The Toxicologist - Society of Toxicology

Novel alternative methods for assessing DNT of chemicals and drugs are therefore
needed. A short term zebrafish embryo assay might give an ethical acceptable, and
cost-efficient test for numerous compounds.
We developed 2 complementary assays with zebrafish embryo and larva as models
to evaluate the developmental neurotoxic potential of chemicals. In these assays locomotor
activity was used as an endpoint; (i) spontaneous tail coilings of embryos
at 24-26 hours post fertilization (hpf) and (ii) swimming behavior of larvae at 120
and 144 hpf. Embryos were exposed within 2 hpf to a compound at a concentration
level which did not induce morphological abnormalities (Selderslaghs et al.,
2009, Repr. Tox.). By means of video footage and tracking software, we determined
frequency and total duration of spontaneous tail coilings in embryos (egg stage) and
analyzed swimming behavior of hatched larvae based on parameters such as distance
moved, velocity and turn angle. Results from controls and exposed embryos
or larvae were compared and based on differences in distribution of data obtained,
effect percentages were determined for each concentration of the compound tested.
To asses whether the proposed assays based on locomotor activity were able to distinguish
developmental neurotoxicants from negative compounds, we selected 6
positive (chlorpyrifos, chlorpromazine, methylmercury, methimazole, propyl
thiouracil, iminodipropionitrile) and 4 negative compounds (saccharin, D-glucose,
acetaminophen, omeprazole). Analysis of the results of this intralaboratory validation
study, revealed that these new methods combined, have a high predictive capacity
and may potentially be integrated in a testing battery to screen for DNT, and
anticipate to 3R.
1413 IMPACT OF TUNGSTEN AND TUNGSTEN ALLOYS ON
HEALTH RISK.
P. G. Gunasekar 1 and M. J. Hooth 2 . 1 NHRC Det Environmental Health Effects
Laboratory, Wright-Patterson Air Force Base, Dayton, OH and 2 Toxicology Branch,
National Toxicology Program, National Institute of Environmental Health Science,
NIH, Research Triangle Park, NC.
Debate of the potential human health effects of tungsten (W) is fostered by widespread
exposure to naturally occurring W in air, soil, water, and the diet and anthropogenic
sources including the use of tungsten alloy (WA) in military munitions.
There is particular concern about the exposure of military personnel to
retained W-based munitions fragments. The cellular and molecular mechanisms of
systemic W toxicity and the role of W speciation in W-induced toxicity remain
poorly defined. Intensive research on the characterization of potential adverse
health effects associated with tungsten exposure is underway and employs multiple
routes of exposure including oral, inhalation and implantation. Other recent studies
have characterized W transport mechanisms, pharmacokinetic parameters, and
biochemical and pathological indices in vitro and in vivo. These efforts have identified
new biomarkers of exposure and effect as well as new opportunities for therapeutic
intervention or management of potential health hazards. This session will
review current research programs as well as describe the recent studies examining
the toxicity and carcinogenicity of embedded tungsten and heavy metal tungsten
alloy pellets and refined corrosion assessments to define the degradation rate of the
pellets. Our panel of experts will discuss the absorption/transport, distribution and
elimination of tungsten and effects on the nervous system and immune system
with particular emphasis on the mechanisms through which W may produce toxic
effects.
1414 THE 2009 TENNESSEE FLY ASH SPILL: AN
ENVIRONMENTAL EMERGENCY CASE STUDY.
M. E. Ottlinger. Office of Emergency Management, U.S. Environmental Protection
Agency, Erlanger, KY.
On December 22, 2008, at approximately 1:00 AM, a retaining wall supporting a
surface impoundment of fly ash sludge at the Kingston Fossil Plant in Harriman,
Tennessee, breached releasing an estimated 5.4 million cubic yards of material into
the Emory and Clinch Rivers and surrounding areas. The release extended over approximately
300 acres of land outside of the containment site. A wave of ash and
water destroyed homes, disrupted electrical and natural gas lines, covered roads and
rail tracks, and necessitated the evacuation of nearby residents. Responders at the
scene pursued a variety of activities intended to assess the extent of both the release
and the potential hazard posed by the event and to contain the spread of any hazardous
materials released into the environment. The roles, responsibilities, and interactions
of various local, state, and federal partners present at the scene had a substantial
impact on response activities. This included oversight of the development
and initiation of a large program of environmental sampling of the air, soil, and
water followed by analysis of the resulting data. The Tennessee fly ash spill is representative
of other environmental emergencies, and is therefore an excellent case
study in which to provide a framework for discussions concerning the role of toxicology
in protecting environmental and human health in affected communities,
and in determining the appropriate roles and actions of the various regulators at the
scene. Information about the formation and toxicological hazards associated with
fly ash will be presented, along with a discussion of the U.S. EPA incident command
structure, regulatory issues, sampling strategies and limitations, as well as integration
of all of this information into effective public health practice following
such emergencies.
1415 CAREER ALTERNATIVES IN TOXICOLOGY: LESSONS
LEARNED.
J. Raucy 1 ,T. D. Landry 2 ,J.E. Trosko 3 and H. K. Hamadeh 4 . 1 Puracyp, Inc.,
Carlsbad, CA, 2 Tecnico Unidad de Gestion Ambiental, Tlaxcala, Tlaxcala, Mexico,
3
Department Pediatrics/Human Development, Michigan State University, East Lansing,
MI and 4 Comparative Biology and Safety Sciences, Amgen, Thousand Oaks, CA.
For individuals who desire to take a career break or those set to retire, many options
are available. There are many avenues to explore including those that involve technical
opportunities for toxicologists and environmental scientists. Of the many opportunities
to explore, the Peace Corps and U.N. volunteer programs offer a myriad
of opportunities for environmental scientists wishing to practice their trade
abroad. In addition to these two examples, other alternatives will be discussed including
those available in academia, which provides its own set of unique experiences.
For example, just how does one go about leaving a career in cancer research
and epigenetic toxicology to become an administrator at the Radiation Effects
Research Foundation in Hiroshima, Japan? There are many positive sides to such a
decision, including work on a historic project in a foreign country and interactions
with scientists who may benefit from your insight; however, there can be disadvantages
as well. Experienced panel members will highlight the “price-paid” for such
decisions. What about options other than academic research, such as toxicologists
with innovative ideas who wish to capitalize on their talents and drive by starting a
biotechnology company? Our panel of experts will provide insight and tips on the
challenges involved in bringing an idea for a commercial product to the market
place. This specific discussion will note the distinct advantages and disadvantages of
embarking on a career change from academia to establishing a biotechnology company.
This last discussion will highlight the specific and unique challenges of starting
a company, including acquisition of intellectual property rights, obtaining
funding, and marketing of products. This session should be of interest to anyone
looking to explore career alternatives off the beaten path.
1416 GENDER DIVERGENT XENOBIOTIC RESPONSES.
K. Gabrielson 3 , D. Fairweather 3 , C. Klaassen 1 and M. Gochfeld 2 . 1 University of
Kansas Medical Center, Kansas City, KS, 2 Robert Wood Johnson Medical School,
Piscataway, NJ and 3 The Johns Hopkins University, Baltimore, MD.
Differences in exposure, anatomy, physiology, biochemistry, and behavior between
males and females dramatically affect the biological response; yet gender differences
have not received adequate attention in toxicology. This session will highlight cutting
edge discoveries within gender divergent biology that have a major impact on
the toxicological response. Both mechanisms and relevant examples of gender-dependent
toxicities will be provided. To fully understand these issues, an overview
will be provided that will allow participants to review recent findings on the divergence
of gene expression between males and females in response to toxic insults influenced
by gender specific drug elimination and cellular efflux. Elegant studies
that demonstrate sex and growth hormonal dependence reveal the importance of
these factors in toxic and therapeutic responses. Further exploration will allow us to
focus on the mechanisms behind gender differences in cation transporter expression
in the GI tract and kidney. Interplay between gender and the underlying nutritional
status of zinc, iron, and calcium, as well as the influence of transporter expression
and toxicity. Essential element deficiencies result in gender specific up-regulation of
transporters, thereby facilitating the transport of toxic metals such as lead and cadmium.
Adequate focus will be provided on the immune system and how steroid
hormones influence immunomodulatory proteins of the toll-like receptor family.
These findings have relevance not only to the toxic response, but also to the pathogenesis
and severity of infectious disease influenced by concurrent toxin exposure.
Finally, gender divergence in gene expression in the heart during cancer therapy will
be addressed and how it affects signal transduction pathways controlling mitochondrial
function and protein translation differently in males and females which will
explain why females are better protected from the cardiotoxic effects of the
chemotherapy.
300 SOT 2010 ANNUAL MEETING