Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Short-term exposure to effluent from bulk drug industries

ABSTRACT: The Patancheru area near Hyderabad in India is recognized as a key link in the global supply chain for many bulk drugs. A central treatment plant receives wastewater from about 90 different manufacturers and the resulting complex effluent has contaminated surface, ground and drinking water in the region. Ecotoxicological testing of the effluent has shown adverse effects for several organisms, including aquatic vertebrates. In an attempt to start investigating how exposure to effluent-contaminated water may affect humans and other terrestrial vertebrates, rats were tube-fed effluent. Results from microarray and quantitative polymerase chain reaction assays indicated, however, no marked effects on hepatic gene expression after five days exposure. Neither did a clinical analysis of blood serum constituents used as biomarkers for human disease reveal any significant changes, nor were there any effects on weight gain. Taken together, we could not find evidence for any acute toxicity in the rat; however, we cannot rule out that higher doses of effluent or a longer exposure time may still be associated with risks for terrestrial vertebrates. 10 rats (5 controls and 5 exposed to effluent) were subjected to microarray analysis. Further information is available in Rutgersson et al., 2010.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Erik Kristiansson

PROVIDER: E-GEOD-23983 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Oral exposure to industrial effluent with exceptionally high levels of drugs does not indicate acute toxic effects in rats.

Rutgersson Carolin C Gunnarsson Lina L Fick Jerker J Kristiansson Erik E Larsson D G Joakim DG

Environmental toxicology and chemistry 20130301 3

The Patancheru area near Hyderabad in India is recognized as a key link in the global supply chain for many bulk drugs. A central treatment plant receives wastewater from approximately 90 different manufacturers, and the resulting complex effluent has contaminated surface, ground, and drinking water in the region. Ecotoxicological testing of the effluent has shown adverse effects for several organisms, including aquatic vertebrates, at high dilutions. In addition, a recent study of microbial com ...[more]

PMID: 23258772

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Project description:Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. About 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for five days. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as EROD activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers, however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. This study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sub-lethal toxicity, as well as illuminate possible causative agents. Two exposure experiments were conducted with control fish and fish exposed to 0.2% effluent. 19 pools of RNA, each containing three fish, were hybrdizied to in situ synthesized custom-made oligonucleotide microarrays. In total, four exposed and four control pools from exposure experiment I and five exposed and six control pools from exposure experiment II were analyzed.

Project description:Wastewater treatment plant (WWTP) effluent-dominated streams provide critical habitat for aquatic and terrestrial organisms but also continually expose them to complex mixtures of pharmaceuticals that can potentially impair growth, behavior, and reproduction. Currently, few biomarkers are available that relate to pharmaceutical-specific mechanisms of action. In the experiment reported in this paper, zebrafish (Danio rerio) embryos at two developmental stages were exposed to water samples from three sampling sites (0.1 km upstream of the outfall, at the effluent outfall, and 0.1 km below the outfall) during base-flow conditions from two months (January and May) of a temperate-region effluent-dominated stream containing a complex mixture of pharmaceuticals and other contaminants of emerging concern. RNA-sequencing identified potential biological impacts and biomarkers of WWTP effluent exposure that extend past traditional markers of endocrine disruption. Transcriptomics revealed changes to a wide range of biological functions and pathways including cardiac, neurological, visual, metabolic, and signaling pathways. These transcriptomic changes varied by developmental stage and displayed sensitivity to variable chemical composition and concentration of effluent, thus indicating a need for stage-specific biomarkers. Some transcripts are known to be associated with genes related to pharmaceuticals that were present in the collected samples. Although traditional biomarkers of endocrine disruption were not enriched in either month, a high estrogenicity signal was detected upstream in May and implicates the presence of unidentified chemical inputs not captured by the targeted chemical analysis. This work reveals associations between bioeffects of exposure, stage of development, and the composition of chemical mixtures in effluent-dominated surface water. The work underscores the importance of measuring effects beyond the endocrine system when assessing the impact of bioactive chemicals in WWTP effluent and identifies a need for non-targeted chemical analysis when bioeffects are not explained by the targeted analysis.

Project description:Our main objectives wereto investigate the molecular mechanisms involved in metal toxicity and detoxification in the field using juvenile yellow perch subjected to differents levels of this metal exposure. Recent local adaptation to pollution has been evidenced in several organisms inhabiting environments heavily contaminated by metals. Nevertheless, the molecular mechanisms underlying adaptation to high metal concentrations are poorly understood, especially in fishes. Yellow perch (Perca flavescens) populations from lakes in the mining area of Rouyn-Noranda (QC, Canada) have been faced with metal contamination for about 90 years. Here, we examine gene transcription patterns of fish reciprocally transplanted between a reference and a metal-contaminated lake and also fish caged in their native lake. After four weeks, 111 genes were differentially transcribed in metal-naÃ¯ve fish transferred to the metal-contaminated lake, revealing a plastic response to metal exposure. Genes involved in the citric cycle and beta-oxidation pathways were under-transcribed, suggesting a potential strategy to mitigate the effects of metal stress by reducing energy turnover. However, metal-contaminated fish transplanted to the reference lake did not show any transcriptomic response, indicating a reduced plastic response capability to sudden reduction in metal concentrations. Moreover, the transcription of other genes, especially ones involved in energy metabolism, was affected by caging. Overall, our results highlight environmental stress response mechanisms in yellow perch at the transcriptomic level and support a rapid adaptive response to metal exposure through genetic assimilation. Comparison between fish Op and OpâOp using a pairwise design corresponding to the cage experiment in the reference lake Opasatica (Op), comparison between fish Du and DuâDu using a pairwise design corresponding to the cage experiment in the metal contaminated lake Dufault (Du), comparison between fish from reference lake transplanted to the metal contaminated lake (OpâDu) and fish from reference lake caged in their own lake (OpâOp) using pairwise design corresponding to the experiment of metal contamination, comparison between fish from metal contaminated lake transplanted to the reference lake (DuâOp) and fish from the metal contaminated lake caged in their own lake (DuâDu) using pairwise design corresponding to the depuration experiment.

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Short-term exposure to effluent from bulk drug industries

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Oral exposure to industrial effluent with exceptionally high levels of drugs does not indicate acute toxic effects in rats.

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