pharmaceuticals and personal care products in the environment: what are the key research questions?...
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Pharmaceuticals and Personal Care Products in the Environment: What are the Key Research Questions?
Alistair BA Boxall, Murray A Rudd, Bryan W Brooks, Daniel J Caldwell, Kyungho Choi,
Silke Hickmann, Elizabeth Innes, Kim Ostapyk, Jane P Staveley, Tim Verslycke
Why a prioritisation exercise?
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Key Questions Approach
Horizon scanning method
Systematic way to identify major research and policy directions
Previous exercises on ecology, conservation, biodiversity and agriculture
Int. J. Agric. Sust. 8(4): 2010
20 Question Exercise
Run by the SETAC Pharmaceuticals Advisory Group (PAG)
Effects and risks of PPCPs
Global exercise
Approach
Web-based survey
Expert workshop (April 2011)
Out of scope: analysis, occurrence, treatment etc
Future dissemination to policy makers and research funders
An ‘ideal’ question
Address important gaps in knowledge
Be answerable through a realistic researchdesign
Have a factual answer that does notdepend on value judgments
Cover a spatial and temporal scale that could realistically be addressed by a research team($10M over 5 years)
Not be answerable by “it all depends” or “yes” or “no”
If related to impact and interventions, should contain a subject, an intervention, and a measurable outcome
Input
North America
Europe
AsiaAfrica
S. America
Australia/NZ
Others
Consultants
Government Scientists
Policy makers and regulators
Academia
NGOs
Industry
Geographical input Sector input
403 Questions
SETAC PAG 20 Question Exercise
General categories of questions
prioritisation of substances for assessment
routes of exposure
bioavailability and uptake
effects assessment
risk
antibiotic resistance
risk management
Prioritisation
What parameters should be used to prioritize PPCPs for research on environmental and human health exposure
and effects?
>4000 PPCPs
propertiesusagemode of actionside effectsQSAR predictionstherapeutic dose etc.
Compoundsof mostconcern
Routes of exposure
What are the environmental exposure pathways for organisms (including humans) to PPCPs in
the environment and are any of these missed in current risk assessment approaches?
?
Bioavailability and uptake
How can the uptake of ionizable PPCPs into aquatic and terrestrial organisms and through
food chains be assessed?
What is the bioavailability of non-extractable residues of PPCPs?
Effects characterisation
How can pharmaceutical preclinical and clinical information be used to assess the potential for adverse environmental impacts of pharmaceuticals?
What can be learned about the evolutionary conservation of PPCP targets across species and life stages in the context of potential adverse outcomes and effects?
How can non-standard ecotoxicological responses (e.g., biomarkers), observed for PPCPs, be translated to traditional ecologically important endpoints such as
survival, growth and reproduction of a species?
Non standard vs traditional endpoints
SETAC 20Q Exercise 2011
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diclof
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ethin
ylestr
adiol
fluox
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ibupr
ofen
indom
etha
cin
keto
cona
zole
napr
oxen
oxyte
tracy
cline
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standard acute
standard chronic
biochemical
cellular
physiological
behavioural
Effects characterisation
How can ecotoxicity test methods, which reflect the different modes of actions of active PPCPs, be developed and implemented in customized risk
assessment strategies?
How can effects from long-term exposure to low concentrations of PPCP mixtures on non-target
organisms be assessed?
Can non-animal testing methods be developed that will provide equivalent or better hazard data compared to
current in vivo methods?
Risk and relative risks
How can regions where PPCPs pose the greatest risk to environmental and human health, either now or in the
future, be identified?
How important are PPCPs relative to other chemicals and non-chemical stressors in terms of biological impacts on
the natural environment?
Do PPCPs pose a risk to wildlife such as mammals, birds, reptiles and amphibians?
Risk and relative risks
How can the environmental risks of metabolites and environmental transformation products of PPCPs be
assessed?
How can retrospective analyses be used to validate prospective risk assessments?
Antibiotic resistance
Does environmental exposure to PPCP residues result in the selection of antimicrobial resistant micro-organisms
and is this important in terms of human health outcomes?
How can the risks to human health, arising from antibiotic resistance selection by PPCPs in the natural
environment, be assessed?
Risk management
If a PPCP has an adverse environmental risk profile what can be done to manage and mitigate the risks?
What effluent treatment methods are effective in reducing the effects of PPCPs in the environment while at the
same time not increasing the toxicity of whole effluents?
How can the efficacy of risk management approaches be assessed?
Ranking of questions
Niagara workshop participants only
Web-based
Participants asked to
select ‘top ranked’ and ‘lowest ranked’ questions from sets of four to generate a top 20 list
identify challenges/barriers to addressing a question
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Ranked order of 20 Important PPCP Questions:Means calculated with Hierarchical Bayesian (HB)95% CI now calculated with sample mean (vs HB)
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How important are PPCPs relative to other chemicals and
non-chemical stressors in terms of biological impacts on the
natural environment?
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What parameters should be used to prioritize PPCPs
for research on environmental and human health exposure
and effects?
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How can pharmaceutical preclinical and clinical information be used to assess the potential for adverse environmental impacts of pharmaceuticals?
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How can effects from long-term exposure to low concentrations of PPCP mixtures on non-target organisms be assessed?
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What is the bioavailability of non-extractable residues of PPCPs?
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Can non-animal testing methods be developed that will provide
equivalent or better hazard data compared to current in vivo
methods?
Follow-up workshops: E. Asia; Australia/NZ
AsiaEurope
Global corporations
N. America
Latin America
Niagara workshop
Additional questions
Global
How can we better communicate risk issues to the public?
Local
What are the risks of natural medicines to the environment?
Should cultural considerations be incorporated into the environmental risk assessment process?
Next steps
Manuscript submitted to EHP - under revision
Dissemination to policy makers etc.
Pellston style workshops on selected questions
Web-based survey to rank questions
Local workshops
Special symposium at SETAC world meeting in Berlin
Acknowledgements
Astrazeneca
Americal Cleaning Institute
Health Canada
Janssen Pharmaceutical Companies of Johnson and Johnson
Workshop delegates and those who submitted questions