CH 13 · notes
How it works
ICH Q3C(R9) classifies residual solvents and lists permitted daily exposures (PDE) or concentration limits. Class 1 solvents (Table 1) have concentration limits only — the guideline does not assign a PDE. Class 2 solvents (Table 2) list a PDE in mg/day and an Option 1 concentration in ppm. Class 3 solvents (Table 3) are acceptable without justification (Class 3 PDEs are 50 mg/day or more) with Option 1 of 5000 ppm. Table 4 lists solvents with no adequate toxicological data for information only — no limits on this page.
Option 1 assumes a product mass of 10 g/day: concentration (ppm) = 1000 × PDE (mg/day) ÷ 10. Option 2 uses the actual maximum daily dose (MDD) in g/day: ppm = 1000 × PDE ÷ MDD. When several components each contribute the same residual solvent, Option 2 summation converts each component's ppm and daily dose to mg/day (ppm × g/day ÷ 1000), sums them, and compares the total with the solvent limit. ICH Q3C expects the summed intake to be less than the limit (not equal).
Worked example
Invented multi-component check for acetonitrile (Class 2, PDE 4.1 mg/day). Component 1 at 200 ppm and 0.5 g/day contributes 0.1000 mg/day. Component 2 at 100 ppm and 1 g/day contributes 0.1000 mg/day. The sum is 0.2000 mg/day, which is below 4.1 mg/day (PASS). With MDD 2 g/day alone, Option 2 for acetonitrile is 1000 × 4.1 ÷ 2 = 2050 ppm. Option 1 for the same solvent is 410 ppm (1000 × 4.1 ÷ 10).
Sources
- ICH Q3C(R9) Residual Solvents (minor revision 2024) — Tables 1–4
- EMA ICH Q3C residual solvents scientific guideline
- USP <467> Residual Solvents — general chapter aligned with ICH Q3C
Last checked 2026-10-17. This page does not replace regulatory judgment.
Related tools
Nitrosamine AI limits are on the nitrosamine limit calculator. Assay precision is on the RSD calculator. Relative response factors are on the RRF calculator.
FAQ
What is Option 1 versus Option 2 in ICH Q3C?
Option 1 converts the permitted daily exposure (PDE) to a concentration assuming 10 g of product per day: ppm equals 1000 times PDE in mg/day divided by 10. Option 2 uses the actual maximum daily dose in g/day in the same formula. Both come from ICH Q3C(R9).
How does Option 2 summation work?
For each component, solvent intake in mg/day equals residual solvent ppm times that component's daily dose in g/day, divided by 1000. Sum those intakes and compare with the solvent limit. The sum must be less than the limit (PASS). Example with invented data: acetonitrile PDE 4.1 mg/day; 200 ppm at 0.5 g/day plus 100 ppm at 1 g/day sums to 0.2000 mg/day (PASS).
What is Class 3 on the solvent table?
Class 3 solvents are shown as acceptable without justification (Class 3 PDEs are 50 mg/day or more), not as a single PDE figure. Option 1 remains 5000 ppm for the default 10 g/day assumption.
What is ICH Q3C Table 4?
Table 4 lists solvents for which no adequate toxicological data was found to set a PDE. This page lists them for information only with no limits; manufacturers justify residual levels.
Why do Class 1 solvents have no PDE here?
ICH Q3C(R9) Table 1 lists concentration limits for Class 1 solvents and does not assign PDE values for those rows. Browse them in the solvent table mode. Option 1, Option 2, and summation need a PDE, so they list Class 2 and Class 3 solvents only.
Does this page replace regulatory judgment?
No. Confirm limits with the applicable authority and the current ICH Q3C / USP <467> text. Values were last checked 2026-10-17. The calculation stays in the browser.