# Human Exposure to Toxic Metals (Cd, Pb, Hg) and Nitrates (NO3-) from Seaweed Consumption
## 1 Introduction  
The consumption of seaweed has long been part of the traditional diet in Asia and is currently growing in popularity in the Western world. According to the Food and Agriculture Organization of the United Nations (FAO), algae production in Europe accounts for 10% of global production [1, 2, 3]. Edible algae can be classified into four main large groups: blue, red, brown, and green algae. Algae stand out for their vitamin B12, omega-3 fatty acids, selenium, iodine, and fiber content [4]. However, in addition to high-value nutrients, they are capable of transferring toxic metals such as cadmium (Cd), lead (Pb), or mercury (Hg) to the consumer. These elements of toxicological relevance are present in marine waters as pollutants, which are characterized by their bioaccumulation in the trophic chain, or nitrates (NO3-) from both natural sources (nitrogen cycle) and anthropogenic sources (fertilizers, intensive livestock, wastewater, etc.) [5, 6, 7]. Cd is a metal that induces tissue damage due to oxidative stress. It is nephrotoxic as it damages the renal tubule; it can cause deterioration of mitochondrial function, andbecause of its divalent nature, it can compete with essential elements such as Zn [8; 9]. The consumption of marine products such as algae, fish, or shellfish is an important source of exposure to Cd [10; 11]. The European Food Safety Authority (EFSA) has set a tolerable weekly intake (TWI) for Cd of 2.5 ug/kg person/week [10]. Pb is one of the most toxic metals known; it is considered carcinogenic (Group 2B) for humans [12]. In adults, it causes cardiovascular, central nervous system, kidney, and fertility problems [13]. It is found in high concentrations in fruits, vegetables, and cereals as a result of the deposition of atmospheric Pb [14; 15]. EFSA has established a benchmark dose (BMDL) value referring to the organospecific toxicity of Pb of 0.63 ug/kg body weight (bw)/day (nephrotoxic effects) and 1.5 ug/kg bw/day (cardiovascular effects) [16]. Hg can be found in the form of different chemical compounds of toxicological relevance [17]. Methylmercury compounds can cause brain damage, psychological disorders, deafness, loss of vision and motor skills, etc. Inorganic mercury compounds can damage the kidneys, liver, and brain [18]. EFSA has set TWI values of 4 ug/kg bw/week (inorganic Hg) and 1.3 ug/kg bw/week (methylmercury) [18]. Nitrates (NO\({}_{3}\)\({}^{-}\) are found naturally in the environment. However, the concentration of these anions has increased as a result of human activity (use of fertilizers, intensive livestock farming, household waste, etc.). Nitrates, once in the body, can be reduced to nitrites by bacterial action and can then promote the formation of N-nitroos compounds, classified as carcinogens by the International Agency for Research on Cancer (IARC) [19]. Nitrates and nitrites are classified by IARC as \"probable human carcinogens\" (Group 2A) under certain conditions [20]. Scientific evidence associates a high exposure to nitrates with an increase in the incidence of gastric, colorectal, esophageal, thyroid, and kidney cancer, among others [6; 21]. Likewise, especially in the case of children, a high intake of these anions is related to blue baby syndrome or methemoglobinemia [6; 22]. Algae are autotrophic organisms that perform photosynthesis; that is, by their very nature, they use nitrogen and its derivatives for their biological cycles. Therefore, these organisms concentrate higher concentrations of nitrates. Despite this, algae are a food that, to date, has not been assigned legal nitrate limits, and this poses a risk for consumers. The World Health Organization (WHO) and EFSA set an acceptable daily intake (ADI) of 3.7 mg/kg bw/day for nitrates [23], which remains in force today, despite recent re-evaluations by EFSA [24; 25].