## 2 Toxicology and Risk Assessment  
Due to its detrimental effect on biological macromolecules, formaldehyde has been recognized since 2004 as a toxic and carcinogen substance (category 1) by international research institutions, including International Agency for Research on Cancer (IARC), United States Environmental Protection Agency (US-EPA), and the European Chemicals Agency [14]. In particular, US-EPA established that the maximum daily FA dosage is 0.2 ug g\({}^{-1}\) of body weight [9; 15] whereas that established by the World Health Organization (WHO) is in the range of 1.5-14 mg d\({}^{-1}\) (7.75 mg d\({}^{-1}\) for an average adult) [16].  
Due to its cosmopolitan presence, millions of people are exposed to FA worldwide environmentally and occupationally [17], it is recognized as the third largest indoor chemical pollutant by the WHO [18]. The highest levels of this pollutant compound are found in certain occupational environments, such as industries related to manufacturing products, textile, and chemical productions, as well as medical institutions using disinfectants and embalming products [19]. Regarding the outdoor environment, FA is produced as both a primary and secondary air pollutant via atmospheric photochemistry [20] with concentrations generally below 0.001-0.002 mg m\({}^{-3}\) in remote areas and urban settings, respectively [21]. Lower levels of environmental exposure come from automobile engines, household materials such as furniture made of pressed wood and carpeting, and tobacco smoke [22]. It is found that the toxicity of smoking 20 cigarettes daily is equivalent to an FA intake of 1 mg d\({}^{-1}\)[6].  
FA can also indirectly be produced in humans and other organisms through normal oxidative cellular and metabolic processes [17]. Possible FA exposure routes are ingestion, inhalation, absorption through the skin, and rarely blood exchange (dialysis) [23]. His endogenous concentration in the blood of human subjects is about 0.1 mM [24]. FA intake can cause chronic and acute effects that depend on many factors such as exposure time and physical fitness [25]. FA ingestion can be responsible for irritation of the eyes and the upper respiratory tract, childhood asthma, allergic skin reactions, and even nasopharyngeal cancer and potentially leukemia [4; 26]. However, high and persistent levels of FA exposure can cause damage to the central nervous system, immune system disorders [27], Alzheimer's disease [28], diabetes, chronic liver and heart disease [29], and gastrointestinal disorders [30]. Further toxicological investigations have shown also clear associations between formaldehyde exposure and tissue damage increases in cell proliferation, DNA damage, inflammation, changes in miRNA expression, and changes in gene expression signatures in direct target regions of exposure [20].  
As a matter of fact, FA can stimulate the cross-linking reaction of intra- and inter-molecular including protein-protein, protein-DNA, or DNA-DNA [28]. Table 1 summarizes different health hazards caused by FA consumption discussed in this section.  
Due to its acute toxicity and volatility, WHO has set a standard daily intake limit to be in the range of 0.005 \(\times\) 10\({}^{-3}\)-0.005 mM, whilst the European Food Safety Authority (EFSA) advocates the daily oral exposure to formaldehyde from the total diet should not exceed 100 mg per day [14].  
Moreover, the European Food Safety Authority (EFSA) summarized the FA level in food, for example, meat and poultry is 5.7-20 mg kg\({}^{-1}\), fish is 6.4-293 mg kg\({}^{-1}\), milk and milk-based products is 0.01-0.80 mg kg\({}^{-1}\), sugar and sweeteners is 0.75 mg kg\({}^{-1}\), fruit and vegetables are 6-35 mg kg\({}^{-1}\), coffee is 3.4-16 mg kg\({}^{-1}\) and alcohol beverages is 0.27-3.0 mg kg\({}^{-1}\)[31].