IRIS

IRIS Bimonthly Public Meeting (Jun 2014)

EPA hosted a Bimonthly IRIS public meeting to provide an opportunity for the public to give input and participate in an open discussion regarding preliminary materials that were prepared for IRIS chemicals prior to the development of the draft assessment. This included the following chemicals:

  • Hexavalent Chromium (Cr(VI))
  • Inorganic Arsenic (iAs)

Note: The preliminary materials for inorganic arsenic and hexavalent chromium present study information using two very different approaches with varying levels of detail.  Inorganic arsenic is exploring the use of a modification of the draft approach developed by the NTP’s Office of Health Assessment and Translation, while hexavalent chromium is using modified approaches under development by the IRIS Program. The IRIS Program intends to evaluate how well each approach facilitates subsequent assessment development, promotes constructive public discussion, and makes efficient use of program resources.

Meeting Objective:

The objective of this public meeting was to obtain input from stakeholders and the public on the studies and data that will be used in the assessments that are under development. Specifically, EPA was seeking input on preliminary materials including draft literature searches and associated search and screening strategies, the approach for selecting primary studies to be included in the evidence tables, the approach for evaluating methodological features of studies, evidence tables, and exposure-response arrays prior to the development of the IRIS assessments.

Dates:

The meeting was held on June 25-27 , 2014 from 9:00am - 5:00 pm Eastern Time.

Location:

The meeting was held at the EPA Conference Center at 2777 South Crystal Drive, Arlington, Virginia 22202. The meeting was also streamed by webinar/teleconference for remote participants.

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Meeting Agenda:

On June 25-27, 2014, EPA hosted a public meeting/webinar in Arlington, VA, to provide an opportunity for the public to give input and participate in an open discussion regarding several IRIS chemical assessments that are under development.

Meeting Documents:

EPA released the draft literature searches and associated search strategies, evidence tables, and exposure response arrays for 2 chemicals to obtain input from stakeholders and the public prior to developing the draft IRIS assessments. Specifically, EPA was interested in comments on the following:

  • Draft literature search strategies
    • The approach for identifying studies
    • The screening process for selecting pertinent studies
    • The resulting list of pertinent studies
  • Preliminary evidence tables
    • The process for selecting studies to include in evidence tables
    • The quality of the studies in the evidence tables

The literature search strategy, which describes the processes for identifying scientific literature, contains the studies that EPA considered and selected to include in the evidence tables. The preliminary evidence tables and exposure-response arrays present the key study data in a standardized format. The evidence tables summarize the available critical scientific literature. The exposure-response figures provide a graphical representation of the responses at different levels of exposure for each study in the evidence table.

The chemicals and associated discussion materials include:

Hexavalent Chromium (Cr(VI)): Catherine Gibbons & Alan Sasso, Assessment Managers

Key Science issues:

  • Science Issue 1: Cancer classification by inhalation. In 1998, EPA classified hexavalent chromium as a "known human carcinogen by the inhalation route of exposure" based on consistent evidence that inhaled chromium causes lung cancer in humans and hexavalent chromium causes cancer in animals. The same conclusion has been reached by other federal, state, and international health agencies. Accordingly, this assessment plans to adopt this conclusion and focus its review of the lung cancer evidence on identifying studies that might improve the quantitative dose-response analysis (see Section 1.3.3 of the Preliminary Material). EPA is seeking public discussion of this plan.
     
  • Science Issue 2: Noncancer hazards to be considered. Based on the hazards identified in recent reviews by other federal, state, and international health agencies and on an examination of the more recently published studies, this assessment plans to focus its review on the potential for respiratory, gastrointestinal, immunological, hematological, hepatic, reproductive, and developmental effects (Section 1.3.5). EPA is seeking public discussion of this plan, including evidence for including additional health effects.
     
  • Science Issue 3: Susceptibility of mice to gastrointestinal toxicity. Diffuse epithelial hyperplasia of the duodenum was observed in the 2-year NTP drinking water bioassay at concentrations as low as 5 ppm (approximately 0.4 mg/kg‑d, Table 3-2). Analogous effects, however, were not observed in rats, suggesting that mice may be more susceptible to gastrointestinal toxicity. EPA is seeking public discussion of (1) toxicokinetic or toxicodynamic factors that might explain the susceptibility of mice to gastrointestinal toxicity and (2) whether other effects in mice may be secondary to gastrointestinal toxicity.
     
  • Science Issue 4: Utility of subchronic histopathological data. A subchronic (90-day) study in rodents observed histopathological effects in the intestinal crypts and villi at high drinking water concentrations, but not at lower concentrations (Table 3-2). EPA is seeking public discussion on the extent to which these subchronic toxicological data can inform the effects of chronic exposure to hexavalent chromium.
     
  • Science Issue 5: Database for reproductive and developmental effects. NTP studies did not observe treatment-related reproductive effects in male or female rats or mice. Other studies have observed reproductive as well as developmental effects in rats and mice, but often at doses exceeding those found to induce gastrointestinal tract effects or maternal toxicity. In addition, methodological or record-keeping anomalies have been identified for some studies (see Section 2.2.2). EPA is seeking public discussion of the overall quality of the database for reproductive and developmental effects.
     
  • Science issue 6: Relation between anemia and oral tumors in rats. The 2-year NTP drinking water bioassay observed squamous cell carcinomas of the oral mucosa at concentrations as low as 60 ppm in female rats (2.4 mg/kg-d) and 180 ppm in male rats (5.9 mg/kg-d) (Table 3-11). Oral tumors were not observed in mice. As hematological effects were observed at a higher incidence in rats versus mice (Table 3-5), it has been suggested that oral tumors are secondary to, or may be exacerbated by, anemia. EPA is seeking public discussion on the occurrence of anemia and its possible relationship to oral tumors.

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Inorganic Arsenic (iAs): Janice Lee & John Cowden, Assessment Managers

Key Science issues:

  • Science Issue 1: Application of NRC recommendations. The preliminary material include an Assessment Development Plan (Section 1) that characterizes scoping, problem formulation, and the overarching approach for the IRIS assessment. EPA is seeking public discussion on the structure and utility of the Assessment Development Plan and whether it has appropriately applied the recommendations from NRC (2013), Critical Aspects of EPA’s IRIS Assessment of Inorganic Arsenic: Interim Report.
     
  • Science Issue 2: Risk-of-bias approach. This assessment uses an approach for evaluating risk-of-bias in human and animal studies. EPA is seeking public discussion on the transparency, appropriateness, and utility of the risk-of-bias approach.
     
  • Science Issue 3: Integrating results of epidemiologic studies. The epidemiologic studies have employed different approaches to exposure characterization, resulting in different dose metrics. EPA is seeking public discussion on approaches it can use to evaluate health effect information across epidemiologic studies.
     
  • Science Issue 4: Concordance of effects between human and animals. NRC (2013) identified a tiered set of health effects for inorganic arsenic. EPA is seeking public discussion on whether animal studies on each endpoint are informative of the potential for similar effects in humans.
     
  • Science Issue 5: Upstream biological events for clinical disease endpoints. NRC (2013) identified a tiered set of health effects for inorganic arsenic. EPA is seeking public discussion to identify upstream biological events (in humans or in animals) that can be used as markers for each of these clinical disease endpoints.
     
  • Science Issue 6: Mode-of-action and adverse outcome pathways. The preliminary materials include mode-of-action summaries and mechanistic data tables intended to facilitate subsequent development of adverse outcome pathways for the health effects of inorganic arsenic. (EPA is presenting this material to stimulate public discussion and has not yet conducted mode-of-action or adverse-outcome-pathway analyses.) EPA is seeking public discussion on (1) the transparency and utility of the mode-of-action summaries and mechanistic data tables, (2) how mechanistic data can inform the hazard identification and dose-response analysis for each hazard, (3) specific hypothesized modes-of-action for the dose-response analysis for each hazard, and (4) whether there are other modes-of-action that warrant consideration.
     
  • Science Issue 7: In-utero exposure leading to disease later in life. Human and animal studies suggest that in-utero exposure to inorganic arsenic may contribute to subsequent development of disease later in life. EPA is seeking public discussion to identify approaches that can be used to evaluate these studies for hazard identification and subsequent dose-response analysis.
     
  • Science Issue 8: Implications of nutritional factors in internal dose and response. (Topic added based upon following comment from public stakeholder) Exposure assessment for study populations compared to the United States population. Populations exposed to high arsenic levels in well water in countries such as Bangladesh and West Bengal also receive increased inorganic arsenic exposure because of their diet and cooking practices as well as from crops grown using contaminated water. In addition, many issues should be considered in assessing exposure to inorganic arsenic when using urinary arsenic levels. In particular, total arsenic in urine is confounded by organic arsenic compounds from the diet. Arsenic species in urine such as DMA may arise from inorganic arsenic methylation as well as directly from its presence in the diet or from ingestion of arsenosugars or other dietary precursor compounds.

Susceptibility to arsenic toxicity and the dose-response relationship may be affected by a number of factors that enhance arsenic toxicity as well as independently increase risk of various diseases (e.g., nutritional deficiencies, smoking, and betel nut use are very important factors for Bangladesh).

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General Comments:

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