v>EPA
EPA/635/R-21/077
IRIS Assessment Plan
www.epa.gov/iris
IRIS Assessment Plan for Inhalation Exposure to Vanadium and
Compounds
(Scoping and Problem Formulation Materials)
May 2021
Integrated Risk Information System
Center for Public Health and Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
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IRIS Assessment Plan for Vanadium (Inhalation)
DISCLAIMER
This document is a public comment draft for review purposes only. This information is
distributed solely for the purpose of public comment. It has not been formally disseminated by
EPA. It does not represent and should not be construed to represent any Agency determination or
policy. Mention of trade names or commercial products does not constitute endorsement or
recommendation for use.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
CONTENTS
AUTHORS | CONTRIBUTORS | REVIEWERS vi
1. INTRODUCTION 1
2. SCOPING AND INITIAL PROBLEM FORMULATION 3
2.1. BACKGROUND 3
2.2. SCOPING SUMMARY 9
2.3. INITIAL PROBLEM FORMULATION 9
2.3.1. PRELIMINARY LITERATURE SURVEY RESULTS 11
2.4. KEY SCIENCE ISSUES 22
3. OVERALL OBJECTIVE, SPECIFIC AIMS, AND DRAFT POPULATIONS, EXPOSURES,
COMPARATORS, AND OUTCOMES (PECO) CRITERIA 25
3.1. SPECIFIC AIMS 25
3.2. DRAFT PECO CRITERIA 26
REFERENCES 30
APPENDIX A. SURVEY OF EXISTING VANADIUM TOXICITY VALUES 35
APPENDIX B. LITERATURE SEARCH STRATEGIES 53
APPENDIX C. PRELIMINARY LITERATURE SEARCH AND SCREENING METHODS 56
APPENDIX D. PRELIMINARY LITERATURE SURVEY SUMMARY 58
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
TABLES
Table 1. Chemical identity and physiochemical properties of vanadium compounds potentially
relevant to inhalation exposure 5
Table 2. EPA program and regional office interest in the assessment of inhalation exposure to
vanadium and compounds 9
Table 3. Population, exposure, comparator, outcome (PECO) criteria for the inhalation exposure
to vanadium and compounds assessment 26
Table 4. Major categories of "Potentially Relevant Supplemental Material" 28
Table A-l. Sources searched for vanadium health effect reference values 35
Table A-2. Details on derivation of the available health effect reference values for inhalation
exposure to vanadium and compounds (current as of May 2020; please consult
citation source entities and other entities in Appendix A, Tables A-2 and A-3 38
Table A-3. Details on inhalation reference values from other agencies 47
Table B-l. Literature search strategies for vanadium compounds 53
FIGURES
Figure 1. IRIS systematic review problem formulation and method documents 2
Figure 2. Available health effect reference values for inhalation exposure to vanadium
pentoxide 7
Figure 3. Available health effect reference values for inhalation exposure to vanadium
compounds, excluding vanadium pentoxide 8
Figure 4. Survey of human studies that met PECO criteria by study design and health systems
assessed 13
Figure 5. Tabular summary of study designs and exposure measurements used in human studies
that met PECO criteria 14
Figure 6. Survey of animal studies that met PECO criteria by study design, species, and health
systems assessed 19
Figure 7. Summary of the vanadium compounds evaluated by study design in the available
animal studies 20
Figure 8. Preliminary summary of multi-exposure chronic animal studies 21
Figure 9. Preliminary summary of multi-exposure subchronic animal studies 22
Figure D-l. Literature survey study flow selection diagram 58
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
ABBREVIATIONS
AD ME absorption, distribution, metabolism, and excretion
ATSDR Agency for Toxic Substances and Disease Registry
CPAD Chemical and Pollutant Assessment Division
CPHEA Center for Public Health and Environmental Assessment
EPA Environmental Protection Agency
HERO Health and Environmental Research Online
IAP IRIS Assessment Plan
IARC International Agency for Research on Cancer
IRIS Integrated Risk Information System
MeSH Medical Subject Headings
MOA mode of action
NTP National Toxicology Program
OAR Office of Air and Radiation
ORD Office of Research and Development
PBPK physiologically based pharmacokinetic
PECO populations, exposures, comparators, and outcomes
PK pharmacokinetic
POD point of departure
RfC reference concentration
RfD reference dose
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
AUTHORS | CONTRIBUTORS | REVIEWERS
Assessment Team
Suryanarayana Vulimiri, Ph.D. (co-Assessment Manager) U.S. EPA/ORD/CPHEA/CPAD
Kathleen Newhouse, M.S. (co-Assessment Manager)
Erin Yost, Ph.D.
David Farrar, Ph.D.
Barbara Glenn, Ph.D.
Elizabeth Radke, Ph.D.
Executive Direction
Wayne E. Cascio, M.D. (CPHEA Director) U.S. EPA/ORD/CPHEA
Samantha Jones, Ph.D. (CPHEA Associate Director)
Kristina Thayer, Ph.D. (CPAD Director)
James Avery, Ph.D. (CPAD Associate Director)
Andrew Kraft, Ph.D. (CPAD Senior Science Advisor)
Paul White, Ph.D. (CPAD Senior Science Advisor)
Janice Lee, Ph.D. (CPAD Toxic Effects Assessment Branch Chief)
Ravi Subramaniam, Ph.D. (CPAD Toxic Effects Assessment Branch Chief)
Contributors and Production Team
Ryan Jones
HERO Director (U.S. EPA/ORD/CPHEA/CPAD)
Vicki Soto
Project Management Team (U.S. EPA/ORD/CPHEA/CPAD)
Dahnish Shams
Project Management Team (U.S. EPA/ORD/CPHEA/CPAD)
Brittany Schulz
Reference Value Array Support (ORAU)
Christine Cai
Systematic Review Support
U.S. EPA/ORD/CPHEA/CPAD)
Channa Keshava
Systematic Review Support
US. EPA/ORD/CPHEA/CPAD)
Paul Reinhart
Systematic Review Support
U.S. EPA/ORD/CPHEA/CPAD)
Carlye Austin
Systematic Review Support
ICF)
Robyn Blain
Systematic Review Support
ICF)
Katherine Duke
Systematic Review Support
ICF)
Alexandra Goldstone
Systematic Review Support
ICF)
Cynthia Lin
Systematic Review Support
ICF)
Alexander Lindahl
Systematic Review Support
ICF)
Shannon McGinnis
Systematic Review Support
ICF)
Amanda Ross
Systematic Review Support
ICF)
Kelly Shipkowski
Systematic Review Support
ICF)
Courtney Skuce
Systematic Review Support
ICF)
Parnian Soleymani
Systematic Review Support
ICF)
Carmen del Castillo
Systematic Review Support
CSU, East Bay, CA)
Raymond Tu
Systematic Review Support
UNC, Chapel Hill, NC)
This document is a draft for review purposes only and does not constitute Agency policy.
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1. INTRODUCTION
The Integrated Risk Information System (IRIS) Program is undertaking an assessment of the
health effects from inhalation exposure to vanadium and compounds. The IRIS Program announced
the initiation of this assessment in December 2019. An assessment of oral exposure to vanadium and
compounds was identified as an Environmental Protection Agency (EPA) priority in December
2018 fhttps://www.epa.gov/iris/iris-program-outlook) and will be performed separately from the
assessment of inhalation exposure
(https://cfpub.epa.gov/ncea/iris drafts/recordisplay.cfm?deid=348792).
IRIS assessments provide high quality, publicly available information on the toxicity of
chemicals to which the public might be exposed. These assessments are a critical part of the
scientific foundation for decisions made in EPA program and regional offices to protect public
health. IRIS assessments also are used by states and local health agencies, other federal agencies,
international health organizations, and other external stakeholders.
As part of the initial steps in assessment development, the IRIS Program undertakes scoping
and initial problem formulation activities. During scoping activities, the IRIS Program consults with
EPA program and regional offices to identify the nature of the hazard characterization needed, the
most important exposure pathways, and the level of detail required to inform Agency decisions. A
broad, preliminary literature survey might also be conducted to assist in identifying the extent of
the evidence and health effects that have been studied for the chemical of interest. Based on the
preliminary literature survey and the scope defined by EPA, the IRIS Program undertakes problem
formulation activities to frame the scientific questions that will be the focus of the assessment. A
summary of the IRIS Program's scoping and problem formulation conclusions are contained in the
IRIS Assessment Plan (IAP).
The IAP is followed by development of a Systematic Review Protocol, which presents
detailed methods for conducting the full systematic review and dose-response analysis, including
any adjustments made to the IAP in response to public input The IAP describes what will be
assessed, and the chemical-specific protocol describes how the assessment will be conducted.
Figure 1 displays the context of the IAP and Systematic Review Protocol in the systematic review
process.
This document is the draft IAP for inhalation exposure to vanadium and compounds—a
summary of the IRIS Program's scoping and initial problem formulation conclusions. It describes
the Agency need for the assessment; objectives and specific aims of the assessment; draft
populations, exposures, comparators, and outcomes (PECO) criteria that outline the evidence
considered most pertinent to address the specific aims of the assessment; and identifies key areas
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
of scientific complexity. Brief background information on uses and potential for human exposure is
provided for context
IRIS Handbook: Standard operating procedures and considerations
Scoping
Systematic
Review Protocol
Literature
Inventory
Study
Evaluation
Data
Extraction
Evidence Derive Toxicity
Integration Values
Initial Probler
Formulation
Assessment
Plans:
What the
assessment
will cover
Literature Refined Organize Evidence Analysis Select and Model
Search Analysis Plan Hazard Review and Synthesis Studies
Protocols: How the assessment will be conducted
- Assessment
/ Developed
Figure 1. IRIS systematic review problem formulation and method
documents.
This document is a draft for review purposes only and does not constitute Agency policy.
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2. SCOPING AND INITIAL PROBLEM FORMULATION
2.1. BACKGROUND
The focus of this document is on inhalation exposure to vanadium and compounds and its
potential impacts on human health. Oral exposure to vanadium compounds is currently under
evaluation in a separate assessment
fhttps://cfpub.epa.gov/ncea/iris drafts/recordisplay.cfm?deid=3487921.
Vanadium is a transition metal that occurs naturally in Earth's crust and is a component of
various minerals and most ores, tars, coal, and petroleum crude oils fWHO. 19881. Natural sources
of vanadium in the air include continental dust, marine aerosol, and volcanic emissions (ATSDR.
20121. Vanadium has been reported to have natural background concentrations in the air ranging
from tenths of a nanogram to a few nanograms (WHO. 20001. The use of heavy oils and bitumen
from tar sands (which are richer in vanadium than conventional oil) and the use of vanadium in
industrial applications (e.g., steel production, vanadium redox-flow batteries, and catalytic
converters) could contribute to the release of vanadium into the environment fSchlesinger etal..
2017: ATSDR. 20121. Fossil fuel combustion is thought to be the major anthropogenic source of
vanadium to the atmosphere (Schlesinger etal.. 2017: ATSDR. 20121. with vanadium pentoxide
found adsorbed onto particulate matter (PM) as a result (Fortoul etal.. 20141. In addition,
occupational exposure to vanadium occurs through the inhalation of dust generated during
vanadium processing and residual oil fly ash during cleaning of oil-burning boilers and furnaces.
Residual oil fly ash is a mixture of different vanadium compounds and other metals and
components of PM (Hauser etal.. 19951.
Vanadium has a complex chemistry, existing in the environment with three common
oxidation states (+3, +4, +5) (Gustafsson. 20191. Among them, vanadium pentoxide (V2O5), a +5
vanadium species, is the most common form of vanadium used for industrial applications such as
metal alloy production and catalytic processes. Evidence from one study suggests thatpentavalent
vanadium, in particular vanadium pentoxide, also can be among the vanadium compounds present
in PM emitted from diesel engines and in PM in urban atmospheric aerosols (Shafer etal.. 20121. In
crude oils, vanadium is present as an organometallic complex, and upon burning in boilers or
furnaces, vanadium is left behind as vanadium pentoxide in the fly ash (IPCS. 20011. Other than
vanadium pentoxide, specific vanadium compounds relevant to environmental inhalation have not
been well characterized.
Following inhalation, at least some vanadium appears to be absorbed in the lungs, as seen
by an increase in blood and urine vanadium levels in experimentally or occupationally exposed
subjects (ATSDR. 20121. Most occupational exposure studies, however, do not identify the form of
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
vanadium compounds to which workers were exposed. Important to note is that vanadium
speciation is a complex function of factors such as pH, redox potential, and vanadium concentration,
which could presumably shift upon inhalation and subsequent absorption. In the aqueous phase,
vanadate species (+5) predominate under oxic conditions and high pH, while vanadyl (+4) occurs
under suboxic conditions and lowpH and trivalent vanadium (+3) occurs under anoxic conditions
(Gustafsson. 2019: Huang et al, 20151. Factors such as pH, local availability of reducing equivalents
[e.g., glutathione-sulfhydryl (SH), nicotinamide adenine dinucleotide (NADH)], and complexation
with biomolecules might cause speciation of vanadium and also might cause it to undergo redox
cycling in the body fNTP. 2008: Bvczkowski and Kulkarni. 1996: Nielsen. 19951.
Existing human health reference values for inhalation of vanadium from federal, state, and
international agencies are depicted, respectively, for vanadium pentoxide and vanadium
compounds (excluding vanadium pentoxide), in Figure 2 and Figure 3 (see Table A-2 and Table A-3,
for a tabular summary, including derivation details; currentas of May 2020). No inhalation
reference concentration (RfC) exists in IRIS. An IRIS assessment addressing inhaled vanadium
pentoxide was developed fU.S. EPA. 20111 but not finalized (see:
https://cfbub.epa.gov/ncea/iris2/chemicalLanding.cfm7substance nmbr=1251. The IRIS Program
published a health effects assessment of vanadium and compounds in 1987 that included a
reference dose (RfD) but not an RfC. EPA's Provisional Peer-Reviewed Toxicity Values (PPRTV)
program developed two assessments of vanadium and compounds: one on vanadium pentoxide
alone fU.S. EPA. 20081 and one on vanadium and its soluble inorganic compounds other than
vanadium pentoxide (U.S. EPA. 20091. The 2008 PPRTV assessment identified inflammation of the
bronchoalveolar region (respiratory effects) as the most sensitive endpoint for inhaled vanadium
pentoxide on the basis of a 16-day exposure study in female rats conducted by the National
Toxicology Program (NTP. 20021: a subchronic provisional (p)-RfC of 0.0001 mg/m3 also was
derived. A chronic p-RfC of 0.000007 mg/m3 or 7E-06 mg/m3 was derived on the basis of
nonneoplastic lesions of the respiratory tract in female rats from the 2002 NTP 2-year vanadium
pentoxide exposure study flJ.S. EPA. 20081. The 2008 PPRTV assessment of vanadium pentoxide
(U.S. EPA. 20081 also concluded that the available evidence for vanadium pentoxide inhalation
exposure is suggestive of carcinogenic potential under the 2005 Guidelines for Carcinogen Risk
Assessment fU.S. EPA. 20051 and derived an inhalation unit risk of 8.3 (mg/m3)-1 on the basis of the
dose-response relationship for alveolar/bronchiolar neoplasms (adenoma and carcinoma) in mice
in the 2-year NTP carcinogenicity study (NTP. 20021. The evidence for the mode of action (MOA)
for vanadium pentoxide tumorigenicity is insufficient, but data provide some support for a
mutagenic MOA and an MOA dependent on cellular cytotoxicity and reparative regeneration fU.S.
EPA. 20081. The 2009 PPRTV assessment (U.S. EPA. 20091 found no human or animal inhalation
studies were available to derive subchronic and chronic p-RfCs or evaluate potential
carcinogenicity for soluble inorganic vanadium compounds other than vanadium pentoxide.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Table 1. Chemical identity and physiochemical properties of vanadium compounds potentially relevant to
inhalation exposure
Name
Elemental
vanadium
Bismuth
orthovanadate
Sodium
orthovanadate
Vanadium
pentoxide
Sodium
metavanadate
Ammonium
metavanadate
Vanadium
dioxide3
CASRN
7440-62-2
14059-33-7
13721-39-6
1314-62-1
13718-26-8
7803-55-6
12036-21-4
DTXSIDb
2040282
20893971
2037269
2023806
3044336
1052533
5065194
Structure
V
3+
Bi
0
1
0= —0
i
cr
Na*
cr
\ .,0
Na*
0' s
O
Oxidation
state
0
+5
+5
+5
+5
+5
+4
Molecular
weight
(g/mol)
50.942
323.918
183.907
181.878
121.928
116.978
82.94
Molecular
formula
V
Bi04V
Na3V04
V2O5
NaVOs
NH4VO3
VO2
Selected
Synonym(s)
Vanadium
Bismuth vanadate(V)
(BiVCM); bismuth(3+)
tetraoxidovana-
date(3"); bismuth
vanadium oxide;
vanadic acid; bismuth
vanadate (BiVCU);
bismuth vanadate
yellow; C.I. Pigment
Yellow 184;
Hostaperm Oxide
Trisodium
tetraoxidovana-
date(3"); sodium
vanadium oxide;
trisodium vanadate;
sodium vanadate(V);
vanadic acid,
trisodium salt
Vanadium oxide; mu-
oxido[tetrakis(oxido)]
divanadium;
divanadium
pentoxide; vanadic
anhydride; vanadin(V)
oxide; vanadium(V)
oxide
Sodium vanadate;
sodium
trioxidovanadate(1_);
sodium vanadium
oxide; sodium
vanadium trioxide;
vanadic acid,
monosodium salt;
sodium vanadate(V)
Ammonium
trioxovanadate(1_);
ammonium
trisoxidovanadate(1_);
ammonium
monovanadate;
ammonium
vanadate(V); vanadic
acid, ammonium salt;
ammonium vanadium
oxide; ammonium
vanadium trioxide
Bisoxidovanadium;
dioxido de vanadio;
dioxyde de vanadium;
divanadium
tetraoxide;
divanadium tetroxide;
vanadium (IV) oxide;
vanadium dioxide;
vanadium(IV) oxide
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Name
Elemental
vanadium
Bismuth
orthovanadate
Sodium
orthovanadate
Vanadium
pentoxide
Sodium
metavanadate
Ammonium
metavanadate
Vanadium
dioxide3
Yellow BV 01;
Irgacolor Yellow 2GTM
Water
solubility
(mol/L)b
"
"
"
"
"
"
1.94 x 102
Melting
Point (°C)c d
1.90 x 103
500°
858
690
630
-
243
Boiling
Point (°C)C
3.00 x 103
-
-
1.75 x 103
-
-
564
Vapor
Pressure
(mmHg)c
aFor vanadium dioxide, the values are predicted values from EPA's CompTox Chemicals Dashboard.
bDTXSIDs are unique substance identifiers used for curation by the EPA's Distributed Structure-Searchable Toxicity (DSSTox) project.
Experimental average values for physiochemical properties are shown here. Median values and ranges for physiochemical properties are also provided on
EPA's CompTox Chemicals Dashboard at httpsi//comptox.epa.gov/dashboard/. If no experimental values were available on EPA's CompTox Chemicals
Dashboard, is shown.
dMelting
point data available from this site: littpsi//www.cliemicalbook.coni/CliemicalProdyctProperty EN CB2331330.htm.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
100.0
too
1.0
m
.£ 0.1
~i
E
c 0.01
0
38
1
fc 0.O01
c
0]
o
o 0.0001
u
0.00001
0 000001
0.0000001
Vanadium Pentoxide Inhalation Reference Values
May Z020
ACUTE
k MOSH IOI H't
Q 4 ^AC-1
~ mHA-Dirtnj iVjQ, dudj'
0 OSMA-CiHlum lume)*
• CA-REL <1 (If t
Ortwr Sirtto Vkfcj*
[ Qttwr St*It Vj1u» | B a f
ATSDfi-MRL il-Udlt
EJ fOtlw* Sm> V tyr)t
j Ottltr Stmt V4ilu»T |
EPAjFPRTV P-RfC >yfJT u
5
EPA'PPRTV p-RfC (Subcftron ic) ^
- EPAjPPRTV p-RfC (Chronic) f
z
o
¦R1VM pTCAt o
Other Stale Value
PPRTV Cancer Risk Range
100.000 1,000,000
* Indicates an occupational value; expert judgement necessary prior to applying these values to the general public,
t Indicates a value that applies to multiple vanadium compounds, including vanadium pentoxide.
Figure 2. Available health effect reference values for inhalation exposure to
vanadium pentoxide.
This includes values applying to vanadium pentoxide; for details, see Table A-2 and Table A-3.
Abbreviations: ACGIH = American Conference of Governmental Industrial Hygienists; ATSDR = Agency for Toxic
Substances and Disease Registry; CA-REL = California reference exposure level; EPA = Environmental Protection
Agency; IDLH = immediately dangerous to life or health; MRL = minimal risk level; NIOSH = National Institute for
Occupational Safety and Health; OSHA = Occupational Safety and Health Administration; PAC = Protective Action
Criteria; PEL = permissible exposure level; PPRTV = Provisional Peer-Reviewed Toxicity Value; pTCA = provisional
tolerable concentration; REL = recommended exposure limit; p-RfC = provisional reference concentration;
RIVM =
; TLV = threshold limit value; V2O5 = vanadium pentoxide.
This document is a draft for review purposes only and does not constitute Agency policy,
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IRIS Assessment Plan for Vanadium (Inhalation)
Vanadium Inhalation Reference Values
1.000.0
100.0
10.0
1.0
0,01
0.001
ACUTE
~ PA&-1 £J|) s
es
CtSHAPIl |f«V. tWAV
'jinjiH riti 'i
PftP7lKllCI«SV>
MAC* iK.M) 4g y W»A»SV>
$- PAC-7 (Vdi«Vt*' PAG-2 (0,&V>
0.1 !F«-1 iVOCM
3> F»PZ
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2.2. SCOPING SUMMARY
During scoping, the IRIS Program met with EPA program and regional offices that had
interest in an IRIS assessment for inhalation exposure to vanadium and compounds to discuss
specific assessment needs. Table 2 summarizes input from this outreach. EPA's Office of
Transportation and Air Quality within the Office of Air and Radiation (OAR) nominated vanadium
compounds (including vanadium pentoxide) for an inhalation exposure assessment under the IRIS
Program. Vanadium has been used as a metal catalyst to control emissions from diesel engines
employed in mobile sources such as on-highway heavy-duty trucks, nonroad equipment, or marine
vessels. Under certain conditions, the use of vanadium in diesel engine emission control devices
can result in the potential for exposures to vanadium compounds, such as vanadium pentoxide. A
vanadium (inhalation) assessment could therefore help inform decisions about potential health
risks from the use of vanadium in these emission control devices.
Table 2. EPA program and regional office interest in the assessment of
inhalation exposure to vanadium and compounds
EPA program
or regional
office
Oral
Inhalation
Statute/Regulation
Anticipated uses/Interest
Office of Air
and Radiation
~
Clean Air Act
Vanadium and compounds are mobile source air
toxics. Toxicological information developed for this
assessment may be used to inform risk
management decisions.
2.3. INITIAL PROBLEM FORMULATION
Systematic review methods were used to identify a preliminary literature inventory for
vanadium and compounds. The ATSDR Toxicologicctl Profile for Vanadium (AT SDR. 2012) was
selected as the starting point for the literature search, because it is the most recent review of health
effects of vanadium and compounds published by a U.S. federal agency. Database searches were
initially conducted on March 28, 2019, by an EPA information specialist using three online
databases (PubMed, Web of Science, Toxline)1 and then repeated on March 9, 2020, to identify
records that had been published since the release of the 2012 ATSDR Toxicological Profile for
Vanadium. The start date for the literature search was selected as 2010 to ensure records
published near the last literature search date for the citations in the ATSDR document were
iThe Toxline database was migrated to PubMed prior to the March 2020 literature search update, so the
Toxline search was conducted only in March 2019.
This document is a draft for review purposes only and does not constitute Agency poiicy.
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captured.2 This literature search strategy is designed to be broad, but like any search strategy,
studies might be missed (e.g., studies published before 2010 thatwere notincluded in the ATSDR
document; cases where the specific chemical is not mentioned in the title, abstract, or keyword
content; or "gray" literature not indexed in the databases listed above). Thus, when additional
references that appeared to meet PECO criteria were identified through curation of references cited
in reviews or other assessments, these references were annotated with the source of the record and
screened using the same methods applied to the rest of the literature inventory. The IRIS Program
also encourages the public to identify any additional missing studies. References should be
submitted to the docket in the form of a public comment. For more information, visit
regulations.gov or the IRIS website (https://www.epa.gov/irisl. All references from the 2012
ATSDR Toxicological Profile for Vanadium, literature searches, and other relevant assessments were
extracted by an EPA information specialist and stored in the Health and Environmental Research
Online (HERO) database ffattpsi//hero.epa.gov/hero/index.cfiii/proiect/Dage/Droiect id/23571.3
Draft PECO criteria (see Table 5) were used to guide screening to identify relevant literature.
Studies that met PECO criteria were summarized briefly using DistillerSR,4 and studies that
did not meet PECO criteria but contained potentially relevant supplemental material were
inventoried. For animal studies, the following information was captured: chemical form, study type
(acute, short term, subchronic, chronic, reproductive, developmental), duration and timing of
treatment, route, species, strain, sex, dose or concentration levels tested, dose or concentration
units, health system and specific endpoints assessed, and a brief summary of findings at the health
system level [null, no-observed-effect level (NOEL), or lowest-observed-effect level (LOEL) based
on author-reported statistical significance with an indication of which specific endpoints were
affected]. For human studies, the following information was summarized: chemical form;
population type (e.g., general population-adult, occupational, pregnant women, infants and
children) and characteristics (e.g., sex ratios) with a short free text description of study population;
study type (e.g., controlled trial, cross-sectional, cohort, case-control); major route of exposure (if
known) and a description of how exposure was assessed; health system and specific outcome(s)
assessed; and a summary of findings at the health system level based on author-reported statistical
significance (null or an indication of any associations found and a description of how the exposure
was quantified in the analysis). These study summaries are referred to as preliminary literature
surveys and are presented using Tableau visualization software (httpsi//www, table an .com/1 in
this IAP.
2Personal correspondence with ATSDR indicated the final literature update for the 2012 Toxicological Profile
for Vanadium was conducted in August 2011.
3EPA's HERO database provides access to the scientific literature behind EPA science assessments. The
database includes scientific references and data from the peer-reviewed literature used by EPA to develop its
health assessment documents.
4DistillerSR is a web-based systematic review software used to screen studies available at
https://www.evidencepartners.com/products/distillersr-systematic-review-software.
This document is a draft for review purposes only and does not constitute Agency policy.
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
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IRIS Assessment Plan for Vanadium (Inhalation)
These methods were implemented in accordance with EPA Quality Assurance policies and
procedures [Quality Policy Procedures5 and CIO 2105.0 fformerlv 5360.1 A216]. Detailed literature
search strategies (Appendix B), literature search and screening methods (Appendix C), and a
literature survey study flow diagram (Appendix D) are provided in the appendices at the end of this
document, and the preliminary literature survey results are described in the following section. The
results obtained from this systematic compilation of the evidence helped inform the specific aims
and key science issues that will be the focus of the assessment.
2.3.1. PRELIMINARY LITERATURE SURVEY RESULTS
The preliminary literature search and screening process identified 97 studies that met
PECO criteria (n = 67 human studies, n = 30 animal studies), and a total of 1,249 studies were
tagged as potentially relevant supplemental material. No physiologically-based pharmacokinetic
(PBPK) models for vanadium or vanadium compounds were identified.
Human studies: A preliminary survey of study designs and health systems assessed in the
human studies that met PECO criteria is provided in Figure 4 with a more detailed summary
provided in Figure 5. The literature search identified 67 human studies including 2 case
reports/case series, 15 case-control studies, 23 cohort studies, 1 controlled trial study, 23 cross-
sectional studies, and 3 ecological studies. Among the cohort studies, four studies involve pregnant
women (Figure 4).
The populations evaluated in the available human studies were general population,
occupational, children, infants, and pregnant women. The predominant health outcomes
investigated included respiratory, cardiovascular, nervous system, and immune system effects.
Fewer studies evaluated developmental, dermal, hematological, hepatic, reproductive, renal, and
endocrine endpoints. Six human studies evaluated cancer, including a cohort study and five case-
control studies.
Regarding exposure classification, the epidemiological literature includes several studies
with exposure to vanadium pentoxide or vanadium (form unknown) measured in the air or in
workers with occupational exposure as boilermakers or in vanadium-containing steel production
facilities (Figure 5). Seven studies reported air levels of vanadium pentoxide and 20 studies
reported vanadium (form unknown) as vanadium dust (2 studies) or as part of PM (12 studies). In
the occupational exposure category, seven studies reported on vanadium pentoxide while nine
studies involved exposure to vanadium (unknown form).
In addition, the literature search identified 40 observational epidemiological studies, which
evaluated the association of health outcomes with total vanadium from biomonitoring, in which the
route of exposure and specific vanadium form were unknown. This included 35 studies (15 case-
5U.S. Environmental Protection Agency Environmental Information Quality Procedures (CIO 2105-P-01.1):
hP^s://www.epa.gov/sites/production/files/2021-04/documents/environmental information quality procedure.pdf.
6U.S. Environmental Protection Agency Environmental Information Quality Policy (CI02105.1):
https://www.epa.gov/sites/proditction/files/2021-04/docitments/environmental information quality poliey.pdf.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
1 control, 9 cross-sectional, and 11 cohort) in which vanadium exposure was evaluated using
2 biomonitoring of blood, urine, hair, semen, cerebrospinal fluid, saliva, nasal lavagate (lavage) or
3 nails. Overall, of the 67 human studies identified, 9 reported presumed exposure to vanadium
4 pentoxide and 58 reported exposure to vanadium (form unknown).
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
infants
children
pregnant
women
cohort
general population
occupational
Health System
case-
control
cohort
ecological
case-
control
cohort
cross-
sectional
case-
control
controlled cross-
cohort
Trial sectional
ecofogtcsl
case
report,/
case series
case" u ^
. cohort
control
cross-
sectional
Grand
Total
Cancer
1
1
6
Cardiovascular
1
3 1
mzm
1
1
6
19
Dermal
2
2
Developmental
1
4-
1 i
1
7
Endocrine
1
1
Gastrointestinal
1
3
4
Hematologic
1
1
3
5
Hepatic
3
3
Immune
1
1
2
111
1
5
13
Metabolic
1
2
1
4
Nervous
1
3
1
1
5
14
Ocular
2
2
Renal
1
1
2
4
Reproductive
2
1
3
Respiratory
2
113
2
6
20
Systemic/Whole Body
1
1
2
4
Other
1
1
2
Grand Total
1
4
1
3
3
2
4
11
6 19
2
2
1 6
12
67
Figure 4. Survey of human studies that met PECO criteria by study design and health systems assessed.
The numbers indicate the number of studies that investigated a particular health system, and not the number of studies that observed an association with
vanadium exposure. If a study evaluated multiple health outcomes or multiple study designs, it is displayed multiple times. Hence, the totals do not
necessarily indicate the number of individual studies for a given health outcome. The interactive version of the figure, including more details on the study
designs and results, is available at the following URL:
https://public.tableau.com/views/VanadiumInhalationIAPVisualizations/ReadMe?:language=en&:displav count=v&:origin=viz share link.
This document is a draft for review purposes only and does not constitute Agency policy,
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IRIS Assessment Plan for Vanadium (Inhalation)
/ Biomonitorirvg Matrix
£
Cnemicai
Heafth System Name Popuiation
Cardiovascular
censi-a| population
Study Design Sex
esse- control both
I'lV:-)'"-
csse- control both
case- control msSe
cower both
- -r-. ----- • --.
biomomtcring
biomemtonr-g
biomon storing
air
bsomonitoring
Reference
Gomez-Tomes et 3L 2019
Leeetai., 2020
O'Brie-'i etat., 201S
Tans etas,, £012
Weinmay;- et si,, 2015
Ssi eta'., 20 IS
SkainyetsL, 2017b
Esdsloni et si.. 2017
Dai etal „ 2016
Domingo-Reiioscsetal., 2019
Jacobs et at .,2012
Subranmsnyam et si., 201S
Wuet si ..2018
SeHetai.,. 2014
3 I
s s
tcmo?t male
cross- sections! both
Vanadium genera! population
pentoxi de occupations^
e report/ case
vanadium occupational-
Vanadium occupations!
psito-ude
cross-sections? not reported
cross- sectior-sl male
Developmental V'snadst/m
Legenc E-ursjieMea.i.
occupations!
Sic-monitoring
occupations!
fciopnonitoring
sccupationsi
sir
ocaspstioiai
bi'omonitoring
biefmonitoring
p'-eci ^ant women
ecciogical born
coroT female
- • • - :
Ye etal., 2013
Msgari e-aL, 2D02
2nsng et sf.., 2Q14
Dai etsl.,2019
Vintirvnsretal., 1SS5
Vintinneret as.. 1955
Zenzand Beg. 1957
Kiviluoto et sL.1981
Lewis, 1S59
Sjo&ecg, 1951
Kiviluoto et sL, 13S1
Lewis.. 1S59
Sjobe-fg, 1S51
Kiviluoto et si ,1981
Lewis, 1959
Sjoberg, 1951
Wilbams. 1852
Wiihsms,. 195Z
Williams, 1S52
Vintinneret s(., 1SS5
V'intinner et at.. 1955
Sjoberg, 1.951
SjDberg, 1351
Sjoberg, 1951
Jisfiaetal., 2G1S
met 51.. ZOj.7
f1L,'S"3!.. ZCUB
I'C.'etrl lC_r
E::i etc 2?_-
Sun stSf., 20l9
Figure 5. Tabular summary of study designs and exposure measurements used in human studies that met
PECO criteria.
In the figure, for studies where vanadium is indicated, the actual form is unknown. The interactive version of the figure, including more
details on the study designs and results, is available at the following URL:
https://public.tableau.com/views/Vanadiumlnhalation IAPVisualizations/ReadMe?:language=en&:displav count=v&:origin=viz share link.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Exposure Measurement / Biomonitorina Matrix
Chemical Exposure
Health System Name Population Study Design Sex Measurement
Endocrine Vanadium pregnant women cohort female biomomtonng
Gastrointestinal Vansdium occupational cross- sections! not reported sir
occupations!
Vanadium occupational cross-sections! mate sir
pentosids
occupational
hiomomtoring
c^c.eoorr..- case n-..?;* sr
Hematologic 'vanadium children cross- secti-onsi both biomonitoring
;- - 5 7- r * *. ------ =--- -. ••---• ........
occupations) cross-sections! not reocwted sif
occupations!
VanBdi-m occupational cross- sectional male sir
pentoxide
Reference
Sunetsl.., 2019
Vintinneret BI..1955
Vintinneretsl.; 1355
_"i'3
Sjoberg, 1951
.r .s::
Sjoberg, 1951
Lewis, 1959
Sjoberg. 1951
Will-isms,. 1952
•
Williams, 1SS2
Lopez-Roc-rigueset.al.
Skainy et si.. Z017b
Vsntsnner eta!., 1955
V'intinneretsl., 1955
Kiviluotoet si-., 1381
SO O J3
_I IT
Hepat":
general population
occupational
cono-n:
cross- sectional
:
;:0'"0'r:
conort
-cross-sectional
both
both
mate
both
both
--- -
. . .
. : t: *:
occupational
biomonitoring
slr
occupations!-
Va nadium general- aooutatian controlled trial
... ....... . ... .
biomonitcnng
not reocted sir
... ... ...
male air
occupations!
biomonitoring
Sodr j Pollitt et si.,
-t: - - «
:
Dai et-at.,.2016
Jacobs et at., 2012
Lees, 1S80
Lees, 1980
Kiviluotoet at., 2979
Kiv iluoto et si... 1979
Woodin et aL 1993
WoodinefcsL, 199S
V'intinrteretai.. 1955
Vintmner et s!„ 1S-5S'
Zen? and Seng, 19 67
t-=
Sjoberg, 1951
Kiviluotoet si.., 1981
: . .r ;
Kiviluoto at si .,1931
Sjoberg, 195.
Legend: Exposure Measurement!
I occupations!
| bicmonitonng
Figure 5. continued.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Exposure Measurement/ Biomonitoring Matrix
Chemical
Exposure
1
J
1 *
= i I !i |
Health System
Name
Population
Study Design
Sex
Measurement
Reference
•5
£
3
^ i
£ S % Sc J
Metabolic
Vanadium
pregnant women
cohort
female
biomonitoring
Wang etal., 2019
¦
general population
case-control
both
biomonitoring
Lietai.. 2017
Wang etal., 2014
¦
¦
Vanadium
occupational
cross- sectional
male
air
Kiviluoto et al., 1931
¦
pentoxide
occupational
Kiviluoto etal., 1931
¦
biomonitoring
Kiviluoto et al., 1981
¦
¦
Nervous
Vanadium
children
case-control
both
biomonitoring
Alqhazo and Rasnaid, 2018
Blaurock-Busch etal., 2012
¦
¦
male
biomonitoring
Tinkovet al., 2019
¦
¦
cohort
both
biomonitoring
SKalny et al., 2017a
¦
general population
case-control
both
biomonitoring
Kihiraetal., 2015
¦
female
biomonitoring
Nayioretal., 1934
¦
not reported
biomonitoring
Roos etal.. 2013
¦
cross- sectional
both
biomonitoring
Paglia etal., 2016
¦
occupational
cross-sectional
male
occupational
Lietai., 2013
¦
not reported
air
Vintinneret al., 1955
¦
occupational
Vintinneretal., 1955
¦
Vanadium
occupational
cross- sectional
male
air
Lewi 5,1959
¦
pentoxide
Sjoberg. 1951
¦
occupational
Barth et al., 2002
Lewis, 1959
5joberg, 1951
¦
¦
¦
biomonitoring
Lewis, 1959
Sjoberg. 1951
¦
¦
¦
case report/ case
male
air
Williams, 1952
¦
series
occupational
Williams, 1952
¦
biomonitoring
Williams, 1952
¦
Ocular
Vanadium
occupation at
cross- sectional
not reported
air
Vintinneretal., 1955
¦
occupational
Vintinneretal., 1955
¦
Vanadium
occupational
cross- sectional
male
air
Lewis, 1959
¦
pentoxide
occupational
Lewi 5,1959
¦
biomonitoring
Lewis, 1959
¦
Otter
Vanadium
general population
cross- sectional
both
biomonitoring
inonuetal.,2019
¦
occupational
cross- sectional
not reported
air
Vintinneretal., 1955
¦
occupational
Vintinneretal., 1955
¦
Renal
Vanadium
general population
cohort
both
biomonitoring
Liu et al., 2019
¦
Vanadium
occupational
cross- sectional
male
air
Kiviluoto et al., 1981
¦
pentoxide
5joberg, 1951
¦
occupational
Kiviluoto etal, 1981
Sjoberg, 1951
¦
¦
biomonitoring
Kiviluoto etal., 1981
Sjoberg, 1951
¦
¦
¦
¦
case report,/ case male
air
Williams, 1952
¦
series
occupational
Williams, 1952
¦
biomonitoring
Willsams, 1952
Legend: Exposure Measurement
| air
| occupational
biomonitoring
Figure 5. continued.
This document is a draft for review purposes only and does not constitute Agency policy,
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IRIS Assessment Plan for Vanadium (Inhalation)
Exposure Measurement/ Biomonitoring Matrix
Chemical
Name
Exposure
Measurement
Reproductive
Vanadium
pregnant women
cohort
female
biomonitoring
Hu et el., 2017
Jin etal., 2018
¦
¦
general population
cross-sectional
male
biomonitoring
Wangetal., 2018
¦
¦
Respiratory
Vanadium
children
cohort
both
air
Gehring et al., 2015
Patel etal., 2009
¦
¦
general population
cohort
male
air
Wu etal, 2013
¦
cross- sectional
both
air
Lagorio et a1,2006
¦
biomonitoring
Li etal., 2019
¦
not reported
air
Bell etal., 2014
¦
occupational
cohort
male
arr
Hauseretal., 1995a
Woodinetal., 1999
Woodin etal., 2000
¦
¦
¦
occupational
Hauseret al., 1995a
Lees, 1980
Woodinetal., 1999
Woodinetal., 2000
¦
¦
¦
¦
biomonitoring
Kim etal., 2003
Lees. 1980
¦
¦
cross- sectional
male
air
Kiviluoto et al.,1979
¦
occupational
Kiviluoto et al., 1979
¦
not reported
air
Vintinneretal., 1955
¦
occupational
Vintinneretal., 1955
¦
Vanadium
general population
controlled triat
male
air
Zenzand Berg, 1967
¦
pentoxide
occupational
cross- sectional
male
sir
Hauser etal., 1995b
Lewis, 1959
Sjoberg, 1951
¦
¦
¦
occupational
Hauser et al., 1995b
Kiviluoto, 1980
Lewis, 1959
Sjoberg, 1951
¦
¦
¦
¦
biomonitoring
Lewis, 1959
5joberg, 1951
¦
¦
¦
case report/ case
male
air
Irsioleretal., 1999
¦
series
Williams, 1952
¦
occupational
Williams, 1952
¦
biomonitoring
irsigleretal.. 1999
Williams, 1952
¦
¦
Systemic/Whole
Vanadium
general population
cohort
both
air
Badalor.i etal., 2017
¦
Body
occupational
cross-sectional
not reported
air
Vintinner et a)., 1955
¦
occupational
Vintinneretal., 1955
¦
Vanadium
occupational
cross- sectional
male
air
Sjoberg, 1951
¦
pentoxide
occupational
Sjoberg, 1951
¦
biomonitoring
Sjoberg. 1951
¦
¦
case report/ case
male
air
Williams, 1952
¦
series
occupational
Williams, 1952
¦
biomonitoring
Williams. 1952
¦
Legend: Exposure Measurement
| air
| occupational
| biomonitoring
Figure 5. continued.
This document is a draft for review purposes only and does not constitute Agency policy.
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1
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3
4
5
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IRIS Assessment Plan for Vanadium (Inhalation)
Animal studies: A preliminary survey of study designs and health effects evaluated in the
animal studies that met PECO criteria is provided in Figure 6.
Most of the available animal studies evaluated exposure to vanadium pentoxide. Only a few
studies evaluated acute or short-term exposure to other vanadium compounds, such as sodium
metavanadate, ammonium metavanadate, vanadium dioxide, sodium vanadate, and bismuth
orthovanadate, of which ammonium metavanadate and sodium metavanadate included only single-
concentration exposure studies (Figure 7). Most studies involved exposure to mice (n = 21), with
several others exposing rats (n = 8), and only one study exposing rabbits and two exposing
nonhuman primates. Of the 30 available animal studies, 10 are multiple exposure studies, 19 are
single concentration studies, and 1 involved both single and multi-exposure experiments.
The study designs most relevant for RfC derivation are chronic, subchronic, reproductive, or
developmental studies that tested multi-exposure concentrations. The designs and author-
reported findings of the identified multi-exposure animal studies are summarized in Figure 8
(chronic studies) and Figure 9 (subchronic studies).
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Health System
acute
nor<-
nurnan rat
primate
rabbit
non-
i-uTiai
pri "nate
short-term
mouse rat
rabbit
subchronic
mouse rat
ncn-
humaf?
P'imaie
chronic
mouse rat
rabbit
Grand
Total
Cancer
1
1
1
Cardiovascular
1
1
2
1
2
1
2
Dermal
1
1
1
Endocrine
1
1
1
2
Gastrointestinal
1
1
1
2
Hematologic
4
1
1
1
5
Hepatic
1
1
1
2
1
1
1
1
3
Immune
1
1
2
3
1
1
1
5
Metabolic
1
1
Nervous
*
2
1
1
7
Renal
1
1
2
1
1
1
1
3
Reproductive
2
1
1
1
1
4
Respiratory
1 1
1
l
2
1
1
1
1
1
11
Systemic/Whole Body
1
KX
1
1
1
1
7
Other
1
1
Grand Total
1 2
1
1
8
6
1
11
1
1
4
1
1
30
Figure 6. Survey of animal studies that met PECO criteria by study design, species, and health systems assessed.
The numbers indicate the number of studies that investigated a particular health system, and not the number of studies that observed an
association with vanadium exposure. If a study evaluated multiple species, study designs, or health outcomes, it is displayed multiple
times. Hence, the totals do not necessarily indicate the number of individual studies for a given health outcome. The interactive version of
the figure, including more details on the study designs and results, is available at the following URL:
https://public.tableau.com/views/VanadiumlnhalationlAPVisualizations/ReadMe?:language=en&:displav count=v&:origin=viz share link.
This document is a draft for review purposes only and does not constitute Agency policy,
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IRIS Assessment Plan for Vanadium (Inhalation)
Chemical Name
acute
short-term
subch conic
chronic
Grand Total
Ammonium metavanadate
1
1
2
Bismuth orthovanadate
1
1
5odium metavanadate
1
1
Sodium vanadate
%
1
Vanadium dioxide
1
1
Vanadium pentoxide
3
13
11
6
1 27
Grand Total
4
15
11
6
30
Figure 7. Summary of the vanadium compounds evaluated by study design in
the available animal studies.
These include both single exposure as well as multi-exposure animal studies. The interactive version
of the figure including more details on the study designs and results is available at the following URL:
https://public.tableau.com/views/Vanadium Inhalation IAPVisualizations/ReadMe?:language=en&:dis
play count=v&:origin=viz share link.
This document is a draft for review purposes only and does not constitute Agency policy,
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IRIS Assessment Plan for Vanadium (Inhalation)
Chemical
Name
Species
Reference Sex
Health System
concentration
levels
Concentration
units
Vanadium
non-human primate
Knecntetal., 1992 male
Respiratory
0,0.1,0.5,1.1
mg/mA3
pentoxide
rat
NT?, 2002 botn
Cancer
0,0.5,1,2
mg/mA3
Cardiovascular
0, 0.5,1, 2
mg/mA3
Dermal
0, 0.5,1, 2
mg/mA3
Endocrine
0,0.5,1,2
mg/mA3
Gastrointestinal
0, 0.5,1,2
mg/m"-3
Hematologic
0,0.5,1,2
mg/mA3
Hepatic
0, 0.5,1, 2
mg/mA3
Immune
0, 0.5,1, 2
mg/m"'3
Nervous
0,0.5,1,2
mg/mA3
Renal
0, 0.5,1, 2
mg/mA3
Reproductive
0,0.5,1,2
mg/mA3
Respiratory
0, 0.5,1, 2
mg/mA3
Systemic/Whole Body
0,0.5,1,2
mg/mA3
mouse
NTP, 2002 both
Cancer
0,1, 2, 4
mg/mA3
Cardiovascular
0,1. 2, 4
mg/mA3
Dermai
0,1, 2,4
mg/mA3
Endocrine
0,1, 2, 4
mg/mA3
Gastrointestinal
0,1.2,4
mg/mA3
Hematologic
0,1, 2,4
mg/mA3
Hepatic
0,1, 2, 4
mg/mA3
Immune
0,1, 2, 4
mg/mA3
Nervous
0,1, 2. 4
mg/mA3
Renal
0,1, 2, 4
rng/mA3
Reproductive
0,1, 2, 4
mg/mA3
Respiratory
0,1, 2, 4
mg/mA3
Systemic/Whole Body
0,1, 2, 4
mg/mA3
Figure 8. Preliminary summary of multi-exposure chronic animal studies.
The interactive version of the figure, including more details on the study designs and results, is available at the
following URL:
https://public.tableau.com/views/VanadiumInhalationIAPVisualizations/ReadMe?:language=en&:displav count=v
&:origin=viz share link.
This document is a draft for review purposes only and does not constitute Agency policy,
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Ail
concentration Concentration
Cnenicsl Name Spec'es Refsreice Sex Health System levels units
Vanadium ?ento*'de 'at T= 2C9I both Cardiovascular 0,1,2,4,8,16 mg/mA3
0, 4,8,16 mg/mA3
Hematologic 0,1, 2, 4, 8,16 nig/mA3
Hepatic 0„ 1,2,4,8,16 mg/mA3
immune 0,1, 2,4, 8,16 mg/mA3
0,4, 8,16 mg/mA3
Renal 0,1, 2, 4, 8,16 mg/mA3
Reproductive 0,1, 2,4, 8,16 mg/mA3
Respiratory 0,1, 2,4, 8,16 mg/mA3
0,4, a. 16 m
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• Key Science Issue #1: Consideration of vanadium speciation and oxidation state.
Considering oxidation status could be important as preliminary examination of findings
from oral exposure studies in rodents appears to indicate increased toxicity of vanadium in
the +5 oxidation state compared to vanadium +4 fRoberts et al. 20161. As noted in Section
2, vanadium in solution can convert between oxidation states and will form different
species as a function of factors including pH, concentration, and redox potential. Study
evaluations for the available inhalation studies, to the extent possible, will consider factors
that could affect vanadium oxidation state and speciation [e.g., study methods that involved
aerosolizing vanadium pentoxide (or other vanadium compound) from solution,
e.g., Gonzalez-Villalva etal. (20111. rather than exposure to vanadium as a dust, e.g., NTP
f'20021]. In addition, data to inform potential conversion between vanadium oxidation state
in the body also will be evaluated and discussed in the assessment
• Key Science Issue #2: Interpretation of data on noncancer respiratory responses to
vanadium pentoxide.
The 2-year NTP (2002) study reports increasing incidences of nonneoplastic lesions in the
upper and lower respiratory tract of rats and mice (both sexes) with increasing vanadium
pentoxide exposure. Responses in all vanadium pentoxide exposure groups were highly
elevated compared to controls. Information on the biology underlying these findings will
aid interpretation of their use for hazard identification. Depending on the hazard
identification decisions, methods for low-dose extrapolation and the associated
uncertainties with any such approaches also would need to be explored and justified.
• Key Science Issue #3: Interpretation of data on rodent tumor responses.
The NTP (20021 study also reports that tumor responses (alveolar/bronchiolar neoplasms)
in male and female mice were highly elevated at all concentrations of vanadium pentoxide
exposure: 70-80% increased incidence at the lowest tested vanadium concentration;
control incidence in male mice was high (44%), but background incidence in females was
very low (2%). Tumor incidence in male rats was elevated slightly but not statistically
significant compared to concurrent controls. Previous reviews analyzed this tumor
incidence against historical controls, which will be useful in interpreting these data as they
are considered in the assessment In summary, aspects of the rodent tumor data noted
above and the uncertainties will be considered in the assessment.
• Key Science Issue #4. Cancer MOA for alveolar/bronchiolar neoplasms.
As summarized in Section 2.1, there is some support for both a mutagenic MOA and an MOA
dependent on cellular cytotoxicity and reparative regeneration (and potentially other
undetermined mechanisms) as suggested in the EPA PPRTV assessment (U.S. EPA. 2008). A
similar lack of a clearly delineated MOA for alveolar/bronchiolar lung tumors with
vanadium pentoxide exposure was proposed in the unfinalized draft IRIS Assessment of
Vanadium Pentoxide (U.S. EPA. 2011). As reported in these reviews, mutagenicity data for
vanadium pentoxide appears generally negative, and some data support a mechanism
involving DNA damage and cell proliferation. Given the potential uncertainties in the
available MOA information and the potential impact of this information on assessment
conclusions, a focused evaluation of the available evidence regarding cancer MOA(s) for
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1 alveolar/bronchiolar neoplasms, including judgments regarding human relevance, is
2 expected to be a key component of the vanadium (inhalation) IRIS assessment.
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3. OVERALL OBJECTIVE, SPECIFIC AIMS, AND
DRAFT POPULATIONS, EXPOSURES,
COMPARATORS, AND OUTCOMES (PECO)
CRITERIA
1 On the basis of the preliminary literature survey (Section 2.3) and identified key science
2 issues (Section 2.4), this section outlines the specific aims and draft PECO criteria that will be used
3 in developing this IRIS assessment The overall objective of this assessment is to identify adverse
4 health effects and characterize exposure-response relationships for these effects of inhalation
5 exposure to vanadium compounds to support development of toxicity values. This assessment will
6 use systematic review methods to evaluate the epidemiological and toxicological literature for
7 vanadium compounds, including consideration of relevant mechanistic evidence. The evaluation
8 conducted in this assessment will be consistent with relevant EPA guidance.7 The systematic
9 review protocol will be disseminated after review of this draft IRIS Assessment Plan and will reflect
10 changes made to the specific aims and PECO criteria in response to public comments.
11 3.1. SPECIFIC AIMS
12 • Identify epidemiological (i.e., human) and toxicological (i.e., experimental animal) literature
13 reporting effects of exposure to vanadium and compounds as outlined in the PECO criteria,
14 and inventory literature that is potentially relevant to the specific aims (e.g., toxicokinetic,
15 mechanistic). The ATSDR Toxicological Profile for Vanadium (ATSDR. 2012) will serve as
16 the starting point for the literature search, because it is the most recent and comprehensive
17 review of health effects of vanadium and compounds published by a U.S. federal agency.
18 Database searches will be conducted to identify records that were published since the
19 literature was last searched for the 2012 ATSDR Toxicological Profile for Vanadium.
20 • Conduct study evaluations (reporting quality, risk of bias, and sensitivity) for individual
21 epidemiological and toxicological studies and PBPK models (if identified in literature
22 searches).
23 • Extract data on relevant health outcomes from epidemiological and toxicological studies
24 included on the basis of study evaluation (full data extraction of low confidence studies may
25 not be performed for poorly studied health effects or for health effects for which extensive
26 medium and high confidence studies exist in the evidence base).
7EPA guidance documents: http://www.epa.gov/iris/basic-information-about-integrated-risk-information-
svstem#guidance/.
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1 • Review and incorporate the available toxicokinetic and mechanistic information, as
2 warranted, to support assessment decisions. The toxicokinetic and mechanistic analyses
3 will focus primarily on the key science issues identified in Section 2.4. The scope of the
4 analysis of mechanistic information will be determined by the complexity and confidence in
5 the phenotypic evidence in humans and animals, the likelihood of the analyses to affect
6 evidence synthesis conclusions for human health, and the directness or relevance of the
7 available model systems for understanding potential human health hazards.
8 • For each evidence stream (i.e., studies in humans, animal studies, and mechanistic or other
9 supplemental studies, as appropriate and depending on data availability), synthesize the
10 evidence across studies, assessing similar health outcomes using a narrative approach.
11 «For each health outcome, determine the strength of the evidence within and across evidence
12 streams to draw evidence integration judgments about the potential for vanadium and
13 compounds exposure to be hazardous to humans. Identify and discuss issues concerning
14 potentially susceptible populations and life stages.
15 • Derive inhalation toxicity values [e.g., reference concentrations (RfCs), cancer risk estimates
16 for inhalation exposure] as supported by the available data.
17 • Characterize uncertainties and identify key data gaps and research needs, such as
18 limitations of the evidence base, limitations of the systematic review, and consideration of
19 dose relevance and pharmacokinetic differences when extrapolating findings from higher
20 dose animal studies to lower levels of human exposure.
21 3.2. DRAFT PECO CRITERIA
22 The PECO criteria are used to identify the evidence that addresses the specific aims of the
23 assessment and to focus the search terms and inclusion/exclusion criteria in a systematic review.
24 The draft PECO criteria for vanadium compounds (Table 3) were based on (1) nomination of the
25 chemical for assessment, (2) discussions with scientists in EPA program and regional offices to
26 determine the scope of the assessment that will best meet Agency needs, and (3) preliminary
27 review of the health effects literature for vanadium compounds (primarily reviews and
28 authoritative health assessment documents) to identify the major health hazards potentially
29 associated with inhalation exposure to vanadium and compounds and key science issues.
Table 3. Population, exposure, comparator, outcome (PECO) criteria for the
inhalation exposure to vanadium and compounds assessment
PECO element
Evidence
Populations
Human: Any population and life stage (occupational or general population, including children
and other potentially sensitive populations).
Animal: Nonhuman mammalian animal species (whole organism) at any life stage (including
preconception, in utero, lactation, peripubertal, and adult stages). Studies of transgenic
animals will be tracked as mechanistic studies under "potentially relevant supplemental
material."
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PECO element
Evidence
Exposures
Relevant forms: Any forms of vanadium.
Human: Any exposure to vanadium compound(s) via the inhalation route, either explicitly
stated or considered plausible based on exposure assessment. Exposure can be based on
administered concentration, biomonitoring data (e.g., urine, blood, or other specimens),
environmental or occupational measurements (e.g., air concentration), or job title or
residence. Studies will be included if biomarkers of vanadium exposure are evaluated but the
exposure route is unclear. Other exposure routes including oral will be tagged as "potentially
relevant supplemental information."
Animal: Any exposure to vanadium compound(s) via the inhalation route. Studies involving
exposures to mixtures will be included only if they include an arm with exposure to a singular
vanadium compound alone, otherwise, they will be tagged as "potentially relevant
supplemental information." Other exposure routes, including intratracheal instillation,
intranasal or oropharyngeal administration, oral, dermal, or injection, will be tagged as
"potentially relevant supplemental information."
Comparators
Human: A comparison or referent population exposed to lower levels (or no
exposure/exposure below detection limits) to vanadium compounds, or exposure for shorter
periods of time, or cases versus controls. However, worker surveillance studies are considered
to meet PECO criteria even if no referent group is presented. Case reports or case series of >3
people will be considered to meet PECO criteria, while case reports describing findings in 1-3
people in nonoccupational or occupational settings will be tagged as "potentially relevant
supplemental information."
Animal: A concurrent control group exposed to vehicle-only treatment, untreated control, or
other treatment group with a different exposure duration time period.
Outcomes
All health outcomes (both cancer and noncancer). In general, endpoints related to clinical
diagnostic criteria, disease outcomes, histopathological examination, or other
apical/phenotypic outcomes are considered to meet PECO criteria and are prioritized for
evidence synthesis over outcomes such as biochemical measures.
PK or PBPK
models
Studies describing pharmacokinetic (PK) or physiologically based pharmacokinetic (PBPK)
models for any form of vanadium will be included.
Classical Pharmacokinetic (PK) or Dosimetry Model Studies: Classical PK or dosimetry
modeling usually divides the body into just one or two compartments, which are not specified
by physiology, where movement of a chemical into, between, and out of the compartments is
quantified empirically by fitting model parameters to ADME (absorption, distribution,
metabolism, and excretion) data. This category is for papers that provide detailed descriptions
of PK models, that are not a PBPK model.
Note: ADME studies often report classical PK parameters, such as bioavailability (fraction of an
inhalation concentration absorbed), volume of distribution, clearance rate, or half-life or half-
lives. If a paper only provides such results in tables with minimal description of the underlying
model or software (i.e., uses standard PK software without elaboration), including
"noncompartmental analysis," it should be listed only as a supplemental material ADME study.
Physiologically Based Pharmacokinetic (PBPK) or Mechanistic Dosimetry Model Studies: PBPK
models represent the body as various compartments (e.g., liver, lung, slowly perfused tissue,
richly perfused tissue) to quantify the movement of chemicals or particles into and out of the
body (compartments) by defined routes of exposure, metabolism, and elimination, and thereby
estimate concentrations in blood or target tissues.
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In addition to the PECO criteria, studies containing supplemental material that also
potentially are relevant to the specific aims will be tracked during the literature screening process.
Table 4 presents major categories of supplemental material. The criteria are used to tag studies
during screening and to prioritize studies for consideration in the assessment based on likelihood
to impact evidence synthesis conclusions for human health. Important to emphasize is that being
tagged as supplemental material does not mean the study is excluded from consideration in the
assessment The initial screening level distinctions between a study meeting the PECO criteria and
a supplemental study are often made for practical reasons, and the tagging structure in Table 3 is
designed to ensure that supplemental studies are categorized for easy retrieval while conducting
the assessment. Studies that meet the PECO criteria are those that are most likely to be used to
develop hazard conclusions and derive toxicity values and will thus undergo individual-level study
evaluation and data extraction, as described in the protocol. For evidence-rich topics, this is most
likely to be epidemiological and toxicological studies. For most IRIS assessments, identifying all
available pharmacokinetic models is also considered critical and, thus, those are generally included
in the PECO criteria. In contrast, the impact on the assessment conclusions of individual studies
tagged as supporting material is often difficult to gauge during the screening phase of the
assessment Studies tagged as supplemental may (1) become critical to the interpretation of other
evidence at the level of needing individual-level study evaluation (e.g., genotoxicity studies when
conducting a cancer MOA is needed); (2) be a single study that contributes to a well-accepted
scientific conclusion and does not need to be evaluated and summarized at the individual-study
level (e.g., dioxin as an aromatic hydrocarbon receptor (AhR) agonist); (3) provide key references
for preparation of certain chapters in an IRIS assessment (e.g., background information on sources,
production, or use; overview of toxicokinetics); or (4) provide context for the rationale for
conducting the assessment or for assessment conclusions (e.g., information on pathways and levels
of exposure). From a practical perspective, determining that all of these studies meet the PECO
criteria during the title and abstract level screening means that the full-text needs to be obtained
for full-text screening for all of them, which would be very time and resource intensive. Thus, the
tagging strategy outlined below allows these studies to be identified at the title and abstract level so
the full text can be retrieved only as needed during the course of conducting the assessment.
Table 4. Major categories of "Potentially Relevant Supplemental Material"
Category
Evidence
Mechanistic studies
Studies reporting measurements related to a health outcome that inform the
biological or chemical events associated with phenotypic effects, in both mammalian
and nonmammalian model systems, including in vitro, in vivo (by any routes of
exposure, includes transgenic models), ex vivo, and in silico studies. Genotoxicity
tests are considered "mechanistic." Studies in which the chemical is used as a
laboratory reagent generally do not need to be tagged (e.g., as a chemical probe
used to measure antibody response).
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Category
Evidence
Nonmammalian model
systems
Studies in nonmammalian model systems, e.g., zebrafish, birds, C. elegans.
Noninhalation route of
administration
Studies in which humans or animals (whole organism) were exposed via a
noninhalation route (e.g., oral, injection, or dermal) and intratracheal, intranasal, or
oropharyngeal routes of exposure. This categorization generally does not apply to
epidemiological studies in which the exposure route may be unclear; such studies
are considered to meet PECO criteria when inhalation exposure is plausible (further
review of these studies will include consideration of whether route attribution can
be inferred). Studies evaluating oral exposure to vanadium compounds are also
under evaluation in a separate IRIS assessment
(https://cfpub.epa.gov/ncea/iris drafts/recordisplay.cfm?deid=348792).
Toxicokinetic (ADME)
Toxicokinetic (ADME) studies are primarily controlled experiments, where defined
exposures usually occur by intravenous, oral, inhalation, or dermal routes, and the
concentration of particles, a chemical, or its metabolites in blood or serum, other
body tissues, or excreta are then measured. These data are used to estimate the
amount absorbed (A), distributed (D), metabolized (M), or excreted/eliminated (E)
through urine, breath, feces.
• The most informative studies are by the inhalation route and involve
measurements over time such that the initial increase and subsequent
concentration decline is observed, preferably at multiple exposure levels. Data
collected from multiple tissues or excreta at a single timepoint, however, also
inform distribution.
• ADME data also can be collected from human subjects who have had
environmental or workplace exposures that are not quantified or fully defined.
To be useful, however, such data must involve either repeated measurements
over a period when exposure is known (e.g., is zero because previous exposure
ended) *or* time- and subject-matched tissue or excreta concentrations
(e.g., plasma and urine, or maternal and cord blood).
• ADME data, especially metabolism and tissue partition-coefficient information,
can be generated using in vitro model systems. Although in vitro data may not
be as definitive as in vivo data, these studies should also be tracked as ADME.
For large evidence bases, separately tracking the in vitro ADME studies may be
appropriate.
*Studies describing environmental fate and transport or metabolism in bacteria are
not tagged as ADME.
Exposure characteristics
(no health outcome
assessment)
Exposure characteristic studies include data that are unrelated to toxicological
endpoints, but which provide information on exposure sources or measurement
properties of the environmental agent (e.g., demonstrate a biomarker of exposure).
Mixture studies
Mixture studies that are not considered to meet PECO criteria because they do not
contain an exposure or treatment group assessing only the chemical of interest.
This categorization generally does not apply to epidemiological studies.
Case reports
Case reports of fewer than three subjects that describe health outcomes after
exposure.
Records with no original
data
Records that do not contain original data, such as other agency assessments,
informative scientific literature reviews, editorials, or commentaries.
Conference
abstracts/abstract only
Records that do not contain sufficient documentation to support study evaluation
and data extraction.
1
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NTP (National Toxicology Program). (2008). Chemical information review document for oral
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toxicological evaluation by the National Toxicology Program [NTP], Research Triangle Park,
NC.
https://ntp.niehs.nih.gov/ntp/htdocs/chem background/exsumpdf/niehs vanadium comp
ounds 508.pdf
OEHHA (California Office of Environmental Health Hazard Assessment). (2008). Acute toxicity
summary- vanadium pentoxide. (CAS Registry Number: 1314-62-1).
Ontario Ministry of Labour. (2018). Current Occupational Exposure Limits for Ontario Workplaces
Required under Regulation 833.
https://www.labour.gov.on.ca/english/hs/pubs/oel table.php
OSHA (Occupational Safety & Health Administration). (1989) Air contaminants; Final rule, 29 CFR
Office of the Federal Register.
OSHA (Occupational Safety & Health Administration). (2019a). Ferrovanadium (dust). (CAS#:
12604-58-9).
OSHA (Occupational Safety & Health Administration). (2019b). Vanadium, respirable dust & fume
(as V205). (CAS #1314-62-1).
httPs://www.osha.gov/chemicaldata/chemResulthtml?recNo=217
Gouvernement du Quebec. (2019) Regulation respecting occupational health and safety.
Mp:i/IeMs^^
2.1.%20r.%2013?csi scan 9222d36c6a354dc6=BQ9xvrMZ+270UP3i0MGuQD0kZigFAAAAX
2.1.%20r.%2013&bcsi scan 9222d36c6a354dc6=KXzmpPueuN0LlAinlOBlZerr85YMAAA
AvhrPTg==&bcsi scan Filename=S-2.1.%20r.%2013
RI DEM (Rhode Island Department of Environmental Management). (2008). Rhode Island Air Toxics
Guidelines, http://www.dem.ri.gov/programs/benviron/air/pdf/airtoxgl.pdf
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Roberts. GK: Stout MP: Savers. Bi Fallacara. Dl nancik. MR: Waidyanatha. Si Hooth. Ml.
(2016). 14-day toxicity studies of tetravalent and pentavalent vanadium compounds in
Harlan Sprague Dawley rats and B6C3F1 /N mice via drinking water exposure. Toxicology
Reports 3: 531-538. http://dx.doi.( toxrep.2016.05.001
Roshchin. IV. (1952). [Hygienic description of production vanadium aerosol]. Gig Sanit 11: 49-53.
Roshchin Idkova. LV: Dusfaen'Mna. AY: Lutsenko. LA: Panov. PV. (1966). The pathogenic
properties of industrial vanadium, ferrovanadium, and vanadium carbide dusts (an
experimental study). Gig Tr Prof Zabol 10: 21-25.
Safe Work Australia. (2018). Workplace exposure standards for airborne contaminants.
https://vyww.safeworkaustralia.gov.au/svstem/files/documents/1804/workDlace-
exposure-standards-airborne-co ntaminants-2 jdf
Schlesinger. WH: Klein. EM: Vengosh. A. (2017). Global biogeochemical cycle of vanadium [Review],
Proc Natl Acad Sci USA 114: E11092-E11100. http://dx.doi.org/10.1073 /pnas.171550
Shafer. MM: Toner. BM: Overdier. IT: Schai akra. SC: Hu. S: Herner. ID: Avala. A. f20121.
Chemical speciation of vanadium in particulate matter emitted from diesel vehicles and
urban atmospheric aerosols. Environ Sci Technol 46: 189-195.
http://dx.doi.org/10.1021/es200463c
Sioberg. SG. (1955). Vanadium bronchitis from cleaning oil-fired boilers. AMA Arch Ind Health 11:
505-512. http://dx.doi.Org/10.1093/occmed/4.l.31
Stokinger. HE. (1981). The metals: Vanadium, V. In GD Clayton; FE Clayton (Eds.), Patty's Industrial
Hygiene and Toxicology: Volume 2A: Toxicology (3rd rev ed., pp. 2013-2033). New York,
NY: John Wiley and Sons.
SWCAA (Southwest Clean Air Agency). (2020). 1314-62-1: Vanadium Pentoxide. Available online at
http://www.swcleanair.org/epages/PollutantDetail.asp?id=717
TCEO (Texas Commission on Environmental Quality). (2018). TRRP protective concentration levels:
April 2018 PCL and supporting tables.
https://www.tcea.texas.gov/remediation/trrp/trrppcls.html
Tiesiema, B: Baars. AI. (2009). Re-evaluation of some human-toxicological Maximum Permissible
Risk levels earlier evaluated in the period 1991-2001. (RIVM Report 711701092).
Bilthoven, the Netherlands: National Institute for Public Health and the Environment
(Netherlands), http://www.rivm.nl/bibliotheek/rapport 092.pdf
U.S. APHC (U.S. Army Public Health Command). (2013). Environmental health risk assessment and
chemical exposure guidelines for deployed military personnel. (Technical guide 230, 2013
revision). Aberdeen Proving Ground, MD.
https://phc.amedd.armv.mil/PHC%20Resource%20Library/TG230-DeplovmentEHRA-
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U.S. EPA (U.S. Environmental Protection Agency). (1993). NATICH Data base report on state, local
and EPA air toxics activities. (EPA-453/R-93-041). Research Triangle Park, NC.
http://nepis.epa. gov/exe/ZyPURL.cgi?Dockey=2 000NS7S.txt
U.S. EPA (U.S. Environmental Protection Agency). (2005). Guidelines for carcinogen risk assessment
[EPA Report], (EPA/630/P-03/001B). Washington, DC: U.S. Environmental Protection
Agency, Risk Assessment Forum, https: //www.epa.gov/sites/production/files/2013-
09/documents/cancer guidelines final 3-25-05.pdf
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
U.S. EPA (U.S. Environmental Protection Agency). (2008). Provisional Peer-Reviewed Toxicity
Values for vanadium pentoxide (CASRN 1314-62-1) [EPA Report], Cincinnati, OH.
U.S. EPA (U.S. Environmental Protection Agency). (2009). Provisional peer-reviewed toxicity values
for vanadium and its soluble inorganic compounds other than vanadium pentoxide (CASRN
7440-62-2 and others): Derivation of subchronic and chronic oral RfDs [EPA Report],
(EPA/690/R-09/070F). Cincinnati, OH.
https://cfpub.epa.gov/ncea/pprtv/documents/Vanadium.pdf
U.S. EPA (U.S. Environmental Protection Agency). (2011). Toxicological review of vanadium
pentoxide (External review draft). (635R11004C).
http://cfpub.epa.gov/ncea/iris drafts/recordisplav.cfm?deid=2 36587
U.S. EPA (U.S. Environmental Protection Agency). (2020). CompTox Chemicals Dashboard.
Washington, DC. https://comptox.epa.gov/dashboard
Vintinner. Fl: Yallenas. R: Carlin. CE: Weiss. R: Macher. C: Ochoa. R. (1955). Study of the health of
workers employed in mining and processing of vanadium ore. AMA Arch Ind Health 12:
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VT ANR (Vermont Agency of Natural Resources). (2018). Air pollution control regulations.
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Washington State Legislature. (2009). Table of ASIL, SQER and de minimis emission values. (WAC
173-460-150). https://apps.leg.wa.gov/WAC/defaultaspx?cite=173-460-150
WHO (World Health Organization). (1987). Air quality guidelines for Europe (1st ed.). Copenhagen,
Denmark: World Health Organization, Regional Office for Europe.
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http://www.inchem.org/documents/ehc/ehc/ehc81.htm
WHO (World Health Organization). (2000). Air quality guidelines for Europe. In WHO Regional
Publications, European Series, No 91 (2nd ed.). Copenhagen, Denmark: World Health
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for-europe
Williams. N. (1952). Vanadium poisoning from cleaning oil-fired boilers. Br J Ind Med 9: 50-55.
http://dx.doi.Org/10.1136/oem.9.l.50
Worksafe (Worksafe New Zealand). (2018). Workplace exposure standards and biological exposure
indices (10th ed.).
Wvers. H. (1946). Some toxic effects of vanadium pentoxide. Occup Environ Med 3: 177-182.
http://dx.doi.Org/10.1136/oem.3.3.177
Zenz. C: Bart] Thiede. WH. (1962). Acute vanadium pentoxide intoxication. Arch Environ
Occup Health 5: 542-546. http://dx.doi.org/10.1080/00039896.1962.10663328
Zenz. C: Berg. BA. (1967). Human responses to controlled vanadium pentoxide exposure. Arch
Environ Occup Health 14: 709-712. doi.org/10.1080/0003989 6.1967.10664824
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
APPENDIX A. SURVEY OF EXISTING VANADIUM
TOXICITY VALUES
1 Table A-l lists websites that were searched for relevant inhalation reference values for
2 vanadium and vanadium compounds, along with indications of the results of the search. In addition
3 to these sources, the ToxVal database on EPA's CompTox Chemicals Dashboard
4 (https://comptox.epa.gov/dashboard/chemical lists/TOXVAL V5] was also searched for both
5 reference values and potential points of departure (PODs) for development of values. Details on
6 derivation of the available health-effect reference values for inhalation exposure to vanadium and
7 compounds are presented in Table A-2 (reference values).
Table A-l. Sources searched for vanadium health effect reference values
Source3
Search results
Query and/or Link
ACGIH
See Table A-2
ACGIH (2009). TLVs and BEIs: Based on documentation of the threshold
limit values for chemical substances and physical agents and biological
exposure indices. Cincinnati, OH: American Conference of Governmental
Industrial Hygienists
AIHA
No results found
{AIHA, 2019, 6514361}. 2019 ERPG/WEEL Handbook. Fairfax, VA: American
Industrial Hygiene Association.
ATSDR
See Table A-2
http://www.atsdr.cdc.gov/toxprofiles/index.asp
https://www.atsdr.cdc.sov/mrls/mrllist.asp
CompTox
See Table A-2
https://comptox.epa.sov/dashboard
CT DEEP
See Table A-2
https://eregulations.ct.gov/eRegsPortal/Browse/getDocument7guicM00
D6A654-0300-CC47-9B95-397D2AD21304}
DFG
No current reference
values found
https://onlinelibrary.wiley.com/doi/book/10.1002/9783527818402
EPA/NRC AEGL
No results found
https://www.epa.gov/aesl/access-acute-exposure-suideline-levels-aesls-
values#chemicals
European
Commission
No results found
https://eur-lex.europa.eu/lesal-
content/EN/TXT/PDF/?uri=CELEX:32017L0164&from=EN
Health Canada
No reference values
found
https://www.canada.ca/en/services/health/publications/healthv-livins.html
http://publications.sc.ca/site/archivee-
archived.html?url=http://publications.sc.ca/collections/collection 2012/sc-
hc/H 128-l-ll-638-ens.pdf
http://publications.sc.ca/site/archivee-
archived.html?url=http://publications.sc.ca/collections/Collection/H46-2-
96-194E.pdf
This document is a draft for review purposes only and does not constitute Agency policy.
35 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Source3
Search results
Query and/or Link
HSA
See Table A-2
https://www.hsa,ie/eng/Publications and Forms/Publications/Latest Publi
cations/chemical agents code of practice 2020,87509,shortcut,html
IDEM
No results found
https
//www,in,gov/idem/toxic/2343,htm
ID DEQ
See Table A-2
https
//adminrules,idaho,gov/rules/current/58/580101,pdf
IFA
See Table A-2
https
//limitvalue,ifa.dguv.de/WebForm gw2,aspx
IRIS
1988 RfD available,
no inhalation values
found
http://www,epa.gov/iris/
JSOH
No results found
https://www,sanei,or,ip/?mode=view&cid=328
MassDEP
See Table A-2
https://www.mass.gov/service-details/massdep-ambient-air-toxics-
guidelines
MDH
See Table A-2
https://www.health.state.mn.us/communities/environment/risk/guidance/
air/table.html
Ml EGLE
See Table A-2
https://www.michigan.gov/documents/deq/di iem-
CleanupCriteriaTSD 527410 7.pdf
NATICH
See Table A-2
https
//nepis,epa,gov/Exe/ZvPDF,cgi/2000NS7S,PDF?Dockev=2000NS7S,PDF
NC DEQ
No results found
https
//files. nc.gov/ncdea/Air%20Qualitv/rules/rules/D1104. pdf
NDEP
See Table A-2
https
//ndep.nv.gov/resources/risk-assessment-and-toxicologv-basic-
comparison-levels
NIOSH
See Table A-2
http://www.cdc.gov/niosh/npg/npgdcas.html
https://www.cdc.gov/niosh/docs/81-123/
NJ DEP
See Table A-2
https://www.state.nj.us/dep/aqpp/downIoads/risk/ToxAII2020.pdf
NYS DEC
No reference values
found
https://www.dec.nv.gov/docs/remediation hudson pdf/techsuppdoc.pdf
OAQPS
No results found
https://www.epa.gov/fera/dose-response-assessment-assessing-health-
risks-associated-exposure-hazardous-air-pollutants
OEHHA
See Table A-2
http://www.oehha.ca.gov/tcdb/index.asp
Ontario Ministry
of Labour
See Table A-2
https://www.labour.gov.on.ca/english/hs/pubs/oel table.php
OR DEQ
No results found
https://www.oregon.gov/dea/FilterDocs/airtox-abc.pdf
OSHA
See Table A-2
https://www.osha.gov/chemicaldata/
PAC Database
See Table A-2
https://edms.energv.gov/pac/Search
PPRTV
See Table A-2
https://www.epa.gov/pprtv/provisional-peer-reviewed-toxicitv-values-
pprtvs-assessments
Publications
Quebec
See Table A-2
http://legisauebec.gouv.ac.ca/en/showdoc/cr/S-
2,l,%20r,%2013?csi scan 9222d36c6a354dc6=BO9xyrMZ+270UP3i0MGuO
D0kZigFAAAAXrM3HA==&bcsi scan filename=S-
2,l,%20r,%2013&bcsi scan 9222d3ScSa354dcS=KXzmpPueuNOLlAinJOBlZ
err85YMAAAAyhrPTg=&bcsi scan filename=S-2,l,%20r,%2013
Rl DEM
See Table A-2
http://www,dem,ri,gov/programs/benviron/air/pdf/airtoxgl,pdf
This document is a draft for review purposes only and does not constitute Agency policy.
36 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Source3
Search results
Query and/or Link
RIVM
See Table A-2
httDsi//www. rivm.nl/bibliotheek/raDDorten/711701092.Ddf
No results found
httDsi//www. rivm.nl/bibliotheek/raDDorten/609021044.Ddf
httDsi//www. rivm.nl/bibliotheek/raDDorten/711701025.Ddf
Safe Work
Australia
See Table A-2
httDsi//www,safeworkaustralia,gov,au/exDosure-standards#exDosure-
standards-in-australia
SWCAA
See Table A-2
htto://www. swcleanair.org
TCEQ
No results found
httDs://www. tceq.texas.gov/toxicologY/dsd/final
See Table A-2
httDsi//www.tceq.texas.gov/remediation/trrD/trrDDcls. html
USAPHC
See Table A-2
httDsi//Dhc.amedd.armv.mil/toDics/envirohealth/hrasm/Pages/TG230.asDX
VT DEC
See Table A-2
httDsi//dec. vermont.gov/sites/dec/files/aac/laws-
regs/documents/AQCD%20Regulations%20ADOPTED Decl32018,Ddf#Dage
=127
WAC
See Table A-2
httDsi//aDDS. leg. wa.gov/WAC/default.asDX?cite=173-460-150
Worksafe
See Table A-2
httDsi//worksafe,govt,nz/toDic-and-industrv/work-related-
health/monitoring/exDosure-standards-and-biological-exDosure-indices/
aACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Levels;
AIHA = American Industrial Hygiene Association; ATSDR = Agency for Toxic Substances and Disease Registry;
CT DEEP = Connecticut Department of Energy & Environmental Protection; DFG = Deutsche
Forschungsgemeinschaft, German Research Foundation; EPA = U.S. Environmental Protection Agency;
HSA = Health and Safety Authority; IDEM = Indiana Department of Environmental Management; ID DEQ = Idaho
Department of Environmental Quality; IFA = Institut fur Arbeitsschutz, The Institute for Occupational Safety and
Health; IRIS = Integrated Risk Information System; JSOH = Japan Society for Occupational Health;
MassDEP = Massachusetts Department of Environmental Protection; MDH = Minnesota Department of Health;
Ml EGLE = Michigan Environment, Great Lakes & Energy; NATICH = National Air Toxics Information Clearinghouse;
NC DEQ = North Carolina Department of Environmental Quality; NDEP = Nevada Division of Environmental
Protection; NIOSH = National Institute for Occupational Safety and Health; NJ DEP = New Jersey Department of
Environmental Protection; NRC = National Research Council; NYS DEC = New York State Department of
Environmental Conservation; OAQPS = Office of Air Quality Planning and Standards; OEHHA = California Office of
Environmental Health Hazard Assessment; OR DEQ = Oregon Department of Environmental Quality;
OSHA = Occupational Safety and Health Administration; PAC = Protective Action Criteria; PPRTV = Provisional
Peer-Reviewed Toxicity Value; Rl DEM = Rhode Island Department of Environmental Management;
RIVM = Rijksinstituut voor Volksgezondheid en Milieu, The Netherlands Institute for Public Health and the
Environment; SWCAA = Southwest Clean Air Association; TCEQ = Texas Commission on Environmental Quality;
USAPHC = United States Army Public Health Center; VT DEC = Vermont Department of Environmental
Conservation; WAC = Washington Administrative Code.
This document is a draft for review purposes only and does not constitute Agency policy.
37 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Table A-2. Details on derivation of the available health effect reference values for inhalation exposure to
vanadium and compounds (current as of May 2020; please consult citation source entities and other entities in
Appendix A, Tables A-2 and A-3
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
Emergency Response
PAC-3
1 h
Ammonium
metavanadate
80
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHa
Final
(DOE. 2018)
Potassium
orthovanadate
160
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHb
Trichlorooxovanadium
120
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHC
Sodium metavanadate
84
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHd
Sodium orthovanadate
130
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHe
Vanadium pentoxide
70
Adopted 1990 IDLH
-
-
(NIOSH.
1994a)
-
Adopted 1990
IDLH
Vanadium sulfate
100
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHf
Vanadium tetrachloride
Vanadium (III) sulfate
130
Based on vanadium
IDLH
—
—
—
—
Based on
vanadium IDLH5
Vanadium trioxide
51
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHh
Vanadium (II) sulfate
heptahydrate
190
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLH'
Vanadyl sulfate
110
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium 1 DLHj
Vanadyl sulfate
pentahydrate
170
Based on vanadium
IDLH
-
-
-
-
Based on
vanadium IDLHk
Vanadium
35
Adopted IDLH
-
-
-
-
Adopted IDLH
This document is a draft for review purposes only and does not constitute Agency policy.
38 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
PAC-2
1 h
Ammonium
metavanadate
0.11
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling1
Potassium
orthovanadate
0.23
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling™
Trichlorooxovanadium
0.17
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling"
Sodium metavanadate
0.12
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling0
Sodium orthovanadate
0.18
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
CeilingP
Vanadium pentoxide
7
LOC
NR
NR
NR
Vanadium sulfate
0.14
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling1*
Vanadium tetrachloride
0.19
Based on vanadium
-
-
-
-
Based on
Vanadium (III) sulfate
compounds REL-
Ceiling
vanadium
compounds REL-
Ceilingr
Vanadium trioxide
0.074
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceilings
This document is a draft for review purposes only and does not constitute Agency policy.
39 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
Vanadium (II) sulfate
heptahydrate
0.27
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling'
Vanadyl sulfate
0.16
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling"
Vanadyl sulfate
pentahydrate
0.25
Based on vanadium
compounds REL-
Ceiling
Based on
vanadium
compounds REL-
Ceiling"
Vanadium
5.8
Based on PAC-3
-
-
-
-
Based on PAC-3W
PAC-1
1 h
Ammonium
metavanadate
0.01
Based on PAC-2
-
-
-
-
Based on PAC-2"
Potassium
orthovanadate
0.021
Based on PAC-2
-
-
-
-
Based on PAC-2*
Trichlorooxovanadium
0.015
Based on PAC-2
-
-
-
-
Based on PAC-2Z
Sodium metavanadate
0.011
Based on PAC-2
-
-
-
-
Based on PAC-2aa
Sodium orthovanadate
0.016
Based on PAC-2
-
-
-
-
Based on PAC-2bb
Vanadium pentoxide
0.64
Based on PAC-2
-
-
-
-
Based on PAC-2CC
Vanadium sulfate
0.013
Based on PAC-2
-
-
-
-
Based on PAC-2dd
Vanadium tetrachloride
0.017
Based on PAC-2
-
-
-
-
Based on PAC-2ee
Vanadium (III) sulfate
Vanadium trioxide
0.0067
Based on PAC-2
-
-
-
-
Based on PAC-2ff
Vanadium (II) sulfate
heptahydrate
0.025
Based on PAC-2
-
-
-
-
Based on PAC-2ss
Vanadyl sulfate
0.015
Based on PAC-2
-
-
-
-
Based on PAC-2hh
This document is a draft for review purposes only and does not constitute Agency policy.
40 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
Vanadyl sulfate
pentahydrate
0.023
Based on PAC-2
-
-
-
-
Based on PAC-2"
Vanadium
3
Adopted
ferrovanadium
NIOSH REL-STEL
"
"
"
"
Adopted
ferrovanadium
NIOSH REL-STEL
Occupational
NIOSH REL-
CeilingJJ
<15 min
Vanadium compounds,
excludes vanadium
metal and vanadium
carbide
0.05
Skin, eye, and
respiratory tract
irritation
NA
NA
NA
Final
(NIOSH.
1977)
NIOSH REL-
STEL
15 min
Ferrovanadium,
vanadium metal, and
vanadium carbide
3
NIOSH REL
(TWA)
10-h TWA
1
Adopted OSHA PEL
as a 10-h TWA
-
-
-
-
Adopted OSHA
PEL as a 10-h TWA
NIOSH IDLH
30 min
Vanadium dust and
fume, as V
35
Rhinorrhea,
sneezing,
lacrimation, and
sore throat in
workers
NR
NR
(Mcturk et
al.. 1956:
Sioberg,
1955;
Vintinner et
al.. 1955:
Williams.
1952)
NR
Final
(NIOSH.
1994a. b)
Ferrovanadium
500
Based on NIOSH
REL (TWA)
"
"
"
"
Based on NIOSH
REL (TWA)kk
Final
(NIOSH /
ILO. 1994)
ACGIHTLV
(TWA)11
8-h TWA
Vanadium pentoxide,
inhalable PM as V
0.05
Bronchitis,
bronchospasm,
cough, rhinorrhea,
conjunctivitis, nasal
hemorrhage,
wheezing, rales,
rhonchi, and
pulmonary disease
NR
NR
(Zenz and
Berg. 1967:
Zenz et al..
1962: Wvers.
1946)
NR
Final
(ACGIH.
2009)
This document is a draft for review purposes only and does not constitute Agency policy.
41 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
Ferrovanadium
1
Bronchitis,
interstitial
sclerosis, and
perivascular edema
in rats exposed for
2 mon; irritation of
eyes and
respiratory tract in
workers
NR
NR
(OSHA. 1989:
Stokinger,
1981;
Roshchin et
al.. 1966:
Roshchin.
1952)
NR
Value suggested
bv Roshchin
(1952)
Final
(ACGIH.
2001)
ACGIH TLV-
STELmm
15 min
3
OS HA PEL-
Ceiling
<15 min
Vanadium pentoxide
fume
0.1
Adopted 1968
ACGIH TLV
(NIOSH.
1977)
Adopted 1968
ACGIH TLV
Final
(OSHA.
2019b)
Vanadium pentoxide
dust
0.5
OS HA PEL
(TWA)nn
8-h TWA
Ferrovanadium
1
Final
(OSHA.
2019a)
Cal/OSHA
PEL (TWA)
8-h TWA
Vanadium pentoxide
0.05
NR
NR
NR
NR
Final
(OSHA.
2019b)
Ferrovanadium
1
Final
(OSHA.
2019a)
Cal/OSHA
PEL-STEL
15 min
3
This document is a draft for review purposes only and does not constitute Agency policy.
42 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
CA-REL°°
Acute (1 h)
Vanadium pentoxide
0.03
Coughing and
increased mucus
production in male
volunteers exposed
for 8 h
0.1 mg/m3
0.3 mg/m3
NOAEL
NOAELadj
(Zenz and
Berg. 1967)
Total UF = 10
UFa = 1
UFh = 10
Duration
adjustment:
C" x t = k, where
n = 2
Final
(OEHHA.
2008)
EPA p-RfC
(PPRTV)pp
Sub-
chronic
Vanadium pentoxide
0.0001
Bronchoalveolar
inflammation in
female rats
exposed for 16 d
1 mg/m3
0.18 mg/m3
0.11 mg/m3
LOAEL
LOAELadj
LOAELhec
(NTP. 2002)
Total UF =
1,000
UFa = 3
UFh = 10
UFl = 3
UFd = 10
Duration adjusted:
(6-h/24-h) x
(5-d/7-d)
HEC Adjusted""
Provisional
(U.S. EPA.
2008)
General Public
Chronic
0.000007
Chronic
inflammation of
the larynx and
epithelial
hyperplasia of the
epiglottis in female
rats
0.5 mg/m3
0.09 mg/m3
0.016 mg/m3
0.0022 mg/m3
LOAEL
LOAELadj
LOAELhec
BMDL10
Total UF = 300
UFa = 3
UFh = 10
UFd = 10
Duration adjusted:
(6-h/24-h) x
(5-d/7-d)
HEC Adjusted"
RIVM pTCA
Chronic
Vanadium compounds
0.001
Toxicity in
laboratory animals
0.5 mg
V2O5/1TI3
1 mg V2O5/1TI3
LOAELra,s
LOAELmice
(NTP. 2002)
Total UF =
1,000
UFa = 10
UFh = 10
UFL = 10
Adopted previous
WHO guideline:
(WHO. 1987)ss
Provisional
(Tiesiema
and Baars.
2009)
ATSDR MRL"
Acute
(1-14 d)
Vanadium compounds
0.0008
Lung inflammation
in female rats
exposed to
vanadium
pentoxide
0.56 mg V/m3
0.1 mg V/m3
0.073 mg
V/m3
LOAEL
LOAELadj
LOAELhec
(NTP. 2002)
Total UF = 100
UFa = 3
UFh = 10
UFL = 3
Duration adjusted:
(6-h/24-h) x
(5-d/7-d)
HEC Adjusted"11
Final
(ATSDR.
2012)
This document is a draft for review purposes only and does not constitute Agency policy.
43 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review
status
Chronic
(>1 y)
0.0001
Degeneration of
respiratory
epithelium of the
epiglottis in male
rats exposed to
vanadium
pentoxide
0.04 mg V/m3
0.0071 mg
V/m3
0.003 mg
V/m3
BMCL10
BMCLadj
BMCLhec
Total UF = 30
UFa = 3
UFh = 10
Duration adjusted:
(6-h/24-h) x
(5-d/7-d)
HEC Adjusted™
General Public (Other State Values)
NDEP BCL
6 y
Vanadium and
compounds
0.000104
Based on chronic
MRL
-
-
-
-
Based on chronic
MRLWW
Final
(NDEP.
2017)
70 y
Vanadium pentoxide
0.000000338
Cancer
0.00830
(lag/m3)"1
PPRTV
Cancer
URF
(U.S. EPA.
2008)
NA
Calculated""
CT DEEP HLV
30 min
Vanadium pentoxide
0.005
NR
NR
NR
NR
Final
(CTDEP.
2015)
8 h
0.001
0.05 mg/m3
ACGIH
TLV-TWA
(ACGIH.
2009)
Total UF = 50
Derivation details
reported to
NATICH: (U.S. EPA.
1993)
Rl DEM AAL
1 h
Vanadium and
compounds
0.0002
Adopted acute MRL
"
"
"
"
Adopted acute
MRL"
Final
(Rl DEM.
2008)
aPAC-3 = IDLH x (NH4VO3 MW -f V atomic mass) = 35 mg/m3 x (116.98 g/mol 4 50.94 g/mol) = 80 mg/m3.
bPAC-3 = IDLH x (K3O4V MW 4 V atomic mass) = 35 mg/m3 x (232.23 g/mol 4 50.94 g/mol) = 160 mg/m3.
cPAC-3 = IDLH x (VOCI3 MW 4 V atomic mass) = 35 mg/m3 x (173.29 g/mol 4 50.94 g/mol) = 120 mg/m3.
The PAC tables state that this value is 120 ppm but following the documented derivation details gives a value of 120 mg/m3; therefore, that the units in the PAC
tables are erroneous is assumed.
dPAC-3 = IDLH x (NaVC>3 MW 4 V atomic mass) = 35 mg/m3 x (121.93 g/mol 4 50.94 g/mol) = 84 mg/m3.
ePAC-3 = IDLH x (Na3VC>4 MW 4 V atomic mass) = 35 mg/m3 x (183.91 g/mol 4 50.94 g/mol) = 130 mg/m3.
fPAC-3 = IDLH x (H2O4SV MW 4 V atomic mass) = 35 mg/m3 x (149.01 g/mol 4 50.94 g/mol) = 100 mg/m3.
gPAC-3 = IDLH x (VCU MW 4 V atomic mass) = 35 mg/m3 x (192.74 g/mol 4 50.94 g/mol) = 130 mg/m3.
PAC-3 = IDLH x [V2(S04>3 MW 4 (2 x V atomic mass)] = 35 mg/m3 x [390.05 g/mol t(2x 50.94 g/mol)] = 130 mg/m3.
hPAC-3 = IDLH x [V2O3 MW 4 (2 x V atomic mass)] = 35 mg/m3 x [149.88 g/mol t(2x 50.94 g/mol)] = 51 mg/m3.
'PAC-3 = IDLH x (H14O11SV MW 4 V atomic mass) = 35 mg/m3 x (273.11 g/mol 4 50.94 g/mol) = 190 mg/m3.
This document is a draft for review purposes only and does not constitute Agency policy.
44 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
JPAC-3 = IDLH x (O5SV MW 4 V atomic mass) = 35 mg/m3 x (163 g/mol 4 50.94 g/mol) = 110 mg/m3.
kPAC-3 = IDLH x (H10O10SV MW 4 V atomic mass) = 35 mg/m3 x (253.08 g/mol 4 50.94 g/mol) = 170 mg/m3.
'PAC-2 = REL x (NH4VO3 MW 4 V atomic mass) = 0.05 mg/m3 x (116.98 g/mol 4 50.94 g/mol) = 0.11 mg/m3.
mPAC-2 = REL x (K3O4V MW 4 V atomic mass) = 0.05 mg/m3 x (232.23 g/mol 4 50.94 g/mol) = 0.23 mg/m3.
"PAC-2 = REL x (VOCI3 MW 4 V atomic mass) = 0.05 mg/m3 x (173.29 g/mol 4 50.94 g/mol) = 0.17 mg/m3.
°PAC-2 = REL x (NaVC>3 MW 4 V atomic mass) = 0.05 mg/m3 x (121.93 g/mol 4 50.94 g/mol) = 0.12 mg/m3.
pPAC-2 = REL x (Na3VC>4 MW 4 V atomic mass) = 0.05 mg/m3 x (183.91 g/mol 4 50.94 g/mol) = 0.18 mg/m3.
qPAC-2 = REL x (H2O4SV MW 4 V atomic mass) = 0.05 mg/m3 x (149.01 g/mol 4 50.94 g/mol) = 0.14 mg/m3.
rPAC-2 = REL x (VCU MW 4 V atomic mass) = 0.05 mg/m3 x (192.74 g/mol 4 50.94 g/mol) = 0.19 mg/m3.
PAC-2 = REL x [V2(S04>3 MW 4 (2 x V atomic mass)] = 0.05 mg/m3x [390.05 g/mol t(2x 50.94 g/mol)] = 0.19 mg/m3.
sPAC-2 = REL x [V2O3 MW 4 (2 x V atomic mass)] = 0.05 mg/m3 x [149.88 g/mol t(2x 50.94 g/mol)] = 0.074 mg/m3.
'PAC-2 = REL x (H14O11SV MW 4 V atomic mass) = 0.05 mg/m3 x (273.11 g/mol 4 50.94 g/mol) = 0.27 mg/m3.
"PAC-2 = REL x (O5SV MW 4 V atomic mass) = 0.05 mg/m3 x (163 g/mol 4 50.94 g/mol) = 0.16 mg/m3.
vPAC-2 = REL x (H10O10SV MW 4 V atomic mass) = 0.05 mg/m3 x (253.08 g/mol 4 50.94 g/mol) = 0.25 mg/m3.
wPAC-2 = PAC-3 4 6 = 35 mg/m3 4 6 = 5.8 mg/m3.
XPAC-1 = PAC-2 4 11 = 0.11 mg/m3 4 11 = 0.01 mg/m3.
yPAC-l = PAC-2 4 11 = 0.23 mg/m3 4 11 = 0.021 mg/m3.
ZPAC-1 = PAC-2 4 11 = 0.17 mg/m3 4 11 = 0.015 mg/m3.
aaPAC-l = PAC-2 4 11 = 0.12 mg/m3 4 11 = 0.011 mg/m3.
bbPAC-l = PAC-2 4 11 = 0.18 mg/m3 4 11 = 0.016 mg/m3.
CCPAC-1 = PAC-2 4 11 = 7 mg/m3 4 11 = 0.64 mg/m3.
ddPAC-l = PAC-2 4 11 = 0.14 mg/m3 4 11 = 0.013 mg/m3.
eePAC-l = PAC-2 4 11 = 0.19 mg/m3 4 11 = 0.017 mg/m3.
ffPAC-l = PAC-2 4 11 = 0.074 mg/m3 4 11 = 0.0067 mg/m3.
ggPAC-l = PAC-2 4 11 = 0.27 mg/m3 4 11 = 0.025 mg/m3.
hhPAC-l = PAC-2 4 11 = 0.16 mg/m3 4 11 = 0.015 mg/m3.
"PAC-1 = PAC-2 4 11 = 0.25 mg/m3 4 11 = 0.023 mg/m3.
^Agencies of Sweden and Switzerland also report a short-term value of 0.05 mg/m3 for vanadium pentoxide (1FA, 2019).
kkIDLH = REL x 500 = 1 mg/m3 x 500 = 500 mg/m3
NIOSH documentation states: "500 is an assigned protection factor for respirators and was used arbitrarily during the Standards Completion Program for deciding
when the "most protective" respirators should be used for particulates."
"Agencies of Australia, Ireland, New Zealand, Belgium, Japan, Poland, Singapore, South Korea, Spain, Switzerland, Ontario, and Quebec report the same values. The
vanadium pentoxide value, furthermore, matches that of Austria, France, the United Kingdom, and Hungary (HSA, 2020; 1FA, 2019; Gouvernement du Quebec,
2019; Ontario Ministry of Labour, 2018; Safe Work Australia, 2018; Worksafe, 2018).
mmAgencies of Australia, Ireland, Belgium, Poland, South Korea, Spain, Ontario, and Quebec report the same values (HSA, 2020; I FA, 2019; Gouvernement du Quebec,
2019; Ontario Ministry of Labour, 2018; Safe Work Australia, 2013).
""Agencies of Denmark and China report the same value (IFA, 2019).
This document is a draft for review purposes only and does not constitute Agency policy.
45 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
°°The Minnesota Department of Health's HRV, New Jersey Department of Environmental Protection's RfC, and Washington State's ASIL are identical to the CA-REL
(MDH, 2019; NJ PEP, 2018; Washington State Legislature, 2009).
ppThe chronic RfC has been adopted by the Nevada Division of Environmental Protection (NDEP, 2017).
""LOAEUhec = LOAELadj x RDDR = 0.18 mg/m3 x 0.616 = 0.11 mg/m3.
rrLOAELHEc = LOAEUdj x RDDR = 0.09 mg/m3 x 0.182 = 0.016 mg/m3.
"Dividing each LOAEL by the uncertainty factor yields a value of 0.0005-0.001 mg V2O5/1T13. RIVM concluded that this was "only marginally different" from the
World Health Organization's 1987 guideline based on human data. WHO's value—no longer in effect—of 0.001 mg V/m3 was thus provisionally applied by RIVM to
vanadium compounds.
"Michigan Environment, Great Lakes and Energy; Nevada Division of Environmental Protection; Pennsylvania Department of Environmental Protection; and New
Jersey Department of Environmental Protection have adopted the chronic MRL as an RfC. The New Jersey Department of Environmental Protection has also
adopted the acute MRL as a short-term RfC with a 24-hour averaging time (U.S. EPA, 2020; NJ PEP, 2018; NDEP, 2017; DEQ, 2015).
uuLOAELhec = LOAELadj x RDDR = 0.1 mg V/m3 x 0.732 = 0.073 mg V/m3.
wBMCLhec = BMCLadj x RDDR = 0.0071 mg V/m3 x 0.423 = 0.003 mg V/m3.
WWBCL = AT t- [ET x EF x ED x (1 MRL)] = (6 yrs. x 365 days/yr. x 24 hrs./day) -f [24 hrs./day x 350 days/yr. x 6 yrs. x (14 0.0001 mg/m3)] = 0.000104 mg/m3.
XXBCL = TR x AT 4 (ET x EF x ED x URF) = (10~6 x 70 yrs. x 365 days/yr. x 24 hrs./day) 4 [24 hrs./day x 350 days/yr. x 26 yrs. x 0.00830 (ng/m3)"1] = 0.000338 ng/m3.
wThe acute MRL listed by the Rhode Island Department of Environmental Management does not match the current value posted by ATSDR. The source for the
Rhode Island Air Toxics Guideline was last updated in September 2008; thus, these values are assumed to be based on old MRLs that were in effect at that time.
AAL = acceptable ambient level; ACGIH = American Conference of Governmental Industrial Hygienists; ADJ = adjusted; ASIL = acceptable source impact level;
AT = averaging time; ATSDR = Agency for Toxic Substances and Disease Registry; BCL = basic comparison level; BMCL = benchmark concentration level;
BMDL = benchmark dose level; Cal/OSHA = California Division of Occupational Safety and Health; CA-REL = California reference exposure level; CT
DEEP = Connecticut Department of Energy and Environmental Protection; DEQ = Department of Environmental Quality; DOE = Department of Energy; ED = exposure
duration; EF = exposure frequency; EPA = Environmental Protection Agency; ET = exposure time; HEC = human equivalent concentration; HLV = hazard limiting value;
H2O4SV = vanadium sulfate; H14O11SV = vanadium (II) sulfate heptahydrate; H10O10SV = vanadyl sulfate pentahydrate; HRV = health risk value; HSA = Health and
Safety Authority; IFA = Institut fur Arbeitsschutz, The Institute for Occupational Safety and Health; IDLH = immediately dangerous to life or health; K3O4V = potassium
orthovanadate; LOAEL = lowest-observed-adverse-effect level; LOC = level of concern; MDH = Minnesota Department of Health; MRL = minimal risk level;
MW = molecular weight; NA = not applicable; NATICH = National Air Toxics Information Clearinghouse; NaV03= sodium metavanadate; Na3V04= sodium
orthovanadate; NDEP = Nevada Division of Environmental Protection; NH4V03= ammonium metavanadate; NIOSH = National Institute for Occupational Safety and
Health; NJ DEP = New Jersey Department of Environmental Protection; NOAEL = no-observed-adverse-effect level; NR = not reported; NTP = National Toxicology
Program; OEHHA = Office of Environmental Health Hazard Assessment; OSHA = Occupational Safety and Health Administration; O5SV = vanadyl sulfate;
PAC = Protective Action Criteria; PEL = permissible exposure level; PPRTV = Provisional Peer-Reviewed Toxicity Value; pTCA = provisional tolerable concentration;
RDDR = regional deposited dose ratio; REL = recommended exposure limit; RfC = reference concentration; Rl DEM = Rhode Island Department of Environmental
Management; RIVM = Rijksinstituut voor Volksgezondheid en Milieu, The Netherlands Institute for Public Health and the Environment; STEL = short-term exposure
limit; TLV = threshold limit value; TR = target risk; TWA = time-weighted average; UFa = animal-to-human variability; UFd = database uncertainty; UFh = interhuman
variability; UFl = LOAEL-to-NOAEL adjustment; URF = unit risk factor; V = vanadium; V2O5 = vanadium pentoxide; VCU= vanadium tetrachloride; V2O3 = vanadium
trioxide; VOCI3 = trichlorooxovanadium; V2(S04>3 = vanadium (III) sulfate; WHO = World Health Organization.
This document is a draft for review purposes only and does not constitute Agency policy.
46 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Table A-3. Details on inhalation reference values from other agencies
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review status
USAPHC
MEG-
Critical
a>
a
USAPHC
MEG-
Marginal
1 h
Ammonium metavanadate
Sodium metavanadate
Sodium orthovanadate
Vanadium sulfate
Vanadium pentoxide
Vanadium tetrachloride
Vanadium (III) sulfate
Vanadium trioxide
Trichlorooxovanadium
Vanadyl sulfate
Vanadium
1 h
Ammonium metavanadate
Sodium metavanadate
Sodium orthovanadate
Vanadium sulfate
Vanadium pentoxide
Vanadium tetrachloride
Vanadium (III) sulfate
Vanadium trioxide
Trichlorooxovanadium
Vanadyl sulfate
Vanadium
0.75
30
130
310
35
130
52
750
110
35
0.32
1.2
1.8
4.5
7.0
0.19
7.4
1.3
1.6
0.50
Adopted 2009 PACs
(DOE. 2009)
Adopted 2009
PACs (rounded to
2 significant
figures)
Final
(U.S. APHC.
2013)
This document is a draft for review purposes only and does not constitute Agency policy.
47 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
Reference
value
Point of
Uncertainty
Notes on
value name
Duration
Vanadium form
(mg/m3)
Health effect
departure
Qualifier
Source
factors
derivation
Review status
USAPHC
1 h
Ammonium metavanadate
0.040
MEG -
Negligible
Sodium metavanadate
0.15
Sodium orthovanadate
0.25
Vanadium sulfate
0.60
Vanadium pentoxide
1.0
Vanadium tetrachloride
0.025
Vanadium (III) sulfate
Vanadium trioxide
1.0
Trichlorooxovanadium
0.15
Vanadyl sulfate
0.20
Vanadium
0.075
8 h
Ferrovanadium
1.0
Adopted ACGIH TLV-TWA
-
-
-
-
Adopted ACGIH
TLV-TWA
Vanadium pentoxide
0.05
Adopted ACGIH TLV-TWA
-
-
-
-
Adopted ACGIH
TLV-TWA
14 d
Ferrovanadium
0.34
Based on ACGIH TLV-TWA
-
-
-
-
Based on ACGIH
TLV-TWA3
Vanadium pentoxide
0.00014
Based on acute MRL
-
-
-
-
Based on acute
MRLb
Vanadium
0.00055
Based on acute MRL
-
-
-
-
Based on acute
MRLC
iy
Ferrovanadium
0.34
Based on ACGIH TLV-TWA
-
-
-
-
Based on ACGIH
TLV-TWAd
Vanadium pentoxide
0.00014
Based on acute MRL
-
-
-
-
Based on acute
MRLe
Vanadium
0.000068
Based on chronic MRL
-
-
-
-
Based on chronic
MRLf
This document is a draft for review purposes only and does not constitute Agency policy.
48 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review status
General Public (Limited Details)
MassDEP
TEL
24 h
Vanadium
0.00027
NR
NR
NR
NR
Values derived in
accordance with
this protocol:
(MassDEP. 2011)
Final
(MassDEP.
2019)
Vanadium pentoxide
0.00014
MassDEP
AAL
ly
Vanadium
0.00027
Vanadium pentoxide
0.00003
WAC ASIL
24 h
Vanadium dust or fume
0.0001
NR
NR
NR
NR
Final
(Washington
State
Legislature.
2009)
SWCAAASIL
24 h
Vanadium pentoxide
0.00017
NR
NR
NR
NR
Adopted 1998
Washington State
ASIL
Final
(SWCAA. 2020)
IDDEQAAC
24 h
Vanadium pentoxide,
respirable dust, and fume
0.0025
NR
NR
NR
NR
Final
(Idaho DEQ)
Ferrovanadium
0.05
VT DEC
HAAS
iy
Vanadium pentoxide
0.00001
NR
NR
NR
NR
Final
(VTANR. 2018)
TCEQ RfC
Chronic
Vanadium
0.00003
NR
NR
NR
NR
Final
(TCEQ. 2018)
ADEQAQG
1 h
Vanadium
0.0015
Based on 24-hr AQG
-
-
-
-
Based on 24-hr
AQGs
Final
(U.S. EPA.
1993)h
24 h
0.0004
Based on vanadium
pentoxide ACGIH TLV
Based on
vanadium
pentoxide ACGIH
TLV'
NDEP AAC
8 h
Vanadium
0.001
NR
0.05 mg/m3
V205
ACGIH
TLV-TWA
(ACGIH.
1991)
Total UF =
42
This document is a draft for review purposes only and does not constitute Agency policy.
49 DRAFT-DO NOT CITE OR QUOTE
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review status
OK Dept. of
Health AAC
24 h
Vanadium
0.0005
NR
0.05 mg/m3
V205
ACGIH
TLV-TWA
(ACGIH.
1991)
Total UP =
100
Pinellas
County Air
Pollution
Control
Board AAC
8 h
Vanadium pentoxide
0.00012
NR
NR
NR
NR
24 h
0.0005
iy
0.02
NDDH ACG
8 h
Vanadium pentoxide
0.0005
NR
0.05 mg/m3
ACGIH
TLV-TWA
(ACGIH.
1991)
Total UF =
100
TX Air
Control
Board AAC
30 min
Vanadium pentoxide
0.0005
NR
NR
NR
NR
Based on
occupational
values
iy
0.00005
VA Air
Pollution
Control AAC
24 h
Vanadium pentoxide
0.0008
NR
0.05 mg/m3
ACGIH
TLV-TWA
(ACGIH.
1991)
Total UFk =
60
Latvia Limit
8 h
Vanadium trioxide
0.5
NR
NR
NR
NR
Final
Value
Vanadium and compounds
1
(IFA. 2019)
IS
c
Vanadium pentoxide fume
0.1
o
IS
c
a>
China Limit
Value
8 h
Vanadium
0.05
NR
NR
NR
NR
c
Finland OEL
8-h TWA
Ferrovanadium, as V
0.5
NR
NR
NR
NR
IS
c
o
Vanadium pentoxide, as V
0.02
IS
a
3
u
u
o
Austria Limit
Value
Short-term
Vanadium pentoxide,
respirable aerosol
0.25
NR
NR
NR
NR
Vanadium, inhalable
1
8 h
aerosol, and vanadium
carbide
0.5
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Reference
value name
Duration
Vanadium form
Reference
value
(mg/m3)
Health effect
Point of
departure
Qualifier
Source
Uncertainty
factors
Notes on
derivation
Review status
HIOH Limit
Value
(Hungary)
Short-term
Vanadium pentoxide,
respirable aerosol
0.2
NR
NR
NR
NR
Romania
Limit Value
15 min
Ferrovanadium
1.5
NR
NR
NR
NR
Vanadium pentoxide
0.1
8-h TWA
Ferrovanadium
0.5
Vanadium pentoxide fume
0.05
Vanadium pentoxide dust
0.1
Denmark
Limit Value
Short-term
Vanadium pentoxide,
inhalable aerosol
0.06
NR
NR
NR
NR
8 h
0.03
Sweden
Limit Value
8 h
Vanadium pentoxide,
inhalable fraction
0.2
NR
NR
NR
NR
SER MAC
(The
Netherlands)
Short-term
Vanadium oxides
0.03
NR
NR
NR
NR
8 h
0.01
aMEG = TLV X IRoccupational t- IRmilitary = 1 mg/m3 X (10 IT13 t- 29.2 IT13) = 0.34 ITlg/m3.
bMEG = MRL x (IRgenerai pop. t- IRmilitary) = 0.0002 mg/m3 x (20 m3/day t- 29.2 m3/day) = 0.00014 mg/m3.
Based on the derivation details provided and information from Rhode Island Department of Environmental Management, it is assumed that an MRL of 0.0002 mg/m3
was in effect when this value was derived.
CMEG = MRL x (IRgenerai pop. t- IRmilitary) = 0.0008 mg/m3 x (20 m3/day t- 29.2 m3/day) = 0.00055 mg/m3.
dMEG = TLV x I Roccupational t- IRmilitary = 1 mg/m3 x (10 m3 t- 29.2 m3) = 0.34 mg/m3.
eMEG = MRL x (IRgenerai pop. t- IRmilitary) = 0.0002 mg/m3 x (20 m3/day t- 29.2 m3/day) = 0.00014 mg/m3.
Based on the derivation details provided and information from Rhode Island Department of Environmental Management, it is assumed that an MRL of 0.0002 mg/m3
was in effect when this value was derived.
fMEG = MRL x (IRgenerai pop. t- IRmilitary) = 0.0001 mg/m3 x (20 m3/day t- 29.2 m3/day) = 0.000068 mg/m3.
gl-hr AQG = 24-hr AQG x 3.8 = 0.0004 mg/m3 x 3.8 = 0.0015 mg/m3.
hThis document was compiled by the U.S. Environmental Protection Agency in 1993. Values from this document may have since been archived or updated by the state
agencies that reported them.
'AQG = TLV t- 126 = 0.05 mg/m3 4-126 = 0.0004 mg/m3.
JA factor of 100 is applied to category A substances.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
kA factor of 60 is applied for noncarcinogens.
AAC = acceptable ambient concentration; AAL = allowable ambient limit, ACG = ambient concentration guideline; ACGIH = American Conference of Governmental
Industrial Hygienists; ADEQ = Arizona Department of Environmental Quality; AQG = air quality guideline; ASIL = acceptable source impact level; DOE = Department of
Energy; EPA = Environmental Protection Agency; HAAS = hazardous ambient air standard; HIOH = Hungarian Institute of Occupational Health; ID DEQ = Idaho
Department of Environmental Quality; IFA = Institut fur Arbeitsschutz, The Institute for Occupational Safety and Health; MAC = maximum admissible concentration;
MassDEP = Massachusetts Department of Environmental Protection; MEG = military exposure guideline; MRL = minimal risk level; NDDH = North Dakota Department of
Health; NDEP = Nevada Division of Environmental Protection; NR = not reported; OEL = occupational exposure limit; PAC = Protective Action Criteria; RfC = reference
concentration; SER = Social and Economic Council of the Netherlands; SWCAA = Southwest Clean Air Agency; TCEQ = Texas Commission on Environmental Quality;
TEL = toxic effects exposure limit; TLV = threshold limit value; TWA = time-weighted average; UF = uncertainty factor; USAPHC = United States Army Public Health
Center; V = vanadium; V2O5 = vanadium pentoxide; VT DEC = Vermont Department of Environmental Conservation; WAC = Washington Administrative Code.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
APPENDIX B. LITERATURE SEARCH STRATEGIES
Table B-l. Literature search strategies for vanadium compounds
Source
Search Strategy
Number of
records
WOS
3/28/2019
3/9/2020
((TS="Ammonium metavanadate" ORTS="Ammonium monovanadate" OR
TS="Ammonium trioxovanadate" ORTS="Monosodium trioxovanadate" OR
TS="Oxosulfatovanadium pentahydrate" ORTS="Sodium metavanadate" OR
TS="Sodium o-vanadate" ORTS="Sodium orthovanadate" ORTS="Sodium
pervanadate" ORTS="Sodium tetraoxovanadate" ORTS="Sodium
trioxovanadate" ORTS="Sodium vanadate" ORTS="Trisodium orthovanadate"
ORTS="Trisodium tetraoxovanadate" ORTS="Trisodium vanadate" OR
TS="Vanadic sulfate" OR TS="vanadium" OR TS="Vanadyl sulfate" OR
TS="Vanadic" ORTS="Vanadin" ORTS="sodium peroxyvanadate" ORTS="Vanadyl
sulfate pentahydrate" ORTS="Ammonium vanadate" ORTS="Divanadium
trioxide" ORTS="Sodium hexavanadate") AND PY=(2010-2019))
((TS="Sodium tetravanadate" OR TS="Sodium vanadite" OR TS="Sulfovanadic
acid" ORTS="vanadium salt" ORTS="Tetrachlorovanadium" ORTS="Trichlorooxo
vanadium" ORTS="Trichlorooxovanadium" ORTS="Trichlorooxovanadium oxide"
OR TS="Vanadic acid" OR TS="Vanadic oxide" OR TS="Vanadious" OR
TS="Vanadosulfuric acid" OR TS="Vanadyl chloride" OR TS="Vanadyl trichloride"
ORTS="Divanadium pentaoxide" ORTS="Divanadium pentoxide" ORTS="Vanadic
acid anhydride" OR TS="Vanadic anhydride" OR TS="Vanadin(V) oxide" OR
TS="Vanadium dust" ORTS="Vanadium fume" ORTS="Vanadium oxide" OR
TS="Vanadium pentaoxide" ORTS="Vanadium pentoxide") AND PY=(2010-2019))
((TS="Vanadium" AND (TS="chloride" ORTS="dichloride" ORTS="oxide" OR
TS="oxychloride" ORTS="oxytrichloride" ORTS="sesquioxide" OR TS="sulfate"
ORTS="sulphate" ORTS="tetrachloride" OR TS="trichloride" ORTS="trioxide"))
AND PY=2010-2019)
24,887
PUBMED
3/28/2019
3/9/2020
«(7440-62-2[rn] OR 00J9J9XKDE[rn] OR 27774-13-6[rn] OR 6DU9Y533FA[rn] OR
13718-26-8[rn] OR 13721-39-6[rn] OR 7803-55-6[rn] OR FL85PX638G[rn] OR
12439-96-2[rn] OR "Ammonium metavanadate"[tw] OR "Ammonium
monovanadate"[tw] OR "Ammonium trioxovanadate"[tw] OR "Monosodium
trioxovanadate"[tw] OR "Oxosulfatovanadium pentahydrate"[tw] OR "Sodium
metavanadate"[tw] OR "Sodium o-vanadate"[tw] OR "Sodium
orthovanadate"[tw] OR "Sodium pervanadate"[tw] OR "Sodium
tetraoxovanadate"[tw] OR "Sodium trioxovanadate"[tw] OR "Sodium
vanadate"[tw] OR "Trisodium orthovanadate"[tw] OR "Trisodium
tetraoxovanadate"[tw] OR "Trisodium vanadate"[tw] OR "Vanadic sulfate"[tw]
OR vanadium[tw] OR "Vanadyl sulfate"[tw] OR Vanadic[tw] OR Vanadin[tw] OR
"sodium peroxyvanadate"[tw] OR "Vanadyl sulfate pentahydrate"[tw] OR 16785-
81-2[rn] OR 12436-28-l[rn] OR 12058-74-l[rn] OR 64082-34-4[rn] OR 10580-52-
6[rn] OR 7718-98-l[rn] OR 1314-34-7[rn] OR 7632-51-l[rn] OR 11115-67-6[rn] OR
7727-18-6[rn] OR "Ammonium vanadate"[tw] OR "Divanadium trioxide"[tw] OR
4,888
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Source
Search Strategy
Number of
records
"Sodium hexavanadate"[tw] OR "Sodium tetravanadate"[tw] OR "Sodium
vanadite"[tw] OR "Sulfovanadic acid"[tw] OR "vanadium salt"[tw] OR
Tetrachlorovanadium[tw] OR "Trichlorooxo vanadium"[tw] OR
Trichlorooxovanadium[tw] OR "Trichlorooxovanadium oxide"[tw] OR "Vanadic
acid"[tw] OR "Vanadic oxide"[tw] OR Vanadious[tw] OR "Vanadosulfuric acid"[tw]
OR "Vanadyl chloride"[tw] OR "Vanadyl trichloride"[tw] OR 1314-62-l[rn] OR
"Divanadium pentaoxide"[tw] OR "Divanadium pentoxide"[tw] OR "Vanadic acid
anhydride"[tw] OR "Vanadic anhydride"[tw] OR "Vanadin(V) oxide"[tw] OR
"Vanadium dust"[tw] OR "Vanadium fume"[tw] OR "Vanadium oxide"[tw] OR
"Vanadium pentaoxide"[tw] OR "Vanadium pentoxide"[tw]) OR (Vanadium[tw]
AND (chloride[tw] OR dichloride[tw] OR oxide[tw] OR oxychloride[tw] OR
oxytrichloride[tw] OR sesquioxide[tw] OR sulfate[tw] OR sulphate[tw] OR
tetrachloride[tw] OR trichloride[tw] ORtrioxide[tw]))) AND ("2010"[PDAT] :
"3000"[PDAT]))
TOXLINE
3/28/2019
@SYN0+@AND+@OR+(@TERM+@rn+7440-62-2+@TERM+@rn+27774-13-
6+@TERM+@rn+13718-26-8+@TERM+@rn+13721-39-6+@TERM+@rn+7803-55-
6+@TERM+@rn+12439-96-2+@TERM+@rn+16785-81-2+@TERM+@rn+12436-
28-l+@TERM+@rn+12058-74-l+@TERM+@rn+64082-34-
4+@TE RM+@ rn+10580-52-6+@TERM+@ rn+7718-98-l+@TERM+@rn+1314-34-
7+@TERM+@rn+7632-51-l+@TERM+@rn+11115-67-6+@TERM+@rn+7727-18-
6+@TE RM+@rn+1314-62-
l)+@RANGE+yr+2010+2019+@NOT+@org+pubmed+pubdart+nih
@SYNO+@AND+@OR+(FL85PX638G+6DU9Y533FA+OOJ9J9XKDE+"Ammonium+m
etavanadate"+"Ammonium+monovanadate"+"Ammonium+trioxovanadate"+"M
onosodium+trioxovanadate"+"Oxosulfatovanadium+pentahydrate"+"Sodium+me
tavanadate"+"Sodium+o-
vanadate"+"Sodium+orthovanadate"+"Sodium+pervanadate"+"Sodium+tetraoxo
vanadate"+"Sodium+trioxovanadate"+"Sodium+vanadate"+"Trisodium+orthovan
adate"+"Trisodium+tetraoxovanadate"+"Trisodium+vanadate"+"Vanadic+sulfate
"+vanadium+"Vanadyl+sulfate"+Vanadic+Vanadin+"sodium+peroxyvanadate"+"V
anadyl+sulfate+pentahydrate"+"Ammonium+vanadate"+"Divanadium+trioxide"+
"Sodium+hexavanadate"+"Sodium+tetravanadate"+"Sodium+vanadite"+"Sulfova
nadic+acid"+"vanadium+salt"+"Trichlorooxo+vanadium"+Tetrachlorovanadium+T
richlorooxovanadium+"Trichlorooxovanadium+oxide"+"Vanadic+acid"+"Vanadiu
m+dust"+"Vanadium+fume"+"Vanadium+oxide"+"Vanadium+pentaoxide"+"Vana
dium+pentoxide"+"Vanadic+oxide"+Vanadious+"Vanadosulfuric+acid"+"Vanadyl
+chloride"+"Vanadyl+trichloride"+"Divanadium+pentaoxide"+"Divanadium+pent
oxide"+"Vanadic+acid+anhydride"+"Vanadic+anhydride"+"Vanadin+V+oxide")+@
RANGE+yr+2010+2019+@NOT+@org+pubmed+pubdart+nih
@SYNO+@AND+vanadium+@OR+(chloride+dichloride+oxide+oxychloride+oxytri
chloride+sesquioxide+sulfate+sulphate+tetrachloride+trichloride+trioxide)+@RA
NGE+yr+2010+2019+@NOT+@org+pubmed+pubdart+nih
15
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
Source
Search Strategy
Number of
records
ATSDR
Toxicological
Profile for
Vanadium
(2012)
References pulled from ATSDR document
363
2008 & 2009
PPRTV
Assessments
References pulled from PPRTV documents
75
2011 IRIS
External
Review Draft
References pulled from V2O5 IRIS document
49
2006IARC
Document
References pulled from IARC document
240
OAR
References provided by Office of Air and Radiation (OAR)
10
TOTAL
25,988 unique items were discovered using this search strategy.
25,988
This document is a draft for review purposes only and does not constitute Agency policy.
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
IRIS Assessment Plan for Vanadium (Inhalation)
APPENDIX C. PRELIMINARY LITERATURE SEARCH
AND SCREENING METHODS
The Agency for Toxic Substances and Disease Registiy (ATSDR) Toxicological Profile for
Vanadium f ATSDR. 20121 was selected as the starting point for the literature search because it is
the most recent review of health effects of vanadium compounds published by a U.S. federal agency.
ATSDR assessments undergo public comment and external peer review. All references from the
2012 ATSDR Toxicological Profile for Vanadium were extracted by an EPA information specialist
and stored in the Health and Environmental Research Online (HERO) database.8
Database searches were then conducted to identify records that had been published since
development of the 2012 ATSDR Toxicological Profile for Vanadium. The databases listed below
were searched for records published between 2010 and 2019. The start date of 2010 was selected
to ensure records published near the time of release of the ATSDR document were captured.
• PubMed (National Library of Medicine)
• Web of Science (Thomson Reuters)
• ToxLine (National Library of Medicine)
Database searches were conducted by an EPA information specialist on March 28, 2019, and
repeated on March 9, 2020,9 and all records were stored in the HERO database. In total, 22,559
unique records were identified after duplicate removal. Because the number of records retrieved
was large, records were imported into Sciome Workbench for Interactive computer-Facilitated
Text-mining (SWIFT) Review software [see also Howard etal. (2016)] to identify those most likely
applicable to human health. In brief, SWIFT Review has preset literature search filters, which were
developed by information specialists, that can be applied to distinguish studies that might present a
health outcome from those that likely do not (e.g., exposure only, analytical methods). The filters
function like a typical search strategy, where studies are tagged as belonging to a certain category
based on terms appearing in title, abstract, keyword, or Medical Subject Heading (MeSH) fields
content The records identified in the literature search for vanadium were filtered using tags in
SWIFT Review for lines of evidence (human, animal, in vitro) and health outcomes (cancer,
8EPA's HERO database provides access to the scientific literature behind EPA science assessments. The
database includes scientific references and data from the peer-reviewed literature used by EPA to develop its
regulations.
9The Toxline database was taken down and migrated to PubMed prior to the March 2020 literature search
update, so the Toxline search was only conducted in March 2019.
This document is a draft for review purposes only and does not constitute Agency policy.
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
IRIS Assessment Plan for Vanadium (Inhalation)
cardiovascular, developmental, endocrine, gastrointestinal, hematological and immune, hepatic,
mortality, musculoskeletal, neurological, nutrition and metabolic, ocular and sensory, renal,
reproductive, respiratory, and skin and connective tissue). The details of the search strategies that
underlie the filters are available at this link. Studies not retrieved using these filters were not
considered further. Studies that included one or more of the search terms in the title, abstract,
keyword, or MeSH fields were exported as a RIS file for screening in DistillerSR.10 as described
below.
This literature search strategy is designed to be broad, but like any search strategy, studies
might be missed (e.g., cases where the specific chemical is not mentioned in title, abstract, or
keyword content; "gray" literature that is not indexed in the databases listed above). Thus, when
additional references that were cited in prior assessments or shared by EPA program offices
(e.g., Office of Air), these references were annotated with respect to the source of the record and
screened using the same methods applied to the rest of the literature inventory. In this evidence
map, additional references were provided by OAR and were identified by manual review of the
following list of final or publicly available draft assessments:
• PPRTV assessment of vanadium pentoxide (U.S. EPA. 2008)
• PPRTV assessment of vanadium and its soluble compounds other than vanadium pentoxide
flJ.S. EPA. 20091
• IRIS External Review Draft assessment of vanadium pentoxide (U.S. EPA. 2011)
• International Agency for Research on Cancer (IARC) document on vanadium pentoxide
flARC. 20061.
10DistiIIerSR is a web-based systematic review software used to screen studies available at
https://www.evidencepartners.com/products/distiIIersr-systematic-review-software.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Vanadium (Inhalation)
APPENDIX D. PRELIMINARY LITERATURE SURVEY
SUMMARY
PubMed
(n = 4,888)
Database Searches (2010—2020)
N = 25,632 after duplicate removal
wos
(n = 24,887)
ToxLine
(n - 15)
N = 25,988 records (after duplicate removal)
SWIFT Review software
identification of potentially relevant studies based on
application of SWIFT-Review evidence stream and
health outcome tags, n = 3,287
T
Other Resources
2012 ATSDR
(n = 363)
2008 &2009PPRTV
(n a 75)
2011 IRIS
(n = 49)
2006 IARC
(n = 241)
OAR
(n = 10)
T
TITLE AND ABSTRACT SCREENING
Title & Abstract Screening
(3565 records after duplicate removal)
T
FULLTEXT SCREENING
Full-Text Screening
(n = 346)
Studies meeting PECO criteria (n = 97)
• Human health effects studies (n = 67)
• Animal health effects studies (n = 30)
• PBPK studies (n = 0)
Studies meeting PECO criteria that also
reported mechanistic or ADME
information (n= 33)
Excluded (n = 2188) Not PECO relevant
Supplemental (n = 1031)
Sum of excluded & supplemental (n = 3219)
Excluded (n = 64) Not PECO relevant
Supplemental (n = 185)
Sum of excluded & supplemental (n = 249)
Tagged as Supplemental (n = 1249 total)
mechanistic (nongenotoxic) (n =589),
mechanistic (genotoxic) (n =94),
non-mammalian model (n = 19),
non-inhalation route (n = 390),
ADME/TK (n = 83),
exposure characteristics (n = 116),
mixture studies (n =51),
case studies or case series (n = 9),
no original data (n = 14-9),
conference abstract (n = 29)
Figure D-l. Literature survey study flow selection diagram,
This document is a draft for review purposes only and does not constitute Agency policy,
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