Influence of microplate material on the sensitivity of growth inhibition tests with bacteria assessing toxic organic substances in water and waste water

In conjunction with aquatic bioassays, the effect of microplate (MP) material on the sensitivity of a cell multiplication inhibition test with luminescent bacteria (as representatives for unicellular organisms) was examined. The tested substances were four organic chemicals of different hydrophobic properties (4-nitrotoluene, 3,5-dichlorophenol, 2-chloroaniline, sodium phenolate) and waste water from a chemical production plant. The study revealed, that (except for sodium phenolate) the toxic response to the testing material was influenced by the MP material. The employment of the common plastic MP led to an underestimation of the biotests results. Therefore it must be taken into consideration, that when using the microplate technique to expose unicellular organisms to toxic chemicals with hydrophobic properties, only MP made of quartz glass should be employed. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 424–428, 1999     

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.     

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)‐induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500 μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154 days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue‐associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high‐dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high‐dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin‐33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin‐3, granulocyte‐macrophage colony‐stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.     

Effects of Louisiana crude oil on the sheepshead minnow (Cyprinodon variegatus) during a life‐cycle exposure to laboratory oiled sediment

Determining the long‐term effects of crude oil exposure is critical for ascertaining population‐level ecological risks of spill events. A 19‐week complete life‐cycle experiment was conducted with the estuarine sheepshead minnow (Cyprinodon variegatus) exposed to reference (uncontaminated) sediment spiked with laboratory weathered South Louisiana crude (SLC) oil at five concentrations as well as one unspiked sediment control and one seawater (no sediment) control. Newly hatched larvae were exposed to the oiled sediments at measured concentrations of < 1 (sediment control), 50, 103, 193, 347, and 711 mg total polyaromatic hydrocarbons (tPAH)/kg dry sediment. Juveniles were exposed through the reproductively active adult phase at measured concentrations of <1 (sediment control), 52, 109, 199, 358, and 751 mg tPAH/kg sediment. Throughout the exposure, fish were assessed for growth, survival, and reproduction. Resulting F1 embryos were then collected, incubated, and hatched in clean water to determine if parental full life‐cycle exposure to oiled sediment produced trans‐generational effects. Larvae experienced significantly reduced standard length (5–13% reduction) and wet weight (13–35% reduction) at concentrations at and above 50 and 103 mg tPAH/kg sediment, respectively. At 92 and 132 days post hatch (dph), standard length was reduced (7–13% reduction) at 199 and 109 mg tPAH/kg dry sediment, respectively, and wet weight for both time periods was reduced at concentrations at and above 109 mg tPAH/kg dry sediment (21–38% reduction). A significant reduction (51–65%) in F0 fecundity occurred at the two highest test concentrations, but no difference was observed in F1 embryo survival. This study is the first to report the effects of chronic laboratory exposure to oiled sediment, and will assist the development of population models for evaluating risk to benthic spawning fish species exposed to oiled sediments. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1627–1639, 2016.     

A comparison of the effects of silver nanoparticles and silver nitrate on a suite of soil dwelling organisms in two field soils

Nanomaterials are increasingly used in a wide range of products, leading to growing concern of their environmental fate. In order to understand the fate and effects of silver nanoparticles in the soil environment, a suite of toxicity tests including: plant growth with Elymus lanceolatus (northern wheatgrass) and Trifolium pratense (red clover); collembolan survival and reproduction (Folsomia candida); and earthworm avoidance, survival and reproduction (Eisenia andrei) was conducted. The effect of silver nanoparticles (AgNP) was compared with the effect of ionic silver (as AgNO₃) in two agricultural field soils (a sandy loam and a silt loam). Lethal (LC50) or sub lethal (IC50) effect levels are presented for all endpoints and demonstrate that in most cases AgNO₃ (i.e. ionic silver) was found to be more toxic than the AgNP across test species. The difference in effects observed between the two forms of silver varied based on test species, endpoint and soil type. In tests that were conducted across different soil types, organisms in the sandier soil had a greater response to the Ag (ionic and nano) than those in soil with a high silt content. Earthworms (avoidance behavior and reproduction) were the most sensitive to both AgNP and AgNO₃, while plant emergence was the least sensitive endpoint to both forms of Ag. The use of a test battery approach using natural field soils demonstrates the need to better quantify the dissolution and transformation products of nanomaterials in order to understand the fate and effects of these materials in the soil environment.     

Effects of silver nanoparticles on the interactions of neuron‐ and glia‐like cells: Toxicity,uptake mechanisms,and lysosomal tracking

Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte‐like, BV‐2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono‐ and co‐culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation. From mono‐culture, ALT took up the most AgNPs and had the lowest cell viability within three cells. Moreover, AgNPs induced H₂O₂ and NO from ALT/activated ALT and BV‐2, respectively. However, AgNPs did not induce cytokines release (IL‐6, TNF‐α, MCP‐1). LPS‐activated BV‐2 took up more AgNPs than normal BV‐2, while the induction of ROS and cytokines from activated cells were diminished. Ca²⁺‐regulated clathrin‐ and caveolae‐independent endocytosis and phagocytosis were involved in the AgNP uptake in ALT, which caused more rapid NP translocation to lysosome than in macropinocytosis and clathrin‐dependent endocytosis‐involved BV‐2. AgNPs directly caused apoptosis and necrosis in N2a cells, while by indirect NP exposure to bottom chamber ALT or BV‐2 in Transwell, more apoptotic upper chamber N2a cells were observed. Cell viability of BV‐2 also decreased in an ALT–BV‐2 co‐culturing study. The damaged cells correlated to NP‐mediated H₂O₂ release from ALT or NO from BV‐2, which indicates that toxic response of AgNPs to neurons is not direct, but indirectly arises from AgNP‐induced soluble factors from other glial cells.     

Screening of non‐steroidal anti‐inflammatory drugs for inhibitory effects on the activities of six UDP‐glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC‐MS/MS

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are used widely to relieve pain and to decrease inflammation. Several clinical studies have reported that NSAIDs inhibit uridine 5′‐diphospho‐glucuronosyltransferase (UGT) enzymes. Therefore, the study evaluated the inhibitory potential of 15 NSAIDs on the activities of six UGT isoforms (i.e. UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes (HLMs). Among the 15 NSAIDs tested here, mefenamic acid and diclofenac inhibited all UGTs tested in this study. Piroxicam and niflumic acid inhibited UGT1A9 activity (IC₅₀ = 73.8 μm and 0.38 μm , respectively) and naproxen selectively inhibited UGT2B7 activity (IC₅₀ = 53.1 μm ), whereas it did not inhibit the other UGTs tested (IC₅₀ > 200 μm ). Diflunisal inhibited the UGT1A1 (IC₅₀ = 33.0 μm ) and UGT1A9 (IC₅₀ = 19.4 μm ). Acetaminophen, fenoprofen, ibuprofen, ketoprofen, meloxicam, phenylbutazone, salicylic acid and sulindac showed negligible inhibitory effects on the six UGTs (IC₅₀ > 100 μm ). These results suggest that some NSAIDs have the potential to inhibit UGTs in vitro. Copyright © 2014 John Wiley & Sons, Ltd.