The US Food and Drug Administration's Office of Food Additive Safety in the Center for Food Safety and Applied Nutrition conducts safety assessments of food additives, including food-contact substances such as polymeric and oligomeric materials that have the potential to migrate to food. Traditionally, little toxicity testing has been conducted on the low-molecular weight oligomeric fraction (< 1000 Da) of these food-contact substances. At lower exposures (≤ 150 μg/person/day), safety has been assessed based on the use of toxicity data on the monomeric components of these polymers as a sufficiently conservative approach for addressing the concern for genetic toxicity and carcinogenicity of the low-molecular weight oligomers (LMWOs). This paper discusses this assumption relative to the available data on these substances and their monomeric components in the context of exposures of ≤ 150 μg/person/day with emphasis on the evaluation of the potential genetic toxicity of these compounds. In most instances, data are available on either the monomers or the monomers' structural class to conservatively address the potential genetic toxicity of the LMWOs. Caveats to this generalization are also discussed. The assessment of LMWOs is important because they can be one of the primary migrants to food from a polymeric food-contact substance.