## 4 Discussion
### Safety of the Nicotine-Free Inhalator  
Peppermint oil is widely used in folk remedies and traditional medicine to treat digestive disorders and nervous system problems because of its antitumor, chemopre, and antimicrobial properties, as well as its beneficial renal and antiallerggenic effects [32; 33; 34]. It is also thought to be effective against cramping, digestive complaints, anorexia, nausea, and diarrhea [32; 33]. Peppermint oil is composed of menthol and menthone, along with several other minor constituents [32]. Although most peppermint research has been conducted on rat models, it is considered a medicinal plant for human diseases. However, peppermint oil has also been found to cause cyst-like changes in the white matter of the cerebellum and nephropathy at overdoses of 40-100 mg/kg per day for 28-90 days [32]. In rats, 80 mg and 160 mg pulegone doses over 28 days caused atonia, weight loss, decreased blood creatinine, and histopathological changes in the liver and the white matter of the cerebellum. Menthol was also observed to cause hepatocellular changes in rats [32]. During the Cosmetic Ingredient Review (CIR) Expert Panel Meeting, the panel expressed concern over oral dosing of peppermint oil, as some studies found evidence of pulegone-based toxicity [35].  
The pulegone and menthofuran in peppermint oil are hepatotoxic; thus, they should be restricted in food and herbal products. The CIR commission should consider the latest risk assessments on pulegone and menthofuran: according to a public statement from the European Medicines Agency on the use of herbal medicinal products, _M. piperita_ (peppermint) oil contains a maximum of 4% pulegone and between 1% and 9% menthofuran [35]. Furthermore, the Scientific Committee on Food (SCF) has concluded that pulegone is mainly metabolized through pathways involving menthofuran, and these two substances show similar toxicity. The authors of \"Essential Oil Safety\" have recommended a maximum daily oral dose of 152 mg for _M. piperita_ oil [36]. This oral restriction is based on an 8% menthofuran and 3% pulegone content, with limits of 0.2 mg/kg/day for menthofuran and 0.5 mg/kg/day for pulegone [35].  
Toxic substances (menthofuran and pulegone) have been detected in vapor analyses of peppermint oil [18], but they were not detected in our nicotine-free inhalator. Levels of aroma substances and VOCs that are detected at lower levels than DNEL or sensory irritation values can be considered as safe. However, the isomenthone and acrolein levels were detected to be higher than those of the DNEL or sensory irritation values that are considered safe (depending on total use time). Acrolein is considered to pose one of the non-cancerous health risk of all hazardous air pollutants [37]. In animal studies, decreased body weight gains were reported in rats, hamsters, monkeys, and rabbits exposed to 0.32-4.9 ppm acrolein. In the intermediate exposure study in rats (61 days, 24 h/day), the NOAEL of 0.06 ppm and LOAEL of 0.32 ppm have been calculated [38]. The acrolein level (0.06 ppm) in the nicotine-free inhalator is the same as NOAEL for intermediate exposure. If daily exposure time is clearly shorter than 24 h, it is considered safe.  
The usage pattern of a nicotine-free inhalator is typically intermittent, such as when the consumer feels a smoking craving. The typical usage time of a nicotine-free inhalator is usually much shorter than a worker's exposure time (8 h). However, if the usage time of a nicotine-free inhalator exceeds eight hours per day, its exposure risk may go beyond guideline levels.