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This function provides the information specified in "info=" (can be single entry or vector) for all chemicals for which a toxicokinetic model can be parameterized for a given species. Since different models have different requirements and not all chemicals have complete data, this function will return different number of chemicals depending on the model specififed.
get_cheminfo(
info = "CAS",
species = "Human",
fup.lod.default = 0.005,
model = "3compartmentss",
default.to.human = FALSE,
median.only = FALSE,
fup.ci.cutoff = TRUE,
clint.pvalue.threshold = 0.05,
suppress.messages = FALSE
)Table (if info has multiple entries) or vector containing a column for each valid entry specified in the argument "info" and a row for each chemical with sufficient data for the model specified by argument "model":
| Column | Description | units |
| Compound | The preferred name of the chemical compound | none |
| CAS | The preferred Chemical Abstracts Service Registry Number | none |
| DTXSID | DSSTox Structure ID (http://comptox.epa.gov/dashboard) | none |
| logP | The log10 octanol:water partition coefficient | log10 unitless ratio |
| MW | The chemical compound molecular weight | g/mol |
| pKa_Accept | The hydrogen acceptor equilibria concentrations | logarithm |
| pKa_Donor | The hydrogen donor equilibria concentrations | logarithm |
| [SPECIES].Clint | (Primary hepatocyte suspension) intrinsic hepatic clearance | uL/min/10^6 hepatocytes |
| [SPECIES].Clint.pValue | Probability that there is no clearance observed. | none |
| [SPECIES].Funbound.plasma | Chemical fraction unbound in presence of plasma proteins | unitless fraction |
| [SPECIES].Rblood2plasma | Chemical concentration blood to plasma ratio | unitless ratio |
A single character vector (or collection of character vectors) from "Compound", "CAS", "DTXSID, "logP", "pKa_Donor"," pKa_Accept", "MW", "Clint", "Clint.pValue", "Funbound.plasma","Structure_Formula", or "Substance_Type". info="all" gives all information for the model and species.
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Default value used for fraction of unbound plasma for chemicals where measured value was below the limit of detection. Default value is 0.0005.
Model used in calculation, 'pbtk' for the multiple compartment model, '1compartment' for the one compartment model, '3compartment' for three compartment model, '3compartmentss' for the three compartment model without partition coefficients, or 'schmitt' for chemicals with logP and fraction unbound (used in predict_partitioning_schmitt).
Substitutes missing values with human values if true.
Use median values only for fup and clint. Default is FALSE.
Cutoff for the level of uncertainty in fup estimates. This value should be between (0,1). Default is `NULL` specifying no filtering.
Hepatic clearance for chemicals where the in vitro clearance assay result has a p-values greater than the threshold are set to zero.
Whether or not the output messages are suppressed.
John Wambaugh, Robert Pearce, and Sarah E. Davidson
When default.to.human is set to TRUE, and the species-specific data,
Funbound.plasma and Clint, are missing from
chem.physical_and_invitro.data, human values are given instead.
In some cases the rapid equilbrium dailysis method (Waters et al., 2008) fails to yield detectable concentrations for the free fraction of chemical. In those cases we assume the compound is highly bound (that is, Fup approaches zero). For some calculations (for example, steady-state plasma concentration) there is precendent (Rotroff et al., 2010) for using half the average limit of detection, that is, 0.005 (this value is configurable via the argument fup.lod.default). We do not recomend using other models where quantities like partition coefficients must be predicted using Fup. We also do not recomend including the value 0.005 in training sets for Fup predictive models.
Note that in some cases the Funbound.plasma and the intrinsic clearance are provided as a series of numbers separated by commas. These values are the result of Bayesian analysis and characterize a distribution: the first value is the median of the distribution, while the second and third values are the lower and upper 95th percentile (that is qunatile 2.5 and 97.5) respectively. For intrinsic clearance a fourth value indicating a p-value for a decrease is provided. Typically 4000 samples were used for the Bayesian analusis, such that a p-value of "0" is equivale to "<0.00025". See Wambaugh et al. (2019) for more details. If argument meadian.only == TRUE then only the median is reported for parameters with Bayesian analysis distributions. If the 95 credible interval is larger than fup.ci.cutoff (defaults to NULL) then the Fup is treated as too uncertain and the value NA is given.
Rotroff, Daniel M., et al. "Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening." Toxicological Sciences 117.2 (2010): 348-358.
Waters, Nigel J., et al. "Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding." Journal of pharmaceutical sciences 97.10 (2008): 4586-4595.
Wambaugh, John F., et al. "Assessing toxicokinetic uncertainty and variability in risk prioritization." Toxicological Sciences 172.2 (2019): 235-251.
# \donttest{
# List all CAS numbers for which the 3compartmentss model can be run in humans:
get_cheminfo()
get_cheminfo(info=c('compound','funbound.plasma','logP'),model='pbtk')
# See all the data for humans:
get_cheminfo(info="all")
TPO.cas <- c("741-58-2", "333-41-5", "51707-55-2", "30560-19-1", "5598-13-0",
"35575-96-3", "142459-58-3", "1634-78-2", "161326-34-7", "133-07-3", "533-74-4",
"101-05-3", "330-54-1", "6153-64-6", "15299-99-7", "87-90-1", "42509-80-8",
"10265-92-6", "122-14-5", "12427-38-2", "83-79-4", "55-38-9", "2310-17-0",
"5234-68-4", "330-55-2", "3337-71-1", "6923-22-4", "23564-05-8", "101-02-0",
"140-56-7", "120-71-8", "120-12-7", "123-31-9", "91-53-2", "131807-57-3",
"68157-60-8", "5598-15-2", "115-32-2", "298-00-0", "60-51-5", "23031-36-9",
"137-26-8", "96-45-7", "16672-87-0", "709-98-8", "149877-41-8", "145701-21-9",
"7786-34-7", "54593-83-8", "23422-53-9", "56-38-2", "41198-08-7", "50-65-7",
"28434-00-6", "56-72-4", "62-73-7", "6317-18-6", "96182-53-5", "87-86-5",
"101-54-2", "121-69-7", "532-27-4", "91-59-8", "105-67-9", "90-04-0",
"134-20-3", "599-64-4", "148-24-3", "2416-94-6", "121-79-9", "527-60-6",
"99-97-8", "131-55-5", "105-87-3", "136-77-6", "1401-55-4", "1948-33-0",
"121-00-6", "92-84-2", "140-66-9", "99-71-8", "150-13-0", "80-46-6", "120-95-6",
"128-39-2", "2687-25-4", "732-11-6", "5392-40-5", "80-05-7", "135158-54-2",
"29232-93-7", "6734-80-1", "98-54-4", "97-53-0", "96-76-4", "118-71-8",
"2451-62-9", "150-68-5", "732-26-3", "99-59-2", "59-30-3", "3811-73-2",
"101-61-1", "4180-23-8", "101-80-4", "86-50-0", "2687-96-9", "108-46-3",
"95-54-5", "101-77-9", "95-80-7", "420-04-2", "60-54-8", "375-95-1", "120-80-9",
"149-30-4", "135-19-3", "88-58-4", "84-16-2", "6381-77-7", "1478-61-1",
"96-70-8", "128-04-1", "25956-17-6", "92-52-4", "1987-50-4", "563-12-2",
"298-02-2", "79902-63-9", "27955-94-8")
httk.TPO.rat.table <- subset(get_cheminfo(info="all",species="rat"),
CAS %in% TPO.cas)
httk.TPO.human.table <- subset(get_cheminfo(info="all",species="human"),
CAS %in% TPO.cas)
# }
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