NCTR Division of Biochemical Toxicology Also referred to as: DBT

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Division Director: Frederick A. Beland, Ph.D.
Deputy Director: Luísa Camacho, Ph.D.

Meet the Principal Investigators — Biochemical Toxicology

About the Division

Mission

Conduct fundamental and applied research designed to define the toxicity and carcinogenic hazards associated with FDA-regulated products and the biological mechanisms of action underlying such hazards.

Goals

Characterize the toxicities and carcinogenic hazards associated with chemicals, specifically those of interest to the FDA.

Strategies

Conduct bioassays, mechanistic studies, and computational modeling in research studies.

Metrics

Provide reports to FDA Product Centers and funding agencies and publishes manuscripts. 

Bisphenol A: Toxicology and Pharmacokenetic Data to Inform Ongoing Safety Assessments
Presented by K. Barry Delclos, Ph.D.

Watch the Recorded Presentation

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2021 Select Accomplishments

Investigating Male Reproductive Toxicities Induced by Cannabidiol and its Main Metabolites

Researchers at NCTR, in collaboration with scientists from the Center for Food Safety and Applied Nutrition, investigated potential male reproductive toxicities and their underlying mechanisms induced by cannabidiol (CBD) and its main metabolites — 7-carboxy-CBD and 7-hydroxy- CBD — using immortalized mouse Sertoli cells and primary human Sertoli cells. Study results showed that CBD inhibited cellular proliferation, disrupted the cell cycle, and altered the cytoskeleton organization. 7-Carboxy-CBD and 7-hydroxy-CBD also inhibited cellular proliferation and decreased DNA synthesis during S-phase of the cell cycle. This research and its findings will help the FDA better define safety concerns regarding CBD. A paper reporting the study findings was published in Food and Chemical Toxicology.

Characterizing Metabolically Competent HepG2 Cells for Assessing Drug-Induced Liver Toxicity 

In a previous study, NCTR scientists developed a battery of HepG2-derived stable cell lines that individually express 14 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). This work has now been expanded to characterize each cell line for its CYP expression and enzyme activity by measuring messenger RNA and protein levels and metabolite formation. The NCTR investigators demonstrated the metabolic stability and response robustness of each of the CYP-overexpressing HepG2 cell lines. These cells can provide a practical in vitro approach for 1) screening drug and chemical metabolism, 2) metabolism-associated drug toxicity investigations, and 3) drug-drug interaction studies. These data were reported in the Journal of Environmental Science and Health, Part C, Toxicology and Carcinogenesis.

Investigating the Toxicokinetics and Toxicity of the Cigarette Smoke Carcinogen NNK

The Center for Tobacco Products (CTP)/NCTR Inhalation Toxicology Core Facility is a joint effort by NCTR and CTP to provide technical expertise in applied inhalation research. Using testing procedures that are compliant with international test guidelines (e.g., Organization for Economic Co-operation and Development), NCTR and CTP scientists have studied the biological responses in experimental animals following well-defined nose-only inhalation exposures. These data are used to quantify the adverse health risks associated with humans using tobacco products. Data from recently completed toxicokinetic, subacute toxicity, and subchronic toxicity studies of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) — a carcinogenic compound found in cigarette smoke — have been published in three manuscripts reporting the results:

• Toxicokinetic and Genotoxicity Study of NNK in Male Sprague Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

• 14-Day Nose-Only Inhalation Toxicity and Haber’s Rule Study of NNK in Sprague-Dawley Rats

• 90-day Nose-Only Inhalation Toxicity Study of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Sprague-Dawley Rats

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2022 Select Research Projects

• Tattoo Pigments
• Cannabidiol (CBD)
• COVID-19

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Resources for You

• DBT Fact Sheet
• NCTR Grand Rounds: "Bisphenol A: Toxicology and Pharmacokenetic Data to Inform Ongoing Safety Assessments (Presentation recorded in Adobe Connect on September 13, 2018)
• Annual Reports
• Meet the Principal Investigators

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