Boxall
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Pharmaceuticals are released into the environment through sewage sludge applied to agricultural soils. Studies have detected various pharmaceuticals in sewage sludge samples at concentrations that could potentially affect soil organisms. Laboratory studies show some pharmaceuticals can accumulate in earthworm tissues. Modeling indicates factors like a drug's properties, soil characteristics, and organism type influence bioaccumulation. While risks to human health are generally low, certain levels of pharmaceutical exposure may subtly affect non-target species like invertebrates through mechanisms related to a drug's mode of action. Further research is still needed to fully understand pharmaceutical impacts on terrestrial environments.
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- Biomonitoring of urine samples found that permethrin exposure peaked 8-16 hours after use and could be detected for up to 144 hours, with an average elimination half-life of 30 hours. Over 50% of subjects exceeded environmental reference values after one-time use.
- Internal exposure increased with hot/humid conditions and physical activity, likely due to higher dermal absorption from increased skin perfusion and sweat. Accumulation may occur with daily use.11.3 Smolders
11.3 SmoldersKate Jones
油
This document summarizes a human biomonitoring study that collected all urine samples from 8 participants over a continuous 6-day period. Biomarkers for metals and organic compounds were measured to understand intra- and inter-individual variability in biomarker concentrations and determine optimal urine sampling strategies. Biomarker levels varied within and between individuals depending on compound half-life and exposure frequency from personal care products. High intra-individual variability was observed for biomarkers with short half-lives like methyl paraben, while cadmium showed low variability. The study provides insights into interpreting biomarker measurements from single spot samples versus multiple samples over time.7.3 Smolders
7.3 SmoldersKate Jones
油
The document discusses a study that measured biomarkers in mothers and children across 17 European countries. The study aimed to perform human biomonitoring in a harmonized way to obtain reliable and comparable data. The document examines whether differences in environmental concentrations and lifestyle factors can explain differences in biomarker levels among countries. It finds that cadmium levels correlated with air emissions and food quality, mercury levels correlated with fish consumption, and cotinine levels in non-smokers correlated with strength of anti-smoking laws. However, limitations included a lack of representative national data and differences in data quality among countries. Continued efforts are needed to improve interpretation through more harmonized datasets.Ad
Boxall
- 1. Side Effects of Medication in the Soil Environment Alistair B A Boxall 1
- 2. Nine species of vultures in the wild numbered 40 million birds in the early 1980s. Today, only about 60,000 birds are left (Vibhu Prakash, Bombay Natural History Society) Boxall et al (2003) ES&T 2
- 3. Pharmaceuticals in sewage sludge Classes of OWCs Detected (Bold face: # of compounds detected; concentrations in mg/kg) Biosolid A Biosolid B Biosolid C Biosolid D Biosolid E Biosolid F Prescrip. Drugs 9 (0.397) 6 (0.514) 8 (0.142) 5 (0.235) 5 (0.187) 5 (0.150) Nonprescrip. Drugs 8 (8.24) 6 (0.890) 6 (0.316) 7 (0.569) 7 (1.38) 7 (1.25) Detergent Metab. 4 (209) 4 (55.8) 4 (12.3) 4 (39.2) 4 (221) 4 (186) Fragrances 3 (6.63) 3 (7.39) 3 (2.14) 4 (7.23) 4 (7.57) 4 (6.15) Pesticides n.d. n.d. n.d. 1 (0.127) n.d. n.d. Fire Retardants 1 (0.600) 2 (1.90) 2 (1.15) 2 (0.548) 1 (0.570) 1 (0.100) PAHs 6 (1.91) 6 (1.23) 6 (0.767) 6 (0.544) 5 (0.331) 5 (0.276) Steroids 4 (275) 4 (42.0) 4 (68.5) 4 (42.7) 4 (306) 4 (198) Oil/Fuel 3 (0.346) n.d. n.d. n.d. 3 (0.249) 3 (0.195) 2 (1.30) 2 (5.90) 2 (5.20) Disinfectants 2 (4.80) 2 (3.91) 2 (1.61) 2 (11.5) 2 (10.6) 3 (8.46) 4 (2.89) 4 (2.24) Other OWCs 4 (1.82) Furlong et al., 2006 3
- 4. Antibiotics Sulfonamides Tetracyclines Fluoroquinolones Lincosamides Antiparasitics Macrocyclic油lactones Benzimidazoles Antiepileptics Antidepressants Anticoagulants Antiinflammatories Persistence in soils 0 DAT 103 DAT 152 DAT 750 500 250 Boxall et al., (2006) JAFC ty lo si n 0 di az in on en ro flo xa ci n flo rf en ic ol le va m is ol ox e yt et ra cy cl ph in e en yl bu ta zo ne su lfa di az in e tr im et ho pr im Concentration (ug/kg) 1000 Boxall et al. (206) JAFC 4
- 5. Runoff Runoff of pharmaceuticals from agricultural land applied with biosolids/manure Runoff sample collection: Pre-application, Post-application Topp et al., (2008) Sci. Tot. Env. Runoff from soils 5
- 6. Test organisms Study compounds and species Compound Log Kow pKa G. pulex N. glauca 5-fluorouracil -0.81 8.02 x caffeine 1.03 0.00 carbamazepine 2.25 - x x carvedilol 3.05 8.00 x x chloramphenicol -0.02 11.0 diazepam 2.70 3.40 diclofenac 4.13 4.10 L. variegatus E. fetida L. terrestris Perrene L. R. sativus x x x x X x x x x X x x x x X x x x X x x x x x x fluoxetine 4.16 10.1 x x moclobemide 1.16 6.20 x x naproxen 3.36 4.50 orlistat 8.19 - salicylic acid 2.3 3.1 x triclosan 5.42 8.10 x x 6
- 7. Fluoxetine Pore油water 0 . 1 5 250 2.5 Soil Earthworm Mean油model油fit 2 200 1.5 150 1 100 0.5 50 0 Pore油water油concentration油(nmol/L) Soil油and油Earthworm油concentration油 (nmol/kg) 300 0 0 200 400 600 Time油(hours) 800 1000 13 Earthworm modeling One油compartment油firstorder油toxicokinetic model油 Based油on油work油by油Ashauer et油al.,油2010 OpenModel software1 Used油measured油pore油water油concentrations Bioconcentration油factors油(BCF)油can油be油calculated油from油 modelled油uptake油and油depuration油rates Model油was油set油to油run油to油equilibrium Where油Cint油is油the油internal油concentration油(nmol/kg油ww),油Cpw油is油the油pore油water油concentration油(nmol/L)油and油kin and油kout the油uptake油 (nmol/kg油ww油d1)油and油elimination油rate油constant油(d1).油1 OpenModel油v.油1.2,油University油of油Nottingham,油2008. 14 7
- 8. Modeling results and bioconcentration Pharmaceutical Steady state? Dissipation油 Kin in test油 (uptake油rate) system (nmol/kg油d1) Kout (depuration rate)油(d1) BCF Carbamazepine Yes 30油% 0.2408 0.1393 2.21 Diclofenac No 0% 0.0363 0.0021 21.46 Fluoxetine Near 20油% 1.1079 0.0471 30.8 Orlistat Near >油50油% 0.0708 0.0016 51.53 15 Effects油of油soil油properties Soil油properties LUFA油Speyer油(Germany)油 characterised soil pH油 Soil油Type (CaCl2) OC油% CEC油 (meq/100g) Type Soil油2.1 5.1 0.74 4 Silty油sand Soil 2.3 6.6 0.97 9 Silty油sand Soil 2.4 7.2 2.99 33 Clayey油loam Soil油5M 7.2 1.23 15 Loamy油sand Soil 6S 7.2 1.69 22 Clayey油loam 8
- 9. Results: Soil properties Soil油type LUFA 2.1 CBZ油BCF(pw) DCF BCF(pw) FLX BCF(pw) 1.30油 28.56 20.42 ORL油BCF(pw) 30.51 LUFA油2.3 1.53 15.04 19.74 115.92 LUFA 2.4 1.61 21.50 16.78 74.40 LUFA油5M 1.05 69.57 19.18 40.82 LUFA油6S 1.56 7.02 16.89 68.36 Species traits Effect油of油species油type油on油uptake? Earthworm油 Lumbricus油terrestris油(3油 6油g) Followed油minimised油design油principles油(i.e.油end油of油uptake油 and油depuration油sampling油only) Four油pharmaceuticals One油soil油type油 Soil油and油pore油water油samples油analysed油 throughout油exposure 9
- 10. Results: species type Pharmaceutical L.油terrestris E.油Fetida Carbamazepine Diclofenac Fluoxetine Orlistat 6.69 83.79 66.90 33.21 2.21 21.46 30.8 51.53 Uptake into crops 10
- 11. Uptake into organisms is also possible 50 Concentration (ug/kg) 45 40 35 30 25 20 15 10 5 ty lo si n et ho pr im tri m fa di az in e su l is ol e ox yt et ra cy cl in e ph en yl bu ta zo ne le va m flo rfe ni co l lo xa ci n en ro f az in di am ox ic ill in on 0 Boxall et al (2006) J. Agric. Food Chem. Drug receptors therapeutic effect Receptor Drug Many receptors also occur in organisms in the natural environment 11
- 12. Potential mechanisms in plants Brain et al., 2008 Effects of Prozac on woodlice 12
- 13. Antibiotic effects microbial biomass community structure functional endpoints respiration iron reduction Ammonification N-mineralisation Nitrification potential to degrade other anthropogenic substances Monteiro and Boxall (2010) ET&C Antibiotic resistance Wellington et al (2013) Lancet ID 13
- 14. Toxicity to dung organisms Taken from Forster et al., 2010 RCR = 9000 (field study >8) Modelling reality Ivermectin (袖g/kg dw) 2500 2000 1500 1000 500 0 0 2 4 6 8 10 12 14 16 18 20 Days Post Dose Excretion profile Medicine use patterns Impact on population Husbandry practices Compound dose response Insect life cycle and behaviour 14
- 15. Are effects caused at the farm scale? modelling insect numbers 10 Number of adults 10 10 10 10 8 7 6 5 4 Mar Apr May Jun Jul Month Aug Sep Oct Nov Risks from food Carter et al. (2014) JAFC 15
- 16. Summary Pharmaceuticals are released into and detected in the natural environment Risks to human health are low Subtle effects are seen in organisms (related to MoA and side effects) Levels of some pharmaceuticals may be high enough to affect terrestrial organisms Understanding much less developed than aquatic environment and many open questions Further Reading Environ Health Persp, 2012, 120(9), 1221-1229 16
- 17. Acknowledgements Melanie Netherton Maja Karlsson Laura Carter Bryan Brooks Sara Monteiro Louise Pope Richard Fussell Richard Williams Tom Bean Hannah Cooper Joanne Parrot 20Q participants European Commission Environment Agency DWI Defra BBSRC Unilever GSK Health Canada 17