Draft Charge to External Reviewers for the IRIS Toxicological Review of Vanadium 

Pentoxide 

July 2011 

The U.S. Environmental Protection Agency (EPA) is seeking an external peer review of the 

scientific basis supporting the human health assessment of vanadium pentoxide that will appear 

on the Agency’s online database, the Integrated Risk Information System (IRIS). IRIS is 

prepared and maintained by the EPA’s National Center for Environmental Assessment (NCEA) 

within the Office of Research and Development (ORD). An existing IRIS assessment for 

vanadium pentoxide, which includes an oral reference dose (RfD), was posted on IRIS in 1987. 

The current draft health assessment includes an RfD, an RfC and carcinogenicity assessment. 

Below is a set of charge questions that address scientific issues in the assessment of vanadium 

pentoxide. Please provide detailed explanations for responses to the charge questions. Please 

consider the accuracy, objectivity, and transparency of EPA’s analyses and conclusions in your 

review. 

General Charge Questions: 

1. Is the Toxicological Review logical, clear and concise? Has EPA clearly presented and 

synthesized the scientific evidence for noncancer and cancer hazard? 

2. Please identify any additional studies that would be likely to make a significant impact on the 

conclusions of the Toxicological Review. 

Chemical-Specific Charge Questions: 

(A) Oral Reference Dose (RfD) for Vanadium Pentoxide 

1. A chronic RfD for vanadium pentoxide has been derived from the subchronic oral dietary 

study (Mountain et al., 1953) in Wistar rats. Please comment on whether the selection of this 

study as the principal study is scientifically supported and clearly described. Please identify and 

provide the rationale for any other studies that should be selected as the principal study. 

2. Decreased red blood cells in male Wistar rats were selected as the critical effect. Please 

comment on whether the selection of this critical effect is scientifically supported and clearly 

described. Please identify and provide the rationale for any other endpoints that should be 

selected as the critical effect. 

3. The NOAEL/LOAEL approach with dosimetric adjustments for calculating the human 

equivalent dose was used to derive the POD. Please comment on whether this approach is 

scientifically supported and clearly described. 
4. Please comment on the rationale for the selection of the uncertainty factors (UFs) applied to 

the POD for the derivation of the RfD. If changes to a UF are proposed, please identify and 

provide a rationale(s). 

(B) Inhalation Reference Concentration (RfC) for Vanadium Pentoxide 

1. A two-year bioassay of vanadium pentoxide in F344 rats (NTP, 2002) was selected as the 

basis for the derivation of the RfC. Please comment on whether the selection of this study as the 

principal study is scientifically supported and clearly described. Please identify and provide the 

rationale for any other studies that should be selected as the principal study. 

2. Laryngeal lesions in female F344 rats were selected as the critical effect for the RfC. Please 

comment on whether the selection of this critical effect is scientifically supported and clearly 

described. Please identify and provide the rationale for any other endpoints that should be 

selected as the critical effect. 

3. Benchmark dose (BMD) modeling was conducted on the incidence of laryngeal lesions in 

female F344 rats in conjunction with dosimetric adjustments for calculating the human 

equivalent concentration to derive the point of departure (POD). Has this approach been 

appropriately conducted and clearly described? Is the benchmark response (BMR) selected for 

use in deriving the POD (i.e. A 10% extra risk of incidence of laryngeal lesions) scientifically 

supported and clearly described? 

4. Please comment on the rationale for the selection of the uncertainty factors (UFs) applied to 

the POD for the derivation of the RfC. Are the UFs scientifically supported and clearly 

described? If changes to the selected UFs are proposed, please identify and provide a rationale. 

(C) Carcinogenicity of Vanadium Pentoxide 

1. Under the EPA’s 2005 Guidelines for Carcinogen Risk Assessment

(www.epa.gov/iris/backgrd.html), vanadium pentoxide is “likely to be carcinogenic to humans” 

by the inhalation route of exposure. Is the cancer weight of evidence characterization 

scientifically supported and clearly described? 

2. EPA has concluded that the available data do not support any specific mode of action for 

vanadium pentoxide-induced lung tumors in mice. Please comment on whether this 

determination is scientifically supported and clearly described. Please comment on data 

available for vanadium pentoxide that may support an alternative mode of action. 

Oral Slope Factor (OSF) 

3. An OSF was not derived due to lack of available studies to characterize the carcinogenic 

potential of vanadium pentoxide administered via ingestion. Is the rationale for not deriving an 

OSF scientifically supported and clearly described? Please identify and provide rationale for any 

studies that should be selected as the principal study. 
Inhalation Unit Risk (IUR) 

4. A two-year bioassay of vanadium pentoxide in B6C3F1 mice (NTP, 2002) was selected for 

the derivation of an IUR. Please comment on whether the selection of this study for quantitation 

is scientifically supported and clearly described. Please identify and provide the rationale for 

any other studies that should be selected for quantitation. 

5. The incidence of respiratory tumors in B6C3F1 male mice was selected to serve as the basis 

for the quantitative inhalation cancer assessment. Please comment on whether this selection is 

scientifically supported and clearly described. Please identify and provide the rationale for any 

other endpoints that should be selected to serve as the basis for the IUR. 

6. The IUR was calculated by low-dose linear extrapolation from the POD (i.e., the lower 95% 

confidence limit on the concentration associated with 71% extra risk of respiratory tumors). Has 

the modeling been appropriately conducted and clearly described?