Human Equivalent Doses and Exposure
Translate experimental findings into human-equivalent dose and exposure predictions for clearer, more defensible safety decisions.
ScitoVation applies fit-for-purpose PBPK modeling, qIVIVE, reverse dosimetry, and exposure analysis to connect biological activity with realistic human exposure estimates. Our assessments help teams evaluate human relevance, compare susceptible populations, prioritize compounds, and determine the most appropriate next step.
Why ScitoVation?
ScitoVation combines scientific consulting with ScitoSim, bringing PBPK/qIVIVE, transcriptomics, evidence synthesis, and toxicological interpretation into one connected workflow.
We start with the decision the evidence needs to support, then select the level of analysis appropriate to the question, available data, and uncertainty.
Biology with exposure: Translate experimental findings into a human-relevant dose and exposure context rather than interpreting biological signals in isolation.
Connected evidence: Bring PBPK/qIVIVE, transcriptomics, literature, and other evidence together rather than treating each analysis separately.
Expert judgment with transparent methods: Keep assumptions, inputs, analytical choices, and interpretation visible so the scientific reasoning can be reviewed and communicated.
Analysis through to interpretation: Our scientists can perform the work as a consulting service using ScitoSim, helping teams move from model output to a defensible safety or regulatory assessment.
How We Translate In Vitro Findings to Human Exposure Predictions
ScitoVation combines in vitro points of departure with chemical-specific kinetic data, qIVIVE, and fit-for-purpose pharmacokinetic or PBPK modeling to estimate the human dose or exposure associated with a biological response. We can account for different routes, populations, and exposure scenarios to put that finding into a more realistic human context.
Prioritizing Estrogen-Active Compounds with qIVIVE
The American Chemistry Council needed a robust New Approach Methodologies (NAMs)-based approach for assessing and prioritizing estrogen-active compounds.
ScitoVation Approach
- Developed and validated a fit-for-purpose assay to measure tissue-specific estrogen responses.
- Converted in vitro points of departure into human-equivalent doses using qIVIVE.
- Compared bioactivity with estimated human exposure using activity-to-exposure ratios.
Client Benefit
- Increased confidence by showing assay-derived human-equivalent doses were lower than or equivalent to in vivo points of departure for 83% of compounds.
- Enabled faster, risk-based prioritization of estrogen-active compounds.
- Provided a practical framework combining bioactivity, qIVIVE, and exposure data to guide further assessment.
Predicting Human-Relevant Inhalation Exposure
Our client needed to determine whether in vivo inhalation points of departure for point-of-contact toxicity could be predicted using human-derived airway models and computational dosimetry.
ScitoVation Approach
- Tested five human-derived airway models and measured barrier integrity and cytotoxicity.
- Used reverse airway dosimetry to calculate rat-equivalent inhaled concentrations associated with the in vitro points of departure.
- Compared predicted concentrations with empirically determined in vivo points of departure.
Client Benefit
- Improved confidence by showing NAM-based model predictions were qualitatively consistent with in vivo findings.
- Clarified how equivalent inhaled concentrations varied across regions of the respiratory tract.
- Provided a practical NAM-based framework for inhalation-risk assessment and further compound prioritization.
How We Assess Susceptibility Across Populations
Age, pregnancy, health status, and physiological differences can all affect how a chemical is absorbed, distributed, metabolized, and eliminated.
ScitoVation uses life-stage and population-specific PBPK modeling to compare internal exposure across susceptible groups and replace broad default assumptions with chemical-specific evidence.
Comparing Internal Exposure Across Susceptible Populations
Our client needed to assess whether children and renally impaired adults could experience different internal exposures than the general adult population.
ScitoVation Approach
- Developed rat and human PBPK models using in vitro metabolism and in vivo kinetic data.
- Modeled exposure in adults, children, and renally impaired adults.
- Used Monte Carlo analysis and internal-dose comparisons to characterize variability and calculate margins of internal exposure and safety.
Client Benefit
- Clarified how internal exposure could differ across susceptible populations.
- Reduced uncertainty by using chemical-specific internal dosimetry rather than external dose alone.
- Supported more precise risk decisions across life stages and health conditions.
Assessing Early-Life Sensitivity to Pyrethroids
The Council for the Advancement of Pyrethroid Human Risk Assessment (CAPHRA) needed to address questions from the U.S. Environmental Protection Agency (USEPA) about whether age-related pharmacokinetic differences justified an additional safety factor for children.
ScitoVation Approach
- Developed a pyrethroid PBPK modeling framework using qIVIVE-derived metabolism data.
- Modeled brain concentrations in adults and children across life stages.
- Calculated chemical-specific adjustment factors for age-related pharmacokinetic differences.
Client Benefit
- Provided chemical-specific evidence that adjustment factors were equal to or less than 1 for the pyrethroids assessed.
- Supported the conclusion that no additional age-related pharmacokinetic factor was needed.
- Replaced a broad default assumption with a more precise, evidence-based assessment.
How We Evaluate the Human Relevance of Animal Findings
Differences in metabolism, exposure route, and biological response can affect whether findings in animals predict human risk.
ScitoVation combines PBPK modeling, internal dosimetry, and transcriptomic analysis to evaluate species differences and determine whether an observed animal response is relevant to people.
Comparing Butylparaben Exposure in Rats and Humans
Our client needed to understand whether animal toxicity findings accurately reflected potential human risk, given differences in butylparaben metabolism and exposure route.
ScitoVation Approach
- Refined rat and human PBPK models across dermal, oral, and intravenous exposure scenarios.
- Compared internal exposure using Cmax and AUC rather than external dose alone.
- Calculated margins of internal exposure for relevant human dermal exposures.
Client Benefit
- Provided a chemical-specific basis for comparing internal exposure across species and routes.
- Reduced uncertainty by accounting for differences in absorption, distribution, metabolism, and excretion.
- Supported a more conservative and biologically relevant risk assessment than external-dose comparisons alone.