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Research and Publications

Title | Problem Statement | Objectives | Progress | Publications | Background | Development Benefits | U.S. Benefits | Potential Impacts | Team

Title

Sustainable Enterosorbent Strategies for the Protection of African Populations from Aflatoxin

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Problem Statement

 We are in a unique position to test a novel, clay-based technology that could achieve major advances in human health for populations exposed to high levels of aflatoxins in the diet. Aflatoxins are harmful by-products of mold growth and (though invisible to the naked eye), are potentially fatal. The aflatoxin problem is longstanding and seemingly inextricable. Aspergillus flavus and parasiticus (the molds primarily responsible for the elaboration of the aflatoxins) are widespread and especially a problem during extended periods of drought. Moreover, aflatoxins are heat stable and survive a variety of food processing procedures, and they occur as "unavoidable" contaminants of many foods (particularly maize and peanut). Also animals can secrete carcinogenic metabolites of aflatoxin in their milk. Consequently, a variety of dairy products (including cheese and ice cream) can be contaminated with these chemicals. Aflatoxin B1 (the most toxic of the aflatoxins) has been strongly implicated as a cause of disease and death in man. Following ingestion, it damages the liver, is a potent carcinogen, and acts to synergize the development of hepatomas when other cancer causing agents (such as hepatitis B virus) are present (Phillips et al., 1994,1995). There is substantial evidence that low level exposure to aflatoxin may cause suppression of the immune system and increased susceptibility to disease (Peska and Bondy, 1994). Aflatoxin is also excreted in mother's milk and may contribute to failures in pregnancy. It also increases the morbidity of children with kwashiorkor in developing countries (Adhikari, 1994). Clearly, the young of all species are very sensitive to aflatoxin. What is not clear is how these actions of aflatoxin contribute to commonly perceived human health problems and child survival in Africa and other developing countries. In light of these problems with aflatoxin, it is clear that effective strategies for the remediation of aflatoxin-contaminated food in developing countries are critical needs.

A safe and practical (clay-based) approach is outlined in this proposal. Our strategies will be based upon the dietary inclusion of inexpensive clay minerals that can act as aflatoxin enterosorbents to tightly sequester and inactivate these poisons in the gastrointestinal tract. As a general rule in toxicology, "the dose makes the poison" and the toxic and carcinogenic effects of aflatoxin are clearly "dose" dependent. We anticipate that NovaSil (HSCAS clay), when included in the diet of humans, will act to block, or significantly diminish exposure to aflatoxins and prevent the adverse effects of these poisons in humans consuming aflatoxin-tainted grains.

We believe that it is appropriate to invest in a project to investigate the consequences of introducing into the diets of a population the clay-based technology described above. This project would have the overall goals of determining if HSCAS clay is effective, acceptable and pays the expected dividends to health and development. An understanding of these outcomes will expedite the optimization, transfer and application of this important technology to other developing countries and the USA. It is anticipated that the collaborative research outlined in this proposal will provide creative, culturally acceptable, economically viable, environmetally benign and sustainable strategies that will benefit human health and well-being around the world.

In this project, our objectives and specific aims are defined within three major phases of study. Phase I and Phase II research will be accomplished at Texas A&M University in College Station and at the Noguchi Memorial Institute for Medical Research in Ghana. In Phase III studies, we propose to determine the feasibility of HSCAS clay as an enterosorbent for aflatoxins via human dietary interventions in Ghana.

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Objectives

1: Phase I Studies: Our first objective will be to characterize and compare the sorption of aflatoxins (and aflatoxin analogs)onto the surfaces of diverse NS clays (in aqueous solution). Indices of chemisorption, ligand specificity, affinity, capacity, enthalpy and Gibbs free energy of adsorption will be determined from equilibrium analysis. 
Indicators: Success of this objective will be based on the in vitro selection of an effective HSCAS clay for biological testing. The thermodynamics of adsorption, ligand specificity, isotherm shape, capacity, and affinity are critical requirements for optimal binding of aflatoxins to NovaSil (NS) clay surfaces and will be used to select the best detoxifying clays for biological testing in Phases II and III of this project. Molecular modeling of clays and aflatoxins will also provide valuable insight into the mechanism(s) and site(s) of toxin adsorption to clay surfaces and help to delineate the types of binding interactions, e.g., complexation, ligand exchange, intercalation within interlayer channels, etc.(see Phase I in the Research Approach for details). 
Estimated Total Objective cost: $

2: Phase II Studies: In our second objective, detoxifying clays that possess the highest capacity, affinity and enthalpy for the sorption of aflatoxins will be screened for toxicity and efficacy using rapid, aflatoxin-sensitive, in vitro bioassays. The least toxic and most acceptable clays (based on biological and chemical analysis) will be further tested for safety and efficacy in pregnant Sprague-Dawley rats and their offspring. The findings from these studies will be compared with results from Phase 1 to verify our experimental paradigm and to select the most effective and least toxic clays for Phase III (human trials). 
Indicators: The success of this objective will be measured by: 1) absence of in vitro toxicity in bioassay systems following clay addition alone, 2) prevention of toxicity in bioassay systems with the inclusion of aflatoxin plus clay, 3) a reduction or elimination of aflatoxin exposure in rats based on well-characterized molecular dosimetry biomarkers in blood and urine, and 4) prevention of adverse health effects and nutrient interactions in rats consuming clay alone or clay plus aflatoxins (see Phase II in the Research Approach for details). 
Estimated Total Objective cost: $

3: Phase III Studies: The prevention of dietary exposure to aflatoxins can greatly reduce unnecessary suffering and significantly lessen the demands for limited health resources in developing countries. In objective 3, short-term human trials will be run in Ghana (in collaboration with the Noguchi Memorial Institute for Medical Research and Ghana University) to establish the feasibility of clay addition to the diet of humans who are exposed to high levels of aflatoxin. Molecular dosimetry biomarkers for aflatoxin will be used to predict exposure and the consequences of dietary inclusions of NS clay. In the event of a significant benefit to human health from this treatment, further research developing delivery mechanisms and extending this practice in long-term studies would be justified. 
Indicators: Multiple biomarkers of aflatoxin exposure in blood and urine will be monitored at regular intervals during each trial in this objective. These biomarkers will be used to determine toxin exposure (acute and chronic) and predict outcomes of NS clay treatment. Success will be measured by: 1) reduced exposure to aflatoxins based on a decrease in multiple biomarker levels in blood and urine, and 2) no adverse health effects associated with the consumption of the NS clay. 
Estimated Total Objective cost: $

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Progress

2002

Equilibrium sorption of aflatoxin B1 (AfB1) to Novasil and NovaSil Plus was investigated using isothermal analysis. The toxin was mixed with clay at different temperatures for 24 h; the concentration of adsorbed toxin (mol/kg) versus the equilibrium concentration in the supernatant (mol/L) was compared to standard isotherms. Data was fitted to multiple isotherm equations including: Langmuir, Freundlich, Toth, and various transforms. NSP was shown to possess a higher capacity for AfB1 (459 nmol/mg) than NS (325 nmol/mg). The enthalpy of AfB1 sorption to NSP was equal to -49.2 kJ/mol suggesting tight binding (or chemisorption) of aflatoxin. The calculated distribution coefficient confirmed high affinity. The sorption of AfB1 to heat-collapsed NSP was reduced by more than 90% suggesting that the interlayer plays a key role in the binding of AfB1 to NSP surfaces.

Other Achievements: Evans Afriyie-Gyawu traveled to Ghana to collect "edible" clay samples from Ghanaian markets for isotherm analysis at TAMU. He visited the Ejura District market, purchased 14 different food samples and three types of edible clay products for laboratory analysis. He met with officials at the Crop Research Institute (CRI) to obtain a permit to transport food and clay samples from Ghana to the U.S. After processing and isothermal analysis, the Ghanaian market clays were not effective binders for aflatoxins. Urine samples from Dr. Jolly (UAB) were analyzed for aflatoxin M1 using antibody cleanup procedures and high performance liquid chromatography with fluorescence detection.

ABSTRACTS AND PUBLICATIONS:

Afriyie-Gyawu et al. 2001. In vitro screening and characterization of potential sorbents for zearalenone. Toxicologist 60(1): Abstract #1954.

Afriyie-Gyawu et al. 2003. Enhanced clay-based enterosorbent for the prevention of aflatoxicosis: In vitro and in vivo characterization. Toxicologist (In press) Abstract.

Afriyie-Gyawu et al. 2003. Prevention of zearalenone-induced hyperestrogenism in prepubertal mice. J. Toxicol. Environ. Hlth. (In preparation).

Wiles, M.W. et al. 2003. Maternal and developmental assessment of montmorillonite clays commonly added to animal feeds: Toxicity evaluation and metal bioavailability in pregnant rats. J. Toxicol. Environ. Hlth. (In preparation).

Previous studies conducted in this project established some important groundwork for future efforts to prevent human aflatoxicosis. NS clay (a calcium montmorillonite clay) has been shown to be efficacious as an enterosorbent of aflatoxins in a variety of animals over short-term exposure periods. Clearly, a long-term (chronic) study of the effects of consuming NS are needed.

Since the clays frequently consumed by some people in the Ashanti region of Ghana were not effective binders of aflatoxins, we decided to proceed with trials to establish the safety and efficacy for humans ingesting a well-characterized calcium montmorillonite clay (NS). The long-term animal trial to establish the safety of NS with animals is producing results that suggest that this clay may also be safe in human studies.

The significance of the urine analysis work is that we now have a clear picture of where to conduct our feasibility studies using the enterosorbent-based application. Also, we have established a rapport and some level of trust with the study participants in Ghana so further studies may be significantly enhanced.

Other Achievements: The study on vitamin A responses to aflatoxin contaminated feeds and the protection of animals from VAD using NSP confirms other studies with other species. This result is of great importance to USAID because of the geographic coincidence of VAD and aflatoxicosis. Preventing aflatoxicosis could greatly decrease the numbers of people across the world who suffer from VAD.

Project #1. Chronic and Sub-chronic Toxicity Studies in Rats

Studies were conducted to evaluate the potential toxicity of long-term (chronic and sub-chronic) dietary exposure to NovaSil clay (NS) using 5 - 6 week old Sprague-Dawley rats (64 males and 66 females). The animals were fed rations containing up to 2.0% (w/w) levels of NS for 28 weeks. Feeding, body weight, and organ weight parameters were all evaluated. Necropsy and histopathological evaluations were conducted on 30 animals (3 rats/sex/group) at day 90, while the remaining 100 animals (10 rats/sex/group) were examined at day 196. Organs/tissues including liver, kidneys, lungs, heart, brain, spleen, tibia, skin, sections of the GI tract, uteri and ovaries were all observed for any anatomic abnormalities and used for subsequent histopathological evaluation. In addition, whole blood samples were analyzed to determine potential changes in the hematological parameters, red and white blood cell counts and morphology between NS-fed rats in comparison to the controls. Serum biochemistry, concentrations of serum and hepatic vitamins A and E, and levels of serum Fe and Zn of the treated animals were all quantified and compared to those of the controls. Statistical analysis of the results has been completed and the manuscript is in preparation for publication.

Project #2. Short-term Safety Evaluation of NovaSil in Humans

A randomized and double-blinded phase I clinical trial was conducted to determine the safety and tolerance of NS in humans and establish dosimetry protocols for long-term efficacy studies. Volunteers (20 - 45 yr in age), were clinically screened for confirmation of their health status. Fifty subjects (23 males and 27 females) were randomly divided into two groups: the low-dose group received 6 capsules containing 1.5 g/day, and the high-dose group received 6 capsules containing 3.0 g/day for a period of 2 wk. NS capsules were distributed to each participant 3 times a day at designated sites. Blood and urine samples were collected before and after the study for laboratory analysis. Each participant completed the trial and compliance was 99.1%. All laboratory analyses, including hematology, minerals, vitamins A and E, and concentrations of selected electrolytes have been completed. Clinical and sub-clinical analyses, before and after NS exposure, have also been evaluated.

Project #1. Chronic and Sub-chronic Toxicity Studies in Rats.

Results of these studies support the use of NS clay dietary interventions for human populations at high risk for aflatoxicosis. This information increased the feasibility of evaluating the safety of NS clay in short-term human trials.

Project #2. Short-term Safety Evaluation of NovaSil in Humans

The information gained from this study, coupled with the chronic and sub-chronic toxicity studies in rats will serve as the basis for use of NS in long-term human intervention trials in populations at high risk for aflatoxicosis in Ghana.

Other Achievements: Single Nucleotide Polymorphism Studies.

Hepatocellular carcinoma (HCC) is a multifactorial disease with various host and environmental factors involved in its etiology. Of these, aflatoxin exposure has been established as an important risk factor in the development of HCC and the presence of aflatoxin-albumin adducts in the blood serves as a valuable indicator of human exposure. In this research, the relationship between a variety of different HCC host factors and the incidence of aflatoxin-albumin adduct levels was studied in a Ghanaian population at risk for HCC. These factors included age, sex, HBV and HCV status and genetic polymorphisms in both microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). Blood samples were analyzed for aflatoxin-albumin adducts, HBV and HCV status. GSTM1 and GSTT1 deletion polymorphisms and mEH exon 3 and exon 4 single nucleotide polymorphisms (SNP) were determined from urine samples. In univariate analysis, age, HBV and HCV status, GSTT1 and mEH exon 3 genotypes were not associated with aflatoxin-albumin adduct levels. However, mean adduct levels were significantly higher in both females and individuals typed heterozygous for mEH exon 4 (vs. wild types). Stratification analysis also showed that gender along with mEH exon 4 genotype and HBV status had a significant effect on adduct levels. Both females typed HBsAg+ and males with mEH exon 4 heterozygote genotypes showed significantly higher adduct levels as compared to the HBsAg- and wild types, respectively. Understanding the relationships between these host factors and the variability in aflatoxin-adduct levels may help in identifying susceptible populations and targeting aflatoxin-specific interventions for humans at high risk for HCC and chronic liver diseases.

The chronic(6.5-month) animal study at TAMU has been completed. Analyses of feed and body weight parameters, organ weights, histopathology, hematology, and clinical chemistry, were all performed and the study results have been published in the journal "Food Additives and Contaminants" and cited on the USAID-Peanut CRSP website. We await the analysis of metal bioavailability in selected tissues from the same study. This study is expected to be completed by the end of May of 2006. Selectivity of NovaSil clay (NS) and similar NS enterosorbents was further characterized. Isothermal methods to determine the affinity of NS clay for vitamin A were developed. It was confirmed that there was no significant binding interaction between vitamin A and NS clays. Other vitamins (vitamin E and riboflavin) are also being characterized in the same manner as vitamin A.

A short-term human safety trial at Texas Tech University using NS was completed and reported in "Food Additives and Contaminants" in the same issue as the chronic study in rodents. The paper has been cited on the USAID Peanut-CRSP website. A Phase IIa intervention trial in Ghanaians was initiated. The IRBs in Ghana and Texas A&M University approved the study protocol. Due to a delay in the approval process, our start date for screening study participants was shifted to the middle of September, 2005. Preparation of the encapsulated NS test article for the project was initiated at a Phamaceutical Company in Colorado Springs.

Chronic Toxicity Studies in Rats: Results of these toxicity studies have increased the feasibility of evaluating the safety of NS clay in short-term human trials. The paper published in a reputable journal, as a result of this study, contributes significantly to the scientific community.

Determination of potential interactions of NS and other enterosorbents with vitamins: Knowledge that NS does not interact with vitamin A and the micronutrients iron and zinc confirms our in vivo results in rats. Also, this evidence suggests that NS will likely not affect vitamin and micronutrient levels in humans during the proposed intervention trials in Ghana. This is highly significant, since these nutrients are vital to growth and development in children in developing countries.

Short-term Safety Evaluation of NovaSil in Humans: The information and knowledge gained from this human study, coupled with the chronic and sub-chronic toxicity studies in rats will serve as the basis for use of NS in short-term human intervention trials in populations at high risk for aflatoxicoses in developing countries such as Ghana.

Other Achievements: NONE

The Phase IIA clinical trial in Ghana has been finalized. Blood and urine samples were collected at specified timepoints in the study. Biomarkers of exposure to aflatoxins were determined in our study group, as well as serum biochemistry and other clinical outcomes. Analyses of the data are ongoing. Further delineation of nutrients and minerals in samples will be accomplished as funding becomes available.

Also, common clays from Ghana are being characterized for their similarities to NovaSil using equilibrium adsorption isotherms.

Awaiting analyses of the data to confirm the safety and efficacy of NovaSil in humans.

Other Achievements: None.

In accordance with the final objectives and work plans for TAM50, the Phase IIa human intervention trial in Ghana has now been completed. Sample collection, data management and statistical analyses have also been finalized. Seven publications will describe the outcomes of important aspects of our clinical intervention trial and human research in Ghana. Two describing genetic biomarkers of variability in aflatoxin-albumin adducts in Ghanaians have been published. Three manuscripts(reporting the study design, clinical outcomes, safety, and efficacy of NovaSil intervention) have been accepted for publication. One (reporting the specificity of NovaSil and lack of interference with important micronutrients) has been submitted and two more (reporting the effects of aflatoxin and NovaSil on selected parameters of the immune system and on levels of serum vitamins A & E) are in preparation. Also, two book chapters reviewing our clinical studies have been published. See below:

Relevant Publications (2007)

1. Afriyie-Gyawu, E., Ankrah, N-A., Huebner, H. J., Ofosuhene, M., Kumi, J., Johnson, N. M., Tang, L., Xu, L., Ofori-Adjei, D., Williams, J. H., Wang, J-S., and Phillips, T. D. 2007. NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis: I. Study design and clinical outcomes. Food Additives and Contaminants (In Press).

2. Dash, B., Afriyie-Gyawu, E., Huebner, H. J., Porter, W., Wang, J-S., Jolly, P. E., and Phillips, T.D. 2006. Noninvasive identification of inter-individual variation in xenobiotic metabolizing enzymes: Implications for cancer epidemiology and biomarker studies. J. Toxicol. Environ. Health A. 69 (13): 1203-1216.

3. Dash, B., Afriyie-Gyawu, E., Huebner, H. J., Porter, W., Wang, J. S., Jolly, P. E., Phillips, T. D. 2007. Determinants of the variability of aflatoxin-albumin adduct levels in Ghanaians. J. Toxicol. Environ. Health Part A. 70 (1): 58-66.

4. Phillips, T. D., Afriyie-Gyawu, E., Williams, J. H., Huebner, H. J., Ankrah, N-A., Ofori-Adjei, D., Jolly, P. E., Johnson, N., Taylor, J. F., Marroquin-Cardona, A., Xu, L., Tang, L., and Wang, J-S. 2007. Reducing Human Exposure to Aflatoxin through use of Clay. Food Additives and Contaminants, Special Section (In Press).

5. Wang, P., Afriyie-Gyawu, E., Tang, Y., Johnson, N. M., Xu, L., Tang, L., Huebner, H. J., Ankrah, N-A., Ofori-Adjei, D., Ellis, W. O., Jolly, P. E., Williams, J. H., Wang, J-S., and Phillips, T. D. 2007. NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis: II. Reduction in biomarkers of aflatoxin exposure in blood and urine. Food Additives and Contaminants (Accepted).

6. Afriyie-Gyawu, E., Wang, Z., Ankrah, N-A., Xu, L., Johnson, N. M., Tang, L., Guan, H., Huebner, H. J., Jolly, P. E., Ellis, W. O., Taylor, R., Brattin, B., Ofori-Adjei, D., Williams, J. H., Wang, J-S., and Phillips, T. D. 2007. NovaSil clay does not affect bioavailability and utilization of vitamins A and E and nutrient minerals in Ghanaians at high risk for aflatoxicosis. Food Additives and Contaminants (Submitted).

7. L. Xu, L. Tang, E. Afriyie-Gyawu, P. Wang1, Y. Tang, Z. Wang1, H. J. Huebner, N.-A. Ankrah, D. Ofori-Adjei, W. O. Ellis, P. E. Jolly, J. H. Williams, J.-S. Wang and T. D. Phillips. 2007. Aflatoxin exposure decreases serum levels of vitamins A & E in Ghanaians at high risk for aflatoxicosis. J. of Nutrition (In preparation).

8. L. Xu, E. Afriyie-Gyawu, Y. Jiang, L. Tang, H. J. Huebner, N.-A. Ankrah, D. Ofori-Adjei, W. O. Ellis, P. E. Jolly, J. H. Williams, J.-S. Wang and T. D. Phillips. 2007. Immune parameters as biomarkers of effect from aflatoxin intervention with Novasil clay. (In preparation).

Book Chapters:

1. Phillips, T.D., Afriyie-Gyawu, E., Wang, J.-S., Williams, J., and Huebner, H. The potential of aflatoxin sequestering clay. 2006. In The mycotoxin factbook: food & feed topics (D. Barug, D. Bhatnager, H. P. van Egmond, J. W. van der Kamp, W. A. van Osenbruggen, and A. Visconti, eds.), pp. 329-346. Wageningen Academic Publishers, The Netherlands.

2. Afriyie-Gyawu, E., Williams, J. H., Huebner, H. J., Ankrah, N-A., Ofori-Adjei, D., Jolly, P. E., Wang, J-S., and Phillips, T. D. NovaSil Clay for the Management of Dietary Aflatoxins in Human Populations. 2007. In Mycotoxins: Detection Methods, Management, Public Health and Agricultural Trade. CABI Publishing Company (In Press).

NS clay, which is commonly included in animal feeds, has significant benefits to the animal industry. These are realized particularly by the swine and poultry industries in developed and developing countries. This is due to the susceptibility of piglets, turkey poults, young chicks, quail, etc. to aflatoxins and the frequent contamination of commodities used to formulate their feeds. Based on numerous studies, it has been shown that NS clay improves growth rates, feed conversions and general health in animals. Moreover, NS inclusion in feeds for lactating dairy animals results in diminished aflatoxin residues in human foods of animal origin including milk and dairy products. Our recent findings from clinical intervention trials with NS are of particular relevance to populations in developing countries where the incidence of aflatoxicosis and infectious disease are often elevated. It is anticipated that NS therapy will be useful for short- and long-term protection of humans who are at high risk for aflatoxicosis. Eventually, the preferred delivery of NS may be through its inclusion in salt (like iodine), taking advantage of its anticaking properties, or as an additive in common groundnut and maize-based foods such as peanut butter and infant formula. These novel NS dose forms will facilitate the prospects of technology transfer and serve to protect both adults and the young at the village level.

Other Achievements: We have trained scientists from Ghana in cutting-edge NovaSil technology, and established effective collaborations with participating Universities in Accra and Kumasi. Based on our efforts under TAM50, we have identified a population in the Ejura-Sekyedumasi District of the Ashanti Region of Ghana which is highly exposed to aflatoxins in the diet. This same population is willing to participate in further long-term studies with NovaSil clay.

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Publications

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Background

  Clay and zeolitic minerals have been utilized extensively in agriculture, industry and medicine. Since earliest recorded history, the Chinese, Egyptians, Greeks and Romans were aware of the numerous properties of clay minerals, and in many instances animals and humans have been reported to eat clay. The reasons for this behavior are not readily apparent but are usually reported as beneficial (Phillips et al., 1995). A reduction in exposure of humans and animals to toxic chemicals in the diet is clearly the best strategy for managing risk and preventing disease. In this respect, certain clay minerals are unique in that they can be used to block the uptake of aflatoxins in the gastrointestinal tract, leading to significantly diminished exposure and chemoprotection from disease. Research, supported in part by the Peanut CRSP, has shown that HSCAS clays, which are commonly used as anticaking agents in animal feeds and bleaching agents for cooking oils, are capable of sorbing aflatoxins in vitro and in vivo (Phillips et al., 1994,1995,1997; Mayura et al., 1998; Phillips, 1999). In numerous studies with collaborators at the USDA/ARS in College Station, Texas, we have reported that a processed HSCAS clay (NovaSil) can act as a safe and effective enterosorbent of aflatoxin when included in the diet at levels of only 0.5% w/w. HSCAS clay has been reported to significantly protect a variety of young animals from aflatoxins, including chicks, turkey poults, pigs, lambs, and rodents. Our studies have also demonstrated the ability of HSCAS to reduce the level of aflatoxin residues in milk from dairy cows and goats, as well as molecular dosimetry biomarkers of aflatoxin exposure in chicks and rodents. See reviews by Phillips et al. (1994,1995) and Phillips (1999) for details and references.

Further research has indicated that NovaSil has a preference for aflatoxins that contain a ketolactone system. Information derived from equilibrium adsorption isotherms and molecular modeling studies have been used to delineate potential sites of action. Our findings support the hypothesis that aflatoxin is sorbed to different sites on NovaSil particles, but especially at surfaces within the interlayer region (Grant and Phillips, 1998; Grant et al., 1998). Importantly, all tests conducted to date have shown that NovaSil clay is safe for inclusion in animal diets and use as an aflatoxin enterosorbent.

REFERENCES:

Adhikari, M., Ramjee, G. and Berjak P. 1994. Aflatoxin, Kwashiorkor and morbidity. Natural Toxins 2:13.

CAST (Council for Agricultural Science and Technology). 1989. In: K. Niyo (ed) Mycotoxins: Economic and Health Risks. Ames, IA: CAST Task Report No. 116. P 1-91.

Grant, P.G. and Phillips, T.D. 1998. Isothermal adsorption of aflatoxin B1 on HSCAS clay. J. Ag. Fd. Chem.46:599-605.

Grant, P.G., Lemke, S.L., Dwyer, M.R. and Phillips, T.D. 1998. Modified Langmuir equation for s-shaped and multisite isotherm plots. Langmuir 14:4292-4299.

Lemke, S.L., Grant, P.G. and Phillips, T.D. 1998. Adsorption of zearalenone by organophilic montmorillonite clay. J. Ag. Fd. Chem. 46:3789-3796.

Mayura, K., Abdel-Wahhab, M.A., McKenzie, K.S., Sarr, A.B., Edwards, J.F., Naguib, K., and Phillips, T.D.. 1998. Prevention of maternal and developmental toxicity in rats via dietary inclusion of aflatoxin sorbents: Hidden risks. Toxicol. Sci. 41:175-182

Miller, J.D. 1996. Mycotoxins. In: K.F., Cardwell (ed). Proceedings of the Workshop on Mycotoxins in Foods in Africa, Nov 6-10, 1995. IITA Cotonou, Benin. p 18-22.

Peska, J.J. and Bondy, G.S. 1994. Immunotoxic effects of mycotoxins. In: J.D.Miller and H.I. Trenholm (eds) Mycotoxins in Grain: Comounds other than Aflatoxin. Eagan Press, St. Paul, MN. p 339-358.

Phillips, T.D., Clement, B.A. and Park, D.L. 1994. Approaches to reduction of aflatoxins in foods and feeds. In: D. Eaton and J. Groopman (eds). The Toxicology of Aflatoxins: Human Health, Veterinary and Agricultural Significance. Academic Press, NY. p 383-406.

Phillips, T.D., Sarr, A.B., and Grant, P.G. 1995. Selective chemisorption and detoxification of aflatoxins by phyllosilicate clay. Natural Toxins 3:204-213.

Phillips, T.D. 1997. Detection and Decontamination of aflatoxin-contaminated food products. In: J.H. Williams, D.G. Cummins, G. Hutto, and A. King (eds) Impacts and Scientific Advances through Collaborative Research on Peanut. Peanut CRSP, Griffin, GA. p 117-130.

Phillips, T.D. 1999. Dietary clay in the chemoprevention of aflatoxin-induced disease. Toxicol. Sci. 52:118-126

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Development Benefits

It has been estimated by the World Bank that 40% of the lost productivity in developing countries is due to diseases modulated by aflatoxin (Miller, 1996). In West African countries, aflatoxin adducts are commonly found at high levels in human blood serum and this finding may be attributed in part to the diet, which is largely composed of maize and peanut (Miller, 1996). Another contributing factor to this enhanced exposure may be the high humidity of the region combined with the difficulties of drying and storing produce at the farm and local village level. Producers commonly sort their crops and retain for consumption the most contaminated fraction. There is little enforcement of regulations where they exist, and little likelihood of enforcement into the future. Clearly, safe and effective clay-based strategies for the remediation of aflatoxin-contaminated foodstuffs would have numerous benefits.

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U.S. Benefits

The impact of aflatoxin contamination on the U.S. peanut industry is hard to quantitate, but losses to peanut growers, shellers, processors and consumers can be dramatic (CAST, 1989). It is anticipated that clay-based enterosorbent technology can be used to prevent or reduce aflatoxin exposure to humans and animals from peanut-derived foods and feeds using numerous methods of delivery, e.g., HSCAS clay in salt and pepper; HSCAS clay in multi-vitamin capsules; HSCAS clay in peanut butter; HSCAS clay in peanut meal, etc. Importantly, the benefits and contributions of this new technology may be far-reaching. For example, food crops may no longer have to be discounted in price or condemned because of aflatoxin contamination. Also, aflatoxin residues in food of animal origin may be eliminated or neutralized via enterosorbents. For example, milk may no longer contain hazardous metabolites of aflatoxin that can enter the food chain. Importantly, general health and well-being of humans and animals may significantly improve with the inclusion of aflatoxin detoxifying clays in the diet.

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Potential Impacts

Significance of the Results

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Team

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