3.1 Nasal symptoms
The results of the physical examinations are shown in Table 1. The proportion of abnormal nasal symptoms, including dry nose, itching nose, running nose, hyposmia, and frequent nosebleeds, in the exposure group (10.1%) was much higher than in the control group (0; p < 0.05). In line with our previous report (Xu et al. 2021), the results in this study suggest that residents living in proximity to electroplating factories might suffer nasal impairment. Animal studies have confirmed metal-induced olfactory impairment, especially Cd-related damage. A German study reported that Cd exposure could impair olfaction in zebrafish and further disrupt their antipredator response (Volz et al. 2020). Another study reported that Cd and Zn, but not As or Cr, could inhibit zebrafish olfaction at environmental concentrations (Heffern et al. 2018). It was also revealed that Cu and Ni exposure impairs the olfactory system of fathead minnows and yellow perch (Dew et al. 2014). Moreover, Cd exposure also induced olfactory impairment in male mice (Wang et al. 2018). Regarding epidemiological studies, occupational exposure to Cd was found to be highly correlated with olfactory dysfunction (Mascagni et al. 2003; Rose et al. 1992; Shaham et al. 1993). In addition, Cr-exposed workers exhibited distinct nasal septum perforations and anosmia in an Indian study (Aiyer &Kumar 2003). The underlying mechanism for the correlations between metal exposure and olfactory dysfunction remains unclear. It has been speculated that Cd may inhibit neurogenesis in the olfactory bulb and hippocampus, contributing to persistent olfaction impairment (Czarnecki et al. 2011; Wang et al. 2018). Further studies are needed to confirm our results and explore the underlying mechanism.
3.2 Metal and metalloid levels
Blood and urinary levels of the metals and metalloids above the LOD are shown in Figs. 1 and 2, as well as Table S2. Urinary levels were adjusted by creatinine levels. Both the blood and urinary levels of As, Cd, and Se in the exposure group were significantly greater than those in the control group (p < 0.05). The blood levels of Mn and Pb and the urinary levels of Cr and Ni in the exposure group were significantly higher compared to the control group (p < 0.05). No significant difference was found between these two groups regarding blood Sb and urinary Pb levels (p > 0.05). We further categorized the data according to different gender and smoking subgroups, and the results are shown in Tables S3–S4. The urinary Cd, Cr, and Se levels in males were significantly below the levels in females (1.70 vs. 2.75 µg/g creatinine, 2.24 vs. 3.21 µg/g creatinine, and 29.28 vs. 40.08 µg/g creatinine, respectively; p < 0.05). The blood Cd levels were significantly higher in the smoking group compared to the non-smoking group (2.43 vs. 1.27 µg/L; p < 0.05). No other prominent discrepancy was found between these subgroups (p > 0.05).
Cd exposure is the most prevalent for workers in the electroplating, battery-production, and pigment industries (Zhang & Reynolds 2019), similarly for residents living near these industries. The mean blood and urinary Cd levels were 1.84 µg/L and 3.09 µg/g creatinine, respectively, in the exposure group of this study—remarkably higher than the levels in the general population in China (B-Cd: 1.34 µg/L in men, 0.49 µg/L in women; U-Cd: 0.38 µg/g creatinine in men, 0.42 µg/g creatinine in women) (Wang et al. 2016a); Korea (B-Cd: 0.59 µg/L) (Eom et al. 2018); Canada (B-Cd: 0.29–0.34 µg/L; U-Cd: 0.33µg/g creatinine) (Haines et al. 2017; Valcke et al. 2019); Japan (U-Cd: 1.3 µg/g creatinine) (Suwazono et al. 2011); Northern Laos (U-Cd: 1.07 µg/g creatinine) (Mizuno et al. 2022); Spain (U-Cd: 0.39 µg/g creatinine) (Grau-Perez et al. 2017); and the United States (B-Cd:0.35 µg/L; U-Cd: 0.21 µg/g creatinine) (Buser et al. 2016; Crinnion 2010). However, the Cd levels in the participants in the present study were not as elevated as those reported in residents from other polluted areas, such as an area in China with high Cd pollution (B-Cd: 3.31 µg/L; U-Cd: 8.97 µg/g creatinine) (Liang et al. 2012); a Cd-contaminated river (U-Cd: 25.82 µg/g creatinine) (Zhang et al. 2014); a zinc-smelting area in Guizhou Province (B-Cd: 4.0 µg/L; U-Cd: 3.7 µg/g creatinine) (Chen et al. 2019); and a tungsten–molybdenum mining area in South China (U-Cd: 11.84 µg/g creatinine) (Cui et al. 2018). Nevertheless, urinary Cd levels were higher than the results in our previous study on the electroplating industries (U-Cd: 2.44 µg/g creatinine) (Xu et al. 2021), an industrial zone in Northwest Shanghai (U-Cd: 2.08 µg/g creatinine) (Jin et al. 2020), and also a coking plant (U-Cd: 1.04–1.17 µg/g creatinine) (Wang et al. 2019). In sum, the results indicated a certain extent of Cd contamination of the local population living around the electroplating industry zone.
Regarding other metals and metalloids, we have listed several recent studies determining the blood or urinary levels of multiple metals in general populations (see Table 2). Except for blood Se, almost all the metal levels in our study were above those in the established literature, including domestic investigations in Wuhan (Wu et al. 2018, Zeng et al. 2019) and Guangzhou (Huang et al. 2022), as well as overseas surveys like the Canadian Health Measures Survey (2007–2019) (Haines et al. 2017), the IMEPOGE study of Northern France (2008–2010) (Nisse et al. 2017), the American National Health and Nutrition Examination Survey (Buser et al. 2016, Yao et al. 2021), and the exploration of Northern Laos (Mizuno et al. 2022). Furthermore, we gained insight through studies on other polluted areas. Compared to residents living in an industrial zone in Northwest Shanghai (B-Pb: 27.02 µg/L; U-As: 69.53 µg/g creatinine) (Jin et al. 2020), the blood Pb and urinary As levels in our subjects were substantially elevated. However, both the blood and urinary Pb levels were far below the body burdens of residents recruited from a zinc-smelting area in China (B-Pb: 131.2 µg/L; U-Pb: 20.6 µg/g creatinine) (Chen et al. 2019). When compared to a study on residents living in the area surrounding a landfill in France (B-Pb: 120.95 µg/L; U-Pb: 4.21 µg/g creatinine) (Cabral et al. 2021), the blood Pb levels were lower in our study, but the urinary Pb levels were higher. Moreover, the population living in the central area near the non-ferrous metal plants in Ath, Belgium (B-Pb: 31.2 µg/L in men, 22.5 µg/L in women; U-Cr: 0.13 µg/g creatinine in men, 0.17 µg/g creatinine in women; U-Ni: 0.65 µg/g creatinine in men, 1.30 µg/g creatinine in women) (Fierens et al. 2016), demonstrated similar blood Pb levels to those in our study, although the Belgian study had higher urinary Cr levels and lower urinary Ni levels. In general, the body burdens of metals and metalloids in our study were widely elevated compared to the general population but fluctuated when compared to the results from studies in other polluted areas.
Table 2
Blood and urinary levels of metals and metalloids in general populations around the world *
Country | B-As | B-Cd | B-Mn | B-Pb | B-Sb | B-Se | U-As | U-Cd | U-Cr | U-Ni | U-Pb | U-Se | |
China a | 10.4 | 1.84 | 20.9 | 35.49 | 2.87 | 120.47 | 107.19 | 3.09 | 3.48 | 2.34 | 16.43 | 42.02 | This study |
China b | 9.1 | 1.45 | 20.11 | 32.89 | 2.74 | 117.03 | 69.73 | 2.52 | 2.43 | 0.42 | 9.21 | 34.14 |
China c | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 | 8.96 |
China b | 2.25 | 0.7 | 12.40 | 17.84 | / | / | / | / | / | / | / | / | (Zeng et al. 2019) |
China c | 1.13 | 0.05 | 0.93 | / | / | 98.74 | / | / | / | / | / | / | (Huang et al. 2022) |
China b | / | / | / | / | / | / | 27.5 | 0.64 | 1.08 | 2.08 | 2.17 | 19.8 | (Wu et al. 2018) |
Canada b | 0.88 | 0.34 | 9.2 | 13 | / | 200 | / | / | / | / | / | / | (Haines et al. 2017) |
France b | 1.67 | 0.39 | 7.71 | 18.8 | 0.05 | / | / | / | / | / | / | / | (Nisse et al. 2017) |
US a | / | 0.52 | / | 1.71 | / | / | 20.49 | 0.4 | / | / | 0.78 | / | (Yao et al. 2021) |
US b | / | 0.35 | / | 1.23 | / | / | / | / | / | / | / | / | (Buser et al. 2016) |
Laos b | / | / | / | / | / | / | 30.0 | 1.07 | / | / | 1.4 | 8.73 | (Mizuno et al. 2022) |
* µg/L for blood levels; µg/g creatinine for urinary levels. |
a Arithmetic mean; b Geometric mean; c Median. |
Overall, our results indicated that residents accustomed to living around the electroplating factories were still bearing high body burdens of metals and metalloids despite the absence of ongoing exposure. Follow-up studies are necessary to determine whether the metal contamination will decline over time after the migration of the electroplating factories.
3.3 Renal assessment
Subjects’ urinary NAG, RBP, and BMG levels were determined to assess early renal impairment. All three indicators were adjusted by urinary creatinine. As shown in Fig. 3 and Table S2, the exposure group displayed higher levels of NAG, RBP, and BMG compared to the control group (0.51 vs. 0.14 mg/g creatinine, 12.79 vs. 9.26 IU/g creatinine, 1.39 vs. 0.78 mg/g creatinine, respectively; p < 0.05). After dividing the data into different gender and smoking subgroups (Table S3-S4), we found that the urinary RBP and BMG levels were significantly higher in males compared to females (1.48 vs. 0.97 mg/g creatinine, 0.58 vs. 0.25, mg/g creatinine, respectively; p < 0.05). Furthermore, the urinary RBP levels in smoking subjects were statistically higher than those in non-smoking subjects (1.53 vs. 1.05 mg/g creatinine; p < 0.05).
NAG, RBP, and BMG have been extensively used as biomarkers for early kidney dysfunction. NAG is an intracellular lysosomal enzyme indicating tubular cell damage (Wang et al. 2016a), while RBP and BMG are low-molecular-weight proteins sensitive to proximal tubular reabsorption dysfunction (Shen et al. 2021). First, we compared our results with the levels in general population. From 2013 to 2014, a total of 1,235 subjects were enrolled in a Chinese study designed to explore low-dose Cd exposure associated with early kidney damage in the general population (Wang et al. 2016a). The NAG levels (10.31 IU/g creatinine in men, 10.09 IU/g creatinine in women) in the Wang et al. study were slightly lower than the levels in our study (11.85 IU/g creatinine in men, 11.0 IU/g creatinine in women), while the BMG levels (0.37 mg/g creatinine in men, 0.28 mg/g creatinine in women) were lower in men but similar in women (0.58 mg/g creatinine in men, 0.25 mg/g creatinine in women). In addition, the NAG (4.2 IU/g creatinine) and RBP (0.19 mg/g creatinine) levels in a pilot study on a subset of the Canadian Longitudinal Study on Aging (Valcke et al. 2019) were far below our results (NAG: 12.79 IU/g creatinine, RBP: 1.48 mg/g creatinine).
Next, we compared our results with studies focused on other polluted areas. A study conducted in 2006 on residents living near an area with high Cd pollution in Zhejiang Province, China (Liang et al. 2012), reported marginally lower levels of NAG (11.8 IU/g creatinine) and BMG (0.42 mg/g creatinine) compared to those in our study. Similarly, the median levels of RBP (0.20 mg/g creatinine) and BMG (0.11 mg/g creatinine) in 168 residents living in an industrial zone in Northwest Shanghai (Jin et al. 2020) were also below the levels in the present study. Another study on adults living in a tungsten–molybdenum mining area in South China (Cui et al. 2018) demonstrated higher median levels of BMG (0.34 mg/g creatinine) but lower median levels of NAG (10.02 IU/g creatinine) and RBP (0.10 mg/g creatinine). Inconsistently, the NAG levels (22.4 IU/g creatinine) in people living in the zinc-smelting area in Guizhou Province, China (Chen et al. 2019), were distinctly greater than those in our study. Compared to our previous study conducted in the same electroplating industry areas (Xu et al. 2021), the NAG levels in our study were slightly lower; however, the BMG levels were much higher (NAG: 12.79 vs. 13.04 IU/g creatinine; BMG: 0.51 vs. 0.25 mg/g creatinine).
Taken together, the renal biomarker levels in this study were generally above the levels in most of the other contemporary studies, suggesting that renal impairment has emerged in the population living near the electroplating industrial zone. Furthermore, the results also suggested that the subjects’ recruitment diversity may have caused the discrepancies in the results. Therefore, the expansion of the sample size in future studies is essential.
3.4 Metal exposure associated with renal dysfunction
In this study, correlations between metal exposure and renal dysfunction were explored. As shown in Fig. 4 and Table S5, positive correlations were discovered among urinary NAG, RBP, and BMG levels (p < 0.05). In addition, urinary BMG levels were strongly correlated with urinary Cd levels (r = 0.223; p < 0.05), while urinary RBP levels were positively correlated with blood Cd levels (r = 0.151, p < 0.05) and urinary Cd, Cr, Ni, and Se levels (r = 0.220, 0.303, 0.162, and 0.306, respectively; p < 0.05).
In agreement with our results, the Canadian Longitudinal Study on Aging also revealed a significant correlation between urinary Cd and RBP levels in the general population (r = 0.21; p < 0.05) (Valcke et al. 2019). In another study focused on populations living near non-ferrous metal plants in Belgium, no correlation was found between Cd and RBP levels in these adults; however, a positive correlation between urinary Cd and RBP levels appeared in the children (r2 = 0.24; p < 0.0001) (Fierens et al. 2016). Moreover, a Brazilian study reported urinary Cd was significantly correlated with RBP levels (β = 0.200, 95% CI: 0.074–0.365) (Martinez et al. 2021).
Despite the similarities among the studies, there are also ubiquitous differences. Discordant with the negative results for NAG in this study, our previous study, together with some of the other studies outlined above have reported positive associations between urinary Cd and NAG levels (Cui et al. 2018, Wang et al. 2016a, Xu et al. 2021). The discrepancies could be attributed to several reasons. First, the various sample sizes and means of subject recruitment may have caused the differentiation. Second, the statistical methods implemented in the studies may differ from one another, generating discrepancy in the results. Third, the distinct metal categories in different investigations may have resulted in the differences in the correlations, as co-exposure to multiple metals could propagate renal tubular dysfunction rather than exposure alone (Chen et al. 2019).
In general, a robust correlation between Cd burden and RBP elevation was revealed in this study. The literature on other metals and metalloids associated with renal biomarkers was rather limited. Therefore, studies with expanded sample size and improved experimental design are needed to verify our results.
3.5 Strengths and limitations
This cross-sectional study determined the blood and urinary levels of multiple metals and metalloids in a general population living in the proximity to a well-known electroplating industrial zone in China; renal impairment was also assessed. The literature has largely focused on occupationally exposed populations, seldom investigating the residents living near electroplating industrial zones. Meanwhile, the indicators for metal determination were usually simplex. Thus, the strengths of this study are as follows: the specific study area, the recruited population, and the multiple metal categories. Nonetheless, there were several limitations. First, the nasal symptoms in our study were self-reported, which may cause investigation bias. Second, we did not determine the metal levels in the environmental samples, and thus the exposure routes for local population remained unclear.