Workgroup report: public health strategies for reducing aflatoxin exposure in developing countries.

Consecutive outbreaks of acute aflatoxicosis in Kenya in 2004 and 2005 caused > 150 deaths. In response, the Centers for Disease Control and Prevention and the World Health Organization convened a workgroup of international experts and health officials in Geneva, Switzerland, in July 2005. After discussions concerning what is known about aflatoxins, the workgroup identified gaps in current knowledge about acute and chronic human health effects of aflatoxins, surveillance and food monitoring, analytic methods, and the efficacy of intervention strategies. The workgroup also identified public health strategies that could be integrated with current agricultural approaches to resolve gaps in current knowledge and ultimately reduce morbidity and mortality associated with the consumption of aflatoxin-contaminated food in the developing world. Four issues that warrant immediate attention were identified: a) quantify the human health impacts and the burden of disease due to aflatoxin exposure; b) compile an inventory, evaluate the efficacy, and disseminate results of ongoing intervention strategies; c) develop and augment the disease surveillance, food monitoring, laboratory, and public health response capacity of affected regions; and d) develop a response protocol that can be used in the event of an outbreak of acute aflatoxicosis. This report expands on the workgroup's discussions concerning aflatoxin in developing countries and summarizes the findings.

Aflatoxin, hepatitis and worldwide liver cancer risks.

Aflatoxins are among the most potent mutagenic and carcinogenic substances known. Differential potency of aflatoxin among species can be partially attributed to differences in metabolism; however, current information on competing aspects of metabolic activation and detoxification of aflatoxin in various species does not identify an adequate animal model for humans. Risk of liver cancer is influenced by a number of factors, most notably carriage of hepatitis B virus as determined by the presence in serum of the hepatitis B surface antigen (HBsAg+ or HBsAg-). About 50 to 100% of liver cancer cases are estimated to be associated with persistent infection of hepatitis B (or C) virus. The potency of aflatoxin in HBsAg+ individuals is substantially higher (about a factor of 30) than the potency in HBsAg- individuals. Thus, reduction of the intake of aflatoxins in populations with a high prevalence of HBsAg+ individuals will have greater impact on reducing liver cancer rates than reductions in populations with a low prevalence of HbsAg+ individuals. The present analysis suggests that vaccination against hepatitis B (or protection against hepatits C), which reduces prevalence of carriers, would reduce the potency of the aflatoxins in vaccinated populations and reduce liver cancer risk.

Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity.

The discovery of acrylamide (AA) in many common cooked starchy foods has presented significant challenges to toxicologists, food scientists, and national regulatory and public health organizations because of the potential for producing neurotoxicity and cancer. This paper reviews some of the underlying experimental bases for AA toxicity and earlier risk assessments. Then, dietary exposure modeling is used to estimate probable AA intake in the U.S. population, and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling is used to integrate the findings of rodent neurotoxicity and cancer into estimates of risks from human AA exposure through the diet. The goal of these modeling techniques is to reduce the uncertainty inherent in extrapolating toxicological findings across species and dose by comparing common exposure biomarkers. PBPK/PD modeling estimated population-based lifetime excess cancer risks from average AA consumption in the diet in the range of 1-4 x 10 (-4); however, modeling did not support a link between dietary AA exposure and human neurotoxicity because marginal exposure ratios were 50-300 lower than in rodents. In addition, dietary exposure modeling suggests that because AA is found in so many common foods, even big changes in concentration for single foods or groups of foods would probably have a small impact on overall population-based intake and risk. These results suggest that a more holistic analysis of dietary cancer risks may be appropriate, by which potential risks from AA should be considered in conjunction with other risks and benefits from foods.