calc_kair: Calculate air:matrix partition coefficients
In httk: High-Throughput Toxicokinetics

calc_kair

R Documentation

Calculate air:matrix partition coefficients

Description

This function uses the methods colleced by Linakis et al. (2020) to calculate air partition coefficients for blood, water, and mucus.

Usage

calc_kair(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  parameters = NULL,
  species = "Human",
  adjusted.Funbound.plasma = TRUE,
  default.to.human = FALSE,
  suppress.messages = FALSE,
  pH = 7.4,
  alpha = 0.001
)

Arguments

`chem.cas`	Chemical Abstract Services Registry Number (CAS-RN) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXISD
`chem.name`	Chemical name (spaces and capitalization ignored) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXISD
`dtxsid`	EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) – if parameters is not specified then the chemical must be identified by either CAS, name, or DTXSIDs
`parameters`	Parameters from the appropriate parameterization function for the model indicated by argument model. Can include parameters "logHenry" and "body_temp", but if not included standard values are looked up from httk tables.
`species`	Species used for body temperature, defaults to "Human"
`adjusted.Funbound.plasma`	Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default).
`default.to.human`	Substitutes missing species-specific values with human values if TRUE (default is FALSE).
`suppress.messages`	Whether or not the output messages are suppressed.
`pH`	pH where ionization is evaluated.
`alpha`	Ratio of Distribution coefficient D of totally charged species and that of the neutral form

Details

The blood:air partition coefficient (PB:A) was calculated as P_B:A = P_B:A * R_B:P / f_up where P_B:A is the blood:air partition, RB:P is the blood:plasma partition ratio, fup is the fraction unbound in the plasma, and P_W:A is the water:air partition coefficient: R * T_body / HLC / P where R is the gas constant (8.314 J/mol/K), T_body is the species-specific body temperature (K) from physiology.data, HLC is the Henry's Law Constant (atm*m^3 / mol), and P is conversion factor from atmospheres to Pascals (1 atm = 101325 Pa).

In the isopropanol PBTK model published by Clewell et al. (2001) it was noted that certain chemicals are likely to be absorbed into the mucus or otherwise trapped in the upper respiratory tract (URT). Following Scott (2014), the air:mucus partition coefficient (PA:M) calculated as log₁₀(1/K_water2air) - (log₁₀(P_ow) - 1) * 0.524 where Pow is the octanol/water partition coefficient

Value

A named list containing the blood:air, water:air, and mucus:air partition coefficients

Author(s)

John Wambaugh and Matt Linakis

References

Linakis, Matthew W., et al. "Development and evaluation of a high throughput inhalation model for organic chemicals." Journal of exposure Science & Environmental Epidemiology 30.5 (2020): 866-877.

Clewell III, Harvey J., et al. "Development of a physiologically based pharmacokinetic model of isopropanol and its metabolite acetone." Toxicological Sciences 63.2 (2001): 160-172.

Scott, John W., et al. "Tuning to odor solubility and sorption pattern in olfactory epithelial responses." Journal of Neuroscience 34.6 (2014): 2025-2036.