Abstracts (PDF file, 1.8MB) - Society for Risk Analysis

SRA 2013 Annual Meeting Abstracts
P.154 Wang, A*; Filer, D; Shah, I; Kleinstreuer, N; Berg, E;
Mosher, S; Rotroff, D; Marinakos, S; El-Badawy, A; Houck, K;
AW, DF, IS, DM, KH: US EPA. NK: ILS. EB: BioSeek Inc. DR:
NC State Univ. SM: Duke Univ.; wang.amy@epa.gov
Comparing bioactivity profiles of diverse nanomaterials
based on high-throughput screening (HTS) in ToxCast
Most of the over 2800 nanomaterials (NMs) in commerce lack
hazard data. Efficient NM testing requires suitable toxicity
tests for prioritization of NMs to be tested. The EPA’s ToxCast
program is evaluating HTS assays to prioritize NMs for
targeted testing. Au, Ag, CeO2, Cu(O2), TiO2, SiO2, and ZnO
nanoparticles, their ion and micro counterparts, carbon
nanotubes (CNTs), asbestos, and pesticides containing
nano-Cu(O) - total 62 samples - were screened at 6 -10
concentrations each for 262 bioactivity/toxicity endpoints in
cells and zebrafish embryos. Cellular stress and immune
response pathways were primarily affected. NM’s core
chemical composition was more important than size for
bioactivity. NMs had similar profiles as their ion counterparts,
suggesting ion shedding was a key factor in mechanism of
action. Ag, Cu, and Zn (nano, ion) were more cytotoxic and
active in more assays than others. While 3 asbestos samples
had similar immune response profiles, 6 CNTs had profiles
distinctive from asbestos. Potential bioactivity targets that were
not directly measured were suggested by reference profiles
similar to our data, e.g. similar profiles of a microtubule
stabilizer interfering with mitosis and our nano-TiO2. Dividing
endpoints into cytotoxicity and various function domains, we
developed a ToxPi-based ranking approach for in vitro
bioactivity. Samples active in more domains at lower
concentrations were ranked higher than samples active in
fewer domains and/or at higher concentrations. Ag, Cu, and Zn
samples were ranked as high in vitro bioactivity; asbestos, Au,
CeO2, some CNTs, and some TiO2 samples were ranked as low.
Recognizing our assays using submerged cells may have limited
sensitivity to inhalation effects, we are exploring prioritization
approaches for various purposes. We demonstrated that HTS
assays can identify affected cellular pathways, predict targets,
and may be useful for ranking NMs for specific purposes. This
abstract does not reflect EPA policy.
T4-F.5 Way, D.H.P.*; Bouder, F.; King's College London;
Maastricht University; dominic.way@kcl.ac.uk
Transparency and risk communication in the european
pharmaceutical sector
In recent years, European pharmaceutical regulators have
increasingly committed to a range of ‘transparency’ initiatives
including releasing safety-related documents and disclosing
committee-meeting minutes. Yet, the regulators – including the
European Medicines Agency (EMA) – continue to be criticised
for lacking ‘transparency’. The debate has now greatly
intensified with many calling for further measures (e.g. journal
editors, politicians, NGOs). In response, the regulators have
overwhelmingly focused on disclosure and access to raw data
or what has been coined “fishbowl transparency”, with
proposals to proactively release clinical trial reports in 2014.
However, transparency is not problem free and can have both
unintended and counterintuitive outcomes. Some have argued
that "fishbowl" rather than reasoned transparency can also lead
to raising public expectations to unrealistic levels. In
conjunction, we have expressed concerns that the regulators
have not tested their strategies for trust and risk
communication leading to a dearth of evidence to inform the
debate. In seeking to inject much needed evidence into this
highly understudied area, this paper presents the results of a
large European survey (N = 5,648) that compares six European
countries. Specifically, the paper conveys results on how
European citizens and patients are likely to react to the
regulators’ “fishbowl" transparency measures including clear
(and surprising) national-level variations
P.81 Webler, TW*; Tuler, SP; Social and Environmental
Research Institute; twebler@seri-us.org
Progress in new tools for participatory vulnerability
analysis to climate stressors
City officials want to better understand how their communities
are vulnerable to climate change. We used social science of
hazard management and deliberative learning to develop a
method for participatory vulnerability assessment that
organizes expert and local knowledge about climate hazards.
Facilitated deliberation promotes learning and is favored by
participants as a “natural” way of carrying out self-governance.
We report here on the results of employing this method in the
City of Boston.
M2-B.3 Weed, DL; DLW Consulting Services, LLC;
douglaslweed@aol.com
On the utility of criteria-based methods of causal
inference
Criteria-based methods have been discussed in the
epidemiologic literature since the late 1950’s and continue to
be used today, with recent extension into the assessment of
toxicologic evidence. This paper will discuss the theoretical and
practical utility of criteria-based methods of causal inference,
including but not limited to Hill’s criteria (i.e. strength,
consistency, dose-response, specificity, temporality, biological
plausibility, experimentation, coherence, and analogy).
Included will be a discussion of how these methods fit within a
broader methodology for assessing causation. Assessing the
utility of criteria-based methods involves: (1) a historical
assessment of the use of these criteria, (2) the use of these
criteria in organizational settings and by toxicology, and (3) the
relationship between these criteria and the scientific method.
Criteria for causation have been continuously used in scientific
practice for 50 years. These criteria represent key concerns of
the scientific method. Examples follow. The criterion of
consistency reflects the scientific principles of replicability and
testability. The criterion of strength (of association) reflects the
basic scientific concept of critically testing alternative
explanations. Experimentation reflects the need to test and
control for alternative hypotheses. Temporality is a key feature
of any causal hypothesis. Specificity reflects the need to test
the hypothesis of interest and not some different hypothesis.
Biological plausibility incorporates biological explanations with
those explanations at the level of human populations by
examining the extent to which the basic causal hypothesis has
been tested in cellular systems and in animal models. Dose
response reflects a basic toxicological principle: the greater the
exposure to a causal agent, the greater the effect. The criteria
and the general scientific method are not only compatible but
inseparable. Challenges to the use of the criteria will
December 8-11, 2013 - Baltimore, MD