**3.1 Toxicity of lead (Pb)**

Lead is the most important toxic heavy metal in the environment because can cause serious environmental contamination and health problems [1, 10]. The main sources of environmental contamination including industrial processes, such as fossil fuel burning, mining, smelting, manufacturing, recycling activities. It is also used for leaded pipes, lead-glazed or lead-soldered containers, leaded paint, leaded gasoline, leaded aviation fuel [10, 22].

The inorganic lead can enter into the human body by inhalation (pulmonary absorption) of contaminated air or by smoking (15%), or by ingestion (gastrointestinal absorption) of food (65%) and water (20%) [1, 3, 22, 23]. Although organic compounds are absorbed through skin, inorganic compounds cannot be absorbed [10].

According to the WHO guidelines, the international level of concern of poisoning with lead is 25 μg/dl of blood for adults and for children, it must be less than 5 μg/dl of blood [23]. Their absorption is influenced by the age and physiological status of the exposed person [22].

However, the nervous system is most affected by exposure to high concentrations of lead, in both children and adults. Because children absorb 4–5 times more ingested lead, it can cause impaired neurobehavioral development, learning disabilities, speech and language handicaps, poor attention span, lower IQ, diminished intelligence, anti-social behavior [10, 22]. At high concentration, lead can produce coma, convulsions and even death on children and may be left with mental retardation and behavioral disorders [10]. In adults it can be manifested headache, poor attention, irritability, loss of memory, dullness [9, 22]. Increased absorption rate was observed when other nutrients such as calcium or iron are lacking. Even at lower concentrations, known as safe levels, children face learning or behavioral problems, decreased intelligence in children [10]. Although it mainly affects the nervous system, the largest amount of lead is found in the kidneys [9, 22].

Research has shown that this heavy metal can cross the placental barrier in pregnant women who have high levels of it in the blood, causing fetal abnormalities such as low IQ level, encephalopathy, neurological disorders, disruption of calcium levels in nerve cells [3]. Pregnant women exposed to lead, can manifest miscarriage, premature birth, reduced birth weight, stillbirth [10, 22].

After absorption, 99% of lead is bound to the hemoglobin, being circulated through the vascular system to soft tissues, bones, liver, kidneys (organs of lead excretion), hair [3, 10, 19], being stored especially in teeth and bones (where in incorporated into the mineral in place of calcium) [10, 22]. The stored Pb can be reintroduced into the bloodstream, especially during pregnancy, exposing the fetus [10].

Lead can produce lungs disorders, reduced pulmonary function, anemia, liver damage, cardiovascular dysfunction, renal impairment, immunotoxicity, disturbance of the balance free radicals-antioxidant system, cognitive impairments [1, 5, 10, 17]. Anemia occurs as a result of the interaction that this metal has with the important enzymes involved in the synthesis of hemoglobin, enzymes that are responsible and transport oxygen. Thus, by retardation of these enzymes, the hemoglobin concentration is reduced [3]. At high concentration, it can produce high risk of hypertension, gastrointestinal disorders, Alzheimer's disease, kidneys damage, interfere in vitamin D metabolism and thyrotoxicity, by affecting the normal function of thyroid gland, [3, 19, 22].

In people with high levels of lead in the blood, there was an impairment of sexual function, manifested by decreased libido, decreased sperm count and their mobility, changes in sperm composition [3, 22].

Also, this metal can cause changes at cellular level, such as decreased cell viability, cell distortion, reduced cohesion, lipid peroxidation, damage of protein folding, stop structural protein synthesis, intra- and inter-cellular signaling, apoptosis, ionic transportation, especially of calcium, cell adhesion, release of neurotransmitters, inhibiting enzymes activity, inhibits mineral absorption, affecting the activities of mitochondria and endoplasmic reticulum, decreases level of glutathione, generation of reactive oxygen species or reducing antioxidants [1, 3, 17, 22]. Lead has ability to inhibit or mimic the activity of calcium and perturbs their intracellular cycling, may interfere with proteins, can be bound to biological molecules and interfering with their function by various mechanisms [22].

Studies demonstrated that lead can produce genetic damage by mechanisms which include inhibition of DNA synthesis and repair, oxidative damage, being considered by the International Agency for Research on Cancer (IARC) as a probable human carcinogen [22].

Studies performed on animal models have shown altered homeostasis, induced kidney damage, decreases of antioxidant levels, decreased body weight, shortened life span, increases of total protein, albumin, histamine, creatinine, decreased red blood cells count [5, 17].
