Chronic effects of exposure to a pharmaceutical mixture and municipal wastewater in zebrafish

Galus, Michal; Jeyaranjaan, Judy; Smith, Emily; Li, Hongxia; Metcalfe, Chris D.; Wilson, Joanna Y.

doi:10.1016/j.aquatox.2012.12.016

Cited by 179 publications

(93 citation statements)

References 45 publications

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“…In particular, the anticonvulsant drug carbamazepine was detected in 63% of tap water tested in these regions (Table 1; Patterton, 2013). Anticonvulsant drugs, such as carbamazepine, levetiracetam, lamotrigine and valproate, have been shown to cause several reproductive endocrine system side-effects in men and women suffering from epilepsy (Table 2; Rättyä et al, 2001;Svalheim et al, 2009;Harden et al, 2010), as well as in fish species exposed to carbamazepine (Galus et al, 2013). In men using levetiracetam and valproate as treatment, it has been shown that these drugs can lead to increased T and steroid hormone-binding globulin (SHBG) levels, which is responsible for the transport of steroid hormones in blood plasma (Rättyä et al, 2001;Harden et al, 2010).…”

Section: Endocrine Disruption Of Detected Pharmaceutical Contaminantsmentioning

confidence: 99%

Review: <i>Pharmaceutical and personal care products (PPCPs) as endocrine disrupting contaminants (EDCs) in South African surface waters</i>

Archer

Wolfaardt

Wyk

2017

WSA

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Globally, water resources are under constant threat of being polluted by a diverse range of man-made chemicals, and South Africa is no exception. These contaminants can have detrimental effects on both human and wildlife health. It is increasingly evident that several chemicals may modulate endocrine system pathways in vertebrate species, and these are collectively referred to as endocrine disrupting contaminants (EDCs). Although the endocrine-disrupting effect of water pollutants has been mainly linked to agricultural pesticides and industrial effluents, other pollutants such as pharmaceuticals and personal care products (PPCPs) are largely unnoticed, but also pose a potentially significant threat. Here we present for the first time in a South African context, a summarised list of PPCPs and other EDCs detected to date within South African water systems, as well as their possible endocrine-disrupting effect in-vitro and in-vivo. This review addresses other factors which should be investigated in future studies, including endocrine disruption, PPCP metabolites, environmental toxicology, and antibiotic resistance. The challenges of removing EDCs and other pollutants at South African wastewater treatment works (WWTWs) are also highlighted. The need for focused research involving both in-vitro and in-vivo studies to detect PPCPs in water systems, and to delineate adverse outcome pathways (AOPs) of priority PPCPs to aid in environmental impact assessment (EIA), are discussed.

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Section: Endocrine Disruption Of Detected Pharmaceutical Contaminantsmentioning

confidence: 99%

Review: <i>Pharmaceutical and personal care products (PPCPs) as endocrine disrupting contaminants (EDCs) in South African surface waters</i>

Archer

Wolfaardt

Wyk

2017

WSA

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“…Galus et al [24] analysed the impact of two concentrations (0.5 and 10 mg l 21 in total) of a mixture of acetaminophen, carbamazepine, gemfibrozil and venlafaxine on zebrafish fecundity, with both exposures having significant effects on cumulative embryo production. Madureira et al [25] described the effect of two concentrations (maximum field-observed concentrations, plus a 10 000 times elevated concentration) of a mixture of carbamazepine, fenofibric acid, propranolol, sulfamethoxazole and trimethoprim on various biomarkers and histopathological parameters in zebrafish.…”

Section: Approaches For Mixture Toxicity Analysis Prediction and Assmentioning

confidence: 99%

“…Ofloxacin alone contributes more than 50%, whereas, on the other end, trimethoprim or enoxacin do not contribute to a significant extent. For further details, see [24].…”

Section: Deviations From Concentration Addition And/or Independent Acmentioning

confidence: 99%

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Backhaus

2014

Phil. Trans. R. Soc. B

114

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Analytical monitoring surveys routinely confirm that organisms in the environment are exposed to complex multi-component pharmaceutical mixtures. We are hence tasked with the challenge to take this into consideration when investigating the ecotoxicology of pharmaceuticals. This review first provides a brief overview of the fundamental approaches for mixture toxicity assessment, which is then followed by a critical review on the empirical evidence that is currently at hand on the ecotoxicology of pharmaceutical mixtures. It is concluded that, while the classical concepts of concentration addition and independent action (response addition) provide a robust scientific footing, several knowledge gaps remain. This includes, in particular, the need for more and better empirical data on the effects of pharmaceutical mixtures on soil organisms as well as marine flora and fauna, and exploring the quantitative consequences of toxicokinetic, toxicodynamic and ecological interactions. Increased focus should be put on investigating the ecotoxicology of pharmaceutical mixtures in environmentally realistic settings.

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“…However, it has been demonstrated that a mixture of acetaminophen, carbamazepine, gemfibrozil and venlaflaxine (in the low µg l -1 range) had a significant impact to fish embryo development in the short term [14]. The chronic impact of drugs (i.e., ecological and evolutionary), either individually or as mixtures, remains unknown [15].…”

Section: Introductionmentioning

confidence: 99%

Fate of drugs during wastewater treatment

Petrie

McAdam

Scrimshaw

et al. 2013

TrAC Trends in Analytical Chemistry

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Recent trends for the determination of pharmaceutical drugs in wastewaters focus on the development of rapid multi-residue methods. These encompass a large number of drugs (up to 90) of varying physicochemical composition (hydrophobicity, molecular weight etc) at ng l -1 concentrations in the aqueous phase of complex heterogeneous matrices. These are well suited for drug determination in secondary effluents which contain detectable concentrations of pharmaceuticals. Drugs are not routinely monitored for in particulate phases of wastewaters despite being essential for fate determination, particularly in secondary processes receiving relatively high concentrations of suspended solids. Secondary effluents tend to contain multiple drugs, often above their proposed legislative targets for consent. Thus, tertiary processing may be considered to enhance drug removal and provide additional environmental protection. However, current analytical methods do not enable the efficacy of tertiary processes to be fully ascertained due to the inherently lower drug concentrations achieved. Existing method optimisation is required to lower detection capabilities for tertiary process monitoring. This would aid the understanding of breakdown reaction completeness and the criticality between parent drug and degradation product concentrations. Numerous degradation products are formed by biological and chemical processes which can exhibit toxicity. The complimentary use of biological assays here would improve understanding of the synergistic toxicological effect of multiple drugs and their degradation products at low concentration. Additionally, tertiary processes receive secondary effluents comprising comparatively high concentrations of dissolved organics (e.g., colloids). However, knowledge of drug behaviour in the charged colloidal fraction of wastewater and its impact to treatment is limited. Monitoring and understanding here is needed to develop tertiary process diagnosis and optimisation.

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Chronic effects of exposure to a pharmaceutical mixture and municipal wastewater in zebrafish

Cited by 179 publications

References 45 publications

Review: <i>Pharmaceutical and personal care products (PPCPs) as endocrine disrupting contaminants (EDCs) in South African surface waters</i>

Review: <i>Pharmaceutical and personal care products (PPCPs) as endocrine disrupting contaminants (EDCs) in South African surface waters</i>

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Fate of drugs during wastewater treatment

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