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

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)

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

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

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

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

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

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

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

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)

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)

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

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

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)

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

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

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)

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

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

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

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

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)

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

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

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/

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