ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION (ADME) IN MAMMALS

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Keywords: Metabolite identification; NMR; HPLC; Mass spectrometry; Absorption; Distribution; Metabolism, Excretion; Kinetics; LSC; In vivo; In vitro; Radiolabeled compounds; Dermal; Gavage; IV; Inhalation; Mass balance; Fullerene; Choline, Dimethylethanolamine; 2¿,2¿¿¿-Dithiobisbenzanilide, 2-Hydroxy-4-methoxybenzophenone, Chromium, Tungsten. The goal of this contract is to provide support of National Toxicology Program (NTP) hazard assessment activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. Projects conducted under this contract are designed to investigate the fate (absorption, distribution, metabolism, and excretion, or ADME) and mechanisms of toxicity of chemicals commonly found in the environment, workplace, or in consumer products. These studies usually involve the use of radiolabeled chemicals, as well as species and strains of animals used in NTP studies of toxicology and carcinogenicity. Data developed by this work are used in the design and interpretation of the NTP studies. In the past fiscal year (2009), studies involving the fate (in vitro and/or in vivo) of cumene, dimethylethanolamine (DMAE), fullerenes, 2¿,2¿¿¿-dithiobisbenzanilide (DTBBA), and 2-hydroxy-4-methoxybenzophenone (HMB), have been conducted under this contract. Additionally, the chromium and tungsten (sodium tungstate) project reports were finalized, accepted by the project officer and submitted for inclusion into the NTP electronic database system. The projects involving cumene and fullerenes were finished and the draft project reports are in preparation by the contractors, prior to submission to the project officer for review and revision. Major progress was made toward characterizing the ADME of DMAE and its interaction with choline in rodents. The DTBBA and HMB projects were new starts in this fiscal year. DTBBA is a high production chemical used as a peptizing agent for rubber, particularly in the tire industry. HMB is used as a UV filter in cosmetic and sunscreen products. There is concern for potential toxicity to humans exposed to these chemicals. Therefore, ADME studies are being conducted for both chemicals to provide data for their toxicological evaluation.