Fumonisin B1 is the most prevalent congener of the fumonisin mycotoxins produced by Fusarium verticilliodies and is considered by many to be the most toxic. Fumonisin B1 has been classified by IARC as a class 2B carcinogen. This is primarily due to evidence suggesting increased exposure to FB1 through contaminated foodstuffs is responsible for increased incidence of esophageal cancer in regions of China and South Africa. Fumonisin B1 exposure has also been implicated in the increased incidence of neural tube defects along the Texas/Mexico border. Therefore the principal goals of this research were to 1) Identify sorbent materials that would be compatible with the chemical characteristics of fumonisin B1 and evaluate their ability to sequester the toxin using established in vitro techniques; 2) evaluate urinary FB1 as a biomarker of exposure from a fumonisin contaminated diet; 3) utilize urinary FB1 as a diagnostic tool to evaluate the efficacy of NS in reducing biomarkers of FB1 bioavailability in a Ghanaian population suspected to be co-exposed to aflatoxins and fumonisins. Isothermal analysis and an alternative animal model were examined and compared to previously published results to determine the sorbent toxin interaction activity in vitro as a predictor of in vivo efficacy. An HPLC method for detection and quantitation of urinary FB1 was developed based on methods previously adapted for primary amine and biomarker analysis. Urinary FB1 was evaluated as an HPLC detectable biomarker using a rodent model. Calcium and sodium montmorillonite clays were selected to interact with the positive charge on FB1 at low pH and sorb the molecule. Ferrihydrite was selected to interact with the negative charge on the FB1 molecule at neutral to high pH. While both polarities of sorbent were effective, montmorillonite clays demonstrated a higher capacity for sorption of FB1 than ferrihydrite. These in vitro results were confirmed in a rodent model where urinary FB1 was reduced 27% in NovaSil treated rats vs. controls. Finally, in a Ghanaian population co-exposed to aflatoxins and fumonisins, urinary FB1 was significantly reduced at 2 time points when the NovaSil treatment was compared to placebo.

Substantial environmental contamination has occurred from coal tar creosote and pentachlorophenol (C5P) in wood preserving solutions. The present studies focused on the characterization and remediation of these contaminants. The first objective was to delineate a sequence of biological changes caused by chlorinated phenol (CP) exposure. In Clone 9 cells, short-term exposure to 10 ?M C5P decreased pH, GJIC, and GSH, and increased ROS generation. Long-term exposure caused mitochondrial membrane depolarization (25 ?M), increased intracellular Ca2+ (50 ?M), and plasma membrane depolarization (100 ?M). Cells were affected similarly by C5P or 2,3,4,5-C4P, and similarly by 2,3,5-C3P or 3,5-C2P. Endpoints were affected by dose, time, and the number of chlorine substituents on specific congeners. Thus, this information may be used to identify and quantify unknown CPs in a mixture to be remediated. Due to the toxic effects observed due to CP exposure in vitro, the objective of the second study was to develop multi-functional sorbents to remediate CPs and other components of wood preserving waste from groundwater. Cetylpyridinium-exchanged low pH montmorillonite clay (CP-LPHM) was bonded to either sand (CP-LPHM/sand) or granular activated carbon (CP-LPHM/GAC). Laboratory studies utilizing aqueous solution derived from wood preserving waste indicated that 3:2 CP-LPHM/GAC and CP-LPHM/sand were the most effective formulations. In situ elution of oil-water separator effluent indicated that both organoclay-containing composites have a high capacity for contaminants identified in wood preserving waste, in particular high molecular weight and carcinogenic PAHs. Further, GAC did not add substantial sorptive capacity to the composite formulation. Following water remediation, the final aim of this work was to explore the safety of the parent clay minerals as potential enterosorbents for contaminants ingested in water and food. Calcium montmorillonite and sodium montmorillonite clays were added to the balanced diet of Sprague-Dawley rats throughout pregnancy. Based on evaluations of toxicity and neutron activation analysis of tissues, no significant differences were observed between animals receiving clay supplements and control animals, with the exception of slightly decreased brain Rb in animals ingesting clay. Overall, the results suggest that neither clay mineral, at relatively high dietary concentrations, influences mineral uptake or utilization in the pregnant rat.

The need to assess human exposures to foodborne and environmental carcinogens, particularly in populations at high risk for cancer and disease, has led to the development of chemical-specific biomarkers. Sensitive biomarkers for aflatoxin and polycyclic aromatic hydrocarbons (PAHs) have been useful in providing information on population exposure and reducing associated public health impacts. Aflatoxins are fungal metabolites found in a variety of foods. Among these toxins, aflatoxin B1 (AFB1) is the most predominant and hepatocarcinogenic. Acutely, AFB1 can cause disease and death, necessitating safe and effective intervention strategies. Inclusion of NovaSil (NS) clay in the diet represents a practical, sustainable approach. NS has been shown to prevent aflatoxicosis in multiple animal species by binding aflatoxins in the gastrointestinal tract, reducing toxin bioavailability. Co-exposure to PAHs, hazardous environmental contaminants, has been shown to increase the risk for hepatocellular carcinoma (HCC). Therefore, objectives of this research were to utilize biomarkers to assess aflatoxin and PAH exposures in susceptible populations in Ghana and the U.S. and to evaluate the safety and efficacy of NS intervention in Ghana (a population at risk for aflatoxicosis). After 3-month intervention with 3.0g NS/day, median aflatoxin M1 (an AFB1 metabolite) was significantly reduced (up to 58 percent) compared to the placebo group. Furthermore, no significant differences were found in levels of nutrient minerals between NS and placebo groups at baseline and 3-months suggesting NS can be used to effectively sorb AFB1 without affecting serum concentrations of important minerals. PAH biomarker results showed participants in Ghana were significantly exposed to high levels of PAHs based on the presence of 1-hydroxypyrene (1-OHP) in the majority of urines (98.9 percent). NS treatment had no effect on 1-OHP levels, further confirming the preferential binding of aflatoxins by NS. U.S. population data from a Hispanic community in Texas with an elevated incidence of HCC demonstrated a lower percentage and level of aflatoxin and PAH biomarkers. Aflatoxin M1 excretion, however, was associated with increased consumption of certain foods prone to aflatoxin contamination; thus, some individuals may be more vulnerable to exposure and associated interactions that increase the risk for HCC (e.g., PAHs or hepatitis infection).