The IC₅₀ or LC₅₀ values obtained from cell culture experiments represent the concentration of a compound that inhibits or kills 50% of cells in vitro. In contrast, the LD₅₀ refers to the dose per body weight that causes 50% lethality in animals such as mice, and it is highly dependent on factors like absorption, metabolism, and distribution. Because of these fundamental differences, there is no direct formula to convert IC₅₀ or LC₅₀ values into LD₅₀.

One main reason for this is that in vitro concentrations do not reflect what happens inside a living organism. In vivo, the compound must pass through barriers like the gastrointestinal tract, bind to plasma proteins, distribute into tissues, undergo metabolism in the liver, and eventually be excreted. All these processes can dramatically alter the effective dose reaching target tissues compared with what is seen in a cell culture dish. Thus, two compounds with similar IC₅₀ values could have very different LD₅₀ values in animals.

If an estimate is needed, researchers often use in vitro to in vivo extrapolation (IVIVE). This involves combining the in vitro toxic concentration with pharmacokinetic parameters such as bioavailability, volume of distribution, and clearance to estimate what dose in mice might produce similar internal exposure. However, this is only an approximation, and the result should be treated as a rough guide to select safe starting doses for animal studies, not as a true LD₅₀ value.

A more reliable approach is to use computational toxicology models (QSAR, PBPK modeling) or follow OECD guidelines that use alternative methods rather than full LD₅₀ testing. These approaches reduce animal use while still allowing researchers to assess toxicity. In summary, while you cannot directly calculate LD₅₀ from IC₅₀/LC₅₀, you can use modeling and pharmacokinetic extrapolation to make cautious estimates, but any claim of LD₅₀ requires proper in vivo testing.

Here’s a simple IVIVE (in-vitro → in-vivo extrapolation) you can use to get a rough mouse dose from a cell IC₅₀/CC₅₀. It’s a starting-dose estimator, not a true LD₅₀.

Step-by-step template

1. Collect inputs

Cell potency: use CC₅₀ (µM). If you only have IC₅₀, treat it as a lower bound.

MW (g/mol).

fu_media = free fraction in your assay medium (≈1 if no serum; with 10% FBS you might assume 0.1–0.5 if unknown).

fu_plasma (mouse plasma free fraction; if unknown, try 0.05–0.3).

Vd (L/kg): ~0.7 for hydrophilic, 2–5 for lipophilic as a rough range.

F (bioavailability): ~1 for i.v./i.p.; 0.1–1 for oral.

k (lethality multiplier): 1–10× the free in-vitro effect level; 3× is a common middle-ground.

2. Convert in-vitro potency to a target free plasma concentration

Convert CC₅₀ (µM) to mg/L:

C_{\text{total, mg/L}} = \text{CC}_{50,\mu M} \times \text{MW} \times 10^{-3}

C_{\text{free, media}} = C_{\text{total, mg/L}} \times f_{u,\text{media}}

C_{\text{target, free plasma}} \approx k \times C_{\text{free, media}}

3. Map target free plasma concentration to a single-dose estimate

For a bolus dose in a one-compartment approximation:

\text{Dose}_{\text{est}} \;(\text{mg/kg}) = \frac{C_{\text{target, free plasma}} \times V_d}{F \times f_{u,\text{plasma}}}

4. Bracket uncertainty and choose a safe start

Compute a range by sweeping plausible values for , , , and . Start below the low end for pilot dosing; this is not a regulatory LD₅₀.

---

Worked example (so you can copy the math)

Assume: CC₅₀ = 50 µM, MW = 300 g/mol, fu_media = 0.3 (10% FBS), fu_plasma = 0.1, Vd = 0.7 L/kg (hydrophilic), F = 0.5 (oral), k = 3.

1. .

2. .

3. .

4. .

If the compound is more lipophilic (Vd ≈ 3 L/kg), the same inputs give ~810 mg/kg oral. For i.p. (F=1) with Vd=0.7, the estimate is ~94.5 mg/kg.

Reminder: This is an approximation to pick cautious starting doses. A numeric LD₅₀ requires in-vivo testing; when possible, use humane OECD acute methods (TG 420/423/425) and/or PBPK modeling to refine before dosing.

Thank you for your interest