Thallium - Toxicology of Metals - page 811

organ concentrations remained constant whatever the
route of administration. Blood contained very little
thallium, indicating rapid equilibration with tissues.
A steep fall in thallium concentration in the blood
was also observed by Rauws (1974) in the fi rst minutes
after intravenous injection of 204 Tl with thallium nitrate
in the rat. An exponential decrease was approached
only after 2 hours. At a steady state, which was reached
after 24 hours, the thallium in the blood was located
predominantly in red blood cells. In chronic feeding
experiments in the rat, Downs et al . (1960) found the
highest concentration in the kidneys, followed by
bone, liver, lung, spleen, and brain.
In man, too, thallium is widely distributed in the tis-
sues, with the highest concentration in the kidneys. In
the fatal case reported by Smith and Doherty (1964),
tissue thallium concentrations were 7.8 mg/kg in the
kidneys, 5.2 mg/kg in the brain, 7 mg/L in the bile,
and 2.29 mg/L in the urine. In the second fatal case
reported by Cavanagh et al . (1974), the concentration
of thallium in the kidneys was 20 mg/kg; heart, 13 mg/
kg; brain (grey matter), 10 mg/kg; skin, 6 mg/kg; and
liver, bone, muscle, 5 mg/kg; with lower concentra-
tions in other tissues.

doubled; this was believed to result from the simul-
taneous tubular secretion of thallium and potassium
(Lund, 1956). Rauws (1974) gave intravenous 204 TlS0 4
to a small group of rats and simulated thallium kinet-
ics on the basis of a three-compartment model. He con-
cluded that a signifi cant exchange of thallium occurred
between the tissues and the intestinal contents, which
he described as an enteroenteral cycle.
Few observations have been made in man. Thallium
was still excreted in urine and feces by a 19-year-old
male 5 months after ingestion of a thallium-contain-
ing rat poison (Arnold et al ., 1964). Barclay et al . (1953)
gave radioactive thallous nitrate and thallous sulfate
orally to one patient with metastatic osteogenic sar-
coma and found the rate of excretion in the urine to be
3.2%/day of the amount remaining in the body. Thal-
lium excretion in both urine and feces may persist for
many weeks despite low plasma levels in poisoned
patients. In unexposed persons, the highest tissue con-
centration of thallium has been found in hair, through-
out its length (Weinig and Zink, 1967) (see Section 6).
In the long term, therefore, hair, and to a lesser extent
nails, provides an important additional route for the
slow excretion of thallium from the body.
Intravenous infusion in pregnant rats of thallium
sulfate containing 204 Tl for periods up to 32 minutes
showed fetal concentrations of thallium in the order
of one fi fteenth of the maternal plasma levels (Gibson
and Becker, 1970). The uptake of thallium by mater-
nal red blood cells, which is known to occur, could
not adequately explain the low level of thallium that
crossed the placenta.

5.3 Excretion
Thallium is excreted in both animal and man by the
kidneys and intestine and also in small part through
hair and into milk. It can also cross the placental bar-
rier (Heyroth, 1947).
In the rat study described previously (Lie et al ., 1960),
excretion of 204 Tl maintained a similar pattern regard-
less of the route of administration. Approximately 6%
of the administered dose had been excreted in the urine
after 1 day, excretion falling to approximately 0.5% by
the tenth day. Again, by whichever route thallium was
administered, fecal excretion exceeded urinary excre-
tion during the 21 days of the study, the fecal/urinary
ratio rising from 2:5 because of a gradual decrease in
thallium excreted in the urine. Thyresson (1951) and
Barclay et al . (1953) in observations on rats also found
fecal excretion to exceed urinary excretion. From obser-
vations on the rat after the intraperitoneal injection of
10 mg thallous sulfate per kg body weight, Lund (1956)
found the principal routes for the elimination of thal-
lium to be the gut and the kidneys. Concentrations of
the metal in gastrointestinal secretions corresponded
with those in the plasma. In rabbits given an intrave-
nous infusion of thallous nitrate (0.5 g/L), thallium was
shown to be excreted by glomerular fi ltration, approxi-
mately half the fi ltered amount being reabsorbed in
the tubules. With the addition of 1% potassium sulfate
to the infusion, the renal clearance of thallium was

5.4 Biological Half-Time
The body burden as a percentage of administered
dose was determined in rats after the administration of
204 Tl by a variety of routes over a period of 21 days (Lie
et al ., 1960). Body clearance was found to occur expo-
nentially with a half-time of 3.3 days whatever the route
of administration. At the end of 21 days (the total period
of observation), 1% of the administered dose remained.
Because, except for hair, there was no day-to-day vari-
ation in relative organ concentration, individual organs
were considered to have similar biological half-times.
With a biological half-time of 3.3 days, it was calcu-
lated that with daily dosing an equilibrium would be
attained at approximately 20 days. Studies by Hologgi-
tas et al . (1980), based on radioactive thallium scanning
and human reports, indicated a half-time on the order of
1.7 days. A biological half-time of approximately 4 days
was also found by Rauws (1974) in his observations with
204 Tl given intravenously in rats (quoted in Section 5.2).
In his three-compartment model, Rauws considered the