NCTR research for NTP is funded by both voluntary allocations and an interagency agreement. Below are FY 2016 projects that were funded through an NIEHS/NTP interagency agreement with FDA. Click the project title for a brief summary.
To characterize the long-term toxicity of orally administered bisphenol A (BPA), including developmental exposure, in NCTR Sprague Dawley rats over a broad dose range. In addition, animals generated in this study will be 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.
To evaluate a range of molecular, morphological, and functional endpoints in rats dosed orally with a wide range of bisphenol A 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 bisphenol A exposure. Assessments will be conducted at various ages (postnatal days 1, 21, and 90, as well as 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) To compare 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 subsequent 90-day recovery period. (2) To compare the dose-response 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.
To evaluate whether or not 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) To develop exposure and dosimetry methods for exposing human air-lung interface airway cultures to aerosolized test agents. (2) To use 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) To perform alkaline single cell gel electrophoresis (Comet) assays to detect both DNA single and double strand breaks using several human cell lines. (2) To perform modified Comet assays using the addition of uracil-DNA glycosylase (UDG) to evaluate the potential underlying mechanism(s) of BCE-associated genotoxicity. (3) To perform 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.