United States
Environmental Protection
1=1 m m Agency
EPA/690/R-09/035F
Final
9-17-2009
Provisional Peer-Reviewed Toxicity Values for
Stable (Nonradioactive) Neodymium Chloride
(CASRN 10024-93-8)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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COMMONLY USED ABBREVIATIONS
BMD
Benchmark Dose
IRIS
Integrated Risk Information System
IUR
inhalation unit risk
LOAEL
lowest-observed-adverse-effect level
LOAELadj
LOAEL adjusted to continuous exposure duration
LOAELhec
LOAEL adjusted for dosimetric differences across species to a human
NOAEL
no-ob served-adverse-effect level
NOAELadj
NOAEL adjusted to continuous exposure duration
NOAELhec
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
RfC
inhalation reference concentration
RfD
oral reference dose
UF
uncertainty factor
UFa
animal to human uncertainty factor
UFC
composite uncertainty factor
UFd
incomplete to complete database uncertainty factor
UFh
interhuman uncertainty factor
UFl
LOAEL to NOAEL uncertainty factor
UFS
subchronic to chronic uncertainty factor
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR STABLE
(NONRADIOACTIVE) NEODYMIUM CHLORIDE (CASRN 10024-93-8)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund
Program.
3)	Other (peer-reviewed) toxicity values, including
<	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
<	California Environmental Protection Agency (CalEPA) values, and
<	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a
Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific
literature using the same methods, sources of data, and Agency guidance for value derivation
generally used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal
review by two U.S. EPA scientists and external peer review by three independently selected
scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multiprogram consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all U.S. EPA programs, while PPRTVs are developed
specifically for the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV document and understand the strengths
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and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or
external parties who may choose of their own initiative to use these PPRTVs are advised that
Superfund resources will not generally be used to respond to challenges of PPRTVs used in a
context outside of the Superfund Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
Neodymium (Nd; CASRN 7440-00-8) is a rare earth element belonging to the
lanthanide1 series of the periodic table. Neodymium compounds are used in carbon-arc lamps
for movie projection, permanent magnets, organic reagents, lasers, and alloys. Neodymium can
form water-soluble compounds (e.g., neodymium chloride and neodymium nitrate) and insoluble
compounds (e.g., neodymium oxide and neodymium hydroxide). Water-soluble neodymium
compounds (e.g., neodymium chloride) can form insoluble hydroxides at neutral or alkaline pH.
In general, the lanthanides can be radioactive or stable. This PPRTV document addresses only
the toxicity of stable (nonradioactive) forms of neodymium and its compounds, and derives a
toxicity value only for neodymium chloride. Neodymium chloride typically is found as the
hexahydrate (CASRN 13477-89-9).
No RfD, RfC, or carcinogenicity assessment for stable, nonradioactive neodymium or
neodymium compounds is available on IRIS (U.S. EPA, 2009). Subchronic or chronic RfDs or
RfCs for neodymium are not listed in the Health Effects Assessment Summary Tables (HEAST)
(U.S. EPA, 1997) or the Drinking Water Standards and Health Advisories list (U.S. EPA, 2006).
No relevant documents are included in the Chemical Assessment and Related Activities (CARA)
list (U.S. EPA, 1991, 1994). The Agency for Toxic Substances and Disease Registry
(ATSDR, 2009) has not produced a Toxicological Profile for neodymium, and no Environmental
Health Criteria Document is available from the World Health Organization (WHO, 2009). The
chronic toxicity and carcinogenicity of neodymium have not been assessed by the International
Agency for Research on Cancer (IARC, 2009) or the National Toxicology Program
(NTP, 2005, 2009). The American Conference of Governmental Industrial Hygienists
(ACGIH, 2008), the Occupational Safety and Health Administration (OSHA, 2009), and the
National Institute of Occupational Safety and Health (NIOSH, 2005) have not established
occupational exposure standards for neodymium. A toxicological review of the lanthanides is
identified that derived toxicity values for several lanthanides—but not for neodymium or its
compounds (TERA, 1999).
'The term "lanthanides" refers to 15 elements with atomic numbers 57 through 71: lanthanum, cerium,
praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium,
erbium, thulium, ytterbium, and lutetium. The term "rare earths" refers to the lanthanide series plus yttrium (atomic
number 39) and scandium (atomic number 21) (Kirk-Othmer, 1995).
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Literature searches were conducted from the 1960s through December 2007 for studies
relevant to the derivation of provisional toxicity values for neodymium. Databases searched
include MEDLINE, TOXLINE (Special), BIOSIS, TSCATS 1/TSCATS 2, CCRIS,
DART/ETIC, GENETOX, HSDB, RTECS, and Current Contents. Reviews of rare earth or
lanthanide toxicity (Haley, 1991; TERA, 1999; Wells and Wells, 2001) also have been consulted
for pertinent information, and the literature search was updated in July 2009.
REVIEW OF PERTINENT LITERATURE
Overview of Rare Earth Chemical Properties
Environmental and occupational exposure to neodymium occurs along with exposure to
other lanthanide and rare earth compounds, including some radioactive isotopes. The lanthanide
series of elements, and the rare earths yttrium and scandium, differ little with regard to chemical
properties (Kirk-Othmer, 1995), and they are difficult to physically separate from one another.
Kirk-Othmer (1995) and Wells and Wells (2001) have reviewed the physical-chemical properties
of the lanthanides. These reviews indicate that elements in this series are highly reactive, have
high melting points, ignite in air, and are active reducing agents. Many of the properties of these
compounds are associated with a phenomenon known as lanthanide contraction, wherein the
radius of ions in the series decreases with atomic number due to the configuration of the outer
electron shell. This results from an increasing positive charge on the nucleus with increasing
atomic number. Solubility also increases with increasing atomic number. Wells and
Wells (2001), in general, contend that toxicity is inversely related to atomic number and
solubility. The rare earth elements are broadly grouped into "light" (La, Ce, Pr, Nd, Sm, Eu, and
Gd) and "heavy" (Y, Tb, Dy, Ho, Er, Tm, Yb, and Lu) classes (Wells and Wells, 2001);
neodymium belongs to the light lanthanide group. For any given lanthanide, soluble forms
include chlorides, nitrates, and sulfates, while insoluble forms include carbonates, phosphates,
and hydroxides. The larger, lighter (smaller atomic number), and less soluble ions have been
observed to deposit primarily in the liver, while the smaller, heavier (larger atomic number), and
more soluble ions are similar in ionic radius to divalent calcium and distribute primarily to bone
(Wells and Wells, 2001). Due to an isoelectric point at a pH <7, lanthanides precipitate readily
at physiological pH.
Human Studies
Human studies have indicated an association between occupational exposure to rare
earths and the occurrence of pneumoconiosis and progressive pulmonary fibrosis
(Wells and Wells, 2001; Palmer et al., 1987). Because distinguishing individual lanthanides is
analytically challenging, it is has been difficult to discern the effects of the individual
lanthanides—both in human cases and animal studies. In addition, the co-occurrence of
2	3
radioactive lanthanides , thorium isotopes , and silica dust has complicated the interpretation of
toxicity—especially with regard to human exposures (Palmer et al., 1987).
2Lanthanide and rare earth isotopes occur as a result of radioactive decay and by nuclear reactions involving neutron
bombardment (Kirk-Othmer, 1995). The primary decay modes for the radioactive isotopes of the rare earths involve
(3 (including electron capture), y, and X-ray emissions. 149Terbium and 151terbium also have a-decay modes with
half-lives ranging from 4 to 18 hours (ICRP, 1983).
3Primary decay mode involves a-emissions.
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Human Exposure to Neodymium and Compounds
The anticoagulant properties of the rare earth metals were studied in the early years of the
twentieth century; investigators were interested in using rare earth metals to treat phlebitis.
These studies involved in vitro measurements of clotting time and in vivo studies using
intravenous administration of various rare earth metal salts in dogs, rabbits, and human
volunteers. None of these studies used oral or inhalation exposure and, as such, do not support
derivation of a subchronic or chronic p-RfD or p-RfC. Studies conducted by Beaser et al. (1942)
are representative of this genre. Beaser et al. (1942) injected human volunteers intravenously
(various experiments and protocols; injections were either administered one time or were
repeated with inconsistently varied doses for up to 17 daily injections) with salts of neodymium
including neodymium nitrate, neodymium lactate and neodymium acetate, at doses ranging from
3-18 mg salt/kg body weight, and measured blood clotting time thereafter for up to several
weeks. The precise protocol varied with each patient due to the exploratory nature of the study,
and the reporting of the methods and results was not always explicit. All salts increased clotting
time (normally about 15 minutes) 2-4 times above normal, peaking at about 1 hour after
injection. Beaser et al. (1942) considered the minimum effective dose to be 5-8 mg/kg body
weight and noted the peak increase to occur within 1 hour of exposure, then to decline.
Beaser et al. (1942) noted that successive injections of small doses could prevent the decline in
clotting time and that doses >14 mg salt/kg body weight (specific salts not specified other than
previous note that nitrates, acetates and lactates were used) rendered the blood "uncoagulable."
Adverse side effects—including fever, chills, muscle aches, abdominal cramps, hemoglobinemia
and hemoglobinuria—were noted in the volunteers and, as such, further experimentation with
rare earth metals as an anticoagulant therapy was discontinued.
Human Exposure to Rare Earth Mixtures
Human toxicity data relevant to environmental exposures to neodymium were limited to
case reports of pneumoconiosis and progressive pulmonary fibrosis in workers exposed to
mixtures of rare earth compounds, including lanthanum, cerium, neodymium, samarium,
praseodymium, terbium, yttrium, lutetium, and europium, in the air (Sulotto et al., 1986;
Kappenberger and Buhlmann, 1975; Husain et al., 1980; Sabbioni et al., 1982; Vocaturo et al.,
1983; Colombo et al., 1983; Vogt et al., 1986; Waring and Watling, 1990; and Deng et al.,
1991). In these case reports, rare earth pneumoconiosis has been characterized by pulmonary
interstitial infiltrates, peribronchial and perivascular lesions and, in some cases, impaired
pulmonary function, dyspnea, cyanosis, and pulmonary fibrosis (Palmer et al., 1987; Wells and
Wells, 2001). The workers in these reports were exposed to fumes generated by carbon-arc
lamps used in movie projection, flood-lighting, printing, photo-engraving, lithography, and
electrowelding (Palmer et al., 1987).
The case reports generally detailed the pulmonary findings of individuals, so there is no
information on population exposures or health effects. Haley (1991) reviewed the case studies
and concluded that the studies were limited by inadequate documentation of work histories and
worker health. None of the case reports provided any quantitative measures of exposure (e.g.,
concentrations of airborne particulates or individual rare earth elements in the areas of exposure).
In addition, the components of rare earth mixtures to which workers were exposed were not
consistent, nor were the medical histories or details of diagnosis and medical follow-up.
Interpretation of the human cases are also confounded by possible exposures to silica dust,
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radioactive rare earths4 and a-emitting contaminants, such as thorium5, that were present in the
occupational setting and have been associated with pneumoconiosis (Palmer et al., 1987).
Haley (1991) proposed that the pneumoconiosis or fibrosis could have resulted from either an
inflammatory response to the dust itself, or irradiation of tissues. However, Haley (1991)
indicated that there was little evidence for a significant contribution from radioactive
contaminants. Palmer et al. (1987) concluded that inhalation exposure to high concentrations of
stable rare earths could produce lesions consistent with pneumoconiosis and progressive
pulmonary fibrosis, and that the potential for inducing these lesions was related to chemical type,
physiochemical form, airborne concentration, and exposure duration.
Although there is evidence for an association between human exposure to rare earth
elements and pneumoconiosis or fibrosis, the relative contribution of neodymium (or any other
individual element) to the development of pneumoconiosis has not been established.
Furthermore, the available human case studies do not contain dose-response information that
could be used to develop provisional toxicity values for any of the stable nonradioactive
lanthanides.
Animal Studies
Oral Exposure—Neodymium and Compounds
Only one repeated dose oral study of neodymium alone (without other rare earth
compounds) has been identified in the literature search. Groups of six male and six female CRW
rats were fed 0, 0.01, 0.1, or 1% dietary neodymium chloride (purity not reported) for 90 days
(Haley et al., 1964). Compound intake is estimated to be 8.4, 84, or 840 mg NdCh/kg-day (4.8,
48, or 483 mg Nd/kg-day) in the males and 9.5, 95, or 950 mg NdC^/kg-day (5.5, 55, or 547 mg
Nd/kg-day) in the females. These doses6 have been calculated using the average body weights of
310 g for males and 210 g for females (data estimated from growth curves) and default food
consumption rates for rats of 0.026 kg/day for males and 0.020 kg/day for females (U.S. EPA,
1988). Body weight and hematology (total erythrocytes, total leucocytes, differential cell count,
platelets, hemoglobin, and hematocrit) were measured biweekly, and histological examinations
(heart, lung, liver, kidney, pancreas, spleen, adrenal, and small intestine) were performed at the
end of the study. No exposure-related histopathological or other changes were observed in either
gender, yielding a freestanding NOAEL of 840 mg NdC^/kg-day in males and 950 mg
NdCh/kg-day in females.
Oral Exposure—Rare Earth Mixtures
Due to their limited gastrointestinal absorption, Hutcheson et al. (1975) hypothesized that
heavy metal oxides could be used as markers in order to measure nutrient intake and utilization
in studies with animals or humans. To determine whether these chemicals could be used safely
for this purpose, Hutcheson et al. (1975) investigated the toxicity of a mixture of lanthanides,
including oxides of lanthanum, samarium, europium, terbium, dysprosium, thulium, and
ytterbium, and other metals, including scandium oxide, chromium oxide, and barium sulfate, in a
3-generation dietary study with CF-1 mice. Groups of 16 female and 8 male weanlings of each
generation were continuously fed diets containing these metals at 0, 1, 10, 100, or 1000 times (X)
4Having primarily (3, y, and X-ray decay modes.
5Thorium 229 has an alpha-decay mode with a half-life of 7340 years; Thorium 226 has an alpha-decay mode with a
half-life of 31 minutes (ICRP, 1983).
6Dose in mg/kg-day = dietary concentration in mg/kg diet x food consumption rate in kg diet/day ^ body weight in
kg, where food consumption rate = 0.026 kg/day for males and 0.020 kg/day for females.
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the amounts proposed for use as markers of dietary intake and utilization. The proposed dietary
marker amount (X) for each chemical was one-fifth of the concentration necessary for estimation
n
by neutron-activation analysis with an error of 5%. Table 1 shows concentrations measured in
basal (control) diets and test diets. The 1000X diet was not analyzed for metal content;
Hutcheson et al. (1975) reported the metal concentrations in the 1000X diets as 10 times that of
the measured concentrations in the 100X diet.
Table 1. Measured Concentrations of Rare Earth
Elements in Control and Test Dietsa
Elementb
Concentration of Element in Diets (mg/kg diet)
Control
1XC
10X
100X
1000Xd
Europium (Eu)
0.04 ± 0.02e
0.08 ±0.02
0.32 ±0.02
2.10 ±0.02
21.0
Samarium (Sm)
0.33 ±0.02
1.64 ±0.13
11.11 ± 1.71
108.00 ±2.00
1080.0
Lanthanum (La)
0.69 ±0.02
1.16 ±0.22
6.08 ± 1.02
62.50 ± 1.20
625.0
Dysprosium (Dy)
0.25 ±0.02
1.44 ±0.07
11.38 ±0.74
102.50 ±2.50
1025.0
Ytterbium (Yb)
0.05 ±0.02
0.19 ±0.02
1.12 ±0.08
12.00 ±0.30
120.0
Scandium (Sc)
0.12 ±0.01
0.22 ±0.01
1.58 ±0.08
13.30 ±0.50
133.0
Terbium (Tb)
0.02 ±0.01
0.80 ±0.06
11.02 ± 1.95
79.95 ±4.25
799.5
aHutcheson et al. (1975).
bConcentrations of Tm, Cr and Ba were not measured in control or test diets.
°1X refers to 1 times the amounts proposed for use as nutritional markers (nominal IX concentrations:
Eu = 0.036 ppm; Sm= 0.80 ppm; La = 0.40 ppm; Dy = 1.20 ppm; Yb = 0.12 ppm; Sc = 0.12 ppm;
Tb = 1.20 ppm; Tm = 0.08 ppm; Cr = 0.02 ppm; and Ba = 0.008 ppm).
Concentrations of elements in the 1000X were not measured. Study authors estimated concentrations as 10 times
higher than those in the 100X diet.
"Means ± SE of 5 samples.
Hutcheson et al. (1975) reported neither dose nor food intake during the study.
Therefore, daily doses of rare earths have been calculated for this review using the average body
weight of mice prior to mating, reported by Hutcheson et al. (1975) as 0.029 kg, and food
consumption estimates, based on the U.S. EPA (1988) allometric equation relating food
consumption (kg food/day) to body weight (kg) for laboratory mammals. Table 2 presents the
estimated doses. Study endpoints included mortality, clinical signs, body weight (all adults prior
to mating and dams at weaning), morphological development, reproductive outcome (number of
females having litters and average litter size), neonatal growth during lactation (pup weaning
weight), and pup growth after lactation (pup body-weight gain from 3 to 6 weeks of age). At
3 months of age in each generation, Hutcheson et al. (1975) collected blood from 5 mice/group
in the control and 100X groups and analyzed it for hematology, including red and white blood
cell counts, red blood cell size, hemoglobin concentration and hematocrit, and serum proteins
and globulins. Gross pathological examinations were performed on 5 mice per group of third
generation adult mice receiving control and 100X diets, but no histopathological examinations
were performed on any animals in the study (Hutcheson et al., 1975).
'Neutron bombardment creates traceable radioactive forms of the various compounds after the experiment is
terminated.
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Table 2. Estimated Doses for Mice Fed Rare Earth Elements in the Dieta
Element0
Dose (mg/kg-day)b
Control
IX
10X
100X
1000X
Europium (Eu)
0.007
0.014
0.058
0.380
3.8
Samarium (Sm)
0.06
0.29
2.0
19.6
195.5
Lanthanum (La)
0.125
0.210
1.101
11.32
113.1
Dysprosium (Dy)
0.045
0.261
2.060
18.56
185.6
Ytterbium (Yb)
0.009
0.034
0.203
2.17
21.7
Scandium (Sc)
0.022
0.040
0.286
2.41
24.1
Terbium (Tb)
0.004
0.145
1.995
14.47
144.7
Total Lanthanides
0.27
0.99
7.7
69
690
aHutcheson et al. (1975).
bDose (mg/kg-day) = Concentration in food (mg/kg food) x 0.00525 kg food/day ^ 0.029 kg bw.
Concentrations in food are from Table 1.
Hutcheson et al. (1975) reported the overall incidence of morbidity and mortality as
<0.5%; data on mortality or clinical signs of toxicity were not reported for individual test groups
or generations of mice. Differences in body weights of treated mice from matched controls were
not statistically significant for all generations prior to mating and dams prior to weaning.
Compared to matched controls, no treatment-related effects on pup body weight at the end of
weaning were observed in any generations. Table 3 summarizes pup body-weight gains during
Weeks 3 to 6 for each generation. In the first generation, body-weight gains were significantly
decreased in the IX, 10X, and 100X groups compared to controls, but they were similar to
controls in the 1000X group. In the second generation, body-weight gains were significantly
increased in the IX group and significantly decreased in the 100X and 1000X groups compared
to controls, but they were similar to controls in the 10X group. In the third generation,
body-weight gains were significantly decreased compared to controls in the 100X group and
were similar to controls in the IX, 10X, and 1000X groups. Hutcheson et al. (1975) concluded
that the observed body-weight-gain patterns were not consistently associated with dietary
concentrations of the mixture, and a correlation analysis performed for this report confirmed this
conclusion.
Hutcheson et al. (1975) observed no effects on hematology or clinical chemistry
parameters in the 100X group, but did not examine other treated groups for these endpoints. No
effects on reproductive parameters or morphological development were observed. Necropsy
performed on third generation control and 100X mice revealed no abnormal findings.
Hutcheson et al. (1975) observed no effects on body-weight gain or survival in the 1000X group;
however, clinical chemistry, hematology, and necropsies were not conducted for this treatment
group. As such, the highest dose group cannot be designated as a NOAEL. The 100X treatment
(69 mg/kg-day of the rare earth mixture) might be considered a freestanding NOAEL based on
the parameters assessed. Reproductive effects observed in studies of some rare earths, including
decreased pregnancy success, decreased litter size, and decreased neonatal weight (Wells and
Wells, 2001) were not observed in this study. However, Hutcheson et al. (1975) did not evaluate
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blood coagulation, which is known to be affected by exposure to rare earths (Wells and Wells,
2001). This study is not useful for assessing neodymium toxicity, as neodymium was not one of
the rare earth elements included in the mixture.
Table 3. Average Daily Weight Gain in CF-1 Mouse Pups Fed a Rare Earth Mixture in
Diet from 3 Weeks to 6 Weeks of Agea
Generation
Weight Gain (g)
Control
IX
10X
100X
1000X
First
0.200 ± 0.009b
0.106 ±0.010c
0.108 ±0.012c
0.134 ±0.013c
0.230 ±0.014
Second
0.296 ±0.013
0.360 ±0.010c
0.328 ±0.017
0.207 ± 0.007°
0.211 ±0.009c
Third
0.258 ±0.012
0.286 ±0.017
0.250 ±0.011
0.133 ±0.006c
0.280 ±0.012
aHutcheson et al. (1975).
bMean±SE.
cSignificantly different matched control (p < 0.01).
Dependence of mean weight gain on dosage was tested using Pearson and Spearman (rank) correlation coefficients
as the test statistics. Weight gain was not significantly dependent on dose. Pearson: F, /? = 0.16; F2p = 0.25; F3p =
0.68; Spearman: Fip = 0.42; F2p = 0.23; F3p = 0.69.
Inhalation Exposure—Neodymium and Compounds
There were no inhalation studies of neodymium or its compounds alone (without other
rare earth compounds).
A study using intratracheal instillation of neodymium oxide (Mogilevskaya and Raikhlin,
1967) demonstrated the development of emphysema and limited development of fibrosis in rats.
An unspecified number of rats (strain, gender, age, weight not reported) were exposed to
neodymium oxide (as 50 mg dust suspended in 0.6% saline) by a single intratracheal instillation.
A group of eight unexposed rats served as controls. Rats were weighed monthly and killed 8
months after exposure. The heart, lungs, and livers were weighed and ratios of organ weight to
body weight were determined. Internal organs (not specified) were examined histologically.
Rats given the dust weighed 17% less than controls at the end of the study (262 ± 18.2 g vs.
317 ± 18.33 g for controls). Absolute organ weights were not presented; the ratios of
heart-to-body-weight and liver-to-body-weight were comparable between exposed and control
rats. The group mean ratio of lung-to-body weight appears to be elevated in exposed rats (1.27,
standard deviation, number of animals not reported) in comparison with controls (0.92, n = 8,
standard deviation not reported), and study authors reported the increase to be statistically
significant. Macroscopic evidence of emphysema was noted. Microscopic examination revealed
the formation of granulomata consisting of giant multinucleate cells containing dust particles,
lymphoid cells, fibroblasts, and histocytes. The granulomata varied in size and were found
around the pulmonary vessels and bronchi and in the interlobular connective tissue and alveolar
septa. Mogilevskaya and Raikhlin (1967) reported that there was very slight formation of
connective tissue fibers (short, thin collagen fibers within the cells in the granulomata) in
comparison with that seen (greater extent) following a similar experiment conducted with
yttrium oxide. There were no changes in pulmonary tissue beyond the areas of dust
accumulation, no neoplastic changes, and no histological changes in unspecified "other internal
organs." This study is of limited utility for toxicity assessment, as data collected after
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intratracheal instillation of neodymium are of uncertain relevance to environmental exposure
pathways (oral, inhalation).
Inhalation Exposure—Rare Earth Mixtures
Studies investigating the effects of respiratory exposure to rare earth mixtures included a
14-day intratracheal study and a 3-year inhalation (whole body) study in guinea pigs exposed to
mixtures containing several (insoluble) rare earth elements, including fluorides and oxides of
cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium,
holmium, erbium, germanium, thulium, ytterbium and lutetium (Schepers, 1955a,b;
Schepers et al., 1955). In the study involving intratracheal instillation, a blend (termed the
high-oxide blend) of carbon (31%), rare earth fluorides (39.6%), rare earth oxides (26.4%) and
potassium sulfate (3%) was ground, suspended in isotonic saline, and anodized. A 50-mg dose
of the high-oxide blend was administered twice (7 days between doses) to a group of 9 guinea
pigs. A second blend (termed the high-fluoride blend) containing carbon (17.0%) graphite
(3.0%>), rare earth fluorides (65.0%>), rare earth oxides (10.0%>), and potassium sulfate (5.0%>) was
prepared in a manner similar to the high oxide blend, and administered on the same schedule to a
second group of 9 guinea pigs. The high fluoride blend was also administered as an aerosol via
inhalation to a group of 75 guinea pigs 8 hours/day, 5V2 days/week, for 3 years.
Schepers (1955a,b) and Schepers et al. (1955) did not report the concentrations of neodymium or
other rare earth constituents in the exposure mixtures, nor did they report the concentration of the
mixture in the aerosol exposure chamber. Rather, they reported only that particle concentrations
were "high" in the early weeks but "leveled off to about 200,000 to 300,000 particles
(1-2 micron diameter) per cubic foot of air.
Following intratracheal instillation, mortality was observed in three guinea pigs receiving
the high-oxide blend (10-11 days postexposure) and in four guinea pigs receiving the
high-fluoride blend (12-29 days postexposure). Schepers et al. (1955) considered the deaths to
be treatment-related. Macroscopic evaluation of the lungs revealed changes consistent with
deposition of inert material (congestion and consolidation with large single or multiple
black-pigmented conglomerate lesions). Histologic evaluation (Schepers, 1955b) of survivors
exposed to the high-oxide dust for up to a year revealed focal aggregation of the dust (cellular
eosinophilia) but no chronic cellular reaction or fibrosis. Schepers et al. (1955a) noted similar
dust deposits in the animals exposed to the high-fluoride blend but these animals developed
transient chemical pneumonitis, subacute bronchitis, and bronchiolitis. As with the other blend,
Schepers (1955a) observed no fibrosis or granulomatosis.
Following long-term inhalation exposure to the high-fluoride blend of rare earths, the
histopathological changes observed in guinea pigs included focal hypertrophic emphysema,
regional bronchiolar structuring, and subacute chemical bronchitis. Schepers (1955a) noted that,
as with the intratracheal instillation studies, pigment was deposited and retained in foci. In
contrast to human occupational exposure cases, no fibrosis or granulomatosis was observed.
The results of this study do not corroborate conclusions drawn by Palmer et al. (1987)
that chronic occupational exposure to stable rare earth dusts results in progressive pulmonary
fibrosis in humans. However, the exposures in the animal and human studies were not strictly
comparable due to differences in exposure components, including the presence of silica dust,
radioactive rare earths, and thorium in the human exposures. Further, as noted by
Palmer et al. (1987), other factors that may explain the differences in human and animal findings
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include chemical type, physiochemical form, dose, and duration of exposure. In any case, the
relevance of studies by Schepers (1955a,b; Schepers et al., 1955) to neodymium toxicity is
uncertain due to the lack of information exposure concentrations and the neodymium content of
the mixtures.
Other Studies
Acute Exposure
Acute Lethality Studies—Acute oral lethality studies have been conducted for
neodymium chloride and neodymium nitrate (see Table 4). Haley et al. (1964) reported an oral
o
LD50 of 3024 mg Nd/kg for neodymium chloride (specific details regarding administration of
test substances were not reported) in male CF1 mice (neither age nor weight were reported).
Mice were observed for 7 days following dosing. Haley et al. (1964) reported clinical signs of
toxicity (including ataxia, writhing, labored respiration, walking on toes with arched back, and
sedation) following either oral exposure or intraperitoneal injection with neodymium chloride or
praseodymium chloride. No further details were provided, and no other information on the
potential neurotoxicity of neodymium or other rare earth metals was identified in the literature
search or reviews. Bruce et al. (1963) reported a lower oral LD50 of 905 mg Nd/kg for
neodymium nitrate, administered by stomach tube in 50% aqueous solution, in female
Sprague-Dawley rats (adults, 190-250 g) observed for 30 days following dosing.
Intraperitoneal acute lethality studies have been conducted for neodymium chloride,
nitrate, citrate, and edetate compounds (see Table 4), resulting in LD50s that often varied by
compound and species. For neodymium chloride, Graca et al. (1957) reported an i.p. LD50 of
81 mg Nd/kg in guinea pigs (300-500grams; age, gender and strain not reported) while
Haley et al. (1964) reported an i.p. LD50 of 346 mg Nd/kg in male CF1 mice. Graca et al. (1957,
1962) noted precipitate at the injection site of animals receiving intraperitoneal injections of
neodymium chloride, indicating that absorption was incomplete and noting that the inflammatory
response associated with the precipitate might complicate the interpretation of toxicity. For
neodymium nitrate, Bruce et al. (1963) reported identical i.p. LD50S in female Sprague-Dawley
rats and female CF1 mice (89 mg Nd/kg).
Graca et al. (1962) tested the acute i.p. lethality of neodymium in citrate and edetate
complexes in mice and guinea pigs. The test materials were described as "chloride-citrate" and
edetate complexes or chelates; however, the exact nature and molecular formulas or weights
were not given. The chelating agents were added to enhance the solubility of the chloride and
prevent injection-site precipitation. Graca et al. (1962) reported i.p. LD50S in units of mg
NdC^/kg rather than in terms of the compound tested or in equivalent dose of the rare earth
alone; it is not clear from the study if this was a reporting error, if the units were converted to
NdCb equivalents, or if all of the test materials were complexes of neodymium chloride. As a
consequence of this uncertainty, the LD50S reported by Graca et al. (1957, 1962) cannot be
considered reliable indicators of the acute i.p. toxicity of the citrate and edetate compounds.
Graca et al. (1957, 1962) reported i.p. LD50S for neodymium citrate ranging from 138.0 to
140.0 mg NdC^/kg in CFW albino mice (age and gender not reported) and from 40.5 to
52.86 mg NdCh/kg in guinea pigs (age, strain and gender not reported) while i.p. LD50S for
neodymium edetate were 126.24 mg NdC^/kg in CFW albino mice and 142.33 mg NdC^/kg in
8Based on an LD50 of 5250 mg NdCl3/kg: the ratio of Nd to CI on the basis of molecular weight is 0.576; 0.576 x
5250 mg NdCl3 = 3024 mg Nd/kg. Similar conversions are used to convert values for other salts, etc. to mg Nd/kg.
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guinea pigs (Graca et al, 1962). These LD50S should be interpreted cautiously, given the
uncertainties outlined above.
TABLE 4. ACUTE LETHALITY OF STABLE NEODYMIUM COMPOUNDS
FOLLOWING ORAL AND PARENTERAL EXPOSURE
COMPOUND
SPECIES/STRAIN
(GENDER)
ROUTE OF
EXPOSURE
LDS0
IN MG ND/KG BODY
WEIGHTa
REFERENCE
Neodymium chloride
Mice/CFl
(male)
oral
(not specified)
3024 (2724-3358)
Haley et al. (1964)

Mice/CFl
(male)
i.p.
346(324-369)
Haley et al. (1964)

Mice/CFW albino
(NR)
i.p.
201 (171—235)b
200b
Graca et al. (1957)
Graca et al. (1962)

Guinea pigs
(gender, strain: NR)
i.p.
81 (57-113)b
85b
Graca et al. (1957)
Graca et al. (1962)
Neodymium nitrate
Rats/Sprague Dawley
(female)
oral
(gavage, 50%
aqueous
solution)
905 (624-1312)
Bruce et al. (1963)

Mice/CFl
(female)
i.p.
89 (73-108)
Bruce et al. (1963)

Rats/Sprague Dawley
(female)
i.p.
89(76-104)
Bruce et al. (1963)

Rats/Sprague Dawley
(female)
i.v.
3.0 (2.3-4.0)
Bruce et al. (1963)

Rats/Sprague Dawley
(male)
i.v.
22 (18-28)
Bruce et al. (1963)
a(): 95% confidence limits, as reported by study authors.
bPrecipitate observed at injection site; inflammatory response associated with precipitate confounds interpretation of
toxicity associated with the chemical itself.
NR: not reported,
i.p.: intraperitoneal injection,
i.v.: intravenous injection.
Bruce et al. (1963) reported intravenous LD50s of 22 and 3.0 mg Nd/kg in male and
female Sprague-Dawley rats, respectively, for neodymium nitrate, indicating that female
Sprague-Dawley rats may be more sensitive than males. Parallel results (i.e., lower i.v. LD50S
for females than for males) for nitrates of neodymium, cerium, and praseodymium in the same
study support the gender difference. Bruce et al. (1963) also tested the hypothesis that the nitrate
ion might be the source of toxicity and found it was not: no effects were observed among
10 female rats within 30 days of i.p. injection of 181 mg/kg sodium nitrate.
Wells and Wells (2001) questioned the validity of intravenous acute lethality data for rare earth
compounds because mortality after exposure to intravenously-administered rare earths has
exhibited a bell-shaped dose-response curve that may be due to the formation of rare earth
colloids in the blood at high doses of the chloride or nitrate compounds.
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The acute lethality data are of limited utility for comparing the relative toxicity of
different neodymium compounds. As noted earlier, the available LD50s for edetate and citrate
forms of neodymium (Graca et al., 1957, 1962) cannot be considered reliable due to uncertainty
in the reported doses. The intravenous lethality data are also questionable due to presumed
formation of colloids in the blood after intravenous administration of high doses of the chlorides
and nitrates. Acute i.p. lethality data for neodymium chloride in mice and guinea pigs and
neodymium nitrate in mice and rats suggest that the acute i.p. toxicity of these neodymium
compounds is of comparable order of magnitude; LD50s ranged between 89 and 346 mg Nd/kg.
It should be noted that the one mouse i.p. LD50 for neodymium nitrate is for female mice
(Bruce et al., 1963), while the LD50s for neodymium chloride are for male mice (Haley et al.,
1964) or for mice of unspecified gender (Graca et al., 1957, 1962). Because gender differences
in the acute lethality of some rare earth compounds has been noted (Bruce et al., 1963;
Wells and Wells, 2001), comparisons between these LD50S is of limited utility for evaluating
relative toxicity of the different compounds. In addition, since precipitate was observed at the
injection site in one of the mouse acute lethality studies of neodymium chloride (Graca et al.,
1957, 1962), the absorption of neodymium chloride may have been affected by the formation of
insoluble hydroxides or protein complexes at the injection site.
The oral acute toxicity data for neodymium chloride and neodymium nitrate are not
comparable, primarily because the studies were conducted in different species, and the available
data do not rule out species differences in absorption or toxicity. Wells and Wells (2001)
reported that the nonmetallic components of rare earth compounds may strongly influence a
compound's acute toxicity. Greater oral toxicity of the neodymium nitrate might be inferred
from the properties of the nitrate anion, if hydrolysis of the nitrate anion in the stomach leads to
the formation of reactive nitrogen compounds such as nitric oxides, nitrous suboxides, and nitric
acid in the gastrointestinal tract. However, the behavior of neodymium nitrate in the gut has not
been studied, and available data do not support potential conclusions that the nitrate anion causes
the observed differences in relative oral toxicities of the nitrate and chloride forms of
neodymium.
Data on the acute oral or parenteral toxicity of insoluble neodymium compounds (e.g.,
oxides or hydroxides) have not been located. While an assessment of the behavior of these
compounds in the gastrointestinal milieu (e.g., dissociation in the stomach and/or small intestine)
might provide some insight into the oral absorption of these compounds, few conclusions
regarding their relative acute toxicity can be drawn in the absence of corresponding parenteral
toxicity data. As with the nitrate form, the potential for formation of reactive species in the gut
upon dissociation of the oxide or hydroxide forms provides a mechanistic basis for potentially
greater toxicity, but this has not been studied.
Other Acute Studies—Beaser et al. (1942) injected rabbits (gender, strain, age body
weight not reported) with neodymium nitrate at doses of 10, 20, 30, and 60 mg/kg body weight
and measured clotting time for 5 hours after injection9. No effect was observed at 10 mg salt/kg.
Clotting times were increased to >120 minutes at the higher doses approximately 1 hour after
injection. Clotting times dropped dramatically between the first and second hours of exposure,
and did not return to normal with the formation of a true clot for days after exposure.
9This experiment is one of many carried out by these investigators and simultaneously reported; neither the methods
nor the results are reported clearly.
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Beaser et al. (1942) reported that phlebitis was observed at the site of injection within 24 hours
of administration, and that edema and necrosis occurred subsequently.
Graca et al. (1964) investigated the effects of acute i.v. exposure to rare-earth element
compounds (chlorides, citrates and edetates) on heart rate, blood pressure, respiration, and
clinical hematology in anaesthetized male and female dogs (breed, number, and gender not
specified). Aqueous solutions of 15 rare earth elements, equivalent to 5% of the chloride, were
injected into a cannula inserted into the left femoral vein. There were 10 doses of 10 mg/kg each
(as the chloride or its equivalent in the chelates) that were injected at 10-minute intervals. For
each element, nine dogs were divided into groups of three, each treated with the chloride, citrate
or edentate; three groups of control dogs were injected with sodium citrate (n = 6), ammonium
versenate (n = 6) or Ringer's solution (n = 12) in the same manner as treated animals. Blood
samples were collected from the right femoral vein before treatment and 0, 10, 30, 60, 100, and
160 minutes after treatment for analysis of erythrocyte, leukocyte and differential cell counts,
prothrombin and coagulation time, hemoglobin, sedimentation and hematocrit. After
160 minutes, the animals were necropsied and liver, spleen, kidney, lung, sternum, mesentery
lymph nodes, heart, adrenal, and ovaries or testes tissues were collected for histopathology.
Heart rate, respiration, and blood pressure were measured at the same intervals as blood samples.
Graca et al. (1964) generally discussed results for the 15 elements and presented them
graphically as change over time after treatment. No statistical analysis for any endpoint was
provided in the report and insufficient details were provided to allow such analyses for this
report. Graca et al. (1964) reported that 14/45 dogs injected with chlorides, 4/45 injected with
citrates, and 1/45 injected with edetates died from treatment—but mortality was not separately
reported for each element. Graca et al. (1964) attributed the deaths to circulatory failure. In
general, the lanthanide chloride compounds as a group were more lethal than the citrate or
edetate compounds. Neodymium chloride produced a -15% decrease in blood pressure 1 hour
after treatment, with a -30% decrease at 100 minutes and -20% at 160 minutes after treatment.
Neodymium edetate had little effect on blood pressure, with a maximal decrease of 12% after
100 minutes and less than 5% by 160 minutes. The effect of neodymium citrate on blood
pressure was more rapid; blood pressure decreased by -12% at 10 minutes and by -30% at
30 minutes, then declined to 10-18%) between 100 and 160 minutes. Injection of neodymium
chloride produced decreases in heart rate that progressed over time by -5% at 10 minutes to
-20-25%) at >100 minutes. Graca et al. (1964) observed a similar pattern, with smaller
decreases in heart rate, for both the citrate and edetate compounds. Respiration rate was
increased at all time points for all neodymium compounds, with the most pronounced change
observed in animals treated with neodymium citrate (approximately 40 to 30% at the 100- and
160-minute observation times, respectively). Prothrombin times measured at the 30-160-minute
assessment points were markedly increased from approximately 5-10 seconds in controls to
>100 seconds for all three compounds at the 60-, 100-, and 160-minute measurement intervals.
Neodymium chloride and neodymium citrate also had prothrombin times >100 seconds at the 30-
minute timepoint. Only neodymium chloride had a markedly increased prothrombin time (55
seconds) at the 10-minute timepoint. With respect to coagulation times, neodymium edetate had
little effect over the 160 minutes of testing. Compared to controls (coagulation times of
approximately 10 minutes), coagulation times were increased to >60 minutes for neodymium
chloride and neodymium citrate at all time points from 30 minutes onward (30, 60, 100,
160 minutes). Graca et al. (1964) observed effects on clotting time for neodymium edetate only
at the 160-minute observation point (-18 minutes). The observed effects on clotting variables
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for neodymium chloride were consistent with the effects observed for other lanthanides tested in
the study—both in terms of the timing of effects and the relative toxicity of the three compounds
tested. Gross and histopathological examinations revealed slight-to-moderate hyperemia of the
lungs (data not reported) only in animals treated with chlorides of the rare-earth elements.
The testicular calcium concentration was increased more than 2-fold higher than that of
controls in ddY mice (body weight = 25-30 grams) given a single i.v. injection of neodymium
chloride (either 20 or 200 [jmoles neodymium chloride/kg; equivalent to 5 and 50 mg
neodymium chloride/kg, respectively10) and assessed 5 days later (Nagano et al., 2000). No
effects on testicular weight or lipid peroxidation were reported. The relevance of the observed
increase in testicular calcium to toxicity is unknown.
Kostova and colleagues (2008, 2005, 2004) have demonstrated that certain complexes of
neodymium and other rare earth metals exhibit antineoplastic, antiproliferative, and other
cytotoxic activity against tumor cells, in vitro. However, in vivo data were not available to
develop dose-response relationships. In addition, these complexes were specially prepared for
experimental medicinal testing and are unlikely to appear as site contaminants.
Toxicokinetics
Based on the available data for other light lanthanides, neodymium is likely to be
absorbed poorly from the gastrointestinal tract, deposited primarily in the liver and secondarily to
bone, and excreted primarily in the feces. The limited oral acute lethality data suggest that
gastrointestinal absorption of neodymium and other rare earths is low. Comparison between
available i.p. and oral LD50S shows that the oral LD50S exceed the corresponding i.p. LD50S,
which probably is due to the limited absorption of the ingested compounds. Wells and Wells
(2001) noted that in general, oral LD50S for rare earth elements are about 10-fold higher than
corresponding i.p. LD50s, and Bruce et al. (1963) found i.v. administration also to be an order of
magnitude more toxic than oral administration. Toxicokinetic information on neodymium and
compounds, and rare earths in general, are discussed in the sections below.
Toxicokinetics of Neodymium and Compounds—Studies evaluating the toxicokinetics
of oral or inhaled neodymium in humans or animals have not been identified. Durbin et al.
147
(1956) investigated the distribution and elimination of Nd in groups of five female
Sprague-Dawley rats following intramuscular injection of 2.3-4.6 |iCi of 147Nd-labeled
neodymium oxide (dose not reported; in 1.1-3.7 jag of a carrier11). Distribution and elimination
of radioisotopes of 14 other lanthanide elements also investigated in the same study. Urine and
147
feces were collected for 4 days after administration; selected tissues were analyzed for Nd
147
upon sacrifice 4 days after dosing. Approximately 30% and 40% of the administered Nd was
distributed to the bone and liver, respectively, and approximately 18% was excreted in urine and
feces after 4 days (data presented graphically); the distribution of the remaining 12% of the
administered dose was presumed by the study authors to be in the remaining animal tissues. The
initial distribution of neodymium was similar to that observed for other light lanthanide elements
147
(Durbin et al., 1956). Although long-term skeletal retention of Nd was not evaluated in the
study, skeletal retention curves for other light lanthanide elements (147Pm and 144Ce) showed two
10e.g., 250.599 g/mole x 20 (imole x 1 x 10"6 molc/|imolc = 0.005 g/mole or 5 mg/mole.
1110 mg of NaCL was added to the radioactive oxide originally dissolved in 6N HC1, then dried. Sodium citrate was
then added and the pH was adjusted to neutral (presumably pH = 7 at 25°C) with 9N NaOH.
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components, a labile component and a fixed component (Durbin et al., 1956). The labile
component represented approximately 33% of the initial skeletal burden, with an elimination
half-life of approximately 15 days; the fixed component represented approximately 66% of the
initial skeletal burden, with no apparent decrease in bone burden up to 256 days after
administration. This corresponded to an elimination half-time exceeding 5 years. Data
regarding the long-term effects of stored stable neodymium were unavailable. However, it
should be noted that such long-term deposition of radioactive neodymium so close to the
bone-marrow—and its stem cells for RBCs and all white cell lines—could have serious health
consequences.
Toxicokinetics of Rare Earths—Several reports have concluded that the toxicokinetics
of light lanthanides (lanthanum, cerium, praseodymium, neodymium, promethium, and
samarium) are similar (Haley,1965; ICRP, 1981; Hirano and Suzuki, 1996; Mode, 1990; Wells
and Wells, 2001); therefore, the toxicokinetic characteristics of other light lanthanide elements
may apply to neodymium.
The oral absorption of several lanthanide compounds, including samarium, lanthanum,
terbium, ytterbium, and europium in humans was investigated in studies on their use as
nonabsorbable fecal markers. Ulusoy and Whitley (2000) reported oral absorption of lanthanide
oxides to range from 5.5 ± 4.5% (mean ± SD) for terbium to 6.5 ± 3.9% for ytterbium.
Fairweather-Tait (1997) reported detecting no absorption of samarium chloride, with recovery of
samarium in the feces exceeding 100% of the administered dose. These results indicate that
lanthanide oxides and chlorides probably are poorly absorbed from the gastrointestinal tract.
Durbin et al. (1956) estimated that experimental animal absorption of chlorides and
oxides of 144Ce, 152'154Eu, 160Tb, and ™Tm following oral exposure was <0.1% of the
administered dose; oral absorption of neodymium chlorides and oxides seem likely to be in the
same range. Absorption of lanthanides following oral exposure is likely to vary with chemical
form (e.g., soluble versus insoluble) and may be markedly enhanced by the presence of oxidizing
agents, such as ferric iron or under fasting conditions (Sullivan et al., 1986; Hirano and Suzuki,
1996). Neodymium chloride (NdCh) is a relatively strong Lewis acid that forms insoluble
hydroxides at neutral or alkaline pH; these reactions may limit the bioavailability of ingested
neodymium chloride relative to more water soluble neodymium salts such as neodymium nitrate.
Following intramuscular injection, absorption of lanthanides from the injection site was
substantially complete (<6.5% not absorbed) within 4 days (Wells and Wells, 2001).
In an unpublished study aimed at developing a model for assessing lung deposition of
promethium from analysis of excreta, Shipler et al. (1975) evaluated the toxicokinetics of
inhalation exposure in 36 rats and 5 dogs exposed to a mixture of samarium oxide (145Sm203)
and promethium oxide (143Pm203). Samarium was added to determine its usefulness as a carrier.
Exposures were 30 minutes (nose only) for rats (strain and gender not reported) and 5 to
10 minutes (whole body) for dogs (breed and gender not reported). The concentrations of
samarium and promethium in the aerosol were not reported. The ratio of145 Sm to 143Pm in the
suspension used to generate the aerosol was about 3:1, and the total concentration of
radioactivity in the aerosol was 0.0216 j_iCi/L for rats and ranged from 0.771 to 7.20 j_iCi/L for
dogs. The mass median aerodynamic diameter (MMAD) of the aerosol was 3.4 |im for the study
in rats and 2.3 |im for the study in dogs.
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Shipler et al. (1975) sacrificed 12 of the 36 rats immediately after exposure for estimation
of the lung burden of each element; remaining rats were sacrificed 14 and 30 days after exposure
(12 rats at each sacrifice). Radioactivity in the lungs of dogs was measured 5 times during the
30-day postexposure period; dogs were sacrificed at the end of the 30-day period. Shipler et al.
(1975) collected urine and feces from all animals throughout the 30-day postexposure period.
Upon sacrifice, the following organs were analyzed for 145 Sm and 143Pm: lungs, blood, liver,
kidney, gastrointestinal tract, gonads, hepatic lymph nodes, tracheobronchial lymph nodes,
heads, pelts, skeleton, and muscle. Among rats, data for 145 Sm in skeleton, kidney, and muscle
were reported only for the 14-day postexposure assessment. Shipler et al. (1975) estimated the
initial lung burden in rats immediately following exposure to be 1.05 |ig Sm203; initial lung
burden in dogs was estimated to range from 0.106 to 1.65 |ig Sn^Cb.
Shipler et al. (1975) reported that samples containing high concentrations of calcium and
sodium salts might have considerable error in radioactivity counts. The distribution of both
145 Sm and 143Pm in rats and dogs were very similar; representative results for 145Sm are reported
here. In rats sacrificed after 14 days, the skeleton, muscle, and kidneys were reported to contain
3.1%, 2.2%, and 0.21% (respectively) of the initial 145Sm lung burden. In rat lungs, 145Sm
content was 62% and 40% of the initial lung burden at 14 and 30 days postexposure,
respectively. In rat livers, 145Sm content was 2.9% and 4.0%> of the initial lung burden on
Postexposure Days 14 and 30, respectively. 145Samarium was eliminated in feces and urine, with
the highest amounts eliminated during the first two days following exposure. Shipler et al.
(1975) reported fecal excretion during the first 2 days of exposure to be more than 3000% of the
initial lung burden. That the fecal excretion of radioactivity far exceeded the calculated lung
burden suggests that most of the aerosol was initially deposited to the nasopharynx and upper
bronchial regions and cleared to the gastrointestinal tract, while much less was deposited in the
pulmonary region. Urinary excretion during the first 2 days after exposure was 26.4% of the
initial lung burden. Plots of both urinary and fecal excretion of radiation reveal a rapid initial
phase over the first few days after exposure, with a slower second phase 10-30 days
postexposure. Shipler et al. (1975) hypothesized that the results indicated two phases of
clearance, the first associated with clearance of material via the gastrointestinal tract to the feces,
and the second associated with clearance from more distal areas of the lung.
Shipler et al. (1975) sacrificed all dogs 30 days after exposure; the initial lung burden
immediately following exposure was not determined. At the end of the 30-day postexposure
period, 145Sm was measured in several organs, including lungs, liver, kidneys, gastrointestinal
tract, spleen, and skeleton; the content varied by individual dog but indicated the greatest
distributions were to the liver and skeleton. Fecal excretion of 145Sm 2 days after exposure
ranged from 64% to 567% of the estimated initial lung burden, indicating substantial deposition
in, or mechanical clearance to, the gastrointestinal tract. Shipler et al. (1975) reported urinary
excretion data for only 1 dog, estimating that 0.3% of the initial lung burden was eliminated in
the urine on Day 2; other time-points were not reported.
The results of these studies in rats and dogs (Shipler et al., 1975) indicate that aerosolized
Sm203 and 143Pm203 were absorbed following inhalation exposure; however, due to substantial
deposition of the material to the gastrointestinal tract, the relative contributions of pulmonary and
gastrointestinal absorption to the overall absorption following inhalation exposure could not be
determined.
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As reviewed by Wells and Wells (2001), heavy lanthanides distribute primarily to the
skeleton while the lighter lanthanides distributed primarily to the liver (45% and 65% of the
administered dose for samarium and lanthanum, respectively). The skeleton is a secondary site
of deposition for the light lanthanides. Excretion of the lanthanides occurs through the urine and
feces in proportions that are dependent upon position of each element in the series. Light
lanthanides, such as neodymium, are excreted primarily in the feces; heavy lanthanides are
excreted primarily in the urine, and the midseries elements are excreted approximately equally.
Based on the available toxicokinetic data from animals and humans,
Taylor and Leggett (2003) published a biokinetic model to predict the disposition of lanthanide
elements in humans. The model consists of compartments for soft tissue (including
subcompartments for slow, intermediate, and rapid turnover), skeleton (six subcompartments for
cortical and trabecular volume, surface, and marrow), kidneys, urinary bladder, urine, blood,
liver (three subcompartments), gastrointestinal tract, gonads, and feces. Based on the available
information, Taylor and Leggett (2003) concluded that elements within the lanthanide series
could be divided into five groups, based on neighboring elements having similar properties, and
derived set-specific parameters for each group on the basis of existing data for rats, humans, and
dogs. In their model, neodymium, promethium, and samarium were treated as a similar group
with common parameters.
Taylor and Leggett (2003) compared predictions from their generic model with existing
human data and existing International Commission on Radiological Protection (ICRP) models
for radioactive promethium and gadolinium. Good agreement between the generic model and
the ICRP models for radioactive promethium and gadolinium was observed for whole-body
retention, urinary and fecal excretion, and absorbed doses to the bone surfaces, bone marrow,
and liver. However, the doses predicted for kidney and testes were three orders of magnitude
higher than those estimated by existing ICRP models. In summary, Taylor and Leggett (2003)
concluded that their model appeared to be adequate for use in general radiological protection,
and could be applied with appropriate caution for the interpretation of data from bioassays.
Genotoxicity
There is limited evidence that stable nonradioactive neodymium has genotoxic activity.
Nonradioactive neodymium oxide induced a dose-related increase in the frequency of
chromosomal aberrations in bone marrow cells of Swiss mice that were treated with single
intraperitoneal doses of 5.30-43.00 mg/lOOg, equivalent to 4.54-36.87 mg Nd/kg
(Jha and Singh, 1995). The maximum number of chromosomal aberrations per cell relative to
negative controls (approximately 7 times higher) was observed in cells harvested 6 hours
postexposure.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfDs FOR NEODYMIUM CHLORIDE
Data on the oral toxicity of subchronic or chronic exposure of humans to stable
neodymium compounds have not been identified. Three animal studies were identified that have
the potential to inform derivation of provisional subchronic RfDs for neodymium compounds.
However, only one of the studies (Haley et al., 1964) provides sufficient information to be
considered quantitatively for the derivation. Hutcheson et al. (1975) provides quantitative
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data —but only for mixtures of lanthanides. Bruce et al. (1963) provides information of the
relative toxicity of neodymium compounds. Information on the toxicity of repeated oral
exposure to neodymium in animals is limited to a single 90-day dietary study of neodymium
chloride in rats (Haley et al., 1964). No effects were observed on the parameters evaluated (body
weight, hematology and histopathology of selected tissues); thus, the highest dose tested
(840 mg NdC^/kg-day or 483 mg Nd/kg-day in males; 950 mg NdC^/kg-day or
547 mg Nd/kg-day in females) was identified as a 90-day NOAEL for neodymium chloride.
Developmental, reproductive, and chronic toxicity studies in animals were not identified. Use of
the NOAEL from Haley et al. (1964) is supported by the fact that, even acutely, neodymium
chloride does not seem to be unusually toxic by the oral route. Haley et al. (1964) also reported
an acute oral LD50 of 3014 mg Nd/kg for neodymium chloride in male mice.
Different chemical forms of neodymium may have different toxic potencies. However,
because only one repeated oral dose study on neodymium alone has been located, data with
which to compare the subchronic or chronic oral toxicity of different neodymium compounds are
not available. The only other data available on the oral toxicity of neodymium were acute oral
LD50s of 3014 mg Nd/kg for neodymium chloride in male mice (Haley et al., 1964) and
905 mg Nd/kg for neodymium nitrate in female rats (Bruce et al., 1963). Due to the limited
information available, it is not possible to determine whether the differences in acute lethality for
the chloride and nitrate compounds reflected differences in toxicokinetics of the neodymium
compounds, differences in sensitivity of the animal species tested (mice vs. rats), gender
differences, or other differences in experimental methods (see discussion under Acute Toxicity).
The limited available data do not provide assurance that a p-RfD based on data for
neodymium chloride would be adequate for other neodymium compounds. While this document
attempts to address the toxicity of the element neodymium, in light of the lack of information on
relative oral toxicity of different neodymium compounds, available data supports derivation of a
p-RfD only for the compound, neodymium chloride.
The subchronic oral toxicity study on neodymium chloride in rats conducted by
Haley et al. (1964) serves as the critical study for derivation of the subchronic p-RfD. The
NOAEL of 840 mg NdC^/kg-day or 483 mg Nd/kg-day in male rats is used to derive a
subchronic p-RfD for neodymium chloride as follows:
NdCl3 Subchronic p-RfD = NOAEL - UF
= 840 mg NdC^/kg-day ^ 1000
= 0.8 or 8 x 10"1 mg NdCb/kg-day
AND
NdCb Subchronic p-RfD as Nd = 483 mg Nd/kg-day ^ 1000
= 0.5 or 5 x 10" mg Nd/kg-day
The composite UF of 1000 is composed of the following:
• A default UF of 10 is applied for interspecies extrapolation to account for potential
pharmacokinetic and pharmacodynamic differences between rats and humans.
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•	A default UF of 10 is applied for intraspecies differences to account for potentially
susceptible individuals in the absence of information on the variability of response in
humans.
•	A full UF of 10 is applied for uncertainty in the database. The critical study used
only six animals per dose group. There are no supporting toxicity, reproductive, or
developmental studies on neodymium alone.
Given the uncertainty in relative potencies of neodymium compounds, this subchronic
p-RfD should be applied only to neodymium chloride.
Confidence in the principal study (Haley et al., 1964) is low. Although both genders
were tested in this study, small numbers of animals were used for each dose group (6/gender),
resulting in the possibility that responses of-10% or more likely would be missed. In addition,
the estimate of food intake was not linked to the growth data, resulting in the possibility that a
subtle effect of Nd on food intake could have been missed, leading to a biased estimate of dose.
The toxicological evaluation in this study is limited to body-weight measures, selected
hematological parameters, and histopathology of a subset of organs. Neither serum chemistry
nor urinalysis endpoints were evaluated, nor were organ weight measurements made. A LOAEL
was not identified. Confidence in the database on neodymium is low. Apart from the critical
study, the only other oral toxicity studies conducted on neodymium are acute lethality studies in
rats and mice. Reproduction and developmental toxicity studies on neodymium are not
available. A reproduction and developmental study on a mixture of lanthanide oxides
(Hutcheson et al., 1975) indicates that the mixture did not affect reproduction or development;
however, this study did not include neodymium in the mixture. Oral toxicokinetic data on
neodymium are lacking; however, based on data on the gastrointestinal absorption of other
lanthanide compounds, oral absorption of neodymium is expected to below. There are no data to
indicate the toxicological endpoint(s) or target organ(s) of subchronic or chronic oral exposure to
neodymium. Low confidence in the subchronic p-RfD follows.
A chronic p-RfD is not derived for neodymium. There are no studies of chronic exposure
to any neodymium compound in any species. The uncertainties about the subchronic point of
departure (POD) from the Haley et al. (1964) neodymium chloride feeding study preclude its
extrapolation to chronic exposures. Toxicokinetic studies of lanthanide elements indicate that
light lanthanides are deposited primarily in the liver and spleen, and, secondarily, in the skeleton.
In their review, Wells and Wells (2001) noted that rare earth chlorides in the liver and spleen are
not readily excreted. In addition, a portion of the skeletal burden of light lanthanides exhibits
extremely slow retention kinetics (e.g. half-time exceeding 5 years in rats; Durbin et al., 1956).
Although long-term skeletal retention of neodymium has not been evaluated, the potential for
prolonged retention of neodymium in the body increases the uncertainty in extrapolating from
subchronic data to estimate effects of chronic exposure. As a consequence of the uncertainty
regarding long-term retention in the body, no chronic p-RfD is derived for any neodymium
compound.
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FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfCs FOR NEODYMIUM
Studies investigating the effects of inhalation exposure of humans and animals are limited
to evaluations on mixtures of rare earth metals containing neodymium or studies involving acute
intratracheal instillation. Evidence for point-of-entry effects (pulmonary lesions) associated with
inhalation of mixtures of rare earth metals (Schepers, 1955a,b; Schepers et al., 1955) indicates
that route-to-route extrapolation from oral data would not be appropriate. The lack of data
precludes derivation of subchronic and chronic p-RfCs for neodymium.
PROVISIONAL CARCINOGENICITY ASSESSMENT FOR NEODYMIUM
Weight-of-Evidence Descriptor
Studies evaluating the carcinogenic potential of oral or inhalation exposure to stable
nonradioactive neodymium in humans or animals have not been identified in the available
literature. Evidence of clastogenic activity was obtained from a study in mice showing an
increase in the frequency of chromosomal aberrations in bone marrow cells of Swiss mice that
were treated with single intraperitoneal doses of neodymium oxide. Under the 2005 Guidelines
for Cancer Risk Assessment (U.S. EPA, 2005), there is "Inadequate Information to Assess [the]
Carcinogenic Potential" of neodymium.
Quantitative Estimates of Carcinogenic Risk
The lack of carcinogenicity data precludes quantitative estimates of cancer risk for stable
nonradioactive neodymium.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2008. 2008 Threshold
Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices.
Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2009. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html.
Beaser, S.B., A. Segal and L. Vandam. 1942. The anticoagulant effects in rabbits and man of
the intravenous injection of salts of the rare earths. J. Clin. Invest. 21:447-454.
Bruce, D.W, B.E. Hietbrink, and K.P. DuBois. 1963. The acute mammalian toxicity of rare
earth nitrates and oxides. Toxicol. Appl. Pharmacol. 5:750-759.
Colombo, F., M. Zanoni, G. Vocaturo et al. 1983. Pneumoconiosi da terre rare.
(Pneumoconiosis due to rare earth metals). Med. Lav. 74:191-197.
Deng, J.F., T. Sinks, L. Elliott et al. 1991. Characterization of respiratory health and exposures
at a sintered permanent magnet manufacturer. J. Ind. Med. 48:609-615.
20

-------
FINAL
9-17-2009
Durbin, P.W., M.H. Williams, M. Gee et al. 1956. Metabolism of the lanthanons in the rat.
Proc. Soc. Exp. Biol. Med. 91:78-85.
Fairweather-Tait, S.J., A.-M. Minihane, J. Eagles et al. 1997. Rare earth elements as
nonabsorbable fecal markers in studies of iron absorption. Am. J. Clin. Nutr. 65:970-976.
Graca, J.G., E.L. Garst, and W.E. Lowry. 1957. Comparative toxicity of stable rare earth
compounds. A.M.A. Arch. Ind. Health. 15:9-14.
Graca J.G., F.C. Davison, and J.B. Feavel. 1962. Comparative toxicity of stable rare earth
compounds. II. Effect of citrate and edetate complexing on acute toxicity in mice and guinea
pigs. Arch. Environ. Health. 5:437-450.
Graca J.G., F.C. Davison, and J.B. Feavel. 1964. Comparative toxicity of stable rare earth
compounds. III. Acute toxicity of intravenous injections of chlorides and chelates in dogs.
Arch. Environ. Health. 8:555-564.
Haley, P.J. 1991. Pulmonary toxicity of stable and radioactive lanthanides. Health Physics.
61:809-821.
Haley, T.J. 1965. Pharmacology and toxicology of the rare earth elements. J. Pharm. Sci.
54(5):663-670.
Haley, T.J., N. Komesu, M. Efros et al. 1964. Pharmacology and toxicology of neodymium and
neodymium chlorides. Toxicol. Appl. Pharmacol. 6:614-620.
Hirano, S. and K.T. Suzuki. 1996. Exposure, metabolism and toxicity of rare earths and related
compounds. Environ. Health Perspect. 104(Suppl 1):85—95.
Husain, M.H., J.A. Dick, and Y.S. Kaplan. 1980. Rare earth pneumoconiosis. J. Soc. Occup.
Med. 30:15-19.
Hutcheson, D.P., D.H. Gray, B. Venugopal et al. 1975. Studies of nutritional safety of some
heavy metals in mice. J. Nutr. 105:670-675.
IARC (International Agency for Research on Cancer). 2009. IARC Monographs on the
Evaluation of Carcinogenic Risks to Humans. Online. http://monographs.iarc.fr/ENG/
Monographs/allmonos90. php.
ICRP (International Commission on Radiological Protection). 1981. Metabolic data for:
Neodymium and samarium. Limits for intakes of radionuclides by workers. Pergamon Press:
New York, NY. ICRP Publication 30, Part 3:53-63.
ICRP (International Commission on Radiological Protection). 1983. Radionuclide
transformations: Energy and intensity of emissions. ICRP Publication 38. Report of a Task
Group of Committee 2 of the International Commission on Radiological Protection on data used
in ICRP Publication 30. Published for the International Commission on Radiological Protection
by the Pergamon Press. New York, NY.
21

-------
FINAL
9-17-2009
Jha, A.M and A.C. Singh. 1995. Clastogenicity of lanthanides: Induction of chromosomal
aberration in bone marrow cells of mice in vivo. Mutat. Res. 341:193-197.
Kappenberger, L. and A.A. Buhlmann. 1975. Lungenveranderungen durch "seltene erden."
(Lung lesions caused by "rare earths"). Schweiz. Med. Wochenschr. 105:1799-1801.
Kirk-Othmer. 1995. "Lanthanides" In: Kirk-Othmer Encyclopedia of Chemical Technology, 4th
Ed, Vol. 14: Imaging Technology to Lanthanides. John Wiley & Sons. New York, NY.
pp.1091-1115.
Kostova, I. 2005. Lanthanides as anticancer agents. Curr. Med. Chem. Anticancer Agents
5:591-602.
Kostova, I., I. Manolov, and P. Stancheva. 2004. Cytotoxic activity of new neodymium (III)
complexes of bis-coumarins. Eur. J. Med. Chem. 39:765-775.
Kostova, I., N. Trendafilova, and G. Momekov. 2008. Theoretical, spectral characterization and
antineoplastic activity of new lanthanide complexes. J. Trace Elem. Biol. 22:100-111.
Mode, V.A. 1990. Review of the literature on the toxicity of rare-earth metals as it pertains to
the engineering demonstration system surrogate test. Revision 1. Lawrence Livermore National
Laboratory, University of California, Livermore, CA.
Mogilevskaya, O. Y. and N.T. Raikhlin. 1967. Rare earth metals. In: Toxicology of the rare
earth metals, Izrael'son, Z.I. ed. Israel Program for Scientific Translations, Jerusalem,
p. 132-141.
Nagano, M., H. Shimada, T. Funakoshi et al. 2000. Increase in testicular calcium in mice
treated with rare earth metals. J. Health Science. 464(4):314-316.
NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to
Chemical Hazards. Online, http://www.cdc.gov/niosh/npg/npgsvn-a.html.
NTP (National Toxicology Program). 2005. 11th Report on Carcinogens. Online.
http://ntp.niehs.nih.gov/index.cfm?obi ectid=32BA9724-FlF6-975E-7FCE50709CB4C932.
NTP (National Toxicology Program). 2009. Management Status Report. Online.
http://ntp.niehs.nih.gov/index.cfm?objectid=78CC7E4C-FlF6-975E-72940974DE301C3F.
Palmer RJ, JL Butenhoff, JB Stevens. 1987. Cytotoxicity of the rare earth metals cerium,
lanthanum, and neodymium in vitro: comparisons with cadmium in a pulmonary macrophage
primary culture system. Environ Res. 43:142-156. Cited in Haley et al., 1991.
OSHA (Occupational Safety and Health Administration). 2009. OSHA Standard 1910.1000
Table Z-l. Part Z, Toxic and Hazardous Substances. Online, http://osha.gov/pls/oshaweb/
owadisp.show document?p table=STANDARDS&p id=9992.
22

-------
FINAL
9-17-2009
Sabbioni, E., R. Pietra, P. Gaglione et al. 1982. Long-term occupational risk of rare-earth
pneumoconiosis: A case report as investigated by neutron activation analysis. Sci. Total
Environ. 26:19-32.
Schepers, G.W.H. 1955a. The biological action of rare earths. II. The experimental pulmonary
histopathology produced by a blend having a relatively high fluoride content. A.M. A. Arch. Ind.
Health. 12:306-316.
Schepers, G.W.H. 1955b. The biological action of rare earths. I. The experimental pulmonary
histopathology produced by a blend having a relatively high oxide content. A.M. A. Arch. Ind.
Health. 12:301-305.
Schepers, G.W.H., A.B. Delahant and A.J. Redlin. 1955. An experimental study of the effects
of rare earths on animal lungs. A.M. A. Arch. Ind. Health. 12:297-300.
Shipler, D.B., J.E. Ballou, B.I. Griffin et al. 1975. Development of a diagnostic model for
147
inhaled promethium oxide—animal studies. Battelle, Pacific-Northwest Laboratory.
Richland, Washington. Document Number BNWL-SA-5464.
Sullivan, M.F., P.S. Ruemmlier, J.L. Ryan et al. 1986. Influence of oxidizing or reducing agents
on gastrointestinal absorption of U, Pm, Am, Cm and Pm by rats. Health Phys. 50(2):223-232.
Sulotto, F., C. Romano, A. Berra et al. 1986. Rare-earth pneumoconiosis: A new case. Am. J.
Ind. Med. 9:567-575.
Sulotto, F., C. Romano, A. Berra et al. 1986. Rare-earth pneumoconiosis: A new case. Am. J.
Ind. Med. 9:567-575.
Taylor, D.M. and R.W. Leggett. 2003. A generic biokinetic model for predicting the behaviour
of the lanthanide elements in the human body. Radiat. Prot. Dosim. 105(1-4): 193-198.
TERA (Toxicology Excellence for Risk Assessment). 1999. Development of Reference Doses
and Reference Concentrations for Lanthanides. Prepared for: U.S. Bureau of Land Management,
National Applied Resource Sciences Center. Online. http://www.tera.org/pubs/Lanthanides.pdf.
Ulusoy, U. and J.E. Whitley. 2000. Profiles of faecal output of rare earth elements and stable
isotopic tracers of iron and zinc after oral administration. Br. J. Nutr. 84:605-617.
U.S. EPA. 1988. Recommendations for and Documentation of Biological Values for Use in
Risk Assessment. Environmental Criteria and Assessment Office, Cincinnati, OH. NTIS
PB179874. Online, http: //cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=34855.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
23

-------
FINAL
9-17-2009
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared for
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2005. Guidelines for Cancer Risk Assessment. Risk Assessment Forum,
Washington, DC. EPA/630/P-03/001F. Online, http://cfpub.epa.gov/ncea/raf/
recordisplav.cfm?deid=l 16283.
U.S. EPA. 2006. 2006 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-06-013. Online, http://www.epa.gov/waterscience/
drinking/standards/dwstandards.pdf.
U.S. EPA. 2009. Integrated Risk Information System (IRIS). Online. Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://cfpub.epa. gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList.
Vocaturo, G., F. Colombo, M. Zanoni, F. Rodi, E. Sabbioni and R. Pietra. 1983. Human
exposure to heavy metals: Rare earth pneumoconiosis in occupational workers. Chest.
83:780-783.
Vogt, P., M.A. Spycher and J.R. Ruttner. 1986. Pneumokoniose durch "seltene erden"
(cer-pneumokoniose). [Pneumoconiosis caused by "rare earths" (cer-pneumoconiosis)].
Schweiz. Med. Wochenschr. 116:1303-1308.
Waring, P.M. and R.J. Watling. 1990. Rare earth deposits in a deceased movie projectionist: A
new case of rare earth pneumoconiosis. Med. J. Aust. 153:726-730.
Wells W.H. and V.L. Wells. 2001. The Lanthanides, Rare Earth Metals. In: Patty's Industrial
Hygiene and Toxicology, 5th Ed., Vol. 3. E. Bingham, B. Cohrssen and C.H. Powell, ed. John
Wiley and Sons, Inc., New York, NY. p. 423-458.
WHO (World Health Organization). 2009. Environmental Health Criteria Monographs. Online.
http://www.inchem.org/pages/ehc.html.
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