Current approaches for the prospective regulatory assessment of chemicals do not account sufficiently for elevated mixture risks. The Mixture Assessment Factor (MAF, better labelled a Mixture Allocation Factor) has been suggested in the EU’s chemical strategy for sustainability as a pragmatic tool to account for potential mixture risks already during the risk and safety assessment of individual chemicals. The aim is to reduce the need for dedicated and data-demanding scenario-specific mixture risk assessments. Several approaches and algorithms for calculating a MAF have been suggested in the literature. This paper provides a comparative overview and argues that the so-called MAFexact is the most promising approach in the context of chemical registration and authorization under regulatory frameworks such as REACH. The MAFexact, which is a member of the larger MAFceiling class, is defined as the maximum fraction of the risk quotient of each chemical that is still acceptable to occur in a mixture, without the sum of risk quotients exceeding 1. This approach ensures a protection level that is similar to the protection level used in the current safety assessment of individual chemicals under REACH. Other MAF approaches either disproportionally impact low-risk substances, without leading to any appreciable risk reduction, or hamper risk communication because they lead to fluctuating residual risks after the MAF application. The paper also presents a case study comparing the different MAF approaches and finally discusses the MAF concept in the wider context of chemical regulation.