Human Subject Experiments Which Are Air Tagged with Radioisotopes of 13N and 41 Ar

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@%aLAWRENCE LIVERMORE NATIONAL LABORATORY Operational Safety Procedure RECEIVED Revised: 07/01/88 HUMAN SUBJECT EXPERIMENTS WHICH ARE A I R TAGGED WITH RADIOISOTOPES OF 13N and 41Ar The Laboratory's basic safety policy is that operations must be planned and conducted in a manner that will prevent injury to personnel or damage to property. The minimum safety rules and practices necessary for achieving an accident-free work environment for the human subject experiments with air tagged with radioisotopes in Building 194 are stated in the Operational Safety Everyone in this building, i.e., visitor, maintenance and service employee, and regularly assigned employee, is required to abide by this procedure and the LLNL Health and Safety Manual to protect himself and other personnel from injury. Regular building personnel are responsible for assisting others in the building to understand the safety regulations relating to what they are doing and to abide by the safety requirements. This procedure was prepared by building management assisted by Hazards Control. Confer with the Hazards Control safety team assigned to this building for interpretation of this procedure .and for planning your operations to comply with safety requirements. Each individual in this building shall use this guidance effectively to avoid injury. This Operational Safety Procedure has been reviewed by: Hazards Control Department Head LLNL Institutional Review Board This Operational Safety Procedure has been authorized by: BOX No. IRB Protocol File FoLDERUecompres s ion Sic kness Studi es With Radioactive Gases

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HUMAN SUBJECT EXPERIMENTS WHICH ARE AIR TAGGED WITH RADIOISOTOPES OF 13N and 41Ar The purpose of this study is to measure the rate of nitrogen and argon uptake and elimination in the body of normal healthy humans. experiments will involve breathing of 13N and 41Ar labelled air for no more than 120 minutes. Any required change in operations that alters the scope or significantly decreases safety control will not be made until a revision or supplement to this procedure has been signed by the person authorized to approve safety control may be made with the joint concurrence of the Lead Experimenter and the Hazards Control Safety Team Leader. Any required change in operations that does not decrease the 1. This procedure authorizes the exposure o f human subjects to the minutes with an accompanying lung dose of approximately 400 mrem to

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Operational Safety P, xe dure The l u n g dose per mCi per liter (initial concentration) for 13N i s approximately 1000 mrem for a 120 minute experiment and for 41Ar is approximately 6400 mrem for a 120 minute experiment. The actual lung dose to participants can be calculated as follows: The breathing gas concentrations will be: Half lives (T112) for the radionuclides are 13N: 10 min. and 41Ar: 109 estimates at t=20 min. for 120 minute exposure. Time elapsed from beam shut-off to administration of gas will be With this in mind, we then obtain the To generate the 13N isotope, high-purity N2 i s irradiated with bremsstrahlung. Some trace of 0 2 always is present and in this ionizing environment, NO2 and N20 forms. The concentration is controlled by minimizing the presence of O2 in the nitrogen. The Operational Controls in section F will reduce the above hazards to an

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Operational Safety P,xe dure Paul Meyer (Ext. 2-9678) is responsible for assuring that all work is performed in conformance with this OSP and the L L N L Health and Safety Manual. In his absence, the experiment will be terminated until a responsible person is trained for the experiment. All participating employees are responsible for performing their work according to the regulations o f this OSP. They are expected to take all reasonable precautions to protect themselves and their fellow employees and to perform only those tasks that they believe can be accomplished safelj. When participants have any doubt regarding the safety of any phase of their work, they are expected to check with the project supervisor before proceeding. The Hazards Control Safety Team assists management to institute and to maintain a low-risk work environment. In addition, Hazards Control may request that management or employees stop an operation when there appears to be an imminent danger to personnel or property (see Health -and Safety Manual Section 1.06). 1. The target gases are: a. Ar: Zero grade argon

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Operational Safety Pr Jcedure 2. Waste gas disposal is achieved with a large volume blower which pumps gas from the site of the experiment to the outside of Bldg. 194 at the All human subjects shall receive a whole body radiation scan by Hazards Control in the Whole Body Counting Facility at Bldg. 253 before and after inhalation of radioactive gases. The radioactive gases shall be filtered with a HEPA filter before inhalation by the subjects. A visual inspection of the filter cartridge gaskets and canister will be made prior to filter installation. Only an approved and tested filter cartridge obtained from Hazards Control Respirator Branch will be installed in the filter canister. Radioactive gas preparation: The evacuated target gas bottle, located in the 0' cave, is filled from a standard gas cylinder containing either high-purity nitrogen (N2) or Zero grade Ar. Upon filling, the gas is irradiated with LINAC-produced I n the case of N2 as target gas, any undesired by-products come from small oxygen concentrations in the gas bottle. This can lead, in principle, to NO2 and N20. Tests performed previously by Hazards Control personnel found concentrations of less than 1 ppm of NO2 and less than 22 ppm of N20 in an irradiated sample. The breathing mixture will be routinely tested for NO2 before it is administered. The breathing mixture will be tested for NO and NO2 before the first experiment covered by this OSP. 1. Evacuate target-gas bottle to less than or equal to 50 microns.

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Operational Safety Prviedure Bleed'radioactive gas, as described below, into plastic bag. Check mixture for NO2. Human subjects will not be exposed to concentrations o f NO2 greater than 3ppm. M i x activated N2 with clean 0 2 to 4 parts *N2 and 1 part 02 i n plastic Navy personnel will cont nuously mon tor and hold 02 concentrat on to A Victoreen 450 ionization chamber survey instrument will be positioned one meter from the center of the plastic bag throughout the 120-minute procedure. This instrument will provide a secondary check on the activity contained i n the bag. survey instrument indicates a level in excess o f 500 mR/hr at the The experiment shall not proceed if the The prepared and tested gas mixture is taken from Trailer 930 to the subject in Bldg. 194 in a plastic bag which is then connected to the breathing valve. The subject then breathes for 120 minutes from the bag. The exhaled gas is passed through a soda lime trap to remove all C02 before returning to the bag. A concentration o f approximately 20% O2 is maintained in the bag and monitored with an oxygen meter during use by Navy personnel. At the end of the 120 minute period the bag is disconnected and the subject breathes room air with the washout being vented to the outside of Bldg. 194.

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Institutional Review Board Lawrence Livermore National Laboratory NOTIFICATION OF APPROVAL Principal 1nvestigator:Paul Meyer Department: Physics Mail Code: 280 Phone Number:2-9678 Project Title: Pulmonary Gas Rates in Man The LLNL Institutional Review Board (Department of Health and Human Services assurance #M-1415) has approved the above request to involve humans as research subjects. IRB PROJECT NUMBER: 8OP-109 APPROVAL DATE: 6/2/88 Full Board Review If the project is to continue, it must be renewed by the expiration date. CONDITIONS OF APPROVAL: A very thorough and complete file on this experiment, including dosimetric data must be maintained The applicable OSP must be updated and approved. The identity of the participants must be protected in any publication of the results, and no medical information about the participants can be publicly divulged. Any adverse reactions to this test must be promptly reported to the LLNL Medical Department. The donor must give hisher informed consent, using the attached consent form with the serial The donor must be given a copy of the signed LLNL consent form. All participants must be given a copy of the attached Experimental Subject's Bill of Rights. The consent form must state that none of the participants are current smokers. The U.S. Navy Human Subjects Protection Committee must approve the project and a copy of that approval must be on file with the LLNZ, I-. Provide to the LLNL IRB the total number of human subjects to be involved in this study.

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Notification of Approval MODIFICATIONS: All protocol changes involving subjects must have prior IRB approval. QUESTIONS: Please contact the Institutional Review Board office at Ext. 2-3883, L452. APPROVAL FOR THE BOARD

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LAWRENCE LIVERMORE NATIONAL LABORATORY Consent to Act as a Human Subject LLNL Institutional Review Board Pulmonary Gas Rates In Man 1. I hereby consent to act as a test subject in the joint Naval Medical Research and Development Command/Lawrence Livermore National Laboratory study entitled Pulmonary Gas Rates in Man (Human Subjects Experiments with Air Tagged with Radioisotopes 13N and 41Ar). I understand that the procedures for conducting this test will involve:l2. Breathing 3N and 41Ar labeled air for up to 120 minutes. 3. I understand that any possible risks and discomforts that may result from the procedure(s) are considered unlikely but include: The discomfort from breathing through a mouthpiece for up to two hours. Any exposure to ionizing radiation carries a risk of causing cancer--in this case potentially of the lung or upper air passages where the most significant part of the radiation dose is delivered. The best estimate of the risk of lung cancer from tis procedure lies between one chance in 100,000 and one chance in 10,000. The radiation exposure to the lung and air passages in this procedure will be less than 0.4 rem. This amount is slightly below the Federal exposure limit for annual exposure of the general population; is one tenth of the permissible annual exposure of radiation workers: and is approximately three to four times the radiation received by the public in most geographical areas of the United States from natural sources and average usage for medical and dental purposes. Since this activity does not involve medical treatment, there is no alternative procedure which might be advantageous to me. At the conclusion of this procedure it is expected that I will be able to function normally immediately. 6. I further understand that this study may result in no direct benefit to me but it may contribute to the understanding of nitrogen uptake and elimination in the body and may therefore, aid in the understanding of decompression sickness and may therefore, be of some benefit to individuals in

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will answer any inquiries I may have at any time concerning the procedures and/or investigation. I am not currently a smoker. Any publication arising from this study will be made without specific reference to my name. I recognize that my participation in this experiment is entirely voluntary and I may refuse to participate or may withdraw at any time without jeopardy. Owing to the scientific nature of the study, the investigator may in his absolute discretion terminate the procedures and/or investigations at I acknowledge the receipt of a signed copy of this consent form and the LLNL Human Subjects Bill Paul Meyer, an employee of the University of California, Lawrence Livermore National Laboratory, is responsible for the conduct of the research in which I am to participate. This research is sponsored by the Naval Medical Research and Development Command; and Lawrence Livermore National Laboratory is providing support. I understand that if I have any complaints or concerns about the procedures, I may address them to Dr. Barton L. Gledhill, Chairman of the Institutional Review Board, in person, by telephone, or in wiiting. Dr. Gledhill can be reached at (415) 422-3883, L-452, Lawrence Livermore National Laboratory, P.O. Box 5507, Livermore, California 94550. and/or such assistants as may be selected (To be completed if Subject is a minor or othenvise unable to sign) Subject is a minor, age Subject is not a minor but is otherwise unable to sign because: Legal Guardian's Signature Date:

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Lawrence Livermore National Laboratory EXPERIMENTAL SUBJECT'S BILL OF RIGHTS The management and staff of the University of California, Lawrence Livermore National Laboratory, wish you to know: Any person who is requested to consent to participate as a subject in a research study involving a medical experiment, or who is requested to consent on behalf of another, has the right to: Be infonned of the nature and purpose of the experiment. Be given an explanation of the procedures to be followed in the medical Be given a description of any attendant discomforts and risks reasonably to be expected from the experiment, if applicable. any drug or device to be utilized. Be given an explanation of any benefits to the subject reasonably to be expected from the experiment, if applicable. Be given a disclosure of any appropriate alternative procedures, drugs or devices that might be advantageous to the subject, and their relative risks and Be informed of the avenues of medical treatment, if any, available to the subject after the experiment, if complications should arise. Be given the opportunity to ask any questions concerning the experiment or the procedures involved. Be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation in the medical experiment without prejudice. Be given a copy of the signed and dated written consent form. Be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence on the subject's decision. If at any time you have any questions regarding a research study, the researcher or hisher assistant will be glad to answer them. You may also seek assistance from the Institutional Review Board which was established for the protection of volunteers in research projects. The Chairman of that Board, Dr. Barton L. Gledhill, may be Friday, or writing to the Institutional Review Board, L-152, Lawrence Livermore National Laboratory, P.O. Box 5507, Livermore, CA 94550.