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_at_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

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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

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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)

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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)

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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

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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

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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

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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

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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)

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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

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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

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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)

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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

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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

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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/

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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