Documents & Resources

Approaches to Evaluation of Solvents for use in Photosafety Testing

March 20, 2024

New Approach Methodologies (NAMs) are routinely used in photosafety testing to evaluate if a test compound has the potential to become more toxic upon exposure and subsequent exposure to light. Three such NAMs to address photosafety are the in chemico UV-Vis Assay, the cell-based 3T3 Neutral Red Uptake (NRU) Phototoxicity Test (PT), and the tissue-based Reconstructed human EpiDermis (RhE) Phototoxicity Test (PT), described under OECD Test Guidelines (TG) 101, 432, and 498, respectively. (more…)

Refinement and Optimization of the Photo-KeratinoSens™ Assay to Evaluate Photoallergy Potential

March 20, 2024

Identification of test chemicals that have the potential to become more reactive, more toxic, or may become phototoxic upon application and subsequent exposure to sunlight is integral to photosafety testing. Several regulatory-based New Approach Methodologies (NAMs) are widely used in the evaluation of phototoxicity and skin sensitization potential. More recently, there has been an increased interest in ability to identify photoallergens. To this end, an innovative photo-KeratinoSens™ assay was established with addition of an irradiation exposure (5 J/cm2 of UVA) to the KeratinoSens™ Skin Sensitization Test (OECD TG 442D), as described in Tsujita-Inoue, et al. (2015). Twelve reference compounds were previously evaluated at IIVS under a protocol adapted from Tsujita-Inoue, et al. (2015), resulting in an accuracy of 58.3% (7/12 correctly predicted), with low sensitivity (50%, 5/10 positives correctly predicted) (Hilberer, et al., 2023).

Toxicity and Inflammatory Response to Common Magic Mouthwashes in a 3D Oral Reconstructed Tissue Model

November 8, 2023

Magic Mouthwash is a general term describing oral rinses prescribed by a doctor for the treatment of pain, inflammation, or infection, commonly as a result of chemotherapy and radiation induced oral sores (oral mucositis). There is no set combination of ingredients for the preparation of a magic mouthwash, rather they are formulated for the individual needs of each patient, selecting from an array of various active ingredients. Although the ingredients most commonly used to formulate Magic Mouthwashes are considered safe as prescribed, the final formulations lack toxicity and inflammatory response data. (more…)

Safety Assessment of Monographed OTC Cold/Cough Medicine Using an In Vitro Testing Platform Based on Human Reconstructed Oral Tissues

November 8, 2023

Over-the-counter (OTC) products are available to alleviate concurrent symptoms of colds and flu. They are primarily based on a combination of decongestants, antitussive and alpha adrenergic agonists, which are well-established pharmaceutical agents covered by U.S. monographs. Many of the active components of the OTC cough/cold drugs are bitter and must be masked using flavoring agents. Bayer internally employed a stringent safety testing program for OTC cough/cold medicine line extensions that require the products to be held in the mouth for a short period using an innovative testing platform based on reconstructed oral tissues. (more…)

The Importance of Supplier Qualification for Vendors of Materials Used in In Vitro Assays

November 7, 2023

Pre-clinical assays, including in vitro assays, rely heavily on suppliers who provide essential products or services. In the current regulatory environment, the burden is placed on the users of these products or services to ensure that the methods employed at the suppliers' facilities meet a sufficient level of quality. Variable results for the same assay controls over time could indicate high lot-to-lot variability of the test system or of critical assay components. (more…)

Cryopreserved human precision-cut lung slices provide an immune competent pulmonary test system for “on-demand” use and long-term cultures

October 20, 2023

Human precision-cut lung slices (hPCLS), considered a highly relevant ex vivo model of the lung, offer native architecture and cells of the lung tissue including respiratory parenchyma, small airways, and immune competent cells. However, the irregular availability of donor lungs has limited the accessibility of this system. As described here, thousands of hPCLS can be created from 1 lung, cryopreserved, and used “on demand” by applying slicing and cryopreservation methodology improvements. (more…)

A Laboratory Method to Measure Skin Surface Staining by Cigarette Smoke

October 20, 2023

Exhaled or side-stream cigarette smoke (CS) may visually stain a consumer’s skin over time. Tobacco heating prod- ucts (THPs) and e-cigarettes (ECs) have reduced staining potential because they do not produce side-stream aerosols and their exhaled aerosols have significantly reduced levels of toxicants, particles and odour. Here we assess discolour- ation of porcine skin in vitro after exposure to particulate matter (PM) or aerosols from CS (3R4F), two THPs (glo and glo sens) and an EC (iSwitch Maxx). (more…)

Ensuring the quality of a test system using the principles of Good In Vitro Method Practices (GIVIMP): A case study of cryopreserved human precision-cut lung slices

October 10, 2023

Human precision-cut lung slices (hPCLS) are a highly relevant 3-dimensional model of the lung. They offer native architecture and cells of the lung tissue including respiratory parenchyma, small airways, and immune competent cells involved in inflammatory and sensitization processes. The scarcity of human lung tissue available for research and the inability to conduct larger scale testing has limited the use of hPCLS as a test system for routine, high-throughput testing. To overcome this barrier, IIVS has refined the methodology behind the cryopreservation, storage, thaw and post-thaw maintenance of human lung slices. As primary tissues have varied quality and responsiveness, a standardized performance characterization (PC) is conducted on all donor batches. (more…)

Key Recommendations from GIVIMP for Test System Suppliers

October 10, 2023

The Organization for Economic Cooperation and Development (OECD) guidance document on Good In Vitro Method Practices (GIVIMP) details a set of quality standards to improve both the quality of and confidence in newly developed, and routinely executed in vitro methods. An important part of (and a source of potential high variability in) any method is the test system. Microphysiological Systems (MPS), including organ-on-a-chip platforms have been used in novel methods for many years. Despite their potential benefits, there are several quality concerns associated with MPS. Two of these concerns are reproducibility and well defined and understood biological relevance, both of which are covered in the GIVIMP guidance. (more…)

Webinar Series on In Vitro Phototoxicity Testing

September 20, 2023

Thank you for joining us for a two-part webinar series on in vitro phototoxicity testing co-organized by the Institute for In Vitro Sciences (IIVS) and PETA Science Consortium International. Part 1 included a methodological overview on phototoxicity assays, and Part 2 covered case studies from industry applying the methods.