1 NCEA Proposed Draft Charge to External Reviewers fo r the

IRIS Toxicological Review of Ammonia

February 2012

Introduction

The U.S. Environmental Protection Agency (EPA) is s eeking an external peer review of the scientific basis supporting the draft Toxicological Review of Ammonia that will appear on the Agency’s online database, the Integrated Risk Infor mation System (IRIS). IRIS is prepared and maintained by the EPA’s National Center for Environ mental Assessment (NCEA) within the Office of Research and Development (ORD). The exis ting IRIS assessment for ammonia includes a chronic reference concentration (RfC) po sted in 1991.

IRIS is a human health assessment program that eval uates qualitative and quantitative risk information on effects that may result from exposur e to specific chemical substances found in the environment. Through the IRIS Program, EPA provide s quality science-based human health assessments to support the Agency’s regulatory acti vities. Combined with specific exposure information, government and private entities use IR IS to help characterize public health risks of chemical substances in site-specific situations in support of risk management decisions.

The external review draft Toxicological Review of A mmonia is based on a comprehensive

review of the available scientific literature on th e human and animal health effects of ammonia, and was developed according to general guidelines f or risk assessment set forth by the National Research Council (1983) and guidelines and technica l reports published by EPA (see Preface). This draft IRIS assessment provides an overview of the data regarding the toxicokinetics of

ammonia in humans and animals and characterizes the potential hazard posed by ammonia exposure for noncancer and cancer health effects, i ncluding the derivation of a chronic inhalation reference concentration (RfC). Additionally, the d raft IRIS assessment includes a qualitative characterization of the human cancer potential.

Charge Questions

Below is a set of charge questions that address sci entific issues in the draft IRIS Toxicological Review of Ammonia. Please provide detailed explana tions for responses to the charge questions. EPA will also consider the Science Advisory Board r eviewer panel comments on other major scientific issues specific to the hazard identifica tion and dose-response assessment of ammonia. Please consider the accuracy, objectivity, and tran sparency 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 be2

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. Increased respiratory irritation and decreased lung function in humans were concluded by

EPA to be adverse effects and selected as the criti cal effect for the derivation of the RfC. Please

comment on whether the selection of this critical e ffect and its characterization is scientifically supported and clearly described. If a different en dpoint is recommended as the critical effect for deriving the RfC, please identify this effect and p rovide scientific 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.