Abstract
The Department of Homeland Security (DHS) lists over 300 “chemicals of concern.” These chemicals
relate to the Chemical Facilities Anti-Terrorism Standard (CFATS). The chemicals on this list were provided by
the U.S. Environmental Protection Agency (EPA), the international Chemical Weapons Convention, and the
Department of Transportation (DOT). A large number of the chemicals on the DHS list are strong oxidizers.
Since the eye is exposed and vulnerable to irreversible damage by strong oxidizers, which may permanently
damage the eye or even cause loss of vision, developing a countermeasure for accidental or malicious ocular
exposure to strong oxidizers is a high priority. The goal of the proposed research is to develop an eye wash
solution containing antioxidants to mitigate damage to the eye caused by strongly oxidative chemical threats.
To preliminarily test the hypothesis that damage induced by oxidative chemicals can be mitigated by a higher
than physiological concentration of a tear antioxidant, we added a tear antioxidant to a 30-minute eye wash
protocol as a treatment for ocular exposure to the strong oxidant chemical hypochlorite. Exposure of the eye to
8.25% hypochlorite followed by washing with saline alone resulted in significant loss of viable cells. However,
when an antioxidant was added to the saline wash solution at 10× its physiological human tear concentration,
eye damage was markedly reduced.
The specific aims will answer the following questions: What is the optimal eye wash protocol and
antioxidant concentration that will mitigate damage? Can preliminary results be further supported and the
mechanism(s) of action better understood by the analysis of additional biochemical measurements including
cell death and lipid and protein oxidation? Is the loss of viability induced by at least three other strong oxidant
chemicals on the Department of Homeland Security (DHS)’s list of chemicals of concern also mitigated by
washing with an antioxidant formulation? To answer these questions, the specific aims will rigorously test the
hypothesis that postexposure washing with antioxidants can reduce loss of viability to the cornea. We will also
test the hypothesis that the antioxidant directly decreases oxidation induced by oxidative corrosives before
they damage a large percentage of the stroma using representative lipid and protein oxidation assays; if there
is no clear relationship between the antioxidant and a reduction in lipid and protein oxidation, alternative cell-
based studies will be used to evaluate the effects of the antioxidant on cell growth and differentiation in this
context. We will also test the hypothesis that the mitigation of damage by the antioxidant is generalizable to
other oxidants.
We anticipate that the following outcomes will be achieved: 1) The unequivocal demonstration of less loss of
viability of the cornea from levels that corrode to levels that are fully reversible within 21 days by washing with
a solution containing antioxidants after hypochlorite-induced damage. 2) Confirmation that the mechanism of
action responsible for the reduced loss of viability is the inactivation of strong oxidants as they corrode ocular
tissue with time, or, as determined by alternative strategies, that washing with antioxidants improves viability
after strong oxidant exposure. 3) Demonstration that an antioxidant eye wash countermeasure can be used for
other strong oxidants on the DHS list of chemicals of concern. These outcomes may establish that tear-related
antioxidants at high concentrations can reduce eye damage caused by strong oxidizing chemicals on the DHS
list of chemicals of concern.
By demonstrating that high concentrations of naturally occurring tear antioxidants can mitigate eye damage,
the proposed exploratory research will increase our understanding of the potential use of antioxidants to
reduce eye damage after accidental exposure to or attack with strong oxidant chemicals.
1