Alternative Testing Strategies for Nanomaterials: State of the Science and Considerations for Risk Analysis.

The rapid growth of the nanotechnology industry has warranted equal progress in the nanotoxicology and risk assessment fields. In vivo models have traditionally been used to determine human and environmental risk for chemicals; however, the use of these tests has limitations, and there are global appeals to develop reliable alternatives to animal testing. Many have investigated the use of alternative (nonanimal) testing methods and strategies have quickly developed and resulted in the generation of large toxicological data sets for numerous nanomaterials (NMs). Due to the novel physicochemical properties of NMs that are related to surface characteristics, the approach toward toxicity test development has distinct considerations from traditional chemicals, bringing new requirements for adapting these approaches for NMs. The methodical development of strategies that combine multiple alternative tests can be useful for predictive NM risk assessment and help screening-level decision making. This article provides an overview of the main developments in alternative methods and strategies for reducing uncertainty in NM risk assessment, including advantages and disadvantages of in vitro, ex vivo, and in silico methods, and examples of existing comprehensive strategies. In addition, knowledge gaps are identified toward improvements for experimental and strategy design, specifically highlighting the need to represent realistic exposure scenarios and to consider NM-specific concerns such as characterization, assay interferences, and standardization. Overall, this article aims to improve the reliability and utility of alternative testing methods and strategies for risk assessment of manufactured NMs.

Advancing Risk Analysis for Nanoscale Materials: Report from an International Workshop on the Role of Alternative Testing Strategies for Advancement.

The Society for Risk Analysis (SRA) has a history of bringing thought leadership to topics of emerging risk. In September 2014, the SRA Emerging Nanoscale Materials Specialty Group convened an international workshop to examine the use of alternative testing strategies (ATS) for manufactured nanomaterials (NM) from a risk analysis perspective. Experts in NM environmental health and safety, human health, ecotoxicology, regulatory compliance, risk analysis, and ATS evaluated and discussed the state of the science for in vitro and other alternatives to traditional toxicology testing for NM. Based on this review, experts recommended immediate and near-term actions that would advance ATS use in NM risk assessment. Three focal areas-human health, ecological health, and exposure considerations-shaped deliberations about information needs, priorities, and the next steps required to increase confidence in and use of ATS in NM risk assessment. The deliberations revealed that ATS are now being used for screening, and that, in the near term, ATS could be developed for use in read-across or categorization decision making within certain regulatory frameworks. Participants recognized that leadership is required from within the scientific community to address basic challenges, including standardizing materials, protocols, techniques and reporting, and designing experiments relevant to real-world conditions, as well as coordination and sharing of large-scale collaborations and data. Experts agreed that it will be critical to include experimental parameters that can support the development of adverse outcome pathways. Numerous other insightful ideas for investment in ATS emerged throughout the discussions and are further highlighted in this article.

Pharmacokinetics of the dermal route of exposure to volatile organic chemicals in water: a computer simulation model.

A kinetic model of dermal absorption of nonpolar organic nonelectrolytes in dilute aqueous solutions is described. The model uses systems dynamics STELLA software and is designed for a Macintosh computer. The model assumes the outer stratum corneum layer of skin to be the rate-determining barrier to dermal absorption and assumes that both stratum corneum and viable epidermal layers have storage capacity for lipophilic solutes. The model predicts between 30 and 94% of experimental results with humans under the same conditions. The degree of departure between experimental and theoretical results is inversely related to the solute's octanol/water partition coefficient, which is consistent with the most recently hypothesized mechanisms of transport of molecules across the dermal barrier. The model has potentially useful applications for risk assessment if used within its defined limits.