This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common byproductsthat are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developedfor monofunctional alkyl bromides, aligning this with the class-specific limit previously defined formonofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetimechronic exposure for the general population (including sensitive subpopulations) by all routes of exposure forpharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methylbromide because of their localized toxicity via that route. Mode of action was an important consideration for acompound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumeda linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumeda non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to bemutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lackof mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficientdata to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- andclass-specific toxicology limits described here may be adjusted for an individual drug substance based ontreatment duration, dosing schedule, severity of the disease and therapeutic indication.