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Dose-response relationship
Risk characterization
Risk management
Limitations/ Uncertainty analysis
Ref
United Arab Emirates
HRA
7 Antibiotics, 1 Analgesic, 1 ß-blocker, 1 Antipsychotic B, C, D, F, G, Sulphapyridine, Risperidone Sulphamethazine, Sulphadiazine, Metoprolol
Reclaimed wastewater Incidental ingestion Recreational dermal contact Occupational exposure Children and adults
Therapeutic dose vs. EDI
Cancer risk and non-cancer risk Risk quotients No associated health risks
-
Associated with toxicity and exposure assessment
Sermejian et al., 2018
Denmark
HRA
1 Sex hormone, 1 Antibiotic, 1 Antineoplastic A, E, Phenoxymethylpenieilin
Sewer, Household ingestion: leaf/root, crops, drinking water, fish, meat, dairy products, inhalation
Daily intake Local vs. Regional
Non-cancer risk Negligible risk
-
Local conditions, selection of drugs as ‘more potentially suspicious’
Christensen, 1998
USA
HRA
1 Analgesic, 1 anticancer, 1 Lipid regulator, 1 Anti-inflammatory A, Acetylsalicyclic acid, Clofibrate, Indomethacin
Ingestion of fish, Drinking water
Non-cancer: HBL vs. EDI For cancer: RSD vs. EDI
Cancer and noncancer risk No appreciable risk
-
Uncertainty factors used Analysis of parent drug (not metabolites) Limited data on methodology
Schulman et al ., 2002
China
HRA
32 pharmaceutical drugs (human and veterinary) from 16 therapeutic classes
Household tap water Age-dependent seasonal exposures (carcinogenic and non-carcinogenic) Ingestion of tap water
Risk: Highest concentration vs. DWEL Age-related risk quotient
Low risk
Risk management and indicator monitoring framework
Age-dependent exposures used for uncertainties in exposure variations
Leung et al ., 2013
Germany
EA
64 various pharmaceuticals from various therapeutic classes
Ingestion Drinking water
Reported concentrations vs. therapeutic dose
-
-
-
Webb et al., 2003
USA
EA
17 veterinary pharmaceuticals classes based on use
Pediatric exposure Various exposure sites Ingestion Dermal contact
-
-
Public awareness, home storage, appropriate product dispensing
Limitations: Data obtained from a single source, inconsistency in recording substance class
Tomasi et al., 2017
Israel
EA
Anticonvulsant: Carbamazepine
Reclaimed wastewater-irrigated vegetables, 34 volunteers, Ingestion
EDI vs. Therapeutic dose
-
-
Small and selective sample, potential for varying food preferences
Paltiel et al., 2016
Belgium
EA
Fentanyl (Analgesic)
Production site Dermal, Inhalation
-
-
-
Analytical procedure assumptions
Nimmen et al., 2006
Iran
EA
Penicillin
Production site Occupational exposure Inhalation
Exposed group vs. Not exposed group
-
-
Control group not measured, No standard sampling device
Farshad et al., 2016
Several studies used
HRA
Different classes of pharmaceuticals (Literature data used)
Crops: wastewater-irrigated, biosolids or manure-amended soil ingestion
Hazard quotient EDI vs. ADI
Minimal risk
-
Exposure to mixtures, All consumed crops assumed to contain the greatest concentrations
Prosser et al., 2015
USA
HRA
4 Antibiotics, 2 analgesics, 1 stimulant B, C, D, Ampicillin, Napoxen, caffeine, Trimethoprim
Domestic groundwater Ingestion ADI, DWEL
Average concentration in water vs. DWEL
Minimal risk
Routine water quality monitoring
Additive/synergistic effect of mixtures not addressed, Risk due to other exposure pathways were not considered
Kibuye et al., 2019
USA/Canada
EA
5 Antibiotics, 1 Analgesic, 1 Antidepressant, 1 hormone, 1 Anti-inflammatory, B, C, D, E, F, G, Fluoxetine, Ibuprofen, Azithromycin
Exposures: Children, recreational, ocupational, Dermal contact with biosolids Ingestion: Biosolids, crops, drinking water
The equivalent of one therapeutic dose or 1 d home exposure was used
-
-
Criteria developed to select representative pharmaceuticals for the study
Brown et al., 2019
ADI, Acceptable Daily Intake; EDI, Estimated Daily Intake; DWEL, Drinking Water Equivalent Level; HBL, Health-Based Level; RSD, Risk-Specific Dose; A, Cyclophosphamide; B, Ofloxacin; C, Acetaminophen; D, Sulphamethoxazole; E, 17α Ethinylestradiol; F, Erythromycin; G, Ciprofloxacin.
In aquatic systems and even in the human body, pharmaceuticals are modified by environmental stressors which subsequently change the exposure scenario (Oskarsson et al., 2014). Although individual pharmaceuticals are used in very small quantities (therapeutic dose), the presence of several similar pharmaceuticals (sharing same mode
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