Veterinary pharmacovigilance. Part 3. Adverse effects of veterinary medicinal products in animals and on the environment

Woodward, K. N.

doi:10.1111/j.1365-2885.2005.00647.x

Cited by 31 publications

(17 citation statements)

References 235 publications

(348 reference statements)

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“…They promote the decomposition of dung [28] in close interaction with microorganisms and other fauna like nematodes and oligochaetes, playing a vital role in maintaining pasture hygiene, nutrient cycling, soil aeration, water percolation, humus content and pasture productivity. The issue of antiparasitics (and/or their metabolites) and their environmental effects are a controversial area [7,17,21,24,30], and the responsible authorities in the European Union (as well as in North America and Japan) require data on the effects of new veterinary antiparasiticals on dung organisms as part of the environmental risk assessment (see Phase II, Part A of the VICH Guidance Paper) [4,29]. Usually these data are obtained from laboratory tests (depending on their results semi-field studies are required), but up to now no standardized test guidelines are available.…”

Section: Introductionmentioning

confidence: 99%

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New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles

Lumaret

Alvinerie²,

Hempel

et al. 2007

Vet. Res.

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-According to European Union recommendations, a test method has been developed to evaluate the effects of veterinary pharmaceuticals on dung feeding insects. This test method was evaluated with the dung beetle Aphodius constans by using fecal residues of ivermectin after a pouron administration. Dung of different age (and thus containing different concentrations of ivermectin) as well as mixtures of highly-contaminated spiked dung with untreated control dung were studied in five test runs in two laboratories. The concentration of ivermectin (active substance; a.s.) in the dung samples was verified analytically. The main test endpoint was the survival of first instar larvae. The LC 50 using dung directly obtained from treated cattle ranged from 470 to 692 µg a.s. kg −1 dung (dry weight; d.w.) and 67 to 97 µg a.s. kg −1 dung (fresh weight; f.w.). Using mixtures, the outcome of two tests was almost identical: 770 to 781 µg a.s. kg −1 dung (d.w.); 109 to 132 µg a.s. kg −1 dung (f.w.). In comparison to the LC 50 values obtained when ivermectin was spiked in control dung at several concentrations (LC 50 880-985 µg a.s. kg −1 dung (d.w.)), the LC 50 values were again very similar. Three conclusions can be drawn from these results. The proposed test method seems to be robust and allows for the initiation of an international validation process (including ringtesting). Because of only small differences found in tests in which the test substance was spiked into control dung and those in which dung from treated cattle was applied, the use of a standard test method is proposed. The effects of ivermectin on ecologically relevant dung beetles obtained in a standardised test method reflect the results from field studies and are in the range of environmentally relevant concentrations.environmental risk assessment / ivermectin / dung beetle / treated dung / screening test

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Section: Introductionmentioning

confidence: 99%

“…Anthelmintics are of considerable value in agriculture, but possibly at an unevaluated cost to the greater environment [10,30]. The determination of effect values of pharmaceuticals on non target organisms are of great interest for the industry, which needs rapid, non expensive and standardized tests.…”

Section: Introductionmentioning

confidence: 99%

New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles

Lumaret

Alvinerie²,

Hempel

et al. 2007

Vet. Res.

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“…The causes and prevalence of liver diseases in dogs and cats are mostly unknown [7], but have also been related to drugs [8,9]. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine.…”

Section: Introductionmentioning

confidence: 99%

The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP

et al. 2013

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BackgroundThe bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine. The aim of this study was to investigate the functional characteristics of feline Bsep in comparison with canine and human Bsep/BSEP with respect to substrate affinities and inhibitory potential of model drugs. Orthologs of all three species were cloned and cell membrane vesicles overexpressing feline, canine and human Bsep/BSEP were prepared for functional analyses.ResultsThe cDNA sequences of the open reading frames of feline, canine and human Bsep/BSEP showed a high similarity between the species. Functional studies demonstrated for all species a tendency to a higher affinity of BSEP/Bsep for the conjugated bile acid taurocholic acid (TCA) than glycocholic acid (GCA), and a higher affinity for GCA than for the unconjugated cholic acid (CA). The inhibitory potency of the model inhibitors cyclosporine A, troglitazone and ketoconazole was characterized against TCA uptake into BSEP/Bsep containing membrane vesicles. All three substances potently inhibited TCA uptake without significant species differences.ConclusionStructure and functional characteristics of cat, dog and human Bsep/BSEP appeared to be very similar, indicating that the properties of this transporter have been highly preserved among the different species. Therefore, inhibition of BSEP by drugs could also be a mechanism in cholestasis and liver disease in veterinary relevant animal species. This model could be used to predict drug-induced liver injury caused by BSEP inhibition at an early stage in veterinary drug development.

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“…Por ende, la evaluación de riesgos de estos productos farmacéuticos es un área de investigación emergente en el ámbito global (HallingSørensen et al, 1998;Daughton & Ternes, 1999;Chapman, 2006;Jjemba, 2006). Una cantidad desconocida de estos componentes son evacuados al ambiente vía las aguas residuales o cuando las heces son usadas con residuos farmacéuticos para la fertilización de tierras agrícolas (Lützhoft et al, 1999;Backhaus et al, 2000;Kümmerer, 2003;Lalumera et al, 2004;Woodward, 2006). Diferentes estudios han demostrados que muchos fármacos y sus metabolitos están presentes en ambientes acuáticos en varias partes del mundo (Bila & Dezotti, 2003).…”

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EVALUACIÓN DEL RIESGO ACUÁTICO DE SIETE PRODUCTOS FARMACÉUTICOS SOBRE Daphnia magna

Iannacone

Alvariño

2009

Ecol. apl.

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ResumenLa evaluación ecotoxicológica de productos farmacéuticos en el ambiente acuático dulceacuícola es un área de investigación emergente a nivel global. El objetivo del presente trabajo fue evaluar el efecto ecotoxicológico agudo de siete productos farmacéuticos ampliamente usados en el Perú: cuatro antimicrobianos (Amoxicilina, Ciprofloxacino y Trimetoprima + Sulfametoxazol), dos analgésicos (Ibuprofeno y Paracetamol), y un sedativo (Diazepan) sobre la pulga del agua Daphnia magna Strauss, 1820 (Crustacea: Daphniidae), y su relación con las principales características fisicoquímicas y de relación de componentes de la molécula, y a partir de estos resultados evaluar su riesgo ambiental acuático. Las pruebas de toxicidad aguda se evaluaron con cinco concentraciones más un control o testigo, y con cuatro repeticiones, en un diseño BCA de 6 x 4. Se observó la siguiente secuencia de ecotoxicidad decreciente en términos de CL 50 (mg·L -1 ) a 96 h de exposición sobre D. magna: diazepan (17,1) > paracetamol (62.3) > ibuprofeno (175) > ciprofloxacino (230.6) > trimetoprima (296) > sulfametoxazol (1480) > amoxicilina (6950). No se encontró relación entre el LogCL 50 y la proporción de producto excretado, el logK ow y la solubilidad de los fármacos empleados. La ecotoxicidad potencial indicó que el diazepan ocasionó el mayor riesgo en el ambiente acuático. En cambio a través del cociente de riesgo solo el paracetamol produjo riesgo en el ambiente acuático. Palabras clave: Amoxicilina, Ciprofloxacino, Daphnia, Diazepan, Ibuprofeno, Paracetamol, Sulfametoxazol, Trimetropima Abstract Ecotoxicological assessment of pharmaceutical products in freshwater environments is an emergent research globally. The aim of this research was to evaluate acute ecotoxicological effects of seven pharmaceutical products widely used in Peru: four antimicrobians (Amoxicillin, Ciprofloxacin and Trimethoprim + Sulfamethoxazole), two analgesics (Ibuprofen and Paracetamol), and a sedative (Diazepan) on freshwater flea Daphnia magna Strauss, 1820 (Crustacea: Daphniidae). Relationships with the main physicochemical characteristics and molecule compounds were also assessed in order to evaluate environmental aquatic risks. Acute toxicity test were evaluated with five concentrations plus a control, with four repetitions, using a 6 x 4 CRB design . The following decreasing ecotoxicity sequence in terms of LC 50 (mg·L -1 ) at 96 h of exposure on D. magna was observed: Diazepan (17.1) > Paracetamol (62.3) > Ibuprofen (175) > Ciprofloxacin (230.6) > Trimethoprim (296) > Sulfamethoxazole (1480) > Amoxicillin (6950). Relationships between LogLC 50 and excreted product proportion, logK ow and solubility of pharmaceutical products were not found. Potential ecotoxicity indicated that Diazepan caused the highest aquatic risk. However, using the quotient risk only Paracetamol produced aquatic risk. Key words: Amoxicillin, Ciprofloxacin, Daphnia, Diazepan, Ibuprofen, Paracetamol, Trimethoprim ________________________________________________________________________...

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Veterinary pharmacovigilance. Part 3. Adverse effects of veterinary medicinal products in animals and on the environment

Cited by 31 publications

References 235 publications

New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles

New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles

The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP

EVALUACIÓN DEL RIESGO ACUÁTICO DE SIETE PRODUCTOS FARMACÉUTICOS SOBRE Daphnia magna

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