NCTR research for NTP is funded by voluntary allocations and an interagency agreement. Below are FY 2017 projects funded through an NIEHS/NTP interagency agreement with FDA. Click the project title for a brief summary.
Characterization of the long-term toxicity of orally administered BPA (bisphenol A), including developmental exposure, in NCTR Sprague Dawley rats over a broad dose range. Animals generated in this study are being assigned to separate protocols for assessment of a range of molecular, morphological, and functional endpoints to determine if these endpoints are predictive of long-term toxic effects or reveal potential effects undetected by standard toxicological evaluations.
Evaluation of a range of molecular, morphological, and functional endpoints in rats dosed orally with a wide range of BPA doses in a chronic toxicology study. The endpoints were selected based on reports from previous animal toxicology or human epidemiology studies, suggesting they are affected by BPA exposure. Assessments are being conducted at various ages (postnatal days 1, 21, and 90 and 6 and 12 months) to determine if any effects observed are predictive of long-term effects evaluated in the companion chronic toxicology study, or if they reveal potential effects undetected by standard toxicological evaluations.
(1) Comparison of the dose-response and temporal dynamics of circulating microRNAs, blood urea nitrogen, and serum creatinine in rats co-exposed to melamine and cyanuric acid over a 90-day treatment period and a subsequent 90-day recovery period. (2) Comparison of the dose-response relationships of the kidney gene expression level of biomarkers of nephrotoxicity and kidney histopathology in rats co-exposed to melamine and cyanuric acid for 90 days and upon a 90-day recovery period.
(1) Assessment of the dose-response relationships of a 90-day dietary exposure to brominated vegetable oil in Sprague-Dawley rats. (2) Evaluation of the bioaccumulation and clearance of inorganic and organic bromine in organs and tissues of Sprague-Dawley rats upon dietary exposure to brominated vegetable oil.
(1) Determination of appropriate doses and survivability for direct oral inorganic arsenic exposure in neonatal Sprague-Dawley rats. (2) Development and refinement of techniques for future, more comprehensive studies. (3) Determination of the early neurobehavioral toxicology of inorganic arsenic exposure on two preweaning behaviors and developmental milestones.
Evaluation of whether drinking water administration of aloin-A and aloin-B to F344 rats exerts similar effects in the rat large intestine when administered at concentrations similar to those in previous NCTR studies on Aloe vera whole leaf extract.
(1) Evaluation of the toxicokinetic profile of high-molecular-weight polyethylene glycols in Sprague-Dawley rats given a single dose of the substances via subcutaneous injection. (2) Evaluation of the bioaccumulation of high-molecular-weight polyethylene glycols in organs/tissues of rats upon repeated subcutaneous injection for 24 weeks. (3) Assessment of the toxicities resulting from the bioaccumulation of the substances.
(1) Development of exposure and dosimetry methods for exposing human air-lung interface airway cultures to aerosolized test agents. (2) Use of previously developed disease-related endpoints and air-lung interface culture exposure methods to evaluate the respiratory toxicity of two known airway toxicants, two presumed nontoxicants, and one compound of current interest.
(1) Performance of alkaline single-cell gel electrophoresis (Comet) assays to detect DNA single- and double-strand breaks using several human cell lines. (2) Performance of modified Comet assays using the addition of uracil-DNA glycosylase to evaluate the potential underlying mechanism(s) of BCE-associated genotoxicity. (3) Performance of recently established modified Comet assays using DNA restriction enzyme, McrBC, which specifically recognizes DNA sites of the form 5'-R(m)C-3' and cuts DNA at methylated Cs for evaluating methylation modification by BCE.