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Behrsing H.,Institute for in Vitro science Inc. | Raabe H.,Institute for in Vitro science Inc. | Manuppello J.,PETA International Science Consortium Ltd. | Bombick B.,R.J. Reynolds Tobacco Company | And 17 more authors.
ATLA Alternatives to Laboratory Animals | Year: 2016

The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobaccoinduced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide.

Lefebvre D.E.,Regulatory Toxicology Research Division | Venema K.,Beneficial Microbes Consultancy | Gombau L.,Leitat Technological Center | Valerio L.G.,U.S. Food and Drug Administration | And 8 more authors.
Nanotoxicology | Year: 2015

Engineered metal/mineral, lipid and biochemical macromolecule nanomaterials (NMs) have potential applications in food. Methodologies for the assessment of NM digestion and bioavailability in the gastrointestinal tract are nascent and require refinement. A working group was tasked by the International Life Sciences Institute NanoRelease Food Additive project to review existing models of the gastrointestinal tract in health and disease, and the utility of these models for the assessment of the uptake of NMs intended for food. Gastrointestinal digestion and absorption could be addressed in a tiered approach using in silico computational models, in vitro non-cellular fluid systems and in vitro cell culture models, after which the necessity of ex vivo organ culture and in vivo animal studies can be considered. Examples of NM quantification in gastrointestinal tract fluids and tissues are emerging; however, few standardized analytical techniques are available. Coupling of these techniques to gastrointestinal models, along with further standardization, will further strengthen methodologies for risk assessment. © 2014 The Author(s). Published by Taylor & Francis.

Bishop P.L.,People for the Ethical Treatment of Animals | Bishop P.L.,PETA International Science Consortium Ltd. | Willett C.E.,The Humane Society of the United States
Birth Defects Research Part B - Developmental and Reproductive Toxicology | Year: 2014

The U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP) currently relies on an initial screening battery (Tier 1) consisting of five in vitro and six in vivo assays to evaluate a chemical's potential to interact with the endocrine system. Chemical companies may request test waivers based on Other Scientifically Relevant Information (OSRI) that is functionally equivalent to data gathered in the screening battery or that provides information on a potential endocrine effect. Respondents for 47 of the first 67 chemicals evaluated in the EDSP submitted OSRI in lieu of some or all Tier 1 tests, seeking 412 waivers, of which EPA granted only 93. For 20 of the 47 chemicals, EPA denied all OSRI and required the entire Tier 1 battery. Often, the OSRI accepted was either identical to data generated by the Tier 1 assay or indicated a positive result. Although identified as potential sources of OSRI in EPA guidance, Part 158 guideline studies for pesticide registration were seldom accepted by EPA. The 93 waivers reduced animal use by at least 3325 animals. We estimate 27,731 animals were used in the actual Tier 1 tests, with additional animals being used in preparation for testing. Even with EPA's shift toward applying 21st-century toxicology tools to screening of endocrine disruptors in the future, acceptance of OSRI will remain a primary means for avoiding duplicative testing and reducing use of animals in the EDSP. Therefore, it is essential that EPA develop a consistent and transparent basis for accepting OSRI. © 2013 Wiley Periodicals, Inc.

Polk W.W.,Integrated Laboratory Systems, Inc. | Sharma M.,PETA International Science Consortium Ltd. | Sayes C.M.,Baylor University | Hotchkiss J.A.,Dow Chemical Company | Clippinger A.J.,PETA International Science Consortium Ltd.
Particle and Fibre Toxicology | Year: 2016

Aerosol generation and characterization are critical components in the assessment of the inhalation hazards of engineered nanomaterials (NMs). An extensive review was conducted on aerosol generation and exposure apparatus as part of an international expert workshop convened to discuss the design of an in vitro testing strategy to assess pulmonary toxicity following exposure to aerosolized particles. More specifically, this workshop focused on the design of an in vitro method to predict the development of pulmonary fibrosis in humans following exposure to multi-walled carbon nanotubes (MWCNTs). Aerosol generators, for dry or liquid particle suspension aerosolization, and exposure chambers, including both commercially available systems and those developed by independent researchers, were evaluated. Additionally, characterization methods that can be used and the time points at which characterization can be conducted in order to interpret in vitro exposure results were assessed. Summarized below is the information presented and discussed regarding the relevance of various aerosol generation and characterization techniques specific to aerosolized MWCNTs exposed to cells cultured at the air-liquid interface (ALI). The generation of MWCNT aerosols relevant to human exposures and their characterization throughout exposure in an ALI system is critical for extrapolation of in vitro results to toxicological outcomes in humans. © 2016 Polk et al.

Sharma M.,PETA International Science Consortium Ltd. | Nikota J.,Environmental Health Science and Research Bureau | Halappanavar S.,Environmental Health Science and Research Bureau | Castranova V.,West Virginia University | And 2 more authors.
Archives of Toxicology | Year: 2016

The increased production and use of multi-walled carbon nanotubes (MWCNTs) in a diverse array of consumer, medical, and industrial applications have raised concerns about potential human exposure to these materials in the workplace and ambient environments. Inhalation is a primary route of exposure to MWCNTs, and the existing data indicate that they are potentially hazardous to human health. While a 90-day rodent inhalation test (e.g., OECD Test No. 413: subchronic inhalation toxicity: 90-day study or EPA Health Effects Test Guidelines OPPTS 870.3465 90-day inhalation toxicity) is recommended by the U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics for MWCNTs (and other CNTs) if they are to be commercially produced (Godwin et al. in ACS Nano 9:3409–3417, 2015), this test is time and cost-intensive and subject to scientific and ethical concerns. As a result, there has been much interest in transitioning away from studies on animals and moving toward human-based in vitro and in silico models. However, given the multiple mechanisms of toxicity associated with subchronic exposure to inhaled MWCNTs, a battery of non-animal tests will likely be needed to evaluate the key endpoints assessed by the 90-day rodent study. Pulmonary fibrosis is an important adverse outcome related to inhalation exposure to MWCNTs and one that the non-animal approach should be able to assess. This review summarizes the state-of-the-science regarding in vivo and in vitro toxicological methods for predicting MWCNT-induced pulmonary fibrosis. © 2016, Springer-Verlag Berlin Heidelberg.

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