Supplementary material
S1 Toxicity values
Species
Group of species
Number of
investigations
Geometric
Mean [µg/l]
Standard deviation
[µg/l]
0.39
Literature
Amoxicillin
(Andreozzi et al.
2004)
(GlaxoSmithKline
2006)
(Laville et al.
2004)
(Laville et al.
2004)
(GlaxoSmithKline
2006)
(GlaxoSmithKline
2006)
(Brain et al. 2004)
1
Synechococcus leopoliensis
Algae, Moss, Fungi
2
1.17
2
Selenastrum capricornutum
Algae, Moss, Fungi
1
530000.00
3
primary
rainbow
trout
Fish
hepatocytes (PRTH) cell line
1
182700.00
4
PLHC-1 cell line
Fish
1
182700.00
5
Oncorhynchus mykiss
Fish
1
1000000.00
6
leopornis macrochirus
1
930000.00
7
Lemna gibba
5
1000.00
8
Daphnia magna
1
2300000.00
9
bacterial short-term genotoxicity
Bacteria
assay
1
20000.00
salmo trutta
Ceriodaphnia dubia
Fish
Crustaceans
1
1
84000.00
4.40
(fass.se 2014)
(fass.se 2014)
Selenastrum caprocornutum
Oncorhynchus mykiss
Daphnia magna
Algae, Moss, Fungi
Fish
Crustaceans
1
1
1
76000.00
100000.00
831000.00
(fass.se 2014)
(fass.se 2014)
(fass.se 2014)
Azithromycin
1
2
Cefuroxime
1
2
3
Ciprofloxacin
Fish; U.S. Exotic/Nuisance
Species
Flowers, Trees, Shrubs,
Ferns
Crustaceans
0.00
(GlaxoSmithKline
2006)
(Hartmann et al.
1998)
1
Selenastrum capricornutum
Algae, Moss, Fungi
1
3.00
2
Pseudomonas putida
Bacteria
2
4.90
4.38
3
Lemna gibba
15
402.87
326.41
2
3.43
2.23
Anabaena flos-aquae
Flowers, Trees, Shrubs,
Ferns
Algae, Moss, Fungi
Pseudomonas putida
Bacteria
1
12692.00
2
Pseudokirchneriella subcapitata
Algae, Moss, Fungi
5
11.54
3
Enterococcus faecalis
Bacteria
1
42.00
4
Daphnia magna
Crustaceans
2
4.70
5
6
Danio rerio
Fish
Activated sludge
Bacteria
bacterial short-term genotoxicity
Bacteria
assay
1
1
1000000
50.00
1
5.00
13
310.00
321.29
4
Clarithromycin
1
7
16.00
2.26
(Kummerer et al.
2000)
(Golet et al. 2002,
LUA 2002)
(Brain et al. 2004)
(Ebert et al. 2011)
(Alexy 2003)
(Harada et al.
2008, Suzuki et al.
2007, Yamashita
et al. 2006, Yang
et al. 2008)
(Alexy 2003)
(Yamashita et al.
2006)
(Isidori et al. 2005)
(Ghosh et al. 2009)
(Hartmann et al.
1998)
Doxycyclin
Lemna gibba
Flowers,
Ferns
1
Xenopus laevis
Amphibians
2
100000.00
0.00
2
Vibrio fischeri
Bacteria
3
1.99
1.35
3
Lemna gibba
Flowers,
Ferns
30
294.30
284.30
1
Trees,
Shrubs,
(Brain et al. 2004)
Levofloxacin
Roxithromycin
Trees,
Shrubs,
(Richards and Cole
2006)
(Backhaus and
Grimme 1999,
Backhaus et al.
2000)
(Brain et al. 2004)
1
Pseudokirchneriella subcapitata
2
Lemna gibba
Algae, Moss, Fungi
Flowers, Trees, Shrubs,
Ferns
2
25
15.00
5
1000
0.00
0.00
(Yang et al. 2008)
(Brain et al. 2004)
Sulfamethoxazole
1
Xenopus laevis
Amphibians
2
100000.00
2
stauropigiana Leopolensis
Algae, Moss, Fungi
1
5.90
3
Selenastrum capricornutum
Algae, Moss, Fungi
1
614.00
4
Pseudomonas putida
Bacteria
1
17393.00
5
Pseudokirchneriella subcapitata
Algae, Moss, Fungi
4
501.00
300.61
6
Lemna gibba
19
74.23
68.79
7
8
Hydra attenuata
Escherichia faecalis
Flowers, Trees,
Ferns
Invertebrates
bacteria
5
1
63000.00
153592.00
50695.17
9
Danio rerio
Fish
30
33848.57
182476.87
10
Cyclotella meneghiniana
Algae, Moss, Fungi
1
1250.00
11
Ceriodaphnia dubia
Crustaceans
1
250.00
12
Caenorhabditis elegans
Worms
14
1459.31
13
Brachionus calyciflorus
Invertebrates
1
25000.00
14
Trimethoprim
Activated sludge
Bacteria
1
50.00
1
Xenopus laevis
Amphibians
2
100000.00
Shrubs,
3703.08
0.00
(Richards and Cole
2006)
(Ferrari et al.
2004)
(Eguchi et al.
2004)
(Alexy 2003)
(Eguchi et al.
2004, Ferrari et al.
2004, Liu et al.
2011, Yang et al.
2008)
(Brain et al. 2004,
Brain et al. 2008)
(Quinn et al. 2008)
(Alexy 2003)
(Isidori et al. 2005,
Madureira et al.
2011)
(Ferrari et al.
2004)
(Ferrari et al.
2004)
(Yu et al. 2011)
(Ferrari et al.
2004)
(Ghosh et al. 2009)
(Richards and Cole
2006)
2
3
4
5
6
7
Synechococcus sp.
Synechococcus leopoliensis
Pseudokirchneriella subcapitata
Nostoc sp.
Microcystis wesenbergii
Microcystis aeruginosa
1
1
3
1
1
1
50000.00
13000.00
28375.00
3100.00
3100.00
100000.00
7
8500.00
19843.14
Hydra attenuata
Algae, Moss, Fungi
Algae, Moss, Fungi
Algae, Moss, Fungi
Algae, Moss, Fungi
Algae, Moss, Fungi
Algae, Moss, Fungi
Flowers, Trees, Shrubs,
Ferns
Invertebrates
8
Lemna gibba
9
5
100000.00
0.00
10
Daphnia magna
Crustaceans
6
13000.00
7668.12
11
Danio rerio
Fish
29
157.00
0.00
12
Brachydanio rerio
Fish
1
100000.00
13
14
Belebtschlamm
Anabaena variabilis
Bacteria
Algae, Moss, Fungi
1
1
50.00
3100.00
10160.18
(Ando et al. 2007)
(Ando et al. 2007)
(Yang et al. 2008)
(Ando et al. 2007)
(Ando et al. 2007)
(Ando et al. 2007)
(Brain et al. 2004)
(Quinn et al. 2008)
(Park and Choi
2008)
(Madureira et al.
2011)
(Halling-Sorensen
et al. 2000)
(Ghosh et al. 2009)
(Ando et al. 2007)
S2 Share of antibiotics in RI using the classical PNEC-approach
Risk index of the classical PNEC-approach (RIalgae)
S3 Conversion of formulas
Hill equation
E
equation from [Chèvre et al. 2006]
1
m
 Dm 

 1
 PNEC 
1 E
 Dm 

 
E
 PNEC 
m
 1 
 95 
  log  
log HC 5  log HC 50  
 5
 slope 
log HC 50  log HC 5  1 

 
slope 
 95 

log  
 5 
 Dm 
1 E 
m log 
  log 

 PNEC 
 E 
1 E 
log 

E 

m
 Dm 
log 

 PNEC 
 95 
log  
 5   slope
 HC 50 
log 

 HC 5 
for E = 0.05; Dm = HC50; PNEC = HC5; slope = m
S4 PNEC values (applied values are printed in bold-face type)
Amoxicillin
1
2
3
Azithromycin
Own data (assessment factor in
brackets) [µg/l]
Literature values (assessment factor
in brackets) [µg/l]
Literature
0.078 (10)
0.1 (100)
10 (n/a)
Own data
(Kummerer and Henninger 2003)
(Turkdogan and Yetilmezsoy 2009)
0.088 (50)
-
0.09 (n/a)
0.15 (100)
Own data
(EcotoxCentre 2013)
(Kummerer and Henninger 2003)
0.6 (100)
(Kummerer and Henninger 2003)
1.1 (100)
(Kummerer and Henninger 2003)
0.04 (100)
(Kummerer and Henninger 2003)
0.15 (100)
76 (1000)
(Kummerer and Henninger 2003)
(fass.se 2014)
3 (100)
0.02 (100)
0.5 (100)
Own data
(Turkdogan and Yetilmezsoy 2009)
(Kummerer and Henninger 2003)
(Halling-Sorensen et al. 2000)
0.04 (100)
0.002 (1000)
Own data
(Kummerer and Henninger 2003)
(Zhang et al. 2012)
0.5 (100)
(Kummerer and Henninger 2003)
Cefaclor
Cefadroxil
Cefixime
Cefuroxime
Ciprofloxacin
0.12 (10)
Clarithromycin
0.94 (5)
Clindamycin
Doxycyclin
0.3 (100)
Own data
(Kummerer and Henninger 2003)
0.04 (100)
4.74 (1000)
Own data
(Kummerer and Henninger 2003)
(Turkdogan and Yetilmezsoy 2009)
0.1 (100)
177 (n/a)
(Kummerer and Henninger 2003)
(Jones et al. 2002)
0.1 (100)
0.15(100)
Own data
(Kummerer and Henninger 2003)
0.59 (10)
0.027 (1000)
0.6 (n/a)
Own data
(Zhang et al. 2012)
(EcotoxCentre 2013)
16 (1000)
60 (n/a)
Own data
(Turkdogan and Yetilmezsoy 2009)
(EcotoxCentre 2013)
0.054 (100)
Levofloxacin
0.1 (100)
Penicillin V
Roxithromycin
Sulfamethoxazole
Trimethoprim
15.7 (10)
S5 Risk index of the species algae and fish
Risk index of the species algae (RIalgae) – remaining RQAB are summed up and displayed as residuals
Risk index of the species fish (RIfish) – remaining RQAB are summed up and displayed as residuals
Literature
Alexy, R. (2003) Antibiotika in der aquatischen Umwelt: Eintrag, Elimination und Wirkung auf Bakterien, Albert-Ludwigs-University Freiburg
Ando, T., Nagase, H., Eguchi, K., Hirooka, T., Nakamura, T., Miyamoto, K. and Hirata, K. (2007) A novel method using cyanobacteria for ecotoxicity test of veterinary
antimicrobial agents. Environmental Toxicology and Chemistry 26(4), 601-606.
Andreozzi, R., Caprio, V., Ciniglia, C., De Champdore, M., Lo Giudice, R., Marotta, R. and Zuccato, E. (2004) Antibiotics in the environment: Occurrence in Italian
STPs, fate, and preliminary assessment on algal toxicity of amoxicillin. Environmental Science & Technology 38(24), 6832-6838.
Backhaus, T. and Grimme, L.H. (1999) The toxicity of antibiotic agents to the luminescent bacterium Vibrio fischeri. Chemosphere 38(14), 3291-3301.
Backhaus, T., Scholze, M. and Grimme, L.H. (2000) The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibrio fischeri. Aquatic
Toxicology 49(1-2), 49-61.
Brain, R.A., Johnson, D.J., Richards, S.M., Sanderson, H., Sibley, P.K. and Solomon, K.R. (2004) Effects of 25 pharmaceutical compounds to Lemna gibba using a
seven-day static-renewal test. Environmental Toxicology and Chemistry 23(2), 371-382.
Brain, R.A., Ramirez, A.J., Fulton, B.A., Chambliss, C.K. and Brooks, B.W. (2008) Herbicidal Effects of Sulfamethoxazole in Lemna gibba: Using p-Aminobenzoic Acid
As a Biomarker of Effect. Environmental Science & Technology 42(23), 8965-8970.
Ebert, I., Bachmann, J., Kuehnen, U., Kuester, A., Kussatz, C., Maletzki, D. and Schlueter, C. (2011) TOXICITY OF THE FLUOROQUINOLONE ANTIBIOTICS
ENROFLOXACIN AND CIPROFLOXACIN TO PHOTOAUTOTROPHIC AQUATIC ORGANISMS. Environmental Toxicology and Chemistry 30(12), 2786-2792.
EcotoxCentre (2013) Proposals for Acute and Chronic Quality Criteria. Ecotoxicology, T.S.C.f.A. (ed).
Eguchi, K., Nagase, H., Ozawa, M., Endoh, Y.S., Goto, K., Hirata, K., Miyamoto, K. and Yoshimura, H. (2004) Evaluation of antimicrobial agents for veterinary use
in the ecotoxicity test using microalgae. Chemosphere 57(11), 1733-1738.
fass.se (2014), trade association for the research-based pharmaceutical companies operating in Sweden (Läkemedelsindustriföreningens AB).
Ferrari, B., Mons, R., Vollat, B., Fraysse, B., Paxeus, N., Lo Giudice, R., Pollio, A. and Garric, J. (2004) Environmental risk assessment of six human pharmaceuticals:
Are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environmental Toxicology and Chemistry
23(5), 1344-1354.
Ghosh, G.C., Okuda, T., Yamashita, N. and Tanaka, H. (2009) Occurrence and elimination of antibiotics at four sewage treatment plants in Japan and their effects
on bacterial ammonia oxidation. Water Science and Technology 59(4), 779-786.
GlaxoSmithKline (2006) Safety data sheet Amoxicillin.
Golet, E.M., Alder, A.C. and Giger, W. (2002) Environmental exposure and risk assessment of fluoroquinolone antibacterial agents in wastewater and river water
of the Glatt Valley Watershed, Switzerland. Environmental Science & Technology 36(17), 3645-3651.
Halling-Sorensen, B., Lutzhoft, H.C.H., Andersen, H.R. and Ingerslev, F. (2000) Environmental risk assessment of antibiotics: comparison of mecillinam,
trimethoprim and ciprofloxacin. Journal of Antimicrobial Chemotherapy 46, 53-58.
Harada, A., Komori, K., Nakada, N., Kitamura, K. and Suzuki, Y. (2008) Biological effects of PPCPs on aquatic lives and evaluation of river waters affected by
different wastewater treatment levels. Water Science and Technology 58(8), 1541-1546.
Hartmann, A., Alder, A.C., Koller, T. and Widmer, R.M. (1998) Identification of fluoroquinolone antibiotics as the main source of umuC genotoxicity in native
hospital wastewater. Environmental Toxicology and Chemistry 17(3), 377-382.
Isidori, M., Lavorgna, M., Nardelli, A., Pascarella, L. and Parrella, A. (2005) Toxic and genotoxic evaluation of six antibiotics on non-target organisms. Science of
the Total Environment 346(1-3), 87-98.
Jones, O.A.H., Voulvoulis, N. and Lester, J.N. (2002) Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Research 36(20),
5013-5022.
Kummerer, K., Al-Ahmad, A. and Mersch-Sundermann, V. (2000) Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater
bacteria in a simple test. Chemosphere 40(7), 701-710.
Kummerer, K. and Henninger, A. (2003) Promoting resistance by the emission of antibiotics from hospitals and households into effluent. Clinical Microbiology
and Infection 9(12), 1203-1214.
Laville, N., Ait-Aissa, S., Gomez, E., Casellas, C. and Porcher, J.M. (2004) Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in
fish hepatocytes. Toxicology 196(1-2), 41-55.
Liu, B., Liu, W., Nie, X., Guan, C., Yang, Y., Wang, Z. and Liao, W. (2011) Growth response and toxic effects of three antibiotics on Selenastrum capricornutum
evaluated by photosynthetic rate and chlorophyll biosynthesis. Journal of Environmental Sciences-China 23(9), 1558-1563.
LUA (2002) Ökotoxikologische Bewertung von Humanarzneimitteln in aquatischen Ökosystemen (Ecotoxicological assessment of human pharmaceuticals in
aquatic ecosystems), Landesumweltamt Brandenburg (Environmental Agency of the German Federal State Brandenburg), Potsdam, Frankfurt (Oder).
Madureira, T.V., Rocha, M.J., Cruzeiro, C., Galante, M.H., Monteiro, R.A.F. and Rocha, E. (2011) The toxicity potential of pharmaceuticals found in the Douro River
estuary (Portugal): Assessing impacts on gonadal maturation with a histopathological and stereological study of zebrafish ovary and testis after sub-acute
exposures. Aquatic Toxicology 105(3-4), 292-299.
Park, S. and Choi, K. (2008) Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems. Ecotoxicology 17(6), 526-538.
Quinn, B., Gagne, F. and Blaise, C. (2008) An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater
effluent on the cnidarian, Hydra attenuata. Science of the Total Environment 389(2-3), 306-314.
Richards, S.M. and Cole, S.E. (2006) A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae. Ecotoxicology 15(8), 647-656.
Suzuki, Y., Komori, K., Miyajima, K. and Yamashita, N. (2007) Evaluation of ecotoxicological effects of chemicals in aquatic environments, National Institute for
Land and Infrastructure Management Ministry of Land, Infrastructure, Transport and Tourism 1, Tsukuba City, Ibaraki Prefecture, Japan.
Turkdogan, F.I. and Yetilmezsoy, K. (2009) Appraisal of potential environmental risks associated with human antibiotic consumption in Turkey. Journal of
Hazardous Materials 166(1), 297-308.
Yamashita, N., Yasojima, M., Nakada, N., Miyajima, K., Komori, K., Suzuki, Y. and Tanaka, H. (2006) Effects of antibacterial agents, levofloxacin and clarithromycin,
on aquatic organisms. Water Science and Technology 53(11), 65-72.
Yang, L.-H., Ying, G.-G., Su, H.-C., Stauber, J.L., Adams, M.S. and Binet, M.T. (2008) Growth-inhibiting effects of 12 antibacterial agents and their mixtures on the
freshwater microalga Pseudokirchneriella subcapitata. Environmental Toxicology and Chemistry 27(5), 1201-1208.
Yu, Z., Jiang, L. and Yin, D. (2011) Behavior toxicity to Caenorhabditis elegans transferred to the progeny after exposure to sulfamethoxazole at environmentally
relevant concentrations. Journal of Environmental Sciences-China 23(2), 294-300.
Zhang, R., Zhang, G., Zheng, Q., Tang, J., Chen, Y., Xu, W., Zou, Y. and Chen, X. (2012) Occurrence and risks of antibiotics in the Laizhou Bay, China: Impacts of river
discharge. Ecotoxicology and Environmental Safety 80, 208-215.