Aflatoxins

1. Aflatoxins John L. Herrman WHO Joint Secretary of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) International Programme on Chemical Safety (IPCS) World Health Organization, Geneva herrmanj@who.int

2. JECFA • Joint FAO/WHO Expert Committee on Food Additives • Advises the Codex Committee on Food Additives and Contaminants and FAO and WHO Member States • Characterizes risk on the basis of evaluation of toxicological, epidemiological and related data and information on intake (risk assessment)

3. Endpoints of assessment for food contaminants (1) • Tolerable intake, expressed on a weekly basis (provisional tolerable weekly intake, PTWI) • “Irreducible level” - that concentration of a substance which cannot be eliminated from a food without involving the discarding of that food altogether, severely compromising the ultimate availability of food supplies

4. Endpoints of assessment for food contaminants (2) • Quantitative risk assessment - relationship between intake of a contaminant and the probability of an adverse response in humans

5. Provisional tolerable weekly intake (PTWI) • Expressed on a weekly basis to emphasize that long-term exposure is important (for contaminants that cumulate in the body) • Provides a “bright line” for the risk manager against which intake can be compared • Adverse effects are seen with many contaminants in the range of exposure for some population groups - difficult to separate risk assessment from risk management

6. Irreducible level • Often referred to as ‘ALARA’ - as low as reasonably achievable • Difficult for risk managers to use because health effects are not quantified • Creates difficulty for the Codex because of widely varying levels of contamination around the world, e.g. aflatoxins

7. Quantitative risk assessment • Determination of the relationship between intake and the probability of an adverse response is difficult with most contaminants because data are lacking • Performed with aflatoxin B1 at the forty-ninth meeting of JECFA in 1997 • Although the PTWIs for lead and cadmium were retained by JECFA in 1999 and 2000, risk assessments were performed at these meetings to provide guidance to risk managers on potential risks posed by these heavy metals to at-risk groups

8. Aflatoxin B1 • Animal toxicity data were evaluated - causes primary liver cancer in most species studied • Assessment was based on epidemiology studies, which found an association between consumption of food contaminated with aflatoxin B1 and liver cancer

9. Assessment of carcino-genicity of aflatoxin B1 • Carcinogenic potency is enhanced in individuals with simultaneous hepatitis B infection • Carcinogenic potency of aflatoxin B1 was estimated in the presence and absence of hepatitis B surface antigen in the serum, which is an indicator of infection with the virus

10. Carcinogenic potency of aflatoxin B1 • For persons negative for hepatitis B virus: 0.01 case per year/100 000 people per ng of aflatoxin B1/kg body weight per day (range 0.002-0.03) • For persons positive for hepatitis B virus: 0.3 case per year/100 000 people per ng of aflatoxin B1/kg body weight per day (range 0.05-0.5); 30-fold higher than in the absence of hepatitis B surface antigen in the serum)

11. Population risks (1) • Two examples • Level of contamination with aflatoxin B1 is low and proportion of population carrying hepatitis B is small (1% of the population) • Level of contamination with aflatoxin B1 is higher with a higher proportion of the population carrying the hepatitis B virus (25% of the population)

12. Population risks (2) • Estimates were based on food consumption data available at the international level • Estimates of contamination in the first example were based on monitoring data from Europe on aflatoxin B1 levels in groundnuts and maize and the “European” diet • Estimates of contamination in the second example were based on monitoring data from China on aflatoxin B1 levels in groundnuts and maize and the “Far Eastern” diet

13. Hypothetical standards • Population risks were calculated on the basis of two hypothetical standards • 10 µg aflatoxin B1/kg groundnuts or maize • 20 µg aflatoxin B1/kg groundnuts or maize • If the more stringent standard were used, more product would be removed from the market, and population risks should be lower

14. Low-risk group – potency • Assumes that 1% of the population carries the hepatitis B virus • Potency: 0.01 x 99% + 0.3 x 1% = 0.013 cancers per year/100 000 people per ng aflatoxin B1/kg body weight per day (range 0.002-0.035)

15. Low-risk group – intake • Intake of aflatoxins20 µg/kg standard - 19 ng per person per day10 µg/kg standard - 18 ng per person per day • Differences are small because the most highly contaminated samples have been removed in both cases

16. Low-risk group – population risks • 20 µg/kg standard • (19 ng x 0.013)/60 kg bw = 0.0041 cancers per year per 100 000 people (range 0.0006 - 0.01) • 10 µg/kg standard • (18 ng x 0.013)/60 kg bw = 0.0039 cancers per year per 100 000 people (range 0.0006 - 0.01) • Reducing the hypothetical standard from 20 to 10 µg/kg yields a reduction in estimated population risk by 2 cancers per year per billion people

17. Higher-risk group – potency • Assumes that 25% of the population carries the hepatitis B virus • Potency: 0.01 x 75% + 0.3 x 25% = 0.083 cancers per year/100 000 people per ng aflatoxin B1/kg body weight per day (range 0.014-0.15)

18. Higher-risk group – intake • Intake of aflatoxins20 µg/kg standard - 125 ng per person per day10 µg/kg standard - 103 ng per person per day • Differences are relatively small because the most highly contam-inated samples have been removed in both cases

19. Higher-risk group – population risks • 20 µg/kg standard • (125 ng x 0.083)/60 kg bw = 0.17 cancers per year per 100 000 people (range 0.03 - 0.3) • 10 µg/kg standard • (103 ng x 0.083)/60 kg bw = 0.14 cancers per year per 100 000 people (range 0.02 - 0.3) • Reducing the hypothetical standard from 20 to 10 µg/kg yields a reduction in estimated population risk by 300 cancers per year per billion people

20. Selected conclusions of JECFA • Vaccination against hepatitis B would reduce the potency of aflatoxins to vaccinated populations and thus the risk of liver cancer • Detectable differences in population risks are unlikely to be exhibited in going from a hypothetical standard of 20 to 10 µg/kg in populations with a low prevalence of hepatitis B in which the mean intake of aflatoxins is low

21. Use of potency estimates • Can be used world-wide because toxicity is an inherent property • Should be updated periodically by JECFA and/or other scientific committees to ensure that they are based upon the latest relevant information

22. Risk determination • Population risks at the international level can, at best, be indicative because precise information on intake is lacking • More precise risk estimates must be made at the national or local level, based on contamination levels and food consumption • Must be careful when using surveillance data because they may not provide a clear picture of the total food supply (may be targeting more heavily contaminated commodities)

23. Vulnerable population groups • JECFA identified carriers of hepatitis B virus as a vulnerable group • Carriers of hepatitis C are probably also at increased risk from consumption of products containing aflatoxin, but quantitative estimates could not be made

24. Population risks vs risks of vulnerable groups • JECFA provided sample calculations of population risks • Population risks can be performed at the national level, which would provide an overall estimate of risk in the country • Estimation of risks of vulnerable groups (carriers of hepatitis B) may be more appropriate at the national level, where a potency of 0.3 cancers per year/100 000 population per ng aflatoxin B1/kg body weight per day is assumed

25. Further details • Report of the forty-ninth meeting of JECFA – WHO Technical Report Series No. 884, 1999 • Toxicological and intake monograph on aflatoxins – WHO Food Additives Series No.40, 1998 • Above documents are available from WHO Marketing and Dissemination (http://www.who.int/dsa/) • Information on estimating intake of food contaminants may be obtained at http://www.who.int/fsf/

26. JECFA summary • Information on evaluations performed by JECFA is available in searchable HTML format at http://www.who.int/pcs/ • Current through the forty-ninth meeting held in 1997 • Updated approximately every two years