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At least 19 recordsLinked to original sources

Determination of germanium in urine and its usefulness for biomonitoring of inhalation exposure to inorganic germanium in the occupational setting.

The present study aimed to assess whether urinary germanium concentration can be used as a biomarker of inhalation exposure to airborne dust from metallic germanium (Ge) or GeO2 in the occupational setting. A novel hydride generation-based method coupled with fow-injection graphite furnace atomic absorption spectrometry (HG/FI-GFAAS) was developed for the determination of urinary germanium. It was found that urinary germanium concentration could be reliably determined by a standard additions method after thorough digestion of the urine and careful pH adjustment of the digest. The limit of detection (LOD) in urine for the HG/FI-GFAAS method was 0.25 microg Ge L(-1). In Belgian control male subjects, the urinary germanium concentration was below this LOD. In 75 workers currently exposed to inorganic germanium compounds, respirable and inhalable concentrations of germanium in the aerosols were measured on Monday and Friday at the job sites using personal air samplers. Spot-urine samples were collected on the same days before and after the work shift. The germanium concentrations of respirable dust correlated very well with those of inhalable dust and represented 20% of the inhalable fraction. Workers exposed to metallic Ge dust were on average ten times less exposed to germanium than those whose exposure involved GeO2 (3.4 versus 33.8 microg Ge m(-3)). This difference was reflected in the urinary germanium concentrations (3.4 versus 23.4 microg Ge g(-1) creatinine). Regression analysis showed that the concentration of germanium in the inhalable fraction explained 42% of the post-shift urinary germanium concentration either on Monday or on Friday, whereas in a subgroup of 52 workers mainly exposed to metallic germanium dust 57% (r = 0.76) of the Monday post-shift urinary germanium was explained. Urinary elimination kinetics were studied in seven workers exposed to airborne dust of either metallic Ge or GeO2. The urinary elimination rate of germanium was characterised by half-times ranging from 8.2 to 18.1 h (on average 12 h 46 min). The present study did not allow discrimination between the germanium species to which the workers were exposed, but it showed fast urinary elimination kinetics for inhalation exposure to dust of metallic Ge and GeO2. It pointed out that urine samples taken at the end of the work shift can be used for biological monitoring of inorganic germanium exposure in the occupational setting.

Air Pollution, Indoor↗

[Respective determination of inorganic germanium and germanium-132 in foods].

Inorganic germanium and carboxyethyl germanium sesquioxide (germanium-132) in health drinks were respectively determined by hydride generation-atomic fluorescence spectrometry (HG-AFS). The conditions of respective determination of inorganic germanium and germanium-132 in natural foods were preliminarily discussed.

Beverages↗

Determination of germanium and some other elements in hair, nail, and toenail from persons exposed and unexposed to germanium.

Inductively coupled atomic emission spectrometry was used for the determination of germanium in hair, nail, and toenail. The levels of germanium in three individuals administered a high concentration of a germanium preparation daily for about 12-16 months were very high: 56.4-173.7; 5.4-35.0; and 14.0-15.8 micrograms g-1 in hair, nail, and toenail, respectively. The levels for normal or unexposed persons are very low and were not detected by the method.

Adult↗

Germanium poisoning: clinical symptoms and renal damage caused by long-term intake of germanium.

We report five patients who have taken inorganic germanium preparations over a prolonged period. In all cases, the renal function deteriorated with no proteinuria or hematuria. Histological examination of the kidneys showed widespread tubular degeneration and interstitial fibrosis with minor glomerular abnormalities. Most patients had gastrointestinal symptoms such as vomiting, anorexia and weight loss; one patient had peripheral neuropathy and myopathy. A considerable amount of germanium was detected in the hair or nails of these patients. These cases clearly show that abuse of inorganic germanium compounds can induce renal damage with various extrarenal manifestations.

Aged↗

Investigation of silver salt metathesis: preparation of cationic germanium(II) and Tin(II) complexes, and silver adducts containing unsupported silver-germanium and silver-tin bonds.

Syntheses of halide derivatives of germanium(II) and tin(II) aminotroponiminate (ATI) complexes and their silver salt metathesis reactions have been investigated. The treatment of GeCl(2) x (1,4-dioxane), SnCl(2), or SnI(2) with [(n-Pr)(2)ATI]Li in a 1:1 molar ratio affords the corresponding germanium(II) or tin(II) halide complex [(n-Pr)(2)ATI]MX (where [(n-Pr)(2)ATI](-) = N-(n-propyl)-2-(n-propylamino)troponiminate; M = Ge or Sn; X = Cl or I). As usually expected, [(n-Pr)(2)ATI]GeCl and [(n-Pr)(2)ATI]SnCl undergo rapid metathesis with CF(3)SO(3)Ag, leading to trifluoromethanesulfonate salts, [[(n-Pr)(2)ATI]Ge][SO(3)CF(3)] and [[(n-Pr)(2)ATI]Sn][SO(3)CF(3)], and silver chloride. However, when the silver source [HB(3,5-(CF(3))(2)Pz)(3)]Ag(eta(2)-toluene) is used, rather than undergoing metathesis, very stable 1:1 adducts [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Ge(Cl)[(n-Pr)(2)ATI] and [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Sn(Cl)[(n-Pr)(2)ATI] are formed (where [HB(3,5-(CF(3))(2)Pz)(3)](-) = hydrotris(3,5-bis(trifluoromethyl)pyrazolyl)borate). The use of the iodide derivative [(n-Pr)(2)ATI]SnI did not change the outcome either. All new compounds have been characterized by multinuclear NMR spectroscopy and X-ray crystallography. The Ag-Ge and Ag-Sn bond distances of [HB(3,5-(CF(3))(2)Pz)(3)]Ag<-- Ge(Cl)[(n-Pr)(2)ATI], [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Sn(Cl)[(n-Pr)(2)ATI], and [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Sn(I)[(n-Pr)(2)ATI] are 2.4142(6), 2.5863(6), and 2.5880(10) A, respectively. A convenient route to [(n-Pr)(2)ATI]H is also reported.

Journal Article↗

Biologic evaluation of a silver-copper-germanium dental casting alloy and a gold-germanium coating alloy.

An Ag-Cu-Ge alloy and an Au-Ge alloy were evaluated for their hemolytic effect on rabbit blood, cytotoxicity to alpha-L fibrosarcoma cells, and allergenic effect on guinea pigs. Neither alloy evoked a significant hemolytic response; cytotoxicity, and that of pure germanium, was no greater than that of ZOE cement; and, on the basis of the guinea pig response, the potential human allergenic response was considered to be Grade I (weak) and Grade II (mild), respectively.

Animals↗

Accumulation of germanium in the tissues of a long-term user of germanium preparation died of acute renal failure.

Acute renal failure developed in a patient accompanied by systemic manifestations such as myopathy and skin rash. The patient, a middle aged house wife, had been taking 600 mg of germanium (Ge) preparation daily for 18 months as an elixir. The main component of the preparation was GeO2 and some organic compound was also present. Histological study of the kidney post mortem showed foamy cell transformation of glomerular epithelia, degeneration of tubular epithelia with red blood cell casts and urate crystals, and a mild proliferation of mesangial matrix. Analysis of the tissue content of Ge, prompted by her history, revealed an increased accumulation of the metal. As compared to a non-user died of liver cirrhosis, the concentration of the metal was higher particularly in the spleen (183X), thyroid gland (175X), psoas muscle (93X), jejunum (76X), and renal cortex (69X). So far, neither accumulation of Ge in humal tissue nor systemic toxicity of the Ge in human has been reported. The relevance of massive accumulation of Ge to the renal failure as well as to other systemic manifestations the patient presented remains to be clarified.

Acute Kidney Injury↗

Hazard assessment of germanium supplements.

Germanium-containing dietary supplements became popular in the 1970s in Japan and later in other countries, as elixirs for certain diseases (e.g., cancer and AIDS). Germanium is not an essential element. Its acute toxicity is low. However, at least 31 reported human cases linked prolonged intake of germanium products with renal failure and even death. Signs of kidney dysfunction, kidney tubular degeneration, and germanium accumulation were observed. Other adverse effects were anemia, muscle weakness, and peripheral neuropathy. Recovery of renal function is slow and incomplete even long after germanium intake was stopped. The total dose of ingested germanium (as dioxide, carboxyethyl germanium sesquioxide, germanium-lactate-citrate, or unspecified forms) varied from 15 to over 300 g; the exposure duration varied from 2 to 36 months. In laboratory animals, elevated germanium in tissues and impaired kidney and liver function were observed in a life-time drinking water (5 ppm germanium) study. Other toxicities associated with ingested germanium products in human cases were also demonstrated in animal studies with germanium dioxide and sometimes other germanium compounds. Based on the evidence of persistent renal toxicity associated with germanium dioxide, the lack of conclusive findings of differential nephrotoxicity of organic germanium compounds, and the possibility of contamination of the organic germanium products with inorganic germanium, it is clear that germanium products present a potential human health hazard.

Administration, Oral↗

Effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.

Through recent research, the trace element, germanium, was found to have an anticancer effect. The purpose of this research was to determine the effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats. Ninety-six 8-week-old Sprague-Dawley male rats were divided into 4 groups, with 24 rats in each group. All received dimethylhydrazine, 20 mg/kg body weight, subcutaneously, once a week for 20 weeks. Except for one control group, the other three groups were subdivided into six groups and administered three different kinds of germanium (inorganic germanium, organic germanium, and natural organic germanium) one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment, respectively. Twenty-four weeks after carcinogen exposure, all surviving animals were sacrificed and examined for intestinal tumors. The number and location of the tumors were recorded and the pathology examined. The incidence of intestinal cancer in the control group (dimethylhydrazine only) was 91 percent; in groups provided with inorganic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 91 and 78 percent; in groups provided with organic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 64 and 64 percent; in groups provided with natural organic germanium one month before and during dimethylhydrazine treatment and during dimethylhydrazine treatment only, it was 50 and 45 percent. From these results, the authors conclude that natural organic germanium has the best prevention effect for intestinal cancer in this animal model (P less than 0.01), followed by organic germanium (P less than 0.05). Inorganic germanium has no effect. However, there is no difference in the cancer prevention effect of germanium provided one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only.

1,2-Dimethylhydrazine↗

Inhibition by germanium oxide of the mutagenicity of cadmium chloride in various genotoxicity assays.

The effects of germanium oxide on the genotoxicity of cadmium chloride were investigated. The incorporation of [3H]thymidine into testicular DNA was inhibited in mice injected ip with 1.35, 1.80 or 2.70 mg cadmium chloride/kg body weight. Germanium oxide (0.05 or 0.1 mg/kg body weight, sc) alone did not affect [3H]thymidine incorporation into testicular DNA but 0.05 mg germanium oxide/kg antagonized the inhibitory effect of 1.35 mg cadmium chloride/kg. However, combinations of the other doses of the two compounds did not show statistically significant antagonistic effects. Cadmium chloride significantly increased the frequencies of micronucleus formation in polychromatic erythrocytes, and of chromosome aberrations in the bone marrow of mice treated with 0.7, 1.4 or 2.7 mg/kg body weight, in a dose-related manner. These effects were inhibited by germanium oxide at doses of 0.1 or 0.5 mg/kg body weight, although germanium oxide alone did not affect micronucleus formation or the chromosome aberration rate. Cadmium chloride produced a dose-related increase in the frequency of sister chromatid exchanges in cultured human lymphocytes at concentrations of 5, 10 or 50 mumol. This effect was also inhibited by germanium oxide (0.05 or 0.1 mumol), although germanium oxide alone had no effect. There was a dose-related increase in the frequency of sperms with abnormal head morphologies from mice treated with 0.6, 1.1 or 2.2 mg cadmium chloride/kg body weight and this too was antagonized by the injection of germanium oxide (0.1 or 0.5 mg/kg body weight). Germanium oxide alone did not affect the frequency of sperm-head abnormalities.

Animals↗

Analytical product study of germanium-containing medicine by different ICP-MS applications.

For several years organo-germanium containing medicine has been used for special treatments of e.g. cancer and AIDS. The active substances contain germanium as beta-carboxyethylgermanium sesquioxide ((GeCH2CH2COOH)203/"Ge-132"), spirogermanium, germanium-lactate-citrate or unspecified forms. For humans, germanium is not essential and in general the toxicity of the mentioned organo-germanium compounds is low. Acute and chronic toxic effects of inorganic germanium dioxide have been demonstrated. It is obvious that especially inorganic germanium has a higher potential of negative effects. Therefore, a widespread analytical product control is indispensable. Inductively coupled plasma mass spectrometry (ICP-MS) is the preferred technique and different applications were developed for controlling various parameters: (i) A speciation method using high performance liquid chromatography (HPLC) coupled with quadrupole (Q-) ICP-MS was developed for the identification of organo-germanium species in medicine. (ii) The nuclear magnetic resonance (NMR) technique was applied to confirm the molecular structure and to determine the molecule concentration. (iii) The total concentration of germanium in the medicine was determined in the diluted sample by high resolution (HR-) ICP-MS. (iv) For a general overview, a multi-element screening method of 56 elements with HR-ICP-MS was developed. The semi-quantitative mode was used for quantification and elements of higher abundance are reported. (v) Investigations about matrix-based interferences on masses of isotopes, which are generally determinable without remarkable problems. Isotopes like e.g. 85Rb, 88Sr, 89y, 90Zr, 93Nb and the isotopes of Ba are strongly interfered by different Ge-based molecules and need to be analysed in a higher resolution mode than used for other common matrices.

Chromatography, High Pressure Liquid↗

Mutagenicity, carcinogenicity and teratogenicity of germanium compounds.

The metalloid germanium has found widespread application in electronics, nuclear sciences and in medicine. General toxicity of germanium is low, except for the tetrahydride germane, and few observations on toxicity of germanium in man exist. Germanium is not carcinogenic and even appears to inhibit cancer development and, in the form of the organic germanium compound, spirogermanium, to destroy cancer cells. Germanium compounds have no mutagenic activity and may, under certain conditions, inhibit the mutagenic activity of other substances. High doses of germanium may result in an increased embryonic resorption, but possible malformations have been reported only after administration of dimethyl germanium oxide to pregnant animals. Germanium may thus be considered an element of rather low risk to man.

Animals↗