IRIS Public Science Meeting (Jul 2021)

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Meeting Details
Meeting Materials

Meeting Details

At IRIS Public Science Meetings, the IRIS Program encourages the scientific community and the public to participate in discussions on IRIS draft assessment materials. The scientific information and perspectives from the meeting would be considered as this assessment progresses.

At this meeting, the IRIS Program invited public discussion on the following draft assessment material:

IRIS Assessment Plan for Inhalation Exposure to Vanadium and Compounds (Scoping and Problem Formulation Materials)

Dates

The meeting was held on July 14, 2021.

Meeting Materials

Meeting Agenda

A preliminary meeting agenda will be posted in early-July 2021.

On July 14, 2021, EPA hosted a public webinar to provide an opportunity for the public to give input and participate in an open discussion regarding the IAP for Inhalation Exposure to Vanadium and Compounds. See the final agenda and meeting presentation materials below:

Inhalation Exposure to Vanadium and Compounds Assessment Managers: Sury Vulimiri and Kathleen Newhouse

IRIS Assessment Plan for Inhalation Exposure to Vanadium and Compounds (Scoping and Problem Formulation Materials)
Literature Search References Sorted by Author (Inhalation Exposure to Vanadium and Compounds)(dynamic literature link - generated by HERO)
Provide comments on these materials in the Inhalation Exposure to Vanadium and Compounds Docket at EPA-HQ-ORD-2020-0182.
Federal Register Notice: May28, 2021 announcing the availability of the draft IRIS Assessment Plan for a 30-day public comment period.

Key Science Topics
What is an IRIS Assessment Plan? An IRIS Assessment Plan (IAP) communicates the plan for assessing each individual chemical to the public. It includes summary information on scoping and initial problem formulation, specific aims and objects for the assessment, identifies key areas of scientific complexity, and it includes the PECO (Populations, Exposures, Comparators, and Outcomes) criteria that outline the evidence considered most pertinent to the assessment. The PECO provides the framework for developing literature search strategies and inclusion/exclusion criteria, particularly with respect to evidence stream (i.e., human, animal, mechanistic), exposure measures and outcome measures. The IRIS Program is seeking a discussion with the public aimed at improving or clarifying the IAP. Below are questions to facilitate the discussion of these science topics: Are the assessment objectives and specific aims articulated clearly? Does the background information and context that is provided support the objectives for the assessment presented in the plan? Does the proposed PECO (Populations, Exposures, Comparators, Outcomes) framework identify the most pertinent evidence to address the stated needs of the Agency programs and regions? Science Topics Key Topic 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 (Roberts et al., 2016). 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., González-Villalva et al. (2011), rather than exposure to vanadium as a dust, e.g., NTP (2002)]. In addition, data to inform potential conversion between vanadium oxidation state in the body also will be evaluated and discussed in the assessment. Key Topic 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 Topic 3. Interpretation of data on rodent tumor responses. The NTP (2002) 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 Topic 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 alveolar/bronchiolar neoplasms, including judgments regarding human relevance, is expected to be a key component of the vanadium (inhalation) IRIS assessment.

Key Science Topics

What is an IRIS Assessment Plan? An IRIS Assessment Plan (IAP) communicates the plan for assessing each individual chemical to the public. It includes summary information on scoping and initial problem formulation, specific aims and objects for the assessment, identifies key areas of scientific complexity, and it includes the PECO (Populations, Exposures, Comparators, and Outcomes) criteria that outline the evidence considered most pertinent to the assessment. The PECO provides the framework for developing literature search strategies and inclusion/exclusion criteria, particularly with respect to evidence stream (i.e., human, animal, mechanistic), exposure measures and outcome measures.

The IRIS Program is seeking a discussion with the public aimed at improving or clarifying the IAP. Below are questions to facilitate the discussion of these science topics:

Are the assessment objectives and specific aims articulated clearly?
Does the background information and context that is provided support the objectives for the assessment presented in the plan?
Does the proposed PECO (Populations, Exposures, Comparators, Outcomes) framework identify the most pertinent evidence to address the stated needs of the Agency programs and regions?

Science Topics

Key Topic 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 (Roberts et al., 2016). 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., González-Villalva et al. (2011), rather than exposure to vanadium as a dust, e.g., NTP (2002)]. In addition, data to inform potential conversion between vanadium oxidation state in the body also will be evaluated and discussed in the assessment.

Key Topic 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 Topic 3. Interpretation of data on rodent tumor responses. The NTP (2002) 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 Topic 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 alveolar/bronchiolar neoplasms, including judgments regarding human relevance, is expected to be a key component of the vanadium (inhalation) IRIS assessment.