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Draft Charge to External Reviewers for the IRIS Tox icological Review of Ammonia

October 2011

Introduction

The U.S. Environmental Protection Agency (EPA) is seeking an external peer review of the draft Toxicological Review of Ammonia that will appear on the Agency’s online database, the Integrated Risk Information System (IRIS). IRI S is prepared and maintained by the EPA’s National Center for Environmental Assessment (NCEA) within the Office of Research and Development (ORD). The existing IRIS assessment fo r ammonia includes a chronic reference concentration (RfC) posted in 1991. The external r eview draft Toxicological Review of Ammonia includes an RfC and a qualitative cancer as sessment.

Charge Questions

Below is a set of charge questions that address sc ientific issues in the draft Toxicological Review of Ammonia. Please provide detailed explana tions for responses to the charge questions.

EPA will also consider reviewer comments on other m ajor scientific issues specific to the hazard identification and dose response assessment of ammo nia. Please identify and provide the rationale for approaches to resolve the issues wher e possible. 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 a nd cancer health effects of ammonia?

2. Please identify any additional peer-reviewed st udies from the primary literature that should be

considered in the assessment of noncancer and cance r health effects of ammonia.

Chemical-Specific Charge Questions:

(A) Oral reference dose (RfD) for ammonia

1. An RfD was not derived for ammonia. Has the sc ientific justification for not deriving an RfD been clearly described in the document? Are there available data to support the derivation of an RfD for ammonia? If so, please identify these data

.

(B) Inhalation reference concentration (RfC) for am monia

1. An occupational epidemiology study of ammonia ( Holness et al., 1989) was selected as the

basis for the derivation of the RfC. Please commen t on whether the selection of this study is scientifically supported and clearly described. If a different study is recommended as the basis for the RfC, please identify this study and provide scientific support for this choice.2

2. Changes in lung function and respiratory sympto ms in humans were concluded by EPA to be

adverse effects and selected as the critical effect for the derivation of the RfC. Please comment

on whether the selection of this critical effect an d its characterization is scientifically supported and clearly described. If a different endpoint is recommended as the critical effect for deriving the RfC, please identify this effect and provide sc ientific support for this choice.

3. The NOAEL/LOAEL approach was used to identify t he point of departure (POD) for

derivation of the RfC. Please comment on whether t his approach is scientifically supported and clearly described.

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

the POD for the derivation of the RfC. Are the UFs appropriate based on the recommendations

described in A Review of the Reference Dose and Reference Concen tration Processes (U.S. EPA, 2002; Section 4.4.5) and clearly described? If cha nges to the selected UFs are proposed, please identify and provide scientific support for the pro posed changes.

(C) Carcinogenicity of ammonia

1. Under EPA’s Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005; www.epa.gov/iris/backgrd.html), the draft Toxicolog ical Review of Ammonia concludes that there is “inadequate information to assess the carc inogenic potential” of ammonia. Please

comment on whether this characterization of the hum an cancer potential of ammonia is scientifically supported and clearly described.

2. The draft Toxicological Review of Ammonia did no t derive a quantitative cancer estimate for

ammonia due to the lack of available studies. Are there available data to support the derivation of a quantitative cancer risk estimate? If so, ple ase identify these data.