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Chemical absorption in human skin

Cite this dataset

Stevens, Jessica et al. (2024). Chemical absorption in human skin [Dataset]. Dryad. https://doi.org/10.5061/dryad.dfn2z3581

Abstract

Whether from environmental and occupational hazards or from topical pharmaceuticals, the human skin comes into contact with various chemicals every day. In vivo experiments not only require large investments of both time and money, but in vivo experiments can also be unethical due to the need to intentionally or incidentally expose humans or animals to toxic chemicals. Comparatively, in vitro experiments offer ethical and financial advantages when combined with the opportunity to selectively choose chemicals for experimentation. With in vivo experimentation being so infeasible, many scientists have chosen to make their in vitro data available publicly. Using these data, a detailed database containing 73 chemicals was created with a robust set of descriptors to be used in connection with mathematical modeling to predict diffusion, permeability, and partition coefficients. This resulting database is tailored to be easily used in various coding languages.

README: Chemical Absorption in Human Skin

https://doi.org/10.5061/dryad.dfn2z3581

The collected data is from in vitro experiments of aqueous vehicle exposure in Franz diffusion cells with human skin. Ellison et al. published data of permeability, partition, and diffusion coefficients for 50 fragrance-relevant chemicals across the individual layers of the skin. Experimental permeability and diffusion coefficients in the dermis for fourteen non-volatile chemicals from Kretsos et al. were included along with calculated permeability and diffusion coefficients in the stratum corneum for nine hydrocortisones from Anderson et al. Additional chemical descriptors were collected (from PaDEL-Descriptor, the EPA's CompTox Chemicals Dashboard, and PubChem) and included within the database with the permeability and diffusion coefficient values.

Description of the data and file structure

The content of each file is described below along with explanations and units (if applicable) of the column headings. Notations have been made in regards to which files are suitable for coding and any required specifications are identified.

  • chemical_descriptors.xlsx: all collected descriptors, suitable for coding
    • Chemical Name: chemical name as it appeared in the original dataset, used for identification
    • CAS Number: Chemical Abstracts Service (CAS) Number, used for identification
    • DSSTox Substance ID: Distributed Structure-Searchable Toxicity (DSSTox) as listed within the EPA's Computational Toxicology Dashboard, used for identification
    • smile: Simplified Molecular Input Line Entry System (SMILES) for the given chemical, used for identification
    • Carbons: number of carbon atoms in the chemical
    • Hydrogens: number of hydrogen atoms in the chemical
    • Nitrogens: number of nitrogen atoms in the chemical
    • Oxygens: number of oxygen atoms in the chemical
    • Chlorines: number of chlorine atoms in the chemical
    • Bromines: number of bromine atoms in the chemical
    • Sulfurs: number of sulfur atoms in the chemical
    • Phosphorus: number of phosphorus atoms in the chemical
    • Fluorines: number of fluorine atoms in the chemical
    • Total Rings: total number of rings in the structure in the chemical
    • Aromatic/Heterocyclic Rings: number of aromatic/heterocyclic rings in the structure of the chemical
    • Benzenes: number of benzene rings in the structure of the chemical
    • Alcohols: number of hydroxyl groups in the structure of the chemical
    • Ethers: number of ether groups in the structure of the chemical
    • Amines: number of amine groups in the structure of the chemical
    • Keytones: number of keytone groups in the structure of the chemical
    • Esters: number of ester groups in the structure of the chemical
    • Amides: number of amide groups in the structure of the chemical
    • Nitriles: number of nitrile groups in the structure of the chemical
    • Nitros: number of nitro groups in the structure of the chemical
    • Density: density of the chemical (g/cm³)
    • Index of Refraction: value for the chemical's index of refraction
    • Molar Refractivity: molar refractivity of the chemical (cm³)
    • Rule of 5 Violations: number of violations to Lipinski's rule of five in the chemical's structure
    • Polarizability: polarizability of the chemical (10⁻²⁴ cm³)
    • Surface Tension: surface tension of the chemical (N/m)
    • Molar Volume: molar volume of the chemical (m³/mol)
    • Hydrogen Bond Donors: number of atoms in the chemical that can supply hydrogen bonds to hydrogen acceptors
    • Hydrogen Bond Acceptors: number of atoms in the chemical that can accept hydrogen bonds from hydrogen donors
    • Rotatable Bonds: number of single bonds in the structure of the chemical that can rotate freely around their axis
    • Topological Polar Surface Area: sum of exposed surface area of the chemical that is capable of polar interactions (Ångströms²)
    • Heavy Atom Count: number of heavy atoms in the chemical
    • Complexity: complexity value of the chemical
    • Henry's Constant: Henry's Constant of the chemical
    • Molecular Weight: molecular weight of the chemical (g/mol)
    • Boiling Point: boiling point of the chemical (°C)
    • Melting Point: melting point of the chemical (°C)
    • Flash Point: flash point of the chemical (°C)
    • Atmospheric Hydroxylation Rate: atmospheric hydroxylation rate of the chemical
    • Bioconcentration Factor: bioaccumulation potential of the chemical
    • Biodegradation Half Life: time required for 50% biodegredation of the chemical (days)
    • Km: Michaelis-Menten constant of the chemical
    • Vapor Pressure: vapor pressure of the chemical (mmHg)
    • Water Solubility: water solubility of the chemical (mol/L)
    • SW: maximum amount of water that can dissolve/absorbed by the chemical at 32°C (mg/cm³)
    • Octanol Air Partition Coefficient: octanol air partion coefficient of the chemical
    • Soil Adsorption Coefficient: soil adsorption coefficient for the chemical
  • epidermis.xlsx: all descriptors (previously described for chemical_descriptors.xlsx) with experimental data from the epidermis layer (70 chemicals), suitable for coding
    • D Epidermis Mean (cm²/s): the chemical's average diffusion coefficient in the epidermis
    • D Epidermis Mean (cm²/h): the chemical's average diffusion coefficient in the epidermis
    • K Epidermis Mean: the chemical's average partition coefficient in the epidermis
    • Vehicle: any additional vehicles used with the chemical
    • Percent of Dose Epidermis: the chemical's percent dose in the epidermis
    • Extent of Linearity Epidermis (h): the chemical's extent of linearity in the epidermis
    • Kp Epidermis (cm/h): the chemical's permeability coefficient in the epidermis
    • Kp Epidermis (cm/s): the chemical's permeability coefficient in the epidermis
    • LogP: the chemical's octanol water partition coefficient
    • LogKp Epidermis (cm/s): log of the chemical's permeability coefficient in the epidermis
    • LogKp Epidermis (cm/h): log of the chemical's permeability coefficient in the epidermis
    • Experimental Lag Time Epidermis (h): the chemical's experimental lag time in the epidermis
  • stratum_corneum.xlsx: all descriptors (previously described for chemical_descriptors.xlsx) with experimental data from the stratum corneum layer (59 chemicals), suitable for coding
    • D Stratum Corneum Mean (cm²/s): the chemical's average diffusion coefficient in the stratum corneum
    • D Stratum Corneum Mean (cm²/h): the chemical's average diffusion coefficient in the stratum corneum
    • K Stratum Corneum FH Mean: the chemical's average partition coefficient in the stratum corneum (fully hydrated)
    • K Stratum Corneum PH Mean: the chemical's average partition coefficient in the stratum corneum (partially hydrated)
    • Vehicle: any additional vehicles used with the chemical
    • LogP: the chemical's octanol water partition coefficient
    • Percent of Dose Stratum Corneum: the chemical's percent dose in the stratum corneum
    • Extent of Linearity Stratum Corneum (h): the chemical's extent of linearity in the stratum corneum
    • LogKp Stratum Corneum (cm/h): log of the chemical's permeability coefficient in the stratum corneum
    • LogKp Stratum Corneum (cm/s): log of the chemical's permeability coefficient in the stratum corneum
    • Kp Stratum Corneum (cm/s): the chemical's permeability coefficient in the stratum corneum
    • Kp Stratum Corneum (cm/h): the chemical's permeability coefficient in the stratum corneum
    • Experimental Lag Time Stratum Corneum (h): the chemical's experimental lag time in the stratum corneum
  • dermis.xlsx: all descriptors (previously described for chemical_descriptors.xlsx) with experimental data from the dermis layer (64 chemicals), suitable for coding
    • D Dermis Mean (cm²/s): the chemical's average diffusion coefficient in the dermis
    • D Dermis Mean (cm²/h): the chemical's average diffusion coefficient in the dermis
    • K Dermis Mean: the chemical's average partition coefficient in the dermis
    • Vehicle: any additional vehicles used with the chemical
    • LogP: the chemical's octanol water partition coefficient
    • Percent of Dose Dermis: the chemical's percent dose in the dermis
    • Extent of Linearity Dermis (h): the chemical's extent of linearity in the dermis
    • Kp Dermis (cm/h): the chemical's permeability coefficient in the dermis
    • Kp Dermis (cm/s): the chemical's permeability coefficient in the dermis
    • LogKp Dermis (cm/s): log of the chemical's permeability coefficient in the dermis
    • LogKp Dermis (cm/h): log of the chemical's permeability coefficient in the dermis
    • Experimental Lag Time Dermis (h): the chemical's experimental lag time in the dermis
  • fragrance.xlsx: all descriptors and experimental data across all layers for the 50 fragrance-relevant chemicals, suitable for coding
  • non_volatile.xlsx: all descriptors and experimental data across all layers for the 14 non-volatile chemicals, suitable for coding
  • hydrocortisones.xlsx: all descriptors and experimental data across all layers for the 9 hydrocortisone chemicals, suitable for coding
  • all_information.xlsx: all descriptors (previously described for chemical_descriptors.xlsx) and experimental data across all chemicals and all layers (all information in the files described previously), suitable for coding
  • time_course_data.xlsx: time course data for cumulative receptor fluid amounts (µg) in 50 fragrance-relevant chemicals sampled from 4 donors across 24 hours
  • notated_database.xlsx: a composite color-coded version of the files chemical_descriptors.xlsx and all_information.xlsx with additional notes, not suitable for coding
  • Krestos_calc.rmd: code for calculating the dermis diffusion constant using the diffusion equation presented by Chen et al. and compared to experimental values obtained from Hewitt et al. and Kretsos et al., requires R
  • Kretsos_dermis_regression.xlsx: a subset of the data that was used for Krestos_calc.rmd

Sharing/Access information

Data was derived from the following sources:
- Ellison, C. A. et al. Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids. Toxicol. Vitro 69, 104990, 10.1016/j.tiv.2020.104990 (2020).
- Kretsos, K., Miller, M. A., Zamora-Estrada, G. & Kasting, G. B. Partitioning, diffusivity and clearance of skin permeants in mammalian dermis. Int. J. Pharm. 346, 6479, 10.1016/j.ijpharm.2007.06.020 (2008).
- Anderson, B. D., Higuchi, W. I. & Raykar, P. V. Heterogeneity effects on permeability-partition coefficient relationships in human stratum corneum. Pharm. Res. 05, 566573, 10.1023/a:1015989929342 (1988).

Code/Software

Krestos_calc.rmd is a notebook created in R with the data from the file 'Kretsos_dermis_regression.xlsx' and uses the libraries 'xlsx', 'readxl', and 'dplyr'.