Applied Water Science. Группа авторов

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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 of action) may cause additive or synergistic exposures, and diversified stressor-receptor effects to non-target species (Daughton and Ternes, 1999). However as shown in Table 2.1, most studies on human health risks were conducted in developed countries (Shulman et al., 2002; Nimmen et al., 2006; Tomasi et al., 2016; Kibuye et al., 2019; Brown et al., 2019). This occurs despite the fact that the presence of pharmaceuticals in the environment is of global concern irrespective of level of industrialization (Kurster and Adler, 2014).

      Research attention on human health risks should focus on

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