Table 1.
Characteristics of studies included for dose-response meta-analysis.
| Study (year) | Design | Cases | Person or Person-years | Exposure Media | Concentration Category | Median | RR (95% CI) | ||
|---|---|---|---|---|---|---|---|---|---|
| Mortality | |||||||||
| CHD | |||||||||
| Chen et al. [15] (2011) | ir | 14 | 20,064 | water (µg/L) | 0.1–12.0 | 2.3 | 1 (referent) | ||
| 16 | 19,109 | 12.1–62.0 | 34.0 | 1.22 | 0.56 | 2.65 | |||
| 15 | 18,699 | 62.1–148.0 | 101.0 | 1.49 | 0.70 | 3.19 | |||
| 26 | 19,380 | 148.1–864.0 | 237.0 | 1.94 | 0.99 | 3.84 | |||
| D’Ippoliti et al. [29] (2015) | ir | 684 | 771,860 | water (µg/L) | < 10 | 7.4 | 1 (referent) | ||
| 573 | 713,276 | 10–20 | 12.9 | 1.40 | 1.19 | 1.64 | |||
| 1014 | 904,129 | > 20 | 29.7 | 1.46 | 1.07 | 2.01 | |||
| Medrano et al. [74] (2010) | ci | 88,566 | 18,978,000 | water (µg/L) | < 1 | 0.7 | 1 (referent) | ||
| 19,709 | 4,803,000 | 1–10 | 3.9 | 1.05 | 1.01 | 1.10 | |||
| 4725 | 1,011,000 | > 10 | 23.3 | 1.02 | 0.96 | 1.08 | |||
| Moon et al. [63] (2013) | ir | 68 | 13,616 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 67 | 13,430 | 5.8–9.7 | 7.5 | 0.99 | 0.70 | 1.41 | |||
| 87 | 12,720 | 9.8–15.7 | 12.4 | 1.18 | 0.83 | 1.69 | |||
| 119 | 12,033 | > 15.7 | 21.8 | 1.71 | 1.19 | 2.44 | |||
| Chen et al. [81] (1996) | ir | 4 | 2748 | water (µg/L) | < 10 | 5 | 1 (referent) | ||
| 5 | 1417 | 10–500 | 255 | 3.30 | 0.80 | 13.69 | |||
| 16 | 4309 | ≥ 510 | 755 | 5.30 | 1.49 | 18.85 | |||
| Wade et al. [79] (2009) | ir | 44 | 14,636 | water (µg/L) | 0–5 | 1.1 | 1 (referent) | ||
| 26 | 9047 | 5.1–20 | 11.8 | 1.07 | 0.64 | 1.78 | |||
| 72 | 21,367 | 20.1–100 | 26.2 | 1.22 | 0.82 | 1.82 | |||
| 17 | 3313 | 100.1–300 | 156.1 | 1.55 | 0.88 | 2.73 | |||
| 2 | 249 | Over 300 | 387.9 | 2.47 | 0.50 | 12.18 | |||
| Farzan et al. [19] (2015) | ir | 57 | 898 | toenail (µg/g) | 0.01–0.07 | 0.05 | 1 (referent) | ||
| 51 | 852 | 0.07–0.11 | 0.09 | 1.13 | 0.77 | 1.67 | |||
| 46 | 754 | 0.11–3.26 | 0.23 | 1.22 | 0.82 | 1.82 | |||
| CVD | |||||||||
| Chen et al. [15] (2011) | ir | 43 | 20,064 | water (µg/L) | 0.1–12.0 | 2.3 | 1 (referent) | ||
| 51 | 19,109 | 12.1–62.0 | 34.0 | 1.21 | 0.80 | 1.84 | |||
| 41 | 18,699 | 62.1–148.0 | 101.0 | 1.24 | 0.80 | 1.93 | |||
| 63 | 19,380 | 148.1–864.0 | 237.0 | 1.46 | 0.96 | 2.20 | |||
| Sohel et al. [80] (2009) | ir | 147 | 114,068 | water (µg/L) | < 10 | 0.7 | 1 (referent) | ||
| 168 | 139,233 | 10–49 | 31.8 | 1.03 | 0.82 | 1.29 | |||
| 463 | 365,496 | 50–149 | 95.0 | 1.16 | 0.96 | 1.40 | |||
| 318 | 241,930 | 150–299 | 201.2 | 1.23 | 1.01 | 1.51 | |||
| 115 | 78,786 | > 300 | 371.5 | 1.37 | 1.07 | 1.77 | |||
| D’Ippoliti et al. [29] (2015) | ir | 2752 | 771,860 | water (µg/L) | < 10 | 7.4 | 1 (referent) | ||
| 2115 | 713,276 | 10–20 | 12.9 | 1.28 | 1.08 | 1.51 | |||
| 3514 | 904,129 | > 20 | 29.7 | 1.36 | 1.06 | 1.74 | |||
| Medrano et al. [74] (2010) | ci | 285,049 | 18,978,000 | water (µg/L) | < 1 | 0.7 | 1 (referent) | ||
| 62,739 | 4,803,000 | 1–10 | 3.9 | 1.02 | 0.99 | 1.06 | |||
| 13,962 | 1,011,000 | > 10 | 23.3 | 1.03 | 0.98 | 1.08 | |||
| Moon et al. [63] (2013) | ir | 86 | 13,616 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 95 | 13,430 | 5.8–9.7 | 7.5 | 1.12 | 0.83 | 1.52 | |||
| 115 | 12,720 | 9.8–15.7 | 12.4 | 1.26 | 0.92 | 1.73 | |||
| 143 | 12,033 | > 15.7 | 21.8 | 1.65 | 1.20 | 2.27 | |||
| Wade et al. [79] (2009) | ir | 97 | 14,636 | water (µg/L) | 0–5 | 1.1 | 1 (referent) | ||
| 42 | 9047 | 5.1–20 | 11.8 | 0.72 | 0.32 | 1.60 | |||
| 113 | 21,367 | 20.1–100 | 26.2 | 0.79 | 0.34 | 1.86 | |||
| 24 | 3313 | 100.1–300 | 156.1 | 0.62 | 0.10 | 3.70 | |||
| 3 | 249 | Over 300 | 387.9 | 1.70 | 0.51 | 5.72 | |||
| Farzan et al. [19] (2015) | ir | 125 | 1987 | toenail (µg/g) | 0.01–0.07 | 0.05 | 1 (referent) | ||
| 103 | 1691 | 0.07–0.11 | 0.09 | 1.04 | 0.80 | 1.35 | |||
| 84 | 1334 | 0.11–3.26 | 0.23 | 0.99 | 0.74 | 1.32 | |||
| Wang, et al. [82] (2005) | ir | 428 | 19,360 | water (µg/L) | <10 | 5.0 | 1 (referent) | ||
| 84 | 2130 | 10–49 | 29.5 | 0.95 | 0.74 | 1.21 | |||
| 116 | 2317 | 50–499 | 274.5 | 1.34 | 1.08 | 1.66 | |||
| 60 | 1165 | ≥500 | 724.5 | 1.80 | 1.36 | 2.38 | |||
| Stroke | |||||||||
| D’Ippoliti et al. [29] (2015) | ir | 660 | 771,860 | water (µg/L) | < 10 | 7.4 | 1 (referent) | ||
| 448 | 713,276 | 10–20 | 12.9 | 1.33 | 1.12 | 1.58 | |||
| 789 | 904,129 | > 20 | 29.7 | 1.44 | 1.16 | 1.78 | |||
| Farzan et al. [19] (2015) | ir | 15 | 233 | toenail (µg/g) | 0.01–0.07 | 0.05 | 1 (referent) | ||
| 16 | 243 | 0.07–0.11 | 0.09 | 1.28 | 0.64 | 2.61 | |||
| 12 | 161 | 0.11–3.26 | 0.23 | 1.10 | 0.50 | 2.40 | |||
| Rahman et al. [17] (2014) | ir | 62 | 38,198 | water (µg/L) | < 10 | 1.7 | 1 (referent) | ||
| 196 | 156,362 | 10–49 | 21.1 | 1.20 | 0.92 | 1.57 | |||
| 271 | 42,579 | > 50 | 102.2 | 1.35 | 1.04 | 1.75 | |||
| Moon et al. [63] (2013) | ir | 6 | 13,616 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 17 | 13,430 | 5.8–9.7 | 7.5 | 1.41 | 0.54 | 3.67 | |||
| 13 | 12,720 | 9.8–15.7 | 12.4 | 2.16 | 0.77 | 6.09 | |||
| 18 | 12,033 | > 15.7 | 21.8 | 3.03 | 1.08 | 8.50 | |||
| Chen et al. [15] (2011) | ir | 43 | 20,064 | water (µg/L) | 0.1–12.0 | 2.3 | 1 (referent) | ||
| 51 | 19,109 | 12.1–62.0 | 34.0 | 1.35 | 0.75 | 2.43 | |||
| 41 | 18,699 | 62.1–148.0 | 101.0 | 1.20 | 0.63 | 2.27 | |||
| 63 | 19,380 | 148.1–864.0 | 237.0 | 1.07 | 0.54 | 2.12 | |||
| Wade et al. [79] (2009) | ir | 53 | 14,636 | water (µg/L) | 0–5 | 1.1 | 1 (referent) | ||
| 16 | 9047 | 5.1–20 | 11.8 | 0.47 | 0.27 | 0.84 | |||
| 41 | 21,367 | 20.1–100 | 26.2 | 0.51 | 0.34 | 0.79 | |||
| 7 | 3313 | 100.1–300 | 156.1 | 0.25 | 1.10 | 2.95 | |||
| 1 | 249 | Over 300 | 387.9 | 1.02 | 0.16 | 6.71 | |||
| Medrano et al. [74] (2010) | ci | 81,368 | 18,978,000 | water (µg/L) | < 1 | 0.7 | 1 (referent) | ||
| 18,327 | 4,803,000 | 1–10 | 3.9 | 1.00 | 0.99 | 1.05 | |||
| 3895 | 1,011,000 | > 10 | 23.3 | 1.02 | 0.95 | 1.09 | |||
| Fatal and non-fatal | |||||||||
| Carotid atherosclerosis disease | |||||||||
| Wu et al. [69] (2006) | cc | 25 | 64 | water (µg/L) | ≤ 50.00 | 25 | 1 (referent) | ||
| 46 | 95 | 50.01–100.00 | 75 | 1.90 | 0.90 | 3.80 | |||
| 89 | 183 | ≥ 100.01 | 125 | 2.60 | 1.30 | 5.00 | |||
| Hsieh et al. [72] (2008) | cc | 17 | 48 | water (µg/L) | < 10 | 5 | 1 (referent) | ||
| 23 | 61 | 10.1–50 | 30 | 1.80 | 1.00 | 3.20 | |||
| 195 | 370 | > 50 | 70 | 1.90 | 1.10 | 3.10 | |||
| Hsieh et al. [73] (2011) | cc | 24 | 55 | water (µg/L) | < 10 | 5 | 1 (referent) | ||
| 31 | 81 | 10.1–50.0 | 30 | 1.53 | 0.67 | 3.50 | |||
| 325 | 720 | > 50.0 | 70 | 2.01 | 1.05 | 3.85 | |||
| CHD | |||||||||
| Wade et al. [83] (2015) | cc | 168 | 305 | water (µg/L) | < 10 | 1.9 | 1 (referent) | ||
| 105 | 236 | 10–39 | 16.0 | 1.23 | 0.78 | 1.93 | |||
| 11 | 26 | > 40 | 58.6 | 4.05 | 1.10 | 14.99 | |||
| Moon et al. [63] (2013) | ir | 202 | 12,146 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 206 | 11,701 | 5.8–9.7 | 7.5 | 1.05 | 0.86 | 1.28 | |||
| 197 | 11,305 | 9.8–15.7 | 12.4 | 0.95 | 0.77 | 1.19 | |||
| 241 | 10,586 | > 15.7 | 21.8 | 1.30 | 1.04 | 1.62 | |||
| James et al. [84] (2015) | ir | 58 | 4806 | water (µg/L) | 1–20 | 5.7 | 1 (referent) | ||
| 18 | 1335 | 20–30 | 25.3 | 1.25 | 0.70 | 2.31 | |||
| 16 | 534 | 30–45 | 35.1 | 2.14 | 1.22 | 3.98 | |||
| 4 | 98 | 45–88 | 50.5 | 3.12 | 1.12 | 9.02 | |||
| Chen et al. [20] (2013) | ir | 61 | 2823 | water (µg/L) | 0.1–25 | 5.1 | 1 (referent) | ||
| 72 | 2718 | 25.1–107 | 57.0 | 1.18 | 0.75 | 1.84 | |||
| 75 | 2770 | 108–864 | 198.5 | 1.54 | 1.02 | 2.31 | |||
| CVD | |||||||||
| Moon et al. [63] (2013) | ir | 265 | 12,146 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 297 | 11,701 | 5.8–9.7 | 7.5 | 1.14 | 0.95 | 1.35 | |||
| 291 | 11,305 | 9.8–15.7 | 12.4 | 1.05 | 0.87 | 1.26 | |||
| 331 | 10,586 | > 15.7 | 21.8 | 1.32 | 1.05 | 1.28 | |||
| Chen et al. [20] (2013) | ir | 114 | 2823 | water (µg/L) | 0.1–25 | 5.1 | 1 (referent) | ||
| 120 | 2718 | 25.1–107 | 57.0 | 1.00 | 0.67 | 1.50 | |||
| 132 | 2770 | 108–864 | 198.5 | 1.49 | 1.06 | 2.11 | |||
| Hypertension | |||||||||
| Wang et al. [71] (2011) | ir | 93 | 618 | water (µg/L) | < 538 | 269 | 1 (referent) | ||
| 103 | 721 | 538–700 | 619 | 1.18 | 0.60 | 2.34 | |||
| 83 | 634 | > 700 | 781 | 0.83 | 0.40 | 1.68 | |||
| Jones et al. [26] (2011) | ir | 418 | 952 | urine (µg/L) | < 4.2 | 2.1 | 1 (referent) | ||
| 451 | 1057 | 4.2 to 8.3 | 6.3 | 1.08 | 0.83 | 1.40 | |||
| 446 | 1090 | > 8.3 to 17.1 | 12.7 | 1.30 | 0.94 | 1.80 | |||
| 446 | 1068 | > 17.1 | 21.5 | 1.17 | 0.75 | 1.83 | |||
| Chen et al. [75] (2007) | cc | 289 | 2242 | water (µg/L) | 0.1–8.0 | 2.8 | 1 (referent) | ||
| 274 | 2116 | 8.1–40.8 | 23.2 | 1.10 | 0.90 | 1.33 | |||
| 273 | 2187 | 40.9–91.0 | 63.9 | 1.03 | 0.85 | 1.25 | |||
| 259 | 2181 | 91.1–176.0 | 128.1 | 1.01 | 0.83 | 1.22 | |||
| 265 | 2184 | 176.1–864.0 | 283.1 | 1.02 | 0.84 | 1.23 | |||
| Islam et al. [67] (2012) | cc | 22 | 291 | water (µg/L) | 10–22 | 15.5 | 1 (referent) | ||
| 19 | 208 | 23–32 | 27.5 | 1.33 | 0.67 | 2.62 | |||
| 13 | 252 | 33–261 | 180.0 | 1.10 | 0.49 | 2.44 | |||
| 12 | 243 | ≥ 262 | 376.0 | 0.96 | 0.42 | 2.23 | |||
| Li et al. [66] (2013) | cc | 29 | 120 | water (µg/L) | < 100 | 61.0 | 1 (referent) | ||
| 30 | 119 | 100 to 350 | 223.8 | 1.20 | 0.63 | 2.29 | |||
| 45 | 121 | > 350 | 427.7 | 1.87 | 1.02 | 3.42 | |||
| Mendez et al. [59] (2016) | cc | 106 | 260 | water (µg/L) | < 25.5 | 12.8 | 1 (referent) | ||
| 106 | 260 | 25.5–47.9 | 36.7 | 1.30 | 0.84 | 2.00 | |||
| 109 | 259 | 47.9–79.0 | 63.5 | 1.27 | 0.82 | 1.94 | |||
| 118 | 259 | ≥ 79.0 | 94.6 | 1.41 | 0.91 | 2.17 | |||
| Hall et al. [16] (2017) | cc | 140 | 323 | water (µg/L) | < 60 | 30.0 | 1 (referent) | ||
| 246 | 482 | 60–859 | 459.5 | 1.33 | 0.98 | 1.79 | |||
| 225 | 450 | > 859 | 1258.5 | 1.42 | 1.04 | 1.92 | |||
| Rahman et al. [70] (1999) | cc | 9 | 114 | water (µg/L) | < 0 | 2 | 1 (referent) | ||
| 50 | 623 | 0–500 | 250 | 1.20 | 0.60 | 2.30 | |||
| 93 | 576 | 500–1000 | 750 | 2.20 | 1.10 | 4.30 | |||
| 55 | 282 | > 1000 | 1250 | 2.50 | 1.20 | 4.90 | |||
| Stroke | |||||||||
| Tsinovoi et al. [36] (2018) | ir | 150 | 637 | water (µg/L) | 2.72–3.72 | 3.3 | 1 (referent) | ||
| 138 | 622 | 4.75–5.88 | 5.3 | 0.97 | 0.73 | 1.30 | |||
| 139 | 624 | 8.26–9.18 | 8.1 | 1.03 | 0.77 | 1.38 | |||
| 119 | 606 | 11.99–16.72 | 13.9 | 0.87 | 0.64 | 1.18 | |||
| 125 | 608 | 26.11–54.81 | 34.1 | 1.01 | 0.74 | 1.36 | |||
| Moon et al. [63] (2013) | ir | 55 | 12,146 | urine (µg/g creatinine) | < 5.8 | 4.2 | 1 (referent) | ||
| 75 | 11,701 | 5.8–9.7 | 7.5 | 1.18 | 0.82 | 1.69 | |||
| 62 | 11,305 | 9.8–15.7 | 12.4 | 1.16 | 0.77 | 1.72 | |||
| 72 | 10,586 | > 15.7 | 21.8 | 1.47 | 0.97 | 2.21 | |||
| Chen et al. [20] (2013) | ir | 50 | 2823 | water (µg/L) | 0.1–25 | 5.1 | 1 (referent) | ||
| 46 | 2718 | 25.1–107 | 57.0 | 0.86 | 0.49 | 1.51 | |||
| 52 | 2770 | 108–864 | 198.5 | 1.38 | 0.84 | 2.27 | |||
| Ersboll et al. [57] (2018) | ir | 486 | 172,202 | water (µg/L) | 0.049–0.573 | 0.435 | 1 (referent) | ||
| 657 | 180,891 | 0.573–0.760 | 0.584 | 1.21 | 1.07 | 1.36 | |||
| 475 | 169,470 | 0.760–1.933 | 1.174 | 1.05 | 0.92 | 1.19 | |||
| 577 | 173,856 | 1.933–25.34 | 2.109 | 1.17 | 1.04 | 1.32 | |||
| CVD markers | |||||||||
| Pulse blood pressure (SBP-DBP ≥ 55 mmHg)) | |||||||||
| Chen et al. [75] (2007) | cc | 205 | 2242 | water (µg/L) | 0.1–8.0 | 2.8 | 1 (referent) | ||
| 252 | 2116 | 8.1–40.8 | 23.2 | 1.39 | 1.14 | 1.71 | |||
| 232 | 2187 | 40.9–91.0 | 63.9 | 1.21 | 0.99 | 1.49 | |||
| 227 | 2181 | 91.1–176.0 | 128.1 | 1.19 | 0.97 | 1.45 | |||
| 233 | 2184 | 176.1–864.0 | 283.1 | 1.19 | 0.97 | 1.46 | |||
| Islam et al. [67] (2012) | cc | 5 | 291 | water (µg/L) | 10–22 | 15.5 | 1 (referent) | ||
| 10 | 208 | 23–32 | 27.5 | 3.87 | 1.22 | 12.2 | |||
| 10 | 252 | 33–261 | 180.0 | 4.32 | 1.23 | 15.11 | |||
| 16 | 243 | ≥ 262 | 376.0 | 7.32 | 2.18 | 24.60 | |||
| QT prolongation | |||||||||
| Chen et al. [85] (2013) | ir | 57 | 371 | water (µg/L) | 0.1–9 | 2.8 | 1 (referent) | ||
| 63 | 369 | 9.5–57 | 30.0 | 1.10 | 0.74 | 1.63 | |||
| 49 | 374 | 58–144 | 95.1 | 0.87 | 0.57 | 1.31 | |||
| 68 | 353 | 145–790 | 254.5 | 1.31 | 0.87 | 1.96 | |||
| Mumford et al. [68] (2007) | cc | 4 | 103 | water (µg/L) | < 21 | 10.7 | 1 (referent) | ||
| 12 | 108 | 100–350 | 199.9 | 3.83 | 1.13 | 12.99 | |||
| 21 | 102 | 430–690 | 568.3 | 8.85 | 2.72 | 28.75 | |||
CVD: cardiovascular disease; CHD: coronary heart disease. RR: Relative risk or approximation of the relative risk (rate ratio, risk ratio, odds ratio). ir: Risks estimated in the studies as rate ratio (incidence-rate data); ci: Risks estimated in the studies as risk ratio (cumulative incidence data); cc: Risks estimated in the studies as an odds ratio (see details reported by Orsini et al. [65]).