Ecotoxicology, 12, 427±437, 2003

# 2003 Kluwer Academic Publishers. Manufactured in The Netherlands.

Toxicity of Lithium to Three Freshwater Organisms and the

Antagonistic Effect of Sodium

LYNN ADAMS KSZOS,1,y JOHN J. BEAUCHAMP2 AND ARTHUR J. STEWART1

1
Environmental Sciences Division, Oak Ridge National Laboratory, P.O. Box 2008, Bethel Valley Road,
Oak Ridge, TN 37831-6422, USA
2
Department of Mathematics, Lipscomb University, Nashville, TN 37204, USA

Accepted January 8, 2003

Abstract. Lithium (Li) is the lightest metal and occurs primarily in stable minerals and salts. Concentrations of
Li in surface water are typically <0.04 mg l 1 but can be elevated in contaminated streams. Because of the
general lack of information concerning the toxicity of Li to common toxicity test organisms, we evaluated the
toxicity of Li to Pimephales promelas (fathead minnow), Ceriodaphnia dubia, and a freshwater snail (Elimia
clavaeformis). In the laboratory, the concentration of Li that inhibited P. promelas growth or C. dubia reproduc-
tion by 25% (IC25) was dependant upon the dilution water. In laboratory control water containing little sodium
(2.8 mg l 1), the IC25s were 0.38 and 0.32 mg Li l 1 and in ambient stream water containing 17 mg Na l 1,
the IC25s were 1.99 and 3.33, respectively. A Li concentration of 0.15 mg l 1 inhibited the feeding of
E. clavaeformis in laboratory tests. Toxicity tests conducted to evaluate the effect of sodium on the toxicity of
Li were conducted with fathead minnows and C. dubia. The presence of sodium greatly affected the toxicity of Li.
Fathead minnows and Ceriodaphnia, for example, tolerated concentrations of Li as great as 6 mg l 1 when
sufficient Na was present. The interaction of Li and Na on the reproduction of Ceriodaphnia was investigated in
depth and can be described using an exponential model. The model predicts that C. dubia reproduction would not
be affected when animals are exposed to combinations of lithium and sodium with a log ratio of mmol Na to
mmol Li equal to at least 1.63. The results of this study indicate that for most natural waters, the presence of
sodium is sufficient to prevent Li toxicity. However, in areas of historical disposal or heavy processing or use, an
evaluation of Li from a water quality perspective would be warranted.

Keywords: lithium; sodium; toxicity; Pimephales promelas; Ceriodaphnia dubia; Elimia clavaeformis

Introduction of the Li resources, distribution and toxicity to

aquatic biota is provided in Kszos and Stewart
Lithium (Li) is the lightest metal, in its elemental (2003). Lithium is widely used in ceramics, glass
form, and is highly reactive as a pure element. and aluminum production (Ober, 2001), and has
Because of its reactivity, Li does not occur naturally some applications for synthetic rubber, pharmaceuti-
as a pure elementÐit occurs instead in stable miner- cals, chemical manufacturing, lubricants, batteries,
als and salts (Bleiwas and Coffman, 1986). A review nuclear reactor coolant and air treatment.
Concentrations of Li in surface waters are typi-
y
To whom correspondence should be addressed: Tel.: (865) 574- cally low (usually < 0.04 mg l 1; Durfor and Becker,
4784; Fax: (865) 576-8143; E-mail: [email protected] 1964; Mathis and Cummings, 1973; Emery et al.,
428 Kszos et al.

1981; Hill and Gilliom, 1993; Tanner, 1995), lettuce remaining was removed with forceps, blotted
although we have documented one case where ambi- dry on paper toweling and weighed to the nearest
ent levels are elevated due to historical waste-disposal 0.01 mg. These measurements were used to deter-
activities at the Department of Energy's (DOE) Y-12 mine lettuce-mass lost due to snail consumption. The
Plant. The toxicity of groundwater from these burial nominal concentrations of Li tested were 0, 0.05, 0.1,
areas to Ceriodaphnia dubia (waterflea; hereinafter 0.15, 0.3, 1.0, 2.0, 5.0, and 10.0 mg Li l 1.
referred to as Ceriodaphnia) and Pimephales prome- The toxicity of Li (as LiCl) to fathead minnows
las (fathead minnow) was due primarily to Li (Kszos and C. dubia was determined using the methods
and Stewart, 2003). Because there was a general described in EPA (1994) and Kszos and Stewart
paucity of information on Li toxicity to aquatic (2003) with the following additions. Tests were con-
biota, we conducted this study to evaluate the toxicity ducted concurrently using two types of water as dilu-
of Li to Ceriodaphnia, fathead minnows and Elimia ent (East Fork Poplar Creek (EFPC) or DMW).
clavaeformis (a freshwater snail). These tests demon- Lithium test solutions were prepared 24 h before test
strated that differences in toxicity could be due to initiation, using stock solutions of LiCl and DMW or
the sodium content of the dilution water. Laboratory EFPC water. The test solutions were stored at 4  C; a
tests with Ceriodaphnia showed that sodium had an subsample of each test concentration was removed
antagonistic effect on Li toxicity that could be daily and warmed to 25  1  C for test solution
described with a model based on the molar ratio of renewal. The conductivity of each dilution was mea-
Li to Na. sured on the first day of the test; the pH, conductivity,
alkalinity and hardness were assessed daily for the
Materials and methods control water. Fifty-ml samples of the three or four
lowest Li concentrations were preserved (pH < 2)
Test organisms with ultrex nitric acid for analysis of Li by inductively
coupled plasma (ICP) emission spectroscopy. Con-
Fathead minnow larvae and Ceriodaphnia for tests centrations of Li in DMW were 0.32 (measured),
reported here were obtained and cultured as described 0.93 (measured), 1.87 (measured), 3 (nominal), and
in Kszos and Stewart (2003). Freshwater snails, 4 (nominal) mg l 1. Concentrations tested in EFCP
E. clavaeformis, are locally abundant and have been water were 0.36 (measured), 0.98 (measured), 1.90
used in other ecotoxicological studies (Burris et al., (measured), 3.0 measured, and 4 (nominal) mg l 1.
1990; Stewart et al., 1993). Snails were collected In 1995, one experiment was conducted with fat-
from a non-contaminated reach of Northwest Tribu- head minnows larvae. The minnows were exposed for
tary located on the DOE Oak Ridge Reservation; they 7 d to nominal Li concentrations of 0.5, 1, 2, and 4 mg
were kept in the laboratory for 48 h in dilute mineral Li l 1 in combination with five (nominal) Na concen-
water (DMW; see Kszos and Stewart, 2003), at 25  C, trations (as Na2SO4, JT Baker, 99.9% pure) of 2.5, 10,
before use. 40, 80, and 160 mg l 1 (see Kszos and Stewart, 2003
for methodology).
Test methods Between 1994 and 1997, two sets of tests with
Ceriodaphnia were conducted to evaluate the influ-
The toxicity of Li (as LiCl, EM Science, 99% pure) to ence of Na on Li's toxicity. In the set of tests, the target
E. clavaeformis was determined using 72 h laboratory nominal Li concentrations were: 1 mg Li l 1 (mea-
tests that used feeding rate (expressed as mg of lettuce sured range ˆ 0.92±1.3 mg l 1), 2 mg Li l 1 (mea-
consumed) as the effect endpoint. The tests were sured range ˆ 1.7±2.1 mg l 1), and 4 mg Li l 1
conducted by exposing groups of snails (12 snails (measured range ˆ 3.4±4.0 mg l 1). Sodium was
per test chamber, three replicate test chambers per added to DMW as sodium sulfate (Na2SO4) at increas-
treatment) to LiCl in DMW. Three fresh lettuce-leaf ing concentrations, ranging from 1.7 to 40 mg Na l 1.
(Lactuca sativa) disks (2 cm diameter) were stapled The combinations of Li (measured) and Na (added)
together, pre-weighed as a group, and added to each tested were 4 mg Li l 1 with 1.7, 3.2, 7, 9.6, 21, and
test chamber at the start of the test. The test media 40 mg l 1 Na; 2 mg Li l 1 with 1.7, 3.5, 7, and 10 mg
was replaced daily, but the lettuce-leaf disks (plus the Na l 1; and 1 mg Li l 1 with 1.7, 3.5, and 7 mg Na l 1.
staples) were left in place. At the end of the test, the The Ceriodaphnia reproduction data (not shown here)
 Toxicity of Lithium 429

revealed a strong relationship between reproduction into each replicate. Water chemistry and analytical
and the ratio of Li to Na in the water. The experimental data were obtained as described previously.
design of these tests did not allow for strong statistical
analysis of the effects of Na on the toxicity of Li Statistical analyses
based on Ceriodaphnia reproduction. Thus, a second
set of experiments was conducted specifically to test The inhibition concentration (IC) was calculated using
for the effects of the Li-to-Na ratio on Ceriodaphnia the Linear Interpolation Method (EPA, 1994) and EPA
reproduction. software (EPA, 1993). Data were expressed as the con-
To further evaluate the effect of sodium and Li on centration that inhibits reproduction of Ceriodaphnia
Ceriodaphnia reproduction, four 7 d Ceriodaphnia or growth of fathead minnows by 25% and 50%.
experiments were used to characterize the toxicity In the tests used to study the effect of Na on the
of the 85 combinations of Li and Na shown in toxicity of Li to Ceriodaphnia, we conducted two types
Table 1. The four experiments were too large to be of statistical analyses in order to justify combining
conducted simultaneously, so controls to evaluate data from the four experiments for further analysis.
test-chamber position (block) and differences in The first analysis used only the animals in the control
reproduction through time were included in each water. A nested analysis of variance (ANOVA; SAS,
experiment (160 control animals in total). Each com- 1985) was used to test for test-chamber position
bination of Li and Na listed in Table 1 was randomly effects and time effects in experiments 1±4. The
assigned to a block by drawing numbers and each of total number of young produced in the first 6 d of
the ten replicates per treatment was randomly the test was the response variable. The ANOVA for
assigned to a position in the block using a random test-chamber position effects and time effects for con-
number generator. Tests 1±3 contained five treat- trol groups showed no significant difference between
ments that contained 700 mg l 1 Na (not shown in tests ( p > 0.70), but did reveal a highly significant
Table 1). The results for these ``high-sodium'' tests test-chamber position effect ( p < 0.01). Examination
are not discussed further because (1) later statistical showed that the mean number of young produced
analyses revealed that the response of Ceriodaphnia by the controls for one block in test 2 was much
to the combinations of Li and 700 mg l 1 Na were lower compared to the controls for all other blocks
controlled by the sodium concentration, and (2) our in that test (10.6 offspring per female, versus a
focus was on responses of the animals in that range of range ˆ 22±30 offspring per female). When data
Na : Li where there is an interaction. The toxicity test from the entire block in test 2 was excluded, the test
procedures used in these four experiments were iden- for effects due to time and test-chamber position
tical to those described earlier, with one exception: within test was not significant (p ˆ 0.13). Because
the Ceriodaphnia neonates (24 h old) used to initiate this analysis showed that the block was suspect,
the tests were first pooled into a large beaker, and all data from the block were excluded from further
individuals were then randomly selected and placed consideration.

Table 1. Experimental design used to test for the effects of Li-to-Na ratio on Ceriodaphnia reproduction. Values in the body of the table (i.e.,
1, 2, 3, 4) indicate experiment number. The combination of 0.20 mg l 1 Li and 13.5 mg l 1 Na, for example, was tested in experiments 1, 2
and 3. Values in parentheses are range of measured values

Sodium midpoint (mg l 1)

Lithium midpoint (mg l 1) 13.5 (11±16) 20.0 (19±21) 38.5 (37±40) 50.5 (48±53) 57.0 (55±89) 74.5 (73±76) 96.5 (83±110)

0.20 (0.18±0.22) 1, 2, 3 1, 2, 3 1, 2, 3
0.39 (0.35±0.43) 1, 2, 3 1, 2, 3 1, 2, 3
0.80 (0.78±0.82) 1, 2, 3 1, 2, 3 1, 2, 3
2.55 (2.5±2.6) 1, 2, 3,4 4 1, 2, 3 4 4 1, 2, 3,4
3.45 (3.4±3.5) 4 4 4 4 4
4.25 (4.1±4.4) 1, 2, 3 4 4 1, 2, 3 4 4 1, 2, 3,4
5.05 (5.0±5.1) 4 4 4 4 4
6.05 (5.9±6.2) 4 4 4 4 4
430 Kszos et al.

We also excluded reproduction data for a few

other individual animals from further analysis, based
on best professional judgement. Of the 1010 neonates
followed in this study, we excluded data on 15
because they were killed accidentally during testing.
We also excluded data on nine neonates because (1)
they were the only death in the 6 d period for that
particular treatment, and (2) these animals produced
significantly fewer young, compared to the other nine
replicates in that treatment. For example, one animal
that we eliminated from statistical analysis produced
only one brood of three offspring in 6 d; the remain-
ing nine replicates for this treatment produced, on an
average, 20.5 offspring per female.
The second analysis involved comparing the
response of animals to a treatment that was repeated Figure 1. Effect of Li on lettuce consumption by the snail,
across all four tests. Treatments were assigned a con- E. clavaeformis (72 h test). Error bars show  SE, for three
centration equal to the midpoint of the measured replicates at each Li concentration tested. C-1 and C-2 represent
concentrations, as indicated in Table 1. Due to the results for two separate controls.
experimental design, the only data that fit this criter-
ion were the treatments of 96.5 mg Na l 1 in combi- using a 24 h test method otherwise identical to that
nation with 2.55 and 4.25 mg Li l 1 (see Table 1). We used for testing E. clavaeformis, revealed similar
used ANOVA to evaluate the variation in the total results: lettuce consumption was reduced by more
number of young produced in the first 6 d of the test than 50% at a Li concentration of about 0.8 mg l 1
in response to Li concentration, test number and the (data not shown).
interaction of Li and test. None of these sources of
variation were significant ( p > 0.08), indicating that
the animal's response to Li and Na were similar Lithium toxicity tests with fathead minnow larvae
across time. This analysis, in combination with the and Ceriodaphnia
analysis of the control reproduction noted above, led
us to conclude that data from all four tests could be Lithium in DMW was 5 to 10 times more toxic than
combined. This analysis also indicated that the small in EFPC water. For Li in DMW, the 25% ICs for
variability in measured concentrations for a particular fathead minnows and Ceriodaphnia were 0.38 and
target concentration (see Table 1 for ranges) did not 0.32 mg Li l 1 respectively. For Li in EFPC water,
affect the test outcome. Thus, we elected to use the the 25% ICs for fathead minnows and Ceriodaphnia
midpoint of the measured concentrations of Li and Na were 1.99 and 3.33 mg Li l 1 respectively. Likewise,
across tests to represent a given concentration (Table 1). the 50% ICs for fathead minnows and Ceriodaphnia
in DMW were 0.57 and 0.72 mg Li l 1 respectively
Results and in EFPC water were 2.47 and >4 mg Li l 1,
respectively. The Li and Na concentrations in DMW
Lithium toxicity test with snails were < 0.04 mg l 1 and 2.8 mg l 1, respectively. The
average Li and Na concentrations in EFPC water
At higher concentrations, the effect of Li exposure < 0.04 mg l 1 and 17.4 mg l 1, respectively.
on E. clavaeformis' activity was evident within the
first several hours. Lettuce consumption by Tests to determine the effects of sodium on
E. clavaeformis was reduced almost 50% at a Li lithium's toxicity
concentration of 0.15 mg l 1, and was severely inhib-
ited at a Li concentration of 0.3 mg l 1 (Fig. 1). Sub- The results of the fathead minnow test are shown
sequent tests of Li's inhibitory effects on Pleurocera in Fig. 2. The survival of minnows in 80 and
unicale unicale (a close relative of E. clavaeformis), 160 mg Na l 1 are not shown because survival was
 Toxicity of Lithium 431

120 concentrations is given in Fig. 4. The responses of

Ceriodaphnia to low concentrations of Li (e.g., 0.20±
2.55 mg l 1) are not shown because at these concen-
100

80
trations there was no significant difference compared
2.5 mg Na/L to the control, except at Na ˆ 700 mg l 1, where
Survival (%)

10 mg Na/L
60 40 mg Na/L Ceriodaphnia reproduction was low regardless of the
concentration of Li. The amelioration of Li toxicity
40 with increasing Na concentration is clearly revealed
in Fig. 4. For example, in DMW containing
20 20.0 mg Na l 1, Li concentrations of 3.45, 4.24,
and 5.05 mg l 1 significantly reduced reproduction
of Ceriodaphnia. In DMW containing 57 mg Na l 1,
0
0 1 2 3 4
Lithium Concentration (mg/L) however, reproduction was not affected in any of
these concentrations.
Figure 2. Survival of fathead minnows (P. promelas) in response
to lithium and sodium in short-term chronic test. The response of Ceriodaphnia to Li and Na was
investigated further by examining the reproductive
response to the molar ratio of the two metals
reduced in the Na ‡ DMW treatments (mean survival (Na : Li). In this analysis, the midpoint concentrations
was 75% at 80 mg l 1 and 32.5% at 160 mg l 1), thus of Li and Na were used, as described in Table 1. The
indicating that sodium was dominating the response. response variable was the mean 6 d reproduction from
Increasing the concentration of Na clearly decreased the replicates for a particular treatment. The number
the toxicity of Li. For example, at 2 mg Li l 1, survi- of replicates used to estimate this mean reproduction
val was 2.5% in DMW containing 2.5 mg Na l 1 but was retained as the weight to associate with each
was only slightly reduced when the water contained observed mean. The log of the Na-to-Li ratio was
10 mg Na l 1 (Fig. 2). Similarly, at 4 mg Li l 1 calculated by taking the natural log of the mmol Na
survival was 0% in water containing only to mmol Li. The plot of Ceriodaphnia reproduction
10 mg Na l 1, but >90% in water containing versus molar ratio is shown in Fig. 5. We used an
40 mg Na l 1 (Fig. 2). The growth data for the exponential model to estimate the dependence of 6 d
minnows in this test are not shown because no clear reproduction on the Na-to-Li ratio:
relationship was identified with varying Li and Na.
Growth of minnows was high in the three lowest Na y ˆ a…x ‡ d†b ecx …1†
treatments (final mean weights of the larvae were where y ˆ 6 day reproduction, x ˆ the Na±Li ratio
0.42±0.46 mg per fish), indicating that the test condi- and a, b, c, and d are parameters to be estimated from
tions were satisfactory (EPA, 1994). the observations on y and x. A weighted non-linear
Survival of Ceriodaphnia exposed to Li was estimation procedure was used to estimate the para-
strongly affected by the concentration of Na. In low- meters where the weight of each observation
sodium water (1.7 mg Na l 1), 1 mg Li l 1 killed all was equal to the number of replicates in the given
of the Ceriodaphnia within 6 d (Fig. 3C). In water mean y. Figure 5 shows the observed data and the
having a Na concentration of 40 mg Na l 1, fitted exponential curve. Table 2 contains the para-
Ceriodaphnia survival was 100% even at a Li meter estimates and other associated estimates for this
concentration of 4 mg l 1 (Fig. 3A). analysis. We also estimated the range of x values
The results of the Ceriodaphnia tests conducted where the predicted reproduction from equation (1)
with various combinations of Li and Na are restricted did not differ significantly from the mean control
to the consideration of effects on reproduction, reproduction (26.2 offspring per female). This was
because by design, the Li and Na levels were selected done by considering the standardized difference
to be lower than the acute toxicity thresholds for Li between the predicted reproduction and the control
and Na. Dunnett's procedure was used to test for reproduction as a function of x, for all values of x
significant differences in Ceriodaphnia reproduction where the absolute value of the standardized dif-
between the control and the treatment groups. A sum- ference was less than 1.96. Standardization was
mary of Ceriodaphnia reproduction for four Li achieved by dividing the difference by its standard
432 Kszos et al.

(A)
100

80
Survival (%)

60
3.2 mg Na/L
40 7 mg Na/L
9.6 mg Na/L
21 mg Na/L
40 mg Na/L
20
A (4 mg Li/L)

0
0 1 2 3 4 5 6 7

(B) 100

80
Survival (%)

1.7 mg Na/L
60 3.5 mg Na/L
7.0 mg Na/L
40 10 mg Na/L

20 B (2 mg Li/L)

0
0 1 2 3 4 5 6 7

(C) 100

80
Survival (%)

60 1.7 mg Na/L
3.5 mg Na/L
40 7.0 mg Na/L

20 C (1 mg Li/L)

0
0 1 2 3 4 5 6 7

Test Day
1 1 1
Figure 3. Survival of C. dubia in response to mixtures of sodium and 4 mg Li l (A), 2 mg Li l (B), and 1 mg Li l (C). Control survival
was 100%.

error. The process described here was used to Discussion

determine the estimated range of x values provid-
ing estimates not differing significantly from the The results of this study show that Li is biologically
control reproduction. Using this approach, for x in active (i.e., toxic) to various aquatic species in labora-
the interval (1.63, 2.06) and the interval (4.79, 6.68), tory tests at concentrations in the range of 0.15±0.5 mg
the predicted 6 d reproduction from (1) and control Li l 1 (this paper, and Long et al., 1998), yet there is
mean did not differ significantly. Therefore, if the little attention paid to Li in limnological or toxicologi-
log ratio mmol Na/mmol Li was >1.63, the reproduc- cal texts. We believe that this is due, at least in part, to
tion of Ceriodaphnia was not different from the con- the fact that Li's toxicity is ameliorated by Na. Fathead
trol mean. At x ˆ 1.816, the predicted value of y minnows and Ceriodaphnia, for example, tolerate con-
is 26.2 (average reproduction of controls), with 95% centrations of Li as great as 6 mg l 1 when sufficient
confidence limits on the estimated mean of (25.5, Na is present (Figs 2±4). Sodium levels in most ambient
26.9). waters typically are high enough to afford protection
 Toxicity of Lithium 433

13.5 mg/L
35 20.0 mg/L
38.5 mg/L
50.5 mg/L
57 mg/L
30 74.5 mg/L
* 96.5 mg/L
Mean Offspring per Female

25 *

* *
*
20
*

15

10 *

*
5 *

0
3.45 4.25 5.05 6.05
Lithium Concentration (mg/L)
Figure 4. Mean (SD) unweighted reproduction (offspring per female) of C. dubia exposed to various combinations of Li and Na. Line
represents average reproduction of controls (n ˆ 151). Asterisks () indicate treatments where reproduction was significantly lower than
control.

35 Table 2. Parameter estimates for exponential model,

Mean 6-d offspring (weighted by number surviving)

y ˆ a(x ‡ d)becx
30
Parameter Estimate Standard error
25 a 23.93 1.263
b 0.8140 0.1245
20 c 0.2375 0.0414
d 0.0863 0.0722
15

10 The finding that Li's toxicity to aquatic organisms

is strongly affected by sodium is perhaps not surpris-
5 ing given that Li ‡ is known to interfere with the
actions of Na ‡ in humans (Klemfuss and Greene,
0
0 1 2 3 4 5 6 1991; Bennett, 1997) and other vertebrates (for exam-
Log ratio mmole Na/mmole Li ple, Kinsella and Aronson, 1981; Yu et al., 1993).
Figure 5. Mean weighted reproduction (offspring per female) of Because Li is an environmental trace element and
C. dubia in relationship to log ratio of Na-to-Li. Average reproduc- effective for treatment of bipolar disorder, much
tion of controls in dilute mineral water (n ˆ 151) was 26.2 offspring information is available on the toxicity of Li to
per female. An exponential model was used to fit the curve to the humans, and on the modifying effect of cations on Li
experimental data. toxicity (Schrauzer and Klippel, 1991). In mammals,
the potential action of Li includes almost every pro-
against the adverse effects of Li in the low part-per- cess involving the cellular uptake or release of sodium,
million or sub-part-per-million range. Thus, Li's toxi- potassium, calcium, or magnesium, the second mes-
city might be thought of as being ``hidden'' by levels senger system (e.g., compound(s) generated within the
of Na that are present in most natural systems. cell as a result of an initial binding by a hormone),
434 Kszos et al.

hormones, and most of the known neurotransmitters 80% at 1.0 mg Li l 1, and survival was only 2.5% at
(Klemfuss and Greene, 1991). The monovalent metal 2 mg Li l 1 (Fig. 2).
cations (Li, Na, K, Rb and Cs) can replace each other One of the highest reported Li tolerance limits
in many cellular processes. Li ‡ also interferes with is that for Colorado squawfish, razorback sucker
Mg2 ‡ and Ca2 ‡ uptake by replacement at binding and bonytail (Hamilton, 1995). In this evaluation,
sites (Williams, 1973). Functional interactions of Li the investigators used reconstituted Middle Green
with other cations include competition for enzyme or River basin water as diluent. This water contained
membrane binding sites (Klemfuss and Greene, 1991). Na at a nominal concentration of 49 mg l 1. Our
In mammals, increasing Na intake increases the excre- results suggest that the toxicity of Li to these species
tion of Li (Thomsen and Leyssac, 1986, 1987). Thus, would be much greater if the water had contained
Na intake can alleviate many of the toxicological less Na.
effects of Li (Venugopal and Lukey, 1978). Very few published data are available with which
Many of the studies on the toxicity of Li to aquatic to compare our Ceriodaphnia test results. Anderson
biota that we reviewed did not provide information (1946) gives a value of 6.5 mg l 1 for (Na and K) in
about the concentrations of Na or other ions in the test Lake Erie water, which was used as a diluent for
medium. The study by Long et al. (1998), for exam- the 64 h threshold concentration of 1.2 mg Li l 1 for
ple, used water from upper Saginaw Bay of Lake D. magna (Anderson, 1948). In our tests, at 48
Huron off Whitestone Point as diluent, but the Na and 72 h, we observed 80% and 60% survival of
concentration in this water was not reported. How- Ceriodaphnia, respectively, in water containing
ever, the water was reported to have a conductivity of 2 mg Li l 1 and 3.5 mg Na l 1 (Fig. 3B). Given that
160±270 mmho cm 1. Presuming a standard bicarbo- 1.64 was the lowest calculated log ratio of (mM
nate composition (see Hutchinson, 1975, Table 69), Na : mM Li) calculated to be not different from con-
the Lake Huron water could reasonably have con- trols for Ceriodaphnia, one can predict that a Na
tained Na at a concentration of 6±11 mg l 1. Tests concentration of about 20.5 mg l 1 would have
to determine Li's toxicity to fathead minnows (Fig. 2) negated the effects of the Li at 1.2 mg Li l 1 in the
showed that Na at 6±11 mg l 1 was sufficient to study by Anderson (1948).
influence minnow survival, at the Li concentrations We found no information that the interaction of Li
of 1.4 and 2.4 mg Li l 1 reported by Long et al. and Na in the aquatic environment had been consid-
(1998). In fact, if the Na concentration had been as ered or measured at the organism level. Most research
great as 40 mg l 1, perhaps no effect on minnow using invertebrates has focused on understanding ion
survival would have been detected at all. Although transport mechanisms at the cellular level by using
it is difficult to compare results of the fathead min- excised membranes (e.g., Shetlar and Towle, 1989;
now tests by Long et al. (1998) with our results (Long Ahearn and Clay, 1989; Ahearn and Franco, 1991;
et al. used 26 d tests, while we used 7 d tests), the Davis et al., 1992). It is reasonable to hypothesize that
range of toxic values for Li in the two studies is the amelioration of Li's toxicity by Na is based
similar. At a Na level of 10 mg l 1, for example, we upon competitive interactions related to Na‡/H‡
found no effect on survival at 1 mg Li l 1 (Fig. 2), and exchange. Grinstein and Wieczorek (1994) provide a
Long et al. (op cit.) reported a 26 d EC50 of 1.0 mg Li review of Na‡/H‡ exchange in animals. In verte-
l 1 and a NOEC of 0.20 mg Li l 1 (at a presumed Na brates, this exchange occurs with a one-to-one stoi-
concentration of 6±11 mg l 1). chiometry and is therefore electroneutral (op. cit.).
The results of our fathead minnow tests also are Ahern et al. (1994) identified a similar electroneutral
similar to those reported by Emery et al. (1981). In Na‡/H‡ exchange in apical membranes of crayfish
the study by Emery et al. (1981), at a presumed Na gills. Additionally, other investigators have identified
level of 3±8 mg l 1 (based on alkalinity of the Colum- a unique type of exchange in some invertebrates,
bia River water used as a diluent), juvenile trout wherein two extracellular Na ions are exchanged
survival in a 10 d test was nearly 100% in 0.5 mg for one intracellular protein (for review see Ahearn
Li l 1, but nearly zero when the concentration et al., 1994). Based on evidence that Daphnia
of Li was greater than 1.0 mg l 1. In our study, at (closely related to Ceriodaphnia) respiratory surfaces
2.5 mg Na l 1, minnow survival was reduced to are similar to those of crayfish (Kikuchi, 1983;
 Toxicity of Lithium 435

Dickson et al., 1991), we expect that a transport sufficient to ameliorate the effects of Li up to about
mechanism such as the Na ‡ /H ‡ exchange system 0.06 mg l 1 for Ceriodaphnia. However, if the
would be present in Ceriodaphnia tissues. Although potential exists for higher concentrations of Li to
we found no studies that evaluated the ability of enter the environment, a concurrent increase in Na
Li to inhibit the ion-exchange process in crayfish, would be necessary to prevent toxicity. Additional
Duerr and Ahearn (1996) reported that external research with more sensitive or region-specific
Li ‡ was an effective competitive inhibitor of the species may be warranted in such cases. Because
exchange process in lobster (Homarus americanus). removal of Li from the aquatic environment is diffi-
Thus, we speculate that the basis for inhibitory effect cult (Kszos and Stewart, 2003), it will be important
of Li on Ceriodaphnia reproduction probably to maintain best management practices for prevent-
stems from competition of Li ‡ with Na ‡ for the ing dissolved lithium from entering the aquatic
exchange of H ‡ . environment. This will become increasingly impor-
At the whole organism level, many studies have tant as the use and processing of Li-rich materials
shown that the toxicity of metals such as Zn, Cu and increases.
Cd can be ameliorated by elevated levels of calcium
(e.g., Rand and Petrocelli, 1985). However, relatively
few specifically address the amelioration of a metal's Acknowledgments
toxicity by sodium (but see Bury et al., 1999; Grosell
et al., 2000). In a review by Hall and Anderson This research was supported by the Y-12 Plant Toxi-
(1995), data on the influence of salinity on the toxi- city Control and Monitoring Program and the Y-12
city of chemicals to aquatic animals were summar- Biological Monitoring and Abatement Program
ized. Similar to our study, the general trend was that (BWXT Y-12 Environment, Safety and Health Divi-
the toxicity of metals such as Cd, Cu, Ni, and Zn sion). Gail Morris, Belinda Konetsky, Kara Kenney,
increased with decreasing salinity. The authors Wilena Session, Jim Sumner, Terry Phipps, and
(op. cit.) attribute this finding to an increase in the Natasha Hunt provided outstanding technical assis-
activity of the free metal ion (e.g., Cd2 ‡ ) under tance. We thank Joe Kszos for his invaluable support,
lower-salinity conditions. Others have proposed mod- and Sylvia Talmage (Oak Ridge National Labora-
els based upon competition of cations for biotic tory), Joyce Ober (US Geological Survey), and three
ligands present on fish gills and in the environment anonymous reviewers for thoughtful, constructive
(Santore et al., 2001). The biotic ligand model reviews that improved the manuscript. Oak Ridge
(op. cit.) showed good agreement with experimental National Laboratory is managed by UT-Battelle,
data when evaluating the effect of Ca and Na with the LLC, for the US Department of Energy under
acute toxicity of copper to fathead minnows. The contract DE-AC0-00OR22725.
authors concluded that Na competes with Cu for
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