The Toxicologist - Society of Toxicology

654 TCDD ADSORBED ONTO NATURAL AND SYNTHETIC
SILICA SUPPRESSES HUMORAL IMMUNITY IN MICE.
N. Kovalova 1, 2 , R. Crawford 2 , B. Kaplan 2 , S. Kim 3 , S. Boyd 3 , B. Teppen 3 , C.
Johnston 5 , T. Pinnavaia 4 and N. Kaminski 1, 2 . 1 Pharmacology & Toxicology,
Michigan State University, East Lansing, MI, 2 Center for Integrative Toxicology,
Michigan State University, East Lansing, MI, 3 Crop & Soil Science, Michigan State
University, East Lansing, MI, 4 Chemistry, Michigan State University, East Lansing,
MI and 5 Soil Chemistry & Mineralogy, Purdue University, W. Lafayette, IN.
2,3,7,8-tetracholordibenzo-p-dioxin (TCDD) is a well-characterized persistent environmental
contaminant that exhibits suppression of primary humoral immune
response in vivo and in vitro. Literature provides some evidence on mechanisms by
which TCDD delivered in corn oil impairs IgM production by B cells. However, it
is not well known if TCDD exposure under environmentally relevant conditions
can lead to immunotoxicity. In present study, mice were treated with TCDD adsorbed
on to synthetic amorphous silica with a mesocellular foam structure and on
to natural silica. The surface area (385 m2g-1), pore volume (2.0 cm3g-1), and average
window size (15 nm) of the synthetic silica allowed for the adsorption of
TCDD as isolated single molecules on the pore walls. On day 3 of TCDD treatment
mice were sensitized with sheep erythrocytes to initiate a humoral immune
response. We found that TCDD adsorbed on to synthetic and natural silica is
bioavailable as measured by the efficacy in suppression of anti-sRBC IgM antibody
forming cell (AFC) response. Interestingly, TCDD produced similar level of suppression
of anti-sRBC IgM AFC response regardless of the vehicle used to deliver
TCDD. These results suggest that TCDD immobilized on various silicate phases in
soils and sediments is bioavailable and able to cause immunotoxicity. (Supported in
part by NIH P42 ES004911).
655 TITANIUM DIOXIDE NANOPARTICLES: LACK OF
IMMUNOSUPRESSIVE AND CONTACT
HYPERSENSITIVITY EFFECTS IN FEMALE MICE.
W. Auttachoat 1 , C. E. McLoughlin 2 , M. J. Smith 1 and K. L. White 1 .
1 Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA and
2 Biomedical Engineering, Virginia Commonwealth University, Richmond, VA.
Titanium dioxide is a white pigment widely used in products such as paints, food,
and cosmetics. US FDA regulates its use as a food color additive at levels not to exceed
1% by weight. Titanium dioxide nanoparticles (NTI) have been reported to
induce liver injury and to decrease interleukin-2 production following oral exposure
for 30 days in mice. However, it remains unclear whether exposure to NTI (<
25 nm diameter) results in immunosuppressive effects (in B6C3F1 mice) or induces
a contact hypersensitivity response (in BALB/c mice). In these studies, immunosuppression
was evaluated using the Plaque Assay (TDAR) to sheep erythrocytes
(sRBC) and the Delayed-Type Hypersensitivity Assay (DTH). Contact
hypersensitivity was evaluated using the Local Lymph Node Assay (LLNA),
Irritancy Response Assay (IRR), and the Mouse Ear Swelling Test (MEST). After
28 days of oral gavage, NTI (1.25-250 mg/kg in 0.5% methylcellulose) produced
no significant effects on the TDAR or on the DTH response to C. albicans.
Furthermore, there were no effects on the weights of the major immune organs
(spleen, thymus). Liver, kidney, and lung weights were also unaffected. Following
dermal exposure for 3 days, NTI (2.5% to 10% w/v in 4:1 acetone olive oil) did
not affect auricular lymph node cell proliferation (LLNA), nor was an irritancy response
produced (IRR), when compared to the vehicle control. Dermal sensitization
(2.5-10%) on the back and subsequent challenge (10%) on the right ear with
NTI produced no significant effects on percent ear swelling when compared the vehicle
irritancy control group in the MEST. In summary, these results demonstrate
that oral exposure to NTI at doses up to 250 mg/kg was not immunosuppressive in
B6C3F1 mice in two functional holistic assays (TDAR, DTH). Furthermore, dermal
exposure to NTI (up to 10% w/v) did not induce contact hypersensitivity in
BALB/c mice. Supported in part by NIEHS Contract ES 05454.
656 ACTIVATED CYTOTOXIC AND HELPER T-CELLS ARE
REDUCED IN C57BL6 MICE EXPOSED TO
TUNGSTATE IN A ONE-GENERATION EXPOSURE.
A. R. Osterburg 1 , C. T. Robinson 2 , V. P. Mokashi 1 , M. G. Stockelman 1 and G.
F. Babcock 2 . 1 Naval Medical Research Unit - Dayton, Wright-Patterson AFB, OH
and 2 Shriners Hospitals for Children and the University of Cincinnati, Cincinnati,
OH. Sponsor: K. Mumy.
Tungstate has been identified as a ground water contaminant at military firing
ranges and can be absorbed by ingestion. In this study, C57BL6 mice were exposed
to sodium tungstate (Na2WO4 2H2O) in their drinking water in a one-generation
model. Previous work in the laboratory demonstrated a reduction in activated cytotoxic
and helper T-cells after 28 and 90-day exposures. Drinking water included
weight adjusted tungstate concentrations of 0, 2, 62.5, 125, and 200 mg/kg/day.
Twenty-four hours prior to euthanasia, mice were given (i.p.) saline, LPS (5
mg/kg), or SEB (20 μg) for controls and to stimulate innate and adaptive immune
responses, respectively. After euthanasia splenocytes, blood, bone marrow and thymus
were collected and stained with lymphocyte and/or myeloid immunophenotyping
panels and analyzed by flow cytometry. In the one-generational exposure, we
observed statistically significant reductions in the quantities of cytotoxic T-cells
(CD3+CD8+CD71+) and helper T-cells (CD3+CD4+CD71+) in SEB treated
mice. Cytotoxic T-cells were 7.98% +/- 0.49 SE and 6.33% +/- 0.49 SE for P and
F1 mice in 0 mg/kg/d tungstate vs. 1.58% +/- 0.23 SE and 2.52% +/- 0.25 SE in
the 200 mg/kg/d of tungstate (P