Are Veterinary Medicines Causing Environmental Risks?

Are Veterinary Medicines Causing Environmental Risks?

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

Ivermectin Equivalents Excretion Profile 1800 1600 1400 1200 1000 800 600 400 200 0 Ivermectin Metabolite 1 Metabolite 2 0 2 4 6 8 10 12 14 16 18 20 Days After Treatment

H H H H 3C H 3C H 3C H 3C H H H H H 2 B 1a Monosaccharide H 24 Hydroxymethyl H 2 B 1a Monosaccharide Ivermectin H 2 B 1a H 3C H H 3C H H 3C H 3C H H H H H 3C H H H 3C Aglycone H H H 3C H 3C H H 3C H 3C H 3 --Desmethyl H 2 B 1a H 24 Hydroxymethyl H 2 B 1a H

Dissipation in the Field Dung collected 3 days after treatment 500 ml dung pats

Ivermectin (µg/kg dw) Ivermectin Persistence in Dung 2500 2000 1500 1000 500 0 0 5 10 15 20 25 30 35 40 Days in Field

Soil sampled directly beneath pats 3 depths 0-1cm 1-3cm 3-5cm For each pat and each time point Transfer of Ivermectin to soil

Ivermectin (ng/g ww) Transfer of Ivermectin to soil 100 80 0-1 cm 1-3 cm 60 40 20 0 7 10 19 38 71 Field Exposure (days)

Concentration (ug/kg) Direct excretion into water Ivermectin Dung, water, sediment Two treatment 6 cycles 5 No detection in water (LD 0.2 ng/l) 4 3 2 1 0 Pretreatment 7 14 21 28 34 42 Treatment 1 Treatment 2 4 7 14 21 Days after treatment

Antibiotics Sulfonamides Tetracyclines Fluoroquinolones Lincosamides Antiparasitics Macrocyclic lactones Benzimidazoles

Concentration (ug/kg) Persistence in soils 1000 750 0 DAT 103 DAT 152 DAT 500 250 0 diazinon enrofloxacin florfenicol levamisole oxytetracycline phenylbutazone sulfadiazine trimethoprim tylosin Boxall et al., (2006) JAFC

Drainflow Concentration (ug/l) Concentrations in drainflow 1000 Kay et al., ET&C 2004 100 10 SCP TC TYL 1 0.1 6 14 21 37 120 196 Days after Treatment

Surface runoff 2 days after slurry application: 47 µg/l SCP (dissolved phase) 8 µg/l TC (dissolved phase) 50 days after application: Less than 0.5 µg/l of both SCP and TC Much greater runoff generated by plot containing tractor wheelings Lots of sediment transported in surface runoff - high concentrations of TC likely

Leaching to groundwater Sampled throughout the soil profile using suction cups Intercepts leaching water Analysed for antibiotics and bromide tracer 3 depths (40, 80, 120 cm)

Field leaching studies Tylosin and oxytetracycline not detected Blackwell et al., Chemosphere2007

Pharmaceuticals in groundwater Class antiinflammatories antibiotics antiepileptics B-blockers X-ray contrast media hormones lipid regulators Examples diclofenac erythromycin, sulfadiazine, oxytetracyline carbamazepine sotalol iopromide estradiol, ethinylestradiol bezafibrate Monteiro and Boxall, 2010

Inputs to aquatic systems Cattle treated with ivermectin pour on Runoff from farmyard monitored continuously Concentrations of ivermectin in runoff detemined by HPLC-FD

Concentration (ng/l) Runoff results 90 Runoff volume (l) 0 10 20 30 40 50 60 70 80 90 100 110 130 150 0 10 20 30 0 10 30 50 10 30 50 0 10 20 80 70 60 50 40 30 20 10 0 1 3 7 10 10 Days after first treatment

Peak concentrations in farmyard runoff Study site/active Concentration of active Maximum measured in product concentration in runoff ( g L -1 ) Site 1 dicyclanil 50 g/l 441.7 ivermectin 8 g/l 0.120 deltamethrin 1 g/l <0.100 cyromazine 6 g/l 104.0 Site 2 ivermectin 5 g/l 0.085

Uptake into crops

Concentration (ug/kg) Uptake into crops 50 45 40 35 30 25 20 15 10 5 0 amoxicillin diazinon enrofloxacin florfenicol levamisole oxytetracycline phenylbutazone sulfadiazine trimethoprim tylosin Boxall et al., JAFC (2006)

Effects on organisms? Limited toxicity to fish, invertebrates and green algae High toxicity to cyanobacteria Some antibiotics appear to be very toxic to terrestrial and aquatic plants Few impacts seen in standard C&N mineralisation studies with soils Effects on microbes can lead to impacts on key ecosystem processes (e.g. degradation of other substances) Human exposure very low

Halling Sorensen, 2000

Is their a risk

Peak concentrations in farmyard runoff Study site/active Concentration of active Maximum measured in product concentration in runoff ( g L -1 ) Site 1 dicyclanil 50 g/l 441.7 LEC of 0.00001 g/l (Garric 2007) ivermectin 8 g/l 0.120 deltamethrin 1 g/l <0.100 cyromazine 6 g/l 104.0 Site 2 ivermectin 5 g/l 0.085

Toxicity to dung organisms Taken from Forster et al., 2010 RCR = 9000 (field study >8)

Ivermectin (µg/kg dw) Modelling reality 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

Number of adults Are effects caused at the farm scale? - modelling insect numbers 10 8 10 7 10 6 10 5 10 4 Mar Apr May Jun Jul Aug Sep ct Nov Month

Antibiotic resistance

Conclusions Veterinary medicines and their metabolites released to and occur in the environment We now have a very detailed understanding of the fate and standard effects of many veterinary drugs in the environment Standard risk assessment approaches suggest limited risk but. We may be missing the important pathways and important endpoints More intelligent approaches could help