Chemical compounds causing severe acute toxicity in heavy liquids used for intraocular surgery.

Perfluorocarbon liquids (PFCLs) have been considered safe for intraocular manipulation of the retina, but since 2013 many cases of acute eye toxicity cousing blindness have been reported in various countries when using various commercial PFCLs. All these PFCLs were CE marked (Conformité Européenne), which meant they had been subjected to evaluation complying with the International Organization for Standardization (ISO) guidelines. These dramatic events raised questions about the safety of PFCLs and the validity of some cytotoxicity tests performed under ISO guidelines. Samples from toxic batches were analyzed by gas chromatography-mass spectrometry combined with Raman and infrared spectrometry. Perfluorooctanoic acid, dodecafluoro-1-heptanol, ethylbenzene and tributyltin bromide were identified and evaluated by a direct contact cytotoxicity test using ARPE-19 cell line, patented by our group (EP 3467118 A1). Perfluorooctanoic acid at a concentration of >0.06 mM and tributyltin bromide at a concentration of ≥0.016 mM were shown to be toxic, whereas the concentration found in the toxic samples reached 0.48 mM, and 0.111 mM, respectively. These finding emphasized the idea that determination of partially fluorinated compounds are not enough to guarantee the safety of these medical devices.

A Polyextreme Hydrothermal System Controlled by Iron: The Case of Dallol at the Afar Triangle.

One of the latest volcanic features of the Erta Ale range at the Afar Triangle (NE Ethiopia) has created a polyextreme hydrothermal system located at the Danakil depression on top of a protovolcano known as the dome of Dallol. The interaction of the underlying basaltic magma with the evaporitic salts of the Danakil depression has generated a unique, high-temperature (108 °C), hypersaline (NaCl supersaturated), hyperacidic (pH values from 0.1 to -1.7), oxygen-free hydrothermal site containing up to 150 g/L of iron. We find that the colorful brine pools and mineral patterns of Dallol derive from the slow oxygen diffusion and progressive oxidation of the dissolved ferrous iron, the iron-chlorine/-sulfate complexation, and the evaporation. These inorganic processes induce the precipitation of nanoscale jarosite-group minerals and iron(III)-oxyhydroxides over a vast deposition of halite displaying complex architectures. Our results suggest that life, if present under such conditions, does not play a dominant role in the geochemical cycling and mineral precipitation at Dallol as opposed to other hydrothermal sites. Dallol, a hydrothermal system controlled by iron, is a present-day laboratory for studying the precipitation and progressive oxidation of iron minerals, relevant for geochemical processes occurring at early Earth and Martian environments.

Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: failure of another indirect cytotoxicity analysis.

AIMS: To report new information related to acute retinal toxicity of Bio Octane Plus, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane. METHODS: This retrospective, descriptive case series reports the occurrence of acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus (batch number 1605148) was used as an endotamponade. Cytotoxicity biocompatibility tests and chemical analyses by Fourier-transformed infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) of the presumed toxic product were performed. RESULTS: Four patients presented with acute severe visual loss after uneventful ocular surgery assisted by Bio Octane Plus (batch number 1605148) as endotamponade. Patients experienced extensive retinal vascular occlusion leading to retinal and optic nerve atrophy. The viability of ARPE-19 cells directly exposed to the suspect batch for 30 min was 0%. The agarose overlay method used by the manufacturer according to European Union regulations and International Organization for Standardization (ISO) International Standards failed to detect toxicity. FTIR spectroscopy showed small differences between the non-toxic and toxic batches. GC-MS analysis showed the presence of bromotributyl stannane (whose toxicity was demonstrated in the dose-response curve) only in the toxic batch of Bio Octane Plus. CONCLUSION: This is the third report of retinotoxicity due to PFO in 4 years. The clinical profiles may be missed as they resemble other postsurgical complications; therefore, more cases worldwide could have gone unreported. Protocols to determine cytotoxicity of intraocular medical devices and approved by the ISO International Standards based on indirect methods have failed and should be revised to ensure safety.

Comparison between direct contact and extract exposure methods for PFO cytotoxicity evaluation.

A series of recent acute blindness cases following non-complicated retinal detachment surgery caused the release of several health alerts in Spain. The blindness was attributed to certain lots of perfluoro-octane (PFO; a volatile and transient medical device). Similar cases have been reported in other countries. This has raised questions regarding the validity of cytotoxicity test methods currently used to certify the safety of PFO lots. The tests were performed according to the International Organization for Standardization (ISO) norms, using the extract dilution method or the indirect contact method as applied to L929 cells, a line derived from mouse fibroblasts. The limitations of those methods have been resolved in this study by proposing a new cytotoxicity test method for volatile substances. The new method requires direct contact of the tested substance with cells that are similar to those exposed to the substance in the clinical setting. This approach includes a few new technical steps that are crucial for detecting cytotoxicity. Our new method detected toxic PFO lots that corresponded to the lots producing clinical blindness, which previous methods failed to detect. The study suggests applying this new method to avoid occurrence of such cases of blindness.

ACUTE RETINAL DAMAGE AFTER USING A TOXIC PERFLUORO-OCTANE FOR VITREO-RETINAL SURGERY.

PURPOSE: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. METHODS: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots. RESULTS: Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity. CONCLUSION: Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.

The 2005 MARTE Robotic Drilling Experiment in Río Tinto, Spain: objectives, approach, and results of a simulated mission to search for life in the Martian subsurface.

The Mars Astrobiology Research and Technology Experiment (MARTE) simulated a robotic drilling mission to search for subsurface life on Mars. The drill site was on Peña de Hierro near the headwaters of the Río Tinto river (southwest Spain), on a deposit that includes massive sulfides and their gossanized remains that resemble some iron and sulfur minerals found on Mars. The mission used a fluidless, 10-axis, autonomous coring drill mounted on a simulated lander. Cores were faced; then instruments collected color wide-angle context images, color microscopic images, visible-near infrared point spectra, and (lower resolution) visible-near infrared hyperspectral images. Cores were then stored for further processing or ejected. A borehole inspection system collected panoramic imaging and Raman spectra of borehole walls. Life detection was performed on full cores with an adenosine triphosphate luciferin-luciferase bioluminescence assay and on crushed core sections with SOLID2, an antibody array-based instrument. Two remotely located science teams analyzed the remote sensing data and chose subsample locations. In 30 days of operation, the drill penetrated to 6 m and collected 21 cores. Biosignatures were detected in 12 of 15 samples analyzed by SOLID2. Science teams correctly interpreted the nature of the deposits drilled as compared to the ground truth. This experiment shows that drilling to search for subsurface life on Mars is technically feasible and scientifically rewarding.

Iron meteorites can support the growth of acidophilic chemolithoautotrophic microorganisms.

Chemolithoautotrophy based on reduced inorganic minerals is considered a primitive energy transduction system. Evidence that a high number of meteorites crashed into the planet during the early period of Earth history led us to test the ability of iron-oxidizing bacteria to grow using iron meteorites as their source of energy. Here we report the growth of two acidophilic iron-oxidizing bacteria, Leptospirillum ferrooxidans and Acidithiobacillus ferrooxidans, on a piece of the Toluca meteorite as the only source of energy. The alteration of the surface of the exposed piece of meteorite, the solubilization of its oxidized metal constituents, mainly ferric iron, and the formation of goethite precipitates all clearly indicate that iron-meteorite-based chemolithotrophic metabolism is viable.