Division of Cellular and Molecular Toxicology

National Institute of Health Sciences(NIHS)

Center for Biological Safety and Research (CBSR)

Research Activity

Research on Food Safety Assessment

To ensure food safety and protect public health, we conduct toxicity studies and collect and review safety information from Japan and abroad on food additives, food-contact materials, and other substances. Through these activities, we generate the information needed to ensure safety and conduct science-based safety assessments.

Research on Food Safety Assessment_fig_title

A study on the development of hazard assessment method for PFAS based on gene expression analysis focusing on their prioritisation and categorization for regulatory purposes

PFAS are presumed to exert toxicity via multiple nuclear receptors, yet their underlying molecular mechanisms remain largely elusive. This study quantifies the biological effects of several PFAS through comprehensive gene expression profiling. By comparing these profiles with those of approximately 160 other chemicals, we aim to elucidate the molecular signaling pathways driving PFAS toxicity and develop toxicity prediction models.

A study on the development of hazard assessment method for PFAS based on gene expression analysis focusing on their prioritisation and categorization for regulatory purposes_fig_title

Development of a Novel Exosome-Based Toxicity Testing Method

Exosomes are a type of extracellular vesicle secreted by various organs and cells and contain RNAs and proteins characteristic of their cells of origin. Because of this property, tumor cell-derived exosomes have been utilized as biomarkers for the early detection of cancer. Our laboratory is developing a non-invasive and comprehensive next-generation toxicity assessment method by using RNAs and other molecules contained in organ-derived exosomes as biomarkers of toxicity.

Development of a Novel Exosome-Based Toxicity Testing Method_fig_title

Refinement of Adverse Outcome Pathways (AOPs) to Advance Hepatotoxicity Assessment

To predict and assess chemically induced hepatotoxicity, we systematically organize existing adverse outcome pathways (AOPs) and, where necessary, re-evaluate the causal and temporal relationships among key toxicity events. Based on the resulting evidence, we aim to refine AOPs and establish a foundation for applying New Approach Methodologies (NAMs), which do not rely on animal testing, to chemical safety assessment.

Refinement of Adverse Outcome Pathways (AOPs) to Advance Hepatotoxicity Assessment_fig_title

Advancement of Acute Toxicity Assessment through Integrated Evaluation of Physiological Information

Conventional acute toxicity testing has relied primarily on mortality and severe toxic signs, making it difficult to capture physiological changes occurring during the progression of toxicity. We therefore conduct research to develop alternative acute toxicity approaches that continuously and integratively acquire and evaluate biological information, including animal behavior, body surface temperature, electroencephalograms, and electrocardiograms. Our goal is to better characterize potential effects on human health while also improving animal welfare. To realize this concept, we are developing ToxQb (“tox-cube”), an integrated monitoring system designed to support comprehensive, physiology-based assessment in acute toxicity studies.

Advancement of Acute Toxicity Assessment through Integrated Evaluation of Physiological Information_fig_title

Emotional and cognitive neurobehavioral toxicity following developmental chemical exposure

Neural circuits in the brain are formed through the precise regulation of signaling between neurons. We focus on the effects of chemical exposure on the developing brain, particularly during prenatal and early-life stages. By examining changes in behavior, neural activity, and gene expression under various exposure conditions, we seek to understand the mechanisms by which chemicals affect the central nervous system.

Emotional and cognitive neurobehavioral toxicity following developmental chemical exposure_fig_title

Development of Novel In Vitro and In Vivo Methods for Assessing Reproductive Toxicity and Its Reversibility

This project aims to develop and characterize complementary in vitro and in vivo methods for evaluating reproductive toxicity and its reversibility. The proposed platform integrates non-invasive longitudinal assessment of the testes using small-animal MRI, organ culture systems for direct monitoring of spermatogenic injury and its recovery, and assays of sperm quality, including the integrity of genetic and epigenetic information transmitted to the next generation. By applying these methods to representative toxicants and pharmaceuticals, we will define their sensitivity, limitations, and applicability domains for use in reproductive toxicity testing.

Development of Novel In Vitro and In Vivo Methods for Assessing Reproductive Toxicity and Its Reversibility_fig_title

Establishment of Integrated Human Health Risk Assessment

We aim to establish a tiered 'integrated human health risk assessment system' that selects and applies appropriate NAMs based on problem formulation to proceed with assessments, conducting conventional animal testing only when those methods alone do not provide sufficient information for assessment.

Establishment of Integrated Human Health Risk Assessment_fig_title