Targeting the environmental risk assessment of pharmaceuticals: Facts and fantasies

Tarazona, José V.; Escher, Beate I.; Giltrow, Emma; Sumpter, John P.; Knacker, Thomas

doi:10.1897/ieam_2009-052.1

Cited by 32 publications

(22 citation statements)

References 58 publications

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“…Tarazona et al [319] analyzed the environmental risk assessment of pharmaceuticals. The screening assessment based exclusively on fate properties, particularly soil adsorption based on the organic carbon adsorption coefficient (K OC ), is not sufficient in some cases because of the extreme toxicity of some molecules.…”

Section: Ecotoxicity Of Mls In Environmental Compartments and Effectsmentioning

confidence: 99%

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

Lumaret

Errouissi²,

Floate³

et al. 2012

CPB

298

215

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The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin doramectin and moxidectin. By comparison, information on compounds such as eprinomectin, emamectin and selamectin is still relatively scarce.

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Section: Ecotoxicity Of Mls In Environmental Compartments and Effectsmentioning

confidence: 99%

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

Lumaret

Errouissi²,

Floate³

et al. 2012

CPB

298

215

View full text Add to dashboard Cite

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“…Biochemical interactions in target and nontarget tissues, side effects, and dose responses of potential pharmaceuticals are studied intensively in humans and laboratory mammals during the drug development and safety evaluation process. Using a mechanism‐based approach, existing data may be useful to guide research efforts when assessing potential specific effects in nontarget organisms such as aquatic invertebrates and fish (Huggett et al 2003; Carvalho et al 2004; Williams et al 2005; Tarazona et al this issue). The recent review of Kreke and Dietrich (2008) gives an excellent overview of the expected potential effects of fluoxetine in fish based on the physiology of the highly conserved serotonin re‐uptake mechanism shared with mammals.…”

Section: Era According To Current Guidelinesmentioning

confidence: 99%

“…Given the intended therapeutic mode of action for fluoxetine, a tailored testing strategy would likely focus on fish, rather than on algal species. Whereas tailoring ERAs is a valuable approach (Tarazona et al this issue), restricting the testing strategy to investigate only potential effects suggested by the mode of action in humans may overlook unexpected effects such as those observed for fluoxetine in algae.…”

Section: Era According To Current Guidelinesmentioning

confidence: 99%

Environmental risk assessment for the serotonin re‐uptake inhibitor fluoxetine: Case study using the European risk assessment framework

Oakes

Coors

Escher

et al. 2010

Integr Envir Assess & Manag

Self Cite

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The serotonin re-uptake inhibitor fluoxetine was selected for an environmental risk assessment, using the most recent European guideline (EMEA 2006) within the European Union (EU)-funded Environmental Risk Assessment of Pharmaceuticals (ERAPharm) project due to its environmental persistence, acute toxicity to nontarget organisms, and unique pharmacokinetics associated with a readily ionizable compound. As a widely prescribed psychotropic drug, fluoxetine is frequently detected in surface waters adjacent to urban areas because municipal wastewater effluents are the primary route of entry to aquatic environments. In Phase I of the assessment, the initial predicted environmental concentration of fluoxetine in surface water (initial PEC(SW)) reached or exceeded the action limit of 10 ng/L, when using both a default market penetration factor and prescription data for Sweden, Germany, and the United Kingdom. Consequently, a Phase II risk assessment was conducted in which green algae were identified as the most sensitive species with a NOEC of <0.6 microg/L. From this value, a predicted no effect concentration for surface waters (PNEC(SW)) of 0.012 microg/L was derived. The PEC/PNEC ratio was above the trigger value of 1 in worst-case exposure scenarios indicating a potential risk to the aquatic compartment. Similarly, risks of fluoxetine for sediment-dwelling organisms could not be excluded. No risk assessment was conducted for the terrestrial compartment due to a lack of data on effects of fluoxetine on soil organisms. The need for a separate risk assessment for the main metabolite of fluoxetine, norfluoxetine, was not conducted because of a lack of fate and effect studies. Based on published data, fluoxetine and norfluoxetine appeared to have a low to moderate bioaccumulation potential, which should be confirmed in formal studies according to OECD guidelines. Exposure assessments for fluoxetine according to the current framework rely heavily on K(OC) and K(OW) values. This approach is problematic, because fluoxetine is predominantly a cationic substance at environmental pH values. Consequently, the fate of fluoxetine (and other ionic substances) cannot be predicted using partition coefficients established for nonionic compounds. Further, published estimates for partition coefficients of fluoxetine vary, resulting in considerable uncertainties in both the exposure and environmental risk assessments of fluoxetine.

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“…Recent concerns regarding the potential of pharmaceuticals to harm nontarget aquatic organisms illustrate how extrapolation of human-focused data can be used to infer potential ecological effects for prioritizing pharmaceutical chemicals/classes for hazard assessment purposes (Boxall et al 2012; Schreiber et al 2011; Tarazona et al 2007). For example, although the estrogen receptor (ER) is well conserved across vertebrate species (Baker 2011), a functional ortholog has not been found in invertebrate species (Baker et al 2008; Thomson et al 2009).…”

Section: Use Of Alternative Species and In Vitro Assays In An Aop Framentioning

confidence: 99%

Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

Perkins

Ankley

Crofton

et al. 2013

Environ Health Perspect

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Background: Traditional animal toxicity tests can be time and resource intensive, thereby limiting the number of chemicals that can be comprehensively tested for potential hazards to humans and/or to the environment.Objective: We compared several types of data to demonstrate how alternative models can be used to inform both human and ecological risk assessment.Methods: We reviewed and compared data derived from high throughput in vitro assays to fish reproductive tests for seven chemicals. We investigated whether human-focused assays can be predictive of chemical hazards in the environment. We examined how conserved pathways enable the use of nonmammalian models, such as fathead minnow, zebrafish, and Xenopus laevis, to understand modes of action and to screen for chemical risks to humans.Results: We examined how dose-dependent responses of zebrafish embryos exposed to flusilazole can be extrapolated, using pathway point of departure data and reverse toxicokinetics, to obtain human oral dose hazard values that are similar to published mammalian chronic toxicity values for the chemical. We also examined how development/safety data for human health can be used to help assess potential risks of pharmaceuticals to nontarget species in the environment.Discussion: Using several examples, we demonstrate that pathway-based analysis of chemical effects provides new opportunities to use alternative models (nonmammalian species, in vitro tests) to support decision making while reducing animal use and associated costs.Conclusions: These analyses and examples demonstrate how alternative models can be used to reduce cost and animal use while being protective of both human and ecological health.Citation: Perkins EJ, Ankley GT, Crofton KM, Garcia-Reyero N, LaLone CA, Johnson MS, Tietge JE, Villeneuve DL. 2013. Current perspectives on the use of alternative species in human health and ecological hazard assessments. Environ Health Perspect 121:1002–1010; http://dx.doi.org/10.1289/ehp.1306638

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Targeting the environmental risk assessment of pharmaceuticals: Facts and fantasies

Cited by 32 publications

References 58 publications

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

Environmental risk assessment for the serotonin re‐uptake inhibitor fluoxetine: Case study using the European risk assessment framework

Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

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