208
repeated exposures, but the kidney that has developed such a tolerance is not normal. Thus, tolerant animals have high urine volumes, a diminished glomerular
filtration rate and a loss of concentrating capacity by the kidney. In his view, the
concentration of 3 μg [U] g
−1
of kidney applied for many years as a guidance level
for limiting occupational exposures was based on tests of chemical toxicity that
were less sensitive and on definitions of chemical toxicity that were less stringent,
than those developed subsequently. Moreover, in the underpinning human studies,
the subjects may have been exposed to kidney concentrations in the order of
3 μg [U] g
−1
of kidney only for very brief periods. Leggett (1989) concluded that it
might be prudent to lower this long-standing guidance level by roughly an order of
magnitude.
More recently, the WHO (2012) has set the tolerable daily intake (TDI) of uranium as 60 μg, based on an epidemiological study by Kurttio et al. (2006) that was
used to define a no-effect group. The value of the 95th percentile of the uranium
exposure distribution for this group was estimated to be 1094 μg d
−1
(95% confidence interval on the 95th percentile was 637–1646 μg d
−1
). The TDI was taken to
be 10% of the lower bound of the 95% confidence interval on the 95th percentile of
the exposure distribution for this group. For comparison, ATSDR (2013) has recommended a MRL value for chronic exposure to uranium by ingestion of 0.2 μg kg
−1
d
−1
.
For a reference adult of mass 70 kg (ICRP 1975), this corresponds to 14 μg d
−1
.
Given the very different bases of derivation, the relatively small difference between
the TDI and MRL values suggests that a robust basis exists for limiting intakes of
uranium by ingestion.
To interpret the WHO TDI in terms of the equivalent kidney concentration, it is
necessary to establish the relationship between the chronic intake rate of uranium
and the maintained kidney concentration that is achieved at equilibrium. Wilson and
Thorne (2015) have shown that an ingestion intake rate of 1 μg [U] d
−1
by adults
corresponds to a maintained kidney concentration of 2.2 × 10
−4
μg [U] g
−1
of the
kidney. Thus, the TDI corresponds to 0.013 μg [U] g
−1
of kidney. This is well below
the value of 0.3 μg [U] g
−1
of kidney that Leggett (1989) considered prudent.
Following from the TDI of 60 μg and based on a water consumption rate of
2 L d
−1
, the WHO (2012) set a provisional guideline value for uranium in drinking
water of 30 μg [U] L
−1
. This may be compared with the value of 20 μg [U] L
−1
adopted in Australia (Jones et al. 2006), and 30 μg [U] L
−1
in the USA (EPA 2005).
To date, no European statutory limits have been imposed for uranium in drinking
water. However, European Directive 98/83/EC stipulates that waters in which alphaemitter concentrations exceed 0.1 Bq L
−1
should be investigated to determine what
corrective action, if any, is required. For natural uranium present without any progeny, 0.1 Bq L
−1
corresponds to 4 μg [U] L
−1
, which is a more stringent restriction
than the values recommended preventing chemotoxic effects.
M. C. Thorne
repeated exposures, but the kidney that has developed such a tolerance is not normal. Thus, tolerant animals have high urine volumes, a diminished glomerular
filtration rate and a loss of concentrating capacity by the kidney. In his view, the
concentration of 3 μg [U] g
−1
of kidney applied for many years as a guidance level
for limiting occupational exposures was based on tests of chemical toxicity that
were less sensitive and on definitions of chemical toxicity that were less stringent,
than those developed subsequently. Moreover, in the underpinning human studies,
the subjects may have been exposed to kidney concentrations in the order of
3 μg [U] g
−1
of kidney only for very brief periods. Leggett (1989) concluded that it
might be prudent to lower this long-standing guidance level by roughly an order of
magnitude.
More recently, the WHO (2012) has set the tolerable daily intake (TDI) of uranium as 60 μg, based on an epidemiological study by Kurttio et al. (2006) that was
used to define a no-effect group. The value of the 95th percentile of the uranium
exposure distribution for this group was estimated to be 1094 μg d
−1
(95% confidence interval on the 95th percentile was 637–1646 μg d
−1
). The TDI was taken to
be 10% of the lower bound of the 95% confidence interval on the 95th percentile of
the exposure distribution for this group. For comparison, ATSDR (2013) has recommended a MRL value for chronic exposure to uranium by ingestion of 0.2 μg kg
−1
d
−1
.
For a reference adult of mass 70 kg (ICRP 1975), this corresponds to 14 μg d
−1
.
Given the very different bases of derivation, the relatively small difference between
the TDI and MRL values suggests that a robust basis exists for limiting intakes of
uranium by ingestion.
To interpret the WHO TDI in terms of the equivalent kidney concentration, it is
necessary to establish the relationship between the chronic intake rate of uranium
and the maintained kidney concentration that is achieved at equilibrium. Wilson and
Thorne (2015) have shown that an ingestion intake rate of 1 μg [U] d
−1
by adults
corresponds to a maintained kidney concentration of 2.2 × 10
−4
μg [U] g
−1
of the
kidney. Thus, the TDI corresponds to 0.013 μg [U] g
−1
of kidney. This is well below
the value of 0.3 μg [U] g
−1
of kidney that Leggett (1989) considered prudent.
Following from the TDI of 60 μg and based on a water consumption rate of
2 L d
−1
, the WHO (2012) set a provisional guideline value for uranium in drinking
water of 30 μg [U] L
−1
. This may be compared with the value of 20 μg [U] L
−1
adopted in Australia (Jones et al. 2006), and 30 μg [U] L
−1
in the USA (EPA 2005).
To date, no European statutory limits have been imposed for uranium in drinking
water. However, European Directive 98/83/EC stipulates that waters in which alphaemitter concentrations exceed 0.1 Bq L
−1
should be investigated to determine what
corrective action, if any, is required. For natural uranium present without any progeny, 0.1 Bq L
−1
corresponds to 4 μg [U] L
−1
, which is a more stringent restriction
than the values recommended preventing chemotoxic effects.
M. C. Thorne