ICCVAM Biennial Report 2018-2019

Throughout 2018 and 2019, NIEHS provided funding for small businesses developing technologies of interest to the Tox21 program. The funding was offered as part of the 2018 and 2019 Omnibus Solicitations of NIH, Centers for Disease Control, and FDA for small business grant applications to support development and commercialization of innovative technologies. Technologies supported by NIEHS included improved or expanded testing methods for toxicity screening, computational approaches for predictive toxicology, and other technologies such as alternative or improved methods for fixing and preserving tissues.

In addition to funding offered via the Omnibus Solicitations, NIEHS offers grants to support development of specific types of technologies targeting specific endpoints. Funding offered in 2018 and 2019 supported development of:

• Technologies to assess exposure of engineered nanomaterials and characterize their effects on biological systems (July 2018).
• Engineered 3D or organotypic in vitro systems using cells from experimental animal models typically used for toxicology testing (October 2019).
• Chemical testing resources and approaches that reflect the genetic diversity among human populations, including panels of human or rodent cells or cell lines, lower organism strains with well-characterized genetic backgrounds, or in silico approaches to enhance the ability to characterize the effects of genetic variation in toxicity testing (December 2019).

Toxicokinetics describes the absorption, distribution, metabolism, and excretion of chemicals and their metabolites by the body. In July 2019, EPA requested applications for a new funding opportunity, Advancing Toxicokinetics for Efficient and Robust Chemical Evaluations. The goal of this funding was to improve the development of chemical toxicokinetic tools and approaches for broader applicability during chemical evaluations. Of particular interest were projects that would increase throughput and predictivity of current IVIVE approaches while reducing the uncertainty of these approaches. Awardees for the grant will be announced in spring 2020.

EPA funds safer chemicals research grants supporting the development of innovative science to support safer, more sustainable use of chemicals in consumer products and chemicals used for other purposes such as pesticides. Using safer, more sustainable chemicals will help to better protect human and environmental health, including sensitive populations like children, elderly, and endangered species. Much of the research funded by these grants also supports the development of alternatives to animal testing.

The following grants under this program were announced or funded during 2018 and 2019:

• Advancing Actionable Alternatives to Vertebrate Animal Testing for Chemical Safety Assessment: promoted the development and use of alternative test methods and strategies that reduce, refine, or replace vertebrate animal testing, including analog/read-across techniques, mathematical models, and tiered-testing approaches. Five grants were awarded for projects in the areas of developmental toxicity, reproductive toxicity, or ecotoxicity testing, with funding beginning in August 2019.
• Systems-Based Research for Evaluating Ecological Impacts of Manufactured Chemicals: funded development of innovative methods to better understand and predict biological and ecological consequences of exposures to manufactured chemicals in environmental systems. Three of the six projects funded by this program were completed in 2018 and 2019; the remaining three grants continue through 2020.
• Organotypic Culture Models for Predictive Toxicology: established research centers to guide the development and evaluation of organotypic culture models to accelerate translational research in predictive toxicology. Four centers were funded beginning in December 2014; funding for two centers concluded in 2019, while two centers will continue to be funded into 2020.
• New Methods in 21st Century Exposure Science: supported research to advance methods for characterizing real-world human exposure to chemicals associated with consumer products in indoor environments. Five projects were funded beginning in 2014; funding for four projects extended into 2018.

In December 2019, NIH accepted applications for Small Business Innovation Research grants to develop methods that improve the reproducibility of iPSC derivation, growth, and differentiation. Projects funded under this grant will address the significant variability currently observed in human iPSCs in reprogramming efficiency, differentiation potential, and cell growth and stability, which is limiting the full application of these tools to research and clinical practice. Eleven NIH Institutes and centers are committing funds to this effort.

Throughout 2018 and 2019, the National Eye Institute, part of NIH, conducted the implementation phase of the 3-D Retina Organoid Challenge. This competition was designed to support development of lab-grown human retinas from stem cells. Organoids developed for the competition will mimic the structure, organization, and function of the human retina, the light-sensitive tissue in the back of the eye. The goal of these models is to advance therapies for degenerative retinal diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. In this phase of the challenge, the National Eye Institute will award up to $100,000 each to as many as six teams whose models best address the challenge's scientific criteria. A team led by Wei Liu, Ph.D., Albert Einstein College of Medicine, received an award in December 2018; additional entries will be accepted and awards granted in fall 2020.