human exposure to PCDDs and PCDFs must be considered.

It is clear from our commentary (Goldman and Silbergeld 2013), that we disagree with Lutter et al. (2013) about whether the public disclosure of all raw data used by the U.S. Environmental Protection Agency (EPA) for making regulatory decisions for chemicals is necessary to ensure the scientific basis for such decisions, and about the extent to which pre-emptive dis-closure (prior to any request) is practical. However, the most important disagreement between us is the basis asserted by Lutter et al. in their commentary for this change in policy. Lutter et al. argued that it is necessary for the U.S. EPA—and anyone else who desires to do so—to reanalyze all data used in their assessments in order to “replicate” the findings and conclusions of the original investigators. Lutter et al. (2013) repeatedly used the terms “replicability” and “replication” as synony-mous with an “independent analysis” of raw data from an existing study. Replication in science is quite different; it involves performance of an independent study with the same hypothesis and then testing the extent to which this independent study reaches the same conclusions. Recalculation of study statistics or other reanalysis of an existing study data set is not a replication. Designing and conducting a replication study does not require access to raw data from the original study; this would abrogate the concept of independence. Moreover, an independent study will by defini-tion utilize different sets of animal models or human populations, and as a consequence may employ different statistical techniques. Their second argument is that disclosure of raw data will assist in identifying sources of scientific bias. We consider this unlikely because the most important sources of bias are usually related to problems in study design or limitations of the data collected. This is not identifiable through data recalculation; however, this type of bias can usually be identified in the text of the original study publication. Lutter et al. (2013) noted (correctly) that applicants to the U.S. EPA for pesticide regis-trations must provide raw data from regulatory testing as part of the package submitted to the U.S. EPA. This is a very special case, in that these studies are neither peer reviewed nor accessible to the public because of the protection sought by industry and extended by law for confidential business information (CBI). The assumption of bias related to these studies is not unreasonable, given that they are conducted by or on behalf of commercial entities seeking to obtain pesticide registration. These studies are rarely published in the scien-tific literature or in any way subject to independent peer review other than review by the U.S. EPA. Many scientists and public policy practitioners consider the CBI cloak as a major impedi-ment to transparency and confidence. Industry could demonstrate their commitment to transparency by declining this protection, thereby increasing the confidence of all. Finally, Lutter et al. (2013) attempted to support their proposal by claiming that journals [Nature and the Proceedings of the National Academy of Sciences of the United States (PNAS)] and an expert body (the Bipartisan Policy Center) agree with them. However, these bodies have neither supported the concept of requiring that all raw data be reported to the the U.S. EPA nor that the U.S. EPA carry out its own independent recalculation. Rather, Nature and PNAS require authors to agree to make data sets (as well as materials and protocols) available to editors, and to others, upon request (Nature Publishing Group 2012; PNAS 2012). One of us (L.R.G.) was a member of the Science for Policy Project; its final report (Bipartisan Policy Center 2009) also recommended this practice. Many journals require data, such as DNA and protein sequences, macro-molecular structures, micro-array data, and crystallo-graphic data, to be made available on publicly accessible databases, but most of these are not “raw data” in the sense that Lutter et al. proposed. Nature also recommends that authors submit clinical trials data to external clinical trials databases (Nature Publishing Group 2012). In summary, we disagree with the argu-ment that raw data from every study used by the U.S. EPA to support a regu-la-tory assess-ment should be made available to the agency and to the public. This proposal does not serve the purpose of “replication” or identi-fica-tion of bias, as asserted by Lutter et al. (2013). In practice, it may generate obstacles to good science and discourage researchers from studying issues of importance in environ-mental health. This proposal would also limit the U.S. EPA from using the results of research published in the peer-reviewed scientific litera-ture by placing studies off-limits if the authors did not submit raw data sets to the the U.S. EPA. Finally, there is no obvious need for these changes. When the U.S. EPA has determined a need to reanalyze data, the current regulatory practice has not impeded such activities. Past history indicates that difficult cases are rare and do not warrant an intrusive and burden-some new requirement for the automatic submission of data from all studies.

We compared serum polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) among residents of two homes to levels among age- and sex-matched comparison subjects. The residents of the two homes consumed contaminated eggs and beef from animals raised at the homes. The animals had greater soil contact than those raised with conventional commercial husbandry practices. The comparison subjects were from a similar rural area, but did not consume home-produced beef and eggs. Serum levels of 2,3,7, 8-substituted tetra-, penta-, and hexaCDDs and penta-, hexa-, and heptaCDFs were increased between 2- and 6-fold in residents from one home; contaminated eggs and beef were consumed by residents for 2-15 years. Elevations were less for those in the other index home, where only home-produced eggs were consumed for 2 years; a 3-fold elevation of 1,2,3,7,8,9-hexaCDD as compared to controls was most apparent. Very strong bivariate correlations among all of the 2,3,7, 8 penta- and hexaCDDs/CDFs were observed. The elevations observed verify that PCDD/PCDF-contaminated food contributed to the body burden of these compounds. The blood levels among the highest exposed participants are generally higher than those observed in other studies of U.S. contaminated-fish consumers and higher than average adipose tissue levels observed in U.S. urban populations. There are sufficient animal toxicologic and human epidemiologic data to recommend that exposures be reduced. In the study area, pentachlorophenol and pentachlorophenol incineration sources have been identified, and the animal contamination and blood elevations probably reflect these sources. Soil reference values and site-specific risk assessments should include estimates of exposures to contamination in home-produced animal products. Such estimates can be verified with limited PCDD/PCDF sampling of animals and humans. Images Figure 1 Figure 2

Speakers and participants in the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods" met in breakout groups to discuss a number of issues including needs for future research. These groups agreed that research should progress quickly in the area of hazard identification and that a need exists for more basic research to understand the mechanisms underlying food allergy. A list of research needs was developed.

There are numerous pesticides and toxic chemicals in the environment that have yet to be evaluated for potential to cause developmental neurotoxicity. Recent legislation and testing initiatives provide an impetus to generating more information about potential hazards to children. In the United States, the 1996 Food Quality Protection Act (FQPA) required the U.S. Environmental Protection Agency (U.S. EPA) to make a finding that a pesticide food use is safe for children. In addition, the law requires U.S. EPA to incorporate an additional 10-fold factor in risk assessments for pesticide residue tolerances to take into account the special sensitivities of infants and children as well as incomplete data with respect to toxicity and exposures. The potential of chemicals in food and drinking water to cause endocrine disruption will also be examined via the Endocrine Disruptor Screening and Testing Program required by the FQPA and the 1996 Safe Drinking Water Act. In addition, a new voluntary chemical information program will provide screening-level information for the some 2,800 high-volume chemicals in commerce in the United States. These initiatives will need to be accompanied by research focused on developmental toxicity for children, including developmental disabilities. Developmental disabilities exact a large toll on children's health in the United States. Three major developmental disabilities--autism, cerebral palsy, and severe mental retardation--each affect substantial numbers of children. We know very little about the etiology of these conditions. A number of priority areas for research are suggested, including a large environmental prospective study of developmental neurotoxicity.

Children may be more susceptible to exposures to environmental toxins than adults and may be more vulnerable to their effects. Because of this, the health care community and those responsible for children need to be alert to possible environmental factors in identifying and responding to the health problems of children. Their focus should be on the causes of the health problem, emphasizing environmental sources, and not on simply treating the symptoms.

To assess the effect of interim clean-up measures on the current health of a community, we conducted a follow-up survey of 193 residents living near the McColl waste disposal site and a comparison area located approximately 5 miles from the site. Results from this survey were compared with results from a similar survey conducted 7 years earlier. Odors were detected at least once per week by 32.7% of "high-exposed" respondents in 1988 compared with 68.5% in 1981, but prevalence odds ratios (PORs) comparing symptom reporting between "high-exposed" and comparison-area respondents were greater than that of the 1981 survey for 89% of symptoms. PORs comparing symptom reporting between these two areas were greater than 2.0 for 64% of symptoms assessed in the current survey. Symptoms reported in excess did not represent a single organ system or suggest a mechanism of response. PORs comparing respondents who were very worried about the environment and those reporting no worry were greater than 2.0 for 86% of symptoms. These finding, along with environmental data from the area, suggest that living near the waste disposal site and being very worried about the environment, rather than a toxicologic effect of chemical from the site, explain excess symptom reporting found in this follow-up study.

We studied dioxin levels in residents of two California households where dioxin contaminated homegrown eggs and beef were found, in order to determine the level of exposure to dioxins. Risk assessments for carcinogenicity and reproductive toxicity showed that theoretical risks exceeded proscribed regulatory levels. Advisory guidelines were issued about consumption of eggs, chicken and beef. Serum samples from exposed and matched rural comparison subjects were analyzed and preliminary dioxin data show statistically significant elevations of 2,3,7,8-penta and hexa dioxin isomers for both homes. Comparison subjects from rural California had lower serum dioxin levels than those previously reported for Missouri and Sweden. Adipose tissue from a resident of one of the homes was tested for dioxins. The resident died six months later and a post mortem retesting of adipose and testing of liver and lung tissues for dioxins was done. No unusual dioxin levels were found; levels of dioxin in adipose remained stable despite six months of not eating contaminated produce. Dioxins were not a contributing cause of death. In this study, dioxin contaminated eggs and beef have elevated 2,3,7,8-tetra, penta and hexa dioxin levels in serum. The ongoing investigation will seek to delineate the source and extent of contamination, and to determine the extent of the exposed population and potential health impacts.

Studies carried out in California, following a fire which involved a pentachlorophenol wood treatment plant have indicated that low concentrations of dioxins and furans in soil can lead to bioaccumulation in chickens and cattle which are in contact with the soil. These compounds were found to distribute into various tissues of the animals and into the eggs of the chickens. A significant change in congener profile and isomer pattern was seen when comparing soils to tissues. Source tests of local incinerators showed quite different congener profile than was seen in soils. Concentrations found in animal products used as food suggest the possibility of excessive human exposure based on modest consumption assumptions.