Germanium - Toxicology of Metals - page 552

1991a,b). Schauss (1991) and Tao and Bolger (1997)
summarized the literature for human Ge toxicity from
dietary supplements and reported approximately 23
cases of germanium-related toxicity worldwide; 21 of
these cases involved Japanese users. The duration of
intakes ranged from 4-24 months, with doses varying
between 14 and 324 g of germanium compounds.

Another organogermanium antitumor agent, carbox-
yethyl Ge sesquioxide, was considered to restore the
impaired immunoresponse in aged C3A/HeJ mice
(Mizushima et al ., 1980). This compound was found to
induce hypotension and bradycardia in the rat by pro-
moting the activation of the parasympathetic efferent
and inhibition of the sympathetic efferent inputs (Ho et
al., 1990). In 1988, the FDA accepted the use of germa-
nium sesquioxide as a food additive, but in 1995, they
issued an alert to remove the food additive on the basis
of its renal toxicity (FDA, 1995). In October 2003, the
FDA refused an entry of 20 kg of bulk Ge sesquioxide
in human dietary supplements, because germanium
has caused nephrotoxicity (kidney injury) and death
when used chronically by humans, even at recom-
mended levels of use (FDA, 2004).

7.1.3.2.2 Neurological Neuropathy involving mostly
the sensory nerves was demonstrated in a 53-year-
old man who took 400 g of germanium oxide as a
health supplement over 14 months (Kim et al ., 1998).
Observations included grade IV motor strength,
negative deep tendon refl ex in the lower extremities,
and persistent tingling sensation of the palms and
soles. A 63-year-old woman consumed 36 mg inorganic
germanium/day for 6 years (total dose equivalent
to 80 gm) and subsequently developed diffi culty
in writing, gait discoordination, and peripheral
neuropathy. The neuronal damage was manifest as
irreversible, and an autopsy showed degeneration
of dorsal root ganglion cells and degeneration of the
dorsal column of the spinal cord. The patient died from
sepsis and pneumonia (Asaka et al ., 1995).

7.3 Carcinogenicity, Mutagenicity,
and Teratogenicity
Studies by Kanisawa and Schroeder (1967) on mice
and by Schroeder et al . (1968) on rats (lifetime exposure
to 5 mg Ge/L in drinking water as sodium germanate)
did not produce any evidence of carcinogenicity of Ge
compounds.
There is no defi nite evidence of mutagenicity of Ge
compounds, although Ge tetrachloride was positive
in the rec-assay (Kanematsu and Kada, 1978). Spirog-
ermanium inhibits DNA and RNA synthesis in HeLa
cells and is cytotoxic in vitro (Schein et al ., 1980).
Dimethylgermanium oxide, an analog of acetone,
was shown to produce a variety of malformations in
chick embryos at 72 and 96 hours of incubation, the
ED 50 being 1.8 and 2.5 mg/embryo, respectively, com-
pared with 17.9 and 25.1 mg/embryo for acetone (Cau-
jolle et al , 1965). Ferm and Carpenter (1970) did not fi nd
any teratogenic or fetotoxic effect in hamsters treated
with sodium germanate (40-100 mg/kg, intravenous
injection, 8-day gestation). Hatano et al . (1981b) did not
observe any adverse effect of Ge dioxide (19, 38, and
75 mg/kg, subcutaneously, pregnant rats) on mothers,
embryos, or newborns. Ge oxide in 0.05 or 0.1 mg/kg
inhibits the dose-related increase in frequency of sperm
with abnormal head morphology after treatment with
cadmium chloride in mice. However, germanium
oxide alone did not have any effect on the frequency of
sperm-head abnormalities (Han et al ., 1992).

7.1.3.2.3 Heart Effects Ingestion of 30 g of GeO 2 as
a remedy in capsule form over 8 months resulted in
remarkable cardiac dilation, vacuolar degeneration of
myocardial cells, and interstitial edema (Matsusaka
et al ., 1988).

7.2 Organometallic Compounds
The toxicity of several trialkylgermanium com-
pounds was studied by Cremer and Aldridge (1964).
Triethylgermanium acetate was toxic to rats in intra-
venous doses of 50 mg/kg body weight, and orally at
250 mg/kg. Tri- N -butylgermanium acetate was toler-
ated orally in single doses up to 375 mg/kg. The tox-
icity of trialkylgermanium compounds was less than
one tenth of the toxicity of triethyltin or triethyllead
and did not seem to have a predominant effect on the
CNS. Among the tetraalkylgermanium compounds
evaluated by Caujolle et al . (1966), the least toxic were
those with saturated normal symmetrical radicals. The
halogenation of organic radicals increased the bio-
logical activity. Higher hexaalkyldigermanium oxides
(butyl-, amyl-, hexyl-) were less toxic than the ethyl
homologs (Bouissou et al ., 1964). Spirogermanium
was neurotoxic to human cancer patients after intrave-
nous administration in doses from 32-160 mg/m 2 . The
reversible effects included lethargy, vertigo, ataxia,
and grand mal seizures (at high doses). Neurotoxic
effects were also observed in dogs (Schein et al ., 1980).

8 TREATMENT TRIALS

Spirogermanium was very effective in suppres-
sion of experimental autoimmune encephalomyeli-
tis induced by myelin preparation from guinea pig