Acute Exposure Guideline Levels for Selected Vol 8.pdf

NOTICE: The project that is the subject of this report was approved by the Board of Directors of the National Research Council, whose members are drawn from the boards of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. . The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences as a parallel organization of outstanding engineers. It is autonomous in governing and electing its members and shares with the National Academy of Sciences responsibility for advising the federal government.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of distinguished members of appropriate professions in the investigation of policy matters relating to the health of the public. Department of the Navy (retired), Oak Harbor, WA FRANZ OESCH, University of Mainz, Mainz, Germany. Scientific review of the proposed risk assessment bulletin of the Office of Management and Budget (2007).

Review of the Department of Defense's Research Program on Low Level Exposures to Chemical Warfare Agents (2005). Review of the Army Technical Manuals on Assessing and Managing Chemical Hazards for Deployed Personnel (2004).

Preface

The committee's review of AEGL documents included oral and written presentations to the committee by the NAC authors of the documents. The committee reviewed the draft documents and provided comments and recommendations on how they could be improved in a series of interim reports. The authors revised the draft AEGL documents based on the advice in the interim reports and submitted them for reconsideration by the committee whenever necessary until the committee was satisfied that the AEGLs were scientifically justified and consistent with 1993 and 2001. Guidance reports of NKR.

The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We would like to thank the following individuals for their review of the ten Committee Interim Reports, which summarize the Committee's conclusions and recommendations for improvement of NAC's AEGL documents for acrolein (Fourteenth Interim Report, 2006), carbon monoxide (Ninth, Eleventh, Thirteenth and Sixteenth Interim Reports, respectively, and 2009, dichloroethene (respectively third, eleventh, thirteenth, fourteenth and sixteenth interim report and 2009), ethyleneimine (fifth, ninth, tenth, twelfth and fourteenth and fourteenth interim report) fluorine (respectively second, eleventh and thirteenth interim report and 2006), hydrazine (respectively second, tenth, twelfth and fourteenth interim reports and 2006), peracetic acid (fourteenth interim report, 2006), propylene imine respectively ninth, tenth, twelfth and fourteenth interim reports and 2006) and sulfur dioxide (thirteenth and fourteenth interim reports, 2005 and 2006 respectively): Deepak Bhalla ( Wayne State University), Joseph Borzelleca (Virginia Commonwealth), Charles Feigleyth University University of South Carolina), David Gaylor (Gaylor & Associates), Sidney Green (Howard University), A. The review of the preliminary report completed in 2005 was supervised by Sidney Green, Jr.

Appointed by the NRC, they were responsible for ensuring that the independent review of interim reports was conducted in accordance with institutional procedures and that all audit comments were carefully considered. Finally, we would like to thank all committee members for their expertise and dedicated efforts during the preparation of this report.

Contents

National Research Council Committee Review of Acute Exposure Guideline

COT has also published guidelines for the development of emergency exposure guidance levels for military personnel and for astronauts (NRC 1986b b). Because of COT's experience in recommending emergency exposure levels for short-term exposures, in 1991 EPA and ATSDR requested that COT develop criteria and methods for developing emergency exposure levels for EHS for the general population. In response to this request, the NRC assigned this project to the COT Subcommittee on Guidelines for the Development of Community Emergency Exposure Levels for Hazardous Substances.

The report of this subcommittee, Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances (NRC 1993), provides step-by-step guidance for establishing emergency exposure levels for EHSs. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations such as infants, children, the elderly, persons with asthma, and persons with other illnesses, it is recognized that individuals subject to idiosyncratic reactions may experience - the effects described at concentrations below the corresponding AEGL. As described in the Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances (NRC 1993) and the NRC Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals (NRC 2001a) reports, the first step in establishing AEGLs for a chemical must collect and review all relevant published and unpublished information.

Uncertainty factors are often used when animal data is used to estimate risk levels for humans. The reports are then reviewed by NAC in response to the public comments, upgraded from "proposed" to "interim" status, and sent to the NRC Committee on Acute Exposure Guideline Levels for final review.

Roster of the

National Advisory Committee for Acute Exposure Guideline Levels

Appendixes

1 Acrolein 1

Acute Exposure Guideline Levels

INTRODUCTION

It has a pungent, pungent odor and is highly irritating to the mucous membranes, especially the upper respiratory tract and eyes. Acrolein is manufactured by air oxidation of propylene and is used as an intermediate in the production of acrylic acid. It is also used as a herbicide, algicide and slimicide, in the cross-linking of protein collagen in leather tanning, as a fixative of histological samples and in the production of perfumes.

The major sources of human exposure to acrolein are from incomplete combustion of organic materials (such as in urban and forest fires), tobacco smoke, and burning of fatty foods (Beauchamp et al. 1985). The chemical structure is depicted below, and the physical and chemical properties of acrolein are shown in Tables 1-2.

HUMAN TOXICITY DATA 1. Acute Lethality

CH-CHO

Nonlethal Toxicity 1. Case Reports

Experimental Studies

Developmental and Reproductive Toxicity
Genotoxicity
Carcinogenicity
Summary
ANIMAL TOXICITY DATA 1. Acute Lethality

Rats
Guinea Pigs
Other Data
Nonlethal Toxicity 1. Nonhuman Primates
Developmental and Reproductive Toxicity
Genotoxicity
Carcinogenicity
Summary

SPECIAL CONSIDERATIONS 1. Metabolism and Disposition

Mechanism of Toxicity
Concurrent Exposure Issues
Structure Activity Relationships
Animal Data Relevant to AEGL-1
Derivation of AEGL-1

SUMMARY OF AEGLS 1. AEGL Values and Toxicity End Points

Other Exposure Criteria
Data Quality and Research Needs

REFERENCES
HUMAN TOXICITY DATA

Acute Lethality
Nonlethal Toxicity
Nonlethal Toxicity
Developmental and Reproductive Toxicity 1. Pigs
Issues Related to Postmortem CO Determination in Humans 1. Potential Factors Influencing COHb Levels
Other Relevant Information 1. Species Variability

SUMMARY OF AEGLs

AEGL Values and Toxicity End Points
Comparison with Other Standards and Criteria
Nonlethal Toxicity 1. Cats

SPECIAL CONSIDERATIONS

Absorption, Distribution, Metabolism and Disposition
Other Relevant Information 1. Species Variability
Temporal Extrapolation

Subjectively perceived irritation and “annoyance” (closest translation; another term could be “anxiety”) by means of a scaled questionnaire; degree of blinking; In the second of the series of experiments, 42 healthy students (17 men and 25 women) participated in an intermittent exposure experiment. Finally, in the third of the series of experiments, 46 healthy students (21 men and 25 women) were exposed (in groups of three) to acrolein at 0.3 ppm for 60 minutes.

There were no deaths in the control group and 14% of the acrolein-exposed animals died. The displacement was achieved by inflating a collapsed double-walled plastic bag into a 20-L bottle containing an "appropriate concentration of acrolein." The desired concentrations were achieved by a dilution stream introduced into the system between the reservoir and the exposure chamber. Applying the standard uncertainty factor of 10 also gives AEGL-2 values in the concentration range where only minor irritation was observed in controlled human studies.

Analysis of the exposure concentration in the room was done using the iodine pentoxide method. CO exposure resulted in an increase in the plateau level of the deep body temperature during exercise of 0.3-0.5C. No studies documenting genotoxic effects of CO in humans were found in the available literature.

No studies have been found in the available literature documenting carcinogenic effects of CO in humans. The Maryland Chief Medical Examiner's Office provided the data. An estimated 62 million people in the United States (about 20% of the population) have one or more types of cardiovascular disease (American Heart Association 2002).

In patients with coronary artery disease, which is the most sensitive subpopulation, effects such as significant changes in the electrocardiogram, a shorter time to onset of angina pectoris and an increase in cardiac arrhythmias begin to occur at exposure concentrations slightly higher than current exposure levels. . air quality guidelines (e.g. US national air quality guideline of 9 ppm for 8 hours) (National Air Pollution Control Administration 1970; 65 Fed. in Klasner et al. 1998 study), acute neurotoxic effects, such as headache, nausea, dizziness, shortness of breath and vomiting was found at a mean COHb of 7.0% (measured after a mean time of 1 hour [to 2 hours] after the children were removed from the CO atmosphere). In the clinic, a measured COHb of about 15-20% in pregnant women (implying a higher end of exposure level) is considered a severe CO intoxication that could require hyperbaric oxygen treatment (Ellenhorn 1997; Tomaszewski 1998).

In patients with coronary artery disease, who constitute the most susceptible subpopulation, effects such as significant electrocardiogram changes, reduced time to onset and increased cardiac arrhythmia begin to occur at exposure concentrations slightly higher than current air quality guidelines, e.g. Actual concentrations achieved ranged from 98.2% to 100.7% of nominal concentrations, indicating reliability and accuracy in exposure concentrations. Therefore, only a modifying factor of 2 was used in the derivation of the cis isomer values.

Therefore, only a modifying factor of 2 was used in the derivation of the cis isomer values.