Associations of urinary polycyclic aromatic hydrocarbon metabolites with neurobehavioral function changes in coke oven workers
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摘要:
目的 探讨某焦化厂工人尿中多环芳烃(polycyclic aromatic hydrocarbons, PAHs)代谢物与神经行为功能改变的关系。 方法 2017年对山西省某焦化厂的672名工人进行基本情况调查、神经行为功能测试和尿中多环芳烃羟基代谢物(polycyclic aromatic hydrocarbons hydroxyl metabolites, OH-PAHs)的检测；于2021年进行随访，共461名工人完成神经行为功能测试。采用WHO推荐的神经行为测试组合(neurobehavioral core test battery, NCTB)对工人神经行为功能进行测试；使用高效液相色谱-串联质谱联用(high performance liquid chromatography with tandem mass spectrometry, HPLC-MS/MS)检测尿中OH-PAHs和尿中可替宁。使用广义线性模型和广义估计方程分析工人尿中OH-PAHs与神经行为功能的关系。 结果 研究对象基线年龄为34(30, 46)岁，男性占比69.2%。纵向研究中，2-羟基萘(2-hydroxynaphthalene, 2-OHNAP)高暴露组的顺序数字跨度(β=-0.50, 95% CI: -0.81~-0.18, P=0.002)和总数字跨度得分(β=-0.77, 95% CI: -1.38~-0.16, P=0.014)降低；2-羟基芴(2-hydroxyfluorene, 2-OHFLU)高暴露组的平均反应时间明显延长(β=26.90, 95% CI: 7.86~45.93, P=0.006)，习惯手提转捷度(β=-1.30, 95% CI: -2.43~-0.17, P=0.024)和非习惯手提转捷度得分(β=-1.19, 95% CI: -2.23~-0.15, P=0.025)降低。 结论 长期暴露于高浓度多环芳烃环境中会导致焦化厂工人神经行为功能降低。 -
关键词:
- 多环芳烃 /
- 神经行为 /
- 神经行为核心测试组合 /
- 广义估计方程
Abstract:Objective To investigate the associations between urinary polycyclic aromatic hydrocarbons (PAHs) metabolites and changes in coke oven workers' neurobehavioral function. Methods In 2017, 672 workers in a coking plant in Shanxi Province were investigated for basic conditions, neurobehavioral function tests and urinary PAHs detection. With follow-up in 2021, a total of 461 workers completed neurobehavioral functional tests. Neurobehavioral function was measured by neurobehavioral core test battery questionnaire. The concentrations of urinary PAHs metabolites and cotinine were determined by high-performance liquid chromatography-mass spectrometry. Generalized linear models and generalized estimation equations were used to analyze the association between urinary PAHs metabolites and neurobehavioral function. Results A total of 461 participants completed the investigation, the age was 34 (30, 46) years, and 69.2% was male at baseline. In the longitudinal study, forward digit span (β=-0.50, 95% CI: -0.81--0.18, P=0.002) and total digit span scores (β=-0.77, 95% CI: -1.38--0.16, P=0.014) were significantly lower in the 2-hydroxynaphthalene (2-OHNAP) high-exposure group; the mean reaction time (β=26.90, 95% CI: 7.86-45.93, P=0.006) was significantly longer in the 2-hydroxynaphthalenc (2-OHNAP) high-exposure group, the preferred hand (β=-1.30, 95% CI: -2.43--0.17, P=0.024) and non-preferred hand Santa Ana dexterity test (β=-1.19, 95% CI: -2.23--0.15, P=0.025) scores were significantly reduced in the 2-OHFLU high-exposure group. Conclusion Long-term exposure to polycyclic aromatic hydrocarbons reduces neurobehavioral function in coke oven workers. -
表 1 2020年中国工业企业接触噪声劳动者分布特征[n(%)]
Table 1. Distribution characteristics of workers exposed to noise in Chinese industrial enterprises in 2020 [n(%)]
变量 总人数
(N=461)∑-OH PAHs低暴露组
(n=230)∑-OH PAHs高暴露组
(n=231)t/χ2值 P值 年龄[M(P25, P75), 岁] 34(30, 46) 42.5(32, 47) 32(30, 44) 5.80 < 0.001 性别 4.20 0.041 男 319(69.2) 146(32.32) 170(36.88) 女 142(30.8) 81(17.57) 61(13.23) 文化程度 2.58 0.275 初中及以下 86(18.66) 49(10.63) 37(8.03) 高中 95(20.61) 43(9.33) 52(11.28) 大专及以上 280(60.74) 138(29.93) 142(30.80) 吸烟 0.39 0.534 否 268(58.13) 137(29.72) 131(28.42) 是 193(41.87) 93(20.17) 100(21.69) 饮酒 4.67 0.031 否 334(72.45) 177(38.39) 157(34.06) 是 127(27.55) 53(11.50) 74(16.05) 饮茶 2.46 0.117 否 283(61.39) 133(28.85) 150(32.54) 是 178(38.61) 97(21.04) 81(17.57) 运动 7.11 0.029 从不运动 150(32.54) 65(14.10) 85(18.44) 偶尔运动 201(43.60) 99(21.48) 102(22.13) 经常运动 110(23.86) 66(14.32) 44(9.54) 夜班 8.81 0.003 无夜班 111(24.08) 69(14.97) 42(9.11) 有夜班 350(75.92) 161(34.92) 189(41.00) 尿中可替宁[M(P25, P75), ng/mL] 46.23(5.00, 1 322.35) 41.65(4.15, 1 322.35) 52.32(5.46, 1 377.96) -1.35 0.178 基线NCTB测试(x±s) 平均反应时间(ms) 449.51±93.57 462.59±99.37 436.48±85.66 3.02 0.003 顺序数字跨度 10.60±2.21 10.38±2.23 10.83±2.19 -2.18 0.030 倒序数字跨度 6.65±2.55 6.62±2.63 6.68±2.49 -0.24 0.808 总数字跨度 17.23±4.23 16.98±4.30 17.48±4.16 1.27 0.203 习惯手提转捷度 43.14±5.95 42.49±5.66 43.79±6.17 2.36 0.019 非习惯手提转捷度 40.67±5.62 39.97±5.54 41.36±5.64 2.67 0.008 数字译码 49.53±14.75 47.25±14.75 51.80±14.42 3.35 0.001 视觉记忆 7.30±1.68 7.12±1.76 7.49±1.59 -2.38 0.018 目标追踪 184.45±44.93 179.77±44.53 189.11±44.94 2.24 0.025 第2次NCTB测试(x±s) 平均反应时间(ms) 472.02±105.14 482.46±116.87 461.63±91.07 3.02 0.003 顺序数字跨度 11.66±2.02 11.65±2.01 11.67±2.04 -2.18 0.030 倒序数字跨度 6.59±2.85 6.26±2.67 6.93±2.99 -0.24 0.808 总数字跨度 18.24±4.09 17.89±3.84 18.59±4.31 1.27 0.203 习惯手提转捷度 42.44±5.96 41.44±6.07 43.44±5.69 -2.36 0.019 非习惯手提转捷度 40.03±5.44 39.51±5.21 41.01±5.25 -2.67 0.008 数字译码 47.56±13.35 45.35±14.22 49.77±12.06 -3.35 0.001 视觉记忆 8.06±3.87 7.77±1.80 8.35±5.16 -2.38 0.018 目标追踪 176.19±43.90 170.23±43.57 184.10±43.59 -2.24 0.025 
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表 2 尿中OH-PAHs分布(n=461)
Table 2. Distribution of urinary OH-PAHs (n=461)
尿中OH-PAHs 检出限 检出率(%) P25
(ng/mL)P50
(ng/mL)P75
(ng/mL)2-OHNAP 0.001 4 99.57 0.13 0.29 0.62 1-OHNAP 0.008 8 77.29 0.01 0.03 0.06 3-OHFLU 0.009 6 85.57 0.01 0.03 0.06 2-OHFLU 0.014 1 96.00 0.07 0.15 0.29 2-OHPHE 0.006 1 100.00 0.12 0.19 0.32 9-OHPHE 0.009 1 99.43 0.07 0.11 0.18 1-OHPHE 0.013 0 89.71 0.03 0.06 0.11 1-OHPYR 0.010 3 99.86 0.06 0.09 0.15
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3a 基线研究中尿中OH-PAHs与神经行为功能的关系(n=461)
3a. Relationship between urinary OH-PAHs and neurobehavioral function at baseline (n=461)
变量 平均反应时间 顺序数字跨度 倒序数字跨度 总数字跨度 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 ∑-OH-PAHs 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -9.81(-25.75~6.13) 0.228 0.08(-0.32~0.49) 0.689 -0.26(-0.75~0.22) 0.282 -0.16(-0.94~0.63) 0.694 2-OHNAP 低暴露组 0.00 0.00 0.00 0.00 高暴露组 5.43(-12.60~23.47) 0.555 -0.37(-0.83~0.09) 0.119 -0.67(-1.21~-0.13) 0.016 -1.11(-1.99~-0.23) 0.013 1-OHNAP 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -13.50(-31.34~4.33) 0.138 0.46(-0.01~0.91) 0.050 -0.13(-0.67~0.40) 0.632 0.42(-0.45~1.29) 0.344 3-OHFLU 低暴露组 0.00 0.00 0.00 0.00 高暴露组 14.24(-4.09~32.57) 0.128 0.06(-0.41~0.53) 0.808 0.18(-0.37~0.73) 0.519 0.12(-0.77~1.02) 0.791 2-OHFLU 低暴露组 0.00 0.00 0.00 0.00 高暴露组 13.17(-5.73~32.07) 0.172 0.35(-0.13~0.83) 0.157 0.46(-0.11~1.02) 0.114 0.98(-0.01~1.90) 0.038 2-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -8.37(-28.08~11.34) 0.405 0.03(-0.47~0.54) 0.893 -0.45(-1.04~0.14) 0.139 -0.52(-1.48~0.45) 0.294 9-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -10.28(-28.14~7.57) 0.259 -0.28(-0.74~0.18) 0.230 -0.29(-0.82~0.25) 0.297 -0.57(-1.44~0.30) 0.201 1-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -5.08(-24.40~14.24) 0.606 -0.01(-0.50~0.49) 0.972 0.03(-0.55~0.61) 0.929 0.06(-0.89~1.00) 0.908 1-OHPYR 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -2.59(-20.14~14.96) 0.772 0.00(-0.45~0.45) 0.988 0.19(-0.34~0.72) 0.479 0.17(-0.69~1.03) 0.699
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3b 基线研究中尿中OH-PAHs与神经行为功能的关系(n=461)
3b. Relationship between urinary OH-PAHs and neurobehavioral function at baseline (n=461)
变量 习惯手提转捷度 非习惯手提转捷度 数字译码 视觉记忆 目标追踪 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 ∑-OH PAHs 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.91(-0.19~2.00) 0.104 0.97(-0.09~2.02) 0.073 1.36(-0.65~3.38) 0.185 0.13(-0.17~0.43) 0.397 5.74(-2.35~13.83) 0.164 2-OHNAP 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 -0.40(-1.64~0.84) 0.528 -0.44(-1.65~0.76) 0.470 -1.02(-3.30~1.26) 0.379 0.10(-0.24~0.44) 0.565 -4.36(-13.53~4.81) 0.352 1-OHNAP 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 -0.40(-1.63~0.82) 0.519 -0.05(-1.24~1.14) 0.932 -0.38(-2.64~1.87) 0.738 -0.22(-0.56~0.12) 0.204 1.03(-8.04~10.11) 0.823 3-OHFLU 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.98(-0.28~2.24) 0.129 0.30(-0.92~1.53) 0.626 -1.58(-3.89~0.74) 0.182 0.40(0.05~0.74) 0.026 3.43(-5.89~12.75) 0.471 2-OHFLU 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 -0.79(-2.09~0.51) 0.236 -0.65(-1.91~0.61) 0.310 0.63(-1.76~3.02) 0.605 0.02(-0.34~0.37) 0.929 -2.57(-12.18~7.04) 0.600 2-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.31(-1.04~1.67) 0.651 0.85(-0.47~2.16) 0.206 1.13(-1.37~3.62) 0.376 -0.09(-0.47~0.28) 0.622 2.31(-7.71~12.33) 0.652 9-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.55(-0.68~1.78) 0.382 0.06(-1.13~1.25) 0.926 0.26(-2.00~2.52) 0.823 0.06(-0.27~0.40) 0.711 5.28(-3.81~14.36) 0.255 1-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.50(-0.83~1.83) 0.460 -0.18(-1.47~1.11) 0.783 0.30(-2.14~2.74) 0.812 0.08(-0.29~0.44) 0.675 -4.03(-13.86~5.79) 0.421 1-OHPYR 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.09(-1.11~1.30) 0.879 0.51(-0.66~1.68) 0.391 1.55(-0.67~3.77) 0.170 -0.07(-0.4~0.26) 0.680 6.76(-2.16~15.69) 0.138
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4a 纵向研究中尿中OH-PAHs与神经行为功能的关系(n=461)
4a. Relationship between urinary OH-PAHs and neurobehavioral function in longitudinal study (n=461)
变量 平均反应时间 顺序数字跨度 倒序数字跨度 总数字跨度 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 ∑-OH PAHs 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -5.54(-20.31~9.23) 0.462 -0.05(-0.32~0.22) 0.701 0.07(-0.31~0.45) 0.718 0.04(-0.51~0.60) 0.873 2-OHNAP 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -3.73(-21.06~13.60) 0.673 -0.50(-0.81~-0.18) 0.002 -0.25(-0.66~0.15) 0.218 -0.77(-1.38~-0.16) 0.014 1-OHNAP 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -8.00(-25.99~9.99) 0.384 0.33(-0.02~0.65) 0.037 -0.02(-0.42~0.38) 0.911 0.37(-0.25~0.99) 0.238 3-OHFLU 低暴露组 0.00 0.00 0.00 0.00 高暴露组 10.04(-8.52~28.61) 0.289 0.09(-0.23~0.41) 0.579 0.09(-0.35~0.53) 0.686 0.11(-0.53~0.75) 0.743 2-OHFLU 低暴露组 0.00 0.00 0.00 0.00 高暴露组 26.90(7.86~45.93) 0.006 0.09(-0.24~0.42) 0.596 0.213 0.45(-0.21~1.11) 0.181 2-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -4.46(-21.92~13.00) 0.617 0.14(-0.21~0.49) 0.427 -0.35(-0.82~0.12) 0.149 -0.27(-0.96~0.42) 0.445 9-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -8.84(-25.93~8.24) 0.310 0.06(-0.25~0.38) 0.691 0.07(-0.37~0.50) 0.765 0.13(-0.51~0.76) 0.698 1-OHPHE 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -8.21(-24.29~7.88) 0.317 -0.09(-0.43~0.25) 0.591 0.18(-0.29~0.65) 0.453 0.11(-0.58~0.79) 0.762 1-OHPYR 低暴露组 0.00 0.00 0.00 0.00 高暴露组 -12.25(-29.33~4.83) 0.160 -0.02(-0.32~0.28) 0.898 0.21(-0.20~0.63) 0.306 0.18(-0.42~0.78) 0.554
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4b 纵向研究中尿中OH-PAHs与神经行为功能的关系(n=461)
4b. Relationship between urinary OH-PAHs and neurobehavioral function in longitudinal study (n=461)
变量 习惯手提转捷度 非习惯手提转捷度 数字译码 视觉记忆 目标追踪 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 β (95% CI)值 P值 ∑-OH-PAHs 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.87(-0.06~1.80) 0.067 0.71(-0.14~1.56) 0.102 1.35(-0.33~3.04) 0.116 0.12(-0.19~0.43) 0.449 5.75(-0.84~12.33) 0.087 2-OHNAP 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.23(-0.82~1.29) 0.664 0.28(-0.67~1.23) 0.560 0.44(-1.48~2.36) 0.652 0.19(-0.19~0.57) 0.327 6.01(-1.52~13.54) 0.118 1-OHNAP 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 -0.14(-1.18~0.90) 0.796 -0.21(-1.16~0.75) 0.671 0.07(-1.79~1.93) 0.940 -0.05(-0.37~0.28) 0.776 -1.47(-9.02~6.08) 0.704 3-OHFLU 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.87(-0.11~1.85) 0.083 0.74(-0.26~1.73) 0.145 -0.74(-2.77~1.29) 0.474 0.23(-0.05~0.52) 0.107 3.39(-4.43~11.21) 0.395 2-OHFLU 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 -1.30(-2.43~-0.17) 0.024 -1.19(-2.23~-0.15) 0.025 -0.25(-2.21~1.71) 0.802 -0.16(-0.46~0.14) 0.287 -3.19(-10.88~4.51) 0.417 2-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.18(-0.95~1.32) 0.749 0.38(-0.75~1.50) 0.510 -0.04(-2.05~1.97) 0.973 0.11(-0.18~0.39) 0.458 0.80(-6.97~8.57) 0.840 9-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.51(-0.44~1.46) 0.292 0.25(-0.71~1.21) 0.605 0.49(-1.40~2.37) 0.614 0.09(-0.19~0.36) 0.541 3.05(-4.22~10.32) 0.411 1-OHPHE 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.49(-0.56~1.54) 0.363 0.30(-0.76~1.35) 0.583 0.25(-1.62~2.12) 0.792 0.03(-0.32~0.37) 0.876 -3.29(-11.02~4.45) 0.405 1-OHPYR 低暴露组 0.00 0.00 0.00 0.00 0.00 高暴露组 0.41(-0.54~1.37) 0.395 0.43(-0.51~1.37) 0.373 1.46(-0.37~3.28) 0.118 0.13(-0.16~0.41) 0.381 3.71(-3.48~10.91) 0.312
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