The difference between hazard and risk: the dose range prevalent in toxicological studies vs real life fragrance exposure

Abstract

Ensuring the safety of fragrances is a priority for both consumers and industry. The Research Institute for Fragrance Materials (RIFM) conducts risk assessments using a transparent framework. In the past, evaluating systemic toxicity relied on animal studies mandated by regulatory requirements; however, RIFM has not conducted new animal toxicity studies for over a decade. Of note, the doses used in these studies far exceed everyday exposure to fragrance ingredients. While toxicologists recognize the gap between test doses and real exposure, it may not be obvious to an average fragrance user. To illustrate this, the No-Observed-Adverse-Effect Levels (NOAEL) and Human Equivalent Doses (HED) of benzaldehyde and p-cymene were determined. As benzaldehyde and p-cymene occur in fragrances and foods, we used intake in food and fragrance use as a comparator. For fragrance exposure, the Creme RIFM Aggregate Exposure model was utilized. Results showed that adverse effect levels require ingesting about 166,000 almonds (for benzaldehyde) or 307,407 raspberries (for p-cymene) daily, or applying 276,660 sprays of benzaldehyde and 37,220 sprays of p-cymene daily. The selected exposure scenarios emphasize that data from animal studies must be viewed in the context of human exposure, highlighting advances in exposure science for realistic risk assessment.