As exposure has been an important public health problem in many countries, causing several adverse effects at different stages of life [24]. There are few reports on UAs in infants, and the reference limits of urinary As are not uniform owing to differences in regions, diets and levels of environmental pollution. In this research, our results here showed that the UAs levels did not follow a normal distribution. Therefore, we identified the upper limit of the total UAs content as 962.35 µg/gCr (unadjusted Cr, 209.56 µg/L). This value was higher than the upper limit of the UAs found in 2–10 years old children in China’s interior (27.51 µg/L or 55.88 µg/gCr) [28] and in other countries (Canada (18 µg/L)[36], the USA(65.4 µg/L) [37], , and Chile (125 µg/L) [38]). Most of the studies were aimed at children over 2 years old, while infants had higher urinary arsenic levels than children, so further attention should be paid to the health problems of foods exposed to As in infants.
We found three major factors affecting total UAs in infants. Breast feeding could affect UAs in infants. Rebelo and Caldas reviewed the studies conducted from 2000 to 2016 to assess the risk of As exposure in breast milk and found that As levels in breast milk were higher among those living in As-contaminated areas [39]. Regional studies in Lebanon have shown that As contamination in breast milk was mainly associated with intake of cereals and fish [40]. Additionally, according to a Chinese study, inorganic As in breast milk posed a health risk in newborns, and thus, breast feeding was a risk factor for elevated UAs [41]. This study also found that breast-feeding was a risk factor for elevated UAs, suggesting that breast-feeding mothers exposed to higher levels of As may be through the transfer of As from breast milk to infants. Since the presence of As in breast milk influences exposure to As among infants, it should be considered as a health problem. Breastfeeding mothers need to be made aware of the As contamination in different food to avoid excessive exposure to As.
Food As contamination could affect total UAs in infants. Xiamen is the main polluted area near the coast of Fujian, and owing to serious marine pollution, marine life is exposed to pollutants. These pollutants enter the food chain, and in turn the human body, through consumption of seafood. Studies showed that the Japanese seabass (Lateolabrax japonicus) and red seabream (Pagrus major) in the coastal waters of south Fujian revealed that the As level in the muscle of the both species was generally higher than Chin’s national standard (༞1.0 microg/g ), and The contents of total mercury and total arsenic in most of the marine cultured oysters in Xiamen Bay were significantly higher than those in other sea areas along the southern coast of Fujian [42, 43]. The detection of vegetable, fruit, seafood and meat consumption and heavy metal content of Xiamen residents showed that arsenic poses the greatest health risk. For residents who consume a large scale of fruits, vegetables and seafood, the carcinogenic risk of arsenic deserves attention [27, 44, 45]. While most studies found that from 2007 to 2015, the survey results on the drinking water quality of Xiamen residents showed that the arsenic content of Xiamen residents' drinking water did not exceed the drinking water national health standard limit (༜0.5mg/L). The arsenic intake of Xiamen residents mainly comes from food[46–49]. In this study, dietary habits were found to be associated with UAs levels in infants. The higher the intake of seafood, the higher the UAs content. Pollution of the marine environment and contamination of seafood in Xiamen[45] are reflected in the UAs level in infants, and they might cause chronic harm to all inhabitants of Xiamen, including infants.
The fluctuations in UAs content with age in infants are related to food sources. The urinary As content among infants aged 1–3 months was significantly higher than that among those aged 3–6 months, which may be because breast milk was the main food source at this stage, and lactating women consume more seafood contaminated with As. An explanation for the positive correlation between the age and total UAs for 6–36-month-old infants is that there may be an increased exposure to exogenous As due to direct consumption of seafood, vegetable, meat and so on, even though their exposure to As from breast milk was reduced. Other studies also found increased urinary As concentrations in infants to be associated with increased exposure to As during the transition to solid food, suggesting the need to minimize exposure during this critical developmental period[50, 51].
In this study, four As species (iAsⅢ, iAsⅤ, MMAV, and DMAV) were detected in the urine samples. Different sources of As exposure, exposure dose and exposure population affect As metabolites, and the toxicity of As varies greatly with its valence state. From the experimental results (Refer Table 2), the As content of DMAV was relatively high, but iAsⅢ had the highest detection rate and its toxicity was found to be much higher than that of DMAV (185 times higher). Therefore, considering the detection rate, toxicity, and As content of iAsⅢ, it could be used as a marker for As exposure. The detection rate and combined toxicity of different As forms are different because the amount and levels of these species might differ in each infant. Although the detection rates for iAsⅢ+DMAV and iAsⅢ+DMAV+iAsⅤ were similar, the toxicity of iAsⅢ+DMAV+iAsⅤ was the highest. We also found that the unmethylated rate for iAsⅢ+DMAV+iAsⅤ was also the highest. Therefore, iAsⅢ+DMAV+iAsⅤ was found to be the most important combination for evaluating the combined toxicity of As exposure in infants.
This study calculated the unmethylated proportion in infants to be 38.57%, It was observed that the lower the age, the higher the concentration of non-methylated As species. However, the the unmethylated proportionin adults ranges from 20–25%, regardless of exposure level [52]. The concentration of non-methylated As species was found to be higher in infants, indicating that infants have a weaker metabolic capacity [53]. The correlation analysis showed that the amount of detectable As species in urine was positively correlated with UAs concentrations. The higher the amount of detectable As species, the lower the unmethylated proportion. A study on the correlation between seafood intake and UAs levels found that seafood intake was a significant factor contributing to the increase in total urinary As and DMA[54]. Hence, in addition to the methylation ability of infants, the intake of seafood may affect the As transformation as well as the total UAs levels in infants[55].
As metabolism is closely related to toxicity, and it exerts its toxicity by inhibiting approximately 200 enzymes involved in cellular energy pathways and DNA synthesis and repair[56]. As metabolic toxicity in processes involved in cardiovascular dysfunction, diabetes development, neurotoxicity, hepatotoxicity, and nephrotoxicity by increasing production of reactive oxygen species (ROS), thereby increasing lipid peroxidation and cell damage[1, 56, 57]. Since the methylation capacity is lower than that of adults, the effect of As toxicity on the growth and development of infants deserves attention. Long-term ingestion of arsenic in food or water will inhibit the immune function of infants, resulting in slow growth and development[58], weight loss and underweight[59]; some studies have found that the neurotoxicity of As will affect the intelligence of adult children, possibly by affecting acetylcholinease activity at synapses[60, 61]. We need to further strengthen the monitoring of metal content in the food intake of infants and nursing mothers, and at the same time, we need to strengthen the effect of environmental arsenic pollution on the accumulation of As in food, and control the risk of As exposure from the food source.