Epidemiology of lead toxicity
Since prehistoric times, people have used lead, a common and valuable metal. Due to its increased availability and mobility in the environment, human exposure to and consumption of this non-essential element has grown dramatically. Global efforts have been put together to emphasize the significance of establishing preventive guidelines towards public health concerns, such as removing all possible sources of lead contamination. Of which, the collaborative work conducted by Harris et al. [92] to establish the third US preventive services task force (USPSTF), supported by the Agency for Healthcare Research and Quality (AHRQ) and two of the AHRQ Evidence-Based Practice Centres (EPC). Thus, it is essential to highlight all potentially dangerous routes of lead poisoning to fulfil the heroic global goal. This study initially aimed to assess the importance of lead toxicity in the MENA region by expert consensus to identify and grade possible lead contamination sources based on the available literature, personal expertise in the field of taxology and final peer-review by the higher organization (MENATOX). All references are re-classified and listed in Table 5.
It is interesting to note that all sources of lead contamination were recovered from 45 studies from various countries in the MENA region. The systematic synthesis was carried out in only 34 studies that passed the MMAT analysis. The distribution of polluted sources of lead MENA was obtained from Iran (n = 9); Malekirad AA et al. [63] 2013, Raissy M [78] 2016, Khatibi-Moghadam H et al. [79] 2016, Daneshparvar M et al. [89] 2016, Ahmadi M et al. [81] 2017, Vahidinia A et al. [82] 2018, Soltaninejad K et al. [87] 2018, Mayel M et al. [90] 2020, Samarghandian S et al. [88] 2021; Saudi Arabia (n = 6); Al-Saleh I et al. [43] 1996, Al-Saleh I et al. [57] 2008, Zolaly MA et al. [60] 2012, Ashraf MW et al. [61] 2012, Salama AK et al. [75] 2016, Chowdhury S et al. [83] 2018; Lebanon (n = 5); Nuwayhid I et al [47] 2001, Nuwayhid I et al [51] 2003, Nasreddine L et al [53] 2006, Korfali SI et al [64] 2013, Bassil M et al [84] 2018; Egypt (n = 3); Mortada WI et al [49] 2001, Mandour RA et al [65] 2013, Moawad EM et al [77] 2016; Kuwait (n = 2); Shaltout A et al [41] 1981, Jallad KN et al [56] 2008; Morocco (n = 2); Bouftini S et al [66] 2014, Laamech J et al [68] 2014; Algeria (n = 1); Cherfi A et al [69] 2014; Iraq (n = 1); Al-Dosky AH et al [59] 2012; Israel (n = 1); Greenberg N et al [76] 2016; Jordan (n = 1); Nusier MK et al [50] 2003; Oman (n = 1); El Tawila M et al [42] 1996; UAE (n = 1); Bener A et al [48] 2000 from the systematic synthesis (n = 34), and two from Ethiopia [58, 71] (include in the DELPHI n = 45) but did not passed MMAT analysis hence not included in the systematic synthesis.
We report lead poisoning in various substances and tissues; blood, urine, breast milk, water, soil, air, and food. In consistency with the reported literature of lead distributions [93], our study reports lead-based paint due to residential route [51, 59, 66, 68, 77, 84, 88], lead polluted water [65, 77, 83], food [42, 53, 57, 69, 78, 84, 88], soil [77, 81], air [76, 77] to be sources of a high significance. In addition, we report other resources, including cosmetics [41, 43, 51, 56, 57, 60, 75, 82], socio-economic and cultural [43, 84], and occupational sources that negatively affected both children and adults of both genders [47, 48, 49, 50, 63, 70, 76, 77, 88], residential factors that were not limited to paints, but extend to overseas the whole condition of a building (building age, status, ventilation, and whether it near to a generating lead source of pollution) [51, 59, 66, 68, 77, 84, 88], cooking habits [51, 60], oral intake of polluted lead substances [60, 83, 88], personal habits such as smoking [61, 84]. Furthermore, our study shows that the pica phenomenon continues to be a burden in children [60, 64]. Interestingly, the current study sheds light on placental lead transfer and breast milk [65, 82, 84], which was found in accordance with previously reported evidence [95]. It is worth mentioning that children were victims of their exposure to occupational sources of lead contamination or parental habits such as smoking. For example, Table 6 illustrates different lead occupations, which negatively affected the children negatively; one study reported that parents were exposed to lead in their jobs [51], [65, 84] asserted lactating mothers exposed to the threat of lead and showed adversely in their children's health conditions, [77] showed evidence of smoking fathers and significant levels of lead in their children's blood. The results of our study indicate that opium impurities remain a huge public health concern in Iran [79, 87, 90].
Paternal source
In the Lebanon-based study by Bassil M et al. in 2018 [84], the study did not just highlight parental leaded sources. It also covered other sources genres such as (residential, food, personal habits and socio-economic) blood lead level/concentration (BLL/BLC) was not quantified. Instead, breast milk was measured and found with a mean concentration of 18.18 ± 13.31 µg/L in 67.61% of the 74 samples. Exposure to lead was associated with living near cultivation activities (p = 0.008), smoking prior to conception (p = 0.046), eating potatoes (p = 0.046), and education level (p = 0.041). The p-value of the previous results indicates a statistical significance based on their predetermined threshold; less or equal to 0.05. Contrary to expectations, this study found that even passive parental smoking is a significant threat to children.
Mandour RA et al. [65] conducted a study in Egypt in 2013 on 104 lactating mothers drinking polluted water and tap water from the surface and groundwater. Compared to nonexposed mothers, women living in dirty locations and those exposed to passive smoking may have higher levels of lead excreted in their breast milk. This may be more dangerous than the daily risk to nursing infants. Long-term exposure to lead plumbing can raise the lead level in tap water, increasing the lead load in infant formula and blood. Mothers drinking surface water have a mean of 0.025 ± 0.006 (range 0.015–0.037), while mothers drinking groundwater exhibited a mean of 0.035 ± 0.007 (range 0.025–0.049), which is highly significant (based on the predetermined p-value of the study to be p 0.001). Mean lead levels of mothers' breast milk (mg/l) as regards passive exposure to smoking: Women passively exposed to smoking (n = 25), range 0.026–0.039 (Mean ± SD:0.038 ± 0.004), nonexposed women not exposed (n = 27) range 0.020–0.031 (Mean ± SD 0.025 ± 0.002) indicated a high significance p-value (based on the predetermined p-value of the study to be p 0.001). The connection between mean lead levels (mg/l) in drinking water and breast milk samples from mothers illustrated a positive relationship. All of the study's female participants had non-occupational lead exposure. They did not have any unique habits, although 25 of the ladies (48.1%) were passive smokers (exposed to smoke). Compared to women who weren't exposed, these women's breast milk had more lead. Similar results were discovered in a study by Kwapuliński and colleagues in 2004 [95]. The computed daily lead consumption in breast milk given in the Mandour RA et al. study [65] showed that infants whose mothers drank surface water would consume 3.81 mg/kg/day, whereas infants whose mothers drank groundwater would consume 5.34 mg/kg/day, exceeding the WHO-permitted value.
Another interesting study is an evidence provided in 2003 by Nuwayhid I et al. [51] on 281 children who attended paediatric clinic ambulatory services at the American University (Lebanon, Beirut). The mean Pb in blood was 66.0 µg/L (SD: 26.3), with a range of 10 to 160 µg/L and a median of 60.0 µg/L. 39 children (14%) had Pb concentrations below 100 µg/L. Compared to children with Pb > 100 µg/L, children with Pb 100 µg/L came from lower-income, less educated homes (P 0.01), and a higher percentage of their fathers and mothers worked in manual labour (P 0.01). Pb levels did not differ statistically significantly by gender, with men having a mean of 67.6 µg/L (SD 26.6) and women having a mean of 64.3 µg/L (SD 25.9) (P = 0.29). A possible explanation for this is due to another risk factor found to be substantially connected with higher Pb, which is the manual parents' occupations which is a risk factor and an essential health warning in a nation where workplace health and safety issues are not given high importance (manual jobs definition). This correlation has been previously noted and connected to children exposed to contaminated clothing at home [96–97].
Socio-economic, demographic and cultural influence
In the reported literature, several definitions define MENA countries. The Middle East and North Africa (MENA) region is made up of the following 21 nations or territories, according to World Bank geographic classification: six members of the Gulf Cooperation Council (GCC) (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates [UAE]), as well as 15 additional nations or territories (Algeria, Djibouti, the Arab Republic of Egypt, Iraq, the Islamic Republic of Iran, Israel, Jordan, Lebanon, Libya, Malta, Morocco, Syria Arab republic and West Bank and Gaza that also sometimes referred as the State of Palestine, (Occupied) Palestinian Territories, Palestinian Authority [98]. Some people, particularly in the sciences like agriculture and meteorology, prefer to use different terms like "WANA" (West Asia and North Africa) or the less popular NAWA due to the geographic uncertainty and Eurocentric nature of the phrase "The Middle East" (North Africa-West Asia). Postcolonial studies have also increased the use of the word WANA. Thus, the WANA region includes 27 countries based on the International Centre for Agricultural Research in Dry Areas (ICARDA). Oman, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Afghanistan, Libya, Lebanon, Algeria, Bahrain, Djibouti, Egypt, Eritrea, Ethiopia, Gaza Strip, Iran, Iraq, Jordan, Mauritania, Morocco, Pakistan, Somalia, Sudan, Syria, Tunisia, Turkey, and Yemen [99]. With respect to the objective of the study to focus on the MENA regions only, this is a necessity due to the fact that cultural norms are unique and different in this compartment of the world [100]. The MENA region has its own environment, cross-sectional adjustment, and languages (Arabic more prevalent), and it is a region more dominant by Islam and its values and principles. An interesting review by Ourfali in 2015 [101] focused on comparing Western and Middle Eastern cultures. It explained many differential variables such as cross-sectional issues, high versus low context cultures, Hofstede's dimension, Power distance, Masculinity versus femininity, Individualism versus Collectivism, Long term versus short-term orientation, Indulgence versus restraint, Uncertainty avoidance and many thoughts between lines.
Our initial search failed to recover lead poisoning based-gunshot in the MENA region. Interestingly, the additional search we did as a backup, recovered two cases in the MENA regions; one patient in Turkey in 2002 [102] and another in Iran in 2018 [103]. Herein, we recommend strongly adapting our methodology of conducting an additional search of solid scientific evidence because data loss might be encountered because of several reasons, such as the various indexing of every published article and its visibility; refer to Fig. 2, which illustrates the PRISMA flowchart (cautiously consider removing redundancy in references). Based on the exact additional search that recovered the two missed lead sources by a gunshot, 13 cases in the United States alone (between 2009 and 2017) and 7 patients in the different non-MENA regions [88], including Colombia (n = 2), Canada (n = 1), Thailand (n = 1), France (n = 1), Brazil (n = 1), The Netherlands (n = 1). The results indicate that gunshots are a significant source of lead poisoning and a burden on public health in the United States. About 115,000 persons in the US each year suffer gun-related injuries [104]. Data from the Adult Blood Lead Epidemiology and Surveillance (ABLES) program show that between 2003 and 2012, 145,811 people in the United States who were 16 years old and had 10 g/dL BLC were reported to ABLES. 457 cases of retained gunshot fragments have been recorded, with a maximum BLC of 306 g/dL [105]. According to these data, we can infer that the gun violence rates are different between MENA countries and the rest of the world. Based on a statistic from Institute for Health Metrics and Evaluation, in 2019 [106], there were 3.96 gun-related deaths per 100,000 persons in the United States, which is the 32nd-highest rate in the world. That was approximately 100 times greater than the rate in the United Kingdom, which was 0.04 deaths per 100,000, and more than eight times higher than the rate in Canada, which had 0.47 deaths per 100,000 people. Numerical figures in MENA regions based on the same comparison (rate of gun-related deaths per 100,000 in 2019); Oman (0.03), Jordan (1.52), Lebanon (1.35), Turkey (1.19), Syria (1.00), Yemen (0.77), Libya (0.68), Iran (0.62), Sudan (0.51). However, due to many variables such as unreported cases, other factors such as political issues, terrorism, racism, religious influence, and restraints, and many others that this issue is not enough to highlight, such numerical figures are placed under significant questions and criticism. Parallel to that is the evidence reported in 2022 by Buil-Gil [107], stating that the analysis of crimes at the micro-level is more susceptible to prejudice than crimes combined at bigger scales. These findings highlight a critical flaw in microlevel mapping, and more work is required to enhance crime estimates.
In the MENA countries, traditional remedies are commonly unified, such as teething powders to relieve teeth pain and the use of Henna (Lawsonia inermis) that possesses dual utilities; as a cosmetic agent and traditional medicine to empower vision, as believed in the countries in the MENA region. Al-Saleh I et al. [43], in 1996, reported the use of Henna, teething powder and a positive relationship to high lead levels in the blood. They highlight socioeconomic and cultural factors proposed as a risk factor for toxicity; eating by hand, commonly observed in MENA countries, and playing in the streets.
20.6% (7/34) of the 34 studies reported lead poisoning sources of residential origin. The residential genre is not an absolute one factor; it co-exists with the environmental genre. An Iraq-based study by Al-Dosky AH et al. [59] in 2012 comprised 820 individuals living in urban, suburban, and rural areas. Age, place of residence, altitude, and distance from a gasoline generator all showed significant variances. Toxic lead levels in the blood (Pb > 10 g/dL) were present in 22.8% of the population and 2.4% of children. Residents who lived in the suburbs (39.7%) or less than 50 meters from a gasoline generator (93.1%) were exposed to high environmental lead levels. A linear relationship was discovered between Pb and atmospheric lead concentrations (r = 0.8).
Similarly, in Morocco in 2014, Bouftini S et al. [66], the average BLL in children living in industrial areas (EP; exposed population) areas was statistically higher (p 0.0001) than in children living in cities (UP; unexposed population), (7.1 ± 4.0 µg/dL), (3.8 ± 1.3 µg/dL) respectively. With a predominance of 21.1%, all poisoned children belonged to the EP group. Children who had been poisoned revealed a few abnormalities during clinical and biological investigations, including anemia, hypocalcemia, and magnesium and iron shortages. No neurological problems or renal diseases were found. The children's follow-up with BLL > 1.00 µg/dL (19 cases). BLL monitoring revealed a significant decline in the prevalence of lead poisoning (p 0.001), which fell from 21.1 to 7.8% and ranged in average blood concentration from 13.675 ± 3.259 to 10.458 ± 3.273 µg/dL (p 0.0001). In our study, we found that children with EP had a significant rate of lead poisoning (21.1%). The study claimed that the relocation of the industrial site, together with the related corrective and preventive actions, has helped reduce exposure and the prevalence of lead poisoning in the aforementioned population. Additionally, our results reported the residential origin of lead poisoning due to building age (> 20 years) [51], residence near cultivation [84], near battery factory [88], living near garbage, collapsed areas, moderately living habitats, urban and suburban regions by [77] that evaluated residential gerne by measuring water, soil, air, in / outside dust, and paint. These findings are consistent with those of Lamech et al. [68] (2014), who showed that mean blood lead levels (BLLs) of children in urban regions were higher (8.236 g/dL) than those in industrial and rural areas (4.823 and 3.599 g/dL, respectively), with no discernible gender difference. BLLs were linked to infant mortality, passive smoking, and traffic volume in the city.
Clinical manifestations
Nearly all organ systems are damaged at high levels of human exposure, but the central nervous system, kidneys, and blood are the most severely affected, leading to death at extreme levels. At low concentrations, there are several impacts, including impairment of psychological and neurobehavioral processes, hemoglobin production, and other metabolic processes. Neurological disorders have been reported in children and adults, with more cases in young children. Our study illustrates encephalopathy in a 20-sample cohort of 1–18 months of age. Two cases passed away before being subjected to therapy [41]. Daneshparvar M et al. [89], in 2016, reported attention deficit/hyperactivity disorder (ADHD) and ADHD-related symptoms such as inattention, hyperactivity, and impulse, or combined IQ problems in children. Our review shows that adults are also affected by lead poisoning, manifesting neurological clinical signs and symptoms [48, 63, 87]. The observed correlation could possibly be explained by the fact that children's brains appear to be affected by the interference of lead with the synaptic pruning process, leading to cognitive and behavioral impairment [108]. Adults with persistent lead poisoning typically develop peripheral neuropathy. According to British and Feldman (1984) [109] and Davis and Svendsgaard [110], the fundamental process and mechanism are not clear. A growing body of evidence indicates that exposure to lead reduces children's and adults' general cognitive ability [111–112]. Children appear to be victims of hematologic disorders that are more prevalent than adults.
Al-Saleh I et al. [43] reported iron deficiency and thalassemia in children, Nuwayhid I et al. [51] documented iron deficiency with and without anaemia in children, Zolaly MA et al. [60] school children aged 6–18 years with anaemia, low Hb, and BLL of 0.45–26.3 µg/dL, Bouftini S et al. [66] studied children living near industrial area and city with anaemia, hypocalcaemia, and deficiencies in magnesium and iron. In agreement with that, Moawad EM et al. [77] reported that BLL was higher than the value of 5 mg/dL in 100% of all workshop children, where the primary victims were young people employed in the ceramics industry and with low hemoglobin, which was observed to be inversely related to BLL and all reported studies. A study reported hematological symptoms in both children and adults by Malekirad AA et al. [63] in battery plant workers aged 33.41 ± 6.88 years and were 439 males only, with low PCV, Hb, and RBC and related to occupational origin. Lead has been shown to cause anaemia in haematological tests by changing the synthesis enzymes in heme and weakening the integrity of erythrocyte cell membranes [113]. Furthermore, basophilic stippling, a symptom of lead poisoning, was also observed in the blood sample of several individuals. It was also recognized that mild lead toxicity affected the peripheral autonomic nervous system and serum rennin BLC levels, which may have contributed to the development of hypertension. The lead also had detrimental effects on the musculoskeletal system, resulting in symptoms including arthralgia and myalgia.
One of the most surprising aspects of the Al-Saleh I et al. data [57] was on 619 Saudi females who sought IVF treatment where they exhibited infertility. The study demonstrated that lead reduces the likelihood of conception at levels lower than the occupational exposure limits to lead in the US (40 mg/dL) and even lower than the current level of concern for preventing lead poisoning in children (10 mg/dL) set by the Centres for Disease Control and Prevention. They observed that fish consumption was positively correlated with blood lead levels in a range of demographic, socioeconomic, and environmental variables. These findings are consistent with the idea that elevated blood lead levels impact infertility and that lead exposure reduction measures may be necessary for women of reproductive age. 88.4% of the study's participants ate fish. From our review, we report sexual problems in the form of reduced sex drive in a study that included only men and was related to occupational origin [63]. Opium consumers appear to suffer mainly from gastrointestinal symptoms based on a randomized, single blinded controlled trial [90], to numerous other signs and disorders; Lead line at the gum tooth line, electrocardiographic evidence of conduction delays (cardiovascular related), cataract patients, hypertension, anemia, increase in liver enzymes, weight loss, constipation, nausea, muscle weakness, wrist drop, pain in the extremities, paraesthesia, reduced vision and hearing, abdominal pain, icterus, constipation, postprandial nausea [87]. The current review reported other clinical manifestations; mild-severe metaphyseal Pb lines by radiographs [43], nausea/vomiting, muscular symptoms, dizziness, fatigue, irritability, memory disturbances, insomnia and allergic conjunctivitis, rhinitis and dermatitis, phlegm, shortness of breath, and asthma (as respiratory symptoms) [48], renal damage [49], nocturia, increased frequency of urination, oedema, drop in deep tendon reflex (musculoskeletal related), concentration impairment, agitation, headache, depression, abdominal pain, palpitation fatigue [63] and muscle pain [70] that can be inferred due to occupational pressure.
Treatments
Although reducing or eliminating lead sources is considered the optimal care of significance in lead exposure, discussing acceptable therapeutic guidelines is vital. Shaltout A et al. [41] in 1981 reported the utilization of BAL. (2.3 dimercaptopropanol) and EDTA (ethyl-enediaminetetra-acetic acid) to treat 1–18 months aged infants with encephalopathy due to lead poisoning. Four patients suffered neurological sequelae, while eleven patients appeared to fully recover. In 2020, Mayel M et al. [90] conducted a RCT on opium addicts using Morphine 0.1 mg/kg + normal saline vs morphine 0.1 mg/kg + normal saline + 1-gram intravenous calcium gluconate. When lead poisoning results from consuming lead-contaminated opium, stomach pain can be reduced by administering intravenous calcium gluconate and morphine. They emphasized the necessity of additional research with a larger sample number to clarify this effect. In addition, interventional investigations are advised to see whether a patient's reaction to calcium salts can exclude lead toxicity in suspected lead-induced stomach pain cases. Samarghandian S et al [88] reported several chatting therapies, (succimer, CaNa2EDTA, DMSA, Succimer + CaNa2EDTA, BAL + penicillamine, BAL + CaNa2EDTA + Penicillamine, and BAL + CaNa2EDTA + succimer).
In the MENA region, there is something referred to as prophetic medicine inspired by the Islamic culture represented by the great prophet Mohammed peace upon him that advocated the use of the so-called "Al-hijamah", also known as suction cup therapy. In a study published in 2015 by Sumeyye Gok et al. [114], wet cupping blood had significantly more significant amounts of all chosen heavy metals (Ag, Hg, Al, Pb) than venous blood. Pb (µg/dL) was 0.96 ± 0.13 and 0.11 ± 0.01 in cups and venous blood, respectively, with a p-value of statistical significance (p < 0.001). It suggests that wet cupping therapy may be used to remove heavy metals from the body, which also goes by the name "triple S procedure," which involves skin suction, scarification, and a second suction. Our findings can guide clinicians because not all chelators are widely available in all nations.
Similarly, the results of [88] are advocated, and in all circumstances, our consensus strongly recommends the analysis case-case basis. In brief [88], CaNa2EDTA and suction cups were often applied to patients under 15. Almost all patients who received these treatments claimed success without experiencing any serious adverse effects. Patients between the ages of 5 and 15 were primarily treated with CaNa2EDTA and succimer. But for patients under five, succimer, succimer and CaNa2EDTA, and a combination of Dimercaprol, CaNa2EDTA, and succimer were often prescribed medications. Chelating therapy is frequently advised for kids with blood concentrations above 70 µg/dl. For kids, DMSA is the drug of choice. Patients with elevated B.L.C. may experience worse symptoms while using CaNa2EDTA alone. CaNa2EDTA has been advised to only be used in conjunction with dimercaprol.
While CaNa2EDTA operates by extracellular chelation, dimercaprol is a tiny molecule that can enter cells and may prevent the worsening of clinical symptoms. BAL, coupled with a CaEDTA infusion, is advised for the first two to three days to treat acute lead encephalopathy and elevated intracranial pressure. Treatment with oral DMSA is an option for patients with BLCs between 45 and g/dL µg/dL but no visible symptoms. Patients with B.L.C.s between 45 and 69 µg/dL typically get DMSA and Dpenicillamine orally. Patients with BLC. levels of more than 70 µg/dL have been advised to take dimercaprol. Intramuscular injection (IM) is required for administration, frequently in conjunction with intravenous CaNa2EDTA. There is no proof that chelating treatment benefits patients with BLCs between 20 and 44 µg/dL. The American Academy of Pediatrics advises Dpenicillamine only when intolerable adverse reactions to both DMSA and CaNa2EDTA occur due to the possibility of side effects. Continued chelation is essential. Lead poisoning has not been authorized for d-penicillamine treatment.
Occupational threat
The occupational origin of lead poisoning was found to be the most redundant genre based on our results. Ten studies out of 34 were of an occupational origin lead poisoning source (29.4%), with the vast majority being affected by males only since males contribute to most of the workforce. In a case-control study by Nuwayhid I et al. [47] in 2001, the average BLL for the 134 men employed in white-collar employment (offices, retail stores) was 12.7 microg/dL (SD 3.7), which is statistically considerably lower than the average BLL for the 157 men employed in blue-collar jobs (18.4 micro g/dL; SD 9.8) (Such as gas station attendants, painters, mechanics). The number of cigarettes smoked, traveling more than three kilometers to work, the years spent in the occupation, and younger ages were all linked to blood lead levels of 15 micro g/dL or greater. Blue-collar employment was also associated with a BLL of at least 20 micro g/dL. Furthermore, Bener A et al. [48] studied 100 heavy industry workers, garage workers, taxi drivers, gas fillers, chemical production workers, painters, 100 storekeepers, and tailors. The difference between the two groups showed a p-value of significance. According to Mortada WI et al. [49] study, exposure to Pb from vehicle exhaust may result in renal damage in traffic police officers. Sensitive indicators of renal impairment caused by exposure to Pb include urine excretion of N-acetyl-β-D-glucosaminidase and albumin. Additionally, measuring Pb levels in blood, hair, and nails is a reliable indicator of Pb toxicity. Pb is studied in significant quantities in blood, nail, hair, and urine. P < 0.001. An interesting study sheds light on the importance of safety measures in the military sector [76]. Before basic training, as well as at other times, the BLL (0.11µg/dL) was considerably (p 0.001) higher than that of trainees (0.00084 g/dL) µg/dL. When compared to day training, night training was linked to a roughly two- to three-fold greater lead concentration during the basic and advanced training periods (p 0.05). Since ballistic baffles and concrete walls are typically used in outdoor ranges for safety reasons, the geographical distribution of airborne lead is further complicated. As a result, the air in these areas may stagnate and increase the levels of exposure to lead. Therefore, personal breathing zone lead levels may exceed the National Institute for Occupational Safety and Health's recommended exposure limit (REL) and OSHA's acceptable exposure limit (PEL) despite outdoor firing ranges having natural ventilation. Lead contamination with a positive correlation was found in other occupations, such as workers in the production line (casting, mixing and charging batteries) [50], lead battery plant workers [63], hospital health workers, shop worker, taxi drivers, mechanics, woodworkers [70], and automobile repair, car batteries, smelters, pottery, radiators, garbage [77].
Surcharge and demands of beauty and health
Some might perceive the above sub-title to be a bit exaggerated. Herein, we show evidence that it is not. Eight studies in our review report various cosmetics as highly hazardous and, to a certain extent, fatal. Shaltout A et al. [41] report Kohl is a type of cosmetics used to create shaded black lines beneath the eyes that are widely propagated in the MENA region to be used as a traditional cosmetics and medicine to strengthen vision as believed. The study evidenced a positive correlation between high BLL that ranged between 60 and 257 µg/dL and the use of Kohl, which unfortunately resulted in the death of two infants due to encephalopathy induced by acute lead exposure. Kohl, in our review, is the most redundant type of cosmetics that is consistent with the scoring obtained by the expert consensus via DELPHI process, which highlights the vast distribution of this agent. Al-Saleh I et al. [43] in Saudi Arabia report the use of Kohl (in aye and umbilical cord at birth), Bokhoor (cosmetics used Widley in the Arabic culture, traditional gesture to the guest, relaxation purpose and spreading pleasant senses in the atmosphere, ancient Egypt for spiritual work) and Henna in 86% of the cohort with a BLL of 13.85–42.57 µg/dL. Another piece of evidence is reported by Nuwayhid I et al. [51], who report positive markers of using Kohl and BLL of 10–160 µg/dL in 281individouls. Vahidinia A et al. [82] conducted a study on 100 lactating mothers. Age, level of education, postpartum BMI, family income, smoking status, employment status, and maternal consumption of fish, fruit, and vegetables did not correlate significantly with hazardous metal concentrations in breast milk. However, Pb levels in breast milk were higher among breastfeeding mothers who used lipstick more frequently than other women (P = 0.037). 94% of the samples had Pb concentrations higher than the WHO recommended limit of 5 µg/L for breast milk (WHO). Other studies reporting cosmetics were traditional and commercial Henna (Lawsonia inermis, weight 229–6598 µg/dL) by Jallad KN et al. [56], Kohl by Al-Saleh I et al. [57], Kohl and lip gloss used by school children documented by Zolaly MA et al. [60]. Substances of lead have been measured in other commercial cosmetics as well, including, Cream (2401.72-4379.24 ppb), Shampoo (592.88-29,683.12 ppb), Soap (164.49- 5812.78 ppb), Toothpaste (1856.34–6313.00 ppb) [75].
On the other hand, Food stuff showed a significant correlation with high BLL, and some studies suggested no current harm; however, they emphasized long-term exposure. In the study by Bassil M et al. [84], the consumption of potatoes had a significance p-value (p = 0.046) with elevated BLL. Shrimp (n = 60) and lobster (n = 60) from the Persian Gulf were analyzed by Raissy M [78] and found to be acceptable limits according to international standards of the Commission of the European Communities 2006, ANZFA 1998 and FAO/WHO 2004. Nevertheless, it should be remembered that regular or excessive eating of shrimp and lobster may result in exposure to levels of lead over the advised limit. Given the importance of Persian Gulf seafood for human consumption and environmental safety, aquatic species in this region should undergo more frequent analyses of harmful metal content. In Algeria, Cherfi A et al. [69] studied different fruits and vegetables and released an obvious risk of lead for beans, onions, carrots, melons, tomatoes, and strawberries. El Tawila M et al. [42] researched different Omani dishes for sources of Pb such as bakery & cereals (Mardoof tamr) 0.026–1.073, fish (Samak Maleh) 0.167–1.750, sweet 0.048–0.547, meat & poultry 0.112–0.786, soups 0.100–0.170, all were within acceptable limits, but the risk lies in overuse. Breads, pastries, pizzas, yoghurt, potatoes and rice for the presence of Pb by Nasreddine L et al. [53]. The study revealed an acceptable range of 2–35 mg kg-1.
Therefore, it is imperative to rule out the cumulative effects of repeated exposure to low lead levels from the use of Henna as a cosmetic or medicinal product. The growing public awareness of the grave harmful effects of cosmetics appears to be the only effective way to stop or at least curtail the use of such a dangerous substance, especially when children are involved.
Environmental exposure of lead
A vital part of the life cycle impacting agriculture and food crops is soil. The quality of soil resources is determined according to their ability to affect human health by exposing humans to toxic components through the food chain. Heavy metals, especially As, Pb, and Cd, are the most dangerous materials that could be discharged into the topsoil by various wastewaters, herbicides, and fertilizers. In 2017, Ahmadi M et al. [81] investigated 54 soil samples for their overall range pollution indices (PI) of 1.29–5.64 in 54 samples with a statistical significance P value. Chowdhury S et al [83] studies 98 water systems; Water distribution system (WDS n = 42), plumbing pipe (PP n = 28), Hot water tanks (HWT n = 28) with water Pb value of 0.018–0.902 µg/dL, 0.013–1.09 µg/dL, 0.014–1.058 µg/dL, respectively. The study was carried out to find a way to predict Pb levels in water systems and promote future preventive measures. Pb concentrations in tap water can be much greater than the WDS depending on stagnation time and plumbing setup, resulting in a higher intake of Pb than the values from WDS or WTP. The study also observed more Pb levels in summer than in winter. The environmental genre is best described as multifaceted, since it is combined with other indispensable factors. The study by Mandour RA et al. [65] reported lactating mothers living in poverty and drinking polluted water negatively impacted the ultimate milk formula in which the study detected lead in breast milk with a p value of significance. Our review also reports environmental genre positively correlated to high PB in water, indoor dust, outdoor dust, paint, soil, water, air, and blood.
Public health challenges, opportunities, and recommendations
Most of the research was conducted in developing countries. In developing nations, where there are wide disparities in the sources and pathways of exposure to lead, this public health problem persists. It is important to note that public health strategies should place high priority on preventing lead exposure. Prevention indicated that there are limitations to policy enforcement and health fairness. Additionally, existing lead regulations primarily concentrate on identifying specific lead sources and hazardous BLCs in surroundings and consumer goods. For most developed countries where environmental lead poisoning remains a public health concern due to rapid industrialization, science-based public health measures, including screening, monitoring, prevention, and evaluation, are essential. Chemical exposures are difficult to quantify and keep track of because they are frequently employed in manufacturing.
However, studies on environmental decontamination and the effects of pollution on human health are possible. Evidence from the United States, Mexico, Japan, and Europe shows that the most efficient strategy to reduce lead exposure for the general population is to phase out leaded gasoline. Based on the World resources institute (USA), in 1998, there were almost 100 countries that still used leaded petrol [115]. However, other sources are equally crucial [116]. "The mistake of the twentieth century", the title of the lead reduction program on leaded gasoline, went viral, and many engaged actively [117]. For example, significant attempts have been made to phase out leaded gasoline from various countries in the MENA and non-MENA regions; Kuwait, Egypt, Bangladesh, Thailand, China, Malaysia, Nicaragua, Haiti, Honduras, India, and Hungary in the past decades [118–119]. Then, the Sultanate of Oman joined the list. Government commitment, incentive programs, comprehensive stakeholder agreement, public understanding, acceptance, and support are needed for this endeavor to be successful worldwide.
Thus, public health initiatives should continue to focus on reducing and preventing lead exposure. Eliminate lead-containing emissions that expose people to lead by reducing the use of lead and its associated compounds. That could be accomplished by: 1) Monitoring the life of marine food goods, 2) Monitoring soils for lead sources, 3) lead from gasoline should be removed as soon as it is practical, along with lead additions in fuels, 4) limiting and full ceasing the use of lead-based paints, 5) Removing lead from food containers, 6) Improving the use of monitoring systems to identify groups at high risk of exposure, 7) Locating, minimizing, and getting rid of the lead that is utilized in conventional medications and cosmetics, 8) Putting more focus on healthy eating, medical treatment, and awareness of socioeconomic factors that can worsen lead's effects, 9) Promote awareness campaigns in at national and broader international level, 10) Enhancing management of occupational lead exposure, 11) Reducing the amount of lead that dissolves in water distribution and treatment systems, 12) Fund rise research to support promising preventive strategies. 13) to focus and trust in cost-effective studies. For example, investments in lead hazard management can provide significant returns, especially if they are made early and in communities most likely to be at risk. The mitigation of lead hazards seems to be well worth the expense, given the significant social consequences of inactivity. The study revealed that an investment in the management of lead paint hazard yields a return of $17–221 or a net savings of $181–269 billion for every dollar spent [120]. 14) to conduct safe clinical trials to validate our reported treatments, especially the wet cup suction (Al-hijamah) due to its simplicity. If future studies have proven their validity, more restrictions must be applied. For more clarification, traditional drug stores in the MENA region have been observed to perform wet cup suction, and some do not follow the regulations of the ministry of health in terms of safety measures, sterilization, and well-trained personnel during the administration of the intervention.
Limitations and Strength
Limitations of our systematic review and expert’s consensus include; missing selective data from some studies. For example, not all studies reported chelation therapy, considering the inclusion criteria for bassline. Thus, results in further identification of possible confounding factors in every study. The strength of the study was several; It is the first attempt to highlight lead exposure in the MENA region with various aspects such as country, authors, publication year, study cohort, source genre, subgenre, tested tissue/substance, lead levels reported in range or mean: SD, sample size, age of study participants, gender, clinical manifestations, treatment, level of evidence and additional remarks whenever applicable. Additionally, the study conducted an additional search that showed substantial recovery of any potential data loss during the initial investigation. Ultimately, all studies included in the systematic analysis underwent MMAT evaluation.