Because of their global distribution, persistence, and tendency to bioaccumulate, concerns about perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are growing. We determined the ...toxicity of PFOS and PFOA in several freshwater organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and the teleost Oryzias latipes. In general, PFOS is approximately 10 times more toxic than PFOA in these organisms. In M. macrocopa, the median lethal concentration (LC50) was 17.95 mg/L for PFOS and 199.51 mg/L for PFOA. Moina macrocopa exhibited greater sensitivity than D. magna to both perfluorinated compounds in both acute and chronic exposures. In the 48-h acute toxicity test, M. macrocopa was approximately two times more sensitive than D. magna. In the 7-d chronic toxicity test, M. macrocopa showed significant reproductive changes at 0.31 mg/L for PFOS, which was approximately seven times lower than the effect concentrations observed over the 21-d exposure in D. magna. Two-generation fish toxicity tests showed that parental exposure to both compounds affected the performance of offspring. Unexposed progeny-generation (F1) fish exhibited elevated mortality and histopathological changes that were correlated with exposure in the parental generation (F0). Continuous exposure from F0 through F1 generations increased the extent of adverse effects. Considering the persistent nature of PFOS and PFOA, more research is required to determine potential consequences of long-term exposure to these compounds in aquatic ecosystems.
Regulatory ecotoxicity testing of chemicals is of societal importance and a large effort is undertaken at the OECD to ensure that OECD test guidelines (TGs) for nanomaterials (NMs) are available. ...Significant progress to support the adaptation of selected TGs to NMs was achieved in the context of the project MARINA (
http://www.marina-fp7.eu/
) funded within the 7th European Framework Program. Eight OECD TGs were adapted based on the testing of at least one ion-releasing NM (Ag) and two inert NMs (TiO
2
). With the materials applied, two main variants of NMs (ion releasing vs. inert NMs) were addressed. As the modifications of the test guidelines refer to general test topics (e.g. test duration or measuring principle), we assume that the described approaches and modifications will be suitable for the testing of further NMs with other chemical compositions. Firm proposals for modification of protocols with scientific justification(s) are presented for the following tests: growth inhibition using the green algae Raphidocelis subcapitata (formerly: Pseudokirchneriella subcapitata; TG 201), acute toxicity with the crustacean Daphnia magna (TG 202), development toxicity with the fish Danio rerio (TG 210), reproduction of the sediment-living worm Lumbriculus variegatus (TG 225), activity of soil microflora (TGs 216, 217), and reproduction of the invertebrates (Enchytraeus crypticus, Eisenia fetida, TGs 220, 222). Additionally, test descriptions for two further test systems (root elongation of plants in hydroponic culture; test on fish cells) are presented. Ecotoxicological data obtained with the modified test guidelines for TiO
2
NMs and Ag NM and detailed method descriptions are available.
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•Acute toxicity of single and combined N-compounds (1:1:1) were determined in shrimp.•LC50 (96 h) were 29.0, 10.6 and 900 mg/L for TAN, NO2−-N and NO3−-N, respectively.•Mixture ...effects of nitrogen compounds were antagonistic (<72 h) and additive (>72 h).
Information on toxicity of nitrogen compounds for Litopenaeus vannamei in coastal ecosystems and culture under low salinity is scarce. Acute toxicity trials were conducted in L. vannamei to determine the single and combined effects of ammonia, nitrite and nitrate at a salinity of 3 g/L. The 96 h-LC50 was 29.0 mg/L for total ammonia nitrogen (TAN); 10.6 mg/L for nitrogen as nitrite (NO2−-N); and 900 mg/L for nitrogen as nitrate (NO3−-N). The joint effects of ammonia, nitrite and nitrate exposure were antagonistic at 24–72 h; and additive from 72 to 96 h. The proposed safety levels of single exposure to TAN, NO2−-N and NO3−-N for L. vannamei are 1.45, 0.53 and 45.0 mg/L, respectively. When in mixture, the proposed level of TAN/NO2−-N/NO3−-N is 0.05 TU (Toxicity Unit) corresponding to 0.48, 0.08 and 14.6 mg/L of TAN, NO2−-N and NO3−-N, respectively.
The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic ...nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.
Large volumes of oil sands process-affected water (OSPW) are produced by the surface-mining oil sands industry in Alberta. Both laboratory and field studies have demonstrated that the exposure to ...OSPW leads to many physiological changes in a variety of organisms. Adverse effects include compromised immunological function, developmental delays, impaired reproduction, disrupted endocrine system, and higher prevalence of tissue-specific pathological manifestations. The composition of OSPW varies with several factors such as ore sources, mining process, and tailings management practices. Differences in water characteristics have confounded interpretation or comparison of OSPW toxicity across studies. Research on individual fractions extracted from OSPW has helped identify some target pollutants. Naphthenic acids (NAs) are considered as the major toxic components in OSPW, exhibiting toxic effects through multiple modes of action including narcosis and endocrine disruption. Other pollutants, like polycyclic aromatic hydrocarbons (PAHs), metals, and ions may also contribute to the overall OSPW toxicity. Studies have been conducted on OSPW as a whole complex effluent mixture, with consideration of the presence of unidentified components, and the interactions (potential synergistic or antagonistic reactions) among chemicals. This review summarizes the toxicological data derived from in vitro and in vivo exposure studies using different OSPW types, and different taxa of organisms. In general, toxicity of OSPW was found to be dependent on the OSPW type and concentration, duration of exposures (acute versus sub chronic), and organism studied.
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•OSPW causes many physiological changes in a variety of organisms.•OSPW toxicity depends on water chemistry, exposure duration and test organisms.•Chemical compositions of OSPW from different tailing ponds are variable.•NAs as well as other chemical constituents contribute to the overall toxicity of OSPW.
The toxicity grade for a bulk material can be approximately determined by three factors (chemical composition, dose, and exposure route). However, for a nanomaterial it depends on more than ten ...factors. Interestingly, some nano-factors (like huge surface adsorbability, small size, etc.) that endow nanomaterials with new biomedical functions are also potential causes leading to toxicity or damage to the living organism. Is it possible to create safe nanomaterials if such a number of complicated factors need to be regulated? We herein try to find answers to this important question. We first discuss chemical processes that are applicable for nanosurface modifications, in order to improve biocompatibility, regulate ADME, and reduce the toxicity of carbon nanomaterials (carbon nanotubes, fullerenes, metallofullerenes, and graphenes). Then the biological/toxicological effects of surface-modified and unmodified carbon nanomaterials are comparatively discussed from two aspects: the lowered toxic responses or the enhanced biomedical functions. We summarize the eight biggest challenges in creating low-toxicity and safer nanomaterials and some significant topics of future research needs: to find out safer nanofactors; to establish controllable surface modifications and simpler chemistries for low-toxic nanomaterials; to explore the nanotoxicity mechanisms; to justify the validity of current toxicological theories in nanotoxicology; to create standardized nanomaterials for toxicity tests; to build theoretical models for cellular and molecular interactions of nanoparticles; and to establish systematical knowledge frameworks for nanotoxicology.
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•Human exposure to the estrogenic food contaminant bisphenol A is low, but widespread.•An accumulation of published “low dose” BPA toxicity studies has been used to imply risk to ...exposed humans.•A review of “low-dose” BPA studies revealed that a minority of studies were conducted in the range of human exposures.•“Low-dose” is non-specific, comprising to exposures ranging over 8–12 orders of magnitude.•Human exposure, not subjective terms such as “low-dose,” should be the standard for reporting toxicity data.
Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed industrialized societies. Structural features similar to estrogen confer the ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in the group of environmental pollutants called endocrine disruptors. References by scientists, the media, political entities, and non-governmental organizations to many toxicity studies as “low dose” has led to the belief that exposure levels in these studies are similar to humans, implying that BPA is toxic to humans at current exposures. Through systematic, objective comparison of our current, and a previous compilation of the “low-dose” literature to multiple estimates of human external and internal exposure levels, we found that the “low-dose” moniker describes exposures covering 8–12 orders of magnitude, the majority (91–99% of exposures) being greater than the upper bound of human exposure in the general infant, child and adult U.S. Population. “low dose” is therefore a descriptor without specific meaning regarding human exposure. Where human exposure data are available, for BPA and other environmental chemicals, reference to toxicity study exposures by direct comparison to human exposure would be more informative, more objective, and less susceptible to misunderstanding.
There is a great need for novel in vitro methods to predict human developmental toxicity to comply with the 3R principles and to improve human safety. Human-induced pluripotent stem cells (hiPSC) are ...ideal for the development of such methods, because they are easy to retrieve by conversion of adult somatic cells and can differentiate into most cell types of the body. Advanced three-dimensional (3D) cultures of these cells, so-called embryoid bodies (EBs), moreover mimic the early developing embryo. We took advantage of this to develop a novel human toxicity assay to predict chemically induced developmental toxicity, which we termed the PluriBeat assay. We employed three different hiPSC lines from male and female donors and a robust microtiter plate-based method to produce EBs. We differentiated the cells into cardiomyocytes and introduced a scoring system for a quantitative readout of the assay—cardiomyocyte contractions in the EBs observed on day 7. Finally, we tested the three compounds thalidomide (2.3–36 µM), valproic acid (25–300 µM), and epoxiconazole (1.3–20 µM) on beating and size of the EBs. We were able to detect the human-specific teratogenicity of thalidomide and found the rodent toxicant epoxiconazole as more potent than thalidomide in our assay. We conclude that the PluriBeat assay is a novel method for predicting chemicals’ adverse effects on embryonic development.
AbstractAzole antifungal drugs are used worldwide to treat a variety of fungal infections such as vulvovaginal candidiasis, particularly in pregnant women who are at increased risk. The aim of this ...study was to mechanistically investigate the endocrine disrupting potential of four commonly used azole antifungal drugs; clotrimazole, miconazole, ketoconazole and fluconazole in vitro using the H295R cell assay and two recombinant, CYP17A1 and CYP19A1 (aromatase), assays. Steroids were quantified using LC–MS/MS. In both recombinant assays, all four azoles inhibited the CYP enzymes investigated, at therapeutically relevant concentrations. However, responses were much more complex in the H295R cell line. Clotrimazole inhibited steroid production in a dose-dependent manner with IC50 values for CYP17A1 and CYP19A1 in the range 0.017–0.184 μM. Miconazole and ketoconazole increased all steroids on the hydroxylase axis (IC 50 MIC: 0.042-0.082 μM, KET: 0.041–1.2 μM), leading to accumulation of progestagens and corticosteroids and suppression of androgens and estrogens, indicating inhibition of CYP17A1, in particular lyase activity. However, ketoconazole suppressed all steroids at higher concentrations, resulting in bell-shaped curves for all steroids on the hydroxylase axis. Fluconazole was found to inhibit CYP17A1-lyase activity, causing suppression of androgens (IC 50 = 114–209 μM) and estrogens (IC 50 = 28 μM). The results indicate that these four azole drugs are highly potent in vitro and, based on plasma Cmax values, may exert endocrine disrupting effects at therapeutically relevant concentrations. This raises concern for endocrine related effects in patients using azole antifungal drugs, particularly when taken during sensitive periods like pregnancy.
The objective of the present work was to evaluate the broadest toxic effect of some synthetic additives of colorants and/or flavors on different body organs and metabolic aspects in rats. A number of ...chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items. However, many of them are toxic after prolonged use. In this experiment, a total of 100 male albino rats of Spargue Dawley strain were divided into 10 groups: G1 was fed basal diet and served as control, G2: basal diet + Brilliant blue (blue dye, No. 2, 124 mg/kg diet), G3: basal diet + carmoisine (red dye, No. 3, 70 mg/kg diet), G4: basal diet + tartrazine (yellow dye, FD & C yellow No. 5, 75 mg/kg diet), G5: basal diet + trans-anethole (4.5 g/kg diet) G6: basal diet + propylene glycol (0.25 g/kg diet), G7: basal diet + vanillin(1.25 g/kg diet), G8: basal diet + Brilliant blue + propylene glycol, G9: basal diet + carmoisine + trans-anethole, G10: basal diet + tartrazine + vanillin for 42 successive days. All food colorants mixed with or without flavor additives induced a significant decrease in body weight, hemoglobin concentration and red blood cell count. Also there was a significant decrease in reduced glutathione content; glutathione-S-transferase and superoxide dismutase activities in both blood and liver compared to control group. On the other hand, a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, bilirubin, urea, creatinine, total protein and albumin were observed in all test groups when compared to control group. Finally, it is advisable to limit the uses of these food colorants and/or food flavor additives especially those used by children.
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