Investigations into the Role of Herbicides and
Other Chemicals in Causing Male-mediated
Development Toxicity
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This synopsis courtesy of Assoc Prof Bill
Webster, University of Sydney
incorporating an update of 16 December 1998 from Diana Oaks
The three-year project (funded by the Department of Veterans'
Affairs) commenced in July 1997 and is designed to investigate
whether paternal exposure to herbicides, such as those used in the Vietnam war, can result in
the an increased incidence of spina bifida or other birth
defects.
Australian soldiers who served in Vietnam were exposed to a
number of herbicide chemical mixtures that may have damaged their
health or reproductive ability. The most frequently used of
these was Agent Orange (11 million gallons sprayed) and this
chemical mixture has been extensively studied to identify and
classify its various toxic properties. The second most used
herbicide mixture was code-name Agent White (5 million gallons
sprayed). Unlike agent orange, there have been very few
studies to examine the toxic properties of Agent White.
Epidemiological studies, in which the incidence of birth
defects is determined in the offspring of Vietnam Veterans and in
control populations, has not resolved the issue and it was
decided to perform studies with experimental animals in an
attempt to get some useful answers. Animal studies have the
advantage that chemical exposure can be precisely measured and
controlled and the effects on the offspring can be examined in
detail.
Briefly, male rats will be exposed to high doses of herbicides
containing 2,4-D and picloram and their offspring will be
examined for birth defects and chromosomal (genetic)
abnormalities. Tissues from the treated rats will also be
examined for evidence of DNA damage. It was decided not to use
dioxin in these initial experiments because although it is a
highly toxic compound found in some herbicides it does not appear
to damage genetic material (DNA).
This study is almost half-way to completion. The
current, incomplete results, do not show any evidence of an
increased incidence of abnormalities. The offspring (fetuses)
will be further examined for genetic abnormalities by examination
of their chromosomes. The work is still in progress.
Other experiments will be performed using a larger range of
chemicals found in herbicides used in Vietnam. In these
experiments particles (mitochondria) derived from rat liver will
be exposed to various combinations of these chemicals and the
effect on mitochondrial function (energy production) will be
measured. These studies will indicate whether certain mixtures of
chemicals lead to enhanced and unexpected toxicity that might not
be predicted from examination of individual chemicals.
An interesting finding has been that the active components of
the formulation (2,4-D) and picloram) showed little or no
toxicity compared with the toxicity of the surfactant present in
the mixture. Surfactants are added to herbicides to aid
penetration and spreading of the active components. It is
unknown what relevance this has to human exposure since the
behaviour of the surfactant in humans has not been studied.
It is possible that ingested surfactants are not absorbed or are
inactivated before they reach important structures.
Using similar techniques, the team is also examining the
formulations known as Agent Orange and Agent Blue. The
results of these experiments are currently being prepared for
publication in a scientific journal.
The people involved in this project are listed below:
At the Dept Anatomy and Histology, University of Sydney:
Assoc Professor Bill Webster,
Dr John Pollak, Hon Research Associate
Ms Diana Oakes (enrolled PhD)
At the Dept of Biomedical Sciences, Cumberland College Campus,
University of Sydney:
Dr Patricia Brown-Woodman
Dr. Helen Ritchie
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