Webinar: Regulatory Initiatives for New Approaches to Traditional Toxicity Testing

This one-hour webinar features presentations by Dr. Jennifer McLain, Deputy Director, Office of Pesticide Programs, Antimicrobial Division and IIVS CEO Dr. Rodger Curren. Dr. McLain discusses the EPA OPP's plans to reduce the use of animal testing in acute toxicity testing and provides suggestions on how stakeholders and EPA can cooperate to advance animal reduction goals. Dr. Curren then talks ...

In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products

Source: IIVS Workshop, April 4-6, 2016 See also Assessment of In Vitro COPD Models for Tobacco Regulatory Science: Workshop Proceedings, Conclusions and Paths Forward for In Vitro Model Use from our Dec. 2014 workshop.

Bridging the Gap Between Regulatory Acceptance and Industry Use of Non-animal Methods

Clippinger, AJ, Hill, E, Curren, R, Bishop, P. Alternatives to Animal Experimentation (ALTEX)

Read article.

Digital Dispensing onto 3D Airway Tissue: Delivery of Patterned, Picoliter Volumes for Direct Apical Surface Coverage with Precise Quantities of Test Material

Source: In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacc…

Evaluation of the Validated In Vitro Skin Irritation Test (OECD TG 439) for the Assignment of EPA Hazard Categories

Progress within the in vitro toxicology field has made available testing platforms based on reconstructed tissue models that are validated to address the skin corrosion and irritation endpoints. While the validated in vitro assays can be used for the hazard identification of chemicals irritant to skin in accordance with the United Nations (UN) Globally Harmonized System (GHS) for Classification and Labeling of Chemicals, they were not calibrated to address the classification system used by the United States Environmental Protection Agency (US EPA).

Improving Sensitivity of the NociOcular Assay to Evaluate Ion Channel Activation by Acidic Cosmetic Ingredients

Source: Pan-American Conference on Alternatives

Improving the Accessibility and Efficiency of the Human Cell Line Activation Test

Source: Pan-American Conference on Alternatives

Mimicking Metabolism Using Human Microsomes in Two In Vitro Assays in Order to Predict the Sensitization Potential of Pro-haptens

Source: Pan-American Conference on Alternatives

The Assessment of Alternate Solvents for Use in the 3T3 Neutral Red Uptake (NRU) Phototoxicity Assay and the Influence of Solvents on the Prediction of Phototoxic Potential of Amiodarone

Source: Pan-American Conference on Alternatives

Evaluation of New Solvents for the Use in the Multi‐Dose Reconstructed Human EpiDermis (RhE) Phototoxicity Assay

The phototoxic potential of test materials after exposure to UVA/visible light is evaluated by the 3T3 Neutral Red Uptake Phototoxicity Assay using Balb/c 3T3 mouse fibroblasts (OECD TG 432). To address challenges related to testing of finished products or materials that are not completely soluble, the Reconstructed Human EpiDermis (RhE) Phototoxicity Assay (INVITTOX Protocol 121) can be used as a stand‐alone or in a tiered approach. Water and sesame oil were recommended solvents for the RhE Assay, however additional solvents may be investigated on a case‐by‐case basis to accommodate a wider variety of test materials. Alternate solvents should first be assessed to ensure that they: 1) do not cause cytotoxicity; 2) do not diminish and/or inhibit phototoxic reactions; and 3) do not interfere with the UVA exposure. We investigated 5% DMSO in Hanks’ Balanced Salt Solution (HBSS), 5% acetone in HBSS, and polyethylene glycol (PEG) and their influence on the prediction of phototoxicity of chlorpromazine, a known phototoxicant. Duplicate tissues (EpiDerm™ from MatTek Corporation, Ashland, MA) were treated with each group for 24 hours, followed by a UVA (~6 J/cm2) or dark exposure, and then a 21 hour post‐exposure period before viability assessment using MTT dye. The assay positive control, 0.02% chlorpromazine in HBSS containing 1% DMSO, was tested concurrently. A test material was considered to have phototoxic potential if it induced a ≥30% difference in viability between tissues exposed to UVA as compared to the dark‐exposed tissues. Our data showed that the solvents performed in a comparable manner to the assay negative control (HBSS) and they did not induce significant toxicity when the viability of the UVA‐exposed and dark‐exposed tissues was compared: 92.9% and 104.8% (5% DMSO), 94.0% and 97.5% (5% acetone), and 81.3% and 90.0% (PEG), respectively. The difference between the viability of the UVA‐exposed or dark‐exposed tissues after treatment with 0.02% chlorpromazine dissolved in 1% DMSO, in 5% DMSO, and in PEG was 60.0%, 59.7%, and 72.5%, respectively. These data indicate that the new solvents we investigated were suitable for use in the detection of phototoxicity. The evaluation of 0.02% chlorpromazine in 5% acetone, as well as additional solvents (e.g. ethanol), is currently ongoing. Our future investigations will concentrate on the assessment of different solvents that can accommodate the phototoxicity testing of novel chemistries.