PNEC Calculated from Chronic Data. 5-fluorouracil Vestel et al abiraterone acetate Vestel et al. 2016

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1 These predicted no-effect concentrations, PNECs, are provided to facilitate environmental risk assessment of pharmaceuticals in surface water downstream of the mixing zone (i.e., not at the point of discharge or entry into the environment) by interested stakeholders. The chronic PNECs were derived from guideline studies (e.g., OECD, USFDA, USEPA) and the application of an appropriate assessment factor. This is the same data required to register a new pharmaceutical in Europe. For some pharmaceuticals, only acute data are available and were used with the appropriate assessment factor. The references are to peer reviewed publications, and also to unpublished internal company documents for a limited number of compounds. Compound Name 5-fluorouracil Vestel et al abiraterone acetate Vestel et al acyclovir Vestel et al AIC (5-amino-1H-imidazole-4- carboxamide) Vestel et al alfuzosin Vestel et al alvimopan Vestel et al anastrozole Vestel et al anidulafungin Vestel et al aprepitant Vestel et al aripiprazole Vestel et al articaine 92 Johnson & Johnson atazanavir Vestel et al atenolol Vestel et al atorvastatin Vestel et al azithromycin Vestel et al bambuterol HCl 71 bedaquiline Vestel et al bezafibrate Vestel et al Page 1 of 6

2 bicalutamide Vestel et al budesonide bupivacaine HCl monohydrate 39 bupropion Vestel et al canagliflozine Vestel et al candesartan Vestel et al capecitabine Vestel et al carisbamate Vestel et al carvedilol Vestel et al casopitant Vestel et al ceftobiprole Vestel et al celecoxib Vestel et al cetirizine 100 Johnson & Johnson chlorthalidone 80 Snape 2015 cimetidine Vestel et al cinacalcet hydrochloride Vestel et al cisapride 1000 Johnson & Johnson clomethiazole edisilate 62 clopidogrel bisulfate Vestel et al codeine 216 or 500 Vestel et al or J&J dalcetrapib Vestel et al Page 2 of 6

3 dapagliflozin 100 Snape 2015 dapoxetine HCl Vestel et al darunavir Vestel et al diazepam Vestel et al diclofenac Vestel et al diphenhydramine 0.1 Johnson & Johnson domperidone Johnson & Johnson doripenem Vestel et al doxorubicin 1.8 Johnson & Johnson dronedarone Vestel et al efavirenz Vestel et al entecavir Vestel et al eplerenone Vestel et al eplivanserin Vestel et al erlotinib HCl Vestel et al esomeprazole Na Vestel et al estradiol Caldwell et a estriol 0.06 Caldwell et al estrone Caldwell et al ethinylestradiol Caldwell et al etoricoxib Vestel et al Page 3 of 6

4 ezetimibe Vestel et al felodipine formoterol fumarate fosamprenavir Ca Vestel et al fulvestrant Vestel et al gefitinib Vestel et al haloperidol Johnson & Johnson hydrochlorothiazide Vestel et al ibuprofen 1 Johnson & Johnson ibrutinib 4 2 Vestel et al irbesartan 704 Vestel et al ketoconazole Vestel et al lamotrigine Vestel et al laropiprant Vestel et al lidocaine hydrochloride linezolid Vestel et al lisinopril dihydrate mepivacaine HCl 59 meropenem 1.5 Snape 2015 metformin Vestel et al methylphenidate HCl Vestel et al Page 4 of 6

5 metoprolol succinate miconazole nitrate Vestel et al montelukast Vestel et al naproxen 4.2 omeprazole Snape 2015 paliperidone Vestel et al pazopanib Vestel et al pregabalin Vestel et al prilocaine HCl propofol Vestel et al propranolol HCl Vestel et al quetiapine fumarate 10 (8) Vestel et al (Murray-Smith) raltegravir Vestel et al ramipril 100 ribavirin Vestel et al ridaforolimus Vestel et al rilpivirine Vestel et al rimonabant Vestel et al rivaroxaban 8.6 Vestel et al ropivacaine HCl 34 rosuvastatin calcium Vestel et al Page 5 of 6

6 saxagliptin Vestel et al simeprevir 0.1 Vestel et al sitagliptin Vestel et al sulfamethoxazole Vestel et al sutent Vestel et al tamoxifen citrate Vestel et al tapentadol Vestel et al taranabant Vestel et al telcagepant Vestel et al terbutaline sulphate ticagrelor Vestel et al topiramate Vestel et al tramadol 73 Vestel et al trimethoprim Vestel et al vicriviroc maleate Vestel et al vorinostat Vestel et al zafirlukast Vestel et al zolmitriptan 100 Vestel et al Page 6 of 6

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