On the fate of triclosan in humans

Sammanfattning: Triclosan is a chlorinated organic compound which, due to its antibacterial properties in vitro, has found widespread use in a variety of products such as textiles, plastics and healthcare products. Humans are directly and chronically exposed to triclosan via dermal and mucosal contact from soap and toothpaste, upon which triclosan is rapidly absorbed into the body. Owing to the hydroxyl group on triclosan and the quick phase II metabolism, the turnover of triclosan in the human body is relatively fast and the plasma half life is less than a day. Nevertheless, triclosan has been found in human blood plasma and milk. A cause for concern in this regard, is that in vitro and in vivo animal studies show that triclosan is able to exert adverse effects on hormone homeostasis and metabolic mechanisms, connected to a diverse array of possible toxicological endpoints. Before this work began, the information about the exposure to triclosan in humans was scarce. Furthermore, the methods for analyzing triclosan in human body fluids lacked sensitivity. There was a need to identify the main sources of triclosan in humans and to investigate the exposure to triclosan in different subgroups of human populations. Also, the fact that triclosan had been found in human plasma warranted further study to examine the transfer rate of triclosan from plasma to milk, and to elucidate if breast milk is a significant source of triclosan to infants. In addition, there was a clear need to study if the in vivo triclosan exposure in humans had an impact on cytochrome P450 3A4 enzyme activity and/or thyroid hormone homeostasis. The scope of this thesis was to contribute to filling these knowledge gaps. Study I describes a sensitive and precise method for the analysis of triclosan in human body fluids, enabling the study of background levels of triclosan. Study II showed that triclosan was omnipresent in plasma and milk from Swedish nursing mothers, and that the level of exposure was highly correlated to the use of triclosan containing personal care products. The transfer rate of triclosan from plasma to milk was low, and the risk of adverse effects from triclosan exposure of the breastfed infant via the milk was judged to be negligible. The results from Study III showed that, apart from some small gender and age variations, the exposure was quite homogenous among serum pools of different genders, ages, regional cohorts and sampling years from the Australian population. Study IV showed that the in vivo exposure to triclosan via toothpaste in humans is not likely to change cytochrome P450 3A4 enzyme activity and/or thyroid hormone homeostasis. While this work shows that there is widespread human exposure to triclosan as a result of the use of triclosan containing personal care products, more research is needed to assess potential negative effects thereof.