IRIS

IRIS Public Science Meeting (May 2018)

EPA hosted an IRIS public science meeting to provide an opportunity for the public to give input and participate in an open discussion regarding the IRIS Assessment Plan (IAP) that was prepared for this IRIS chemical prior to the development of the draft assessment.

This included the following chemical: Ammonia and Ammonium Salts Noncancer Oral

Meeting Details
Meeting Materials

Meeting Objective

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 (IAP) for Ammonia and Ammonium Salts Noncancer Oral.

Dates

The meeting was held on May 23, 2018.

Meeting Agenda

On May 23, 2018, 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 Ammonia and Ammonium Salts Noncancer Oral. See the final agenda and meeting presentation:

Final Agenda for the May 2018 IRIS Public Science Meeting(1 pp, 140 K, About PDF)
EPA's Presentation on the Ammonia IAP at the May 2018 IRIS Public Science Meeting(26 pp, 2 MB, About PDF)

Ammonia Assessment Manager: Vincent Cogliano

IRIS Assessment Plan (IAP) for Ammonia and Ammonium Salts Noncancer Oral
Review comments submitted on these materials in the Ammonia docket at EPA-HQ-ORD-2018-0132.
Federal Register Notice: April 16, 2018 announced the availability of the IAP for a 30-day public comment period.

Key Science Topics
What is an IRIS Assessment Plan? An IRIS Assessment Plan, or IAP, communicates to the public the plan for assessing each individual chemical and includes summary information on the IRIS Program’s scoping and initial problem formulation, objectives and specific aims for the assessment, and it includes the PECO (Populations, Exposures, Comparators, and Outcomes) criteria that outline the evidence considered most pertinent to the assessment; and identification of key areas of scientific complexity. 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 topic: 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. Endogenous production of ammonia. The body produces ammonia during the metabolism of amino acids. Most production occurs in the intestines during the digestion of meat and other sources of protein, and a smaller amount occurs in the mouth from the reaction of saliva with food particles. Many animal studies have investigated the effect of oral exposure to ammonia on upper-digestive-tract irritation, on hyperammonemia, or on metabolic acidosis. These studies have reported clear dose–response relationships and have not attributed any part of these effects to endogenous production. The assessment will consider whether endogenous production of ammonia might complicate dose–response relationships for irritation, hyperammonemia, or metabolic acidosis, and if so, how to disentangle the effects of oral exposure to ammonia and its endogenous production. *Key Topic 2. Infection with Helicobacter pylori.* Endogenous production of ammonia also occurs in individuals infected with H. pylori, which survives in the stomach by producing ammonia to reduce stomach acidity. In individuals infected with H. pylori, oral exposure to ammonia would add to the concentration of ammonia in the stomach associated with H. pylori infection. Some studies in uninfected rats have investigated stomach irritation from oral exposures that correspond to stomach concentrations of ammonia in humans infected with H. pylori. The assessment will consider the use of these oral studies in uninfected rats in developing reference doses for oral exposure. Key Topic 3. Decision not to include an evaluation of potential carcinogenicity. There are several studies pertinent to an evaluation of potential carcinogenicity, including two occupational case–control studies, four studies of cancer in experimental animals, and three initiation–promotion studies (see Section 2.2 of the IAP). Because these studies are not likely to be useful for deriving toxicity values for cancer, the assessment plan has chosen to limit the scope of the assessment by not pursuing an evaluation of potential carcinogenicity.

Key Science Topics

What is an IRIS Assessment Plan? An IRIS Assessment Plan, or IAP, communicates to the public the plan for assessing each individual chemical and includes summary information on the IRIS Program’s scoping and initial problem formulation, objectives and specific aims for the assessment, and it includes the PECO (Populations, Exposures, Comparators, and Outcomes) criteria that outline the evidence considered most pertinent to the assessment; and identification of key areas of scientific complexity. 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 topic:

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. Endogenous production of ammonia. The body produces ammonia during the metabolism of amino acids. Most production occurs in the intestines during the digestion of meat and other sources of protein, and a smaller amount occurs in the mouth from the reaction of saliva with food particles. Many animal studies have investigated the effect of oral exposure to ammonia on upper-digestive-tract irritation, on hyperammonemia, or on metabolic acidosis. These studies have reported clear dose–response relationships and have not attributed any part of these effects to endogenous production.

The assessment will consider whether endogenous production of ammonia might complicate dose–response relationships for irritation, hyperammonemia, or metabolic acidosis, and if so, how to disentangle the effects of oral exposure to ammonia and its endogenous production.

Key Topic 2. Infection with Helicobacter pylori. Endogenous production of ammonia also occurs in individuals infected with H. pylori, which survives in the stomach by producing ammonia to reduce stomach acidity. In individuals infected with H. pylori, oral exposure to ammonia would add to the concentration of ammonia in the stomach associated with H. pylori infection. Some studies in uninfected rats have investigated stomach irritation from oral exposures that correspond to stomach concentrations of ammonia in humans infected with H. pylori.

The assessment will consider the use of these oral studies in uninfected rats in developing reference doses for oral exposure.

Key Topic 3. Decision not to include an evaluation of potential carcinogenicity. There are several studies pertinent to an evaluation of potential carcinogenicity, including two occupational case–control studies, four studies of cancer in experimental animals, and three initiation–promotion studies (see Section 2.2 of the IAP).

Because these studies are not likely to be useful for deriving toxicity values for cancer, the assessment plan has chosen to limit the scope of the assessment by not pursuing an evaluation of potential carcinogenicity.

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