Pharmaceuticals and Personal Care Products in the Environment: What are the Key Research Questions? Alistair BA Boxall, Murray A Rudd, Bryan W Brooks,

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?

0

100

200

300

400

500

600

700

800

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Publication year

Num

ber

of p

ublic

atio

ns

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

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

10

100

1000

diclof

enac

ethin

ylestr

adiol

fluox

etine

ibupr

ofen

indom

etha

cin

keto

cona

zole

napr

oxen

oxyte

tracy

cline

prop

anolo

l

Effe

ct c

once

ntra

tion

(mg/

l)

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

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

Ranked order of 20 Important PPCP Questions:Means calculated with Hierarchical Bayesian (HB)95% CI now calculated with sample mean (vs HB)

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

How important are PPCPs relative to other chemicals and

non-chemical stressors in terms of biological impacts on the

natural environment?

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

What parameters should be used to prioritize PPCPs

for research on environmental and human health exposure

and effects?

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

How can pharmaceutical preclinical and clinical information be used to assess the potential for adverse environmental impacts of pharmaceuticals?

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

How can effects from long-term exposure to low concentrations of PPCP mixtures on non-target organisms be assessed?

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

What is the bioavailability of non-extractable residues of PPCPs?

-10.0

-5.0

0.0

5.0

10.0

15.0

20.0

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Statement

Mea

n Sc

ore

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

Contact details:

[email protected]

Pharmaceuticals Advisory Groupopen to everyone

www.setac.org