A critical review of environmental exposure, metabolic transformation, and the human health risks of synthetic musks

Synthetic musks (SMs) have been widely used as fragrance ingredients in various daily consumer products. Due to their mass production and usage, the presence of SMs has been reported in environmental and human biological samples, raising global concerns over human health effects. This review outlines the current knowledge on human exposure pathways and internal exposure to environmental SMs. The biotransformation of SMs in humans is also highlighted. Compared to exposure through inhalation and oral ingestion pathways, dermal contact from SMs-containing personal care products is the dominant pathway, accounting for 82-93% of total human SMs daily exposure. After penetrating the skin barrier, SMs can be absorbed by the dermis, causing potential skin irritation. Regarding internal human exposure, around half of the limited studies focused on breast milk, indicating considerable risks for vulnerable global populations (e.g. pregnant women and babies). The health effects of SMs are assessed synergistically based on the existing data and our calculated toxicological predictions. SMs could induce endocrine disruption and mutagenic toxicity according to historical analysis of data. Our computational toxicology data suggested negative impacts on the cardiovascular system for the first time. However, caution should be applied when interpreting adverse health effects using the available data, as the effective toxic doses of different SMs in laboratory studies were greater than actual environmental concentrations in most cases. Based on an analysis of research progress, this review also proposed the need to study the relationship between long-term low-dose exposure and adverse human health effects in future research.