Although TR and AR are cultivated and have been used for hundreds of years, relevant bacterial resistances to ITCs have not as yet been reported. The safety of systemic TR/AR administration up to 1200/480 mg daily was demonstrated in a clinical trial [
17]. Adverse side effects were significantly lower in a TR/AR group than an antibiotic group [
16]. Negative effects on the gut microbiota were not observed. Moreover, the treatment costs with TR/AR are substantially lower than with antibiotic prescriptions. Additionally, chlorhexidine, which has been considered the gold standard in dental plaque control [
23], is also cytotoxic, as reported for human gingival fibroblasts, osteosarcoma cells and osteoblasts [
24,
25]. Moreover, human saliva can to some extent inactivate the antibacterial effects of chlorhexidine against some oral bacteria, inducing selective processes in the bacterial populations of human saliva [
26]. Furthermore, a correlation of resistance towards chlorhexidine and different medically relevant antibiotics cannot be excluded due to the similar mechanisms of resistance which include multidrug efflux pumps and cell membrane changes as reported in an own review of the literature [
27]. Another frequently used oral health product is Listerine® [
28]. Although there is accumulating evidence that Listerine® is effective in improving oral health, the absence of systematic toxicological studies means that an accurate safety assessment cannot be made [
29]. Hence, new natural antibacterial compounds such as ITCs from plants could be promising components for dental oral care. However, the direct comparison of ITCs effects on oral pathogens with standard antibiotics or chlorhexidine is still pending, which must be acknowledged as a limitation of our study approach.