Showing papers in "Journal of Toxicology and Environmental Health-part B-critical Reviews in 2015"

Inhalation Exposure to Carbon Nanotubes (CNT) and Carbon Nanofibers (CNF): Methodology and Dosimetry

Abstract: Carbon nanotubes (CNT) and nanofibers (CNF) are used increasingly in a broad array of commercial products. Given current understandings, the most significant life-cycle exposures to CNT/CNF occur from inhalation when they become airborne at different stages of their life cycle, including workplace, use, and disposal. Increasing awareness of the importance of physicochemical properties as determinants of toxicity of CNT/CNF and existing difficulties in interpreting results of mostly acute rodent inhalation studies to date necessitate a reexamination of standardized inhalation testing guidelines. The current literature on pulmonary exposure to CNT/CNF and associated effects is summarized; recommendations and conclusions are provided that address test guideline modifications for rodent inhalation studies that will improve dosimetric extrapolation modeling for hazard and risk characterization based on the analysis of exposure-dose-response relationships. Several physicochemical parameters for CNT/CNF, including shape, state of agglomeration/aggregation, surface properties, impurities, and density, influence toxicity. This requires an evaluation of the correlation between structure and pulmonary responses. Inhalation, using whole-body exposures of rodents, is recommended for acute to chronic pulmonary exposure studies. Dry powder generator methods for producing CNT/CNF aerosols are preferred, and specific instrumentation to measure mass, particle size and number distribution, and morphology in the exposure chambers are identified. Methods are discussed for establishing experimental exposure concentrations that correlate with realistic human exposures, such that unrealistically high experimental concentrations need to be identified that induce effects under mechanisms that are not relevant for workplace exposures. Recommendations for anchoring data to results seen for positive and negative benchmark materials are included, as well as periods for postexposure observation. A minimum data set of specific bronchoalveolar lavage parameters is recommended. Retained lung burden data need to be gathered such that exposure-dose-response correlations may be analyzed and potency comparisons between materials and mammalian species are obtained considering dose metric parameters for interpretation of results. Finally, a list of research needs is presented to fill data gaps for further improving design, analysis, and interpretation and extrapolation of results of rodent inhalation studies to refine meaningful risk assessments for humans.

Exposures and Health Outcomes in Relation to Bioaerosol Emissions From Composting Facilities: A Systematic Review of Occupational and Community Studies

Abstract: The number of composting sites in Europe is rapidly increasing, due to efforts to reduce the fraction of waste destined for landfill, but evidence on possible health impacts is limited. This article systematically reviews studies related to bioaerosol exposures within and near composting facilities and associated health effects in both community and occupational health settings. Six electronic databases and bibliographies from January 1960 to July 2014 were searched for studies reporting on health outcomes and/or bioaerosol emissions related to composting sites. Risk of bias was assessed using a customized score. Five hundred and thirty-six papers were identified and reviewed, and 66 articles met the inclusion criteria (48 exposure studies, 9 health studies, 9 health and exposure studies). Exposure information was limited, with most measurements taken in occupational settings and for limited time periods. Bioaerosol concentrations were highest on-site during agitation activities (turning, shredding, and screening). Six studies detected concentrations of either Aspergillus fumigatus or total bacteria above the English Environment Agency’s recommended threshold levels beyond 250 m from the site. Occupational studies of compost workers suggested elevated risks of respiratory illnesses with higher bioaerosol exposures. Elevated airway irritation was reported in residents near composting sites, but this may have been affected by reporting bias. The evidence base on health effects of bioaerosol emissions from composting facilities is still limited, although there is sufficient evidence to support a precautionary approach for regulatory purposes. While data to date are suggestive of possible respiratory effects, further study is needed to confirm this and to explore other health outcomes.

Techniques and Protocols for Dispersing Nanoparticle Powders in Aqueous Media—Is there a Rationale for Harmonization?

Abstract: Selecting appropriate ways of bringing engineered nanoparticles (ENP) into aqueous dispersion is a main obstacle for testing, and thus for understanding and evaluating, their potential adverse effects to the environment and human health. Using different methods to prepare (stock) dispersions of the same ENP may be a source of variation in the toxicity measured. Harmonization and standardization of dispersion methods applied in mammalian and ecotoxicity testing are needed to ensure a comparable data quality and to minimize test artifacts produced by modifications of ENP during the dispersion preparation process. Such harmonization and standardization will also enhance comparability among tests, labs, and studies on different types of ENP. The scope of this review was to critically discuss the essential parameters in dispersion protocols for ENP. The parameters are identified from individual scientific studies and from consensus reached in larger scale research projects and international organizations. A step-wise approach is proposed to develop tailored dispersion protocols for ecotoxicological and mammalian toxicological testing of ENP. The recommendations of this analysis may serve as a guide to researchers, companies, and regulators when selecting, developing, and evaluating the appropriateness of dispersion methods applied in mammalian and ecotoxicity testing. However, additional experimentation is needed to further document the protocol parameters and investigate to what extent different stock dispersion methods affect ecotoxicological and mammalian toxicological responses of ENP.

Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products

Abstract: Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches.

The Elizabeth River Story: A Case Study in Evolutionary Toxicology

Abstract: The Elizabeth River system is an estuary in southeastern Virginia, surrounded by the towns of Chesapeake, Norfolk, Portsmouth, and Virginia Beach. The river has played important roles in U.S. history and has been the location of various military and industrial activities. These activities have been the source of chemical contamination in this aquatic system. Important industries, until the 1990s, included wood treatment plants that used creosote, an oil-derived product that is rich in polycyclic aromatic hydrocarbons (PAH). These plants left a legacy of PAH pollution in the river, and in particular Atlantic Wood Industries is a designated Superfund site now undergoing remediation. Numerous studies examined the distribution of PAH in the river and impacts on resident fauna. This review focuses on how a small estuarine fish with a limited home range, Fundulus heteroclitus (Atlantic killifish or mummichog), has responded to this pollution. While in certain areas of the river this species has clearly been impacted, as evidenced by elevated rates of liver cancer, some subpopulations, notably the one associated with the Atlantic Wood Industries site, displayed a remarkable ability to resist the marked effects PAH have on the embryonic development of fish. This review provides evidence of how pollutants have acted as evolutionary agents, causing changes in ecosystems potentially lasting longer than the pollutants themselves. Mechanisms underlying this evolved resistance, as well as mechanisms underlying the effects of PAH on embryonic development, are also described. The review concludes with a description of ongoing and promising efforts to restore this historic American river.

The One Health Perspective in Trace Elements Biomonitoring.

Abstract: Health risks in both animals and humans are associated with chronic exposures to levels of trace elements (TE) eliciting toxic and/or antinutritional effects, including excess exposures to some essential elements. Interferences with essential TE may also lead to secondary nutritional deficiencies and/or imbalances. Although research is still required, biomarkers of exposure, including bioavailability, for TE are established tools for human biomonitoring that can also be applied to animal surveillance. Biomarkers of effect as well as, where available, of susceptibility and bioavailability are necessary to understand whether an ongoing exposure may pose a current or future health concern. In the field of animal health the use of biomarkers is less developed and less widespread than in human health; however, under a One Health perspective, animal biomonitoring can provide important information on the interfaces among humans, animals, and the environment, supporting the prevention and management of health risks. Therefore, a transfer of knowledge from human biomonitoring to farm or free-ranging animals is critical in a risk assessment framework from farm to humans. Advantages and critical aspects in designing and conducting integrative biomonitoring activities in humans and animals were critically reviewed focusing on biomarkers of exposure, effect, susceptibility, and bioavailability for toxic and essential TE. Highlighted aspects include TE metabolism, bioaccessibility, and interactions. Farm or free-ranging animals may provide noninvasive matrices suitable for evaluating animal welfare, environmental stressors, food safety, and potential risks for human health, as proposed by the interdisciplinary concept of One Health.

Methodologies for determining the sources, characteristics, distribution, and abundance of asbestiform and nonasbestiform amphibole and serpentine in ambient air and water.

Abstract: Anthropogenic and nonanthropogenic (erosion) processes contribute to the continuing presence of asbestos and nonasbestos elongated mineral particles (EMP) of amphibole and serpentine in air and water of urban, rural, and remote environments. The anthropogenic processes include disturbance and deterioration of asbestos-containing materials, mining of amphibole- and serpentine-bearing rock, and disturbance of soils containing amphibole and serpentine. Atmospheric dispersal processes can transport EMP on a global scale. There are many methods of establishing the abundance of EMP in air and water. EMP include cleavage fragments, fibers, asbestos, and other asbestiform minerals, and the methods employed do not critically distinguish among them. The results of most of the protocols are expressed in the common unit of fibers per square centimeter; however, seven different definitions for the term "fiber" are employed and the results are not comparable. The phase-contrast optical method used for occupational monitoring cannot identify particles being measured, and none of the methods distinguish amphibole asbestos from other EMP of amphibole. Measured ambient concentrations of airborne EMP are low, and variance may be high, even for similar environments, yielding data of questionable value for risk assessment. Calculations based on the abundance of amphibole-bearing rock and estimates of asbestos in the conterminous United States suggest that amphibole may be found in 6-10% of the land area; nonanthropogenic erosional processes might produce on the order of 400,000 tons or more of amphibole per year, and approximately 50 g asbestos/km(2)/yr; and the order of magnitude of the likelihood of encountering rock bearing any type of asbestos is approximately 0.0001.

Windows of Sensitivity to Toxic Chemicals in the Development of Cleft Palates

Abstract: Cleft lip and cleft palate are among the most common birth defects worldwide. There is a genetic component to the development of these malformations, as well as evidence that environmental exposures and prescription drug use may exacerbate or even produce these manifestations. Thus, it is important to understand the underlying mechanisms and when these exposures affect development of the growing fetus. The purpose of this investigation was to critically review the available literature related to orofacial cleft formation following chemical exposure and identify specific time frames for windows of sensitivity. Further, an aim was to evaluate the potential for predicting effects in humans based on animal studies. Evidence indicates that chemical causes of cleft palate development are due to dose and timing of exposure, susceptibility of the species (i.e., the genetic makeup), and mechanism of action. Several studies demonstrated that dose is a crucial factor; however, some investigators argued that even more important than dose was timing of exposure. Data show that the window of sensitivity to environmental teratogens in the development of cleft palates is quite narrow and follows closely the window of palatogenesis in the fetus of any given species.

Improving Concordance in Environmental Epidemiology: A Three-Part Proposal

Abstract: In observational research, evidence is usually derived from multiple studies, and any single result is rarely considered sufficient for public health decision making Despite more than five decades of research and thousands of studies published, the ability to draw robust conclusions regarding the presence or absence of causal links between specific environmental exposures and human health remains limited To develop policies that are protective of public health and can withstand scrutiny, agencies need to rely on investigations of satisfactory quality that follow sufficiently concordant protocols in terms of exposure assessment, outcome ascertainment, data analysis, and reporting of results Absent such concordance, the ability of environmental epidemiology studies to inform decision making is greatly diminished Systems and tools are proposed here to improve concordance among environmental epidemiology studies Specifically, working systems in place in other fields of research are critically examined and used as guidelines to develop analogous policies and procedures for environmental epidemiology A three-part path forward toward more concordant, transparent, and readily accessible environmental epidemiology evidence that parallels ongoing efforts in medical research is proposed The three parts address methods for improving quality and accessibility of systematic reviews, access to information on ongoing and completed studies, and principles for reporting The goals are to increase the value of epidemiological research in public health decision making and to stimulate discussions around solutions proposed herein

Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein.

Abstract: The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.

Benzene Exposures and Risk Potential for Vehicle Mechanics from Gasoline and Petroleum-Derived Products.

Abstract: Benzene exposures among vehicle mechanics in the United States and abroad were characterized using available data from published and unpublished studies. In the United States, the time-weighted-average (TWA) airborne concentration of benzene for vehicle mechanics averaged 0.01-0.05 ppm since at least the late 1970s, with maximal TWA concentrations ranging from 0.03 to 0.38 ppm. Benzene exposures were notably lower in the summer than winter and in the Southwest compared to other geographic regions, but significantly higher during known gasoline-related tasks such as draining a gas tank or changing a fuel pump or fuel filter. Measured airborne concentrations of benzene were also generally greater for vehicle mechanics in other countries, likely due to the higher benzene content of gasoline and other factors. Short-term airborne concentrations of benzene frequently exceeded 1 ppm during gasoline-related tasks, but remained below 0.2 ppm for tasks involving other petroleum-derived products such as carburetor and brake cleaner or parts washer solvent. Application of a two-zone mathematical model using reasonable input values from the literature yielded predicted task-based benzene concentrations during gasoline and aerosol spray cleaner scenarios similar to those measured for vehicle mechanics during these types of tasks. When evaluated using appropriate biomarkers, dermal exposures were found to contribute little to total benzene exposures for this occupational group. Available data suggest that vehicle mechanics have not experienced significant exposures to benzene in the workplace, except perhaps during short-duration gasoline-related tasks, and full-shift benzene exposures have remained well below current and contemporaneous occupational exposure limits. These findings are consistent with epidemiology studies of vehicle mechanics, which have not demonstrated an increased risk of benzene-induced health effects in this cohort of workers. Data and information presented here may be used to assess past, current, or future exposures and risks to benzene for vehicle mechanics who may be exposed to gasoline or other petroleum-derived products.

Mathematical Models for Estimating the Risks of Bovine Spongiform Encephalopathy (BSE).

Abstract: When the bovine spongiform encephalopathy (BSE) epidemic first emerged in the United Kingdom in the mid 1980s, the etiology of animal prion diseases was largely unknown. Risk management efforts to control the disease were also subject to uncertainties regarding the extent of BSE infections and future course of the epidemic. As understanding of BSE increased, mathematical models were developed to estimate risk of BSE infection and to predict reductions in risk in response to BSE control measures. Risk models of BSE-transmission dynamics determined disease persistence in cattle herds and relative infectivity of cattle prior to onset of clinical disease. These BSE models helped in understanding key epidemiological features of BSE transmission and dynamics, such as incubation period distribution and age-dependent infection susceptibility to infection with the BSE agent. This review summarizes different mathematical models and methods that have been used to estimate risk of BSE, and discusses how such risk projection models have informed risk assessment and management of BSE. This review also provides some general insights on how mathematical models of the type discussed here may be used to estimate risks of emerging zoonotic diseases when biological data on transmission of the etiological agent are limited.