1. www.tfda.or.tz 1 Aflatoxin exposure, health impacts, risk assessment and database Aflatoxin Stakeholders’ Workshop 3-4 December, 2012 Dar es Salaam, Tanzania Candida Philip Shirima

2. www.tfda.or.tz 2 Aflatoxins They are toxic and fungal metabolites Produced (A. flavus, A. parasiticus and rare A. nomius) Types: aflatoxins B1 (AFB1) and B2 (AFB2), (AFG1) and G2 (AFG2). Aflatoxin B1 occurs most frequently and is most toxic and carcinogenic

3. www.tfda.or.tz Human exposure to aflatoxins Dietary exposure – The main source of human exposure to aflatoxins Exposure is through consumption of aflatoxins contaminated food. Contamination of maize and groundnuts is of particular concern- dietary staples including children complementary foods. The presence of aflatoxins metabolites in breast milk (AFM1) provides main source of aflatoxins exposure for lactating newborn infants and breast feeding young children Exposure from animal food products; poultry 3

4. www.tfda.or.tz Toxicokinetics of aflatoxin 4 Absorption Gastro – Intestinal Track Metabolism/ Distribution Liver (metabolism site) DNA, AF-alb Adducts) Blood Circulation (AF-albumin) Kidney Excretion Urine (metabolites) AFB1-N7-guanine Breast milk (metabolite) AFM1 Faeces (un-metabolised)

5. www.tfda.or.tz Quantitative evaluation of the likely intake of aflatoxin via food. The extent of exposure to aflatoxins depends on the level of the toxin in different foods and on the level of consumption of those foods 5 Aflatoxins exposure assessment

6. www.tfda.or.tz Ways of assessing exposure to aflatoxins-1 Food measurement: 1.Use levels of aflatoxin contamination in food and quantities of food consumption Probably daily intake (PDI) 6 Aflatoxin Contamination in food (ng/gm) Food consumption (gm/day) Body weight (Kg) Aflatoxins exposure (ng/kg-bw/day)

7. www.tfda.or.tz Ways of assessing exposure to aflatoxins-2 Use of biomarkers of aflatoxin exposure Biomarkers are a measure of a cellular, biochemical or molecular change in biological media (human tissues, cells or fluids), which is informative with respect to assessing an exposure Use of biomarkers requires understanding of the mechanisms of aflatoxin actions 7

8. www.tfda.or.tz Ways of assessing human exposure to aflatoxins-3 Use of biomarkers of aflatoxin exposure Biomarkers of aflatoxin exposure include:- Urinary aflatoxin metabolites, such as AFB1-N7- guanine and AFM1 AF-albumin in blood serum, DNA adducts AFM1 in breast milk These metabolites are well validated as biomarkers of aflatoxin exposure. 8

9. www.tfda.or.tz Completed study -Iringa, Kilimanjaro, Tabora and Mtwara: Aflatoxin occurance: 18% in maize Contamination level: range 1 to 158 μg/kg Ongoing studies: Iringa, Kilimanjaro and Tabora (TFDA & Leeds University) -Use of biomarkers in the evaluation of dietary exposure to aflatoxins and fumonisins among young children. -Association of children growth and exposure to the mycotoxins Hanang, Kilosa and Rungwe (TFDA and Ghent University) Strategies for reducing mycotoxins contamination and exposure:- -Application of GPHP and dietary approaches /diversification Aflatoxin research work by TFDA

10. www.tfda.or.tz Aflatoxins and health effects Aflatoxins are toxic in humans and animals Carcigonen: AFB1 has been classified as a group 1 human carcinogen by the IARC (1993). Associated with aflatoxicosis: acute poisoning which results in direct liver damage and subsequent illness or death (Kenya in 2004) The liver: Target organ for both acute and chronic aflatoxin toxicity High aflatoxin exposure is associated with impairment of child growth, particularly stunting; the underlying mechanisms are unclear 10

11. www.tfda.or.tz Aflatoxins and health effects Immune suppression effects Hepatopmegaly (liver enlargement) (in Kenyan school children) Nutritional interference effects: -Aflatoxins bind covalently to DNA resulting in decreased protein synthesis -Selenium concentrations were found to be significantly and inversely correlated to AF-albumin adducts concentrations 11

12. www.tfda.or.tz Why affects child growth? Hypothesis: 1.Intestine permeability and absorption impaired 2.liver toxicity inhibit IGFs production which affect the growth axis 3.Immune function suppression may enhance infectious disease e.g. diarrhoea 4.Epigenetic changes occurred at early life exposure may have effect

13. www.tfda.or.tz Develops an estimate of the risks Identifies appropriate measures Implement appropriate measures Communicates with stakeholders about the risks and measures applied 13 Aflatoxin risk analysis

14. www.tfda.or.tz Aflatoxin database Need for a centralised aflatoxin database -Food consumption data (AF susceptible foods) -Aflatoxin contamination data (to be coordinated) -Exposure assessment (e.g conventional & biomarkers) -Aflatoxin risk analysis -Findings from aflatoxin studies Useful source of information for status of aflatoxin contamination, exposure and health effects in Tanzania Combine and share findings from various independent studies Good/accessible source of information for formulating sound strategies for AF control 14

15. www.tfda.or.tz 15