Which toxicity test is mandatory and cannot be waived during preclinical investigations of a new chemical entity?

Genotoxicity testing is mandatory in preclinical investigations of new chemical entities because it assesses the potential for the compound to cause damage to the genetic material within a cell, which can lead to mutations and cancer. Regulatory agencies emphasize the importance of understanding whether a drug possesses genotoxic properties due to its implications for human health and safety. Discovering that a compound is genotoxic can have significant ramifications during drug development, as it raises concerns about the possible long-term effects of exposure to the drug.

Acute toxicity, while also an important test, does not hold the same level of mandatory status across all programs since some scenarios allow for waivers or alternative approaches based on the chemical nature or prior data. Carcinogenicity testing typically is required but may not be mandated in all early phases of investigation; certain products may qualify for a waiver depending on the exposure and expected use. Reproductive toxicity studies are crucial as well, but they can also sometimes be deferred based on specific circumstances and available data. Therefore, among all these categories, genotoxicity remains the critical test that must be completed without the possibility of waiver during preclinical development.