Inhalation toxicity of cyclic semi-volatile methylsiloxanes: Disentangling the conundrum of phase-specific adaptations from adverse outcomes.

This paper compares the phase-specific inhalation toxicity of the cyclic semi-volatile methylsiloxanes (cVMSs) D4, D5 and D6. The objectives of this paper are to re-analyze information from acute to chronic inhalation studies on rats with these cVMSs to identify the unifying principles of phase-specific toxicity at the portal-of-entry and if they depend on acute, acute-on-chronic or chronic mechanisms. This re-analysis supports the hypothesis that concentrations must be high enough to exceed the vapor saturation at any given temperature for stabilizing the aerosol phase and evoking phase-specific effects at sites of the respiratory tract susceptible to the cVMSs-specific physicochemical properties amphiphilicity and surface tension. In summary, the portal-of-entry effects and related findings appear to be acute in nature and specific to liquid aerosol. The repeated inhalation exposure studies with D4 and D5 up to two years in duration did not reveal chronic aggravations of portal of entry outcomes. Findings at a pulmonary location where amphiphilic surfactant molecules are present appear to be caused by the acute adaptation to deposited dose. Such outcome should better be described as a high-dose liquid aerosol phenomenon imparted by the physicochemical properties "liquid" and "hydrophobic". This calls for a phase-specific human risk characterization of cVMSs.

Magnetite Hydrosols with Positive and Negative Surface Charge of Nanoparticles: Stability and Effect on the Lifespan of Drosophila melanogaster.

This paper presents sols of uncoated and citric acid-coated Fe3O4 nanoparticles obtained by a combination of coprecipitation and sonochemistry methods. A stable concentrated CA-Fe3O4 sol synthesized by a combination of coprecipitation with an inconvenient Fe2+/Fe3+ ratio, modification with citric acid and US treatment was obtained for the first time. A comparative analysis of the composition and morphology of nanoparticles was performed. The sols are oppositely charged and behave as a typical ferrofluid. The citric acid-modified sol is aggregatively stable over wider ranges of pH and electrolyte concentration, but it becomes less stable with the temperature increase. DLVO calculations showed that steric repulsion forces are a vital factor contributing to increased aggregative stability in a modified Fe3O4 sol. The experiments have revealed the magneto-optical effect in a modified Fe3O4 sol with an electrolyte concentration of 0.025-0.075 M caused by a high potential barrier and a deep secondary minimum in pairwise interaction curves. The "pK spectroscopy" mathematical model to describe the potentiometric curves of synthesized magnetite sols was used for the first time. According to potentiometric titration, the ions of the electrolyte practically do not contribute to formation of a surface charge in modified Fe3O4 with a change in pH due to blocking the magnetite surface by citric acid molecules. Drosophila melanogaster was used as a model to show that Fe3O4 in chronic exposure has a low toxic effect.

Towards uterus tissue engineering: a comparative study of sheep uterus decellularisation.

Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication and rejection episodes. Repeated uterine bioengineering studies on rodents have shown promising results using decellularised scaffolds to restore fertility in a partially impaired uterus and now mandate experiments on larger and more human-like animal models. The aim of the presented studies was therefore to establish adequate protocols for scaffold generation and prepare for future in vivo sheep uterus bioengineering experiments. Three decellularisation protocols were developed using vascular perfusion through the uterine artery of whole sheep uteri obtained from slaughterhouse material. Decellularisation solutions used were based on 0.5% sodium dodecyl sulphate (Protocol 1) or 2% sodium deoxycholate (Protocol 2) or with a sequential perfusion of 2% sodium deoxycholate and 1% Triton X-100 (Protocol 3). The scaffolds were examined by histology, extracellular matrix quantification, evaluation of mechanical properties and the ability to support foetal sheep stem cells after recellularisation. We showed that a sheep uterus can successfully be decellularised while maintaining a high integrity of the extracellular components. Uteri perfused with sodium deoxycholate (Protocol 2) were the most favourable treatment in our study based on quantifications. However, all scaffolds supported stem cells for 2 weeks in vitro and showed no cytotoxicity signs. Cells continued to express markers for proliferation and maintained their undifferentiated phenotype. Hence, this study reports three valuable decellularisation protocols for future in vivo sheep uterus bioengineering experiments.

Evaluation of Ototoxicity of an Antifog Agent and the Suspected Underlying Mechanisms: An Animal Study.

Use of rigid endoscopes has become widespread in middle ear surgeries, thereby attracting attention to the safety of antifog agents. However, few studies on the ototoxicity of antifog agents have been conducted. The purpose of this study was to evaluate hair cell damage and the underlying mechanisms caused by antifog agents using zebrafish larvae. We exposed zebrafish larvae at 3 days postfertilization to various concentrations of the antifog agent, Ultrastop (0.01, 0.02, 0.04, and 0.08%) for 72 hours. The average number of hair cells within 4 neuromasts of larvae, including supraorbital (SO1 and SO2), otic (O1), and occipital (OC1), in the control group were compared to those in the exposure groups. Significant hair cell loss was observed in the experimental groups compared to that in the control group (P < .01; control: 53.88 ± 4.85, 0.01%: 45.08 ± 11.70, 0.02%: 41.36 ± 12.00, 0.04%: 35.36 ± 16.18, and 0.08%: 15.60 ± 7.53 cells). Concentration-dependent increase in hair cell apoptosis by terminal deoxynucleotidyltransferase (TDT)-mediated dUTP-biotin nick end labeling assay (control: 0.00 ± 0.00, 0.01%: 3.48 ± 2.18, 0.02%: 9.64 ± 5.75, 0.04%: 17.72 ± 6.26, and 0.08%: 14.60 ± 8.18 cells) and decrease in the viability of hair cell mitochondria by 2-(4-[dimethylamino] styryl)-N-ethylpyridinium iodide assay (control: 9.61 ± 1.47, 0.01%: 8.28 ± 2.22, 0.02%: 8.45 ± 2.72, 0.04%: 7.25 ± 2.44, and 0.08%: 6.77 ± 3.26 percentage of total area) were observed. Antifog agent exposure can cause hair cell damage in zebrafish larvae, possibly by induction of mitochondrial damage with subsequent apoptosis of hair cells.

Application of conventional molecular dynamics simulation in evaluating the stability of apomyoglobin in urea solution.

In this study, we had exploited the advancement in computer technology to determine the stability of four apomyoglobin variants namely wild type, E109A, E109G and G65A/G73A by conducting conventional molecular dynamics simulations in explicit urea solution. Variations in RMSD, native contacts and solvent accessible surface area of the apomyoglobin variants during the simulation were calculated to probe the effect of mutation on the overall conformation of the protein. Subsequently, the mechanism leading to the destabilization of the apoMb variants was studied through the calculation of correlation matrix, principal component analyses, hydrogen bond analyses and RMSF. The results obtained here correlate well with the study conducted by Baldwin and Luo which showed improved stability of apomyoglobin with E109A mutation and contrariwise for E109G and G65A/G73A mutation. These positive observations showcase the feasibility of exploiting MD simulation in determining protein stability prior to protein expression.

[Toxicity of 4-Chlorophenol Solution Under Electrochemical Reduction-oxidation Process].

The Pd-Fe/graphene multi-functional catalytic cathode was prepared by UV-assisted photocatalytic reduction. The catalytic cathode and a Ti/IrO2/RuO2 anode consisting of both three-electrode system (two cathodes) and two-electrode system (one cathode) were designed for the degradation of 4-chlorophenol in aid of olectrochemical reducing and oxidizing processes. The concentrations of the intermediates and products were monitored by high performance liquid chromatography (HPLC), total organic carbon (TOC), and ion chromatography (IC). The theoretical toxicity was calculated according to the formula. The actual toxicity of the solution during the degradation process was detected using the luminescent bacteria. The comparison of the actual toxicity and theoretical toxicity was performed to analyze the trend of the two systems. The results showed that the toxicity of the solution in anode compartment first increased and then decreased, but the toxicity in cathode compartment decreased during the whole degradation for both systems. This trend could be attributed to the intermediate formed, benzoquinone. Through the analysis of correlation, the correlation coefficient was 1 of the theoretical toxicity and actual toxicity at the level of P = 0.01, which indicated the result of toxicity was reliable. The toxicity of three-electrode system was lower than that of two-electrode system after 120 mm. The three-electrode system was considered to be better than the two-electrode system. Therefore, the detection of actual toxicity in electrochemical reducing and oxidizing process for the degradation of chlorophenols in the actual industry has wide application prospect.

Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung.

Oxidative stress and inflammatory response are the key events in the pathogenesis of chronic airway diseases. The consumption of electronic cigarettes (e-cigs) with a variety of e-liquids/e-juices is alarmingly increasing without the unrealized potential harmful health effects. We hypothesized that electronic nicotine delivery systems (ENDS)/e-cigs pose health concerns due to oxidative toxicity and inflammatory response in lung cells exposed to their aerosols. The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS) may be inhaled directly into the lung during a "vaping" session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used), and occurs during the process of e-liquid vaporization. Unvaporized e-liquids were oxidative in a manner dependent on flavor additives, while flavors containing sweet or fruit flavors were stronger oxidizers than tobacco flavors. In light of OX/ROS generated in ENDS e-liquids and aerosols, the effects of ENDS aerosols on tissues and cells of the lung were measured. Exposure of human airway epithelial cells (H292) in an air-liquid interface to ENDS aerosols from a popular device resulted in increased secretion of inflammatory cytokines, such as IL-6 and IL-8. Furthermore, human lung fibroblasts exhibited stress and morphological change in response to treatment with ENDS/e-liquids. These cells also secrete increased IL-8 in response to a cinnamon flavored e-liquid and are susceptible to loss of cell viability by ENDS e-liquids. Finally, exposure of wild type C57BL/6J mice to aerosols produced from a popular e-cig increase pro-inflammatory cytokines and diminished lung glutathione levels which are critical in maintaining cellular redox balance. Thus, exposure to e-cig aerosols/juices incurs measurable oxidative and inflammatory responses in lung cells and tissues that could lead to unrealized health consequences.

A new medium for Caenorhabditis elegans toxicology and nanotoxicology studies designed to better reflect natural soil solution conditions.

A new toxicity test medium for Caenorhabditis elegans is presented. The test solution is designed to provide a better representation of natural soil pore water conditions than currently available test media. The medium has a composition that can readily be modified to allow for studies of the influences of a range of environmentally relevant parameters on nematode biology and toxicology. Tests conducted in the new medium confirmed that nematodes' reproduction was possible at a range of solution pH levels, offering the potential to conduct toxicity studies under a variety of conditions. A test to establish silver nanoparticle and dissolved silver nitrate toxicity, a study type not feasible in M9 or agar media due to precipitation and nanoparticle agglomeration, indicated lower silver nanoparticle (median effective concentration [EC50] of 6.5 mg Ag/L) than silver nitrate (EC50 0.28 mg Ag/L) toxicity. Characterization identified stable nanoparticle behavior in the new test medium.

Hydroxyl radical induced degradation of ibuprofen.

Pulse radiolysis experiments were used to characterize the intermediates formed from ibuprofen during electron beam irradiation in a solution of 0.1mmoldm(-3). For end product characterization (60)Co γ-irradiation was used and the samples were evaluated either by taking their UV-vis spectra or by HPLC with UV or MS detection. The reactions of OH resulted in hydroxycyclohexadienyl type radical intermediates. The intermediates produced in further reactions hydroxylated the derivatives of ibuprofen as final products. The hydrated electron attacked the carboxyl group. Ibuprofen degradation is more efficient under oxidative conditions than under reductive conditions. The ecotoxicity of the solution was monitored by Daphnia magna standard microbiotest and Vibrio fischeri luminescent bacteria test. The toxic effect of the aerated ibuprofen solution first increased upon irradiation indicating a higher toxicity of the first degradation products, then decreased with increasing absorbed dose.

Evaluation of the genotoxic potential of reactive black 5 solutions subjected to decolorizing treatments by three fungal strains.

The genotoxic potential of solutions of the textile dye "Reactive Black 5" that were subjected to decolorizing treatments with the fungal strains Coriolopsis polyzona MUCL33483, Penicillium sp. MUBA001 and Pycnoporus sp. MUBA002 was tested. The genotoxicity of the solutions was determined by evaluation of micronuclei formation in Vicia faba root cells and calculation of a damage index (MN(ID)). Non-treated Reactive Black 5 solutions (50-1000 ppm) caused a statistically significant increase in micronuclei formation and, by then, in damage index. Solutions of dye treated with C. polyzona MUCL33483 and Pycnoporus sp. MUBA002 showed color loss, probably due to enzymatic breakdown of the colorant, but maintenance or even an increase in genotoxicity. On the other hand, the Penicillium sp. strain MUBA001 caused decolorization of the dye, apparently by adsorption on mycelia, and, for solutions that initially contained 50 ppm of colorant, an elimination of the genotoxicity was observed after three weeks of treatment.

Cytotoxicity effects of cryoprotectants as single-component and cocktail vitrification solutions.

Cryoprotectant (CPA) cytotoxicity constitutes a challenge in developing cryopreservation protocols, specifically in vitrification where high CPA concentrations are necessary to achieve the ice-free, vitreous state. Few cytotoxicity studies have investigated vitrification-relevant concentrations of CPAs, and the benefits and disadvantages of cocktail solutions and of incorporating non-permeating solutes have not been fully evaluated. In this study, we address these issues by determining the cytotoxicity kinetics for dimethylsulfoxide (Me(2)SO) and 1,2-propanediol (PD) on alginate-encapsulated ßTC-tet mouse insulinomas for a range of concentrations and temperatures. Cytotoxicity kinetics were also determined for two cocktails, DPS (3M Me(2)SO+3M PD+0.5M sucrose) and PEG400 (1M Me(2)SO+5M PD+0.34M poly(ethylene)glycol with M.W. of 400). PD was found to be more cytotoxic than Me(2)SO at higher concentrations and temperatures. This was reflected in PEG400 being more cytotoxic at room temperature than PEG400 at 4°C or DPS at either temperature. Addition of non-permeating solutes increased the cytotoxicity of cocktails. Furthermore, results indicate that CPA cytotoxicity may not be additive and that combining CPAs may increase cytotoxicity synergistically. Finally, when comparing cytotoxic effects towards encapsulated HepG2 and ßTC-tet cells, and towards ßTC-tet cells in capsules and in monolayers, CPAs appear more cytotoxic towards cells with higher metabolic activity. The incorporation of these results in the rational design of CPA addition/removal processes in vitrification is discussed.

Vitrification of human ovarian tissue: effect of different solutions and procedures.

OBJECTIVE: To test the effect of different vitrification solutions and procedures on the morphology of human preantral follicles. DESIGN: Pilot study. SETTING: Gynecology research unit in a university hospital. PATIENT(S): Ovarian biopsies were obtained from nine women aged 22-35 years. INTERVENTION(S): Ovarian tissue fragments were subjected to [1] different vitrification solutions to test their toxicity or [2] different vitrification methods using plastic straws, medium droplets, or solid-surface vitrification before in vitro culture. MAIN OUTCOME MEASURE(S): Number of morphologically normal follicles after toxicity testing or vitrification with the different treatments determined by histologic analysis. RESULT(S): In the toxicity tests, only VS3 showed similar results to fresh tissue before and after in vitro culture (fresh controls 1 and 2). In addition, this was the only solution able to completely vitrify. In all vitrification procedures, the percentage of normal follicles was lower than in controls. However, of the three protocols, the droplet method yielded a significantly higher proportion of normal follicles. CONCLUSION(S): Our experiments showed VS3 to have no deleterious effect on follicular morphology and to be able to completely vitrify, although vitrification procedures were found to affect human follicles. Nevertheless, the droplet method resulted in a higher percentage of morphologically normal follicles.

Response of Pediculus humanus humanus (Pediculidae: Phthiraptera) to water or 70% ethanol immersion and determination of optimal times for measuring toxic effects.

Human pediculosis is caused by Pediculus humanus humanus (Linnaeus 1758) and Pediculus humanus capitis (De Geer 1767). We studied the response of body lice to immersion in water and ethanol 70% and determined the optimal times for measuring knockdown and mortality. After immersion in water, all lice remained alive from 5 min to 22 h for both times of exposure. A low proportion of lice were affected after 2 min of immersion in ethanol in the 10-min exposure test, but recovered completely after 5 min. Different proportions of lice were affected between 2 and 7 h after immersion in ethanol, depending on the immersion time. However, a high proportion of lice recovered after 22 h. The results suggest that the optimal times for measuring early knockdown effects of insecticides are the 5-min to 7-h interval for water and 5-min to 1-h interval for ethanol. On the other hand, the best time for measuring mortality is 22 h after immersion. These results should improve the interpretations of the effects of pediculicides in immersion bioassays.

Trace metal phytotoxicity in solution culture: a review.

Solution culture has been used extensively to determine the phytotoxic effects of trace metals. A review of the literature from 1975 to 2009 was carried out to evaluate the effects of As(V), Cd(II), Co(II), Cu(II), Hg(II), Mn(II), Ni(II), Pb(II), and Zn(II) on plants grown in solution. A total of 119 studies was selected using criteria that allowed a valid comparison of the results; reported toxic concentrations varied by five orders of magnitude. Across a range of plant species and experimental conditions, the phytotoxicity of the trace metals followed the trend (from most to least toxic): Pb approximately Hg >Cu >Cd approximately As >Co approximately Ni approximately Zn >Mn, with median toxic concentrations of (muM): 0.30 Pb, 0.47 Hg, 2.0 Cu, 5.0 Cd, 9.0 As, 17 Co, 19 Ni, 25 Zn, and 46 Mn. For phytotoxicity studies in solution culture, we suggest (i) plants should be grown in a dilute solution which mimics the soil solution, or that, at a minimum, contains Ca and B, (ii) solution pH should be monitored and reported (as should the concentrations of the trace metal of interest), (iii) assessment should be made of the influence of pH on solution composition and ion speciation, and (iv) both the period of exposure to the trace metal and the plant variable measured should be appropriate. Observing these criteria will potentially lead to reliable data on the relationship between growth depression and the concentration of the toxic metal in solution.

Pulmonary emphysema induced by cigarette smoke solution and lipopolysaccharide in guinea pigs.

Exposure of animals to cigarette smoke for longer than 3 months leads to the development of chronic obstructive pulmonary disease (COPD) showing pulmonary emphysema. We attempted to create a COPD model with emphysema that could be established in a shorter period of time. Guinea pigs were intratracheally treated once a day on days 0-3, 5-8, 10-13 and 15-18 with a cigarette smoke solution (CSS), which was prepared by bubbling a stream of smoke into saline. Additionally, lipopolysaccharide (LPS) was administered intratracheally as an exacerbation factor on days 4, 9 and 14. By day 19, there was a gradual elevation of specific airway resistance (sRaw). In addition, both residual volume and functional residual capacity were found to be significantly higher on day 19. In the lungs, there was a marked increase in leukocytes, especially neutrophils. Histologically, we observed epithelial hyperplasia and emphysema. On the other hand, daily oral administration of theophylline during the administration of CSS and LPS suppressed the sRaw increase and the epithelial hyperplasia, but not other functional structural changes. In conclusion, we established an experimental COPD model in guinea pigs by using intratracheal instillations of CSS and LPS over a considerably shorter term than has been reported for other models.

Oral lead exposure induces dysbacteriosis in rats.

OBJECTIVES: Lead's (Pb(II)) possible role in intestinal pathologies of microbial etiology remains mostly unknown. The aim of this study was to examine the effects of lead on the gut microbial community and its interactions with rat intestinal epithelium. METHODS: The lead-induced changes in different intestinal microbial groups (lactose-positive lac(+) and -negative lac(-) E.coli strains, lactobacilli and yeasts) were followed separately by the colony-forming unit (CFU) method. Samples were taken from outbred white rats subjected to different exposure schedules. Additionally, the impact of different lead doses on microbial adhesion to cultured intestinal cells (IEC-6) was investigated. Finally, the lead accumulation and distribution were measured by means of atomic absorption spectrometry. RESULTS: For the first time it was shown that oral lead exposure causes drastic changes in the gut microbial community. Proportional to the lead dose received, the relative number of lactose-negative E.coli cells increased dramatically (up to 1,000-fold) in comparison to the other microbial groups during 2 wk of exposure. Considering the number of microbes in the intestine, such a shift in intestinal microflora (dysbacteriosis) is very significant. Adhesion studies showed certain stimulating effects of lead on E. coli attachment to rat intestinal epithelium as compared to Lactobacillus attachment. CONCLUSIONS: The mechanisms providing the apparent competitive success of the lac(-) group are unclear but could be related to changes in surface interactions between microbial and host cells. This study may provide important clues for understanding the pathological effects of metal dietary toxins in human beings.

Analysis of propolis from Baccharis dracunculifolia DC. (Compositae) and its effects on mouse fibroblasts.

This paper confirms Baccharis dracunculifolia DC. (Compositae) as the main botanical source of the propolis from southeastern Brazil (state of São Paulo) investigated to ascertain specific biological activity in relation to mouse NIH-3T3 fibroblasts, skin cells directly involved in the cicatrization processes. Flavonoid and total phenolic compounds were determined by spectrophotometry, and chemical composition by HPLC; the chromatographic profile, characterized largely by flavonoids and aromatic acids, was found to be qualitatively similar to that of Baccharis dracunculifolia DC. The adsorption of phenolic compounds in the propolis to skin powder was also investigated, and 68% of these compounds adsorbed to the skin powder. At concentrations from 0.12 to 7.81 microg/ml, the propolis revealed no statistical significant differences from its control solutions; however, at concentrations of 31.25 microg/ml or more, the propolis was toxic to NIH-3T3 cells. Thus, the propolis from Baccharis dracunculifolia DC. (Compositae) presents an in vitro concentration-dependent toxicity on mouse NIH-3T3 fibroblasts.

Pathochemical toxicity of perfluorocarbon-5070, a liquid test performance fluid previously used in dialyzer manufacturing, confirmed in animal experiment.

In the light of clustered deaths in late 2001 associated with hemodialysis (HD), this article analyzes the pathochemical toxicity of the perfluorocarbon-5070 (PF-5070), a liquid used as test performance fluid for detecting capillary leaks during dialyzer manufacturing. Residual PF-5070 in some Athane dialyzers of the involved brands was infused in the injured patients during hemodialysis. The clinical presentation was in contrast with other previously described severe reactions to HD. Foam material was discovered in the right ventricle and caval vein of the patients who underwent postmortem examination. Deaths were attributed to gas embolism without the external causes identified. To explore the pathochemical toxicity of the inert liquid PF-5070, an animal model was developed. In a rabbit model, single slug intravenous injections as bolus of increasing doses of PF-5070 were performed. In a first set of experiments, three groups of three rabbits were administered increasing doses of PF-5070 at 4, 40, or 160 microl/kg. After intravenous injection, the animals were observed for clinical signs of adverse effects and underwent autopsy after death. Doses were normalized to animal body weight to allow comparison with supposed patient exposure. Five of nine rabbits died soon after PF-5070 dosing: One rabbit died within 4 h in the 4 microl/kg group, one rabbit died within 30 min in the 40 microl/kg group, and three rabbits died within 30 min in the 160 mul/kg group. In a second set of experiments, six rabbits were injected with a lethal dose of PF-5070 to analyze clinical symptoms and pathophysiology. All rabbits died on the day of dosing and displayed neurologic disorders (paralysis, nystagmus, rigidity, convulsions), then breathing abnormalities (rapid breathing, salivation, dark mucous membrane), and fatal collapse. Autopsy of rabbits showed evidence of gas retention in the lung tissue and gas bubbles in the right cardiac cavities. Histologic findings included alveolar hemorrhage with pulmonary edema, cerebellum, and cortex patchy areas of infarction. Single-dose intravenous administration of PF-5070 reproduced in a rabbit model the pathophysiologic effects observed in the hemodialysis patients. Severity of the symptoms observed in the animals was dose-dependent. Clinical and pathologic findings can be explained by the capacity of perfluorocarbon to emulsify blood at body temperature, to increase partial pressure in the pulmonary capillary bed, and to form bubbles in the pulmonary capillary circulation, thus blocking lung and visceral perfusion. Such experimental findings indicate the toxicity of PF-5070 administered intravenously and make the pathochemical toxicity link with the hemodialysis-related deaths caused by the presence of residues of PF-5070 in the Althane dialyzers. We conclude, in light of this outbreak and the subsequent investigations, that liquid PF-5070 is a highly toxic compound when administered intravenously because of its emulsifying properties. The use of PF-5070 or any liquid fluorocarbon compounds in medical devices with blood contact and particularly in the dialyzer manufacturing should be considered with caution.

Toxicity increases in ice containing monochlorophenols upon photolysis: environmental consequences.

The toxic effects of photoproducts formed upon the photolysis of 2- and 4-chlorophenol (CP) frozen solutions in polycrystalline ice phase were determined with a bacterial luminescence test (Vibrio fisheri), and in vitro biomarker assay for dioxin-like effects (inductions of AhR-dependent luciferase in H4IIE-luc cells) and compared to the toxic effects of products of the same photoreaction in aquatic phase. Coupling photoproducts formed in ice samples (3'-chlorobiphenyl-2,4'-diol and 3-chlorobiphenyl-2,2'-diol from 2-CP photolysis and 5-chlorobiphenyl-2,4'-diol from 4-CP photolysis) were found to be more toxic to V. fisheri than parent CPs and elicited significant inductions of dioxin-like effects (the effective concentrations EC50 approximately 3 x 10(-5) mol L(-1) corresponded to known weaker ligands of AhR, such as nonplanar polychlorinated biphenyls or polycyclic aromatic hydrocarbons). To complete the picture, a photoproduct formed from 4-CP (5-chlorobiphenyl-2,4'-diol) was synthesized, and a detailed toxicity assessment with purified compound confirmed the results obtained with irradiated samples. Our findings support a recently proposed model according to which solar radiation can trigger the formation of new types of organic pollutants in polar ice or tropospheric ice cloud particles, presenting possibly greater risk to the environment than the parent compounds.