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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
[email protected]
JECFA
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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)
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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)
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Quantitative risk assessment relationship between intake of a
contaminant and the probability of
an adverse response in humans
Provisional tolerable
weekly intake (PTWI)
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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
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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
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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
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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 carcinogenicity of aflatoxin B1
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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
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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)
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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)
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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
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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
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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
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Intake of aflatoxins
20 µg/kg standard - 19 ng per
person per day
10 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
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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
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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
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Intake of aflatoxins
20 µg/kg standard - 125 ng per
person per day
10 µg/kg standard - 103 ng per
person per day
Differences are relatively small
because the most highly contaminated samples have been
removed in both cases
Higher-risk group –
population risks
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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
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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
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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
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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
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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
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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
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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
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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