What does science tell us about using fragrance over time?
Often, our body’s response to a single exposure or even a few exposures to a substance (what we call acute exposure) does not provide a complete picture of how this interaction may affect us.
With the “repeated dose” toxicity endpoint, the Research Institute for Fragrance Materials (RIFM) examines the effects of frequent and regular ingredient exposures over a prolonged period. For example, we use fragranced products daily for most of our lives (what we call chronic exposure), so repeated dose studies better simulate real-life conditions.
Repeated dose toxicity differs from endpoints like skin sensitization or local respiratory toxicity in that we investigate an ingredient’s potential systemic rather than local effects. Whereas “local” refers to an ingredient’s effects on one particular organ or site, such as the skin or the lungs, “systemic” refers to an ingredient’s general effects on the body, such as changes to multiple organs.
RIFM scientists study systemic effects by evaluating “ADME,” which stands for four aspects of how an ingredient interacts with the human system over time: Absorption, Distribution, Metabolism, and Excretion.
Absorption refers to an ingredient’s potential to enter the body.
Distribution refers to where in the body an ingredient might travel.
Metabolism is a more complicated process wherein the body naturally breaks down a substance to use and eliminate it. The substance may change its molecular structure during this process, and scientists refer to these new, temporary structures as metabolites.
Excretion refers specifically to the elimination of the ingredient from the body.
It is important to reiterate that RIFM does not perform any new animal testing for the human health endpoints, including repeated dose toxicity. Hence, RIFM continues to rely on existing study data to assess repeated dose toxicity and, when needed, may use read-across or the Threshold of Toxicological Concern (TTC). Moreover, RIFM collaborates with scientists worldwide to investigate New Approach Methodologies (NAMs) to reliably study repeated dose toxicity effects without testing on animals. For example, one NAM currently being investigated is the Human Dynamic Multi-Organ Plate (HuDMOP), an in vitro platform created by IONTOX by LifeNet Health LifeSciences to simulate absorption, distribution, and metabolism across multiple organs.
Senior Scientist Kaushal Joshi, PhD, leads RIFM’s Repeated Dose and Reproductive Toxicology research and safety assessment programs.