Read our latest publication with Bristol-Myers Squibb regarding a tiered testing strategy for occupational hazards of pharmaceutical intermediates now published in the Cutaneous and Ocular Toxicology Journal. Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on employees' eyes and skin can now be assessed using validated in vitro methods. Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. BMS and IIVS have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods (OECD TG 435, OECD TG 437, OECD TG 439.) Read the full article.
A framework for the assessment of novel next-generation tobacco and nicotine products with the potential to reduce health risks compared with cigarettes should integrate scientific studies incorporating nonclinical, clinical, and population studies approaches. These products should have lower emissions and exhibit reduced biological effects compared with those of cigarettes, ideally approaching those of smoking cessation. The products should also be acceptable cigarette alternatives for current smokers, while not appealing to nonsmokers or former smokers. Validating harm reduction and promoting regulatory acceptance of the assessment methods require a collaborative approach by industry, independent reviewers, the public health community, and regulatory agencies. This article summarizes the science and approaches applied and considered to substantiate tobacco harm reduction in the light of regulatory requirements. Read the full article.
The U.S. Food and Drug Administration has regulatory authority over tobacco products, including conventional cigarettes and next generation products (NGPs) such as e-cigarettes and tobacco heating products (THPs). There is a desire by the industry, regulators and animal protection organizations to incorporate non-animal test methods for tobacco product and NGP assessment. When assessing respiratory effects in vitro, reliable exposure systems that deliver aerosols to cellular/tissue cultures (such as human reconstructed airways or lung slices) at the air–liquid interface are needed. Using nicotine dosimetry, we report the characterization of a Vitrocell VC1 in our laboratories (IIVS, USA). Nicotine, generated from a 3R4F reference cigarette or NGP (e-cigarette and THP) aerosols at source and the exposure interface (culture media), was assessed using ultra-high-performance liquid chromatography–tandem mass spectrometry. These data were compared to published dosimetry data for the same products, generated at a different laboratory (BAT R&D, Southampton, UK), on different exposure systems (VC10 and Borgwaldt RM20S) to confirm repeatability. Read the full article.
To address ocular device induced phototoxicity, an in vitro 3T3 Neutral Red Uptake Phototoxicity test (OECD 432) for chemicals has been modified. Soft contact lenses formulated with three different photo-absorbing compounds and chemical solutions of these compounds were evaluated.
Alternative methods, including the validated 3T3 Neutral Red Uptake (NRU) Phototoxicity assay (OECD TG 432) may be used as a pre-clinical test to address phototoxicity. Currently, there are no validated alternative test methods to identify photoallergens; however, there are several validated alternative test methods to address skin sensitization, including the Direct Peptide Reactivity Assay (DPRA) (OECD 442C). To address photoallergy, we utilized the 3T3 Phototoxicity assay in combination with a modified photo-DPRA assay to determine if these assays were able to 1) identify compounds with phototoxicity potential and 2) discriminate between photoirritants and photoallergens.
Robust non-animal models and assays for pulmonary toxicology are required to make competent product development and risk assessments for new materials requiring toxicity testing. Three in vitro assays (goblet cell hyperplasia , ciliary beat frequency , and MUC5AC quantitation) were evaluated for performance and reproducibility. To assess these assays, 6 laboratories contributed data using a common protocol utilizing IL-13 as an inducer of adverse mucociliary-relevant tissue changes. MatTek EpiAirway™ and Epithelix MucilAir™ 3D tissue models were used to evaluate endpoints using histology for GCH, software-based applications, Cilia FA and SAVA, for CBF, and ELISA assay for MUC5AC.
E-vapor product liquids contain a variety of ingredient combinations that should be assessed for human risk. One human lung-relevant testing platform with reasonable throughput, is human precision-cut lung slices (HuPCLS). HuPCLS are arguably the most complex non-animal model of the lung, retaining native architecture and immune-competent cells over multi-week culture periods. HuPCLS were exposed to three concentrations (0.1%, 0.5%, and 1.2%) of propylene glycol (PG; an E-vapor product constituent) continuously for 16-days. Exposure-effects were evaluated biochemically (WST-8 assay) and histologically (viability assessment of H&E stained slides). Positive control treatments consisted of 10 µM Phortress and 13 µM bleomycin.
While data are still being collected and analyzed, there were at least 1,300 accidental electronic liquid (e-liquid) exposures reported as of 2013. Deaths have occurred as a result of ingestion of e-liquid with the effects being attributed primarily to nicotine. The Food and Drug Administration (FDA) sought to regulate e-liquid through the Tobacco Control Act passed in 2009. In 2014, the FDA issued its “Deeming” proposals for public comments, which covered e-liquid manufacturing; the Final Rule giving the FDA authority to regulate e-liquids was released on May 5th, 2016. This study investigated the oral irritation of 3 different formulations of e-liquid using an in vitro time course assay in the reconstructed tissue model EpiOral™ (MatTek Corporation, Ashland, MA, USA). All products were from the same manufacturer, contained 1.2% nicotine and differed only in their flavorings.
The US-FDA has regulatory authority over tobacco products, including conventional cigarettes and next generation products (NGPs) such as e-cigarettes and tobacco heating products (THPs). There is a desire by the industry, regulator and animal protection organizations to incorporate non-animal test methods for tobacco product and NGP assessment. When assessing respiratory effects in vitro, reliable exposure systems that deliver aerosols to cellular/tissue cultures at the air-liquid interface are needed.