Ms. Brenna M. Smith
EOHSI
170 Frelinghuysen Road
Piscataway, NJ 08854
Phone: 732-445-0120
Fax: 732-445-0959
Email: brensm@eohsi.rutgers.edu
Projects are approved by an IRB located at: Univ. of Wash., Univ. of Med. & Dent of NJ, & Rutgers Univ.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M1183, M1467, M1370
Number of Human Subjects Projects reported: 6
Project Identifier: CRESP-96-27-0009-E
Project Title:
Laboratory Evaluation of Field Collected Cells
Principal Investigator:
Dr. Timothy K. Takaro
Principal Investigator's Institution: University of Washington
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
Protocol/Subproject Identifier: 27-0009-E
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 26, 1997
IRB Approval Number: 27-0009-E
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 13
Type of Human Subjects Involvement:
Heat stress is a significant exposure for remediation workers at hazardous waste sites. This study will determine if mRNA heat shock proteins up-regulate in heat-stressed Hanford remediation workers, and if this biomarker can be used to assess risk from such an exposure.
Uroepitheleal cells are harvested from routine urine collections at the Hanford site, and the mRNA activity is analyzed in the laboratory at the University of Washington. The subjects are workers at the Hanford Nuclear Reservations tank farms that were recruited for this study on heat stress. The tank farms at Hanford are located along the Columbia River and often experience summer temperatures above 90 degrees Fahrenheit. Because of the extremely hazardous contents of the tanks, and the poor characterization of their contents, fully self-contained occlusive suits are often worn by workers in this area.
Methods
Voided urine sample are collected before and after the work shift. Following the measurement of specific gravity and the pH, the sample is centrifuged, and the cell pellet is collected and resuspended in a solution containing RNAse inhibitors. The resuspended cells are then frozen on dry ice, and are transported to the laboratory. Commercially available cDNA stress response gene probes are used to characterize the induction of the stress response in uroepithelial cells. The probes include genes coding for the heat stress proteins of the Hsc70 family, and more general stress response genes, such as, thiol glutathione, Gadd43, Gadd153 and p21(Waf1). Because there is a wide variation in the species and quantity of mRNA induction depending upon the cell type, this study aims to identify the stress genes that are most responsive in the transitional uroepithelieal cells harvested in a routinely voided urine sample.
The only samples obtained from the subjects are routine voided spot urine samples collected in privacy. University of Washington investigators will not know the identity of the subjects at any time. Data are identified by a number with the consent form, which is the only document having both a name and number. A member of a cooperating research group from Michigan State University will maintain the identification information.
Adverse effects are not anticipated as subjects will only provide investigators with a urine specimen.
Project Identifier: CRESP-96-X-0720
Project Title:
A Descriptive Analysis of Variables Related to Public Education, Outreach, and Risk Communication at the Savannah River Site
Principal Investigator:
Dr. Bryan Williams
Principal Investigator's Institution: Environmental and Occupational Health Sciences Institute
Project started in: 1996
This project ended in Fiscal Year 1997.
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: September 06, 1996
IRB Approval Number: x-0720
Number of Human Subjects who participated in this project/protocol during
09/06/96 - 09/06/97: 1,671
Type of Human Subjects Involvement:
A two year longitudinal descriptive study of factors related to risk communication will be conducted at the Savannah River Site (SRS), of which is a Department of Energy hazardous waste site. The purpose of this study will be at least twofold: (1) to identify, define and prioritize salient public health education, outreach and risk communications at the SRS.
A random sample of approximately 1,200 subjects will be drawn from 19 counties within approximately a 25 mile radius of the SRS, using random digit dialing software and random number tables to select names from public phone and census databases.
Both population telephone surveys and personal interviews will be used to gather information concerning the research variables. Random follow-up field interviews will be conducted at households that do not possess a phone. Follow-up interviews are necessary because phone surveys may preclude 20% of the sample from study participation. Once identified through the randomization process, subjects will be asked to voluntarily participate in the study. Participating subjects will be assigned a 4 digit code to identify the order in which they were sampled and to provide a means for identification for longitudinal follow-up. Prior to participating in the study, subjects will be read an informed consent form and asked to provide either verbal (phone surveys) or written (personal interviews) informed consent for their participation. Subjects will be informed of any and all risks/benefits associated with the study, and will be informed that they may terminate their participation at any time. All responses will be kept strictly confidential and will be presented and published in aggregate form, thus, responses will not be linked with a given respondents identity. All data will be kept in a secure area and will only be accessible to the primary investigators.
Data collection will take approximately 4-6 weeks for completion. Data collection will take place over a two year span at six month intervals. Phone and face-to-face interviews will take approximately 10-15 minutes for completion. Hence, a given subject's total time investment would be about an hour, assuming full participation over the two year period of study. A survey instrument has been developed and will be field-tested prior to actual data collection. The instrument is the Risk Communication Profile Instrument (RCPI). The RCPI has been subjected to several levels of review throughout the Department of Environmental and Community Medicine and the Environmental and Occupational Health Sciences Institute.
Project Identifier: CRESP-97-041-96
Project Title:
Cohort Study of Former Employees of a Chloralkalai Plant in Brunswick, Georgia
Principal Investigator:
Dr. Howard Frumkin
Principal Investigator's Institution: Emory University, School of Public Health
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
Protocol/Subproject Identifier: 041-96
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 05, 1997
IRB Approval Number: 041-96
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 175
Type of Human Subjects Involvement:
This study is a subproject of a study that was initiated at Emory University. The original project, as well as an amendment to allow this subproject, was approved by the Emory University Human Investigations Committee.
The original project investigates adverse health effects among approximately 200 former employees of a choralkalai plant in Brunswick Georgia, and 200 unexposed controls. In the plant, chlorine products were manufactured using mercury from 1956 through 1994. The toxic exposure from mercury is of primary interest. In recent years, considerable concern has arisen locally about the plant, and it was named a Superfund site in 1995. The larger study is conducted in collaboration with the Glynn County Health Department. Two new scientific questions being addressed are the role of the dimercapto succinic acid (DMSA) chelation challenge in assessing the level of exposure to mercury, and the effect of mercury on urinary porphyrin profiles. Three additional hypotheses are also being addressed, relating to the neurobehavioral, renal, and reproductive toxicity of mercury; this part of the study serves to replicate previous findings.
This subproject for which we are reporting, examines some biochemical aspects of urothelial cells collected from the urine of chloralkalai plant workers occupationally exposed to mercury. The subproject requires no additional urine than that which was supplied for the original study.
Methods
This subproject involves centrifuging the samples, decanting the supernatant, resuspending the pelleted cellular material and freezing it. The collected cells are then examined by members of the University of Washington (UW) laboratory for indications of mercury-induced changes in mRNA expression.
Human Subject Involvement
The risks to humans, as stated in the original application, are minimal and include the possibility of invasion of privacy through disclosure of medical information, the discomfort of phlebotomy and nerve conduction testing, and possible adverse effects of DMSA. The protocol describes how each of these risks will be controlled. The most serious potential risk, that of adverse reaction to DMSA, is very low in the context of only two doses of the medication. Individuals who are G-6-PD deficient, who may react adversely (based on one reported case) will not receive the medication.
This subproject does not have any personal identification information from the human subjects.
In this period, samples have been collected, minimally processed, and stored. Analysis for mercury induced gene expression changes will occur in 1998. Porphyrin analysis has been completed.
Project Identifier: CRESP-97-26-0807-B/C
Project Title:
Human Reproductive Endocrine Effects of Controlled Toluene Exposure
Principal Investigator:
Dr. Elaine M. Faustman
Principal Investigator's Institution: University of Washington
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
Protocol/Subproject Identifier: 26-0807-B/C
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 06, 1997
IRB Approval Number: 26--0807-B/C
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 20
Type of Human Subjects Involvement:
inhalation exposure for occupational exposure research
The goal of this project is to determine whether the inhalation of volatile solvents, at levels permitted under current regulatory guidelines for occupational exposure, affects blood levels of reproductive hormones which are involved in regulating sperm production in men and egg maturation and release in women. Such hormone measurements could then potentially be used to monitor the reproductive health of exposed workers, providing an early warning of those at risk for more serious reproductive effects.
This study evaluates the effects of exposure to solvents on reproductive hormones, luteinizing hormone and follicle stimulating hormone in men and women. It requires frequent blood sampling before, during and after a 3 hour exposure to solvents by inhalation. Prior to the study, potential participants are asked to fill out a medical history questionnaire and are given a brief physical examination. On the day prior to the scheduled exposure, women of child bearing potential will provide a blood sample of 5 ml from an arm vein for a pregnancy test.
Each subject who is not pregnant will then be given two controlled exposures on separate days at least one month apart to toluene vapor in filtered air. The exposures may last two hours and are not more than the level of toluene permitted for workers on an 8 hour day, working lifetime basis (50 parts per million). At the beginning of each exposure day, a small plastic tube is inserted into a vein in the arm and will remain in place for the day. A local anesthetic, lidocaine, will be used at a dose of 0.1-0.3 ml to avoid discomfort during this procedure. During an 8 hour period, beginning before exposure and ending after the exposure, each subject will be asked to give a total of 28 blood samples (one half teaspoonful or less) from the arm vein.
The risk from chemical exposure to males and non-pregnant females is low--the exposure will be less than allowable occupational levels and will occur only twice. If a female is pregnant at the time of exposure, there is a small risk of damage to the embryo which could lead to spontaneous abortion or a birth defect. The risks associated with the catheter are encountered in any peripheral venipuncture: possible infection, irritation and inflammation of the vein and leakage of blood into the tissue surrounding the blood vessel.
Data from subjects is anonymous but coded, with the key to the coding kept in a separate locked location.
This project was started in November, 1996, and also received funding from an NIEHS Center pilot grant. Further, the investigator subsequently applied and was awarded additional funding through NIOSH (#1-R03-0H03468-01).
Project Identifier: CRESP-97-27-0228-C
Project Title:
Screening for Chronic Beryllium Disease at Hanford
Principal Investigator:
Dr. Timothy K. Takaro
Principal Investigator's Institution: University of Washington
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1997
IRB Approval Number: 27-0228-C
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 15
Type of Human Subjects Involvement:
Workers at Hanford have been exposed to beryllium during fuel fabrication and possibly other activities at the site. The extent of this exposure is unknown because surveillance for beryllium effects have not been comprehensive in coverage and the monitoring tests which have been used have not been sensitive. Quantifying the extent of beryllium exposure and disease is important not only to optimize the surveillance and treatment of former workers, but also because of the potential risk to clean-up workers in the future. These risks should be evaluated prior to remediation activities and adequate precautions should be taken to prevent associated devastating health effects. This project assesses the level of sensitization in workers at risk for berylliosis due to historic exposure at Hanford, and it aims to determine the feasibility of establishing a medical monitoring program for current remediation workers potentially exposed to beryllium.
Methods
Forty milliliters of peripheral blood are obtained from each participant using standard venipuncture techniques. Lymphocytes are isolated by Ficoll-Paque (TM) density centrifugation, washed and suspended in RPMI medium supplemented with 10% fetal bovine serum, 1L-2 (50 U/ml) and anti-CD28 mAB (1 mg/ml). They are cultured to a population of 2.5 x 10-5 cells per well in flat bottom 96-well microtitre plates. Cells are cultured alone and with varied concentrations of beryllium salt BeSO4. Non-specific lymphocyte proliferation in the presence of a mitogen is also measured.
During the last 4-6 hours of incubation, cells are pulsed with tritiated thymidineoxyriboside to measure blastogenesis. Following this labelling, they are harvested and counted on a liquid scintillation counter with data expressed as counts per minute.
Brominated deoxyuridine (BrdU; 150mM) is added to the cultures and protected from light. After three days of growth, cell cycle analysis is performed. Cell nuclei are stained with Hoechst 33258 and ethidium bromide and analyzed by flow cytometry. Analysis of cells remaining in G1, 72 hours after anti-CD3 stimulation is then made using the technique of Rabinovitch et al.
Involvement of Human Subjects
To participate in the study, investigators obtained names of potential subjects from DOE. Subjects responding are requested to provide information about work experience, exposures, smoking, and health status; provide 40 ml of peripheral blood; and provide permission to review employment and medical records to determine the extent of beryllium exposure that worker may have encountered.
The standard venous blood draw is slightly painful at the moment of venipuncture. Rarely, local transient swelling occurs and there is an extremely rare risk of infection from the procedure.
Personal identification information is kept in a separate location from other information. Subjects sign an informed consent form that has been approved by the human subjects review committee.
In this period, the primary emphasis has been on identifying subjects and characterizing their exposure. Another major point of emphasis has been the development a quantitative decision analytic framework for the use of biomarkers in medical surveillance. Very few human specimens have been received during this initial period.
This project is also supported by a NIOSH grant which is looking at Former Worker's Exposure.
Project Identifier: CRESP-97-27-0295-X
Project Title:
Analysis of Gene Expression Changes in Isolated Uroepithelial Cells
Principal Investigator:
Dr. Elaine M. Faustman
Principal Investigator's Institution: University of Washington
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
Protocol/Subproject Identifier: 27-0295-X
IRB Review:
Type of Review: Expedited
Most Recent Approval: May 12, 1997
IRB Approval Number: 27-0295-X
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 9
Type of Human Subjects Involvement:
The purpose of this study is to analyze gene expression changes in isolated uroepithelial cells from individuals exposed to fly ash (at a coal-fired power plant in Slovakia). Dr. Janice Yager, at the Electric Power Research Institute, provided the urine samples, which will be analyzed by Dr. Sandra Kirchner.
The role of this project is solely to receive aliquots of coded urine samples (we do not receive any human identification information), isolate the UE cells, amplify the RNA and look for gene expression changes.
This project is a very small pilot study which examines the feasibility of using field-collected urine samples for gene expression biomarker studies.