TECHNICAL REPORT DATA
(fleate rtad Instntetiora on tfte reverse be fan completing}
!-. REPOI.T NO.
EPA/600/8-88/061
2.
,3. RECIPIENT'S ACCESSION NO.
PB88-176383
4. TITLE AND SUBTITLE
Health Effects Assessment for Vanadium and Compounds
6. REPORT DATE
0. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
I. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
5. SUPPLEMENTARY NOTES
6. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order 12991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfDs or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Croup
8. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (Tha Report)
Unclassified
21. NO. Of PAGES
2O. SECURITY CLASS (Thit page)
Unclassified
22. PRICE
EPA furm 2220-1 (R»». 4-77) PNKVIOU* EDITION is OMOLKTC
v-
hi
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EPA/600/8-88/061
July, 1987
HEALTH EFFECTS ASSESSMENT
FOR VANADIUM AND COMPOUNDS
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
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DISCLAIMER
This document has been reviewed In accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
This report presents a brief summary and evaluation of Information
relevant to a preliminary Interim assessment of adverse health effects
associated with vanadium and compounds. All estimates of acceptable Intakes
and carcinogenic potency presented 1n this document should be considered as
preliminary and reflect limited resources allocated to this project.
Pertinent toxlcologlc and environmental data were located through on-line
literature searches of the Chemical Abstracts, TOXLINE and the CHEMFATE/
DATALOG data bases. The basic literature searched supporting this document
1s current up to May, 1986. Secondary sources of Information have also been
relied upon 1n the preparation of this report and represent large-scale
health assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1983a. Reportable Quantity Document for Vanadyl Sulfate.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for Vanadium (V)
Oxide (Vanadium Pentoxlde). Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Emergency and Remedial
Response, Washington, DC.
U.S. EPA. 1985a. Health and Environmental Effects Profile for
Vanadium Pentoxlde. Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1986a. Integrated Risk Information System (IRIS).
Reference dose (RfD) for oral exposure for vanadium pentoxide.
Online. (Verification date 2/26/86). Office of Health and
Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH.
The Intent In these assessments 1s to suggest acceptable exposure levels
for noncardnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfDs (formerly AIS) or subchronlc reference dose, Is
an estimate of an exposure level that would not be expected i.o cause adverse
effects when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the Hfespan).
111
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This type of exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants In ambient air or water where lifetime
exposure 1s assumed. Animal data used for RFD$ estimates generally
Include exposures with durations of 30-90 days. Subchronlc human data are
rarely available. Reported exposures are usually from chronic occupational
exposure situations or from reports of acute accidental exposure. These
values are developed for both Inhalation {RfD$i) and oral (RfD-so)
exposures.
The RfD (formerly AIC) 1s similar In concept and addresses chronic
exposure. It Is an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the Ufespan [see U.S. EPA (1980) for a discussion of this concept]. The
RfD 1s route-specific and estimates acceptable exposure for either oral
(RfD0) or Inhalation (RfDj) with the Implicit assumption that exposure
by other routes Is Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development Is explained In U.S.
EPA (1984).
For compounds for which there 1s sufficient evidence of cardnogenlcUy
RfOs and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980). Since cancer 1s a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-j*s have been computed, 1f appro-
priate, based on oral and Inhalation data 1f available.
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ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate
Interpretation and use of the quantitative estimates presented.
Several subchronlc and chronic oral studies In animals with various
compounds of vanadium were found 1n the available literature. A 90-day
drinking water study using rats with sodium metavanadate Indicated that this
compound 1s more toxic than vanadium pentoxlde or vanadyl sulfate (Domingo
et al., 1985). A NOAEL of 0.55 mg vanadlum/kg/day, associated with mild
lesions 1n lungs, spleen and kidney 1n this study, was used as the basis of
an RfD§0 for vanadium of 0.4 mg/day. The RfD$o for sodium vanadate 1s 1
mg/day for a 70 kg human. In the absence of suitable subchronlc studies for
vanadium pentoxlde and vanadyl sulfate, the RfDg from chronic studies can
be adopted as an RfD$g- The RfDg for sodium vanadate can be obtained
from the RfD$o by using an additional uncertainty factor of 10 to account
for extrapolation of subchronlc study to chronic. This RfDg Is 0.1 mg/day
for a 70 kg human. The RfOg for vanadium pentoxlde can be obtained from
chronic dietary study (Stoklnger, 1981). A NOAEL of 10 ppm of vanadium 1n
diet corresponds to 18 ppm of vanadium pentoxlde and an RfDg of 0.009
mg/kg/day or an RfDg of 0.6 mg/day for vanadium pentoxlde. The RfDg for
vanadium sulfate can be obtained from chronic water Intake study 1n rats and
mice (Schroeder and MHchener, 1975); 5 ppm of vanadium In water corresponds
to a vanadium Intake of 0.9 mg/kg/day 1n rats and 0.7 mg/kcj/day 1n mice.
The RfDg 1s obtained by using an uncertainty factor of 100. A more
conservative value In mice corresponds to an RfDg for vanadium of 0.5
mg/day or an RfDg for vanadyl sulfate of 1.6 mg/day. The most conserva-
tive RfOg of 0.04 mg/day vanadium can then be obtained from the RfDg for
sodium vanadate. This number may be overly conservative since H 1s more
than an order of magnitude smaller than the RfDg for vanadium obtained
from the chronic studies.
Data were Insufficient to derive RfD$j or RfDj values for vanadium
or Us compounds. Vanadium appears to be more toxic by Inhalation than by
Ingestlon. The maximum CS of 32.9 for vanadium was based on persistent
cough, dyspnea and wheezing In humans exposed to vanadium pentoxlde at
0.02-3.2 mg/m3 occupatlonally for 8 years.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and John Helms (Office of
Toxic Substances) was the Project Officer. The final documents 1n this
series were prepared for the Office of Emergency and Remedial Response,
Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and K1m Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
3.2. CHRONIC
3.2.1. Oral
3.2.2. Inhalation
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation. ....
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
4.2. BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
4.3. OTHER RELEVANT DATA
4.4. HEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfDs)
6.1.1. Oral (RfDso)
6.1.2. Inhalation RfDST)
Paqe
. . . 1
. . . 4
. . . 4
. . . 4
. . . 6
. . . 6
. . . 6
. . . 8
. . . 9
. . . 9
. . . 11
. .. . 14
. . . 14
. . . 14
. . . 15
, , . 16
. . . 16
. . . 16
16
16
. . . 16
. . . 16
. . . 16
. . . 17
. . . 19
. , . 20
. . . 20
. . . 20
. . . 22
V11
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TABLE OF CONTENTS
Page
6.2. REFERENCE DOSE (RFD) ................... 22
6.2.1. Oral (RfD0) ................... 22
6.2.2. Inhalation (RfOj) ................ 24
6.3. CARCINOGENIC POTENCY (<*) ................ 25
6.3.1. Oral ....................... 25
6.3.2. Inhalation .................... 25
7. REFERENCES ............................ 26
APPENDIX: Summary Table for Vanadium and Compounds .......... 35
V111
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LIST Of ABBREVIATIONS
BCF Bloconcentratlon factor
CAS Chemical Abstract Service
CS Composite score
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
MTD Maximum tolerated dose
NOAEL No-observed-adverse-effect level
ppm Parts per million
RBC Red blood cell
RfO Reference dose
RfDj Inhalation reference dose
RfOQ Oral reference dose
RfD$j Subchronlc Inhalation reference dose
RfDgQ Subchronlc oral reference dose
RMCL Recommended maximum contamination levels
RVj Dose-rating value
RVe Effect-rating value
TLV Threshold limit value
TWA Time-weighted average
WBC White blood cell
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Vanadium Is a metal that Is a member of the first transition series of
the Periodic Table. Vanadium Is widely distributed In low abundance
throughout the earth's crust and 1s also found 1n trace amounts In fossil
fuels. The llthosphere contains -0.01 wt/4 vanadium and few deposits contain
>l-2 wtX of this element. Vanadium has oxidation states of *2, *3, +4 and
*5 (Baroch, 1983), and usually occurs 1n some oxidized form such as metal
vanadate (NLM, 1986). Physical properties of vanadium and some of Us
compounds are presented In Table 1-1.
In water, vanadium can exist In both soluble forms and as a precipitate.
Vanadium deposited In water by wet and dry deposition may reenter the atmo-
sphere as sea salt aerosol particles generated at ocean surfaces (Arlmoto et
a!., 1985). Monitoring data that show at least 100-fold higher concentra-
tion of vanadium 1n sediment than In aqueous solution Indicate that vanadium
can precipitate out of solution and accumulate In sediments. Vanadium from
water can be taken up and accumulated by fish. BCFs of 365-630 were
observed In different fish (Sadlq and Za1d1, 1985; He1t et al., 1984; Tsui
and McCart, 1981).
It 1s reported that vanadium In the air Is solely a result of Industrial
processes. For example, 1n the lower Delaware River valley, the principal
sources are emissions from the combustion of vanadium-rich fuel oils 1n
refineries, power plants and other Industries. A secondary source Is
partlculate emissions from the catalytic processing of petroleum 1n
refineries. Upon emission during combustion, vanadium oxides combine Into
partlculate fly ash. Lower oxides of vanadium will ultimately oxidize to
V-0,., especially at the high temperatures encountered In combustion
0108h -1- 02/17/87
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stacks (100-500°C). Vanadium pentoxlde may also exist In equilibria with
sulfur and compounds resulting from stack reactions with S(L. The resi-
dence time of vanadium In the atmosphere has been estimated to be 0.36 day.
Deposition 1s the only likely sink for the vanadium emissions. It was
estimated using Stoke's law for settling rates that the residence time of
the fly ash vanadium pentox1de/H_SO. aerosols should be -1 day. Ralnout
would be expected to be an additional mechanism for removal from air (U.S.
EPA, 1985a).
The half-lives of vanadium and Us compounds In soil could not be
located In the available literature. Vanadium pentoxlde Is sufficiently
soluble In water (8000 mg/i at 20°C) to Indicate potential for soil
mobility by leaching. It 1s possible that leaching may be hindered by the
formation of chemical complexes between vanadium and soil constituents.
Vanadium pentox1de/H_SO. that may deposit on soil from the atmosphere
will be transported to natural waters by runoffs (U.S. EPA, 1985a).
0108h - -3- 10/27/86
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
In humans, Ingested vanadium Is absorbed poorly by the gastrointestinal
tract. Only 0.1-1.OX of a 100 and 125 rag dose of dlammonlum oxytartaro-
vanadate was absorbed gastrolntestlnally, and 60% of the absorbed dose was
excreted by the kidneys within 24 hours (Curran et al., 1959). Only
2.6^1.6% of the radioactivity from a 0.3 mg/kg dose of vanadium from
4*V2°5 administered by gavage was absorbed by 70-day-old female
Fischer rats (Conklln et al., 1982). Dlmond et al. (1963) administered
orally to humans, tablets containing 25 mg of ammonium vanadyl tartara-te 1-4
times/day. Six subjects were treated for 45-68 days. Varying amounts of
vanadium were excreted In the urine, suggesting unpredictable absorbtlon.
Wlegman et al. (1982) studied Intestinal absorbtlon and secretion of
radioactive vanadium In Sprague-Dawley rats. Vanadium was administered 1n a
sodium metavanadate form by gavage (5/ymol, corresponding to 0.255 mg).
After 4 days, -18% of the dose was excreted In urine and ~69% was recovered
1n stool. The remainder was retained 1n various organs and tissues. In an
experiment where 1 ml of A1(OH)3 gel was given to the rats at the same
time when vanadlan was administered, aluminum hydroxide decreased absorbtlon
of vanadium, which was evidenced by decreased urine recovery of vanadium
(~8% of administered dose). Stool recovery of vanadium Increased to ~86%.
2.2. INHALATION
Several studies have reported that vanadium was Identified In the blood,
feces and, 1n most studies, the urine of some, but not all, workers after
occupational exposure to vanadium pentoxlde dust, Indicating that absorption
occurred as a result of vanadium pentoxlde Inhalation (SJoberg, 1956;
Williams, 1952; Vlntenner et al., 1955; Lewis, 1959; Zenz and Berg, 1967;
0108h -4- " 07/17/87
-------
Ross, 1983). Although Vlntenner et al. (1955) reported vanadium In the
blood of Peruvian workers exposed to high (0.018-58.82 mg V/m3) and low
(0.0004-2.116 mg V/m3) exposure levels of vanadium pentoxlde to be 0.041
and 0.036 mg/100 cc, respectively, they also detected 0.031 mg/100 cc of
vanadium In the blood of the control group of workers who were not occupa-
tlonally exposed to vanadium pentoxlde.
Conklln et al. (1982) reported that 100% of an Intratracheal dose of
-0.3 mg V/kg administered as radlolabeled vanadium pentoxlde, 4*V2°5'
was absorbed by 70-day-old female Fischer rats. The rats were housed In
steel metabolism cages and groups of four were killed within 1 hour, within
1/2 day and at 1, 3, 5 and 7 days after 48V2°5 administration. About
40% of the recovered radioactivity had been cleared from the lungs within 1
hour, and -90% had been cleared within 3 days. Clearance from the lung was
primarily Into blood, Hver and bone, Indicating rapid absorption from this
site. By posttreatment day 3, -40% of the radioactivity had been recovered
In the urine. Similar results were obtained for 48V02C1.
0108h -5- 07/16/87
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Dlmond et al. (1963) gave human subjects (five females and
one male) 25 mg tablets of ammonium vanadyl tartrate up to 4 times/day for
45-68 days. Gastrointestinal difficulties (black, loose stools, Increased
Intestinal activity and cramps) were noted 1n the treated subjects; however,
hematologlcal Indices and clinical chemistry were essentially unchanged.
Three of the female subjects excreted elevated levels of 17-ketosterolds and
!7-hydroxcort1costero1ds compared with normal values obtained 1n this
laboratory. Control data was not reported (NIOSH, 1977), and the subjects
were given a chollnerglc-blocklng drug to lessen the gastrointestinal
symptoms, which make Interpretation of these results difficult.
Franke and Moxon (1937) fed groups of 10 rats of both sex;es 25 and 50
ppm vanadium from sodium metavanadate In a wheat diet for 100 days.
Controls were given the same diet without added vanadium. Growth rate was
depressed 1n a dose-related manner 1n both treated groups as compared with
controls. Diarrhea occurred 1n the 50 ppm group. No effect on hemoglobin
values was observed. No other parameters of toxlclty were evaluated.
Domingo et al. (1985) gave groups of 10 male Sprague-Dawley rats 0, 5,
10 and 50 ppm sodium metavanadate In drinking water for 3 months. Treatment
with the compound did not affect food consumption, weight gain, protein
utilization, relative organ weights or clinical chemistry Indicators of
liver function or damage. Slight Increases 1n blood urea and uric acid 1n
the 50 ppm group suggested an alteration In renal function. Hlstopatho-
loglcal examination was limited to heart, lungs, liver, kidney, spleen,
stomach, and small and large Intestines of Ahree rats from each group.
0108h -6- 07/16/87
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"Mild hlstologlcal changes" consisting of hypertrophy and hyperplasla of the
white pulp 1n the spleen, m1crohemorrhag1c fod 1n the kidney and Infiltra-
tion of mononuclear leukocytes 1n the lungs, mostly In the perlvascular
regions, occurred 1n all treated groups, but were most evident at 50 ppm.
The Investigators concluded that sodium metavanadate was "generally well
tolerated" at all concentrations.
Susie and Kentera (1986) gave groups of 15 male Long-Evans rats 0 or 300
ppm ammonium vanadate In the diet for 2 months to measure effects on pulmo-
nary circulation. Body weight, heart rate, mean femoral artery pressure,
cardiac output, total peripheral resistance, left ventricular weight and
hematocrH values were unaffected. Right ventricular systolic (p<0.01),
right ventricular mean pressures (p<0.001) and pulmonary vascular resistance
(p<0.05) (the ratio of right ventricular systolic pressure/cardiac output)
were statistically significantly Increased 1n treated rats. Right ventricu-
lar hypertrophy was evident as Increased relative right ventricular weight.
The authors concluded that pulmonary hypertension was evident In these rats,
with the caveat that the method used to calculate pulmonary vascular
resistance (see above) assumes that changes 1n right ventricular systolic
pressure reflect mean pulmonary artery pressure, which may be erroneous.
Groups of five male Wlstar rats were treated with vanadium pentoxlde at
levels of 0, 25 or 50 ppm of dietary vanadium for 35 days, at which time
levels were Increased to 100 and 150 ppm, respectively, for the two treated
groups and continued for an additional 68 days (Mountain et a!., 1953). At
the end of 103 days, the rats Ingesting vanadium pentoxlde gained more
weight than the control rats, although food consumption was reported to be
similar In all groups. There was a decrease In the amount of cystlne In the
hair of the rats exposed to the high level of vanadium pentoxlde. The
0108h -7- 10/27/86
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amount of cystlne In the hair of the rats exposed to the low level of vana-
dium pentoxlde remained nearly constant on average, while the amount of the
changes In the cystlne content of the hair In treated rats was statistically
different from controls. Gross and microscopic examination of the hair
revealed structural changes that resembled those observed 1n cystlne-
defldent rats. There was a significant decrease In the RBC count and blood
hemoglobin concentration of rats exposed to the high level of vanadium
pentoxlde; these parameters In rats exposed to the low level of vanadium
pentoxlde were slightly decreased, but significance was not reported.
Gorskl and Zaporowska (1983) gave rats ammonium vanadate (200 ppm
vanadium) 1n drinking water and observed decreased body growth, erythrocyte
number, hemoglobin concentration and hematocrlt after 2 months. After 3
months of vanadium exposure, "all the parameters only had a decreasing
tendency." Liver and kidney degeneration was observed In some of the rats.
Few details were provided 1n this brief abstract.
3.1.2. Inhalation. Several reports describe case histories and experi-
mental studies of people exposed to relatively high concentrations of vana-
dium pentoxlde for a short period of time ranging from a few hours to a few
days (Husk and Tees, 1982; Zenz et al., 1962; Sjoberg, 1955, Hlilllams, 1952;
McTurk et al., 1956; Zenz and Berg, 1967). All developed respiratory symp-
toms (wheezing, cough, dyspnea), which occurred during exposure or within a
few days and usually subsided within 7-14 days; some developed asthma (Husk
and Tees, 1982).
In an experiment by Zenz and Berg (1967), two volunteers exposed to 1 mg
VpOc/m3 for 8 hours developed symptoms characteristic of vanadium
Inhalation, Including a persistent cough. Upon accidental exposure for 5
minutes to a heavy cloud of vanadium pentoxlde dust 3 weeks after the
0108h -8- 02/17/87
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Initial exposure, the same two volunteers developed severe respiratory
distress, and coughing continued for a week. In the same study, five
volunteers exposed to 0.2i0.06 mg/m3 of vanadium pentoxlde for 8 hours
developed a cough that lasted 7-10 days. Pulmonary function tests showed no
detectable changes after any of these exposures when compared with pre-
exposure results.
Suglura (1978) exposed an unspecified number of rats and mice to 1-2
mg/m3 of vanadium pentoxlde for 6 hours/day for 3 months. No effects on
growth rate, lung size, blood chemistry or histology were reported In the
mice or rats exposed to 0.1-0.4 mg/m3 of vanadium pentoxlde. At the
higher concentration, however, the rats had a decreased growth rate and
enlarged lungs and the mice had thickened alveolar walls and congested
lungs. Few details were provided 1n this brief abstract.
3.2. CHRONIC
3.2.1. Oral. Stoklnger et al. (1953) administered dietary vanadium
pentoxlde to rats at levels of 10 and 100 ppm vanadium for their lifetimes.
The criteria used to evaluate the toxldty Included hematology, rate of body
weight gain and a "fairly comprehensive" hlstopathologlcal examination
(Stoklnger, 1985). Except for a reduction In hair cystlne content, no
significant signs of toxldty In rats were reported. Rats fed 100 ppm
exceeded growth of the controls for the first 7 months of the diet. There-
after, the average group weight was slightly lower than the controls, but
more rats survived for longer periods than did the controls.
Schroeder and MUchener (1975) gave groups of 54 Swiss mice/sex 5 ppm of
vanadium metal In the drinking water (added as vanadyl sulfate) for life.
Weight measurements showed that the vanadium-treated male mice were signifi-
cantly heavier than their controls at five out of eight age Intervals (30,
0108h -9- 10/27/86
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60, 90, 180 and 540 days of age). The treated female mice also generally
weighed more than their controls throughout the experiment, but the Increase
was statistically significant only at 540 days of age (the terminal age
group). Body weights of males at 540 days were 45.5 vs. 40.6 g for
controls, and of females, 43.2 vs. 36.3 g for controls. Male and female
mice fed vanadium also had longer Hfespans (higher mean age at death) and a
statistically significant higher longevity (mean age of last surviving 10%)
than controls. In males, the median llfespan and mean longevity of the
treated and control mice were 578 vs. 556 days and 880 vs. 763 days, respec-
tively. The values In the treated and Control female mice were 620 and 565
days (mean age at death), and 878 and 790 days (mean longevity), respec-
tively. Gross pathological examination for tumors and microscopic examina-
tion of "some" sections from the heart, lung, kidneys and spleen following
natural death revealed no remarkable compound-related effects.
In a related similarly designed study, 5 ppm vanadium from vanadyl
sulfate was added to the drinking water of 52 male and 61 female Long-Evans
rats from the time of weaning to natural death (Schroeder et al.. 1970).
Control groups comprised 52 male and 54 female rats. Growth rate, survival
and longevity were found to be similar among the vanadium-treated and
control rats. Fasting glucose levels were significantly elevated In the
treated female rats, but nonfastlng glucose levels were normal In both male
and female. Fasting serum cholesterol levels were significantly elevated In
treated males and significantly depressed 1n treated females when compared
with respective control values, but the below normal serum cholesterol level
In the females may have been related to Insufficient levels of dietary
chromium. Mean heart weights and mean heart-to-body weight ratios at death
showed that the hearts of the treated male rats weighed 4X more than those
of controls, but these changes were not found to be significantly different.
0108h -10- 10/27/86
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Vanadyl sulfate was not Found to be tumorIgenlc, as evidenced by the
Incidence of grossly visible tumors at necropsy following natural death; and
limited histologlcal examinations of the heart, lungs, kidneys, liver and
spleen of treated rats were apparently unremarkable.
3.2.2. Inhalation. SJoberg (1950) presented the case histories of 36
workers (ranging In age from 20-59 years) 1n a vanadium factory In Sweden
who were exposed to vanadium pentoxlde at concentrations ranging from
0.05-5.58 mg/ma. Vanadium was detected 1n the blood and urine of exposed
Individuals, and some of the workers had developed eczema or a hypersensl-
t1v1ty to vanadium detectable with a skin patch test. Severe respiratory
Irritation was the most prevalent symptom, but slight changes In blood,
hemoglobin concentrations, heart palpitations upon exertion, weakness and
neuroasthenlc symptoms were observed occasionally. Blood pressure was not
Increased and there were no gastrointestinal or urinary tract symptoms and
no discoloration of the tongue; chronic changes, such as pneumonoconlosls,
flbrosls or emphysema, were not detected. The short observation period of
the Sjoberg (1956) report (-2 years), however, may not have been sufficient
to detect chronic effects of vanadium exposure.
Lewis (1959) studied the effects of vanadium pentoxlde exposure, usually
ranging from 0.018-0.38 mg vanad1um/m3, but with one concentration at
0.925 mg vanad1um/m3, In 24 men aged 38-60 years. Average duration of
exposure was 2.5 years. The control group consisted of 45 men selected at
random who were similar to the vanadium-exposed group In age range, economic
status and job activity except that they were not occupatlonally exposed to
vanadium. Incidence of respiratory distress (cough, bronchospasm, pulmonary
congestion) was Increased 1n vanadium-exposed workers, but there was no
0108h -11- 02/17/87
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difference In electrocardiograms, hematocrlts or clinical urlnalyses between
the exposed and control groups. The author concluded that there were no
permanent effects from chronic vanadium exposure.
Tebrock and Hachle (1968) evaluated 250 workers exposed to levels of
vanadium pentoxlde ranging from 0.02-3.2 mg/m3 (mean=0.844 mg/m3) over
an 8-year period. Conjunctivitis, tracheobronchltls and contact dermatitis
were the most prevalent clinical observations. No changes 1ri hematology,
pulmonary function or blood pressure were noted, although a transient
Increase In blood pressure was reported In some Individuals who did not take
proper precautions 1n areas of high vanadium levels. Tebrock and Machle
(1968) concluded that exposure to vanadium pentoxlde caused no permanent
adverse systemic effects 1n spite of the observation that there were some
chronic changes In the mucus membranes.
Symanskl (1939) found severe Irritation of the respiratory system and
conjunctiva but no adverse systemic effects from chronic exposure to
vanadium pentoxlde, based on the study of 19 workers exposed to unknown
concentrations for a few months to several years. A control group was not
provided. According to NIOSH (1977), Symanskl (1954) Indicated 1n a
follow-up report that emphysema may have resulted from exposure to vanadium
pentoxlde In two workers during a 9- and a 13-year period.
Vlntenner et al. (1955) evaluated three groups of vanadium mining and
process workers 1n Peru who had been employed for 1-10 years. The control
group (n=37) was not exposed to vanadium pentoxlde 1n the workplace; the
second group (n=39) was exposed to a low level of vanadium pentoxlde ranging
from 0.004-2.116 mg vanad1um/m3; the third group (n=39) was exposed to a
high level of vanadium pentoxlde ranging from 0.018-58.82 mg vanad1um/m3.
0108h -12- 10/27/86
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The amount of vanadium detected In the blood of workers from whom blood was
taken was not reported. Vanadium levels detected 1n the urine appeared to
be significantly higher 1n the workers occupatlonally exposed to high levels
of vanadium pentoxlde. Vanadium levels In the urine from workers exposed to
low concentrations of vanadium pentoxlde appeared similar to those levels In
the urine from controls.
The percentage of workers who complained of cough, chest pain, expecto-
ration, headache, dyspnea, palpitations, tiredness, night sweating and
weakness was highest 1n the group exposed to the high level of vanadium
pentoxlde, lowest In the control group and Intermediate In the group exposed
to low levels of vanadium pentoxlde (Vlntenner et al., 1955). The only com-
plaint more prevalent 1n the low- than In the high-exposure group was colic.
In addition, Vlntenner et al. (1955) reported that vanadium pentoxlde-
exposed workers had more eye complaints, such as Itching, swelling and
burning sensation, as well as an Increased Incidence of perlodontal disease.
In an ep1dem1olog1cal study, Klvlluoto et al. (1981a) evaluated a group
of 63 males (mean age=36.5+9.6 years) who were exposed to vanadium pentoxlde
1n the workplace at time-weighted mean concentrations ranging from 0.012-2.3
mg vanad1um/m3 for an average of 10.8 years. The control group consisted
of 22 males (mean age=31.9+00.2 years) who were not occupatlonally exposed
to vanadium pentoxlde. Analysis of blood and urine samples from 16-18
vanadium pentoxlde-exposed workers and of urine samples from 16-17 controls
revealed that the serum vanadium concentration was 0.22^0.14 ymol/a.
(0.011 mg/i) and the urinary vanadium concentration 0.26^0.17 vmol/8.
(0.013 mg/i) In vanadium pentoxlde workers, whereas the urinary vanadium
content was less than the detection limit of 0.04 ymol/i (0.002 mg/a)
1n the controls. Evaluation of blood enzyme levels, blood protein levels,
0108h -13- 02/17/87
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hematologlcal parameters and WBC counts Indicated that there were no vana-
dium pentoxlde-related differences between the exposed and control workers.
Although there were statistically significant differences between exposed
and control workers for serum albumin, chloride, urea, blllrubln and
conjugated blllrubln, Klvlluoto et al. (1981b) Indicated that the observed
differences were not biologically significant. No evaluation of symptoms
(I.e., cough or dyspnea) was presented In this report. No long-term Inhala-
tion studies In animals were available.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenldty and reproduc-
tive effects of vanadium and compounds by the oral route could not be
located 1n the available literature; however, Roshchln and Kozlmov (1980)
observed that 20 dally Intraperltoneal Injections of 0.85 mg/kg Na-VO.
decreased sperm motmty and osmotic resistance In rats. Sterility of males
and Increased mortality of spermatozplds was observed as well. Subcutaneous
Injection of 0.85 mg/kg/Na3VO. on day 4 of pregnancy decreased pre-
1mplantat1on survival by 50%. Carlton et al. (1982) studied the
teratogenldty of ammonium vanadate using Syrian golden hamsters. Twenty
pregnant hamsters per dose group received 0, 0.47, 1.88 and 3.75 mg/kg of
ammonium vanadate by 1.p. Injection on gestation days 5 through 10.
Pregnant females were killed on day 15, opened and uterus was observed for
resorptlon sites and live and dead Implantations. All fetuses were removed
and observed for malformations. There was a statistically significant
Increase In skeletal abnormalities and a decrease In the maleifemale ratio.
However, the small number of malformed offspring and the lack of a clear cut
dose-response did not allow a definitive assessment of teratogenldty.
0108h -14- 07/17/87
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3.2.2. Inhalation. Pertinent data regarding the teratogenldty or repro-
ductive effects of vanadium and compounds by Inhalation could not be located
In the available literature.
3.4. TOXICANT INTERACTIONS
Dlmond et al. (1963) found that trlglyclamol chloride lessened symptoms
of gastrointestinal distress In humans given oral doses of ammonium vanadyl
tartrate (see Section 3.1.1.). Thompson et al. (1984) observed that feeding
rats a "purified diet* with 25 ppm of vanadium as vanadyl sulfate during the
postlnltlatlon stages of marine mammary carclnogenesls Induced by 1-methyl-
1-nltrosourea blocked the carcinogenic response as exhibited by reducing
cancer Incidence, the average number of cancers/rat and by prolonging the
median cancer-free time.
Wright (1968) found that levels of 500-2000 jig/g of chromium 1n the
diet effectively overcame growth depression and mortality In rats fed 20
mg/kg vanadate 1n the diet.
Ascorbic add and ethylenedlamlnetetraacetate were effective as anti-
dotes 1n experimental vanadium poisonings of mice, rats and dogs (Mitchell
and Floyd, 1954). Routes of administration were not specified In the
summary of this study (NAS, 1974).
0108h -15- 07/16/87
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4. CARCINOGENICITY
4.1. HUNAN DATA
4.1.1. Oral. Pertinent data regarding the oral carclnogenlclty of
vanadium and compounds could not be located In the available literature.
4.1.2. Inhalation. In an early ep1dem1olog1cal study of the effects of
several Industrial pollutants (smoke and some of Its components Including
3,4-benzopyrene, beryllium, molybdenum, vanadium and arsenic) on cause of
death, Stocks (I960) found positive correlations between the Incidence of
deaths from lung cancer (r=0.770) and cancers of other body sites (excluding
the stomach) In males (r=0.556) and exposure to vanadium In air In 23 local-
ities In Northern England and Wales. When the Influence of beryllium and
molybdenum were eliminated, however, the correlation coefficient was reduced
to 0.347, which Is not statistically significant.
4.2. BIOASSAYS
4.2.1. Oral. Administration of 5 ppm vanadlum/l (from vanadyl sulfate)
to mice and rats 1n drinking water for life was not tumorlgenlc; however,
hlstopathologlcal examination was limited (Schroeder and HUchener, 1975;
Schroeder et al., 1970) (see Section 3.2.1.). Schroeder and Balassa (1967)
administered 5 mg/l of vanadium as vanadyl sulfate 1n drinking water to 23
male and 29 female mice. No effects on longevity, hlstopathology or number
of tumors were observed.
4.2.2. Inhalation. Pertinent data regarding the carclnogenlclty of
Inhaled vanadium 1n animals could not be located 1n the available literature.
Vanadium pentoxlde has been approved by the National Toxicology Program
for an Inhalation toxicology study (NTP, 1986).
4.3. OTHER RELEVANT DATA
Kanematsu et al. (1980) reported that vanadium pentoxlde did not In-
crease the frequency of reverse mutations In the spot test using Escher1ch1a
0108h -16- 07/16/87
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coll (strains B/r WP2 and WP2) or Salmonella typhlmurlum (strains TA98,
TA100, TA1535, TA1537 and TA1538). However, vanadium pentoxlde, ammonium
vanadate and VOC1? were positive In the rec assay system using a
recombination-proficient (H17 Recf) and a recombination-deficient (mA5
Rec") strain of Bacillus subtlUs at concentrations of 0.5, 0.4 and 0.3 M,
respectively (Kada et al., 1980; Kanematsu et al., 1980).
Stoner et al. (1976) Investigated the production of lung adenoma In
strain A mice following multiple l.p. Injections of 13 metallic compounds,
Including vanadium (111) 2,4-pentaned1one; no significant Increase 1n the
average number of lung tumors was observed.
4.4. WEIGHT OF EVIDENCE
Although the epidemiology study by Stocks (1960) found a positive corre-
lation between vanadium and other pollutants In Industrial pollution and
deaths from cancer, particularly lung cancer, when the Influence of the
pollutants beryllium and molybdenum was removed, the correlation was no
longer statistically significant. Since other data on humans are not
available to compare with the findings of Stocks (1960), the evidence for
carclnogenlclty 1n humans Is most appropriately judged to be Inadequate.
Three chronic exposure studies were performed using experimental
animals. These Include a lifetime study In rats with dietary vanadium
pentoxlde (Stoklnger et al., 1953) and lifetime drinking water studies 1n
rats (Schroeder et al., 1970) and mice (Schroeder and MHchener, 1975) with
vanadyl sulfate. The MTO was not approached 1n any of these experiments,
and hlstopathology evaluation was not comprehensive. The lack of an
observed tumorlgenlc response In these experiments should not be Interpreted
as a fully valid evaluation for lack of carclnogenlclty of Ingested
vanadium. The carclnogenlclty of Inhaled vanadium In animals has not been
0108h -17- 07/17/87
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tested. It 1s most appropriate, therefore, to consider that existing data
are not sufficient to adequately evaluate the carclnogenlclty of vanadium 1n
laboratory animals.
IARC has not classified vanadium as to the weight of evidence for
cardnogenldty to humans. The EPA weight of evidence classification for
vanadium 1s Group D, not classifiable (U.S. EPA, 1986b).
0108h -18- 07/16/87
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5. REGULATORY STANDARDS AND CRITERIA
U.S. EPA (1986a) derived an RfD for vanadium pentoxlde of 0.02 mg/kg/day
or 1 mg/day for a 70 kg man based on the NOAEL of 35.7 ppm vanadium
pentoxlde In food associated with decreased hair cystlne In a rat chronic
oral study (Stoklnger et al., 1953). This RfD Is erroneous because of a
miscalculation In the dose; the RfD for vanadium pentoxlde from the
Stoklnger et al. (1953) study should be 0.009 mg/kg/day, or 0.6 mg/day for a
70 kg human. U.S. EPA (1985b) did not propose an RMCL for vanadium because
"preliminary analysis Indicated limited potential for drinking water
exposure." Vanadium will be considered 1n later phases of the National
Primary Drinking Water Regulations.
ACGIH (1986) recommended a TLV-TWA of 0.05 mg/m3 (as v^) for
resplrable dust and fumes based primarily on the findings of Zenz and Berg
(1967) who observed coughing and Increased mucus 1n human volunteers exposed
to 0.1 mg/m3 vanadium pentoxlde dust. NIOSH (1977) recommended a TWA
concentration limit of 1 mg/m3 for up to 10 hours/day for a 40-hour work
week for vanadium. OSHA (1985) adopted a celling of 0.5 mg/m3 and 0.1
mg/m3 for vanadium pentoxlde dust and fumes, respectively.
0108h -19- 07/16/87
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE OOSE (RfDJ
3
6.1.1. Oral (RfDSQ). Oral exposure to vanadium compounds 1s associated
with Increased Intestinal activity, cramping (Dlmond et al., 1963) and
diarrhea (Dlmond et al., 1963; Franke and Moxon, 1937), elevated systemic
blood pressure, pulmonary hypertension and right ventricular hypertrophy
(Susie and Kentera, 1986), disturbed protein assimilation, particularly the
sulfur-containing ami no acids such as cystlne (Domingo et al., 1985;
Mountain et al., 1953; Stoklnger et al., 1953), reduced kidney function
(Domingo et al., 1985), reduced erythrocyte count and blood hemoglobin
concentration (Mountain et al., 1953; Franke and Moxon, 1937; Gorskl and
Zaporowska, 1983) and reduced rate of body weight gain In growing animals
(Franke and Moxon, 1937; Gorskl and Zaporowska, 1983). The Individual
studies In humans (Dlmond et al., 1963) and most of those In animals (Franke
and Moxon, 1937; Susie and Kentera, 1986; Mountain et al., 1953; Gorskl and
Zaporowska, 1983) do not sufficiently evaluate the endpolnts of toxldty
associated with vanadium so that any one study may be used with confidence
as the basis for an RfDSQ for vanadium. The most comprehensive subchronlc
oral study was performed by Domingo et al. (1985) 1n which groups of 10 male
Sprague-Dawley rats were provided with drinking water containing sodium
metavanadate at 0, 5, 10 and 50 ppm for 3 months. By correcting for the
atomic weight of vanadium and using body weight and water Intake data
provided by the Investigators (assuming control, low and middle group rat
data are Identical; actual data provided for controls and high group rats)
corresponding vanadium dosages of 0, 0.27, 0.55 and 2.74 mg/kg/day can be
estimated. Kidney function appeared to be compromised 1n the high group as
OlOSh -20- 07/16/87
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blood urea nitrogen and uric add were both elevated. H1ld hlstologlcal
lesions were observed In the lungs, kidneys and spleens of all treated
animals examined, most noticeably In the high group.
Interpretation of the biological significance of the hlstopathologlcal
lesions caused by sodium metavanadate In rats at vanadium equivalent doses
of 0.27 and 0.55 mg/kg/day Is complicated by the lack of lesions at com-
parable doses In lifetime studies with dietary vanadium pentoxlde In rats
(Stoklnger et al., 1953) and drinking water studies with vanadyl sulfate In
mice (Schroeder and MHchener, 1975) and rats (Schroeder et al., 1970). In
the dietary study, no hlstologlcal lesions were observed with vanadium
pentoxlde at 10 or 100 ppm vanadium (0.5 and 5.0 mg/kg/day, assuming a food
factor of 0.05). In the drinking water studies wHh vanadyl sulfate, no
hlstologlcal lesions In mice or rats were noted at 5 ppm vanadium, the only
concentration tested. These concentrations correspond to vanadium dosages
of 0.9 mg/kg/day 1n mice and 0.7 mg/kg/day In rats.
These data suggest that sodium metavanadate may be the more toxic of the
vanadium compounds tested. This Is consistent with the 100-day study using
rats where sodium metavanadate In diet at a vanadium concentration of 25 ppm
caused growth retardation and Increased mortality (Franke and Moxon, 1937).
The conservative approach to risk assessment suggests that an RfD-0 for
vanadium be derived from the Domingo et al. (1985) experiment with sodium
metavanadate, and RfDSQ values for other vanadium compounds be derived
from applicable studies of these compounds. The middle dose In the Domingo
et al. (1985) experiment, corresponding to 0.55 mg vanadlum/kg/day 1s desig-
nated a NOAEL, since the Investigators concluded that the test compound was
"generally well tolerated" at all levels of exposure and because no hlsto-
pathologlcal lesions were observed with comparable or higher doses of
0108h -21- 07/16/87
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vanadium In lifetime studies In rats and mice. An RfDSQ for vanadium of
0.006 mg/kg/day or 0.4 mg/day for a 70 kg man 1s derived by application of
an uncertainty factor of 100 to the NOAEL of 0.55 mg/kg/day. RfDSQ values
for sodium metavanadate are 0.01 mg/kg/day or 1.0 mg/day for a 70 kg human.
Since no suitable subchronlc studies were found for calculation of an
RfDSQ for vanadium sulfate and vanadium pentoxlde, the RfDQ derived from
chronic studies can be adopted as an RfOso for these compounds.
6.1.2. Inhalation (RfDSI). The subchronlc studies summarized In
Section 3.1.2. failed to Identify NOAELs or LOAELs, or were Insufficiently
reported to be useful for quantitative risk assessment. An RfDSI for
vanadium cannot be derived from the existing data.
6.2. REFERENCE DOSE (RfD)
6.2.1. Oral (RfDQ). Chronic oral studies with compounds of vanadium
Include a lifetime dietary study In rats with vanadium pentoxlde (10 and 100
ppm vanadium) (Stoklnger et a!., 1953) and lifetime drinking water studies
with vanadyl sulfate (5 ppm vanadium) 1n mice (Schroeder and MHchener,
1975) and rats (Schroeder et al., 1970). The only compound-related effects
reported were reduced levels of cystlne In the hair of rats In the dietary
study and minor serum fasting glucose and cholesterol concentration changes
1n rats In the drinking water studies. Since the biological significance of
these observations Is doubtful (fasting serum cholesterol was elevated 1n
males and depressed 1n females), all of these studies Identify NOAELs.
An RfOQ value for vanadium can be obtained from chronic drinking water
study with vanadium sulfate In mice (Schroeder and HHchener, 1975) and rats
(Schroeder et al., 1970). A NOAEL of 5 ppm corresponds to vanadium Intake
of 0.9 mg/kg bw/day In mice and 0.7 mg/kg bw/day In rats. Using an uncer-
tainty factor of 100, one can obtain an RfDQ of 0.009 mg/kg/day 1n mice
0108h -22- 07/16/87
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and 0.007 mg/kg/day In rats. If we adopt a more conservative value In rats,
the RfOQ for vanadium Is 0.007 mg/kg/day or 0.5 mg/day for a 70 kg human.
The corresponding RfOQ for vanadium sulfate Is 0.02 mg/kg/day or 1.5
mg/day for a 70 kg human. The RfDQ for vanadium pentoxlde can be obtained
from chronic dietary study using rats (Stoklnger et al., 1953). A NOAEL of
10 ppm of vanadium In diet corresponds to Intake In rats of 0.9 mg/kg bw/day
of vanadium pentoxlde. Using an uncertainty factor of 100, one can calcu-
late an RfDQ for vanadium pentoxlde of 0.009 mg/kg/day or 0.6 mg/day for a
70 kg human. An RfDQ for sodium vanadate can be obtained from the RfDSQ
by using an uncertainty factor of 10 to extrapolate from subchronlc to
chronic exposure for sodium metavanadate. This RfD0 1s then 0.001
mg/kg/day or 0.1 mg/day for a 70 kg human.
CSs have been derived for oral exposure to vanadium pentoxlde 1n two
U.S. EPA (1983b, 1985a) analyses and for vanadyl sulfate In one U.S. EPA
(1983a) analysis. The largest CS for oral exposure to vanadium pentoxlde
was 10, based on deaths observed In rats {Stoklnger et at., 1953} fed diets
containing 2000 ppm vanadium (U.S. EPA, 1983b). For vanadyl sulfate, the
highest CS was 3.8 based on minor clinical chemistry changes In rats
(Schroeder et al., 1970) exposed to 5 ppm vanadium 1n their drinking water
(U.S. EPA, 1983a). Corresponding CSs for vanadium, based on recalculation
of the MEDs corrected for vanadium rather than the compounds, are 10 and 4.5
from vanadium pentoxlde and vanadyl sulfate, respectively. A CS can also be
derived based on the lesions observed In the lungs, spleens and kidneys of
rats exposed to sodium metavanadate In the drinking water associated with a
vanadium Intake of 0.27 mg/kg/day (Domingo et al., 1985). A body weight of
0.330 kg 1s estimated from Initial body weight and weight gain data provided
by the Investigators. Be applying a correction factor of the cube root of
OlOSh -23- 07/16/87
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the ratio of rat to reference human body weight, a human MED of 3.2 mg/day
Is calculated. No uncertainty factor Is applied to expand from subchronlc
to chronic exposure (see above). The corresponding RV. Is 4.7. An RV
of 6 1s chosen to represent the lesions noted above, resulting 1n a CS for
vanadium of 28.2. The magnitude of the CS for vanadium based on sodium
metavanadate, compared with vanadium pentoxlde and vanadyl sulfate, reflects
the greater toxUHy of that compound.
6.2.2. Inhalation (RfOJ. Several human chronic occupational exposure
studies were found In the available literature (Symanskl, 1939, 1954;
Vlntenner et a!., 1955; Klvlluoto, 1981a,b); however, exposures were not
sufficiently quantltated, clinical symptoms were not evaluated, or these
studies did not define NOAELs, and consequently they are not useful for
quantitative risk assessment.
The ACGIH (1986) TLV of 0.05 mg/ma for vanadium pentoxlde dust and
fumes, based upon the studies summarized above, 1s likewise considered
Inadequate for the basis of an RfD,. An RfO, Is not derived because the
available data are Inadequate.
The U.S. EPA (1985a) derived several CSs for the exposure of humans to
atmospheric vanadium pentoxlde. The selected CS was 30.1, calculated for
persistent cough, dyspnea and wheezing (RV =7) In humans occupationally
exposed to 0.02-3.2 mg/m3 of vanadium pentoxlde for 8 years (Tebrock and
Machle, 1968). The MED was 6.0 mg/day. A corresponding MED for vanadium Is
3.4 mg/day, which corresponds to an RV, of 4.7 and a CS for vanadium of
32.9. This CS 1s chosen as most stringently representing the toxldty of
Inhaled vanadium and Indicates the greater toxldty of vanadium by the
Inhalation route compared with the oral route.
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6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. Human oral cardnogenlcHy data were not available. Animal
studies have not shown a carcinogenic response for vanadyl sulfate by the
oral route (Schroeder et a!., 1970; Schroeder and Kitchener, 1975), although
the available data are judged Inadequate to properly evaluate the carcino-
genic potential 1n animal test systems. Data were not available for other
vanadium compounds; therefore, no q,* was derived.
Vanadium pentoxlde has been approved for an Inhalation toxicology study
by the National Toxicology Program (NTP, 1986).
6.3.2. Inhalation. Stocks (1960) suggested that atmospheric exposure to
vanadium 1n combination with other pollutants may be carcinogenic to humans;
however, the available data were Inadequate to assess the carcinogenic
potential by Inhalation for vanadium alone.
0108h -25- 07/16/87
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0108h -31- 07/16/87
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0108h -32- 07/16/87
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0108h -34- 07/16/87
-------
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