Human Interindividual Variability in 

Parameters Related to Susceptibility 

for Toxic Effects

General Interindividual Variability Database

Straw Man Database and Papers, Including Price et al. (2002) Interspecies Paper and Data

Old General Interindividual Variability Database

Interspecies and Interindividual Variability in In Vitro Enzyme Measurements for Input to PBPK Models

Child/Adult/Elderly Databases and Acrylamide PBPK

Particle Variability Database

Age-Related Differences in Carcinogenesis

Chlorpyrifos Pharmacokinetics and Pharmacodynamics

Web Site Description (Back to Top)

This web site allows you to download either summary data/analyses or detailed individual data sets that we used to derive our estimates of interindividual variability for various publications and ongoing work. The files below are organized into four groups:

(1) Our General Interindividual Variability Database consists of the data we have used to derive estimates of overall interindividual variability in two published papers. The oldest two published papers are:

Hattis, D. Banati, P., Goble, R., and Burmaster, D. "Human Interindividual Variability in Parameters Related to Health Risks, Risk Analysis, Vol. 19, pp. 705-720, 1999.

Hattis, D., Banati, P., and Goble, R. "Distributions of Individual Susceptibility Among Humans for Toxic Effects--For What Fraction of Which Kinds of Chemicals and Effects Does the Traditional 10-Fold Factor Provide How Much Protection?" Annals of the New York Academy of Sciences, Volume 895, pp. 286-316, December, 1999.

The database in the state that it was as of the latter paper is documented in the section below entitled "Old Interindividual Variability Database". Updated files parallel to these but based on more recent analyses and additions to the data are contained in the first section below entitled "Current/New Interindividual Variability Database"

(2) Our Child/Adult/Elderly Database consists of comparative pharmacokinetic data for adults and children of various ages that we have assembled and analyzed in work for EPA under a subcontract from the State of Connecticut under their cooperative grant agreement no. 827195-0 and a direct EPA contract to Clark University RFQ No. DC-03-00009. Also included in this section is a report on Comparative Child/Adult PBPK Modeling for Acrylamide.

(3) Our Particle Variability Database assembles data we analyzed in work with EPA ORD researchers in a cooperative agreement under (# CR 827023-01). The draft paper resulting from this work was published in Risk Analysis:

      Hattis, D., Russ, A., Goble, R., Banati, P., and Chu, M. “Human Interindividual Variability in Susceptibility to Airborne Particles,” Risk Analysis, Vol. 21(4), pp. 585-599 (2001).

This paper can be found among the files contained in the third part of this website.

(4) Our “Age-Related Differences in Carcinogenesis” section includes data and analyses of rodent cancer bioassay results. These were created under an EPA cooperative grant agreement (CR 829746-01). Two papers from this work have been published in Environmental Health Perspectives:


Hattis, D., Goble, R., Russ, A., Chu, M, and Ericson, J. 2004. "Age-Related Differences in Susceptibility to Carcinogenesis: A Quantitative Analysis of Empirical Animal Bioassay Data," Environmental Health Perspectives, 112(11): 1152-1158, August 2004. Paper may be downloaded from http://www.ehponline.org/members/2004/6871/6871.html.

Hattis, D., Goble, R., and Chu, M. "Age-Related Differences in Susceptibility to Carcinogenesis. II. Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens." Environmental Health Perspectives 113: 509-516, April, 2005. Paper may be downloaded from http://www.ehponline.org/members/2005/7564/7564.html.

The data files included in this site are Microsoft Excel workbooks. References and text explanations of the methodology for assembling and analyzing the database are provided in the form of Microsoft Word files. In some cases the files may download to your computer as .bin files. If this happens, you will need to decompress the file before it will be usable. To decompress a .bin file into an Excel workbook, use Aladdin Expander under MS Windows or StuffIt Expander under MacOS.

General Interindividual Variability Database (Back to Top)

Current/New Interindividual Variability Database

A summary of the interindivdual variability data assembled here is contained in the Excel file blow labeled "Interindividual Database". Bibliographic references are contained in the Word file, "Data Source References".

The database files below contain worksheets for each source paper, showing the data used and any calculations made using that data.

Numbers after the names of compounds in the lists below indicate that we found more than one useful source paper for that compound.

In some cases, the detailed pharmacokinetic and pharmacodynamic data files analyzed in the "Interindividual Database 12/00" file can be found in the Adult/Child and Particle Database sections of this website. The very latest version of the database is in the file "Int dbase 5-05updated.xls" below.

For more details on this database see database description.

Data Source References

 Interindividual Database 12/00

 Database File 1

  • Acetaminophen 1
  • Acetaminophen 2
  • Acetyl-L-Carnitine
  • Alfentanil 1
  • Alfentanil 2
  • Amikacin 1
  • Amikacin 2
  • Ampicillin
  • Antipyrine 1
  • Antipyrine 2
  • Antipyrine 3
  • Antipyrine 4
  • Antipyrine 5
  • Antipyrine6

Database File 2

  • Aspirin
  • Befloxatone
  • Bromazepam
  • Brotizolam
  • Buprenorphine
  • Butorphanol
  • Chromium
  • Cimetidine 1
  • Cimetidine 2
  • Clobazam
  • Clonidine
  • Dicumarol
  • Diltiazem
  • Dixyrazine
  • Dofetilide
  • Doxepin
  • Ethambutol
  • Ethosuximide
  • Fentanyl

Database File 3

  • Gentamicin
  • Fluvastatin
  • Haloperidol
  • Hexobarbital
  • Indocyanine Green
  • Kanamycin
  • Lead
  • Lithium
  • Lorazepam 1
  • Lorazepam 2
  • Mefruside
  • Metoclopamide
  • Metoprolol
  • Metronidazole
  • Mexiletine
  • Midazolam 1
  • Midazolam 2
  • Morphine 1
  • Morphine 2
  • Moxonidine
  • Nicotine 1
  • Nicotine 2

 

Database File 4

  • Nifedipine 1
  • Nifedipine 2
  • Nifedipine 3
  • Nifedipine 4
  • Nifedipine 5
  • Nitrazepam
  • Norepinephrine
  • Nortriptyline 1
  • Nortriptyline 2
  • Nortriptyline 3
  • Oxycodone
  • Oxytocin
  • Phenacetin
  • Phenylbutazone 1
  • Phenylbutazone 2
  • Phenylpropanolamine 1
  • Phenylpropanolamine 2

Files to be added to this database file :

  • Insulin
  • Propranolol
  • Propylthiouracil
  • Quinidine
  • Sulfadimine
  • Timolol
  • Tolbutamide
  • Trichloroethylene
  • Trimazosin

Database File 5

  • Praziquantel
  • Prazosin
  • Prifinium Bromide
  • RRR-alpha-tocopherol
  • Sulfinpyrazone
  • Terbutaline
  • Theophylline 1
  • Theophylline 2
  • Theophylline 3
  • Thiamine
  • Thiocolchicoside
  • Ticlopidine
  • Triazolam
  • Trimethoprim 1
  • Trimethoprim 2
  • Valproic Acid
  • Viloxazine

Database File 6

  • Allylamine

Database File 7

  • Methylmercury

Compilation File 1

T1/2  (Elimination Half Life) and Cl (Clearance) Parameters

Compilation File 2

Cmax (Maximal Concentration) Parameter

Compilation File 3

AUC (Area Under the Concentration Curve)

Compilation File 4

Vd (Volume of Distribution) Parameter

Straw Man Database and Paper (Back to Top)

(The straw man database is a followup to the general interindividual database 12/00)

Old General Interindividual Database Files (Back to Top) 

(Updates of these database files are previously listed above)

The database files contain worksheets for each source paper, showing the data used and any calculations made using that data.

Numbers after the names of compounds in the lists below indicate that we found more than one useful source paper for that compound.

For more details on this database see database description

Database File 1

  • Acetaminophen 1
  • Acetaminophen 2
  • Acetyl-L-Carnitine
  • Alfentanil 1
  • Alfentanil 2
  • Amikacin 1
  • Amikacin 2
  • Amitriptyline 1
  • Amitriptyline 2
  • Ampicillin
  • Antipyrine 1
  • Antipyrine 2
  • Antipyrine 3
  • Antipyrine 4
  • Antipyrine 5
  • Antipyrine 6

Database File 2

  • Aspirin
  • Befloxatone
  • Bromazepam
  • Brotizolam
  • Buprenorphine
  • Butorphanol
  • Chromium
  • Cimetidine 1
  • Cimetidine 2
  • Clobazam
  • Clonidine
  • Dicumarol
  • Diltiazem
  • Dixyrazine
  • Dofetilide
  • Doxepin
  • Ethambutol
  • Ethosuximide
  • Fentanyl

Database File 3

  • Gentamicin
  • Fluvastatin
  • Haloperidol
  • Hexobarbital
  • Indocyanine Green
  • Insulin
  • Kanamycin
  • Lead
  • Lithium
  • Lorazepam 1
  • Lorazepam 2
  • Mefruside
  • Metoclopamide
  • Metoprolol
  • Metronidazole
  • Mexiletine
  • Midazolam 1
  • Midazolam 2
  • Morphine 1
  • Morphine 2
  • Moxonidine
  • Nicotine 1
  • Nicotine 2

Database File 4

  • Nifedipine 1
  • Nifedipine 2
  • Nifedipine 3
  • Nifedipine 4
  • Nifedipine 5
  • Nitrazepam
  • Norepinephrine
  • Nortriptyline 1
  • Nortriptyline 2
  • Nortriptyline 3
  • Oxycodone
  • Oxytocin
  • Phenacetin
  • Phenylbutazone 1
  • Phenylbutazone 2
  • Phenylpropanolamine 1
  • Phenylpropanolamine 2
  • Propranolol
  • Propylthiouracil
  • Quinidine

Database File 5

  • Praziquantel
  • Prazosin
  • Prifinium Bromide
  • RRR-alpha-tocopherol
  • Sulfinpyrazone
  • Sulfadimine
  • Timolol
  • Tolbutamide
  • Trichloroethylene
  • Trimazosin
  • Terbutaline
  • Theophylline 1
  • Theophylline 2
  • Theophylline 3
  • Thiamine
  • Thiocolchicoside
  • Ticlopidine
  • Triazolam
  • Trimethoprim 1
  • Trimethoprim 2
  • Valproic Acid
  • Viloxazine

Database File 6

  • Allylamine

Database File 7

  • Methylmercury

Database File 8

  • Ammonia

Database File 9

  • Acrolein

Database File 10

  • Suramin

Database File 11

  • Talc

Database File 12
Please note that this database is currently unavailable.

  • Haloperidol

Database File 13
Please note that this database is currently unavailable.

  • Ibuprofen

Compilation File 1 T1/2 (Elimination Half Life) and Cl (Clearance) Parameters

Compilation File 2 Cmax (Maximal Concentration) Parameter

Compilation File 3 AUC (Area Under the Concentration Curve) parameter

Compilation File 4 Vd (Volume of Distribution) Parameter. This database is currently unavailable.

Interspecies and Interindividual Variability in In Vitro Enzyme Measurements for Input to PBPK Models (Back to Top)

This section reports results and underlying databases for a project to assemble databases of interspecies differences and human interindividual variability in vitro enzyme measurements for input into PBPK models. The overall report of this work is the Word file "EnzPKT3report10_24.doc" Other files give the databases and analysis resultsfiles beginning with "App2..." pertain to the interspecies database and analysis; files beginning with "App3..." pertain to the interindividual database and analysis.


Comparative Child/Adult Pharmacokinetic Database (Back to Top)

Elderly Database

Analysis of Individual Papers

Presentation Given in California (Microsoft Word)

9/01 Central Database (Microsoft Excel)
The central database contains references to workbooks of complete analysis.

  • Alfentanil
  • Amobarbital
  • Ampicillin
  • Antipyrene
  • Bromsulphalein
  • Busulfan
  • Bupivacaine
  • Caffeine
  • Cimetidine
  • Clavulanic Acid
  • Fentanyl
  • Furosemide
  • Gentamicin
  • Ketamine
  • Lignocaine
  • Lorazepam
  • Mepivicaine
  • Metoclopramide
  • Midazolam
  • Morphine
  • Nifedipine
  • Oxazepam
  • Paracetamol (Acetaminophen)
  • Piperacillin
  • Quinidine
  • Remifentanil
  • Teniposide
  • Theophylline
  • Ticarcillin
  • Tobramycin
  • Tolbutamid
  • Triazolam
  • Valproic Acid
  • Vancomycin
  • Zidovudine

9/01 Adult Workbook (Microsoft Excel)
Worksheets:

  • Bupivacaine
  • Caffeine
  • Cimetidine1
  • Cimetidine2
  • Fentanyl
  • Furosemide
  • Gentamicin
  • Lignocaine
  • Lorazepam
  • Metoclopramide
  • Midazolam1
  • Midazolam2
  • Morphine1
  • Morphine2
  • Nifedipine1
  • Nifedipine2
  • Piperacillin
  • Theophylline1
  • Theophylline2
  • Tobramycin
  • Triazolam
  • Vancomycin

9/01 Child Workbook (Microsoft Excel)
Worksheets:

  • Alfentanil
  • Bupivacaine
  • Caffeine
  • Cimetidine
  • Clavulanic Acid
  • Fentanyl
  • Furosemide1
  • Furosemide2
  • Gentamicin1
  • Gentamicin2
  • Lignocaine
  • Lorazepam
  • Metoclopramide
  • Midazolam
  • Morphine1
  • Morphine2
  • Nifedipine
  • Paracetamol
  • Quinidine
  • Teniposide
  • Theophylline1
  • Theophylline2
  • Theophylline3
  • Theophylline4
  • Theophylline5
  • Theophylline6
  • Ticarcillin
  • Tobramycin
  • Valproic Acid
  • Vancomycin

9/01 Combined (Adult and Child) Workbook (Microsoft Excel)
Worksheets:

  • Alfentanil
  • Amobarbital
  • Antipyrene
  • Busulfan
  • Gentamicin
  • Mepivicaine
  • Oxazepam

Databases for Reganal

Particle Variability Database  (Back to Top)

Human Interindividual Variability In Susceptibility to Airborne  Particles
The Particle Variability Database pertains to this article which was submitted to Risk Analysis

Deposition Studies Data

Clearance Data

Age-Related Differences in Carcinogenesis  (Back to Top)

This final technical report for CR 829746-01 contains electronic files of our draft papers and protocols for the use of our Excel models in Microsoft Word, a series of models and databases prepared in Microsoft Excel, and some Powerpoint presentations of project work. The contents are arranged as follows:

Age-Related Differences in Susceptibility to Carcinogenesis: A Quantitative Analysis of Empirical Animal Bioassay Data

This is a PDF file of our first paper, as accepted for publication in Environmental Health Perspectives

Age-Related Differences in Susceptibility to Carcinogenesis II. Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens

This is the final draft of our second paper, also in format for submission to Environmental Health Perspectives--Hattis, D., Goble, R., and Chu, M.

Calculation Protocols

This gives protocols for running the model calculations for both:

    the likelihood models (using the animal cancer bioassay data to derive maximum likelihood fits and confidence limits for the relative changes in risks per daily dose for the fetal, birth-weaning, and weaning-60 day periods) andthe Monte Carlo simulations of uncertainties in early life-stage related risks contained in our "Generic Lifetime RR model.xls"

Age CA data and anal

This contains all the model and database files in Excel

Proliferation Studies

This is a database of a modest number of cell proliferation studies prepared by Jen Ericson.

Mice, Radiation, and Cancer Folder

This is a series of excel files giving our analyses of age-related differences in susceptibility to radiation carcinogenesis. Data from the underlying papers are contained in a series of worksheets in the workbook labeled "Mice, Radiation and Cancer". The other files ending in "mod" analyze subsets of the data designated in the titles of each workbook. Each of these consists of a "Central Est Model" worksheet, where the maximum likelihood fits to the data are derived, and a series of other worksheets in which upper or lower confidence limits are derived for each of the parameters describing the susceptibility of individual life stages relative to adults.

Radiation Data

The file analyzing all the radiation data.

Radiation Results

The file summarizes the results.

Three other subdirectories have similar contents to the folder described just above.

Contlikelihood Models and Results

Analyzing the chemical continuous dosing data.

Singdoselikelihood Models and Results

Analyzing the chemical discrete dosing data.

CombContSingdose Models and Results

Analyzing the combined set of chemical continuous and discrete dosing data.

The "Organ Weight Data" subdirectory includes our analyses of body and organ weights. Other files contain data for different organs not ultimately used in our main analysis.

Organ Growth Data (Human Interp)

Human data and the translations of individual fractions of sexual maturity body weight into human age equivalents are derived in this file.

Mouse Organ Weights (An Interp)

Mouse data are analyzed and human equivalent times summarized in this file.

Barton Sprague Dawley Data

The primary analysis of rat body weight data.

NHANES3 Weight and BMI

Our major analyses of human data from the Third National Health and Nutrition Survey.

Other Uncertainty Modeled Analysis For the Second Cancer Age Paper

Male Female Mut Deviations

Our analysis of chemical-chemical deviations of observed cancer transformations relative to model "predictions" for the male and female combined discrete and continuous dosing model for mutagenic carcinogens.

Kilborn Paper

Summarizes data on developmental milestones in different species.

Monte Carlo Simulation of Risks Constant Lifetime Dosing

LifetimeRR result sum
MG/KG FemaleLife RR Model
MG/KG MaleLife RR Model
MG/KG^.75 FemaleLife RR Model
MG/KG^.75 MaleLife RR Model

Includes Excel spreadsheets for our Monte Carlo simulation model of the effects of lifetime dosing at either a constant mg/kg body weight-day rate or a mg/kg body weight^3/4-day rate. Each of the four analyses is based on the uncertainties described in our second paper. Columns A-L, lines 1-76 give the input distributional data. Columns O-CV for 5000 lines is the Monte Carlo simulation model itself, where each line represents an independent trial (random draw of all model parameters and calculations if intermediate and outcome variables). The next set of columns is an area of sorting results, and distributionall results of the simulation of intermediate and outcome prameters are given in columns DM-DN. One final file, "LifetimeRR result sum.xls", summarizes the results.


The following Powerpoint presentations were made in the process of this work. Not all the contents have been updated to reflect current results.

Chlorpyrifos Pharmacokinetics and Pharmacodynamics (Back to Top)

 

Please send comments and suggestions to dhattis@aol.com.
Last updated March 2013