1、Veterinary Pharmaceuticals:Potential Environmental Impact and Treatment Strategies presented at the Emerging Pollutants Workshop hosted by US EPA Region 5 John L.Cicmanec,DVM,MS,ACLAM NRMRL,US EPA,Cincinnati,OHAcknowledgementsDr.Craig Adams,Univ.of Missouri-RollaDr.Lars Angenent,Washington Univ.Dr.T
2、horsen Christian,University of BonnDr.Thomas Heberer,Technical Univ.BerlinDr.Barry Hooberman,FDAKenneth Loftin,Univ.of Missouri-RollaDr.David Sedlak,Univ.California,BerkeleyZhimin Qiang,Univ.of Missouri-RollaA Beef Cattle CAFO OperationA Typical Poultry CAFO OperationGroups of CompoundsnAntibioticsn
3、AnthelminticsnHormones;steroids and bovine ST nPesticidesnVaccinesnX-Ray contrast media,iodine&barium basedPotential Endocrine Disrupting ChemicalsnTrenbolone acetate(RevalorR,FiniplexR)nMelengestrol acetatenEstradiol benzoatenRactopamine(ProleanR)nTestosterone proprionatenHuman chorionic gonadotrop
4、innProstaglandinsTrenbolone&MelengestrolnLittle is known about their fate after excretion by the animalnTrenbolone half-life when stored as liquid manure is 267 daysnIn farm field studies Trenbolone was detected at the end of fertilization period and Melengestrol was detected at harvestWhere Does Ra
5、ctopamineFit In?n adrenergic agonist;nPartitions energy from fat growth to lean growth;nIncreases protein accretion and muscle growth;nIncreases muscle fiber diameterImpacts of Improved Feed EfficiencynRAC-fed pigs require less feed for equivalent lean gain(12.7%)nFewer natural resources are needed
6、for crop production for the swine industry when utilizing RAC(Carroll,et al.,2001).nRAC-fed pigs take 4 less days to a constant market weight.Swine UnitsGestation buildingGrowth/Finishing buildingsHog HeavenEstradiol(ppb)Testosterone(ppb)Cattle19 3.5n.d.Swine152 2.421 18Municipal31 5.429 7.3Humans a
7、nd Farm Animal Waste as a Source of Steroid HormonesCategories of Antibiotics Sulfonamides sulfamethoxazole,etcQuinolones-CiprofloxacinBeta-lactams-penicillins,cephalosporinsAminoglycosides-streptomycin,gentamycinMacrolides erythromycin,tylosinInjectable Form of 2 AntibioticsRelative Antibiotic Use
8、for Animals&HumansEurope3902 tons used for farm animals;7000 tons used for humans(1998)Europes human population is 390 million peopleCattle 19.8 millionSwine-8.8 millionSheep-6.4 millionPoultry-1 billion United States15,100 tons used for farm animals;4800 tons used for humans(1997)USA human populati
9、on is 270 million peopleCattle-97 millionSwine 59 millionSheep 7.8 millionPoultry 1.8 billionRelative Antibiotic Use Humans&Animals(continued)*In Europe the ratio is 7:4 in favor of humansBecause of relatively low animal populationsnIn the United States the ratio is 15:5 in favor of animals because
10、of larger animal numbers nNote:For all animal populations an adjustment was made for body size 4 pigs=1 cow 100 chickens =1 cowUse of Antibiotics as Growth Promoters in EuropenIn 1997,before controls,annual use was 1599 tons(separate from treatment of microbial diseases)nIn 1999,after controls were
11、introduced the annual use dropped to 786 tonsAnimal Antibiotics in the EnvironmentnPresently in Europe only 4 antibiotics-monensin,avilamycin,flavomycin,&salinomycin are approved for animal usenPrimarily the macrolides&sulfonamides persist in the environmentnTetracyclines,penicillins&fluoroquinolone
12、s rapidly degradenConcentrations found-usual 1-5 ng/L but can range up to 300 ng/L Tylosin as a feed-additive for swine macrolide antibiotic Tylan by Eli Lilly&Co 20 g/ton dry feed mechanism and resistance similar to lincosamide and streptogramin B typeAnaerobic degradation of TylosinSwine waste:1.6
13、 mg/liter tylosin+dehydroxi-tylonolide(breakdown product)Digester(effluent):always 26 years Used as growth promoter at sub-therapeutic levelsnHuman Drug-Synercid Streptogramin-Quinupristin/Dalfopristin combination Approved for therapy in US(1999)Active against Gram-positive bacteria -“drug of last r
14、esort”Danish StudyStreptogramin resistance020406080100199519961997199819992000%resistance024681012Consumption in TonnesEffect of Antibiotics on Field Crops(Jjemba)nPharmaceuticals such as chlorotetracycline,metronidazole,and sulfamethoxine are toxic to plants such as soybeans,poinsettia,and corn at
15、concentrations of 10-160 ppm Richmond Rd.Squires Rd.WTP InletSpillwayBoatRamp18PastureJacobsonParkCampKearneyXXXXXXXSamling SiteProcesses to Remove PharmaceuticalsSorption to particlesUltraviolet lightBacterial degradationReverse osmosisOthersOccurrence of Pharmaceuticals in Surface Water and Ground
16、 Water in Germany(Heberer,2001)Compound Surface g/L Ground g/LClofibric acid 4.6 0.7Diclofenac 3.0 0.3Ibuprofen 0.8 0.2Salicylic acid 3.4 1.2Occurrence of Pharmaceuticals in Wastewater(U.S.)Compound Concentration ExcretionAcetominophen 61 ug/L conjugatesIbuprofen 37 ug/L conjugatesAmoxicillin 27 ug/
17、L original formCephalexin 14 ug/L original formPenicillin 4 ug/L original formGemfibrozil 3 ug/L original formRanitidine 3 ug/L no informationSorption Data for Selected VPsCompound log Kow pKa Tetracycline -1.19 3.3,7.7,9.7Cipro 0.4 5.9,8.9Avermectin 3.19 Tylosin 3.5 7.1Sulfamethazine 0.89 2.6,7.6Me
18、tronidazole 0.02 2.4Chloramphenicol 1.14 Ceftiofur(NaxcelR)nApproved by FDA for treating respiratory disease in cattle with no withholding time for milknBacillus stearothermophilus test will detect levels of 50 ppb in milk;but when used according to directions none is detected in the milkWhat we can
19、 Learn from Studies of Human PharmaceuticalsnMost persistent drugs are diazepam,carbamazepine,bezafibrate,&iopromidenElimination from wastewater depends primarily upon sludge retention timenFor activated sludge systems 4-5 days are needed;for nitrogen removal 8-20 daysSummarynPresently antibiotic-re
20、sistance and Endocrine Disrupting Chemicals have been shown to have the greatest potential for causing environmental damagenThe vast quantities of compounds and wide-spread distribution make Veterinary Pharmaceuticals a significant environmental challengenProduct control and distribution is more complex than for Human Pharmaceuticals
