Project Identifier: LLNL-95-94-117
Project Title:
Direct Measurement of Uptake of Toxic Chemicals from Water, Soil & Dust into Human Skin In Vivo, Phase I: Aqueous Expos
Principle Investigator:
Dr. Kenneth T. Bogen
Project started in: 1995
Project Funding Information:
Project did not receive funding in Fiscal Year 1995.
Project did not use human subjects in Fiscal Year 1995.
Explanation:
No funding/human subjects in FY 95. IRB approved protocol 1/18/95, but project start delayed due to funding agency issue
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 18, 1995
IRB Approval Number: 94-117
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
See abstract.
See Abstract.
Summary & Purpose:
In three experiments to be conducted under this protocol, a single (1) human subject will receive an extremely low total dose (<250 nCi and <1µg) involving two (2) 14C-radiolabeled chemicals (chloroform and trichloroethylene) via dermal exposure to the forearm. In each experiment, each of four application sites will be sampled by a superficial shave biopsy that removes 1 to 5 mg (~2 mm2) of tissue from the outer skin layers. The samples will be analyzed for 14C-radiolabel uptake by accelerator mass spectrometry (AMS), a highly sensitive technique allowing measurements of extremely small uptakes that present a negligible health risk to the research subject.
The project will provide critical human in vivo validation for a much larger series of parallel data on dermal uptake of key environmental contaminants (namely, certain chlorinated solvents and pesticides) to be obtained using an in vitro method involving human cadaver skin. These data are needed to accurately assess human exposures to environmental chemicals through the dermal exposure route. The data obtained will be used to establish more detailed procedures to be included in a future protocol applicable to nine additional subjects in a second phase of AMS-based research on human dermal uptake of several environmental pesticides via two additional dermal exposure media (soil and household dust), which are of critical concern to the funding agency. Chloroform and trichloroethylene were selected for use in Phase I because results from these studies will be directly comparable to previous results we have obtained using similar AMS and other procedures applied to skin in vitro and hairless guinea pig skin in vivo. In parallel with the experiments involving a human subject under this protocol, we will be conducting similar experiments using human cadaver skin in vitro (LLNL Protocol 94-118 [Certification of Exemption], Approved 19 Nov. 1994). The present experiments will allow the first direct comparisons of dermal uptake and its kinetics in vivo using AMS methods applied to human skin tissue, thereby providing a firm basis for extrapolating more easily obtained in vitro AMS results applied to human cadaver skin in setting safety standards for drinking water and hazardous waste sites. Such data cannot be obtained using only experimental animals, due to (1) substantial interspecies variation in dermal permeability for chemicals and (2) very limited data currently available upon which to base valid animal-to-human extrapolations of in vivo dermal uptake of chemicals specifically from soil, dust or water (the media of interest to the sponsoring agency).
Potential Hazards:
Each experiment will expose the volunteer to a total of 80 nCi plus <1 µg of 14C-radiolabeled test compound. The subject will not be used for more than three experiments, each separated by at least two weeks, and applications will not be repeated at the same location on the subject. The whole-body-equivalent dose corresponding to the 3-experiment maximum 240-nCi exposure is estimated to be approximately 0.5 mrem, or <0.01% of the ~300-mrem U.S. average annual exposure to ionizing radiation from natural background sources (National Council on Radiation Protection (NCRP) and Measurements, 1987, Ionizing Radiation Exposure of the Population of the United States, NCRP No. 93, NCRP, Washington, DC). The corresponding local dose to (a total of ~12 cm2 of) skin is estimated to be <500 mrem. These experimental maximum doses correspond to upper-bound estimates for total increased lifetime risks of 0.1 and 0.01 per million respectively for cancer and for transmitting inherited disease. Acute toxic effects from the chemicals and doses to be used are not expected, and any related cancer risk is considered to be negligible (all chemical doses to be administered are below the corresponding acceptable daily intakes defined by current, applicable California and U.S. Environmental Protection Agency regulations (maximum applied doses = 0.35 micrograms/day for either compound, for a total of 3 days separated by at least 2 weeks, which is <10% of the corresponding acceptable levels for daily intake over a lifetime). In no case will a particular application site on a subject be used if it exhibits any sign of cut, abrasion, discoloration, or abnormality of any kind.