IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

ANNEX 291
incidence (JECFA, 2001; see Section 5). However, uncertainty remains regarding (1) the
health effects of occasional high exposures occurring due to unusual weather patterns, in
comparison with those due to normal chronic exposure; (2) the effect of combinations of
mycotoxins, e.g. aflatoxins and fumonisins, on cancer risk; and (3) the broader health
effects of aflatoxin exposure. Under the latter consideration, the most important aspects
are (1) the greater sensitivity of children to acute toxicity of aflatoxins as compared with
adults; (2) the in-utero effects of aflatoxins, known to cross the placenta; (3) the immunosuppressive
effects of aflatoxins, which may influence susceptibility to infectious
disease; (4) the suppressive effects of aflatoxins on growth; and (5) the interactions
between HCV, HBV and aflatoxins in liver cancer development in various populations
in the world.
The areas mentioned are important ones for future research, to provide information
of direct relevance to public health decisions regarding aflatoxin exposure.
5. Previous Recommendations
Although some countries with fully developed market economies have enforced
regulations on aflatoxins for some 30 years, it is only recently that a broader consensus
has been developed on the impact of aflatoxins and other agriculturally important toxins
on human populations. The health effects include those resulting from exposure in foods,
from reductions in the quality of the crops affected and from reduced animal production.
The health consequences of lowered income are also pertinent in some communities.
This consensus was reached when the Joint Food and Agriculture Organization/World
Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA) established
an hypothetical standard for aflatoxins (JECFA, 1998), provisional maximum
tolerable daily intakes (PMTDIs) for deoxynivalenol and fumonisins and a provisional
tolerable weekly intake (PTWI) for ochratoxin A (JECFA, 2001). For aflatoxin and
fumonisin, exposure in excess of the PMTDI occurs in much of Africa as well as parts
of Asia and South America.
JECFA attempted to separate the portion of risk of liver cancer attributable to aflatoxin
from the risk attributable to other factors (JECFA, 1998, 2001). JECFA modelled
dose–response curves from laboratory animal studies as well as human epidemiological
studies of aflatoxin carcinogenicity. The risk of liver cancer from aflatoxin consumption
was significantly higher (perhaps 30-fold) in individuals who were chronically infected
with hepatitis B virus (hepatitis B surface antigen (HBsAg)-positive) than in those who
were not (HBsAg-negative).
It was concluded that populations such as those in western Europe and the USA with
a low prevalence of HBsAg-positive individuals or populations with a low mean intake
of aflatoxins are unlikely to achieve a decrease in liver cancer cases from more stringent