[Discussion] Be cautious applying carbon-fluorine bonds in drug delivery

By Christian Sonne, Su Shiung Lam, Ki-Hyun Kim, and Yong Sik Ok
February 4, 2020
DOI: 10.1016/j.chemosphere.2020.125971

As reported in Chemosphere by Colles et al. (2020), there is multiple pathways for human exposure to poly- and perfluoroalkyl substances (PFAS). Now, a new chemical formation of C-F bonds in drug delivery lead to concerns for human exposure as these inert chemical formations are resistance to metabolic degradation and excretion.

According to a new study in Nature, the synthesis of N-trifluoromethylamides containing carbon-fluorine (C-F) bonds now offers new opportunities for the invention of human medicine in the pharmaceutical industry because of their polarity-induced stimulation to efficiently interact with biological receptors and enzymes (Clayden, 2019Scattolin et al., 2019). A careful look at the components nonetheless leads to suspicion whether they can exert potentially harmful side effects in humans given that their physicochemical properties are similar to the industrially produced chemicals per- and polyfluoroalkyl substances (PFAS). These repellent chemicals, when used in for example GoreTex, Teflon, and fire foam, are extremely toxic to humans and lead to impairment of reproduction and suppression of the immune system as well as cancer promotion (Im et al. 2019).

Despite these new substances are short length carbon chains with short half-life and thereby less toxic than PFAS it is still far from clear and should be investigated further including the break-down products in drinking water (Kotthoff and Bücking 2018). For example, emerging evidence has suggested that PFBS, a short-chain PFAS with only four carbon atoms and commonly used as a replacement for long-chain PFAS, is still associated with adverse health outcomes (Liu et al. 2020). The proposed new pharmaceutical chemicals may therefore have undesired effects such as reduced responses to vaccinations, infertility, auto immunity, and in worst-case also cancer.

In the light of the potential risk associated with C-F bonds, we recommend to restrict their use just like the neuro-toxic compound Thiomersal used as an antiseptic and antifungal organo-mercury compound in vaccine production only (Geier et al. 2015). In Michigan in the US, historical PFAS pollution by the Wolverine Worldwide tannery has caused an array of human health problems such as high cholesterol, ulcerative colitis, thyroid disease, testicular cancer, kidney cancer as well as pregnancy-induced high blood pressure (Talpos 2019). Because of this and other cases, the global production and sale of organic fluorinated compounds being banned through the Stockholm Convention to avoid adverse effects on humans and wildlife (Stockholm Convention 2018). This should be a red alert with respect to the pharmaceutical (industrial) use of carbon-fluorine due to its significant risk as aforementioned.

Caution should be taken when considering exposing humans to novel drugs and chemicals with containing C-F structures. We therefore urge to collect more evidence on the toxic properties from N-trifluoromethylamides in humans, with special caution for pregnant women due to risk of foetal and neonatal neuro-endocrine development (Grandjean et al. 2014). No or reduced consumption of these upcoming novel chemicals should be implemented to safeguard the health of the coming generations as claimed by the Lancet Commission on Pollution and Health (Landrigan et al. 2018).


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