IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

Several studies have been reported on the effect of aflatoxin on isolated alveolar
macrophages, but only few experiments in intact animals. One such study involved male
Fischer 344 rats and female Swiss mice that were exposed to aflatoxin B 1 by either
aerosol inhalation or intratracheal instillation. Nose-only inhalation exposure of rats to
aflatoxin B 1 aerosols suppressed alveolar macrophage phagocytosis at an estimated dose
of 16.8 μg/kg bw. The effect persisted for about two weeks. The effects after intratracheal
exposures were similar but occurred at approximately 10-fold higher doses. Additionally,
intratracheal administration of aflatoxin B 1 suppressed the release of tumour necrosis
factor α (TNFα) and inhibited peritoneal macrophage phagocytosis (Jakab et al., 1994).
The overall picture from studies of immunosuppressive effects of aflatoxins in
animals is of increased susceptibility to bacterial and parasitic infections and an adverse
effect on acquired immunity, as evidenced by experimental challenge with infectious
agents after vaccination (reviewed by Denning, 1987). In contrast to the evidence of the
immunosuppressive action of aflatoxins in animal studies, evidence in humans comes
only from in-vitro experiments. Extremely low doses of aflatoxin B 1 (0.5–1.0 pg/mL) in
cultures of human monocytes in vitro were shown to decrease phagocytosis and microbicidal
activity against Candida albicans (Cusumano et al., 1996). Concentrations as low
as 0.05 pg/mL were shown to reduce the release of interleukins 1 and 6 and TNFα
(Rossano et al., 1999). Mycotoxin-induced immune disruption may influence susceptibility
to childhood infections, but may also increase later susceptibility to hepatocellular
carcinoma through the child’s reduced immune response to hepatitis B virus (HBV) and
risk of subsequent development of chronic HBV-carrier status (see Section 4.5.3).
4.3 Reproductive and developmental effects
Reproductive and developmental effects of aflatoxins were reviewed in the previous
monograph (IARC, 1993). Aflatoxins cross the placental barrier, and there is some evidence
that concentrations in cord blood are higher than those in maternal blood
(Lamplugh et al., 1988). Malformations and reduced fetal weight have been found in
mice administered high doses (32–90 mg/kg bw) of aflatoxin intraperitoneally. No
corresponding effect was seen after oral treatment (Tanimura et al., 1982; Roll et al.,
1990). In rats, decreased fetal weight and behavioural changes, but not malformations,
have been found at dose levels of around 2–7 mg/kg bw (Sharma & Sahai, 1987).
4.3.1 Humans
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Several studies have reported high levels of free aflatoxins in maternal and umbilical
cord blood in humans living in areas where consumption of large amounts of food highly
contaminated with aflatoxins is suspected or has been demonstrated in previous studies.
However, the chemical analysis in each study relied on a single method and the results
were not confirmed by other means. A number of studies have reported effects in infants,