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CARBOXYETHYLGERMANIUM SESQUIOXIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Carboxyethylgermanium sesquioxide was originally synthesized in Japan in 1967 (Goodman, 1988). Some individuals, especially in Japan, take germanium compounds to "maintain good health" (Okuda et al, 1987). Carboxyethylgermanium sesquioxide has been investigated for antineoplastic, anti-infective, and analgesic properties.

Specific Substances

    1) GE 132
    2) bis carboxyethyl germanium sesquioxide
    3) 2-carboxyethylgermanium sesquioxide
    4) carboxyethylgermanium sesquioxide
    5) 3,3'-(Dioxodigermoxanylene) dipropanoic acid
    6) Dipropanoic acid carboxyethylgermanium sesquioxide
    7) 3,3'-(Germanoic anhydride) dipropanoic acid
    8) GERMANIUM, CARBOXYETHYL-SESQUIOXIDE
    9) ORGANOGERMANIUM

Available Forms Sources

    A) USES
    1) Carboxyethylgermanium sesquioxide is being investigated as having analgesic properties (Komuro et al, 1986; Hachisu et al, 1983), a protectant effect in cirrhosis (Sharpe, 1987) and infection (Aso et al, 1985; Suzuki & Pollard, 1984), and antitumor activity in test animals (Tsutsui et al, 1976; Suzuki et al, 1986; Kumano et al, 1985).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) ACUTE TOXICITY - No acute toxicity has been reported in humans or animals. Carboxyethylgermanium sesquioxide is thought to be of very low toxicity. No significant effects occurred in animals given fairly high doses.
    B) CHRONIC TOXICITY - The primary toxicity from chronic ingestion of germanium is to the kidney; anorexia and one case of paresthesias have been reported. In many of the cases reported from Japan, the specific germanium compound was either unknown or not stated. It is still not clear how much toxicity is due to carboxyethylgermanium sesquioxide and how much may be due to inorganic germanium contamination.
    0.2.7) NEUROLOGIC
    A) One case of glove and stocking paresthesias, which did not resolve after cessation of therapy with carboxyethylgermanium sesquioxide, was reported following chronic ingestion.
    0.2.8) GASTROINTESTINAL
    A) Anorexia may occur following chronic ingestion, in cases of renal failure.
    0.2.10) GENITOURINARY
    A) Cases of renal failure after 300 to 600 mg for 4 or 5 months has been reported.
    0.2.20) REPRODUCTIVE
    A) No teratogenicity was reported in rats given up to 1000 mg/kg/day.

Laboratory Monitoring

    A) No routine laboratory tests are needed after acute ingestion unless otherwise clinically indicated. Monitor renal function after chronic ingestion.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because these agents are generally toxic on a chronic rather than acute basis, gastric decontamination is usually not indicated.
    B) The renal failure associated with chronic use has been treated by discontinuation of carboxyethylgermanium sesquioxide therapy and, in severe cases, hemodialysis.

Range Of Toxicity

    A) Cases of renal failure after 300 to 600 mg daily for 4 or 5 months have been reported.

Clinical Effects

Summary Of Exposure

    A) ACUTE TOXICITY - No acute toxicity has been reported in humans or animals. Carboxyethylgermanium sesquioxide is thought to be of very low toxicity. No significant effects occurred in animals given fairly high doses.
    B) CHRONIC TOXICITY - The primary toxicity from chronic ingestion of germanium is to the kidney; anorexia and one case of paresthesias have been reported. In many of the cases reported from Japan, the specific germanium compound was either unknown or not stated. It is still not clear how much toxicity is due to carboxyethylgermanium sesquioxide and how much may be due to inorganic germanium contamination.

Neurologic

    3.7.1) SUMMARY
    A) One case of glove and stocking paresthesias, which did not resolve after cessation of therapy with carboxyethylgermanium sesquioxide, was reported following chronic ingestion.
    3.7.2) CLINICAL EFFECTS
    A) PARESTHESIA
    1) CASE REPORT - Glove and stocking hypesthesia and paresthesia in the extremities, without motor defect, was seen in a patient who ingested and unknown amount of a germanium health food compound (unknown if germanium dioxide or carboxyethylgermanium sesquioxide) for 18 months.
    a) Eight months after discontinuation of the germanium, the paresthesias were unchanged (Okuda et al, 1987).

Gastrointestinal

    3.8.1) SUMMARY
    A) Anorexia may occur following chronic ingestion, in cases of renal failure.
    3.8.2) CLINICAL EFFECTS
    A) LOSS OF APPETITE
    1) CASE REPORT - Anorexia and thirst were reported in a patient experiencing renal failure due to a 5 month course of carboxyethylgermanium sesquioxide (Okuda et al, 1987).

Genitourinary

    3.10.1) SUMMARY
    A) Cases of renal failure after 300 to 600 mg for 4 or 5 months has been reported.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) CASE REPORTS - Renal failure was reported in a 47- and 55-year-old who took 300 to 600 mg of carboxyethylgermanium sesquioxide daily for 4 to 5 months (Okuda et al, 1987).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) Anemia was reported after chronic use of a carboxyethylgermanium sesquioxide preparation (Okuda et al, 1987).

Reproductive

    3.20.1) SUMMARY
    A) No teratogenicity was reported in rats given up to 1000 mg/kg/day.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) RATS - No teratogenicity was reported in rats given up to 1000 mg/kg/day (Sugiya et al, 1986; Nagai et al, 1980; Sugiya et al, 1986a) Shimpo & Nori, 1980).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No routine laboratory tests are needed after acute ingestion unless otherwise clinically indicated. Monitor renal function after chronic ingestion.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No specific lab work (CBC, electrolytes) is needed unless otherwise clinically indicated.
    4.1.3) URINE
    A) URINALYSIS
    1) Hematuria, proteinuria, and glycosuria were not seen in the cases of carboxyethylgermanium sesquioxide-associated renal failure reported by Okuda et al (1987).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No routine laboratory tests are needed after acute ingestion unless otherwise clinically indicated. Monitor renal function after chronic ingestion.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Because these agents are generally toxic on a chronic rather than acute basis, gastrointestinal decontamination is usually not indicated. There are no human data to indicate the toxic acute dose of carboxyethylgermanium sesquioxide.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Because of the chronic nature of this poisoning, gastric decontamination is usually not necessary. A human acute toxicity dose has not been established.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Discontinue use of the carboxyethylgermanium sesquioxide and provide symptomatic and supportive care.
    B) HEMODIALYSIS
    1) Dialysis has been used to treat the acute renal failure.
    2) In one case where a 55-year-old with a peak BUN of 134 milligrams/deciliter was treated with dialysis for 7 sessions.
    a) The patient's azotemia began to decrease after the third week and although the patient was discharged 46 days post admission, fourteen months later the BUN was still 47 milligrams/deciliter (Okuda et al, 1987).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Dialysis has been used as a treatment of renal failure, but has not been established or tried as a method to hasten the elimination of germanium in these patients.

Range Of Toxicity

Summary

    A) Cases of renal failure after 300 to 600 mg daily for 4 or 5 months have been reported.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) 150 to 1000 milligram/day sublingually in divided doses for treatment of chronic Epstein-Barr virus syndrome (Faloona & Levine, 1988).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Carboxyethylgermanium sesquioxide is thought to be of very low toxicity (Okuda et al, 1989).
    B) CASE REPORTS
    1) A 47-year-old patient who ingested 300 to 600 milligrams per day for 4 to 5 months developed renal failure (Okuda et al, 1987).
    C) ANIMAL DATA
    1) No significant toxicity was found at fairly high doses (Nagata et al, 1978; Nagai et al, 1980; Kagoshima & Onishi, 1986; Sugiya et al, 1986b).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1250 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)MOUSE:
    a) 5600 mg/kg (RTECS, 2001)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 1670 mg/kg (RTECS, 2001)
    4) LD50- (ORAL)RAT:
    a) 7050 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Carboxyethylgermanium sesquioxide is a known antineoplastic, immunopotentiator, and interferon-inducer (Okuda et al, 1987).

Toxicologic Mechanism

    A) Carboxyethylgermanium sesquioxide appears to cause prolonged renal dysfunction without urinary abnormalities. Mild tubular degeneration and atrophy with or without interstitial edema has been observed (Okuda et al, 1987).

Physicochemical

Physical Characteristics

    A) solid

Molecular Weight

    A) Not available

References

General Bibliography

    1) Aso H, Suzuki F, & Yamaguchi T: Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiol Immunol 1985; 29:65-74.
    2) Faloona GR & Levine SA: The use of organic germanium in chronic Epstein-Barr virus syndrome (CEBVS): an example of interferon modulation of herpes reactivation. J Orthomolecular Med 1988; 3:29-31.
    3) Goodman S: Therapeutic effects of organic germanium. Medical Hypotheses 1988; 26:207-215.
    4) Hachisu M, Takahashi H, & Koeda T: Analgesic effect of novel organogermanium compound, GE-132. J Pharmacobiodyn 1983; 6:814-820.
    5) Kagoshima M & Onishi T: Metabolic fate of 2-carboxyethylgermanium sesquioxide (3); continual administration. Ohyoh Yakuri (Applied Drug Science) 1986; 32:89-92.
    6) Komuro T, Kakimoto N, & Katayama T: Inhibitory effects of GE-132 (carboxyethyl germanium sesquioxide) derivatives on enkephalin-degrading enzymes. Biotechnol Appl Biochem 1986; 8:379-386.
    7) Kumano N, Ishikawa T, & Koinumaru S: Antitumor effect of the organogermanium compound GE-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice. Tohoku J Exp Med 1985; 146:97-104.
    8) Nagai H, Hasegawa K, & Shimpo K: Reproductive study of rats intraperitonealy treated with carboxyethylgermanium sesquioxide (GE-132). Ohyoh Yakuri (Applied Drug Science) 1980; 20:271-280.
    9) Nagata T, Nagata T, & Aramaki Y: Chronic intravenously toxicity study with carboxyethylgermanium sesquioxide in beagle-dogs. Ohyoh Yakuri (Applied Drug Science) 1978; 16:613-636.
    10) Okuda K, Okagawa K, & Kawakami K: Renal failure caused by long-term use of a germanium preparation as a elixer. Clin Nephrol 1989; 31:219-224.
    11) Okuda S, Kiyama S, & Yukinori OH: Persistent renal dysfunction induced by chronic intake of germanium-containing compounds. Current Therap Res 1987; 41:265-275.
    12) Sharpe RJ: Endogenous gamma interferon production may protect against hepatic cirrhosis and administration of exogenous gamma interferon may protect individuals prone to cirrhosis. Med Hypotheses 1987; 22:415-419.
    13) Sugiya Y, Eda K, & Yoshida K: Reproductive and teratogenic studies of carboxyethylgermanium sesquioxide (Ge-132) (1); fertility study in rats by intravenous administration. Ohyoh Yakuri (Applied Drug Science) 1986; 32:113-121.
    14) Sugiya Y, Sakamaki S, & Satoh H: Reversibility study in rats after two months' oral administration of carboxyethylgermanium sesquioxide (Ge-132) in rats. Ohyoh Yakuri (Applied Drug Science) 1986b; 31:1191-1200.
    15) Sugiya Y, Yoshida K, & Sakamaki S: Reproductive and teratogenic studies of carboxyethylgermanium sesquioxide (Ge-132) (2); teratogenesis study in rats by intravenous administration. Ohyoh Yakuri (Applied Drug Science) 1986a; 32:123-138.
    16) Suzuki F & Pollard RB: Prevention of suppressed interferon gamma production in thermally injured mice by administration of a novel organogermanium coumpound, GE-132. J Interferon Res 1984; 4:223-233.
    17) Suzuki F, Brutkiewicz RR, & Pollard RB: Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (GE-132). Anticancer Res 1986; 6:177-182.
    18) Tsutsui M, Kakimoto N, & Axtell DD: Crystal structure of "carboxyethyl germanium sesquioxide". J Am Chem Soc 1976; 98:8287-8289.
    19) Vouk V: Germanium. In: Friberg L, Nordberg GF, Vouk V (Eds), Elsevier, North Amsterdam, Holland, 1979, pp 421-428.