E. Spencer Williams

Global Assessment of Bisphenol A in the Environment: Review and Analysis of Its Occurrence and Bioaccumulation

Because bisphenol A (BPA) is a high production volume chemical, we examined over 500 peer-reviewed studies to understand its global distribution in effluent discharges, surface waters, sewage sludge, biosolids, sediments, soils, air, wildlife, and humans. Bisphenol A was largely reported from urban ecosystems in Asia, Europe, and North America; unfortunately, information was lacking from large geographic areas, megacities, and developing countries. When sufficient data were available, probabilistic hazard assessments were performed to understand global environmental quality concerns. Exceedances of Canadian Predicted No Effect Concentrations for aquatic life were >50% for effluents in Asia, Europe, and North America but as high as 80% for surface water reports from Asia. Similarly, maximum concentrations of BPA in sediments from Asia were higher than Europe. Concentrations of BPA in wildlife, mostly for fish, ranged from 0.2 to 13 000 ng/g. We observed 60% and 40% exceedences of median levels by the US Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey in Europe and Asia, respectively. These findings highlight the utility of coordinating global sensing of environmental contaminants efforts through integration of environmental monitoring and specimen banking to identify regions for implementation of more robust environmental assessment and management programs.

Coal-Tar-Based Pavement Sealcoat and PAHs: Implications for the Environment, Human Health, and Stormwater Management

Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20−35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments—including stormwater runoff, lake sediment, soil, house dust, and most recently, air—contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them.

Cancer risk from incidental ingestion exposures to PAHs associated with coal-tar-sealed pavement.

Recent (2009-10) studies documented significantly higher concentrations of polycyclic aromatic hydrocarbons (PAHs) in settled house dust in living spaces and soil adjacent to parking lots sealed with coal-tar-based products. To date, no studies have examined the potential human health effects of PAHs from these products in dust and soil. Here we present the results of an analysis of potential cancer risk associated with incidental ingestion exposures to PAHs in settings near coal-tar-sealed pavement. Exposures to benzo[a]pyrene equivalents were characterized across five scenarios. The central tendency estimate of excess cancer risk resulting from lifetime exposures to soil and dust from nondietary ingestion in these settings exceeded 1 × 10(-4), as determined using deterministic and probabilistic methods. Soil was the primary driver of risk, but according to probabilistic calculations, reasonable maximum exposure to affected house dust in the first 6 years of life was sufficient to generate an estimated excess lifetime cancer risk of 6 × 10(-5). Our results indicate that the presence of coal-tar-based pavement sealants is associated with significant increases in estimated excess lifetime cancer risk for nearby residents. Much of this calculated excess risk arises from exposures to PAHs in early childhood (i.e., 0-6 years of age).

An initial probabilistic hazard assessment of oil dispersants approved by the united states national contingency plan

Dispersants are commonly applied during oil spill mitigation efforts; however, these industrial chemicals may present risks to aquatic organisms individually and when mixed with oil. Fourteen dispersants are listed on the U.S. Environmental Protection Agency (U.S. EPA) National Oil and Hazardous Substances Pollution Contingency Plan (NCP). Availability of environmental effects information for such agents is limited, and individual components of dispersants are largely proprietary. Probabilistic hazard assessment approaches including Chemical Toxicity Distributions (CTDs) may be useful as an initial step toward prioritizing environmental hazards from the use of dispersants. In the present study, we applied the CTD approach to two acute toxicity datasets: NCP (the contingency plan dataset) and DHOS (a subset of NCP listed dispersants reevaluated subsequent to the Deepwater Horizon oil spill). These datasets contained median lethal concentration (LC50) values for dispersants alone and dispersant:oil mixtures, in two standard marine test species, Menidia beryllina and Mysidopsis bahia. These CTDs suggest that dispersants alone are generally less toxic than oil. In contrast, most dispersant:oil mixtures are more toxic than oil alone. For the two datasets (treated separately because of differing methodologies), CTDs would predict 95% of dispersant:oil mixtures to have acute toxicity values above 0.32 and 0.76 mg/L for Mysidopsis and 0.33 mg/L and 1.06 mg/L for Menidia (for DHOS and NCP, respectively). These findings demonstrate the utility of CTDs as a means to evaluate the comparative ecotoxicity of dispersants alone and in mixture with different oil types. The approaches presented here also provide valuable tools for prioritizing prospective and retrospective environmental assessments of oil dispersants.

Application of chemical toxicity distributions to ecotoxicology data requirements under REACH.

The European Unions REACH regulation has further highlighted the lack of ecotoxicological data for substances in the marketplace. The mandates under REACH (registration, evaluation, authorization, and restriction of chemicals) to produce data and minimize testing on vertebrates present an impetus for advanced hazard assessment techniques using read-across. Research in our group has recently focused on probabilistic ecotoxicological hazard assessment approaches using chemical toxicity distributions (CTDs). Using available data for chemicals with similar modes of action or within a chemical class may allow for selection of a screening point value (SPV) for development of environmental safety values, based on a probabilistic distribution of toxicity values for a specific endpoint in an ecological receptor. Ecotoxicity data for acetylcholinesterase inhibitors and surfactants in Daphnia magna and Pimephales promelas were gathered from several data sources, including the U.S. Environmental Protection Agencys ECOTOX and Pesticides Ecotoxicity databases, the peer-reviewed literature, and the Human and Environmental Risk Assessment (HERA) project. Chemical toxicity distributions were subsequently developed, and the first and fifth centiles were used as SPVs for the development of screening-predicted no-effect concentrations (sPNECs). The first and fifth centiles of these distributions were divided by an assessment factor of 1,000, as recommended by REACH guidance. Use of screening values created using these techniques could support the processes of data dossier development and environmental exposure assessment, allowing for rigorous prioritization in testing and monitoring to fill data gaps.

The transgenic mouse assay as an alternative test method for regulatory carcinogenicity studies—Implications for REACH

REACH, an EU regulation that requires the submission of safety data in support of the protection of human and environmental health, mandates that registration should be achieved with the minimum amount of animal testing possible. Under REACH, a two-year carcinogenicity assay may be required for certain chemicals produced at >1000 metric tonnes per year. In addition, some chemicals that are found to be genotoxic will also require testing. Alternative methods have been explored in an attempt to improve the predictivity of this bioassay as well as to reduce the number of animals used for such testing. This research has focused on the use of transgenic/knockout mouse models. Study results from selected models indicate that they are useful in hazard identification, even if they are not entirely suitable for risk assessment on their own. Carcinogenic hazard assessment can be greatly enhanced and animal use reduced if the traditional two-year rat bioassay is combined with a well conducted transgenic mouse assay. Importantly, the use of transgenic animals to supplement a traditional two-year carcinogenicity study may help reduce the number of false negatives, one of the unstated goals of REACH via the precautionary principle.

Interpreting REACH guidance in the determination of the derived no effect level (DNEL)

Under the new European chemicals regulation, REACH, a new safety value, the Derived No Effect Level (DNEL) must be established for all chemicals manufactured, imported or used in the EU in quantities greater than 10 metric tonnes per year. The DNEL is to be calculated for all relevant exposure pathways, exposure populations, and endpoints of toxicity. The EU has published guidance on how to derive the DNEL, but this guidance has yet to be put into practice and is in some places not prescriptive. Using the Agency for Toxic Substances and Disease Registry (ATSDR) dataset, we have determined inhalation DNELs for styrene. In doing so, we considered what effect key decisions would have on the calculated DNEL. The resulting DNELs were then compared to existing risk criteria values or occupational exposure limits. General population DNELs were generally more conservative than analogous risk criteria (ranging from approximately 0.05 to 2.5 ppm). Worker DNELs are lower than existing occupational standards (ranging from approximately 0.4 to 20 ppm). To our knowledge, this work represents the first rigorous application and interpretation of the EU guidance for determination of a DNEL and will prove useful as a model for determination of other DNELs under REACH.

Development and application of a novel method for high‐throughput determination of PCDD/Fs and PCBs in sediments

A selective pressurized liquid extraction technique was developed for the simultaneous extraction of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) from contaminated sediments. The final method incorporated cleanup adsorbents (Florisil, alumina, and silica) into the extraction cell in a 1:1 ratio of matrix to individual adsorbent (w/w). Sulfur, a common interference found in sediments, was successfully removed by placing activated copper in the extraction bottle prior to extraction. No additional postextraction cleanup was required, and sample throughput was reduced to 2.5 h per sample. Target analytes were quantified using high-resolution gas chromatography/electron-capture negative ionization mass spectrometry and verified by high-resolution gas chromatography/high-resolution mass spectrometry. Though mean analyte recoveries (n = 3) of PCDD/Fs and dl-PCBs were 84 ± 5.8% and 70 ± 8.4%, respectively, mean surrogate recoveries for all PCDD/Fs using this novel method were greatly improved compared with US Environmental Protection Agency (USEPA) method 1613 (∼25-155%) and USEPA method 8290a (40-135%). After development, the method was used to examine surficial sediment samples from the San Jacinto River waste pits, a Superfund site in Houston, Texas, USA. In all samples, PCDD/Fs and dl-PCBs were detected, and the contaminant concentrations ranged over 5 orders of magnitude.

Toward the Design of Less Hazardous Chemicals: Exploring Comparative Oxidative Stress in Two Common Animal Models.

Sustainable molecular design of less hazardous chemicals presents a potentially transformative approach to protect public health and the environment. Relationships between molecular descriptors and toxicity thresholds previously identified the octanol-water distribution coefficient, log D, and the HOMO-LUMO energy gap, ΔE, as two useful properties in the identification of reduced aquatic toxicity. To determine whether these two property-based guidelines are applicable to sublethal oxidative stress (OS) responses, two common aquatic in vivo models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio), were employed to examine traditional biochemical biomarkers (lipid peroxidation, DNA damage, and total glutathione) and antioxidant gene activation following exposure to eight structurally diverse industrial chemicals (bisphenol A, cumene hydroperoxide, dinoseb, hydroquinone, indene, perfluorooctanoic acid, R-(-)-carvone, and tert-butyl hydroperoxide). Bisphenol A, cumene hydroperoxide, dinoseb, and hydroquinone were consistent inducers of OS. Glutathione was the most consistently affected biomarker, suggesting its utility as a sensitivity response to support the design of less hazardous chemicals. Antioxidant gene expression (changes in nrf2, gclc, gst, and sod) was most significantly (p < 0.05) altered by R-(-)-carvone, cumene hydroperoxide, and bisphenol A. Results from the present study indicate that metabolism of parent chemicals and the role of their metabolites in molecular initiating events should be considered during the design of less hazardous chemicals. Current empirical and computational findings identify the need for future derivation of sustainable molecular design guidelines for electrophilic reactive chemicals (e.g., SN2 nucleophilic substitution and Michael addition reactivity) to reduce OS related adverse outcomes in vivo.

Human Health Risk Assessment for Pharmaceuticals in the Environment: Existing Practice, Uncertainty, and Future Directions

Globally, several thousand substances are produced for pharmaceutical and biomedical applications in humans. The production tonnage of these compounds is astronomical, ranging to hundreds of tons annually. Based on data collected by the National Center for Health Statistics, individuals who visited their physician recorded an average of almost seven medications taken per person. As expected, this number increases dramatically in older persons to almost 20 medications per person after age 65. As the global population ages, the use of pharmaceuticals to alleviate age-related conditions can reasonably be expected to increase. Further, the ongoing development of large markets such as China and India will further increase the magnitude of pharmaceutical consumption. In general, it has been believed that the environmental concentrations of APIs are too low to constitute a risk to human health in developed countries, and several studies have been conducted to assess this perspective. However, a recent poll among expert stakeholders reported that 62% of those interviewed believed that pharmaceuticals in the environment (PIE) represent a risk to human health. In recent years, higher potential exposure levels in developing countries, potable water reuse and public health concerns regarding antibiotic resistance are receiving increased attention. Here we provide a critical examination of the state of human health risk assessment for human pharmaceuticals in the environment. We further identify important uncertainties and future research needs.