How is a Permitted Daily Exposure calculated?

PDE equals the NOAEL times body weight divided by the product of five adjustment factors (F1 species, F2 individual variability, F3 study duration, F4 severity, F5 LOAEL-to-NOAEL).

Exposure Limits — PDE / ADE / OEL Calculator

Point of Departure

NOAEL mg/kg/day

NOAEL = No Observed Adverse Effect Level — the highest repeat-dose level in the pivotal toxicology study that produced no adverse effect, in mg/kg/day. This is the point of departure the whole calculation scales from. If only a LOAEL (Lowest Observed Adverse Effect Level) is available, raise F5 below to compensate.

Species (F1)

F1 is the interspecies modifying factor from ICH Q3C / EMA — it corrects for differences in metabolism and sensitivity between the tested animal species and humans. Smaller or more physiologically distant species carry a larger factor (e.g. mouse F1 = 12) than species closer to human physiology (e.g. dog F1 = 2).

F2 indiv.

F3 duration

F4 severity

F2 (individual variability) accounts for differences in sensitivity across the human population — default 10. F3 (study duration) scales up the factor for short studies that don't cover a full lifetime or chronic exposure — up to 10 for a study far shorter than the intended human exposure duration. F4 (severity) increases the factor for severe, irreversible, or difficult-to-monitor toxicity (e.g. teratogenicity, carcinogenicity) — typically 1–10.

F5 NOAEL/LOAEL

Human weight kg

F5 is applied only when the point of departure is a LOAEL rather than a true NOAEL — leave at 1 if you entered a genuine NOAEL above; raise to 2–10 if the lowest tested dose already showed an adverse effect. Human weight is the reference body weight used to convert the per-kg PDE into a total daily mg dose — default 50 kg per ICH Q3C / EMA (a conservative, sex/size-inclusive reference weight, lower than the 60 kg used for HED/MRSD).

Worker inhalation volume m³ / 8 h (OEL)

The volume of air a worker breathes during an 8-hour shift, used only to convert the ADE into an OEL (Occupational Exposure Limit) for airborne/handling exposure risk — default 10 m³ (light industrial work). Does not affect the PDE/ADE result itself.

Add MACO cleaning limit

MACO (Maximum Allowable Carryover) is the residue limit for cleaning validation when this product's equipment is shared with a different "next" product. It answers: how much of this compound can remain on shared equipment without exceeding a safe dose in the next product made on that line?

Next product min batch size mg

The smallest batch size (total product mass, mg) of the next product manufactured on the shared equipment — using the smallest batch is conservative, since carryover is diluted least into a small batch.

Next product max daily dose mg/day

The highest daily dose (mg/day) a patient could receive of the next product — the higher this is, the more residue a patient could ingest, so this drives the limit down.

Shared surface area cm², optional

Optional. The shared equipment's product-contact surface area, used to convert the MACO mass limit into a swab/rinse concentration limit (µg/cm²) for analytical verification.

PDE = ADE = (NOAEL × body weight) / (F1×F2×F3×F4×F5). OEL (8-h TWA) = ADE / inhalation volume. MACO = ADE_prev × MinBatch_next / MaxDailyDose_next. Confirm every modifying factor against the guideline before GMP use.

Ready to calculate.

Results

Enter a NOAEL and click Calculate PDE to see the PDE/ADE, OEL and OEB band here.

How the PDE / ADE and OEL are derived

A Permitted Daily Exposure (PDE) — also called an Acceptable Daily Exposure (ADE) — is a health-based limit for how much of a compound a person can be exposed to each day without adverse effect. It underpins cleaning validation in shared facilities and worker-safety limits.

The PDE equation

Starting from a No-Observed-Adverse-Effect Level (NOAEL), the PDE applies a chain of adjustment factors and a reference body weight (default 50 kg):

PDE (mg/day) = (NOAEL × body weight) / (F1 × F2 × F3 × F4 × F5)

Factor	Accounts for	Typical range
F1	Animal-to-human extrapolation	2–12
F2	Individual variability	10
F3	Study duration	1–10
F4	Severity of the effect	1–10
F5	Use of a LOAEL instead of a NOAEL	1–10

From PDE to OEL and OEB

An Occupational Exposure Limit (OEL, an 8-hour airborne average) is derived from the same health-based point of departure and typical breathing/work assumptions, and is then placed into an Occupational Exposure Band (OEB 1–5) for handling controls.

Worked example

A subchronic rat study gives a NOAEL of 5 mg/kg/day:

PDE = (5 × 50) / (F1 5 × F2 10 × F3 5 × F4 1 × F5 1)
= 250 / 250 = 1 mg/day

Reference: ICH Q3C(R9) Appendix 3; EMA guideline on health-based exposure limits (2014).

Frequently asked questions

Are PDE and ADE the same thing?

Effectively yes — they are the same health-based daily limit. "PDE" is the term used in ICH/EMA guidance; "ADE" is the equivalent term popularised by ISPE. Both use the same NOAEL-and-adjustment-factor approach.

How is the OEB band chosen?

The airborne OEL is mapped onto a banded scale (typically five bands spanning roughly >1000 µg/m³ down to <1 µg/m³); a lower OEL means a higher, more stringent band with tighter containment.

What is the MACO used for?

The Maximum Allowable Carryover translates the health-based limit into the amount of a product that may remain on shared equipment before the next product is made — the quantitative basis of cleaning-validation acceptance limits.