Michael Dellarco

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

Background: Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. Objectives: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. Methods: Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatograpy–tandem mass spectrometry using isotope dilution. Results: The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. Conclusions: The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions. Citation: Arbuckle TE, Marro L, Davis K, Fisher M, Ayotte P, Bélanger P, Dumas P, LeBlanc A, Bérubé R, Gaudreau É, Provencher G, Faustman EM, Vigoren E, Ettinger AS, Dellarco M, MacPherson S, Fraser WD. 2015. Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort. Environ Health Perspect 123:277–284; http://dx.doi.org/10.1289/ehp.1408187

A 21st century roadmap for human health risk assessment

Abstract The Health and Environmental Sciences Institute (HESI)-coordinated Risk Assessment in the 21st Century (RISK21) project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment, and involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. This paper provides a brief overview of the tiered RISK21 framework called the roadmap and risk visualization matrix, and articulates the core principles derived by RISK21 participants that guided its development. Subsequent papers describe the roadmap and matrix in greater detail. RISK21 principles include focusing on problem formulation, utilizing existing information, starting with exposure assessment (rather than toxicity), and using a tiered process for data development. Bringing estimates of exposure and toxicity together on a two-dimensional matrix provides a clear rendition of human safety and risk. The value of the roadmap is its capacity to chronicle the stepwise acquisition of scientific information and display it in a clear and concise fashion. Furthermore, the tiered approach and transparent display of information will contribute to greater efficiencies by calling for data only as needed (enough precision to make a decision), thus conserving animals and other resources.

Risk assessment in the 21st century: roadmap and matrix.

Abstract The RISK21 integrated evaluation strategy is a problem formulation-based exposure-driven risk assessment roadmap that takes advantage of existing information to graphically represent the intersection of exposure and toxicity data on a highly visual matrix. This paper describes in detail the process for using the roadmap and matrix. The purpose of this methodology is to optimize the use of prior information and testing resources (animals, time, facilities, and personnel) to efficiently and transparently reach a risk and/or safety determination. Based on the particular problem, exposure and toxicity data should have sufficient precision to make such a decision. Estimates of exposure and toxicity, bounded by variability and/or uncertainty, are plotted on the X- and Y-axes of the RISK21 matrix, respectively. The resulting intersection is a highly visual representation of estimated risk. Decisions can then be made to increase precision in the exposure or toxicity estimates or declare that the available information is sufficient. RISK21 represents a step forward in the goal to introduce new methodologies into 21st century risk assessment. Indeed, because of its transparent and visual process, RISK21 has the potential to widen the scope of risk communication beyond those with technical expertise.

Using national and local extant data to characterize environmental exposures in the national children's study: Queens County, New York.

Objective The National Children’s Study is a long-term epidemiologic study of 100,000 children from 105 locations across the United States. It will require information on a large number of environmental variables to address its core hypotheses. The resources available to collect actual home and personal exposure samples are limited, with most of the home sampling completed on periodic visits and the personal sampling generally limited to biomonitoring. To fill major data gaps, extant data will be required for each study location. The Queens Vanguard Center has examined the extent of those needs and the types of data that are generally and possibly locally available. Data In this review we identify three levels of data—national, state and county—and local data and information sets (levels 1–3, respectively), each with different degrees of availability and completeness, that can be used as a starting point for the extant data collection in each study location over time. We present an example on the use of this tiered approach, to tailor the data needs for Queens County and to provide general guidance for application to other NCS locations. Conclusions Preexisting and continually evolving databases are available for use in the NCS to characterize exposure. The three levels of data we identified will be used to test a method for developing exposure indices for segments and homes during the pilot phase of NCS, as outlined in this article.

Comparison of Wipe Materials and Wetting Agents for Pesticide Residue Collection from Hard Surfaces

Different wipe materials and wetting agents have been used to collect pesticide residues from surfaces, but little is known about their comparability. To inform the selection of a wipe for the National Childrens Study, the analytical feasibility, collection efficiency, and precision of Twillwipes wetted with isopropanol (TI), Ghost Wipes (GW), and Twillwipes wetted with water (TW), were evaluated. Wipe samples were collected from stainless steel surfaces spiked with high and low concentrations of 27 insecticides, including organochlorines, organophosphates, and pyrethroids. Samples were analyzed by GC/MS/SIM. No analytical interferences were observed for any of the wipes. The mean percent collection efficiencies across all pesticides for the TI, GW, and TW were 69.3%, 31.1%, and 10.3% at the high concentration, respectively, and 55.6%, 22.5%, and 6.9% at the low concentration, respectively. The collection efficiencies of the TI were significantly greater than that of GW or TW (p<0.0001). Collection efficiency also differed significantly by pesticide (p<0.0001) and spike concentration (p<0.0001). The pooled coefficients of variation (CVs) of the collection efficiencies for the TI, GW, and TW at high concentration were 0.08, 0.17, and 0.24, respectively. The pooled CV of the collection efficiencies for the TI, GW, and TW at low concentration were 0.15, 0.19, and 0.36, respectively. The TI had significantly lower CVs than either of the other two wipes (p=0.0008). Though the TI was superior in terms of both accuracy and precision, it requires multiple preparation steps, which could lead to operational challenges in a large-scale study.

ISEA2007 panel: Integration of better exposure characterizations into disaster preparedness for responders and the public

An expert panel was convened in October 2007 at the International Society for Exposure Analysis Annual Meeting in Durham, NC, entitled “The Path Forward in Disaster Preparedness Since WTC—Exposure Characterization and Mitigation: Substantial Unfinished Business!” The panel prospectively discussed the critical exposure issues being overlooked during disaster responses and highlighted the needs for an optimal blending of exposure characterizations and hazard controls within disaster settings. The cases were made that effective and timely exposure characterizations must be applied during responses to any disaster, whether terrorist, manmade, or natural in origin. The consistent application of exposure sciences across acute and chronic disaster timelines will assure that the most effective strategies are applied to collect the needed information to guide risk characterization and management approaches. Exposure sciences must be effectively applied across all phases of a disaster (defined as rescue, reentry, recovery, and rehabitation—the four Rs) to appropriately characterize risks and guide risk-mitigation approaches. Failure to adequately characterize and control hazardous exposures increases the likelihood of excess morbidity and mortality. Advancing the infrastructure and the technologies to collect the right exposure information before, during, and immediately after disasters would advance our ability to define risks and protect responders and the public better. The panel provided conclusions, recommendations, and next steps toward effective and timely integration of better exposure science into disaster preparedness, including the need for a subsequent workshop to facilitate this integration. All panel presentations and a summary were uploaded to the ISES1 website (http://www.iseaweb.org/Disaster_Preparedness/index.php).

Assessment of Exposure to VOCs among Pregnant Women in the National Children’s Study

Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children’s Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N-acetyl-S-(benzyl)-l-cysteine (BMA), and paint use was positively associated with the xylene metabolites 2-methylhippuric acid (2MHA) and 3-Methylhippuric acid & 4-methylhippuric acid (3MHA + 4MHA). A near-significant (p = 0.06) relationship was observed between acrylamide metabolites and observation of incense.

A major milestone for the National Children's Study.

In January 2009, after 8 years of planning and development, the National Children’s Study (NCS; http://www.nationalchildrensstudy.gov/Pages/default.aspx) will begin enrollment and data collection at the first of the initial, or Vanguard, locations, in Duplin County, North Carolina, and in Queens, New York. In spring 2009, the remaining five Vanguard locations will join them, followed by 29 additional locations in 2010 and more in the following 2 years. The NCS, a national longitudinal cohort study of 100,000 children to be followed from early pregnancy to adulthood, will examine how environmental exposures, interacting with genetic factors and medical access, affect children’s health and development. Beginning enrollment caps a remarkable journey from a bold vision to a reality that was sometimes unpredictable and cloaked in uncertainty. The NCS began after assertions from both the President’s Task Force on Environmental Health and Safety Risks to Children and the Children’s Health Act of 2000 that a multiagency consortium should carry out a large longitudinal study. Since its inception, the planning and development of the NCS have been led by the National Institute of Child Health and Human Development, along with a consortium of lead agencies that includes the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the U.S. Environmental Protection Agency. With broadly defined environmental exposures and all of children’s health and developmental outcomes of concern, the NCS calls for equally broad input by scientific experts, communities, and involved groups. To meet this need, the study has committed to gathering the best input possible through its Federally Chartered Advisory Committee; Interagency Coordinating Committee; over 20 working groups representing > 2,500 clinicians, scientists, and community members; public, peer, and agency reviews; and active participation by the network of Study Centers across the country. The NCS provides opportunities for related investigations by affiliated and nonaffiliated investigators through adjunct studies conducted at NCS study locations or through analysis of data collected in the NCS to address a wide range of additional questions beyond the core study hypotheses. The study can be expanded to cover even broader maternal, fetal, and child health research. The processes for thoroughly considering the development of methods, proposed changes, and ongoing input are being established through working teams composed of scientists at the various Study Centers, federal agencies, and elsewhere. These teams are organized according to the various issues being addressed in the NCS, such as genetics/epigenetics and genomics/epigenomics, health disparities, environmental exposure, neurodevelopment and cognition, nutrition, and physical/clinical measures. The nationally representative sampling strategy is probably the most unique and demanding challenge. A representative sample offers the best opportunity to apply the findings of the NCS to all children in the United States. Enrolling and retaining a representative sample of participants will require full engagement of all of the communities involved. Thus, this national study must also become a community study at the level of participating neighborhoods and counties, with input and ownership by community advisory boards, community organizations and institutions, and local citizens. In spite of the size and the breadth of the NCS, it cannot meet all of the needs and expectations of its supporters. A sample with 100,000 subjects will, by its very size and cost, limit the depth and complexity of many measures. The sample size may prohibit many specialized procedures and technologies, and many questions that investigators want to ask will also be beyond the reach of this study. The advantages of the NCS that other studies cannot do are its capacity to address compelling problems that are uncommon and to examine interactions between various environmental exposures and genetic factors that require a large sample and detailed measures of multiple exposures and outcomes across life stages. The capability to study possible effects and relationships of many exposure factors on multiple outcomes provides both considerable cost-effectiveness and research opportunities not otherwise available. Access to the necessary resources will be an ongoing challenge, dependent upon many factors, especially the ability of the NCS to fulfill its promise. Findings from the NCS will ultimately benefit all Americans by providing researchers, health care providers, and public health officials with information from which to develop prevention strategies, health and safety guidelines, and possibly new treatments and cures for disease. As we mark the true beginning of this ambitious study, it is appropriate to recognize that the NCS belongs to all of us—scientists, communities, and families. Realizing its goals will require our continued effort, investment, and ownership.

Assessment of Noise Exposure to Children: Considerations for the National Children's Study

Evidence has been accruing to indicate that young children are vulnerable to noise in their physical environment. A literature review identified that, in addition to hearing loss, noise exposure is associated with negative birth outcomes, reduced cognitive function, inability to concentrate, increased psychosocial activation, nervousness, feeling of helplessness, and increased blood pressure in children. While increasing attention has been given to the health effects of noise in children, research about noise exposure is sparse and often the measure of exposure is simply proximity to a noise source. The U.S. National Childrens Study (NCS) provides a unique opportunity to investigate noise exposures to pregnant women and children using a number of assessment modalities at different life stages. Measurement of noise levels in homes and other environments, personal dosimetry measurements made over a period of days, and questionnaires addressing sources of noise in the environment, annoyance to noise, perceived noise level, use of head phones and ear buds, noisy activity exposures, and occupational exposures, are planned for evaluation within the NCS Vanguard pilot study. We describe the NCS planned approach to addressing noise exposure assessment in study visits over a childs lifetime.

Using exposure bands for rapid decision making in the RISK21 tiered exposure assessment

Abstract The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the Twenty-first Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, that is, exposure is used as the second step (after problem formulation) to define and focus the assessment. This paper describes the exposure tiers of the RISK21 matrix and the approaches to adapt readily available information to more quickly inform exposure at a screening level. In particular, exposure look-up tables were developed from available exposure tools (European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) for worker exposure, ECETOC TRA, European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) for consumer exposure, and USEtox® for indirect exposure to humans via the environment) and were tested in a hypothetical mosquito bed netting case study. A detailed WHO risk assessment for a similar mosquito net use served as a benchmark for the performance of the RISK21 approach. The case study demonstrated that the screening methodologies provided suitable conservative exposure estimates for risk assessment. The results of this effort showed that the RISK21 approach is useful for defining future assessment efforts, focusing assessment activities and visualizing results.