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Dissolution of Inorganic Lead (Pb) Compounds in Synthetic Sweat to Assess Risk of Dermal Exposure

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  • Description:
    It is estimated that over 4.53x108 kg of inorganic lead (iPb) compounds were manufactured in the U.S. in 2020. Over 1.4 million U.S. workers have dermal exposures to iPb compounds in several industries with loading of iPb on hands varying widely (0.005-16.1 µg/cm2). In vitro skin studies suggest that dermal exposures to iPb could increase blood lead levels (BLLs) by as much as 6.3 µg/ dl. However, these studies did not evaluate the dissolution of iPb compounds in skin surface film liquids (SSFLs) (including both synthetic sweat and sebum) to determine the potential for Pb ion formation. Dissolution is a critical factor to determine dermal bioaccessibility and is different than solubility. Dissolution measures ion formation in SSFLs, does not necessarily reach equilibrium, and can be influenced by physiochemical interactions with the components in SSFLs. Dissolution data can be used to model bioavailability via dermal absorption using both the concentration of dissolved ions in sweat, and the permeation rate (Kp) of chemicals through the skin. As far as we know, the dissolution of iPb compounds under biologically relevant conditions has not been published. The study objectives were to 1) determine the pH-dependent static dissolution of four iPb compounds in SSFLs: Pb2+ nitrate (PbN), Pb2+ acetate (PbA), Pb2+ oxide (PbO), Pb2+/4+ red oxide (PbRO); 2) evaluate iPb dissolution kinetics; and 3) provide screening estimates of the potential impact of these compounds on BLLs (assuming exposure to hands only). Statistical analysis using SAS® to fit negative exponential functions to data and calculate dissolution parameters were completed. Using the output from these data analyses, along with dermal loading estimates of Pb compounds in workplace settings, provides a starting estimate for the concentration of Pb ions potentially available in the sweat layer on skin. Estimated concentration of Pb ions available on the skin was used along with available permeability coefficients (Kp) to provide more robust understanding for the potential for dermal bioavailability of these compounds. The iPb compounds are bioaccessible in SSFLs; PbN and PbA have greater dissolution at 8 h (36.4-61.1%) compared to PbO and PbRO (0.01-2.5%). pH has a statistically significant effect on bioaccessibility for all four compounds tested. Screening estimates suggest that BLLs may be increased by 0.7-8 µg/ dL for these iPb compounds. The screening level estimates based on this model suggest that the impact on BLLs warrants a more comprehensive assessment. In occupational settings where other routes of exposure to iPb may be relevant, dermal exposure estimates may represent a significant relative source contribution to overall body burden of Pb exposure. Examination of the impact of dermal exposures on BLLs could be incorporated into physiologically-based pharmacokinetic models (PBPK) to provide a more robust understanding of n the impact on BLLs. Given the potential for Pb ion availability to enable dermal absorption of Pb as demonstrated in this study and previously in the literature, reducing Pb exposure on skin may be important for reducing overall worker exposure to iPb. More research is needed including dissolution of iPb particles from industrial settings and the impact of particle size on dissolution. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1096-6080
  • Document Type:
  • Genre:
  • Place as Subject:
  • CIO:
  • Division:
  • Topic:
  • Location:
  • Volume:
    192
  • NIOSHTIC Number:
    nn:20067225
  • Citation:
    Toxicologist 2023 Mar; 192(S1):441
  • CAS Registry Number:
  • Federal Fiscal Year:
    2023
  • Peer Reviewed:
    False
  • Source Full Name:
    The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
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  • Main Document Checksum:
    urn:sha-512:67a08aeca1334c6642dec1c833c51ec3b167243439b2b8162e0a2de2d6e7d6ddbe27899ea2a65208083cd7807dc1fa2578d06c27df1b39ff778cb2dc4d093c07
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  • File Type:
    Filetype[PDF - 1.07 MB ]
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