Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

OBJECTIVE: To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. ANIMALS: 8 healthy neonatal calves. PROCEDURES: Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. RESULTS: Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections.

Subacute pulmonary toxicity of copper indium gallium diselenide following intratracheal instillations into the lungs of rats.

OBJECTIVES: The aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8-wk-old rats. METHODS: Male Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined. RESULTS: None of the CIGS-treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg-treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS-treated groups, and the severity of these lesions worsened with the passage of time. CONCLUSION: The present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats.

Pharmacokinetics of gallium nitrate after oral administration in adult horses--pilot study.

Gallium (Ga), a metal in group IIIA of the periodic table, has shown a remarkable activity against bone resorption and could therefore possibly prove useful in the treatment of certain diseases in sport horses, for example navicular disease. The aim of this study was to gain more information concerning the kinetics of Ga after oral administration of gallium nitrate (GaN) in adult horses. Six horses received a single dose of 10 mg/kg of GaN mixed with the food ration. Absorption was slow (T(max) = 10 ± 3 h, T(½abs) = 2 ± 0.8 h), and a C(max) of 26 ± 11 µg/L was achieved. Excretion followed a one-phase elimination model, with a long half-life (T(½el) = 52 ± 14 h). By means of a mathematical model, we estimated that the plasmatic levels should reach 93 µg/L (1.33 µm) at steady state, following the repeated daily administration of 10 mg/kg of GaN. A three times lower concentration has been demonstrated as effective in inhibiting the osteolytic activity of osteoclasts in vitro. The results of this study suggest that the administration of oral GaN at a rate of 10 mg/kg per day may be considered for future clinical studies.

Co-administration of meso 2,3-dimercaptosuccinic acid monoesters reduces arsenic concentration and oxidative stress in gallium arsenide exposed rats.

1. Gallium arsenide (GaAs), a semiconductor, exerts toxicity as a result of its constitutive moieties; that is, gallium and arsenic that becomes dissociated after exposure. The present study focuses on reducing arsenic concentration from the target organs using monoesters of meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination. 2. Animals were exposed to GaAs (0.0014 mol/kg, orally for 8 weeks) and then treated with monoisoamyl DMSA (MiADMSA), monocyclohexyl DMSA (MchDMSA) or monomethyl DMSA (MmDMSA) either individually (0.3 mmol/kg, orally) or in combination (0.15 mmol/kg each, orally) for five consecutive days. 3. GaAs exposure significantly inhibited blood δ-aminolevulinic acid dehydrogenase (ALAD), suggesting alterations in the heme synthesis pathway. Whereas a significant increase in blood, liver and kidney reactive oxygen species accompanied by an increase in lipid peroxidation points to the involvement of oxidative stress in GaAs toxicity. 4. GaAs also significantly disturbed glutathione metabolism. Hepatic and renal catalase activity decreased significantly, whereas hepatic and renal superoxide dismutase activity, as well as serum transaminases activity, showed marginal increase. Treatment with MiADMSA in combination with MchDMSA showed better therapeutic efficacy compared with other treatments in the aforementioned variables. 5. Co-administration of MiADMSA with MchDMSA provided better therapeutic effects, including reduction of arsenic burden, compared with all other treatments.

Measurement of glomerular filtration rate with chromium-51 ethylene diamino tetraacetic acid in the presence of gallium-67 citrate: a novel method for the solution of the problem.

Chromium-51 (5¹Cr)-ethylene diamino tetraacetic acid plasma clearance is commonly used in glomerular filtration rate measurements. In the presence of additional radionuclides in plasma samples, glomerular filtration rate may be seriously underestimated and a correction of the crosstalk interference may be necessary. This type of correction is problematic in the case of gallium-67 (67Ga) mainly because of the close vicinity of its 300 keV photopeak with that of the 320 keV photopeak of 5¹Cr. A novel method of calculating and removing the interfering 67Ga counts within the 5¹Cr counting window, based on the different decay rates of the two radionuclides, is presented, requiring two series of sample counting in the 5¹Cr counting window only, separated by a 3-day interval. This method was developed to solve a clinical problem and then it was validated by a controlled 67Ga contamination of plasma samples with known counts from 5¹Cr-ethylene diamino tetraacetic acid.

Pharmacokinetics of gallium maltolate after intragastric administration in adult horses.

OBJECTIVE: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in adult horses. ANIMALS: 6 adult horses. PROCEDURES: Feed was withheld for 12 hours prior to intragastric administration of GaM (20 mg/kg). A single dose of GaM was administered to each horse via a nasogastric tube (time 0). Blood samples were collected at various time points from 0 to 120 hours. Serum was used to determine gallium concentrations by use of inductively coupled plasma-mass spectroscopy. Noncompartmental and compartmental analyses of serum gallium concentrations were performed. Pharmacokinetic models were selected on the basis of the Akaike information criterion and visual analysis of plots of residuals. RESULTS: Serum concentration data for 1 horse were such that this horse was considered an outlier and excluded from noncompartmental and compartmental analyses. Noncompartmental analysis was used to determine individual pharmacokinetic parameters. A 1-compartment model with first-order input and output and lag time was selected as the best-fit model for the data and used to determine mean ± SD values for maximum observed serum concentration (0.28 ± 0.09 µg/mL), time of maximum concentration (3.09 ± 0.43 hours), time to the first measurable concentration (0.26 ± 0.11 hours), apparent elimination half-life (48.82 ± 5.63 hours), area under the time-concentration curve (20.68 ± 757 h•µg/mL), and apparent volume of distribution (73,493 ± 18,899 mL/kg). CONCLUSION AND CLINICAL RELEVANCE: Further studies are necessary to determine the bioavailability of GaM after intragastric administration in adult horses.

The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques.

Transition metal-based drugs exhibit high affinity to the soft donors of human serum proteins, especially of the high-abundance protein HSA and of transferrin (Tf), whereas Ga(III) salts are known to bind to Tf and other iron-containing metalloproteins, thereby interfering with the iron metabolism. Herein, the utilization of CE-MS methods for studying the binding behavior of a therapeutic gallium nitrate formulation and the anticancer drug candidate Tris(8-oxyquinolinato)gallium(III) to Tf and HSA under simulated physiological conditions is described. Both the Ga(III) salt and the complex were found to bind to Tf exclusively in the presence of carbonate, however, at different kinetics and to a different extent. Fe(III) induces the release of the Ga ions due to the higher affinity constant and also prevents the Ga(III) species from accessing the iron-binding pockets of Tf. In contrast, only low affinity to HSA was observed and even when present at ca. 20-fold excess, the majority of the Ga was attached to Tf.

Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals.

OBJECTIVE: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals. ANIMALS: 6 healthy neonatal foals. PROCEDURES: Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy. RESULTS: Mean +/- SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 +/- 311 ng/mL; time to peak serum concentration, 4.3 +/- 2.0 hours; area under the serum concentration versus time curve, 40,215 +/- 8,420 ng/mL/h; mean residence time, 39.5 +/- 17.2 hours; area under the moment curve, 1,636,554 +/- 931,458 ng([h](2)/mL); and terminal half-life, 26.6 +/- 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 +/- 195 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.

Lipid peroxidation in workers exposed to aluminium, gallium, indium, arsenic, and antimony in the optoelectronic industry.

OBJECTIVE: The objective of this study was to investigate whether exposure to aluminum, gallium, indium, arsenic, and antimony induces lipid peroxidation in humans. METHODS: Whole blood and urine levels of 103 exposed electronic industry workers and 67 referents were analyzed by use of inductively coupled plasma mass spectrometry. Malondialdehyde (MDA), the product of lipid peroxidation, was determined by high-performance liquid chromatography. RESULTS: The mean plasma MDA level in the 103 workers was significantly higher than that in 67 referents. The levels of MDA in the exposed workers were correlated significantly with the levels of urinary gallium and arsenic. CONCLUSIONS: Malondialdehyde as an index of lipid peroxidation can be induced by gallium and arsenic exposure. By reducing exposure to these metals, biologic effects such as lipid peroxidation may also be diminished.

Antimicrobial activity of gallium against virulent Rhodococcus equiin vitro and in vivo.

Rhodococcus equi, a facultative intracellular bacterium, causes severe pneumonia in foals. Evidence suggests that most foals become infected very early in life, when they have immature or ineffective innate immune responses. This study evaluated the antimicrobial activity of gallium against R. equi, as a potential chemoprophylactic and therapeutic agent. Rhodococcus equi was grown in media with various concentrations of gallium nitrate (GN), with and without excess iron. GN significantly inhibited growth and killed R. equi, and these effects were abolished with excess iron. Antimicrobial effects of Ga appear to be related to its interference with iron metabolism. Mice were treated orally with gallium maltolate (GaM), 10 or 50 mg/kg BW, or distilled H2O prior to and after experimental infection with R. equi. Six days post-infection, organs were harvested and R. equi concentrations assessed, and serum gallium concentrations determined. GaM was absorbed in a dose-dependent manner, and R. equi tissue burdens were greater in control mice than in all GaM-treated mice. GaM may aid in the control of disease by preventing development of overwhelming R. equi tissue burdens prior to the establishment of requisite innate and adaptive immune responses.

Biological monitoring of exposures to aluminium, gallium, indium, arsenic, and antimony in optoelectronic industry workers.

The main objective of this study was to investigate aluminum, gallium, indium, arsenic, and antimony exposures on blood and urine levels in the optoelectronic workers. One hundred seventy subjects were enrolled in this cohort study. Whole blood and urine levels were determined by inductively coupled plasma-mass spectrometry. Blood indium and urine gallium and arsenic levels in the 103 workers were significantly higher than that in 67 controls during the follow-up period. In regression models, the significant risk factors of exposure were job title, preventive equipment, Quetelet's index, sex, and education level. The findings of this study suggest that gallium, indium, and arsenic exposure levels may affect their respective levels in blood and urine. The use of clean, preventive equipment is recommended when prioritizing the administration of safety and hygiene in optoelectronics industries.

Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats.

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1), GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication.

Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats.

Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in the electronics industry. Exposure to GaAs in the semiconductor industry is a potential occupational hazard because cleaning and slicing GaAs ingots to yield the desired wafer could generate GaAs particles. The ability of GaAs to induce oxidative stress has not yet been reported. The present study reports the role of oxidative stress in GaAs-induced haematological and liver disorders and its possible reversal overturn by administration of meso-2,3-dimercaptosuccinic acid (DMSA) and one of its analogue, monoisoamyl DMSA (MiADMSA), either individually or in combination with oxalic acid. While DMSA and MiADMSA are potential arsenic chelators, oxalic acid is reported to be an effective gallium chelator. Male rats were exposed to 10 mg/kg GaAs orally, 5 days a week for 8 weeks. GaAs exposure was then stopped and rats were given a 0.5 mmol/kg dose of succimers (DMSA or MiADMSA), oxalic acid or a combination of the two, intraperitoneally once daily for 5 consecutive days. We found a significant fall in blood delta-aminolevulinic acid dehydratase (ALAD) activity and blood glutathione (GSH) level, and an increased urinary excretion of delta-aminolevulinic acid (ALA) and an increased malondialdehyde (MDA) level in erythrocytes of rats exposed to GaAs. Hepatic GSH levels decreased, whereas there was an increase in GSSG and MDA levels. The results suggest a role of oxidative stress in GaAs-induced haematological and hepatic damage. Administration of DMSA and MiADMSA produced effective recovery in most of the above variables. However, a greater effectiveness of the chelation treatment (i.e. removal of both gallium and arsenic from body organs) could be achieved by combined administration of succimer (DMSA) with oxalic acid since, after MiADMSA administration, a marked loss of essential metals (copper and zinc) is of concern.

Co, Fe and Ga chelates for cell labelling: a potential use in PET imaging?

The radiolabelling of blood cellular elements with PET radionuclides offers a higher sensitivity and resolution than conventional imaging, but short-lived PET radionuclides have limited clinical use in cell labelling. Medium half-life PET radionuclides, such as 55Co (t1/2 = 18.2 h), 52Fe (t1/2 = 8.3 h) and 66Ga (t1/2 = 9.4 h), enable quantitative uptake and cell kinetic studies with radiolabelled blood cellular elements. Co(II) oxine, Co(III) tropolonate, Fe(III) oxine, Ga(III) oxine and Ga(III) MPO were prepared using gamma-emitting radionuclides and a number of cell labelling parameters were investigated. The uptake of 57Co(II) oxine into erythrocytes was only 37%, and 65% of the activity eluted from the cells in cell-free plasma within 30 min. In contrast, high leukocyte and erythrocyte labelling efficiencies (> 90%) were obtained with 57Co(III) tropolonate containing cobalt carrier and the elution in cell-free plasma over 4 h was < 8%. High labelling efficiencies were also observed with 59Fe(III) oxine and 67Ga-MPO and the elution from leukocytes over 4 h was < 25%. We conclude that Co(III) tropolonate, Fe(III) oxine and Ga-MPO may be useful for radiolabelling leukocytes for PET investigations.

Osteomielite de face em hemofílicos aidéticos: avaliaçäo cintigráfica / Facial osteomyelitis in haemophiliacs aids patients: scintigraphic evaluation

Säo relatados seis casos de osteomielite de face, que surgiram como complicaçäo de sinusite crônica em pacientes hemofílicos aidéticos. A verificaçäo da velocidade de hemossedimentaçäo elevada nestes pacientes levou à suspeita de osteomielite. O diagnóstico foi confirmado pela cintigrafia óssea com 99mTc- MDP positiva. A velocidade de hemossedimentaçäo e os estudos com citrato de 67-Gálio foram obtidos para acompanhar a evoluçäo da terapia. Os resultados sugerem que a cintigrafia com MDP é sensível e específica para detecçäo precoce de osteomielite em sinusite; e os achados com Gálio, valiosos no acompanhamento da infecçäo

Uptake of aluminum and gallium into tissues of the rat: influence of antibody against the transferrin receptor.

Transport of aluminum and gallium from blood into rat tissues following continuous i.v. infusion of metals in different chemical forms has been investigated. Tissue uptake of aluminum and gallium was similar and highly dependent on the chemical species of the metals. Aluminum and gallium accumulated in liver and spleen when infused in the chloride form. Raised citrate markedly enhanced aluminum and gallium uptake into renal cortex and bone; in contrast with gallium-transferrin, citrate increased uptake of 67Ga into renal cortex and bone by 8- and 14-fold respectively. Uptake of 67Ga with citrate into renal cortex was around 3 times smaller than that of aluminum. The antitransferrin receptor antibody OX-26 enhanced 67Ga uptake from gallium citrate into all rat tissues. 67Ga from purified gallium-transferrin was also taken into all tissues in the presence of OX-26, the effect being greatest in renal cortex and bone. No influence of antibody on aluminum transport into rat tissues was, however, observed when aluminum was infused in the citrate form. Therefore, transport of aluminum and gallium into tissues is not similar under all conditions. Transport of each metal occurs into all tissues in the presence of antitransferrin receptor antibody. The potential for such transport is much greater in the case of gallium. Transport of aluminum and gallium citrate complexes appears important especially in the renal cortex and bone.

Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.

Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in electronic industry. Exposure to GaAs in the semiconductor industries could be a possible occupational risk. The aim of the present study was to determine the dose-dependent effect of single oral exposure to GaAs (500, 1000, or 2000 mg/kg) on some biochemical variables in heme synthesis pathway and few selected physiological variables at d 1, 7, and 15 following administration. The results indicate that GaAs produced a significant effect on the activity of delta-aminolevulinic acid dehydratase (ALAD) in blood and heart (particularly at d 7) following exposure to 2000 mg/kg, whereas urinary delta-aminolevulinic acid (ALA) excretion was elevated only at d 7. No marked influence of GaAs on blood hemoglobin, zinc protoporphyrin, and packed cell volume was noticed. Blood glutathione (GSH) was significantly reduced at d 7, but remained unchanged at two other time intervals. On the other hand, heart GSH contents remained uninfluenced on GaAs exposure. Most of the physiological variables, viz. blood pressure, heart and respiration rate, and twitch response, remained unchanged, except for some minor alterations observed at d 7 and 15 following exposure to GaAs at a dose of 2000 mg/kg. Blood gallium concentration was not detectable in normal animals and rats exposed to 500 mg/kg GaAs. Blood arsenic concentration was, however, detectable even at the a lower dose level and increased in a dose-dependent manner. All these changes showed a recovery pattern at d 21, indicating that the alterations are reversible.

Gallium-transferrin binding in treated and untreated Parkinson's disease.

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.

The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.