Experiences gained through the Environmental Classification System for Pharmaceuticals Andreas Woldegiorgis, Ph. D. Conference on Sustainable Development and Pharmaceuticals, Uppsala 10-11/11, 2009. Overview. Background The PEC/PNEC relationship PEC and human metabolism
Conference on Sustainable Development and Pharmaceuticals,
Uppsala 10-11/11, 2009
Overview System for Pharmaceuticals
The PEC/PNEC relationship
PEC and human metabolism
PEC and STP-removal
PNEC data in the fass.se system
The role of the system reviewer
A case study from the fass.se system
Frogs, fish and pharmaceuticals a troubling brew System for Pharmaceuticals
Prozac, other drugs detected in streams and their inhabitants
By Marsha Walton CNNFriday, November 14, 2003 Posted: 9:14 AM EST (1414 GMT)
Two tapdpoles after 57 days of development in the lab. The one on the right, which has yet to sprout limbs, was exposed to fluoxetine, also known as Prozac.
(CNN) --A number of aquatic and amphibian species are being exposed to small amounts of everything from Prozac to perfume to birth control pills that make their way into U.S. rivers and streams.
And scientists now have evidence that this "cocktail" of pharmaceuticals, in high enough quantities, can lead to problems that may be serious enough to prevent wildlife from reproducing. It's not yet clear how the buildup over time could affect the species.
In 2002, 80 percent of streams sampled by the U.S. Geological Survey showed evidence of drugs, hormones, steroids and personal care products such as soaps and perfumes. The U.S.G.S. tested 139 rivers in 30 states.
Effects in the environment (and in the media..)
Or; System for Pharmaceuticals
Approximatively 550 peer-reviewed articles published on the issue
"pharmaceuticals in the environment" between 1991-2008.
...~ 65 % published rather recently, 2006 and onwards...
Thus; System for Pharmaceuticals
Any classification system of the environmental risks of
pharmaceuticals implemented 2005 must be considered as a
'living' system in which improvements and new
methodology can easily be implemented.
Predicted No Effect Concentration System for Pharmaceuticals
Predicted Environmental ConcentrationBasic principles of Environmental Risk Assessment (ERA)
Predicted concentration of the substance in the environment is related to the toxicity of the substance towards organisms living in the environment.
PEC / PNEC
Estimation of the Surface water PEC in µg/l System for Pharmaceuticals
"A" ; sold amount annually [kg]
Or, in a simplified way...
Consumption in kg
Nr of liters of water that the Swedish population uses annually
Thus, the system requires an exact estimation of the sold
amount of any given pharmaceutical!!!
Refinement (reduction...) of the PEC-value possible; System for Pharmaceuticals
Metabolism in the human body;
from the fass.se-guideline;"...Identification of the metabolites, including specification of
conjugates, which may de-conjugate to the parent compound in a sewage treatment plant.
...Pharmacological activity (or eco-toxicity, if known) of the metabolites compared with the
Fate of the pharmaceutical upon passage of the waste water treatment plant;
If no eco-toxicological data on the main metabolite can
be found, PEC should NOT be reduced based on metabolism!
PEC-reduction should be based on either the SimpleTreat-model, OECD 303-experiments,
or extensive measurements!
(Strujis J, 1996, TGD (Ref. 4), Part II, Chapter 3, Appendix II)
"R" = f(OECD301/302-data, logH and logKow)
The PNEC data in the fass.se system; System for Pharmaceuticals
Data should reflect tests performed on 3 trophic levels; algae, crustaceans and fish.
In order to ensure acceptable safety margin when going from lab tests on x individuals
to an entire population in the environment; a safety factor (AF) is applied. Thus;
If only short term acute data available then AF = 1000
If chronic long-term data are available from all 3 trophic levels, then AF = 10
PNEC data in the fass.se-system are mostly; System for Pharmaceuticals
1) provided by the companies from standard tests performed during the ERA process.
2) reflecting acute and short-term testing conditions (thus seldom chronic data)
3) mostly data not taking the specific mode-of-action of the pharmaceutical into
4) never 'calculated' or estimated based on structure-activity relationships (SARs/QSARs)
Consequently, PNEC data currently used leave room for improvements when more
appropriate data becomes available!!
(along with data on biodegradation and bioaccumulation).
The transparency (and availability) renders the system attractive to anybody interested;
(authorities, stake holders, other companies).
detected in all
detected in any of
the 28 effluents
IVL Screening data on digested sludge System for Pharmaceuticals
Detected in all digested
1.6 – 310 ng/g DWFate of Sertraline ?
Citalopram easily reaches the
the archipelago through
the effluent discharge in Saltsjön
sludge is transported 2000 km
to Lapponia where it is used as
Which is the more favourable choice for the environment?