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Examination of Factors Associated with the Dermal Penetration and Absorption of Inorganic Lead (Pb) Compounds for Occupational Risk Assessment

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2022, PhD, University of Cincinnati, Medicine: Industrial Hygiene (Environmental Health).
Inorganic Lead (iPb) exposure continues to be a public health issue in occupational settings, with an estimated 1,465,000 U.S. workers having dermal exposures to iPb compounds. Four specific aims were completed to explore the potential for percutaneous absorption of iPb compounds. The first aim was to review published literature on iPb dermal studies to identify/calculate percutaneous absorption values (Kp and diffusion rate). Eleven articles containing relevant data were identified. Average diffusion rates for the pool of animal and human skin data ranged from 10-7 to 10-4 mg/cm2/h, and Kp values ranged from 10-7 to 10-5 cm/h. Most studies (92%) were not conducted using standard test guideline methods, and there is low confidence in the percutaneous absorption parameters estimates A second aim was to determine the pH-dependent dissolution of iPb compounds (Pb Nitrate (PbN), Pb Acetate (PbA), Pb Oxide (PbO), Pb Red Oxide (PbRO)) in synthetic sweat (SSFL) and understand the dissolution kinetics of these compounds for up to 72 h. At 8 h, PbN and PbA exhibit dissolutions from 36.4% – 61.1%, while PbO and PbRO range from 0.1% – 2.5%, with pH having a significant effect (p<0.05) on dissolution for all four compounds. PbA and PbN exhibit similar dissolution patterns, with rapid dissolution during the first 8 h, and slower dissolution between 8 and 24 h. PbO at both pH levels, and PbRO at pH 5.3, show similar patterns of dissolution but did not reach a slower dissolution until 24 h. PbRO at pH 6.5 slowly releases Pb ions into the SSFL through 72 h. A third aim was to conduct pilot studies of percutaneous absorption of PbN using human skin in a Franz cell assay over 24-72 h. Four studies conducted found Pb ion in washed skin layers ranging from 8.9% – 31.5% of the mass of Pb applied. This is likely an underestimate of the Pb in washed skin, since Pb could not be fully accounted for in recovery studies of skin due to methodological issues to fully dissolve skin. Pb was only sporadically found in receptor fluids, which may be due to selection of phosphate buffer saline as a receptor fluid, which precipitates as Pb phosphate when mixed with PbN. Further studies are needed to determine appropriate receptor solutions and skin dissolution methodologies to determine Pb content. A final aim was to provide a screening model, based on Kp values and dissolution parameters for iPb compounds in SSFL, to estimate the impact of dermal exposures on blood lead levels (BLLs). The model suggests that dermal exposures may increase BLLs by as much as 0.7 µg/dL for PbRO, 1.1 µg/dL for PbO, and 1.5–8 µg/dL for PbN and PbA. The screening estimates for PbO, PbA, and PbN exceed 1 µg/dL, which is the typical level of detection (LOD) for detecting Pb in blood. These results suggest that the impact of dermal exposures to some iPb compounds may increase BLLs beyond a de minimus additional exposure, suggesting the need for a more comprehensive evaluation of dermal absorption.
John Reichard, PharmD Ph.D. (Committee Member)
Gerald Kasting, Ph.D. (Committee Member)
Christine Whittaker, Ph.D. (Committee Member)
Glenn Talaska, Ph.D. (Committee Member)
M. Maier, Ph.D. (Committee Member)
157 p.

Recommended Citations

Citations

  • Niemeier, R. (2022). Examination of Factors Associated with the Dermal Penetration and Absorption of Inorganic Lead (Pb) Compounds for Occupational Risk Assessment [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649771501283059

    APA Style (7th edition)

  • Niemeier, Richard. Examination of Factors Associated with the Dermal Penetration and Absorption of Inorganic Lead (Pb) Compounds for Occupational Risk Assessment. 2022. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649771501283059.

    MLA Style (8th edition)

  • Niemeier, Richard. "Examination of Factors Associated with the Dermal Penetration and Absorption of Inorganic Lead (Pb) Compounds for Occupational Risk Assessment." Doctoral dissertation, University of Cincinnati, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649771501283059

    Chicago Manual of Style (17th edition)