Background and Purpose: Ionones and related compounds are used in food products as flavor ingredients; however, Health Guidance Values (HGVs) are available for a limited number of these chemicals. Additionally, less is known about ionone use in non-food items such as perfumes. Our study evaluated the existing toxicological data on ionones and related compounds to determine whether it is scientifically possible to establish oral, inhalation, and dermal Maximum Acceptable Group Levels (MAGLs). Methods: A review of ionones and related compounds was conducted, which included basic physicochemical properties, classified hazards, absorption by the oral and inhalation routes, as well as metabolism and elimination. Where appropriate, evaluation of empirical data was supplemented with Quantitative Structure-Activity Relationship (QSAR) predictions from OECD QSAR Toolbox. Subsequently, a quantitative risk assessment was conducted with an emphasis on exposures by the inhalation and oral route, considering whether route-to-route extrapolations were feasible in the absence of inhalation data. Dermal exposure route was also considered. Different approaches were followed as appropriate for the derivation of the oral, inhalation, and dermal Points of Departure (PoD), depending on the available toxicological information and the toxicological effects evaluated (e.g., systemic or local). Results: Ionones and related compounds were considered for grouping based on their similarity. The results found no evidence for major differences in biological or toxicological effects across the compounds; however, damascones were found to be slightly more toxicologically potent than other ionones and related compounds. The limited empirical data indicated that ionones and related compounds had low to moderate acute toxicity, had a similar range of No-Observed-Adverse-Effect Level (NOAEL) and Lowest-Observed-Adverse-Effect Level (LOAEL) values in subchronic toxicity studies with similar systemic toxicities (i.e., weight and organ weight changes, histological effects in the liver and kidneys, hematological effects). The ionones and related compounds were also not likely to be developmental or reproductive toxicants at doses that did not elicit maternal toxicity. Further, some of the ionones and related compounds (e.g., alpha-iso-methylionone) were flagged as potential skin irritants. Additionally, some compounds, particularly damascones, had some indication be skin sensitizers. Regarding metabolism, the empirical data and general chemistries did not suggest that the overall metabolic processes would be significantly different between these compounds, except for damascones, which were more likely to form epoxide intermediates. The in silico data showed a greater degree variation across compounds than would be expected based on empirical data. It was noted that ionone, methyl-ionone, damascone, damascenone, allyl-ionone, irone, and iso-methylionone, had the same toxic hazard classification (Low, class I) and health endpoint alerts (carcinogenicity, mutagenicity, skin sensitization, and skin irritation). Based on toxic hazard classification and endpoint alert similarities, the other potential subgroups identified were (i) Dihydro-ionone and dehydrodihydro-ionone, sharing the same toxic hazard classification (Low, class I) and health endpoint alerts (skin sensitization and skin irritation), and (ii) ionol, dihydro-ionol, and dehydrodihydro-ionol, sharing the same toxic hazard classification (Low, class I) and health endpoint alerts (eye irritation). Based on the data reviewed, it was concluded that MAGL derivation would be justified if PoDs for the worst-case scenario are used.Conclusions: In the absence of HGVs  for the majority of ionones and related compounds, the derived MAGLs can be used as guidance for risk assessment purposes.