Predictive models for nanotoxicology: current challenges and future opportunities.

Characterizing the risks posed by nanomaterials is extraordinarily complex because these materials can have a wide range of sizes, shapes, chemical compositions and surface modifications, all of which may affect toxicity. There is an urgent need for a testing strategy that can rapidly and efficiently provide a screening approach for evaluating the potential hazard of nanomaterials and inform the prioritization of additional toxicological testing where necessary. Predictive toxicity models could form an integral component of such an approach by predicting which nanomaterials, as a result of their physico-chemical characteristics, have potentially hazardous properties. Strategies for directing research towards predictive models and the ancillary benefits of such research are presented here

Assuring access to data for chemical evaluations

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

Aneuploidy: a common and early evidence-based biomarker for carcinogens and reproductive toxicants.

Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells. In this paper we review 1) the contributions of aneuploidy to cancer, infertility, and developmental abnormalities; 2) techniques for assessing aneuploidy in precancerous and malignant lesions and in sperm; and 3) the utility of aneuploidy as a biomarker for integrated chemical assessments of carcinogenicity, and reproductive and developmental toxicity

Contribution of Company Affiliation and Social Contacts to Risk Estimates of Between-Farm Transmission of Avian Influenza

BACKGROUND: Models of between-farm transmission of pathogens have identified service vehicles and social groups as risk factors mediating the spread of infection. Because of high levels of economic organization in much of the poultry industry, we examined the importance of company affiliation, as distinct from social contacts, in a model of the potential spread of avian influenza among broiler poultry farms in a poultry-dense region in the United States. The contribution of company affiliation to risk of between-farm disease transmission has not been previously studied. METHODOLOGY/PRINCIPAL FINDINGS: We obtained data on the nature and frequency of business and social contacts through a national survey of broiler poultry growers in the United States. Daily rates of contact were estimated using Monte Carlo analysis. Stochastic modeling techniques were used to estimate the exposure risk posed by a single infectious farm to other farms in the region and relative risk of exposure for farms under different scenarios. The mean daily rate of vehicular contact was 0.82 vehicles/day. The magnitude of exposure risk ranged from <1% to 25% under varying parameters. Risk of between-farm transmission was largely driven by company affiliation, with farms in the same company group as the index farm facing as much as a 5-fold increase in risk compared to farms contracted with different companies. Employment of part-time workers contributed to significant increases in risk in most scenarios, notably for farms who hired day-laborers. Social visits were significantly less important in determining risk. CONCLUSIONS/SIGNIFICANCE: Biosecurity interventions should be based on information on industry structure and company affiliation, and include part-time workers as potentially unrecognized sources of viral transmission. Modeling efforts to understand pathogen transmission in the context of industrial food animal production should consider company affiliation in addition to geospatial factors and pathogen characteristics. Restriction of social contacts among farmers may be less useful in reducing between-farm transmission

Arsenic: A Roadblock to Potential Animal Waste Management Solutions

The localization and intensification of the poultry industry over the past 50 years have incidentally created a largely ignored environmental management crisis. As a result of these changes in poultry production, concentrated animal feeding operations (CAFOs) produce far more waste than can be managed by land disposal within the regions where it is produced. As a result, alternative waste management practices are currently being implemented, including incineration and pelletization of waste. However, organic arsenicals used in poultry feed are converted to inorganic arsenicals in poultry waste, limiting the feasibility of waste management alternatives. The presence of inorganic arsenic in incinerator ash and pelletized waste sold as fertilizer creates opportunities for population exposures that did not previously exist. The removal of arsenic from animal feed is a critical step toward safe poultry waste management

Genomic differences between nasal Staphylococcus aureus from hog slaughterhouse workers and their communities.

New human pathogens can emerge from the livestock-human interface and spread into human populations through many pathways including livestock products. Occupational contact with livestock is a risk factor for exposure to those pathogens and may cause further spreading of those pathogens in the community. The current study used whole genome sequencing to explore nasal Staphylococcus aureus obtained from hog slaughterhouse workers and their community members, all of whom resided in a livestock-dense region in rural North Carolina. Sequence data were analyzed for lineage distribution, pathogenicity-related genomic features, and mobile genetic elements. We observed evidence of nasal S. aureus differences between hog workers and non-workers. Nasal S. aureus from hog workers showed a greater lineage diversity than nasal S. aureus from community residents. Hog worker isolates were less likely to carry the φSa3 prophage and human-specific immune evasion cluster genes than community resident isolates (φSa3 prophage: 54.5% vs. 91.7%, Benjamini-Hochberg (BH) corrected p = 0.035; immune evasion cluster genes: 66.7% vs. 100%, BH p = 0.021). Hog worker isolates had a lower prevalence and diversity of enterotoxins than community resident isolates, particularly lacking the enterotoxin gene cluster (39.4% vs. 70.8%, BH p = 0.125). Moreover, hog worker isolates harbored more diverse antibiotic resistance genes, with a higher prevalence of carriage of multiple resistance genes, than community resident isolates (75.8% vs. 29.2%, BH p = 0.021). Phylogenetic analysis of all ST5 isolates, the most abundant lineage in the collection, further supported separation of isolates from hog workers and non-workers. Together, our observations suggest impact of occupational contact with livestock on nasal S. aureus colonization and highlight the need for further research on the complex epidemiology of S. aureus at the livestock-human interface

An approach to assessment of endocrine disruption in the National Children's Study.

In this article we consider the importance of assessing endocrine disruption in a large new cohort that has been proposed, the National Children's Study (NCS). We briefly review evidence that endocrine disruption is a potentially important hypothesis for human studies and weigh the need to assess endocrine disruption in the NCS. We note the salient features of earlier, similar cohort studies that serve as reference points for the design of the NCS. Finally, we discuss features of the NCS that would allow or enhance assessment of endocrine disruption, even if endocrine disruption were not a primary hypothesis motivating the study. At this time, the evidence supporting endocrine disruption in humans with background-level exposures is not strong. Thus, a compelling rationale for the NCS will probably need to be based on core hypotheses that focus on other issues. Nonetheless, if properly designed, the NCS could serve as an excellent resource for investigating future hypotheses regarding endocrine disruption