Preclinical research arithmetic. Never a dose for a person. This scales an animal no-effect dose to a human-equivalent figure by body surface area. That figure is one input to a regulated first-in-human process involving a full toxicology package, an IND and an ethics committee. It is not a dose, not a recommendation, and not safe to take. Open for the full scope limits.
What this tool actually computes
Body-surface-area normalisation between species using the Km factors from the FDA's 2005 guidance on estimating the maximum safe starting dose in initial clinical trials, then the customary tenfold safety factor to give a maximum recommended starting dose.
That is allometric arithmetic. It carries no information about the compound beyond the number you typed.
Not accounted for, at all
- Anything pharmacokinetic. No absorption, bioavailability, half-life, accumulation on repeat dosing, Cmax or AUC. Two compounds with the same HED can have completely different exposure.
- Species metabolism. Humans and rodents differ in CYP isoforms, plasma protein binding and metabolite profiles. A metabolite that is minor in rat can be the toxic one in human, and BSA scaling cannot see it.
- Pharmacodynamics. No receptor affinity, potency, selectivity or target expression differences between species.
- Route and formulation. An oral NOAEL does not scale to an intravenous dose, and salt form, excipients and release profile all change exposure.
- Who is taking it. No hepatic or renal impairment, age, pregnancy, paediatric scaling, genetic polymorphism, comorbidity or drug interaction.
- Local and immune toxicity. Injection-site reactions, irritancy and immunogenicity do not scale by surface area.
BSA scaling is the wrong method for whole classes of compound. The guidance itself directs mg/kg scaling for biologics, and monoclonal antibodies in particular should not be scaled this way.
What the number is not
A maximum recommended starting dose is the lowest dose at which a supervised trial may begin, chosen to be far below any expected effect. It is not a therapeutic dose, not an effective dose, and not a dose anyone takes outside a clinical trial with a physician, an ethics approval and rescue arrangements in place.
TGN1412 produced catastrophic multi-organ failure in six healthy volunteers at a dose 500 times below the animal NOAEL, calculated correctly by the method of its day. Correct arithmetic is not safety.
That case is why NOAEL scaling is no longer the accepted starting point for immunomodulatory biologics. Regulators moved to MABEL, the minimum anticipated biological effect level, derived from receptor occupancy and in-vitro pharmacology in human cells rather than from an animal dose. This page implements the BSA route only, so for any compound where MABEL is the appropriate basis, the number here is not merely imprecise: it is the wrong quantity.
Never use this for
- Any dose taken by any person, including yourself. Not for self-medication, supplementation, nootropics, peptides, or so-called biohacking.
- Veterinary dosing or dosing an animal in your care.
- Writing a clinical trial protocol, an IND, or a regulatory submission.
- Setting occupational exposure limits or an acceptable daily intake.
- Any decision that a qualified toxicologist, pharmacologist or physician has not reviewed.
What the real process looks like
A GLP toxicology package in at least two species, identification of the most appropriate species, NOAEL selection with pharmacokinetic support, a starting dose justified in an IND, review by a regulator and an ethics committee, a qualified investigator, dose escalation with stopping rules, and monitoring. This page replaces none of that.
Dose Translation
Calculate Human Equivalent Dose (HED) from Animal NOAEL.
1. Standard Conversion (Appendix B)
When animal weights are within the standard FDA "working range", the conversion uses fixed Km factors:
2. Km Factor Derivation
The Km factor represents the ratio of body weight to body surface area. It is calculated as:
3. Reference Values (Table 3)
| Species | Ref Weight | Range (kg) | BSA (m2) | Km |
|---|
4. Dynamic Conversion (Power Formula)
If an animal's weight falls outside the standard range, the calculator auto-switches to the Power Formula to maintain accuracy:
5. BSA Estimation Logic
The tool estimates Body Surface Area (BSA) using the inverse of the Km definition: BSA = Weight / Km. By calculating the theoretical Km first (using allometry), we derive a BSA that accurately reflects the animal's geometry (BSA ∝ Weight0.67), rather than assuming a fixed ratio.
Compare how Km shifts when you assume Body Surface Area (BSA) is fixed vs. when it scales allometrically.
Why Linear Scaling Fails (The Square-Cube Law)
In biology, scaling an animal's weight linearly does not scale its surface area linearly. This is known as the Square-Cube Law:
- Volume (Weight) increases by the cube of length (L3).
- Surface Area increases by the square of length (L2).
Therefore, Surface Area is proportional to Weight raised to the power of 2/3 (or 0.67).
The Error: The "Linear Km" calculation assumes Surface Area grows 1:1 with Weight. This underestimates the Km factor for larger animals, leading to potentially dangerous overdoses when scaling from small to large species.