pharmaceuticals as environmental pollutants – current situation and ongoing research christina...
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Pharmaceuticals as environmental pollutants – current situation and ongoing research Christina Rudén Royal Institute of Technology (KTH) [email protected]. General introduction Ongoing research Needs. Pharmaceuticals in the environment. - PowerPoint PPT PresentationTRANSCRIPT
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
Veterinary Drugs
Large and increasing use of pharmaceutials
• General: Large and increasing usage (high volume substances)
Human PharmaceuticalsVia sewage treatment plants to the aquatic environment
From treated animals to the terrestrial environment
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 RudénEvolutionary 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 RudénEvolutionary 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.
Mouse
Christina RudénEvolutionary 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.
Fish Frog
Christina RudénEvolutionary 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.
Water fleaFlyWorm
Christina RudénEvolutionary 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.
BacteriaPlantsAmoebaYeast
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 TysklindDepartment of Chemistry, Umeå University, SwedenBjörn Arvidsson Swedish Defence Research AgencyJari 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
Concentration of pharmaceuticals in fish plasma
Human therapeutic blood plasma conc
Effluent water from 3 waste water treatment plants
Exposure of fish
Concentration of pharmaceuticals in fish plasma
Human therapeutic blood plasma conc
= Effect Ratio
The lower the effect ratio the higher probability of an effect
Results BCF-studies
0.01 0.1 1 10 100 1000 10000
Beclometasone
Levonorgestrel
Haloperidol
Risperidone
Cilazapril
Verapamil
Ketoprofen
Diltiazem
Meclozine
Memantine
Sertraline
Diclofenac
Tramadol
Orphenadrine
Ibuprofen
Oxazepam
Naproxen
Carbamazepine
Safety factor
Effect ratio
0.01 0.1 1 10 100 1000 10000
Beclometasone
Levonorgestrel
Risperidone
Cilazapril
Verapamil
Ketoprofen
Diltiazem
Meclozine
Memantine
Sertraline
Diclofenac
Tramadol
Orphenadrine
Ibuprofen
Oxazepam
Naproxen
Carbamazepine
Safety factor
Effect ratio
Christina Rudén
• 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?
Needs
The Stockholm Water project
Main results:• 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)
“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
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 ofenergy and resources
• For Sweden, the additional cost for extratreatment 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]
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Thank you!