Chuck Miller rellim at MAILHOST.TCS.TULANE.EDU
Mon Jul 6 17:34:11 EST 1998

There are volumes of information on aflatoxin(s).
See the Bionet.toxicology FAQ for ways to search for this information.

Here are a few recent articles from a MEDLINE search.

Biometrics 1998 Jun;54(2):739-753

Investigations of the problems of assessing aflatoxin levels in

Giesbrecht FG, Whitaker TB

Department of Statistics, North Carolina State University, Raleigh
27695-8203, USA. giesbrec at stat.ncsu.edu
In this study, a number of probability distributions that have been used to
model the occurrence of aflatoxin in peanuts
are compared. Two distributions, the compound gamma and the negative
binomial, are shown to have special appeal in
that both can be justified by reasoning from the fundamental biological and
stochastic processes that generate the
aflatoxin. Since method of moments and maximum likelihood give consistent
estimates of parameters in both models,
practical considerations suggest using the former. One hundred twenty data
sets, each consisting of fifty observations,
were not sufficient to provide goodness-of-fit tests to establish either as
superior to the other as a model. Both models
fit the data well, appreciably better than other models examined. An
attractive aspect of the compound gamma and the
negative binomial distributions is that, as a consequence of their
theoretical underpinnings, both involve parameters that
have meaningful interpretations. In the compound gamma, the alpha parameter
reflects the shape of the kernel-to-kernel
aflatoxin content distribution, the lambda parameter reflects the number
(or frequency) of contaminated kernels in the
sample, and the beta parameter is a scale parameter. In the negative
binomial, the two parameters can be used as
measures of mean or location and shape.

Poult Sci 1998 Jun;77(6):812-819

Dietary exposure of broiler breeders to aflatoxin results in immune
dysfunction in progeny chicks.

Qureshi MA, Brake J, Hamilton PB, Hagler WM Jr, Nesheim S

Department of Poultry Science, North Carolina State University, Raleigh
27695-7608, USA. m_qureshi at ncsu.edu

Broiler breeder hens were fed diets amended with 0 and 10 mg/kg (Trial 1)
or 0, 0.2, 1, or 5 mg/kg (Trial 2) of
aflatoxin (AF). Fertile eggs collected during 14 d of AF feeding were
examined for AF residues. Various
immunological endpoints were examined in chicks hatched from these eggs.
Eggs collected at 7 d of AF feeding (Trial
1) had 0.15 to 0.48 ng/g of AFB1 and 0.22 to 0.51 ng/g of aflatoxicol,
whereas eggs collected at 14 d of AF feeding
had 0.05 to 0.60 ng of AFB1/g and 0.19 to 1.20 ng of aflatoxicol/g. In both
trials, AF dietary exposure resulted in
embryonic mortality and reduction in hatchability compared to controls. The
AF progeny chicks in Trial 2 had total
anti-SRBC antibodies similar to the controls during the primary antibody
response. However, at 5 and 7 d after
secondary SRBC injection, the antibody levels in the 1 and 5 mg/kg AF
groups were lower than those of controls.
Depression in anti-Brucella abortus antibodies occurred only in chicks from
the 5 mg/kg AF group. Furthermore,
phagocytosis of SRBC and reactive oxygen intermediate production by
macrophages from AF progeny chicks were
reduced as compared with the control chicks. The findings of this study
imply that the progeny chicks from hens
consuming a AF-amended diet may be increasingly susceptible to disease
owing to suppression of humoral and cellular

Mutat Res 1998 Feb 26;398(1-2):183-187
Inhibitory effects of ellagic acid on the direct-acting mutagenicity
of aflatoxin B1 in the Salmonella microsuspension assay.

Loarca-Pina G, Kuzmicky PA, de Mejia EG, Kado NY

Departamento de Investigacion y Posgrado, Facultad de Quimica, Universidad
Autonoma de Queretaro, Qro., Mexico.
Ellagic acid (EA) is a phenolic compound that exhibits both antimutagenic
and anticarcinogenic activity in a wide range
of assays in vitro and in vivo. It occurs naturally in some foods such as
strawberries, raspberries, and grapes. In the
previous work, we used the Salmonella microsuspension assay to examine the
antimutagenicity of EA against the
potent mutagen aflatoxin B1 (AFB1) using tester strains TA98 and TA100.
Briefly, the microsuspension assay was
approximately 10 times more sensitive than the standard
Salmonella/microsome (Ames) test in detecting AFB1
mutagenicity, and EA significantly inhibited mutagenicity of all AFB1 doses
in both tester strains with the addition of
S9. The greatest inhibitory effect of EA on AFB1 mutagenicity occurred when
EA and AFB1 were incubated together
(with metabolic enzymes). Lower inhibition was apparent when the cells were
first incubated with EA followed by a
second incubation with AFB1, or when the cells were first incubated with
AFB1 followed by a second incubation with
EA alone, all with metabolic enzymes. The result of these sequential
incubation studies indicates that one mechanism of
inhibition could involve the formation of an AFB1-EA chemical complex. In
the present study, we further examine the
effect of EA on AFB1 mutagenicity, but without the addition of exogenous
metabolic enzymes. We report the
mutagenicity of AFB1 in the microsuspension assay using TA98 and TA100
without the addition of S9. Neither the
concentrations of AFB1 (0.6, 1.2, and 2.4 microg/tube) nor the
concentrations of EA (0.3, 1.5, 3, 10, and 20
microg/tube) were toxic to the bacteria. The results indicate that AFB1 is
a direct-acting mutagen, and that EA inhibits
AFB1 direct-acting mutagenicity.

Ann Trop Med Parasitol 1997 Oct;91(7):787-793

Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin
addicts and food poisoning: research on the influence of aflatoxins
on child health in the tropics.

Hendrickse RG

University of Liverpool, U.K. ralphgh at liv.ac.uk

Similarities between the geographical and climatic prevalences of
kwashiorkor and of exposure to dietary aflatoxins,
and between the biochemical, metabolic and immunological derangements in
kwashiorkor and those in animals
exposed to aflatoxins, prompted investigation of the associations between
kwashiorkor and aflatoxins. Studies in
Africa in the 1980s indicated a role for these toxins in the pathogenesis
of the disease. Paediatric cases of kwashiorkor
are less prone to severe Plasmodium falciparum malaria than normal
children. In mice infected with P. berghei,
aflatoxin exposure inhibits parasite growth and ameliorates morbidity.
Aflatoxins occur in < or = 40% of samples of
breast milk from tropical Africa, usually as low concentrations of the
relatively non-toxic derivatives of aflatoxin B1
(AFB1) but sometimes as high concentrations of the very toxic AFB1. This
could explain kwashiorkor in breast-fed
babies. Aflatoxin exposure occurs in > or = 30% of pregnancies in tropical
Africa and the toxins are often in cord
blood, sometimes at extremely high concentrations. Aflatoxins are now
incriminated in neonatal jaundice and there is
circumstantial evidence that they cause perinatal death and reduced
birthweight. Aflatoxin-induced immunosuppresion
may explain the aggressive behaviour of HIV infection in Africa. There are
similarities between observations on HIV
cases in Africa and those on heroin addicts in Europe, where 'street'
heroin is frequently contaminated with aflatoxin.
Aflatoxins were found in 20% of random urine samples from heroin addicts in
the U.K. and the Netherlands.
Aflatoxins have also been incriminated in episodes of food poisoning which
have been associated with serious
morbidity and mortality, particularly among young children.

Hepatology 1998 Jun;27(6):1563-1566

Dietary iron overload as a risk factor for hepatocellular carcinoma
in Black Africans.

Mandishona E, MacPhail AP, Gordeuk VR, Kedda MA, Paterson AC, Rouault TA, Kew MC

Department of Medicine, University of the Witwatersrand Medical School,
Johannesburg, South Africa.

Although the iron-loading disease, hereditary hemochromatosis, has a strong
causal association with hepatocellular
carcinoma (HCC), the carcinogenic potential of dietary iron overload in
Black Africans is not known. We investigated
this potential by evaluating iron status, alcohol consumption, markers for
hepatitis B (HBV) and C virus (HCV)
infections, and exposure to dietary aflatoxin B1 in 24 rural patients with
this tumor, 48 race-, sex-, and age-matched
hospital-based controls, and 75 related or unrelated close family members
of the cancer patients. Iron overload was
defined as a raised serum ferritin concentration in combination with a
transferrin saturation > or = 60%, and was
confirmed histologically when possible. Among 24 patients and 48 hospital
controls, the risk of developing HCC in
the iron-loaded subjects was 10.6 (95% confidence limits of 1.5 and 76.8)
relative to individuals with normal iron
status, after adjusting for alcohol consumption, chronic HBV and HBC
infections, and exposure to aflatoxin B1. The
risk of HCC in subjects with HBV infection was 33.2 (7.2, 153.4) (odds
ratio [95% confidence limits]), HCV
infection 6.4 (0.3, 133.5), and alcohol consumption 2.0 (0.5, 8.2).
Aflatoxin B1 exposure did not appear to increase
the risk of HCC. The population attributable risk of iron overload in the
development of HCC was estimated to be
29%. Among 20 cancer patients and 75 family members, the risk of developing
HCC with iron overload was 4.1 (0.5,
32.2). We conclude that dietary iron overload may contribute to the
development of HCC in Black Africans.

Environ Health Perspect 1998 Jun;106(Suppl 3):827-832

Approaches to Environmental Exposure Assessment in Children.

Weaver VM, Buckley TJ, Groopman JD

Department of Environmental Health Sciences, Johns Hopkins University
School of Hygiene and Public Health,
Baltimore, Maryland.

An improved understanding of the contribution made by environmental
exposures to disease burden in children is
essential, given current increasing rates of childhood illnesses such
asthma and cancer. Children must be routinely
included in environmental research. Exposure assessment, both external
(e.g., air, water) and internal dose (e.g.,
biomarkers), is an integral component of such research. Biomarker
measurement has some advantages that are unique
in children. These include assessment of potentially increased absorption
because of behaviors that differ from adults
(i.e., hand-to-mouth activity); metabolite measurement, which can help
identify age-related susceptibility differences;
and improved assessment of dermal exposure, an important exposure route in
children. Environmental exposure
assessment in children will require adaption of techniques that are
currently applied in adult studies as well as
development of tools and validation of strategies that are unique for
children. Designs that focus on parent-child study
units provide adult comparison data and allow the parent to assist with
more complex study designs. Use of equipment
that is sized appropriately for children, such as small air pumps and badge
monitors, is also important. When
biomarkers are used, biologic specimens that can be obtained noninvasively
are preferable. Although the current need
is primarily for small focused studies to address specific questions and
optimize research tools, the future will require
establishment of large prospective cohorts. Urban children are an important
study cohort because of relatively high
morbidity observed in the urban environment. Finally, examples of completed
or possible future studies utilizing these
techniques are discussed for specific exposures such as benzene,
environmental tobacco smoke, aflatoxin, volatile
organic compounds, and polycyclic aromatic hydrocarbons.

Cancer Epidemiol Biomarkers Prev 1998 May;7(5):441-447

Detectable levels of serum aflatoxin B1-albumin adducts in the
United Kingdom population: implications for aflatoxin-B1 exposure
in the United Kingdom.

Turner PC, Dingley KH, Coxhead J, Russell S, Garner CR

The Jack Birch Unit for Environmental Carcinogenesis, Department of
Biology, University of York, Heslington,
United Kingdom.

This study aimed to estimate aflatoxin B1 (AFB1) exposure in the United
Kingdom population by measuring levels of
serum AFB1-albumin (alb), using immunoassay and high-performance liquid
chromatography (HPLC) with
fluorescence detection. A self-questionnaire on dietary habits from 104
volunteers (47 men and 57 women) in York
was completed, and blood samples were collected. Serum alb was extracted,
and AFB1-lysine (lys), the digest product
of AFB1-alb, was isolated and measured. A sensitive ELISA (detection limit,
approximately 1.4 pg of AFB1-lys) was
developed. A good correlation was found between calibration of ELISA
results and scintillation counting, for rats
dosed with [3H]AFB1 (r = 0.972; P < 0.001). This ELISA was subsequently
used to analyze human serum alb. For
United Kingdom human sera, the mean adduct levels were 29.3 +/- 14.8 pg
AFB1-lys equivalents (eq) mg albumin
(males) and 26.9 +/- 14.4 pg AFB1-lys eq/mg alb (females). Confirmation of
the ELISA data was sought using
reversed-phase HPLC with fluorescence detection. HPLC chromatograms of
digested York serum alb were compared
to digested serum alb for humans from Qidong County, People's Republic of
China, and from AFB1-dosed rats.
These all gave similar HPLC profiles. Each sample contained fluorescent
material that coeluted with and just before the
AFB1-lys standard. Fluorescent fractions were found to be inhibitory in a
separate anti-AFB1-lys ELISA, indicating
that these earlier fluorescent peaks contained AFB1 residues. Our results
suggest that measurable internal AFB1
exposure may be occurring in some United Kingdom individuals, albeit at
lower levels than those seen for areas with
high AFB1 exposure. The source of this exposure may reflect the known
difficulties in accurately monitoring regulated
imported foodstuffs and/or the lack of regulations on other potentially
contaminated imports. However, no positive
correlations were found between our AFB1-lys measurements and any dietary
questionnaire information. Animal
studies, as well as human studies, have been important in developing
exposure and internal adduct relationships in
humans. Based on this literature, our AFB1-alb data indicate a mean daily
exposure of 3 microg of AFB1 and a mean
internal dose in liver DNA of 5.9 adducts/10(7) nucleotides. We believe
this may be an overestimate of the AFB1
exposure level in the United Kingdom, and further studies are needed to
accurately relate external dose and internal
AFB1 biomarkers in humans.

Dr. Charles A. Miller, III,   rellim at mailhost.tcs.tulane.edu
Dept. Environmental Health Sciences, SL29
Tulane-Xavier Center for Bioenvironmental Research and
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Ave.
New Orleans, LA 70112
(504)585-6942, fax (504)584-1726
Bionet.toxicology newsgroup: http://www.bio.net/hypermail/TOXICOLOGY

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