United States
Environmental Protection
1=1 m m Agency
EPA/690/R-07/020F
Final
5-30-2007
Provisional Peer Reviewed Toxicity Values for
Stable Lutetium
(CASRN 7439-94-3)
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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Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and
Liability Act of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
NAAQS	National Ambient Air Quality Standards
NOAEL	no-ob served-adverse-effect level
NOAEL(ADJ)	NOAEL adjusted to continuous exposure duration
NOAEL(HEC)	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
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p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
ppb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
l^g
microgram
[j,mol
micromoles
voc
volatile organic compound
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5-30-2007
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
STABLE LUTETIUM (CASRN 7439-94-3)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in 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 EPA's Integrated Risk Information System (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 EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all 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 five-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 manuscripts 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 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.
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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 manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other 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 EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
An assessment for stable, nonradioactive lutetium is not available on IRIS (U.S. EPA,
2007), the HEAST (U.S. EPA, 1997), or the Drinking Water Standards and Health Advisories
list (U.S. EPA, 2004). No relevant documents were located in the Chemical Assessment and
Related Activities (CARA) list (U.S. EPA, 1991, 1994). AT SDR (2006), NTP (2006), IARC
(2006) and WHO (2006) have not produced documents regarding lutetium. Comprehensive
literature searches were conducted in 1998 of the following databases: TOXLINE (1965-1998),
CANCERLINE (1970-1998), MEDLINE (1966-1998), GENETOX, DART, CCRIS, CHEMID,
RTECS, EMIC, ETICBACK and TSCATS for toxicity studies of lutetium. Update literature
searches were conducted from 1998 through June 2003 in: TOXLINE (supplemented with
BIOSIS and NTIS updates), CANCERLIT, MEDLINE, CCRIS, GENETOX, HSDB,
DART/ETICBACK, EMIC/EMICBACK, RTECS and TSCATS. An update literature search
covering 2003 through November 2005 was conducted in the following databases: MEDLINE,
TOXLINE SPECIAL, TOXCENTER BIOSIS, TSCATS, CCRIS, DART/ETIC, GENETOX,
HSDB, RTECS and CURRENT CONTENTS. Searches of Medline and Current Contents from
November 2005 to April 2006 were also conducted.
REVIEW OF PERTINENT DATA
Human Studies
No data regarding the toxicity of lutetium to humans following oral exposure were
located. Lutetium Texaphyrin (Lu-Tex) has been used in the treatment of age-related macular
degeneration. The reported effective dose range was 2 to 4 mg/kg-day of Lu-Tex (Pharmacyclic,
1999). The Texaphyrin moiety is a large porphyrin structure with a number of side chains and is
probably at least as important as lutetium, itself, for its biological action. Therefore, any dose-
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response information for the compound cannot be applied to the assessment of lutetium, alone.
Details of the responses encountered in clinical trials were not reported. In addition, even an
approximate molecular weight for Lu-Tex cannot be estimated, such that the dose range for
lutetium cannot be determined.
No data regarding the toxicity of lutetium to humans following inhalation exposure were
located. The pulmonary toxicity of inhaled rare earth compounds, in general, has been the
subject of debate, especially with regard to the relative contributions of radioactive contaminants
versus stable elements in the development of progressive pulmonary interstitial fibrosis (Haley,
1991; Beliles, 1994). In particular, although it is known that stable rare earths compounds can
produce a static, foreign-body-type lesion consistent with benign pneumoconiosis, there is
uncertainty whether they can also induce interstitial fibrosis that progresses after termination of
exposure. Human inhalation toxicity data on stable rare earth elements mainly consist of case
reports on workers exposed to multiple lanthanides (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; Deng et al., 1991).
No data regarding the carcinogenicity of stable lutetium in humans were located.
Animal Studies
Groups of six male and six female CRW rats were fed 0, 0.01, 0.1 or 1% lutetium
chloride (purity not reported) in the diet for 90 days (Haley et al., 1964). Food intake was not
reported. Compound intake, as lutetium chloride (trichloride), was estimated to have been 8.1,
81 or 810 mg/kg-day in males, and 9.5, 95 or 950 mg/kg-day in females, using body weight
(growth curve) data reported in the study and food consumption estimates based on allometric
scaling (U.S. EPA, 1988). Based on the weight-fraction of lutetium in lutetium chloride (0.622),
the corresponding lutetium intakes were calculated to be 5.0, 50 and 504 mg/kg-day for males
and 5.9, 59 or 590 mg/kg-day for females. Body weight and hematology (total erythrocytes,
total leukocytes, differential cell count, platelets, hemoglobin and hematocrit) were measured
biweekly, and gross and histological examinations (heart, lung, liver, kidney, pancreas, spleen,
adrenal and small intestine) were performed at the end of the study. No exposure-related
changes in these endpoints were observed in either sex. No adverse effects were identified in
this study, making the high dose of 504-590 mg Lu/kg-day a freestanding NOAEL.
Animal inhalation toxicity data on stable rare earths mainly consist of a few inhalation or
intratracheal studies on some rare earth mixtures and some single compounds (Schepers, 1955a,
1955b; Schepers et al., 1955; Ball and Van Gelder, 1966; Abel and Talbot, 1967; Mogilevskaya
and Raikhlin, 1967). No lutetium-specific data were found, however. A comprehensive
assessment of the human and animal data by Haley (1991) concluded that the evidence suggests
that inhalation exposure to high concentrations of stable rare earths can produce lesions
compatible with pneumoconiosis and progressive pulmonary fibrosis, and that the potential for
inducing these lesions is related to chemical type, physiochemical form, and dose and duration of
exposure.
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No data regarding the carcinogenicity of stable lutetium in animals were located in the
available literature. No histological changes were found in rats that were orally-exposed to
lutetium chloride for 90 days (Haley et al., 1964), but this study is inadequate for assessing
carcinogenic effects due to insufficient duration of exposure and lack of a post-treatment
observation period.
Other Studies
Acute oral and intraperitoneal LD50 values of 4416 and 196 mg Lu/kg, respectively, were
determined for lutetium chloride in 50 male CF1 mice observed for 7 days (Haley et al., 1964).
Symptoms of acute lutetium chloride toxicity included ataxia, writhing, labored respiration,
walking on toes with back arched and sedation (Haley et al., 1964). The peak death rate was
reached at 48 hours after exposure, but some deaths occurred at 24 hours. Acute intraperitoneal
LD50 values of 108 and 125 mg Lu/kg were determined for lutetium nitrate in female mice and
rats, respectively, observed for 30 days (Bruce et al., 1963). Graca et al. (1962) reported an LD50
of 135 mg/kg for lutetium citrate (84 mg Lu/kg) administered intraperitoneally in mice observed
for 168 hours, and an LD50 of 81 mg/kg for lutetium citrate (50 mg Lu/kg) in guinea pigs treated
similarly.
Durbin et al. (1956) evaluated the metabolism and elimination of radioisotopes of 15
lanthanide elements in groups of 5 female Sprague-Dawley rats (including 177Lu given in
intramuscular doses of 7.3 to 29 ju.Ci). Animals treated with 177Lu were sacrificed after 1, 4 and
16 days. Urinary and fecal excreta were collected daily for the first 4 days and twice weekly
thereafter; upon necropsy, radioactivity was measured in various tissues. Although details of the
method used to estimate absorption were not provided, the authors reported that gastrointestinal
absorption of gavage doses of 144Ce, 152'154Eu, 160Tb and 170Tm was less than 0.1% of the
administered dose, suggesting that oral absorption of lutetium is likely to be low. Based on
graphical presentation of the results, approximately 20% of the absorbed dose of 177Lu was
excreted, 65% deposited in bone and less than 5% deposited in liver (remaining 10% not
quantified by tissue) 1 day after injection. Although long-term skeletal retention of 177Lu was
not evaluated in the study, the authors reported that the half-life for elimination from the skeleton
of the heavier lanthanides (lutetium is a heavy lanthanide) was about 2.5 years, based on data
collected for 160Tb and 170Tm over 256 days.
Graca et al. (1964) investigated the effects of intravenously-administered compounds
(chlorides, citrates and edetates) of rare-earth elements on heart rate, blood pressure, respiration
and clinical hematology in male and female dogs (breed and number/sex not specified).
Aqueous solutions of the compounds (equivalent to 5% of the chloride) of 15 rare earth elements
were injected into a cannula inserted into the left femoral vein. Ten doses of 10 mg/kg (as
chloride) each were injected under anesthesia at 10-minute intervals. For each rare-earth
element, nine dogs were divided into groups of three each treated with the chloride, citrate and
edetate. 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
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160 minutes, the animals were necrospied and tissues were collected for histopathology (liver,
spleen, kidney, lung, sternum, mesentery lymph nodes, heart, adrenal and ovaries or testes).
Heart rate, respiration and blood pressure readings were made at the same intervals as blood
samples.
Results for the 15 elements were discussed generally and presented graphically as change
over time after treatment (Graca et al., 1964). Some animals died from treatment (14/45 treated
with chlorides, 4/45 treated with citrates, and 1/45 treated with edetates), but the mortality was
not reported by element. In general, the chloride compounds were more toxic than the citrate or
edetate compounds. Lutetium chloride treatment resulted in a transient spike in blood pressure
(150% of pretreatment values) and heart rate (about 130% of pretreatment values) at 60 minutes
post-treatment; results for the citrate and edetate appeared to be within the range of control
values, based on the graphs. Respiratory rates appeared to be within control values for all
lutetium compounds. Lutetium chloride resulted in increases in prothrombin time (to more than
100 seconds by 100 minutes after treatment, compared to a maximum of 10 seconds for control
animals) and coagulation time (to more than 60 minutes by 1 hour after treatment, compared
with a maximum of about 10 minutes for control animals). No statistical analysis of these effects
was provided in the report. Neither the citrate nor the edetate of lutetium resulted in comparable
changes. The effect on clotting parameters was generally consistent among almost all of the
rare-earth elements, especially the chloride compounds. Visual observation of pooled blood at
incision sites provided additional evidence of the effect of rare-earth elements on clotting
parameters, but the authors did not report the incidence or the specific treatment group(s) where
this was observed. Gross and histopathological examinations revealed slight to moderate
hyperemia of the lungs, only in animals treated with chlorides of the rare-earth elements.
Nakamura et al. (1997) administered lutetium chloride intravenously to Wistar-KY rats.
In each of three experiments, single doses of 10 or 20 mg Lu/kg were administered via the tail
vein. In the first experiment, three rats/dose were sacrificed 2 hours after dosing and blood was
collected to assess the partitioning of lutetium between serum and blood cell fractions. Lutetium
was primarily found in the serum (85.8 and 83.9% for the low and high dose, respectively). In
the second experiment, five rats/dose were sacrificed 1 day after dosing, and blood, liver, spleen,
kidneys, and femurs were collected for analysis of lutetium and calcium content. Lutetium was
primarily deposited in the liver (63.5 and 67.0%> for low and high doses, respectively) and bone
(15.2 and 10.9%> for low and high doses, respectively). At the high dose, lutetium administration
resulted in significantly (p<0.05) increased concentrations of calcium in the liver (3.7-fold),
spleen (2.8-fold), lungs (1.3-fold) and kidneys (1.2-fold). In the final experiment, 3-5 rats were
treated with 10 mg Lu/kg and sacrificed 1 or 3 days after dosing for evaluation of serum
chemistry (aspartate aminotransferase, alanine aminotransferase, total cholesterol, phospholipids,
triglycerides, total bile acids and bilirubin) and hepatic lipids (phospholipids, triglycerides and
total cholesterol). Neither serum enzymes nor hepatic lipids were changed from control values
in rats treated with lutetium chloride. The authors concluded that heavy rare-earth elements
(including Lu) did not induce hepatotoxicity.
No genotoxicity data for stable lutetium were located.
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DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR STABLE LUTETIUM
Information on the toxicity of repeated oral exposure to lutetium is limited to a single
subchronic dietary study in rats (Haley et al., 1964); this study was selected as the critical study
for the p-RfD. No effects were observed on the parameters evaluated, so the highest of the three
tested doses (504-590 mg/kg-day) was identified as a freestanding NOAEL. The only other
information available on the oral toxicity of lutetium is an oral LD50 in male mice (4416 mg
Lu/kg).
The free-standing NOAEL reported by Haley et al. (1964) was used to derive a
subchronic p-RfD of 0.5 mg/kg-day for lutetium. An uncertainty factor (UF) of 1000 was
applied to the NOAEL to derive the subchronic p-RfD:
Subchronic p-RfD = NOAEL / UF
= 504 mg/kg-day / 1000
= 0.5 or 5E-1 mg/kg-day
The UF of 1000 includes a factor of 10 for extrapolation from rats to humans, 10 for protection
of sensitive individuals and 10 for deficiencies in the subchronic toxicity database, including lack
of oral toxicity data in a second species, neurotoxicity data, given the overt neurotoxicology
effects at high does, developmental and a multi-generation reproductive toxicity study.
A chronic p-RfD was not derived for lutetium. There are no studies of chronic exposure
to lutetium in any species. A study using radioactive lutetium reported substantial deposition of
177Lu to bone, and estimated a half-life of 2.5 years for elimination of heavier lanthanides (which
would include lutetium) from the skeleton (Durbin et al., 1956). The potential for prolonged
retention of lutetium in the body increases the uncertainty in extrapolating the toxicological
effects observed in a subchronic study to effects after chronic exposure. Consequently, no
chronic p-RfD was derived for lutetium.
Confidence in the principal study is low. Although both sexes were tested in this study, a
very small number of animals were used for each dose group (six per sex). The toxicological
evaluation in this study was 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. An effect level (i.e., LOAEL) was not
identified. Confidence in the subchronic database on lutetium is low. Apart from the critical
study, the only other information on oral toxicity is an oral LD50 in mice. Oral absorption of
lutetium is likely to be low based on limited data from other rare-earth elements (Durbin et al.,
1956). There are no data to indicate the toxicological endpoint(s) or target organ(s) of
subchronic or chronic oral exposure to lutetium. In addition, there is no information on potential
neurotoxicity, apart from the observation of clinical signs of neurological effects (e.g., ataxia,
sedation) at lethal doses in mice (Haley et al., 1964). No studies of the reproductive or
developmental effects of stable lutetium are available. Studies using injection routes of exposure
indicate that lutetium exposure may affect clotting parameters and that it can increase the
calcium concentration in a number of organs. It is not clear whether these effects may occur
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after oral exposure, as they were not studied by Haley et al. (1964). Low confidence in the
subchronic p-RfD follows.
FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfCs FOR STABLE LUTETIUM
No pertinent data regarding the toxicity of repeated inhalation exposure to stable lutetium
were located in the available literature. Derivation of a p-RfC for stable lutetium is precluded by
the lack of appropriate inhalation toxicity data.
PROVISIONAL WEIGHT-OF-EVIDENCE CLASSIFICATION FOR
STABLE LUTETIUM
No carcinogenicity or genotoxicity data were located for stable lutetium. One subchronic
oral toxicity study of lutetium chloride in rats was inadequate to assess carcinogenic potential.
As the available data are insufficient to assess carcinogenic potential in animals or humans, they
are consistent with the hazard descriptor, "inadequate information to assess carcinogenic
potential," as specified by the U.S. EPA (2005) Cancer Guidelines.
QUANTITATIVE ESTIMATES OF CARCINOGENIC RISK FOR
STABLE LUTETIUM
Derivation of quantitative estimates of cancer risk for lutetium is precluded by the lack of
data demonstrating carcinogenicity associated with lutetium exposure.
REFERENCES
Abel, M. and R.B. Talbot. 1967. Gadolinium oxide inhalation by guinea pigs: A correlative
functional and histopathologic study. J. Pharmacol. Exp. Therap. 157: 207-213.
ATSDR (Agency for Toxic Substances and Disease Registry). 2006. Toxicological Profile
Information Sheet. U.S. Department of Health and Human Services, Public Health Service.
Atlanta, GA. Online, http://www.atsdr.cdc.gov/toxpro2.html. Accessed May 15, 2006.
Ball, R.A. and G. VanGelder. 1966. Chronic toxicity of gadolinium oxide for mice following
exposure by inhalation. Arch. Environ. Health. 13: 601-608.
Beliles, R.P. 1994. The Lanthanides. In: Patty's Industrial Hygiene and Toxicology, Fourth
edition, Volume 2, Part C. G.D. Clayton and F.E. Clayton, Ed. John Wiley and Sons, Inc., New
York, NY. p. 2048-2065.
9

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5-30-2007
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 and G. Vocaturo. 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. Characterisation of respiratory health and exposures
at a sintered permanent magnet manufacturer. J. Ind. Med. 48: 609-615.
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.
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(6): 809-821.
Haley, T.J., N. Komesu, M. Efros et al. 1964. Pharmacology and toxicology of lutetium
chloride. J. Pharm. Sci. 53:1186-1188.
Husain, M.H., J.A. Dick and Y.S. Kaplan. 1980. Rare earth pneumoconiosis. J. Soc. Occup.
Med. 30: 15-19.
IARC (International Agency for Research on Cancer). 2006. IARC Agents and Summary
Evaluations. Online, http://www-cie.iarc.fr/. Accessed May 15, 2006.
Kappenberger, L. and A.A. Buhlmann. 1975. Lungenveranderungen durch «seltene erden».
(Lung lesions caused by "rare earths"). Schweiz. Med. Wochenschr. 105: 1799-1801.
Mogilevskaya, O.Y. and N.T. Raikhlin. 1967. Rare Earth Metals. In: Izrael'son, Z.I. Ed.
Toxicology of the Rare Earth Metals. Israel Program for Scientific Translations, Jerusalem,
p. 132-141.
Nakamura Y., Y.Tsumura, Y. Tonogai, et al. 1997. Differences in behavior among chlorides of
seven rare earth elements administered intravenously to rats. Fundam. Appl. Toxicol. 37:106-
116.
NTP (National Toxicology Program). 2006. Management Status Report. Online. http://ntp-
server.niehs.nih.gov/. Accessed May 15,2006.
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Pharmacyclic. 1999. Pharmacyclic Announces Clinical Results with Lutetium Texaphyrin for
Treatment of Age-Related Macular Degeneration. PRNewswire, July 28, 1999, pp 1048.
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. 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. 1955b. 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., 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.
Sulotto, F., C. Romano and A. Berra. 1986. Rare-earth pneumoconiosis: A new case. Am. J.
Ind. Med. 9: 567-575.
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.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC.
EPA/540/R-97/036. NTIS PB97921199.
U.S. EPA. 2004. 2004 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. Winter, 2004. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf. Accessed May 15, 2006.
U.S. EPA. 2005. Guidelines for carcinogen risk assessment. Risk Assessment Forum,
Washington, DC; EPA/630/P-03/001F. Federal Register 70(66): 17765—17817. Available online
at http://www.epa.gov/raf
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U.S. EPA. 2007. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/. Accessed May 15,2006.
Vocaturo, G., F. Colombo, M. Zanoni et al. 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.
WHO (World Health Organization). 2006. Online Catalogs for the Environmental Criteria
Series. Online, http://www.who.int/pcs/pubs/pub_ehc_alph.htm. Accessed May 15, 2006.
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