Download Sport Diver Lecture 4

Pharmaceuticals as environmental pollutants –
current situation and ongoing research
Christina Rudén
Royal Institute of Technology (KTH)
[email protected]
Christina
Rudén
Pharmaceuticals in the environment
1. General introduction
2. Ongoing research
3. Needs
Christina
Rudén
Large and increasing use of pharmaceutials
Human Pharmaceuticals
Via sewage treatment plants
to the aquatic environment
Veterinary Drugs
From treated animals
to the terrestrial environment
• General: Large and increasing
usage (high volume substances)
Christina
Rudén
Pharmaceuticals in the aquatic environment
• Active pharmaceutical ingredients are in general stabile
molecules; Many pass through sewage treatment plants
• Little less than 200 active pharmaceutical ingredients have
been identified in effluents from sewage treatment plants
and surface waters
• In general in very low concentrations: nano- to micrograms
per litre water
– (1 nanogram = 0,000 000 001 gram, 1 microgram = 0,000 001
gram)
Christina
Rudén
Pharmaceuticals are biologically active
• Pharmaceuticals are carefully designed to be safe
for the treated patient
• But: they are also designed to specifically and
potently interact with biological molecules i.e. have
an effect at low concentrations
• Each pharmaceutical has a more or less specific
drug target (mode-of-action)
Christina
Rudén
Pharmacology vs. toxicology
• A drug-target can be a biological receptor, e.g. an
enzyme, an ion channel, or a transport protein
• Pharmaceuticals are designed to interact with its
target and have as few other, side-effects as
possible
• Drug targets are well conserved through the
evolution of species, i.e. they occur in many
different species
Christina
Rudén
Evolutionary conservation of drug targets
Gunnarsson, L., Jauhiainen, A., Kristiansson, E., Nerman, O., Larsson, D.G.J. (2008). Evolutionary Conservation
of Human Drug Targets in Organisms used for Environmental Risk Assessments. Environmental Science and
Technology, 42 (15), 5807–5813.
Christina
Rudén
Evolutionary conservation of drug targets
Mouse
Gunnarsson, L., Jauhiainen, A., Kristiansson, E., Nerman, O., Larsson, D.G.J. (2008). Evolutionary Conservation
of Human Drug Targets in Organisms used for Environmental Risk Assessments. Environmental Science and
Technology, 42 (15), 5807–5813.
Christina
Rudén
Evolutionary conservation of drug targets
Fish
Frog
Gunnarsson, L., Jauhiainen, A., Kristiansson, E., Nerman, O., Larsson, D.G.J. (2008). Evolutionary Conservation
of Human Drug Targets in Organisms used for Environmental Risk Assessments. Environmental Science and
Technology, 42 (15), 5807–5813.
Christina
Rudén
Evolutionary conservation of drug targets
Water flea
Fly
Worm
Gunnarsson, L., Jauhiainen, A., Kristiansson, E., Nerman, O., Larsson, D.G.J. (2008). Evolutionary Conservation
of Human Drug Targets in Organisms used for Environmental Risk Assessments. Environmental Science and
Technology, 42 (15), 5807–5813.
Christina
Rudén
Evolutionary conservation of drug targets
Bacteria
Plants
Amoeba
Yeast
Gunnarsson, L., Jauhiainen, A., Kristiansson, E., Nerman, O., Larsson, D.G.J. (2008). Evolutionary Conservation
of Human Drug Targets in Organisms used for Environmental Risk Assessments. Environmental Science and
Technology, 42 (15), 5807–5813.
Christina
Rudén
Current legislation
• EMEA requires environmental risk
assessment for new registrations. The
Technical Guidelines are from 2006
• Based on data from standardized toxicity
tests developed to identify unspecific
toxicity (Industrial chemicals / effects on
survival and reproduction)
Christina
Rudén
Pharmacology and ”toxicity”
− Example:
• Pharmaceuticals designed to treat depression
will affect the central nervous system (uptake of
signal substances in nerve synapses)
• The pharmaceutical can affect the fish nervous
system
• Altered behavior caused by antidepressants has
been observed in laboratory studies
• Altered behavior will reduce survival in the
environment
• The regulatory standard tests will not cover
such an effect
Christina
Rudén
We need tests that cover pharmacological effects
− Pharmaceuticals that affect:
• The nervous system – behavioral tests (fish)
• Metabolising enzymes – enzyme induction assays (fish)
• Estrogenic effects -- vitellogenin (fish)
• Androgenic effects – Colour change and development
(Guppy)
• No regulatory standards!
Christina
Rudén
Environmental Risk Assessment
•
Comparison of
(1) Water concentrations that is expected not to affect
organisms, based on laboratory experiments (Predicted No
Effect Concentration; PNEC)
(2) Water concentrations predicted (or measured) in the
environment (Predicted Environmental Concentration; PEC)
PEC/PNEC is a risk ratio (if >1 then the exposure is of concern )
Bioconcentration of 18
human pharmaceuticals into
blood plasma of fish
exposed to treated sewage
effluents
Jerker Fick, Richard H. Lindberg, Mats Tysklind
Department of Chemistry, Umeå University, Sweden
Björn Arvidsson
Swedish Defence Research Agency
Jari Parkkonen and D. G. Joakim Larsson
University of Gothenburg
• Three Swedish Sewage Treatment plants
• Juvenile fish (Rainbow trout)
• 2 Weeks exposure to 100% treated effluent
Effluent water from
3 waste water
treatment plants
Exposure of fish
Effluent water from
3 waste water
treatment plants
Exposure of fish
Concentration of
pharmaceuticals in
fish plasma
Effluent water from
3 waste water
treatment plants
Exposure of fish
Human therapeutic
blood plasma conc
Concentration of
pharmaceuticals in
fish plasma
Effluent water from
3 waste water
treatment plants
Exposure of fish
Human therapeutic
blood plasma conc
Concentration of
pharmaceuticals in
fish plasma
= Effect Ratio
The lower the effect ratio the higher probability of an effect
Results BCF-studies
Beclometasone
Levonorgestrel
Haloperidol
Risperidone
Cilazapril
Verapamil
Ketoprofen
Safety factor
Diltiazem
Meclozine
Memantine
Sertraline
Diclofenac
Tramadol
Orphenadrine
Ibuprofen
Oxazepam
Naproxen
Carbamazepine
0.01
0.1
1
10
Effect ratio
100
1000
10000
Christina
Rudén
Needs
• More research about exposures and effects
• More relevant test methods (Standardisation? Regulatory
acceptance?)
• Improved European legislation
• Waste water treatment that removes chemicals
• Other actions towards (up-stream) risk management?
The Stockholm Water project
Main results:
“Pharmaceuticals occurrence in the water
environment,
preventive measures,
and possible treatment methods”
A four-year project funded by the
City of Stockholm, run by Stockholm
Water Company
• Modern operating WWTPs do not remove all pharmaceuticals
(APIs)
• Persistent and water soluble APIs are present in the receiving
waters of the Stockholm WWTP effluents
• 13 of 82 APIs are found also in drinking water, however at low
concentrations (~1 ng/L)
The Stockholm Water project
• Sludge from WWTPs contains low levels of
some APIs
• Through upstream source control, a minor
part of the APIs can be prevented from
reaching the sewers
• Additional treatment with low dose ozone
or activated carbon reduces the APIs in
waste water without causing negative
effects on the aquatic environment
• Membrane methods such as reversed
osmosis also work well but at higher energy costs
• Biological treatment or UV/hydrogen peroxide will not be
sufficient
The Stockholm Water project
• The introduction of full scale
complementary treatment must be
weighed against higher consumption of
energy and resources
• For Sweden, the additional cost for extra
treatment would amount to € 20 - € 150
per person and year
• The techniques do not have any effect
on the WWTP sludge quality
• Await research results on aquatic effects
before a decision is taken to add new treatment to
WWTPs!
For more information: [email protected]
Thank you!
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