## 2 Seafood Contaminants
### PAHs  
PAHs are a class of organic compounds consisting of two or more fused benzene rings, deriving from the incomplete combustion or pyrolysis of organic materials. Natural sources of PAHs include volcanoes, forest fires and petroleum seeps, while the combustion of fossil fuels, oil and wood are among the main anthropogenic sources [27; 28]. Due to their physicochemical properties, PAHs are persistent pollutants, in that they can stay in the environment for long periods [29]. They represent the largest share among the main organic contaminants present in the marine environment, due to marine traffic and possible accidents involving oil tankers [30]. Although most PAHs are metabolized a short time after uptake, thanks to their lipophilic nature, a fraction accumulates in lipid-containing tissues such as liver, eggs and muscle [8]. The most important non-occupational source of human exposure to PAHs is the consumption of contaminated food, including seafood [31], especially mollusks and crustaceans [32]. Sixteen PAHs are categorized as priority environmental pollutants, and some of them are deemed to be probable human carcinogens by the US Environmental Protection Agency (US-EPA), with benzo(a)pyrene (B(a)P) arousing more concern because of being the most carcinogenic, teratogenic and toxic compound [33]. The most used biomarkers of PAH exposure are metabolites of PAHs, particularly 1-hydroxypyrene (1-OHP), and PAH-DNA or protein adducts. 1-OHP is the principal product of pyrene metabolism [34], and its urinary excretion has been attributed mainly to the ingestion of PAHs through the diet [35]. Rather, PAH-DNA adducts, which are the products of the Phase I metabolism of PAHs, are deemed a biomarker that integrates multiple BB(a)P exposure routes (including inhalation, dermal absorption, and ingestion) and reflects a biologically effective dose [36]. PAH-DNA adduct formation is significantly influenced by individual susceptibility, which is linked to specific genetic polymorphisms [36; 37]. Urine PAHs metabolites and, to a less extent, PAH-DNA adducts are also related to parent air PAH exposures, both at elevated exposures in occupational cohorts, and at low levels of air pollution [34; 38]. The EU set a maximum level of B(a)P in seafood to be sold ranging from 2 ug/kg wet weight, for muscle meat of fish (other than smoked fish), to 10 ug/kg for bivalve mollusks [21]. Concerning human exposure, the US-EPA set an RfD for several PAH compounds, including anthracene (0.3 mg/kg day\({}^{-1}\)), acnaphathene (0.06 mg/kg day\({}^{-1}\)), fluorescein (0.04 mg/kg day\({}^{-1}\)), fluoranthene (0.04 mg/kg day\({}^{-1}\)), pyrene (0.03 mg/kg day\({}^{-1}\)), naphthalene (0.02 mg/kg day\({}^{-1}\)) and B(a)P (0.0003 mg/kg day\({}^{-1}\)). Several findings point to an important role of genetic diversity in shaping individual susceptibility to Hg [39] and PAHs [40] exposure, and consequently some authors claim the urgent need to include this factor in risk assessment and decision making [41]. Moreover, Hg and PAHs, similar to several other environmental toxicants [42], can impact the human epigenome through different mechanisms, and some of the epigenetic alterations driven by these two substances were shown to be associated with adverse health effects [43; 44]. Being a semi-enclosed sea, delimited by highly industrialized countries and characterized by large deposits of cinnabar (HgS), the Mediterranean Sea is at a high-risk for contamination by toxic compounds [45], and evidence exists that significant anthropogenic chemical inputs into the Mediterranean began in prehistoric times [46]. In line with this, several studies have shown higher levels of contaminants in marine organisms from the Mediterranean Sea compared to those from other geographic areas [47].