## 3 Formaldehyde-Induced Epigenetic Effects  
Formaldehyde-induced epigenetic changes, such as DNA methylation [21; 28; 29], histone modifications [30; 31; 32], as well as alterations in non-coding microRNAs (MiRNAs) [33; 34; 35; 36] have been investigated both in occupational and experimental settings (Table 1). The following paragraphs will attempt to summarize such effects with the aim to point out currently available data and critical issues that require further epidemiological research in order to also conceive epigenetic contribution to risk assessment and management strategies. Figure 1: Flow diagram of literature search. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**EXPERIMENTAL** & **EPIGENETIC** & **EXPERIMENTAL DESIGN** & **MAN RESULTS** & **REFERENCES** \\
**SETTING** & **OUTCOMES** & & & & \\ \hline \multicolumn{6}{c}{**HUMAN INVESTICATION**} \\ \hline \hline \multicolumn{6}{c}{} \\  & & & & Median personal PA environmental exposure (ppm): \\  & & & group A (n. 8): 0.013; group B (n. 15): 0.035; group C (n. 26): 0.07. & \\ Brazilian hairlessness, & & & measured through personal (samples) & \(\checkmark\) & Median biological monitoring levels of formic acid \\ hairlesser assistants, & & & fitted in volunteers breathing zone) and & before exposure (mg/L): group A: 25.99; group B: \\ receptions, manuscripts, & & area passive samples (8-h work shift). & 24.80; group C: 19.33. Median biological monitoring & \\ and managers (n. 41E;SM) & & Global DNA methylation was assessed & levels of formic acid after exposure (mg/L): group A: \\ Mean age \(\pm\) SD: 31.04 \(\pm\) & & in whole blood samples were collected & 21.49; group B: 20.70; group C: 22.44. & \\
10.46 years & & & after 8-h of work. & Higher median levels of global DNA methylation \\ Years working in beauty & & Biological monitoring of formic acid & were determined in groups B (4.559) and C (4.29\%) \\ salons (median: 6 years) & & was performed on urine samples & compared to group A (3.12\%). & \\ No unexpected controls & & collected at the beginning of the work & \(\checkmark\) Statistically significant positive correlation was \\ were enrolled. & & shift and again 8 h after the first & \(\checkmark\) & found between global DNA methylation and FA in \\  & & & the personal passive samples (rs \(\pm\) 0.307, p: 0.032). & \\  & & & & No significant increase in biological monitoring \\  & & & & findings could be observed between the 3 groups. \\ \hline \hline \multicolumn{6}{c}{**IN VIVO EXPERIMENTS**} \\ \hline \hline \multicolumn{6}{c}{} \\  & & & & \(\checkmark\) FA exposure affected the expression levels of 108 \\  & & & miRNAs in nose samples, specifically, 84, 59, and 0 \\  & & & miRNAs altered in the 7, 2 and 28-day plus 7 \\  & & & day-recovery groups, respectively. & \\  & & & day-recovery groups, respectively. & \\  & & & & In the WPCs, FA exposure altered the expression of \\  & & & of exposure were considered: 7, 28, 28 & 40 miRNAs.3; 81, and 3 miRNAs at the 3 different \\  & & & days plus a 7-day recovery period, & \\ Male Fischer rats & MicroRNAs & unexposed controls. & & \\  & & & Multiple samples were collected from the nasal epithelium, circulating & \\  & & & mononuclear WPCs, and BM cells. & \\  & & & Microarray analysis employed to assess & \\  & & & \(\checkmark\) 69\% rat known miRNAs. & \\ \hline \end{tabular}
\end{table} 
Table 1: Studies addressing epigenetic formaldehyde (FA) effects in humans, animals, and cellular models.