Intra-tracheal administration increases gallium availability in lung: implications for antibacterial chemotherapy.

The emergence of pan-resistant strains in nosocomial settings underscores the urgent need of novel therapies targeting vital bacterial functions. Bacterial iron metabolism is a fascinating target for new antimicrobials. Iron mimetic metal Ga(III) has been repurposed as an antimicrobial drug, in pre-clinical studies and recent clinical studies have raised the possibility of using Ga(III) for the treatment of P. aeruginosa pulmonary infection. Ga(III) has been approved by FDA for the treatment of cancer, autoimmune and bone resorption disorders. However, some critical issues affect the therapeutic schedule of Ga(III), principally the intra-venous (i.v.) administration, and the nephrotoxicity caused by prolonged administration. Ga(III) aerosolization could represent a viable alternative for treatment of lung infections, since delivery of antimicrobial agents to the airways maximizes drug concentration at the site of infection, improves the therapeutic efficacy, and alleviates systemic toxic effects. We demonstrate the advantage of inhaled vs i.v. administered Ga(III), in terms of bio-distribution and lung acute toxicity, by using a rat model. In vivo results support the use of Ga(III) for inhalation since intra-tracheal Ga(III) delivery improved its persistence in the lung, while the i.v. administration caused rapid clearance and did not allow to attain a significant Ga(III) concentration in this organ. Moreover, local and systemic acute toxicity following intra-tracheal administration was not observed, since no significant signs of inflammation were found. At this stage of evidence, the direct administration of Ga(III) to the lung appears feasible and safe, boosting the development of Ga(III)-based drugs for inhalation therapy.

Cytotoxicity Assessment of Gallium- and Indium-Based Nanoparticles Toward Human Bronchial Epithelial Cells Using an Impedance-Based Real-Time Cell Analyzer.

The semiconductor manufacturing sector plans to introduce III/V film structures (eg, gallium arsenide (GaAs), indium arsenide (InAs) onto silicon wafers due to their high electron mobility and low power consumption. Aqueous solutions generated during chemical and mechanical planarization of silicon wafers can contain a mixture of metal oxide nanoparticles (NPs) and soluble indium, gallium, and arsenic. In this work, the cytotoxicity induced by Ga- and In-based NPs (GaAs, InAs, Ga2O3, In2O3) and soluble III-V salts on human bronchial epithelial cells (16HBE14o-) was evaluated using a cell impedance real-time cell analysis (RTCA) system. The RTCA system provided inhibition data at different concentrations for multiple time points, for example, GaAs (25 mg/L) caused 60% inhibition after 8 hours of exposure and 100% growth inhibition after 24 hours. Direct testing of As(III) and As(V) demonstrated significant cytotoxicity with 50% growth inhibition concentrations after 16-hour exposure (IC50) of 2.4 and 4.5 mg/L, respectively. Cell signaling with rapid rise and decrease in signal was unique to arsenic cytotoxicity, a precursor of strong cytotoxicity over the longer term. In contrast with arsenic, soluble gallium(III) and indium(III) were less toxic. Whereas the oxide NPs caused low cytotoxicity, the arsenide compounds were highly inhibitory (IC50 of GaAs and InAs = 6.2 and 68 mg/L, respectively). Dissolution experiments over 7 days revealed that arsenic was fully leached from GaAs NPs, whereas only 10% of the arsenic was leached out of InAs NPs. These results indicate that the cytotoxicity of GaAs and InAs NPs is largely due to the dissolution of toxic arsenic species.

Microbial toxicity of gallium- and indium-based oxide and arsenide nanoparticles.

III-V semiconductor materials such as gallium arsenide (GaAs) and indium arsenide (InAs) are increasingly used in the fabrication of electronic devices. There is a growing concern about the potential release of these materials into the environment leading to effects on public and environmental health. The waste effluents from the chemical mechanical planarization process could impact microorganisms in biological wastewater treatment systems. Currently, there is only limited information about the inhibition of gallium- and indium-based nanoparticles (NPs) on microorganisms. This study evaluated the acute toxicity of GaAs, InAs, gallium oxide (Ga2O3), and indium oxide (In2O3) particulates using two microbial inhibition assays targeting methanogenic archaea and the marine bacterium, Aliivibrio fischeri. GaAs and InAs NPs were acutely toxic towards these microorganisms; Ga2O3 and In2O3 NPs were not. The toxic effect was mainly due to the release of soluble arsenic species and it increased with decreasing particle size and with increasing time due to the progressive corrosion of the NPs in the aqueous bioassay medium. Collectively, the results indicate that the toxicity exerted by the arsenide NPs under environmental conditions will vary depending on intrinsic properties of the material such as particle size as well as on the dissolution time and aqueous chemistry.

Assessing chronic toxicity of aluminium, gallium and molybdenum in tropical marine waters using a novel bioassay for larvae of the hermit crab Coenobita variabilis.

A novel bioassay is presented that allows for the estimation of the chronic toxicity of contaminants in receiving tropical marine environments. Relevant procedures to identify contaminants of concern and evaluate hazards associated with contamination in these environments have long remained inadequate. The 6-day bioassay is conducted using freshly hatched planktonic larvae of the hermit crab Coenobita variabilis and is targeted at generating environmentally relevant, chronic toxicity data. The developmental endpoint demonstrated consistently high control performance and was validated through the use of copper as a reference toxicant. In addition, the biological effects of aluminium, gallium and molybdenum were assessed. The endpoint expressed high sensitivity to copper (EC10 = 24 µg L-1) and moderate sensitivity to aluminium (EC10 = 312 µg L-1), whereas gallium and molybdenum elicited no obvious effects, even at high concentrations (EC10 > 6000 µg L-1), providing valuable information on the toxicity of these elements in tropical marine waters for derivation of water quality guidelines or testing of compliance limits.

Ecotoxicity assessment of ionic As(III), As(V), In(III) and Ga(III) species potentially released from novel III-V semiconductor materials.

III-V materials such as indium arsenide (InAs) and gallium arsenide (GaAs) are increasingly used in electronic and photovoltaic devices. The extensive application of these materials may lead to release of III-V ionic species during semiconductor manufacturing or disposal of decommissioned devices into the environment. Although arsenic is recognized as an important contaminant due to its high toxicity, there is a lack of information about the toxic effects of indium and gallium ions. In this study, acute toxicity of As(III), As(V), In(III) and Ga(III) species was evaluated using two microbial assays testing for methanogenic activity and O2 uptake, as well as two bioassays targeting aquatic organisms, including the marine bacterium Aliivibrio fischeri (bioluminescence inhibition) and the crustacean Daphnia magna (mortality). The most noteworthy finding was that the toxicity is mostly impacted by the element tested. Secondarily, the toxicity of these species also depended on the bioassay target. In(III) and Ga(III) were not or only mildly toxic in the experiments. D. magna was the most sensitive organism for In(III) and Ga(III) with 50% lethal concentrations of 0.5 and 3.4mM, respectively. On the other hand, As(III) and As(V) caused clear inhibitory effects, particularly in the methanogenic toxicity bioassay. The 50% inhibitory concentrations of both arsenic species towards methanogens were about 0.02mM, which is lower than the regulated maximum allowable daily effluent discharge concentration (2.09mg/L or 0.03mM) for facilities manufacturing electronic components in the US. Overall, the results indicate that the ecotoxicity of In(III) and Ga(III) is much lower than that of the As species tested. This finding is important in filling the knowledge gap regarding the ecotoxicology of In and Ga.

The growth and uptake of Ga and In of rice (Oryza sative L.) seedlings as affected by Ga and In concentrations in hydroponic cultures.

Limited information is available on the effects of gallium (Ga) and indium (In) on the growth of paddy rice. The Ga and In are emerging contaminants and widely used in high-tech industries nowadays. Understanding the toxicity and accumulation of Ga and In by rice plants is important for reducing the effect on rice production and exposure risk to human by rice consumption. Therefore, this study investigates the effect of Ga and In on the growth of rice seedlings and examines the accumulation and distribution of those elements in plant tissues. Hydroponic cultures were conducted in phytotron glasshouse with controlled temperature and relative humidity conditions, and the rice seedlings were treated with different levels of Ga and In in the nutrient solutions. The growth index and the concentrations of Ga and In in roots and shoots of rice seedlings were measured after harvesting. A significant increase in growth index with increasing Ga concentrations in culture solutions (<10mgGaL-1) was observed. In addition, the uptake of N, K, Mg, Ca, Mn by rice plants was also enhanced by Ga. However, the growth inhibition were observed while the In concentrations higher than 0.08mgL-1, and the nutrients accumulated in rice plants were also significant decreased after In treatments. Based on the dose-response curve, we observed that the EC10 (effective concentration resulting in 10% growth inhibition) value for In treatment was 0.17mgL-1. The results of plant analysis indicated that the roots were the dominant sink of Ga and In in rice seedlings, and it was also found that the capability of translocation of Ga from roots to shoots were higher than In. In addition, it was also found that the PT10 (threshold concentration of phytotoxicity resulting in 10% growth retardation) values based on shoot height and total biomass for In were 15.4 and 10.6µgplant-1, respectively. The beneficial effects on the plant growth of rice seedlings were found by the addition of Ga in culture solutions. In contrast, the In treatments led to growth inhibition of rice seedlings. There were differences in the phytotoxicity, uptake, and translocation of the two emerging contaminants in rice seedlings.

Restoration of growth by manganese in a mutant strain of Escherichia coli lacking most known iron and manganese uptake systems.

The interplay of manganese and iron homeostasis and oxidative stress in Escherichia coli can give important insights into survival of bacteria in the phagosome and under differing iron or manganese bioavailabilities. Here, we characterized a mutant strain devoid of all know iron/manganese-uptake systems relevant for growth in defined medium. Based on these results an exit strategy enabling the cell to cope with iron depletion and use of manganese as an alternative for iron could be shown. Such a strategy would also explain why E. coli harbors some iron- or manganese-dependent iso-enzymes such as superoxide dismutases or ribonucleotide reductases. The benefits for gaining a means for survival would be bought with the cost of less efficient metabolism as indicated in our experiments by lower cell densities with manganese than with iron. In addition, this strain was extremely sensitive to the metalloid gallium but this gallium toxicity can be alleviated by low concentrations of manganese.

Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii.

Bacteremia caused by Acinetobacter baumannii is a highly lethal complication of hospital-acquired pneumonia. In the present study, we investigated the serum resistance, gallium nitrate tolerance and heme consumption of A. baumannii strain LAC-4 which was recently reported to display high virulence in a mouse pneumonia model with extrapulmonary dissemination leading to fatal bacteremia. This strain showed enhanced growth in mouse and fetal bovine serum that was independent of complement and was not observed with regular growth media. The LAC-4 strain was found to possess a high tolerance to gallium nitrate (GaN), whereas serum synergized with GaN in inhibiting A. baumannii strain ATCC 17978. We found that LAC-4 contains a heme oxygenase gene and expresses a highly efficient heme consumption system. This system can be fully blocked in vitro and in vivo by gallium protoporphyrin IX (GaPPIX). Inhibition of heme consumption by GaPPIX completely abrogated the growth advantage of LAC-4 in serum as well as its tolerance to GaN. More importantly, GaPPIX treatment of mice intranasally infected with LAC-4 prevented extrapulmonary dissemination and death. Thus, we propose that heme provides an additional source of iron for LAC-4 to bypass iron restriction caused by serum transferrin, lactoferrin or free gallium salts. Heme consumption systems in A. baumannii may constitute major virulence factors for lethal bacteremic isolates.

Comparative acute toxicity of gallium(III), antimony(III), indium(III), cadmium(II), and copper(II) on freshwater swamp shrimp (Macrobrachium nipponense).

BACKGROUND: Acute toxicity testing were carried out the freshwater swamp shrimp, Macrobrachium nipponense, as the model animal for the semiconductor applied metals (gallium, antimony, indium, cadmium, and copper) to evaluate if the species is an suitable experimental animal of pollution in aquatic ecosystem. RESULTS: The static renewal test method of acute lethal concentrations determination was used, and water temperature was maintained at 24.0 ± 0.5°C. Data of individual metal obtained from acute toxicity tests were determined using probit analysis method. The median lethal concentration (96-h LC50) of gallium, antimony, indium, cadmium, and copper for M. nipponense were estimated as 2.7742, 1.9626, 6.8938, 0.0539, and 0.0313 mg/L, respectively. CONCLUSIONS: Comparing the toxicity tolerance of M. nipponense with other species which exposed to these metals, it is obviously that the M. nipponense is more sensitive than that of various other aquatic animals.

Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants.

Pseudomonas aeruginosa PA14 cells resistant to the novel antimicrobial gallium nitrate (Ga) were developed using transposon mutagenesis and by selecting spontaneous mutants. The mutants showing the highest growth in the presence of Ga were selected for further characterization. These mutants showed 4- to 12-fold higher Ga minimal inhibitory growth concentrations and a greater than 8-fold increase in the minimum biofilm eliminating Ga concentration. Both types of mutants produced Ga resistant biofilms whereas the formation of wild-type biofilms was strongly inhibited by Ga. The gene interrupted in the transposon mutant was hitA, which encodes a periplasmic iron binding protein that delivers Fe³âº to the HitB iron permease; complementation of the mutant with the hitA gene restored the Ga sensitivity. This hitA mutant showed a 14-fold decrease in Ga internalization versus the wild-type strain, indicating that the HitAB system is also involved in the Ga uptake. Ga uptake in the spontaneous mutant was also lower, although no mutations were found in the hitAB genes. Instead, this mutant harbored 64 non-silent mutations in several genes including those of the phenazine pyocyanin biosynthesis. The spontaneous mutant produced 2-fold higher pyocyanin basal levels than the wild-type; the addition of this phenazine to wild-type cultures protected them from the Ga bacteriostatic effect. The present data indicate that mutations affecting Ga transport and probably pyocyanin biosynthesis enable cells to develop resistance to Ga.

Evaluation of the carcinogenicity of gallium arsenide.

Gallium arsenide (GaAs) is an important semiconductor material. In 2-year inhalation studies, GaAs increased the incidence of lung tumors in female rats, but not in male rats or male and female mice. Alveolar proteinosis followed by chronic active inflammation was the predominant non-neoplastic pulmonary findings. IARC classified GaAs as carcinogenic to humans (group 1) based on the assumption that As and Ga ions are bioavailable. The European Chemical Agency Risk Assessment Committee concluded that GaAs should be classified into Carcinogenicity Category 1B (presumed to have carcinogenic potential for humans; ECHA). We evaluate whether these classifications are justified. Physico-chemical properties of GaAs particles and the degree of mechanical treatment are critical in this evaluation. The available data on mode of action (MOA), genotoxicity and bioavailability do not support the contribution of As or Ga ions to the lung tumors in female rats. Most toxicological studies utilized small particles produced by strong mechanical treatment, destroying the crystalline structure. The resulting amorphous GaAs is not relevant to crystalline GaAs at production and processing sites. The likely tumorigenic MOA is lung toxicity related to particulate-induced inflammation and increased proliferation. It is concluded that there is no evidence for a primary carcinogenic effect of GaAs.

Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function.

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clean-room staff fabricating and characterizing the nanowires are at risk of exposure, emphasizing the importance of investigating their possible toxicity. Here we investigated the effects of gallium phosphide nanowires on the fruit fly Drosophila melanogaster. Drosophila larvae and/or adults were exposed to gallium phosphide nanowires by ingestion with food. The toxicity and tissue interaction of the nanowires was evaluated by investigating tissue distribution, activation of immune response, genome-wide gene expression, life span, fecundity and somatic mutation rates. Our results show that gallium phosphide nanowires applied through the diet are not taken up into Drosophila tissues, do not elicit a measurable immune response or changes in genome-wide gene expression and do not significantly affect life span or somatic mutation rate.

Chemical-genomic profiling identifies genes that protect yeast from aluminium, gallium, and indium toxicity.

Aluminium, gallium, and indium are group 13 metals with similar chemical and physical properties. While aluminium is one of the most abundant elements in the Earth's crust, gallium and indium are present only in trace amounts. However, the increased use of the latter metals in novel technologies may result in increased human and environmental exposure. There is mounting evidence that these metals are toxic, but the underlying mechanisms remain poorly understood. Likewise, little is known about how cells protect themselves from these metals. Aluminium, gallium, and indium are relatively insoluble at neutral pH, and here we show that they precipitate in yeast culture medium at acidic pH as metal-phosphate species. Despite this, the dissolved metal concentrations are sufficient to induce toxicity in the yeast Saccharomyces cerevisiae. By chemical-genomic profiling of the S. cerevisiae gene deletion collection, we identified genes that maintain growth in the presence of the three metals. We found both shared and metal-specific genes that confer resistance. The shared gene products included functions related to calcium metabolism and Ire1/Hac1-mediated protection. Metal-specific gene products included functions in vesicle-mediated transport and autophagy for aluminium, protein folding and phospholipid metabolism for gallium, and chorismate metabolic processes for indium. Many of the identified yeast genes have human orthologues involved in disease processes. Thus, similar protective mechanisms may act in yeast and humans. The protective functions identified in this study provide a basis for further investigations into toxicity and resistance mechanisms in yeast, plants, and humans.

Evaluation of the male reproductive toxicity of gallium arsenide.

Gallium arsenide is an important semiconductor material marketed in the shape of wafers and thus is not hazardous to the end user. Exposure to GaAs particles may, however, occur during manufacture and processing. Potential hazards require evaluation. In 14-week inhalation studies with small GaAs particles, testicular effects have been reported in rats and mice. These effects occurred only in animals whose lungs showed marked inflammation and also had hematologic changes indicating anemia and hemolysis. The time- and concentration-dependent progressive nature of the lung and blood effects together with bioavailability data on gallium and arsenic lead us to conclude that the testicular/sperm effects are secondary to hypoxemia resulting from lung damage rather than due to a direct chemical effect of gallium or arsenide. Conditions leading to such primary effects are not expected to occur in humans at production and processing sites. This has to be taken into consideration for any classification decision for reproductive toxicity; especially a category 1 according to the EU CLP system is not warranted.

Corrosion Resistance and Cytocompatibility of Magnesium-Calcium Alloys Modified with Zinc- or Gallium-Doped Calcium Phosphate Coatings.

In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 µm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω-1 cm-2 sn upon doping with Zn and Ga, respectively. The Ecorr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104 cells/cm2) and Ga-doped (6.3 × 104 cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103 cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.

The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source.

Gallium ions have previously been shown to exhibit antibacterial and antibiofilm properties. In this study, we report differential bactericidal activities of two gallium complexes, gallium desferrioxamine B (Ga-DFOB) and gallium citrate (Ga-Cit). Modeling of gallium speciation in growth medium showed that DFOB and citrate both can prevent precipitation of Ga(OH)(3), but some precipitation can occur above pH 7 with citrate. Despite this, Ga-Cit 90% inhibitory concentrations (IC(90)) were lower than those of Ga-DFOB for clinical isolates of Pseudomonas aeruginosa and several reference strains of other bacterial species. Treatment with Ga compounds mitigated damage inflicted on murine J774 macrophage-like cells infected with P. aeruginosa PAO1. Again, Ga-Cit showed more potent mitigation than did Ga-DFOB. Ga was also taken up more efficiently by P. aeruginosa in the form of Ga-Cit than in the form of Ga-DFOB. Neither Ga-Cit nor Ga-DFOB was toxic to several human cell lines tested, and no proinflammatory activity was detected in human lung epithelial cells after exposure in vitro. Metabolomic analysis was used to delineate the effects of Ga-Cit on the bacterial cell. Exposure to Ga resulted in lower concentrations of glutamate, a key metabolite for P. aeruginosa, and of many amino acids, indicating that Ga affects various biosynthesis pathways. An altered protein expression profile in the presence of Ga-Cit suggested that some compensatory mechanisms were activated in the bacterium. Furthermore, the antibacterial effect of Ga was shown to vary depending on the carbon source, which has importance in the context of medical applications of gallium.

The growth and uptake of gallium (Ga) and indium (In) of wheat seedlings in Ga- and In-contaminated soils.

The emerging contaminants gallium (Ga) and indium (In) are extensively used in advanced industries and are considered as toxic to humans. Limited information is available on the dynamics of Ga and In in soil-upland crop systems. Therefore, this study aimed to investigate the effects of Ga and In on the growth and uptake of Ga and In by wheat plants grown in Ga- and In-contaminated soils. The wheat seedlings were planted in soils of different properties spiked with various Ga and In concentrations (50, 100, 200, and 400 mg kg-1). The plant-available Ga, In, and Al in the soils were extracted by 0.02 M CaCl2, and their concentrations in plant tissues of wheat seedlings and plant biomass were determined after harvesting. The results indicated that the Al toxicity of wheat seedlings increased with Ga and In concentrations in acidic soils. Indium phytotoxicity was found in both neutral and acidic soils. Plant analysis results indicated that the concentration of Ga and In in roots was approximately one order of magnitude higher than that in the shoots of wheat seedlings, and the capability for Ga translocation from roots to shoots was higher than for In. The results of this study suggest that the dynamics of Ga and In in soil-upland crop systems is strongly dependent on the soil properties, such as pH and Al availability.

Dermal absorption of gallium antimonide in vitro and pro-inflammatory effects on human dermal fibroblasts.

Gallium antimonide (GaSb) is a group III-V compound semiconductor with a comparatively narrow band gap energy (0.73 eV at 300 K) that allows efficient operation in the near-infrared region. This property may be useful in developing new biomedical instruments such as epidermal optoelectronic devices. The present study investigated the absorption of GaSb in pig skin in vitro for 24 h using Franz cells. A donor solution was prepared by soaking GaSb thin films in synthetic sweat. The results showed that both gallium and antimony penetrated the skin, and permeation and resorption occurred for gallium. Histopathological findings showed no inflammatory responses in pig skin exposed to GaSb for 24 h. Cytotoxicity was significantly elevated after 3 and 7 days, and pro-inflammatory cytokines and IL-8 levels were low after 1 and 3 days but elevated 7 days following the direct culturing of human dermal fibroblasts (HDF) on GaSb thin films. These results demonstrate that the short-term cytotoxicity and pro-inflammatory effect of GaSb on HDF were relatively low.

The suitability of gallium as a substitute for aluminum in tracing experiments.

Aluminum is a toxic metal whose complex aquatic chemistry, mechanisms of toxicity and trophic transfer are not fully understood. The only isotope of Al suitable for tracing experiments in organisms-(26)Al-is a rare, costly radioisotope with a low emission energy, making its use difficult. Gallium shares a similar chemistry with Al and was therefore investigated as a potential substitute for Al for use in aquatic organisms. The freshwater snail, Lymnaea stagnalis was exposed to either Al or Ga (0.0135 mM) under identical conditions for up to 40 days. Behavioural toxicity, metal accumulation in the tissues, and sub-cellular partitioning of the metals were determined. Al was more toxic than Ga and accumulated to significantly higher levels in the soft tissues (P < 0.05). The proportion of Al in the digestive gland (DG; detoxificatory organ) relative to other tissues was significantly lower than that of Ga (P < 0.05) from day 14 onwards. There were also differences in the proportions of Al and Ga associated with heat stable proteins (HSPs) in the digestive gland, with significantly more HSP present in the DGs of snails exposed to Al, but significantly less Al than Ga associated with the HSP per unit mass protein present. From this evidence, we conclude that Ga may be of limited use as a tracer for Al in animal systems.

The toxicology of gallium oxide in comparison with gallium arsenide and indium oxide.

Gallium arsenide (GaAs) and indium oxide (In2O3) are used in electronic industries at high and increasing tonnages since decades. Gallium oxide (Ga2O3) is an emerging wide-bandgap transparent conductive oxide with as yet little industrial use. Since GaAs has received critical attention due to the arsenic ion, it seemed reasonable to compare its toxicology with the respective endpoints of Ga2O3 and In2O3 toxicology in order to find out if and to what extent arsenic contributes. In addition, the toxicology of Ga2O3 has not yet been adequately reviewed, Therefore, this review provides the first evaluation of all available toxicity data on Ga2O3. The acute toxicity of all three compounds is rather low. Subchronic inhalation studies in rats and mice revealed persistent pulmonary alveolar proteinosis (PAP) and/or alveolar histiocytic infiltrates down to the lowest tested concentration in rats and mice, i.e. 0.16 mg Ga2O3/m3. These are also the predominant effects after GaAs and In2O3 exposure at similarly low levels, i.e. 0.1 mg/m3 each. Subchronic Ga2O3 exposure caused a minimal microcytic anemia with erythrocytosis in rats (at 6.4 mg/m3 and greater) and mice (at 32 and 64 mg/m3), a decrease in epididymal sperm motility and concentration as well as testicular degeneration at 64 mg/m3. At comparable concentrations the hematological effects and male fertility of GaAs were much stronger. The stronger effects of GaAs are due to its better solubility and presumed higher bioavailability. The database for In2O3 is too small and subchronic testing was at very low levels to allow conclusive judgements if blood/blood forming or degrading and male fertility organs/tissues would also be targets.