Antimony - Toxicology of Metals - page 351

increases in urinary antimony levels are seen in cases of
exposure to very low levels of antimony in air (Iavicoli
et al ., 2002).

7.1.2 Systemic Effects and Dose-Response
Relationships

In a study of the effects of subchronic oral expo-
sure of Wistar rats to antimony or antimony trioxide,
growth retardation was observed. The addition of 0.1%
or 1.0% antimony or 1.0% antimony trioxide to the diet
for 12 weeks resulted in a decrease in body weight that
returned to normal after 12 weeks on an antimony-
free diet (Hiraoka, 1986). A decrease in body weight
was also observed in a study of Sprague-Dawley rats
exposed to potassium ammonium tartrate in drink-
ing water at concentrations of 0.5, 5, 50, or 500 mg/L
for 13 weeks. As with the study by Hiraoka, the rats
returned to their normal weight within several weeks
post exposure (Poon et al ., 1998).

7 EFFECTS AND DOSE-RESPONSE
RELATIONSHIPS

7.1 Animals
The major sites of accumulation of antimony in ani-
mals after oral exposure, other than the gastrointestinal
tract, are the liver, kidney, bone, lung, spleen, and thy-
roid. This accumulation, however, is not dose-related
(Sunagawa, 1981). With peroral exposure, both acute
and chronic, antimony potassium tartrate is more toxic
than antimony trioxide and pentoxide. In dogs and cats,
acute symptoms such as vomiting and diarrhea were
produced by antimony potassium tartrate in doses on
the order of 10 mg/kg. Antimony trioxide and pentox-
ide could be given to the same animals in doses above
100 mg/kg for months without toxic manifestations
(Bradley and Fredrick, 1941; Flury, 1927). In a long-
term study, rats given 5 mg/L as antimony potassium
tartrate in drinking water showed a signifi cantly short-
ened average length of life (about 15%) compared with
controls (Schroeder et al ., 1970). Rats given a diet con-
taining 0.5-2% antimony or antimony trioxide had a
decreased weight gain (Sunagawa, 1981).

7.1.2.1 Circulatory System Effects
Intravenous injections of antimony produce an acute
circulatory response with a drop in blood pressure
(Chopra, 1927; Cotten and Logan, 1966). Pathological
ECG changes have been observed. In dogs injected
for 4 days with antimony potassium tartrate, 5 mg/kg
body weight, one of the most prominent features was
inversion of the T wave (Girgis et al ., 1970). Several of
the dogs died as a result of the treatment.
Chronic effects with parenchymatous degeneration
in the myocardium were observed on histopathological
examination of hearts from rats and rabbits exposed to
3.1 and 5.6 mg/m 3 as antimony trisulfi de for 6 weeks
(Brieger et al ., 1954). On the other hand, Watt (1983),
in his long-term study on swine exposed to antimony
trioxide (1.6 and 4.2 mg Sb/m 3 ), found no evidence of
cardiovascular effects.

7.1.1 Local Effects and Dose-Response
Relationships

After inhalation of antimony trioxide at an average
concentration of 45 mg/m 3 , 2-3 hours daily for several
weeks, guinea pigs showed interstitial pneumonitis
(Dernehl et al ., 1945). Rats and rabbits exposed to anti-
mony trioxide (90-125 mg Sb 2 0 3 /m 3 during 100 hour/
month) for periods of up to 14 months, in addition
to pneumonitis, also developed lipoid pneumonia,
fi brous thickening of alveolar walls, and focal fi brosis
(Gross et al ., 1951; 1955). Rabbits seemed to be more sus-
ceptible than rats (Gross et al ., 1955). Watt (1983) used
148 female CDF-rats and 8 miniature swine to examine
the long-term toxicity of inhaled antimony trioxide.
Both species were divided into a control group, a low-
exposure (1.6 mg Sb/m 3 ), and a high-exposure group
(4.2 mg Sb/m 3 ). The animals were exposed for 6 hours
a day, 5 days per week, for about 1 year. In the mini-
ature swine, there were no histopathological changes
in the lungs, but in the rats, there were pronounced
morphological changes in the lung with focal fi brosis,
adenomatous and pneumonocytic hyperplasia, and
cholesterol clefts. The histopathological changes were
most pronounced in the high-exposure group.

7.1.2.2 Liver and Kidney Effects
Fatty degeneration occurred in the convoluted
tubules of the kidney and the liver after a single admin-
istration of 60 mg antimony potassium tartrate solution
to rabbits. The kidney changes appeared a few hours
after the administration, and preceded the changes in
the liver (Franz, 1937). Fatty degeneration in the liver,
but no effects in the kidney, was recorded in an inhala-
tive exposure study on guinea pigs (Dernehl et al ., 1945).
Long-term peroral exposure to high doses of antimony
may also induce signs of liver toxicity. Sunagawa (1981)
gave rats 0.5-2% antimony and antimony trioxide in
the diet. After 24 weeks, the most exposed animals had
elevated serum levels of a liver enzyme, GOT.

7.1.2.3 Endocrine Effects
Antimony is among a group of metal ions, termed
metalloestrogens, shown to bind to estrogen recep-
tors and cause estrogen agonist responses in vitro and