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Exposure to arsenic through breast milk from mothers exposed to high levels of arsenic in drinking water: Infant risk assessment
Food Control 106 (2019) 106669
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Exposure to arsenic through breast milk from mothers exposed to high levels of arsenic in drinking water: Infant risk assessment
T
Fateme Samieea, Mostafa Leilib,∗, Javad Faradmalc, Zahra Torkshavanda, Gholamreza Asadid a
Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran Department of Environmental Health Engineering, Research Center for Health Sciences, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran c Department of Biostatistics and Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran d Kaboodrahang Health and Medical Center, Vice-Chancellor in Health Affairs, Hamadan University of Medical Sciences, Hamadan, Iran b
A R T I C LE I N FO
A B S T R A C
Keywords: Human breast milk Arsenic Hamadan Hazard quotients (HQ)
Heavy metal toxicity is related with a number of diseases, but the problem increases many-fold when toxic metals are found in breast milk, the basic food item in a vulnerable age group. Twenty milk samples from lactating women were collected from rural areas of arsenic-affected districts of Kaboodrahang city, Iran. Arsenic levels in drinking water were also analyzed. As controls, 20 breast milk samples and 8 drinking water samples were also collected from two villages southwest of Kaboodrahang city, where no groundwater arsenic contamination has been reported. Mean ( ± SD) arsenic concentration was 10.75 ( ± 7.62) μg/L in study samples and 7.73 ( ± 4.01) μg/L in control samples. Unacceptable non-carcinogenic health risk levels or hazard quotients for arsenic were found in 55% of breastfed infants in the contaminated areas and 41% of breastfed infants in the non-contaminated area. The results showed that the levels of arsenic in both contaminated and non-contaminated areas were high. This suggest that arsenic probably enters the mother's milk from other sources such as food crops in the study area. Our results indicate a potential risk of arsenic toxicity in infants in rural areas in Kaboodrahang city via the consumption of mothers' breast milk.
1. Introduction Study on biological monitoring in toxicological research is of great importance for assessing human health risks. Toxic heavy metal pollution is one of the most important environmental problems that humans are exposed to by various pathways (Gürbay et al., 2012). Of the known elements, approximately 80% are either metals or metalloids. The presence of some heavy metals such as iron, manganese, zinc and copper are essential for healthy life. These metals, however, can become harmful beyond the permissible limits. Nevertheless, some metals, such as arsenic, cadmium, lead, and mercury, even in small amounts are hazardous and toxic to humans and other living things (Graeme & Pollack, 1998). Breastmilk considered as the perfect food for human baby as it contains all of the essential nutrients, antibodies and other important factors for growth and development (Vahidinia et al., 2018). Many characteristics of breast milk make it a unique natural method of nutrition. However, because contaminants may be transmitted through
the food chain and breast milk (Le Huërou-Luron, Blat, & Boudry, 2010; Ojuri et al., 2019; Pimentel et al., 2018; Ursinyova & Masanova, 2005; Walia, Kapoor, & Farber, 2018), their safety and quality assurance are essential. In this regard, many studies have been conducted to assess respective health risks from various foodstuffs, baby formula, and breastmilk (Bogalho et al., 2018; Campagnollo, Gonzales-Barron, Pilão; Cadavez, Sant’Ana, & Schaffner, 2018; Cantú-Cornelio et al., 2016; Kabak, 2012; Lee, Jeong, Park, & Lee, 2018; Martinez-Miranda, RoseroMoreano, & Taborda-Ocampo, 2019; Samiee, Vahidinia, Taravati Javad, & Leili, 2019; Wang, Lien, & Ling, 2018). Cantú-Cornelio et al. (2016) reported that 89% of breast milk samples contained Aflatoxin M1 (AFM1) in a range of 3.01–34.24 ng/L and concluded that that breast-fed infants in the central region of Mexico, may be exposed to significant levels of this toxin through mother's breast milk. In another study, it was found that that there may be a potential risk of toxic metals for infants via the consumption of mothers' breast milk (Samiee et al., 2019). Arsenic (As) is a metalloid that occurs in many minerals, usually in
∗
Corresponding author. School of Public Health, Hamadan University of Medical Sciences, Shaheed Fahmideh Ave, Hamadan, 6517838695, Iran. Tel.: +988138380398; fax: +988138380509. E-mail addresses: [email protected] (F. Samiee), [email protected], [email protected] (M. Leili), [email protected] (J. Faradmal), [email protected] (Z. Torkshavand), [email protected] (G. Asadi). https://doi.org/10.1016/j.foodcont.2019.05.034 Received 2 March 2019; Received in revised form 29 May 2019; Accepted 29 May 2019 Available online 31 May 2019 0956-7135/ © 2019 Elsevier Ltd. All rights reserved.
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agriculture (potatoes and other vegetables) and animal husbandry, i.e. goat and sheep breeding. The diet of the population is mainly of animal origin (meat and milk products), supplemented with vegetables, maize and rice. The study included 20 healthy lactating women aged 20–37 years from each village. Questionnaires were given to each woman who agreed to participate in the study. The questionnaire contained items on the mother's education, age, height, and weight after pregnancy, family monthly income, and smoking habits. All samples were collected during August 2017 and September 2017. Among the 20 lactating mothers, 2 women had arsenic-related skin lesions, that were not excluded from the study. As controls, water and breast milk samples were collected from two villages where no groundwater arsenic contamination has been reported. Breast milk samples were collected from 20 healthy volunteers aged 19–40 years.
combination with sulfur and metals, and also as a pure elemental crystal. Exposure to arsenic in the human body is mainly due to water intake and seafood, especially shellfish (Panel, 2009). In the environment, As is found both in organic and in inorganic (iAs) forms. More than 80% of inorganic arsenic is readily absorbed in the gastrointestinal tract and is excreted mainly through urine (Abadin et al., 2007). As is a toxic metal, thus the International Agency for Research on Cancer (IARC) classified iAs as group 1 carcinogens, i.e., carcinogenic to humans (IARC, 1994), and Agency for Toxic Substances and Disease Registry (ATSDR) considered it as neurotoxic, genotoxic, embryotoxic with a half-life (plasma) of 3–4 h (ATSDR, 2007). In many countries such as Bangladesh, Argentina, and Pakistan, long-term exposure to arsenic through drinking water has been deliberated as a substantial public health issue, where high As concentrations has been reported (450 μg/L) (Rahman et al., 2010; Vahter, 2008). The maximum contaminant level (MCL) or guideline value for arsenic in drinking-water recommended by the US Environmental Protection Agency (US EPA) and World Health Organization (WHO) is 10 μg/L (USEPA, 2001; WHO, 2011a) to protect or decrease its harmful effects. Childhood is a time of severe exposure to arsenic, and there is conclusive evidence of associations between mother's exposure to arsenic during pregnancy and fetal loss, fetal growth disorder, reduced role of thymus gland, and increased neonatal death rate (Ahmed et al., 2012; Fängström et al., 2008). In 2010, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) concluded that the provisional tolerable weekly intake (PTWI) previously accepted for arsenic (15 µg/ kg bw, or 2.1 µg/kg bw/day) was no longer safe for humans, and established a benchmark dose of 0.5% extra risk (BMDL0.5) of 3 µg/ kg bw/day as the reference point for risk assessment (WHO, 2011b). To assess the exposure to arsenic of children being nursed by arsenic-exposed women, we investigated the concentrations of arsenic in milk samples from lactating women who live in contaminated rural areas of Kaboodrahang city in western Iran, where sources of drinking water have a relatively high arsenic content of about 150 μg/L.
2.2. Chemicals All reagents were of analytical reagent grade. All chemicals and metal stock standard solutions were obtained from Merck (Darmstadt, Germany) and Fluka (Buchs SG, Switzerland). 2.3. Sample collection 2.3.1. Drinking water Drinking water samples were collected once from the public water distribution system of each village in 50 mL acid-washed plastic bottles (Islam et al., 2014) at different times during August to September 2017, when the breast milk samples were also collected. The bottles were then sealed tightly with parafilm tape, labeled, and kept refrigerated in the field. 2.3.2. Breast milk From each mother, 10 mL of breast milk was collected in Falcon® BD polyethylene tubes. Breast milk samples were collected at 20 days to 24 months postpartum. All milk samples were stored at approximately 4 °C immediately after collection and were transported to the laboratory. Samples were stored at −20 °C prior to analysis (Samanta et al., 2007).
2. Materials and methods 2.1. Study area and population The study was conducted in two rural villages (A and B) among seven arsenic-affected villages in West Kaboodrahang city, Hamadan province, Iran. Village A has a total area of 0.36 km2 and a population of 505, and village B has a total area of 0.39 km2 and a population of 647. The study area is situated about 100 km west of the regional capital city, Hamadan (Fig. 1). In this area groundwater is the main source of water that is used for household and agriculture purposes, keeping in mind that the available surface and rain water were not considered in this study. The local economy of theses villages is based on rudimentary
2.4. Arsenic measurements Samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) apparatus. Analytical method and quality control measures were reported in our previous published work (Taravati Javad et al., 2018). The typical limit of detection achieved in routine operation during arsenic sample analysis was calculated as 1 μg/L. 2.5. Quality assurance/quality control (QA/QC) QC and QA measures were also accomplished based on our previous study (Taravati Javad et al., 2018). Percent recoveries of the analysed metals in the reference materials were found to be in the range 92–106%. During the analytical work, together with each series of 20 samples, always at least one blank and one reference material was run and analyzed. 2.6. Estimation of daily intake from breastfeeding Risk assessment is the determination of quantitative or qualitative estimate of risk related to a well-defined situation and a recognized threat (Samiee et al., 2019). Daily arsenic intake in breastfed infants was estimated with the following equation (Anderson et al., 1994):
Fig. 1. Location of the study area and selected villages. 2
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Daily inake (μg/kg − bw/day) Milk consumption (L/d) × Concentration (μg/L) = Body weight (kg)
groundwater was not contaminated with arsenic) were below the detection limit of 1 μg/L. The highest levels of arsenic (2 μg/L) were also well below the 10 μg/L, the limit recommended by WHO as a guideline value for arsenic in drinking water.
(1)
The non-carcinogenic risk was calculated as the hazard quotient (HQ) by dividing estimated daily intake from breastfeeding by a reference dose of arsenic (0.3 μg/kg/day) (Schoeny, Patterson, Swartout, & Tuxen, 1990). A hazard quotient less than or equal to 1 indicates an acceptable level and HQ greater than 1 are probabilities of adverse noncarcinogenic health risks (USEPA, 2001). The reference values for the daily intake of breast milk and body weight were based on the previous studies results (Dewey, Finley, & Lönnerdal, 1984; Dewey & Lönnerdal, 1983; Ksiazyk & Weker, 2007).
4. Discussion 4.1. Arsenic exposure in exposed population In light of the increased vulnerability of infants, the determination of toxic contaminant levels in breast milk is of great importance. Our results indicate that the entire population in our study area, including lactating mothers, is at risk of exposure to arsenic from various sources, such as drinking water and vegetable products. Heavy metals such as arsenic are known to be the most toxic contaminants found in human milk (Anderson et al., 1994). The presence of heavy metals in human milk indicates the possible exposure of mother with these toxic pollutants. Heavy metals such as arsenic, lead, mercury and cadmium also affect infant health negatively. Heavy metals are considered as an important toxic contaminants of human breast milk as it can be a route of maternal excretion (Yurdakö;k, 2015). It was shown that the prolonged exposure to arsenic in children may result in lower intelligence quotient (IQ) scores. It has also been shown that exposure to arsenic in the uterus and early childhood may rise mortality in young adults. In addition, arsenic can affect pregnant women or their infants through inhalation or ingestion, however, the main effects have not been well documented. Studies in animals have shown that high levels of arsenic that cause disease in pregnant women can also cause low birth weight, fetal abnormalities, and even fetal death. Arsenic can also go through a placenta, hence be found in embryonic tissues (Kim & Kim, 2015). Different levels of arsenic have been reported in human breast milk (Xia et al., 2016). In the present study, the mean ( ± SD) and median arsenic concentrations in breast milk were 10.75 ( ± 7.62) and 8.80 μg/ L, respectively. Arsenic levels in breast milk samples were higher than the detection limit (1 μg/L) in 95% of samples, and the levels in all samples were higher than 0.2–0.6 μg/L, the limit recommended by the WHO for this contaminant in breast milk (Bartmess, 1990). We found the maximum As concentration of 30.1 μg/L, which is near to the maximum values of 49 μg/L reported by Samanta et al. (2007) and 38 μg/L reported by Watanabe et al. (2003). Moreover, mean arsenic levels in our study were higher than the mean arsenic concentrations found in Croatia (0.2 μg/L), Italy (0.3 μg/L) (Miklavčič et al., 2013), United Arab Emirates (0.89 μg/L), and Slovenia (0.04 μg/L) (Hornung & Reed, 1990), but were lower than those reported for the Philippines (18.9 μg/L) (Parr et al., 1991). In a study conducted in a mining community in Ghana, the average amount of arsenic in human milk samples was reported as 27.5 μg/L, which was about three times as much as the limit recommended by the WHO in drinking water, and much greater than in a non-mining region of the country, where the mean levels was 1.54 μg/L with a range of 0.00–6.22 μg/L (Bansa et al., 2017). Fängström et al. (2008) reported that arsenic concentrations in urine were considerably lower in particularly breastfed infants than in those consuming other foodstuffs. Greater mean concentrations of arsenic (3.6–14 µg/L) were detected in colostrum (Almeida, Lopes, Silva, & Barrado, 2008), and decreased considerably in intermediate and mature (Almeida et al., 2008; Islam et al., 2014). Ahmed et al. (2012) and Fängström et al. (2008) also measured arsenic excretion via breast milk and found low As concentrations, leading them to conclude that special breastfeeding protects infants from exposure to arsenic. A comparable conclusion was reported by Carignan et al. (2015) in a region of the USA with relatively low concentrations of arsenic in the water (<1 µg/L). In a study in west Bengal (India) (Samanta et al., 2007) similar to ours, the mean concentration of arsenic in breast milk (19.6 μg/L) in a region with high levels of arsenic in water (220 μg/L) was much higher
2.7. Statistics The data were analyzed with SPSS v.21.0 for Windows (SPSS Inc., Chicago, IL, USA). The results are presented with median, mean values and ranges for arsenic levels in breast milk. 3. Results 3.1. Characteristics of lactating women The main socio-demographic characteristics of the study participants was shown in Table 1. As seen, mean maternal age ± SD was 29.15 ± 5.78 years (ranged from 20 to 37 years). Three (15%) mothers were older than 35 years. Thirty-six (90%) mothers had been educated for less than 8 years. The monthly income was US$300 or more in 15 (37.5%) families and less than US$300 in 25 (62.5%) families. 3.2. Concentration of arsenic in drinking water and milk samples from lactating women The distributions of arsenic in water and breast milk samples is shown in Fig. 2. All drinking water samples (four from each village) were collected from the public water distribution system in the study area. As seen in the histogram of arsenic concentrations in drinking water (Fig. 2a), 2 samples (25%) contained ≤50 μg/L arsenic, 2 samples (25%) had arsenic concentrations of 101–150 μg/L, 2 samples (25%) had concentrations between 151 and 200 μg/L, and 2 samples (25%) had concentrations ≥ 200 μg/L. The highest concentration of arsenic in drinking water samples was measured to be 366 μg/L. The distribution of arsenic concentrations in milk samples is shown in Fig. 2b, and summary statistics for breast milk concentrations are shown in Table 2. The maximum arsenic concentration in milk samples was 30.10 μg/L and the median was 8.80 μg/L. Arsenic concentrations in 6 of 8 control water samples collected from two villages (where the Table 1 Socio-demographic characteristics of the study participants. Demographic information
Mean ± SD (range), N (%)
Age (y) Body weight (kg) Height (m) BMI (kg/m2) after pregnancy Education High school and below College and above Occupation Housewife Other job Smoking No Yes Number of pregnancies Number of live births
29.15 ± 5.78 (20‒37) 58.65 ± 9.94 (45‒81) 1.58 ± 0.04 (1.52–1.63) 23.82 ± 3.80 (17.22–33.20) 18 (90) 2 (10) 20 (100) 0 (0) 20 (100) 0 (0) 2.10 ± 0.20 (1‒3) 2.00 ± 0.79 (1‒3)
3
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Fig. 2. Distribution of arsenic in drinking water (a) and breast milk samples (b) in the study area.
(Concha, Vogler, Nermell, & Vahter, 1998). The mechanism for eliminating arsenic from human milk is not clear, and the agents that can affect its elimination are not yet known (Samanta et al., 2007). However, it has been reported that arsenic methylation during pregnancy and lactation can probably protect fetuses and infants from arsenic exposure (Vahter, 2009).
Table 2 Summary statistics for arsenic concentrations (μg/L) in water and breast milk samples from lactating women.
As in water a As in breast milk b Control As in water c As in breast milk
No. of samples
Mean
Median
Min.
Max.
N (%) > WHO recommended limit
8 20
157.44 10.75
158.00 8.80
9 3
366 30.10
6 (75) 20 (100)
8 20
0.5 7.73
0.25 7.40
0.25 3.20
2 15.40
0 (0) 18 (90)
4.2. Estimation of daily intake through breastfeeding When breast milk is insufficient or unavailable, cow or goat milk was diluted with contaminated water and is used to feed the baby. Therefore, the arsenic body burden in the babies we studied reflected the following cumulative effects: (i) amount of arsenic transported to the baby via the cord blood, (ii) level of arsenic in breast milk, and (iii) concentration of arsenic in the drinking water, if babies were given contaminated water. Although cord blood is an important factor in newborn infants (Samanta et al., 2007), in the present study we investigated the amount of arsenic transported to the baby only through breast milk. The PTWI of arsenic is 2.1 µg/kg bw/day (WHO, 2011b). The average body weight of babies in the present study was also estimated according to WHO Child Growth Standards (Ksiazyk & Weker, 2007). The non-carcinogenic health risk was determined for breastfeeding infants, accordingly. The distribution of point estimated daily intake (EDI) values of arsenic in contaminated and non-contaminated areas is presented in Fig. 3. The median daily intake of arsenic in contaminated areas was estimated at 0.9 μg/kg-bw/day, and the 95th percentile value of daily intake was 3.41 μg/kg-bw/day. The HQ for arsenic exposure exceeded 1.0 in 55% of breastfed infants in contaminated areas. The infants in our study appear to have been exposed to lower levels of arsenic than infants in a study from India (2.57 μg/kg-bw/day) (Samanta et al., 2007), but higher levels than infants in the USA (0.04 μg/kg-bw/day) (Carignan et al., 2015), Portugal (0.82 μg/kg-bw/day) (Almeida et al., 2008) and Japan (0.25 μg/kg-bw/day) (Sakamoto, Chan, Domingo, Kubota, & Murata, 2012). A lower median arsenic intake (0.02 μg/kg-bw/day, or 0.14 μg/kg-bw/week) was estimated by (Sternowsky, Moser, & Szadkowsky, 2002) in 3-month-old German infants (6 kg; 790 mL/day). These authors considered exposure to be safe, because it was much lower than the PTWI of 15 μg/kg-bw/week. However, HQ for arsenic exposure exceeded 1.0 for 41% of breastfed infants in non-contaminated areas that we assessed. These results suggest a potential risk from arsenic for some infants in rural areas of Kaboodrahang via the consumption of mothers’ milk. Heavy metals are classified in the environmental pollutants category due to their toxic effects on the organisms. Many studies have also shown that bladder and kidney cancers are higher in the people who have had long-term exposure to arsenic. Pulmonary disease, developmental effects, diabetes and cardiovascular disease are other undesirable health effects of long-term exposure to inorganic arsenic (WHO,
a WHO recommended guideline value for drinking water 10 μg/L (WHO, 2011a). b WHO recommended limit for As in breast milk 0.2–0.6 μg/L (Bartmess, 1990). c For samples below the limit of detection (LOD), a proxy value, i.e. LOD divided by square root 2, was used for statistical analysis (Xia et al., 2016).
than in areas with low arsenic levels in water (< 3 μg/L), where the mean concentration in breast milk was only 2.5 μg/L. These results contrast with our findings and suggests that arsenic probably enters the mother's milk from sources other than drinking water. High concentrations of arsenic in drinking water have been reported in many parts of the world (Ng, 2005). In addition to drinking water, food crops have also been considered important pathways for arsenic intake by humans (Stone, 2008), because plants can take up arsenic from the surface soils. Previous studies found that irrigation with As-contaminated waters can increase arsenic retention in soils via adsorption on soil exchange complexes (Saha & Ali, 2007). As a result, arsenic-contaminated soils and irrigation waters may increase the levels of this element food crops via plant uptake mechanisms. Interestingly, among all agricultural crops, rice accumulates the greatest concentrations of this element, probably due to its greater irrigation water requirements (Lynch, Greenberg, Pollock, & Lewis, 2014; Stone, 2008) reviewed and assessed more than 6500 data points on inorganic As and its intermediates in food, including seafood and special foods for kids, and found the seaweed/algae, rice and its byproducts as the foods with the maximum level of iAs. Arsenic concentrations in breast milk reported in earlier studies were typically low (median 1.0 μg/kg), and arsenic was frequently in the form of trivalent iAs (Tillett, 2008). However, some studies, including the present work, reported the high levels of arsenic in breast milk. This finding might be due to the exposure with high concentrations of arsenic via drinking water and dietary intake, and the eating seafood, particularly shellfish by mothers (Samanta et al., 2007). The exposure of babies to arsenic via drinking water and/or formula prepared with drinking water has also been considered an important source. There is evidence that the transfer of arsenic to the mammary glands is limited, which in turn protect newborns against As exposure 4
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Fig. 3. Distribution of estimated daily intake (EDI) of arsenic in infants living in (a) contaminated areas and (b) non-contaminated areas.
Funding information
2018). Arsenic is also associated with adverse pregnancy outcomes and infant mortality, with impacts on child health (Quansah et al., 2015), and exposure in utero and in early childhood has been linked to increases in mortality in young adults due to multiple cancers, lung disease, heart attacks, and kidney failure (Farzan, Karagas, & Chen, 2013).
This project was financially supported by the School of Public Health, Hamadan University of Medical Sciences (Grant number: 9604132341). Compliance with ethical standards
4.3. Study limitations Ethical approval was obtained from the Human Research Ethics Committee, Medical University of Hamadan, Iran. Breastfeeding mothers provided their informed written consent, agreed to provide samples, and received no payment for their participation.
The main limitations of this study are: 1) Due to the low population of the studied villages, the number of samples were also low, which reduced the precision of our analysis; 2) We did not determine the arsenic levels in irrigation waters or soils, or its uptake by crops, nor did we investigate the relationship between these factors; 3) We did not measure arsenic concentrations in urine, hair or nail samples of infants, nor did we test their correlation with concentrations in their mothers’ urine, hair or nails; 4) We did not study variables such as the consumption of rice and its byproducts, seafood, or vegetables (times per week or month), and also did not investigate insecticide application in the study area. Therefore, the possible effects of these factors on the levels of arsenic in breast milk remains to be determined. The possible associations between increased arsenic concentrations in breast milk and its concentrations in fish, rice and vegetables should also be evaluated in a prospective, longitudinal study.
Conflicts of interest The authors declare that they have no conflict of interest. Acknowledgements The authors would like to thank the Hamadan University of Medical Sciences‒Deputy of Health staff for cooperation in sample collection and all lactating mothers who voluntarily participated in the study. We thank K. Shashok (AuthorAID in the Eastern Mediterranean) for improving the use of English in the manuscript. References
5. Conclusions Abadin, H., Ashizawa, A., Stevens, Y., Llados, F., Diamond, G., Sage, G., et al. (2007). Toxicological profile for lead. Atlanta, GA, USA: Agency for Toxic Substances and Disease Registry. Ahmed, S., Ahsan, K. B., Kippler, M., Mily, A., Wagatsuma, Y., Hoque, A. W., et al. (2012). In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis. Toxicological Sciences, 129(2), 305–314. Almeida, A. A., Lopes, C. M., Silva, A. M., & Barrado, E. (2008). Trace elements in human milk: Correlation with blood levels, inter-element correlations and changes in concentration during the first month of lactation. Journal of Trace Elements in Medicine & Biology, 22(3), 196–205. Anderson, M., Dewey, K., Frongillo, E., Garza, C., Haschke, F., Kramer, M., et al. (1994). WHO working group on infant growth: An evaluation of infant growth. Geneva, Switzerland: World health organization. ATSDR – Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. Atlanta, GA: Division of Toxicology. Bansa, D. K., Awua, A. K., Boatin, R., Adom, T., Brown-Appiah, E. C., Amewosina, K. K., et al. (2017). Cross-sectional assessment of infants' exposure to toxic metals through breast milk in a prospective cohort study of mining communities in Ghana. BMC Public Health, 17(1), 505. Bartmess, J. E. (1990). Minor and trace elements in breast milk: Report of a joint WHO/ IAEA collaborative study. Journal of Human Lactation, 6(1), 28–29. Bogalho, F., Duarte, S., Cardoso, M., Almeida, A., Cabeças, R., Lino, C., et al. (2018). Exposure assessment of Portuguese infants to Aflatoxin M1 in breast milk and
In breastfeeding mothers the pollutants may affect both the mother's milk and the infants. It is therefore important for governments or local health authorities to determine the levels of toxic contaminants in foods which pose a risk to the wider population. Furthermore, it is essential to implement regulations to prevent potential contamination. Arsenic concentrations in breast milk samples in the present study were high in women living in both arsenic-contaminated and non-contaminated areas, and there was no significant difference in the mean concentration of arsenic between breast milk samples from women living in contaminated and non-contaminated areas. This suggests that arsenic probably enters the mother's milk from other sources, for example from seafood and rice. Unacceptable non-cancer health risk levels were found for arsenic in 55% of breastfed infants in the contaminated area and 41% in the non-contaminated area. In light of these results, we suggest that the arsenic levels in irrigation waters and soils, and its uptake by crops should be investigated along with the relationships between these levels. 5
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Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water. International Archives of Occupational and Environmental Health, 71(1), 42–46. Dewey, K. G., Finley, D. A., & Lönnerdal, B. (1984). Breast milk volume and composition during late lactation (7-20 months). Journal of Pediatric Gastroenterology and Nutrition, 3(5), 713–720. Dewey, K. G., & Lönnerdal, B. (1983). Milk and nutrient intake of breast-fed infants from 1 to 6 months: Relation to growth and fatness. Journal of Pediatric Gastroenterology and Nutrition, 2(3), 497–506. Fängström, B., Moore, S., Nermell, B., Kuenstl, L., Goessler, W., Grandér, M., et al. (2008). Breast-feeding protects against arsenic exposure in Bangladeshi infants. Environmental Health Perspectives, 116(7), 963. Farzan, S. F., Karagas, M. R., & Chen, Y. (2013). In utero and early life arsenic exposure in relation to long-term health and disease. 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Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh. Environmental Health, 13(1), 101. Kabak, B. (2012). Aflatoxin M1 and ochratoxin A in baby formulae in Turkey: Occurrence and safety evaluation. Food Control, 26(1), 182–187. Kim, Y.-J., & Kim, J.-M. (2015). Arsenic toxicity in male reproduction and development. Development & reproduction, 19(4), 167. Ksiazyk, J., & Weker, H. (2007). New feeding plan for infants in Poland, since 2007. PEDIATRIA WSPOLCZESNA, 9(1), 9. Le Huërou-Luron, I., Blat, S., & Boudry, G. (2010). Breast-v. Formula-feeding: Impacts on the digestive tract and immediate and long-term health effects. Nutrition Research Reviews, 23(1), 23–36. Lee, J., Jeong, J.-H., Park, S., & Lee, K.-G. (2018). Monitoring and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in processed foods and their raw materials. Food Control, 92, 286–292. Lynch, H. 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Exposure to arsenic through breast milk from mothers exposed to high levels of arsenic in drinking water: Infant risk assessment
T
Fateme Samieea, Mostafa Leilib,∗, Javad Faradmalc, Zahra Torkshavanda, Gholamreza Asadid a
Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran Department of Environmental Health Engineering, Research Center for Health Sciences, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran c Department of Biostatistics and Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran d Kaboodrahang Health and Medical Center, Vice-Chancellor in Health Affairs, Hamadan University of Medical Sciences, Hamadan, Iran b
A R T I C LE I N FO
A B S T R A C
Keywords: Human breast milk Arsenic Hamadan Hazard quotients (HQ)
Heavy metal toxicity is related with a number of diseases, but the problem increases many-fold when toxic metals are found in breast milk, the basic food item in a vulnerable age group. Twenty milk samples from lactating women were collected from rural areas of arsenic-affected districts of Kaboodrahang city, Iran. Arsenic levels in drinking water were also analyzed. As controls, 20 breast milk samples and 8 drinking water samples were also collected from two villages southwest of Kaboodrahang city, where no groundwater arsenic contamination has been reported. Mean ( ± SD) arsenic concentration was 10.75 ( ± 7.62) μg/L in study samples and 7.73 ( ± 4.01) μg/L in control samples. Unacceptable non-carcinogenic health risk levels or hazard quotients for arsenic were found in 55% of breastfed infants in the contaminated areas and 41% of breastfed infants in the non-contaminated area. The results showed that the levels of arsenic in both contaminated and non-contaminated areas were high. This suggest that arsenic probably enters the mother's milk from other sources such as food crops in the study area. Our results indicate a potential risk of arsenic toxicity in infants in rural areas in Kaboodrahang city via the consumption of mothers' breast milk.
1. Introduction Study on biological monitoring in toxicological research is of great importance for assessing human health risks. Toxic heavy metal pollution is one of the most important environmental problems that humans are exposed to by various pathways (Gürbay et al., 2012). Of the known elements, approximately 80% are either metals or metalloids. The presence of some heavy metals such as iron, manganese, zinc and copper are essential for healthy life. These metals, however, can become harmful beyond the permissible limits. Nevertheless, some metals, such as arsenic, cadmium, lead, and mercury, even in small amounts are hazardous and toxic to humans and other living things (Graeme & Pollack, 1998). Breastmilk considered as the perfect food for human baby as it contains all of the essential nutrients, antibodies and other important factors for growth and development (Vahidinia et al., 2018). Many characteristics of breast milk make it a unique natural method of nutrition. However, because contaminants may be transmitted through
the food chain and breast milk (Le Huërou-Luron, Blat, & Boudry, 2010; Ojuri et al., 2019; Pimentel et al., 2018; Ursinyova & Masanova, 2005; Walia, Kapoor, & Farber, 2018), their safety and quality assurance are essential. In this regard, many studies have been conducted to assess respective health risks from various foodstuffs, baby formula, and breastmilk (Bogalho et al., 2018; Campagnollo, Gonzales-Barron, Pilão; Cadavez, Sant’Ana, & Schaffner, 2018; Cantú-Cornelio et al., 2016; Kabak, 2012; Lee, Jeong, Park, & Lee, 2018; Martinez-Miranda, RoseroMoreano, & Taborda-Ocampo, 2019; Samiee, Vahidinia, Taravati Javad, & Leili, 2019; Wang, Lien, & Ling, 2018). Cantú-Cornelio et al. (2016) reported that 89% of breast milk samples contained Aflatoxin M1 (AFM1) in a range of 3.01–34.24 ng/L and concluded that that breast-fed infants in the central region of Mexico, may be exposed to significant levels of this toxin through mother's breast milk. In another study, it was found that that there may be a potential risk of toxic metals for infants via the consumption of mothers' breast milk (Samiee et al., 2019). Arsenic (As) is a metalloid that occurs in many minerals, usually in
∗
Corresponding author. School of Public Health, Hamadan University of Medical Sciences, Shaheed Fahmideh Ave, Hamadan, 6517838695, Iran. Tel.: +988138380398; fax: +988138380509. E-mail addresses: [email protected] (F. Samiee), [email protected], [email protected] (M. Leili), [email protected] (J. Faradmal), [email protected] (Z. Torkshavand), [email protected] (G. Asadi). https://doi.org/10.1016/j.foodcont.2019.05.034 Received 2 March 2019; Received in revised form 29 May 2019; Accepted 29 May 2019 Available online 31 May 2019 0956-7135/ © 2019 Elsevier Ltd. All rights reserved.
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agriculture (potatoes and other vegetables) and animal husbandry, i.e. goat and sheep breeding. The diet of the population is mainly of animal origin (meat and milk products), supplemented with vegetables, maize and rice. The study included 20 healthy lactating women aged 20–37 years from each village. Questionnaires were given to each woman who agreed to participate in the study. The questionnaire contained items on the mother's education, age, height, and weight after pregnancy, family monthly income, and smoking habits. All samples were collected during August 2017 and September 2017. Among the 20 lactating mothers, 2 women had arsenic-related skin lesions, that were not excluded from the study. As controls, water and breast milk samples were collected from two villages where no groundwater arsenic contamination has been reported. Breast milk samples were collected from 20 healthy volunteers aged 19–40 years.
combination with sulfur and metals, and also as a pure elemental crystal. Exposure to arsenic in the human body is mainly due to water intake and seafood, especially shellfish (Panel, 2009). In the environment, As is found both in organic and in inorganic (iAs) forms. More than 80% of inorganic arsenic is readily absorbed in the gastrointestinal tract and is excreted mainly through urine (Abadin et al., 2007). As is a toxic metal, thus the International Agency for Research on Cancer (IARC) classified iAs as group 1 carcinogens, i.e., carcinogenic to humans (IARC, 1994), and Agency for Toxic Substances and Disease Registry (ATSDR) considered it as neurotoxic, genotoxic, embryotoxic with a half-life (plasma) of 3–4 h (ATSDR, 2007). In many countries such as Bangladesh, Argentina, and Pakistan, long-term exposure to arsenic through drinking water has been deliberated as a substantial public health issue, where high As concentrations has been reported (450 μg/L) (Rahman et al., 2010; Vahter, 2008). The maximum contaminant level (MCL) or guideline value for arsenic in drinking-water recommended by the US Environmental Protection Agency (US EPA) and World Health Organization (WHO) is 10 μg/L (USEPA, 2001; WHO, 2011a) to protect or decrease its harmful effects. Childhood is a time of severe exposure to arsenic, and there is conclusive evidence of associations between mother's exposure to arsenic during pregnancy and fetal loss, fetal growth disorder, reduced role of thymus gland, and increased neonatal death rate (Ahmed et al., 2012; Fängström et al., 2008). In 2010, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) concluded that the provisional tolerable weekly intake (PTWI) previously accepted for arsenic (15 µg/ kg bw, or 2.1 µg/kg bw/day) was no longer safe for humans, and established a benchmark dose of 0.5% extra risk (BMDL0.5) of 3 µg/ kg bw/day as the reference point for risk assessment (WHO, 2011b). To assess the exposure to arsenic of children being nursed by arsenic-exposed women, we investigated the concentrations of arsenic in milk samples from lactating women who live in contaminated rural areas of Kaboodrahang city in western Iran, where sources of drinking water have a relatively high arsenic content of about 150 μg/L.
2.2. Chemicals All reagents were of analytical reagent grade. All chemicals and metal stock standard solutions were obtained from Merck (Darmstadt, Germany) and Fluka (Buchs SG, Switzerland). 2.3. Sample collection 2.3.1. Drinking water Drinking water samples were collected once from the public water distribution system of each village in 50 mL acid-washed plastic bottles (Islam et al., 2014) at different times during August to September 2017, when the breast milk samples were also collected. The bottles were then sealed tightly with parafilm tape, labeled, and kept refrigerated in the field. 2.3.2. Breast milk From each mother, 10 mL of breast milk was collected in Falcon® BD polyethylene tubes. Breast milk samples were collected at 20 days to 24 months postpartum. All milk samples were stored at approximately 4 °C immediately after collection and were transported to the laboratory. Samples were stored at −20 °C prior to analysis (Samanta et al., 2007).
2. Materials and methods 2.1. Study area and population The study was conducted in two rural villages (A and B) among seven arsenic-affected villages in West Kaboodrahang city, Hamadan province, Iran. Village A has a total area of 0.36 km2 and a population of 505, and village B has a total area of 0.39 km2 and a population of 647. The study area is situated about 100 km west of the regional capital city, Hamadan (Fig. 1). In this area groundwater is the main source of water that is used for household and agriculture purposes, keeping in mind that the available surface and rain water were not considered in this study. The local economy of theses villages is based on rudimentary
2.4. Arsenic measurements Samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) apparatus. Analytical method and quality control measures were reported in our previous published work (Taravati Javad et al., 2018). The typical limit of detection achieved in routine operation during arsenic sample analysis was calculated as 1 μg/L. 2.5. Quality assurance/quality control (QA/QC) QC and QA measures were also accomplished based on our previous study (Taravati Javad et al., 2018). Percent recoveries of the analysed metals in the reference materials were found to be in the range 92–106%. During the analytical work, together with each series of 20 samples, always at least one blank and one reference material was run and analyzed. 2.6. Estimation of daily intake from breastfeeding Risk assessment is the determination of quantitative or qualitative estimate of risk related to a well-defined situation and a recognized threat (Samiee et al., 2019). Daily arsenic intake in breastfed infants was estimated with the following equation (Anderson et al., 1994):
Fig. 1. Location of the study area and selected villages. 2
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Daily inake (μg/kg − bw/day) Milk consumption (L/d) × Concentration (μg/L) = Body weight (kg)
groundwater was not contaminated with arsenic) were below the detection limit of 1 μg/L. The highest levels of arsenic (2 μg/L) were also well below the 10 μg/L, the limit recommended by WHO as a guideline value for arsenic in drinking water.
(1)
The non-carcinogenic risk was calculated as the hazard quotient (HQ) by dividing estimated daily intake from breastfeeding by a reference dose of arsenic (0.3 μg/kg/day) (Schoeny, Patterson, Swartout, & Tuxen, 1990). A hazard quotient less than or equal to 1 indicates an acceptable level and HQ greater than 1 are probabilities of adverse noncarcinogenic health risks (USEPA, 2001). The reference values for the daily intake of breast milk and body weight were based on the previous studies results (Dewey, Finley, & Lönnerdal, 1984; Dewey & Lönnerdal, 1983; Ksiazyk & Weker, 2007).
4. Discussion 4.1. Arsenic exposure in exposed population In light of the increased vulnerability of infants, the determination of toxic contaminant levels in breast milk is of great importance. Our results indicate that the entire population in our study area, including lactating mothers, is at risk of exposure to arsenic from various sources, such as drinking water and vegetable products. Heavy metals such as arsenic are known to be the most toxic contaminants found in human milk (Anderson et al., 1994). The presence of heavy metals in human milk indicates the possible exposure of mother with these toxic pollutants. Heavy metals such as arsenic, lead, mercury and cadmium also affect infant health negatively. Heavy metals are considered as an important toxic contaminants of human breast milk as it can be a route of maternal excretion (Yurdakö;k, 2015). It was shown that the prolonged exposure to arsenic in children may result in lower intelligence quotient (IQ) scores. It has also been shown that exposure to arsenic in the uterus and early childhood may rise mortality in young adults. In addition, arsenic can affect pregnant women or their infants through inhalation or ingestion, however, the main effects have not been well documented. Studies in animals have shown that high levels of arsenic that cause disease in pregnant women can also cause low birth weight, fetal abnormalities, and even fetal death. Arsenic can also go through a placenta, hence be found in embryonic tissues (Kim & Kim, 2015). Different levels of arsenic have been reported in human breast milk (Xia et al., 2016). In the present study, the mean ( ± SD) and median arsenic concentrations in breast milk were 10.75 ( ± 7.62) and 8.80 μg/ L, respectively. Arsenic levels in breast milk samples were higher than the detection limit (1 μg/L) in 95% of samples, and the levels in all samples were higher than 0.2–0.6 μg/L, the limit recommended by the WHO for this contaminant in breast milk (Bartmess, 1990). We found the maximum As concentration of 30.1 μg/L, which is near to the maximum values of 49 μg/L reported by Samanta et al. (2007) and 38 μg/L reported by Watanabe et al. (2003). Moreover, mean arsenic levels in our study were higher than the mean arsenic concentrations found in Croatia (0.2 μg/L), Italy (0.3 μg/L) (Miklavčič et al., 2013), United Arab Emirates (0.89 μg/L), and Slovenia (0.04 μg/L) (Hornung & Reed, 1990), but were lower than those reported for the Philippines (18.9 μg/L) (Parr et al., 1991). In a study conducted in a mining community in Ghana, the average amount of arsenic in human milk samples was reported as 27.5 μg/L, which was about three times as much as the limit recommended by the WHO in drinking water, and much greater than in a non-mining region of the country, where the mean levels was 1.54 μg/L with a range of 0.00–6.22 μg/L (Bansa et al., 2017). Fängström et al. (2008) reported that arsenic concentrations in urine were considerably lower in particularly breastfed infants than in those consuming other foodstuffs. Greater mean concentrations of arsenic (3.6–14 µg/L) were detected in colostrum (Almeida, Lopes, Silva, & Barrado, 2008), and decreased considerably in intermediate and mature (Almeida et al., 2008; Islam et al., 2014). Ahmed et al. (2012) and Fängström et al. (2008) also measured arsenic excretion via breast milk and found low As concentrations, leading them to conclude that special breastfeeding protects infants from exposure to arsenic. A comparable conclusion was reported by Carignan et al. (2015) in a region of the USA with relatively low concentrations of arsenic in the water (<1 µg/L). In a study in west Bengal (India) (Samanta et al., 2007) similar to ours, the mean concentration of arsenic in breast milk (19.6 μg/L) in a region with high levels of arsenic in water (220 μg/L) was much higher
2.7. Statistics The data were analyzed with SPSS v.21.0 for Windows (SPSS Inc., Chicago, IL, USA). The results are presented with median, mean values and ranges for arsenic levels in breast milk. 3. Results 3.1. Characteristics of lactating women The main socio-demographic characteristics of the study participants was shown in Table 1. As seen, mean maternal age ± SD was 29.15 ± 5.78 years (ranged from 20 to 37 years). Three (15%) mothers were older than 35 years. Thirty-six (90%) mothers had been educated for less than 8 years. The monthly income was US$300 or more in 15 (37.5%) families and less than US$300 in 25 (62.5%) families. 3.2. Concentration of arsenic in drinking water and milk samples from lactating women The distributions of arsenic in water and breast milk samples is shown in Fig. 2. All drinking water samples (four from each village) were collected from the public water distribution system in the study area. As seen in the histogram of arsenic concentrations in drinking water (Fig. 2a), 2 samples (25%) contained ≤50 μg/L arsenic, 2 samples (25%) had arsenic concentrations of 101–150 μg/L, 2 samples (25%) had concentrations between 151 and 200 μg/L, and 2 samples (25%) had concentrations ≥ 200 μg/L. The highest concentration of arsenic in drinking water samples was measured to be 366 μg/L. The distribution of arsenic concentrations in milk samples is shown in Fig. 2b, and summary statistics for breast milk concentrations are shown in Table 2. The maximum arsenic concentration in milk samples was 30.10 μg/L and the median was 8.80 μg/L. Arsenic concentrations in 6 of 8 control water samples collected from two villages (where the Table 1 Socio-demographic characteristics of the study participants. Demographic information
Mean ± SD (range), N (%)
Age (y) Body weight (kg) Height (m) BMI (kg/m2) after pregnancy Education High school and below College and above Occupation Housewife Other job Smoking No Yes Number of pregnancies Number of live births
29.15 ± 5.78 (20‒37) 58.65 ± 9.94 (45‒81) 1.58 ± 0.04 (1.52–1.63) 23.82 ± 3.80 (17.22–33.20) 18 (90) 2 (10) 20 (100) 0 (0) 20 (100) 0 (0) 2.10 ± 0.20 (1‒3) 2.00 ± 0.79 (1‒3)
3
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Fig. 2. Distribution of arsenic in drinking water (a) and breast milk samples (b) in the study area.
(Concha, Vogler, Nermell, & Vahter, 1998). The mechanism for eliminating arsenic from human milk is not clear, and the agents that can affect its elimination are not yet known (Samanta et al., 2007). However, it has been reported that arsenic methylation during pregnancy and lactation can probably protect fetuses and infants from arsenic exposure (Vahter, 2009).
Table 2 Summary statistics for arsenic concentrations (μg/L) in water and breast milk samples from lactating women.
As in water a As in breast milk b Control As in water c As in breast milk
No. of samples
Mean
Median
Min.
Max.
N (%) > WHO recommended limit
8 20
157.44 10.75
158.00 8.80
9 3
366 30.10
6 (75) 20 (100)
8 20
0.5 7.73
0.25 7.40
0.25 3.20
2 15.40
0 (0) 18 (90)
4.2. Estimation of daily intake through breastfeeding When breast milk is insufficient or unavailable, cow or goat milk was diluted with contaminated water and is used to feed the baby. Therefore, the arsenic body burden in the babies we studied reflected the following cumulative effects: (i) amount of arsenic transported to the baby via the cord blood, (ii) level of arsenic in breast milk, and (iii) concentration of arsenic in the drinking water, if babies were given contaminated water. Although cord blood is an important factor in newborn infants (Samanta et al., 2007), in the present study we investigated the amount of arsenic transported to the baby only through breast milk. The PTWI of arsenic is 2.1 µg/kg bw/day (WHO, 2011b). The average body weight of babies in the present study was also estimated according to WHO Child Growth Standards (Ksiazyk & Weker, 2007). The non-carcinogenic health risk was determined for breastfeeding infants, accordingly. The distribution of point estimated daily intake (EDI) values of arsenic in contaminated and non-contaminated areas is presented in Fig. 3. The median daily intake of arsenic in contaminated areas was estimated at 0.9 μg/kg-bw/day, and the 95th percentile value of daily intake was 3.41 μg/kg-bw/day. The HQ for arsenic exposure exceeded 1.0 in 55% of breastfed infants in contaminated areas. The infants in our study appear to have been exposed to lower levels of arsenic than infants in a study from India (2.57 μg/kg-bw/day) (Samanta et al., 2007), but higher levels than infants in the USA (0.04 μg/kg-bw/day) (Carignan et al., 2015), Portugal (0.82 μg/kg-bw/day) (Almeida et al., 2008) and Japan (0.25 μg/kg-bw/day) (Sakamoto, Chan, Domingo, Kubota, & Murata, 2012). A lower median arsenic intake (0.02 μg/kg-bw/day, or 0.14 μg/kg-bw/week) was estimated by (Sternowsky, Moser, & Szadkowsky, 2002) in 3-month-old German infants (6 kg; 790 mL/day). These authors considered exposure to be safe, because it was much lower than the PTWI of 15 μg/kg-bw/week. However, HQ for arsenic exposure exceeded 1.0 for 41% of breastfed infants in non-contaminated areas that we assessed. These results suggest a potential risk from arsenic for some infants in rural areas of Kaboodrahang via the consumption of mothers’ milk. Heavy metals are classified in the environmental pollutants category due to their toxic effects on the organisms. Many studies have also shown that bladder and kidney cancers are higher in the people who have had long-term exposure to arsenic. Pulmonary disease, developmental effects, diabetes and cardiovascular disease are other undesirable health effects of long-term exposure to inorganic arsenic (WHO,
a WHO recommended guideline value for drinking water 10 μg/L (WHO, 2011a). b WHO recommended limit for As in breast milk 0.2–0.6 μg/L (Bartmess, 1990). c For samples below the limit of detection (LOD), a proxy value, i.e. LOD divided by square root 2, was used for statistical analysis (Xia et al., 2016).
than in areas with low arsenic levels in water (< 3 μg/L), where the mean concentration in breast milk was only 2.5 μg/L. These results contrast with our findings and suggests that arsenic probably enters the mother's milk from sources other than drinking water. High concentrations of arsenic in drinking water have been reported in many parts of the world (Ng, 2005). In addition to drinking water, food crops have also been considered important pathways for arsenic intake by humans (Stone, 2008), because plants can take up arsenic from the surface soils. Previous studies found that irrigation with As-contaminated waters can increase arsenic retention in soils via adsorption on soil exchange complexes (Saha & Ali, 2007). As a result, arsenic-contaminated soils and irrigation waters may increase the levels of this element food crops via plant uptake mechanisms. Interestingly, among all agricultural crops, rice accumulates the greatest concentrations of this element, probably due to its greater irrigation water requirements (Lynch, Greenberg, Pollock, & Lewis, 2014; Stone, 2008) reviewed and assessed more than 6500 data points on inorganic As and its intermediates in food, including seafood and special foods for kids, and found the seaweed/algae, rice and its byproducts as the foods with the maximum level of iAs. Arsenic concentrations in breast milk reported in earlier studies were typically low (median 1.0 μg/kg), and arsenic was frequently in the form of trivalent iAs (Tillett, 2008). However, some studies, including the present work, reported the high levels of arsenic in breast milk. This finding might be due to the exposure with high concentrations of arsenic via drinking water and dietary intake, and the eating seafood, particularly shellfish by mothers (Samanta et al., 2007). The exposure of babies to arsenic via drinking water and/or formula prepared with drinking water has also been considered an important source. There is evidence that the transfer of arsenic to the mammary glands is limited, which in turn protect newborns against As exposure 4
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Fig. 3. Distribution of estimated daily intake (EDI) of arsenic in infants living in (a) contaminated areas and (b) non-contaminated areas.
Funding information
2018). Arsenic is also associated with adverse pregnancy outcomes and infant mortality, with impacts on child health (Quansah et al., 2015), and exposure in utero and in early childhood has been linked to increases in mortality in young adults due to multiple cancers, lung disease, heart attacks, and kidney failure (Farzan, Karagas, & Chen, 2013).
This project was financially supported by the School of Public Health, Hamadan University of Medical Sciences (Grant number: 9604132341). Compliance with ethical standards
4.3. Study limitations Ethical approval was obtained from the Human Research Ethics Committee, Medical University of Hamadan, Iran. Breastfeeding mothers provided their informed written consent, agreed to provide samples, and received no payment for their participation.
The main limitations of this study are: 1) Due to the low population of the studied villages, the number of samples were also low, which reduced the precision of our analysis; 2) We did not determine the arsenic levels in irrigation waters or soils, or its uptake by crops, nor did we investigate the relationship between these factors; 3) We did not measure arsenic concentrations in urine, hair or nail samples of infants, nor did we test their correlation with concentrations in their mothers’ urine, hair or nails; 4) We did not study variables such as the consumption of rice and its byproducts, seafood, or vegetables (times per week or month), and also did not investigate insecticide application in the study area. Therefore, the possible effects of these factors on the levels of arsenic in breast milk remains to be determined. The possible associations between increased arsenic concentrations in breast milk and its concentrations in fish, rice and vegetables should also be evaluated in a prospective, longitudinal study.
Conflicts of interest The authors declare that they have no conflict of interest. Acknowledgements The authors would like to thank the Hamadan University of Medical Sciences‒Deputy of Health staff for cooperation in sample collection and all lactating mothers who voluntarily participated in the study. We thank K. Shashok (AuthorAID in the Eastern Mediterranean) for improving the use of English in the manuscript. References
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