CH 18 · notes
How it works
The EMA guideline on health-based exposure limits for shared facilities derives a permitted daily exposure (PDE) with the same equation as ICH Q3C Appendix 3: point of departure times a body-weight adjustment, divided by F1 × F2 × F3 × F4 × F5. The point of departure may be a NOAEL, a LOAEL, or another PoD. Body weight (often 50 kg for an adult) applies only when that dose is per kilogram. A point of departure that is already mg/day or µg/day is not multiplied by body weight. µg values are converted to mg by dividing by 1000 before the division.
F1 through F5 are entered directly. Reference values from the guidelines are noted beside the fields; they are not applied automatically. The calculation trail writes the substituted equation. Use the resulting PDE (mg/day) on the MACO / HBEL calculator with the next product's batch size and maximum daily dose. Last checked 2026-10-17.
Not a toxicological assessment. This applies the EMA permitted daily exposure equation only and does not replace expert judgment or a product-specific HBEL.
Worked example
Invented rat NOAEL: 5 mg/kg/day, body weight 50 kg, F1 5, F2 10, F3 1, F4 1, F5 1. Load example fills the same numbers. PDE = 5.000 mg/day.
Sources
- EMA HBEL / PDE guideline (Nov 2014) — PDE derivation; HBEL for shared-facility risk identification
- ICH Q3C(R9) Residual Solvents (minor revision 2024) — Tables 1–4
FAQ
What is a PDE (permitted daily exposure)?
A PDE is a health-based exposure limit: a substance-specific dose, in mg/day, that is unlikely to cause an adverse effect if a person is exposed at or below it every day for a lifetime. EMA uses the PDE as the HBEL for shared-facility risk identification. This page calculates it from a NOAEL or other point of departure divided by F1 × F2 × F3 × F4 × F5, multiplying by body weight only when the point of departure is per kilogram.
When is body weight used?
Body weight is the weight adjustment in the EMA and ICH Q3C equation when the point of departure is mg/kg/day or µg/kg/day. Those guidelines use 50 kg for an adult. If the point of departure is already mg/day or µg/day, body weight is not applied.
What are F1 through F5?
They are the uncertainty factors in ICH Q3C Appendix 3, which the EMA shared-facility guideline uses for PDE derivation. F1 extrapolates between species (mouse 12, rat 5, rabbit 2.5, dog 2, monkey 3, other animal 10; 1 when the data are already human). F2 is interindividual variability, usually 10. F3 adjusts study length. F4 covers severe toxicity such as teratogenicity. F5 is up to 10 when only a LOAEL is available. Enter the factors that match the study; this page does not choose them for you.
Does this replace a toxicology assessment?
No. Not a toxicological assessment. This applies the EMA permitted daily exposure equation only and does not replace expert judgment or a product-specific HBEL. Confirm the point of departure and uncertainty factors with a qualified toxicologist and the current EMA and ICH text. Values were last checked 2026-10-17.
How do I use this PDE in a cleaning limit?
The MACO calculator takes this PDE in mg/day, with the next product’s minimum batch size and maximum daily dose, to derive a health-based carryover limit. Historical 1/1000 dose and 10 ppm values on that page are alert-limit comparisons only.