The antibiotic chloramphenicol (CAP) is banned from food production. Besides being a medicinal product, CAP is also a natural product, produced by Streptomyces Venezuelae. The lack of scientific data hampers setting of an Acceptable Daily Intake (ADI). Consequently, a maximum residue limit (MRL) in food could not be established. This was then translated into a zero tolerance using the so-called Minimum Required Performance Limit (MRPL) level, viz. the achievable detection limit in food, to guide the zero tolerance policy. The MRPL is clearly not relevant to food safety and human health but is solely related to analytical technological capabilities. The increase in the latter enables detection at ever-lower levels and ignores toxicological relevance. We here provide arguments to use a Threshold of Toxicological Concern (TTC) for CAP that can accommodate developing toxicological insights.