IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

228
lordosis and reduction in conception rates and litter sizes, were observed in Druckrey rats
exposed to 7.5 mg/kg bw aflatoxin B 1 per day for 14 days. An aflatoxin B 1 blood concentration
of 86.2 [μg/L] ppb was found in the exposed animals (Ibeh & Saxena, 1997a).
Female Druckrey rats were given oral doses of 7.5 or 15 mg/kg bw aflatoxin B 1 daily
for 21 days. Dose-dependent reductions were seen in the number of oocytes and large
follicles. The blood hormone levels and sex organ weight were also disturbed (Ibeh &
Saxena, 1997b).
Male mature rabbits were given oral doses of 15 or 30 μg/kg bw aflatoxin B 1 every
other day for nine weeks followed by a nine-week recovery period. Body weight, relative
testes weight, serum testosterone, ejaculate volume, sperm concentration and sperm
motility were reduced and the number of abnormal sperm was increased in a dosedependent
manner. These effects continued during the recovery period. Simultaneous
treatment with ascorbic acid (20 mg/kg bw) alleviated the effects of exposure to aflatoxin
B 1 during the treatment and recovery period (Salem et al., 2001).
The reproductive performance of female mink (Mustela vison) given a diet containing
5 or 10 ppb [μg/kg] total aflatoxins from naturally contaminated corn for 90 days
was not impaired compared with a control group. Body weights of the kits were significantly
decreased at the 10-ppb dose at birth and in both exposed groups at three weeks
of age. Kit mortality was highest in the 10-ppb group and reached 33% by three weeks
of age. In the 10-ppb dose group, analysis of milk samples showed very low concentrations
of aflatoxin metabolites (Aulerich et al., 1993).
In an experiment to determine the effects of aflatoxin B 1 (2–16 ppb [μg/L] in
medium) on the in-vitro fertilizing ability of oocytes and epididymal sperm of albino rats,
a significant reduction of the mean number of oocytes fertilized was observed, as well as
a significant decrease in sperm motility (Ibeh et al., 2000).
4.4 Genetic and related effects
4.4.1 Humans
(a) General
IARC MONOGRAPHS VOLUME 82
DNA and protein adducts of aflatoxin have been detected in many studies of human
liver tissues and body fluids (IARC, 1993). Some studies related the level of adducts
detected to polymorphisms in metabolizing enzymes, in order to investigate interindividual
susceptibility to aflatoxin.
Wild et al. (1993b) measured serum aflatoxin–albumin adducts in 117 Gambian
children in relation to GSTM1 genotype and found no difference in adduct levels by
genotype.
In a larger study of 357 adults in the same population, aflatoxin–albumin adduct
levels were examined in relation to genetic polymorphisms in the GSTM1, GSTT1,
GSTP1 and epoxide hydrolase genes. Only the GSTM1-null genotype was associated
with a modest increase in aflatoxin–albumin adduct levels and this effect was restricted