Tin - Toxicology of Metals - page 830

(McLean et al ., 1983). Stannic chloride had been found
to be a potential clastogen showing an age-related ele-
vation of mitotic index, chromosome aberration, sis-
ter-chromatid exchanges, and micronuclei formation
in blood lymphocyte culture from tin miners (Ghosh
et al ., 1988).
It is known that bad breath odor is mainly caused by
volatile compounds formed by the catabolism of sul-
fur-containing amino acids by bacteria located in the
crypts of the tongue and in periodontal pockets (van
Steenberghe, 1997). Tin compounds can inhibit the for-
mation of the volatile compounds through production
of insoluble tin sulfi de.

of soluble tin compounds and ameliorating effect of
supplementary dietary iron and copper are reported.
Schafer et al . (1985) reported an oral LD 50 of 775 mg/kg
body weight for tin (II) oxide in deer mice.
ATSDR (Agency for Toxic Substances and Disease
Registry) has evaluated the noncarcinogenic oral dose
data for inorganic tin but did not derive a chronic oral
minimal risk level (MRL), because the lowest dose
tested, 0.7 mg Sn/kg per day as stannous chloride,
reduced survival in a 42-month drinking water study
in rats (Schroeder et al ., 1968). However, ATSDR did
derive an intermediate-duration of MRL of 0.3 mg/
kg/day on the basis of a NOAEL of 32 mg Sn/kg/day
(as stannous chloride) for hematological effects in rats
in a 13-week dietary study (de Groot et al ., 1973). Mam-
mary adenocarcinoma, uterine sarcoma, and adenocar-
cinoma near the jaw occurred in a group of rats, which
were fed a diet containing 2% chlorostannate for more
than 1 year (Roe et al ., 1965); 16% of B6C3F1 mice fed
with stannous chloride at a concentration of 2000 mg/
kg (or 0.2%) for period of 105 weeks developed hepato-
cellular adenomas or carcinomas (National Toxicology
Program, 1981). A similar increase has been seen with
the incidence of histolytic lymphomas among female
mice. Injection of metallic tin powder into Lewis rats
caused the enlargement of draining lymph nodes and
intense hyperplasia of plasma cells (Levine and Saltz-
man, 1996). Another group has shown that no adverse
effects were noted nor was there any difference in
tumor incidence in a group of mice receiving over sev-
eral generations sodium chlorostannate either at 1000
or 5000 mg/kg Sn in the drinking water or stannous
oleate at 5000 mg/kg in the diet (Walters and Roe,
1965). It has been shown that the exposure of rats to tin
at concentration 50-600 mg/kg in the drinking water
resulted in a signifi cant decrease in the bone compres-
sive strength (Ogoshi et al ., 1981).
Tin toxicity may involve the inhibition of certain
key enzymes. The chronic administration of stannous
chloride at a dose of 10 mg/100g body weight twice
weekly for 4-6 weeks has been shown to cause the car-
diac hypertrophy in stroke-prone hypertensive rats.
The tin-induced increase in left ventricular heme oxy-
genase level, as well as cGMP content, has been accom-
panied by a decrease in left ventricular weight/body
weight ratio (Seki et al ., 1999).
In vitro exposure of K562 cells to stannous chloride
resulted in loss of viability and DNA damage in a dose-
response manner (Dantas et al ., 2002). The DNA dam-
age was linked to tin-mediated formation of reactive
oxygen species. It has been suggested that tin can inter-
fere with heme formation by competitive antagonism
with iron, zinc, and copper (Pekelharing et al ., 1994).
The high-tin diet depresses copper status in rats. The

7.1.2 Systemic Effects and Dose-Response
Relationships

7.1.2.1 Animals
Tin is considered an essential nutrient for growth in
the rat, and a tin-defi cient diet leads to reduced growth
(Krigman and Silverman, 1984; Yokoi et al ., 1990b).
In animals, a low-tin diet results in poor growth, alo-
pecia or bilateral hair loss, hearing loss, and reduced
feeding effi ciency. Dietary tin defi ciency can cause
imbalances of essential metals, causing an increase in
calcium and a decrease in the concentration of zinc,
copper, and manganese (Yokoi et al ., 1990b). However,
chronic administration of stannous chloride at the dose
of 10 mg/100g can cause signifi cant, but reversible,
growth retardation of Wistar-Kyoto rats (Escalante
et al ., 1991). The addition of stannous chloride to rat
diet at a concentration of 10-200 mg/kg for 28 days did
not change the body weight of rats; however, there was
a linear inverse response of feed intake (Pekelharing
et al ., 1994).
Oral administration of tin at a dose of 45 mg/kg
weight induced vomiting and diarrhea in cats (Omori,
1966). Cats fed orange juice containing 540 mg/kg of
tin, providing a dose of 5.4 mg/kg weight, had vomit-
ing, and incidences of vomiting were increased with
higher doses (Benoy et al ., 1971). Neurological damage
and renal damage have been reported in rats exposed
to stannous chloride (Conine et al ., 1976). There were
marked differences in the toxicity of stannic and stan-
nous oxide and salts in Wistar rats when given orally.
Animals were fed diets containing 0, 0.03, 0.1, 0.3, or
1% tin salts or oxides for either 4 or 13 weeks showed
no adverse effects, such as changes in mortality and
body and organ weight at low doses but had growth
retardation at high doses (de Groot et al ., 1973). The
insoluble tin compounds were shown to be relatively
harmless, whereas cationic tin compounds soluble in
water or dilute acids can be very toxic because of high
absorption from gastrointestinal tract. The high toxicity