The Authoritative Germanium Sesquioxide Resource

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Analytical •AntimutagenicAntioxidant •Antiviral •Arthritis •Atherosclerosis •Bioavailability •CancerCataracts  •Cervix •DNA Repair •Fibrosis •Free Radical ScavengingHazards •Heart •History •Immune SystemKidneysInflammation •Liver •Osteoporosis •Pain Management Pharmacology •Reviews •Safety •Uterus

[Subacute and subchronic oral toxicity of beta-bis carboxyethyl sesquioxide of germanium in the rat] J Toxicol Clin Exp. 1991 Dec;11(7-8):421-36.

Anger F, Anger JP, Guillou L, Sado PA, Papillon A.

Laboratoire de Toxicologie, UFR des Sciences Pharmaceutiques et Biologiques, Rennes, France.

After a brief recall of toxicological data about germanium compounds, the authors relate subacute and subchronic oral toxicities of beta bis carboxyethyl-germanium sesquioxide in rats. During 28 days and six months, male and female animals have received 1 mg/kg/day. No particular toxic symptoms, no behaviour trouble except a small decrease of body weight, in male rats, at the end of the 6-month experimentation, were observed. A light decrease of erythropoiesis and a general stimulation of cellular metabolism has been noticed after 28 days. The only marked effect was a moderate renal deficiency characterized by a tubular disease with presence of cylinders, swelling of tubulus cells and floculus amounts after 6 months. Germanium urinary excretion was constant and linked to the received dose. Six months later, no preferential accumulation in organs was observed.


Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide.
Kidney Int. 1991 Nov;40(5):882-90.

Sanai T, Okuda S, Onoyama K, Oochi N, Takaichi S, Mizuhira V, Fujishima M.

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.

Effect of potential antidotes on the acute toxicity, tissue disposition and elimination of selenium in rats. Res Commun Chem Pathol Pharmacol. 1989 Dec;66(3):441-50.

Paul M, Mason R, Edwards R.

Toxicology Research Unit (Medical Research Council of New Zealand), University of Otago Medical School, Dunedin.

Treatment of male Wistar rats with sodium selenate (2.24 mg Se/kg, s.c.) inhibited their body weight gain for 24 hr, after which the animals recovered. Intraperitoneal injections of sodium-2,3-dimercaptopropane-1-sulphonic acid (60 mg/kg), meso-2,3-dimercaptosuccinic acid (50.9 mg/kg) and calcium disodium ethylenediamine-tetraacetate (500 mg/kg) 15 min after Se had no protective effect, whilst 2,3-dimercaptopropanol (15 mg/kg) inhibited the recovery of the Se-treated animal. Sodium diethyldithiocarbamate (DDTC, 70 mg/kg, i.p.) reduced the Se-induced loss of body weight but had no effect on the tissue disposition of 75Se when injected 15 min, 3 hr or 6 hr after a s.c. injection of sodium [75Se] selenite (50 microCi, 17.4 micrograms Se/kg). The citrate salts of bismuth (2.5 and 5 mg Bi/kg, s.c.), antimony (1.5 and 3 mg Sb/kg, s.c.) and germanium (40 mg Ge/kg, s.c.) also reduced the selenate-induced loss of body weight, whilst germanium citrate (40 mg Ge/kg) and bis-carboxyethyl germanium sesquioxide (80, 200 and 400 mg Ge/kg) promoted significant dose-related increases in the 24 hr urinary excretion of 75Se when given 15 min after sodium [75Se] selenite (30 microCi, 0.5 mg Se/kg, s.c.).

Safety, Kidneys
Influence of propagermanium (SK-818) on chemically induced renal lesions in rats. J Toxicol Sci. 1994 Oct;19 Suppl 2:131-43.

Asano K, Yamano M, Haruyama K, Ikawa E, Nakano K, Kurono M, Wada O.

Department of Pharmacology, Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co. Ltd., Japan.

A histopathological study was performed to examine the influence of propagermanium and germanium dioxide (GeO2) on chemically induced renal lesions in rats. Animals were treated with adriamycin or mercuric chloride to induce glomerular or proximal tubular damage, and then given drinking water containing propagermanium (480 or 2,400 ppm solution) or GeO2 (300 or 1,500 ppm solution: equivalent to propagermanium in terms of germanium contents). The distal tubular epithelium after 8 weeks dosage with the 1,500 ppm solution of GeO2 was characterized by vacuolization and deposits of PAS-positive material not only in adriamycin-treated rats, but also in normal rats. In contrast, propagermanium administration was not associated with any alternation in the changes induced by adriamycin or mercuric chloride. We previously clarified that propagermanium had no biochemical influence on the renal function of these renal injured rats. The histological demonstration that this compound does not exert renal toxicity, even when given at a high dosage to renal injured rats, further indicates that it would not exacerbate renal dysfunction already present. This confirms that propagermanium may be a safe compound for use in individuals with compromised kidneys.

Cancer, Physiology, Safety
Organic germanium: its toxic effect and function in medical care.  Zhonghua Yi Xue Za Zhi. 1993 Aug;73(8):454-6.

Kong X.

PMID: 8111643 [PubMed - indexed for MEDLINE]

Safety, Toxicity
Oral single- and repeated-dose toxicity studies on Geranti Bio-Ge Yeast, organic germanium fortified yeasts, in dogs.  J Toxicol Sci. 2004 Dec;29(5):555-69.

Lee JS, Park JI, Kim SH, Lee HY, Hwang ZZ, Park CB, Sohn TU, Shin S, Kang JK, Kim YB.

Biotoxtech Co., Ltd., Ochang Scientific and Industrial Complex, Cheongwon, Korea.

Single- and 13-week repeated-dose toxicities of Geranti Bio-Ge Yeast, organic germanium fortified yeasts, were investigated in dogs. Both sexes of Beagle dogs were orally administered once at a dose of 2,000 mg/kg in single-dose toxicity or daily for 13 weeks at doses of 500, 1,000 or 2,000 mg/kg in repeated-dose toxicity tests. In single-dose toxicity test, no animal dead, moribund, or showing clinical signs or changes in body weight gain was found. In repeated-dose toxicity study, there were no considerable changes in ophthalmoscopy and urinalysis. Several alterations were observed in electrocardiography, hematology and blood biochemistry, including heart rate, R-R interval, QT correcting, reticulocytes, activated partial thromboplastin time and albumin/globulin ratio in only male dogs, but not in females, administered with Geranti Bio-Ge Yeast in a dose-independent manner. In gross findings, several cases of abnormal findings were observed in both control and treatment groups, showing diffuse dark brown to black discoloration of liver, in a dose-independent manner. In microscopic examination, mild lesions, including cholestasis and inflammatory cell foci in liver, kidneys and prostate, were found sporadically in both control and treatment groups. In spite of some alterations in electrocardiography, hematology, blood biochemistry, gross and microscopic findings, such effects were not considered to include toxicopathological significance, based on the marginal changes within normal ranges and lack of dose-dependency, consistent time-course and gender relationship. Taken together, it is suggested that no observed adverse effect level (NOAEL) of Geranti Bio-Ge Yeast is considered to be 2,000 mg/kg in dogs, and that long-term treatment in clinical trials might not exert adverse effects. PMID: 15729010 [PubMed - indexed for MEDLINE]


Safety, Toxicity
Oral single- and repeated-dose toxicity studies on Geranti Bio-Ge yeast, organic germanium fortified yeasts, in rats.  J Toxicol Sci. 2004 Dec;29(5):541-53.

Lee JS, Park JI, Kim SH, Park SH, Kang SK, Park CB, Sohn TU, Jang JY, Kang JK, Kim YB.

Biotoxtech Co., Ltd., Ochang Scientific and Industrial Complex, Cheongwon, Korea.

Single- and 13-week repeated-dose toxicities of Geranti Bio-Ge Yeast, organic germanium fortified yeasts, were investigated in rats. Both sexes of Sprague-Dawley rats were orally administered once at a dose of 2,000 mg/kg in single-dose toxicity or daily for 13 weeks at doses of 500, 1,000 or 2,000 mg/kg in repeated-dose toxicity tests. In single-dose toxicity test to determine dose levels in repeated-dose toxicity study, the body weight gain was suppressed at 2,000 mg/kg, although no death, clinical signs and pathological findings related to the treatment were observed. In repeated-dose toxicity test, there were no clinical signs in animals administered up to 2,000 mg/kg, except one rat died due to a gavage error. In addition, no significant changes in feed consumption and body weight gain were obtained during the treatment period, in spite of week-to-week fluctuation of water consumption. There were no considerable changes in ophthalmoscopy, urinalysis, hematology and serum biochemistry, except a significant decrease in albumin/globulin ratio in males treated with 1,000 mg/kg. In contrast, a significant increase in relative heart weight was observed in both male and female rats treated with a high dose (2,000 mg/kg) of Geranti Bio-Ge Yeast. In microscopic examination, mild lesions were found sporadically in both control and treatment groups in a dose-independent manner. In spite of some alterations in water consumption, serum biochemistry and organ weights, such effects were not considered to include toxicopathological significance, based on the lack of dose-dependency, consistent time-course and gender relationship. Taken together, it is suggested that no observed adverse effect level (NOAEL) of Geranti Bio-Ge Yeast is considered to be over 2,000 mg/kg in rats, and that long-term oral intake in humans might not exert adverse effects. PMID: 15729009 [PubMed - indexed for MEDLINE]

Safety, Toxicity, Mutagenicity
Mutagenicity, carcinogenicity and teratogenicity of germanium compounds.  Mutat Res. 1997 Dec;387(3):141-6.

Gerber GB, Leonard A.

Teratogenicity and Mutagenicity Unit, Catholic University of Louvain, Brussels, Belgium.

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. PMID: 9439710 [PubMed - indexed for MEDLINE]


Safety, Toxicity, Cancer
Cancer risks for humans from exposure to the semiconductor metals.  Scand J Work Environ Health. 1993;19 Suppl 1:101-3.

Fowler BA, Yamauchi H, Conner EA, Akkerman M.

Program in Toxicology, University of Maryland, Baltimore 21227.

Of the semiconductor metals, only arsenic has been extensively studied as a human carcinogen and systemic toxicant. Recent studies have shown, however, that gallium, arsenic, and indium are capable of producing marked alterations in cellular gene products. After acute in vivo administration indium and thallium have been shown to produce decreases in the activity of some drug-metabolizing enzymes dependent on cytochrome P-450; therefore these metals would be capable of interfering with the metabolism of organic carcinogens. Selenium is essential for the activity of the enzyme glutathione peroxidase, which modulates the active intermediates generated by drug-metabolizing enzyme systems. Germanium produces toxicity in a number of organ systems. Antimony produces lung and circulatory system effects. Overall, available data suggest that these metals or metalloids are capable of biologically altering several cellular defense mechanisms involved in the carcinogenic process and that further studies are needed to determine the associated risks. PMID: 8159952 [PubMed - indexed for MEDLINE]


Safety, Toxicity, Hazards, Physiology
Toxicity of an organic Germanium compound: deleterious consequences of a "natural remedy".  Schweiz Med Wochenschr. 1992 Jan 8;122(1-2):11-3.

Raisin J, Hess B, Blatter M, Zimmermann A, Descoeudres C, Horber FF, Jaeger P.

Medizinische Universitatspoliklinik, Inselspital, Bern.

Reports mainly from Japan, recommend germanium (Ge)-containing compounds as "anti-cancer" and "immunostimulatory" remedies. We report on a 25-tear-old woman with stage II HIV disease who consumed a total of 47 g Ge as Ge-lactate-citrate 18%. She developed severe renal insufficiency (creatinine clearance 7 ml/min/1.73 m2, proteinuria 0.28 g/d) and hepatomegaly. Biopsies revealed tubulointerstitial nephropathy with vacuolar degeneration, mainly of distal tubular epithelia, and severe liver steatosis. Tissue Ge content in kidney and liver biopsy specimens was increased 68-and 140 fold respectively. In agreement with previous reports, renal dysfunction persisted 9 months later (creatinine clearance 11 ml/min/1.73 m2). PMID: 1594900 [PubMed - indexed for MEDLINE]

Safety, Hazards, Physiology
Accumulation of germanium in the tissues of a long-term user of germanium preparation died of acute renal failure.  J Toxicol Sci. 1985 Nov;10(4):333-41.

Nagata N, Yoneyama T, Yanagida K, Ushio K, Yanagihara S, Matsubara O, Eishi Y.

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. PMID: 3831368 [PubMed - indexed for MEDLINE]

Safety, Hazards, Physiology
Abuse of Germanium Associated With Fatal Lactic Acidosis

Nephron  1992; 62:351-356

Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastic cancer disease.  We observed a patient with nonmetastactic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol /l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominately in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis.Urnine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high.  Lactic acidosis may have been caused by the combined, germanium-Induced renal and hepatic failure (underutilization), but it remains to be seen Whether germanium can affect lactate production and/or metabolism directly.

Safety, Hazards, Physiology
Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. Am J Kidney Dis. 1993 May;21(5):548-52.

Hess B, Raisin J, Zimmermann A, Horber F, Bajo S, Wyttenbach A, Jaeger P.

Policlinic of Medicine, University Hospital, Berne, Switzerland.

Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma-glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue. PMID: 8488824 [PubMed - indexed for MEDLINE]

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