Effects of exposure to neonicotinoids on estrogen homeostasis in pregnant women
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摘要:
目的 探究孕妇新烟碱类杀虫剂暴露对雌激素稳态的影响。 方法 选取上海市某一行政区151名孕妇作为研究对象,对孕妇进行问卷调查和随机尿液收集。采用超高效液相色谱串联四级杆飞行时间质谱仪测定尿液中8种新烟碱类杀虫剂(噻虫嗪、噻虫胺、吡虫啉、啶虫脒、噻虫啉、烯啶虫胺、氯噻啉和呋虫胺)、4种代谢物(去甲基噻虫嗪、去甲基噻虫胺、5-羟基-吡虫啉和去甲基啶虫脒)和3种雌激素(雌酮、雌二醇、雌三醇)。采用方差分析和多元线性回归分析孕妇新烟碱类杀虫剂暴露对雌激素水平的影响。 结果 孕妇尿液中新烟碱类杀虫剂及其代谢物总检出率为93.38%,总浓度中位数为2.66 μg/g。啶虫脒及N-去甲基-啶虫脒检出率最高(78.15%),吡虫啉及5-羟基-吡虫啉检出率最低(12.58%)。方差分析发现尿液中检出噻虫嗪及N-去甲基-噻虫嗪的孕妇雌酮水平更高,而尿液中检出噻虫胺及N-去甲基-噻虫胺的孕妇雌二醇和雌三醇水平更低。多元线性回归分析发现,尿液中全部新烟碱类杀虫剂水平与雌酮水平呈正相关(β=0.137,95% CI:0.019~0.256)。尿液中噻虫嗪及N-去甲基-噻虫嗪水平和啶虫脒及N-去甲基-啶虫脒水平与雌酮水平呈正相关(β=0.154,95% CI:0.032~0.275;β=0.157,95% CI:0.028~0.286)。 结论 上海市孕妇可能普遍暴露于新烟碱类杀虫剂,且孕期新烟碱类杀虫剂暴露可能影响雌激素稳态。 Abstract:Objective To investigate the effect of neonicotinoids (NEOs) on estrogen homeostasis during pregnancy. Methods A total of 151 pregnant women in one administrative district of Shanghai were selected as study participants. A questionnaire survey was used and urine samples were collected. The concentrations of eight NEOs (thiamethoxam, clothianidin, imidacloprid, acetamiprid, thiacloprid, nitenpyram, midaclothiz and dinotefuran), four metabolites (N-desmethyl-thiamethoxam, N-desmethyl-clothianidin, 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid) and three estrogens (estrone, estradiol and estriol) in their urine were determined by ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. ANOVA and multiple linear regression were used to analyze the effect of NEOs exposure levels on estrogen levels in pregnant women. Results The detection rate of NEOs and their metabolites in urine samples of pregnant women was 93.38%, with a median urinary NEOs concentration of 2.66 μg/g. The acetamiprid and N-desmethyl-acetamiprid had the highest detection rate (78.15%), while the imidacloprid and 5-hydroxy-imidacloprid had the lowest. ANOVA found that higher urinary estrone levels in pregnant women with detectable thiamethoxam and N-desmethyl-thiamethoxam, while lower urinary estradiol and estriol levels in pregnant women with detectable clothianidin and N-desmethyl-clothianidin. Multiple linear regression analysis showed a positive association between urinary all NEOs levels and estrone levels in pregnant women regression coefficient (β=0.137, 95% CI: 0.019-0.256). Urinary thiamethoxam and N-desmethyl-thiamethoxam levels, and urinary acetamiprid and N-desmethyl-acetamiprid levels were positively correlated with estrone levels in pregnant women (β=0.154, 95% CI: 0.032-0.275; β=0.157, 95% CI: 0.028-0.286). Conclusions Pregnant women in Shanghai may be generally exposed to NEOs, and the exposure level of NEOs during pregnancy may affect estrogen homeostasis. -
Key words:
- Pregnant women /
- Neonicotinoid pesticides /
- Estrogen homeostasis /
- Urine /
- Exposed
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表 1 孕妇尿液中新烟碱类杀虫剂暴露情况
Table 1. Neonicotinoids exposure in pregnant women
新烟碱杀虫剂Neonicotinoids 总体All (n=151) 孕早期(< 13周) First trimester (< 13 weeks)(n=54) 检出率/% Detection rate/% 浓度百分位数① Concentration percentile ① 检出率/% Detection rate/% 浓度百分位数① Concentration percentile ① 50 th 95 th 50 th 95 th 噻虫嗪及N-去甲基-噻虫嗪Thiamethoxam and N-desmethyl-thiamethoxam 68.87 0.41 4.43 66.67 0.31 2.33 噻虫嗪Thiamethoxam 68.87 0.41 4.43 66.67 0.31 2.33 N-去甲基-噻虫嗪N-desmethyl-thiamethoxam — — — — — — 噻虫胺及N-去甲基-噻虫胺Clothianidin and N-desmethyl-clothianidin 76.16 0.69 6.96 77.78 0.65 5.87 噻虫胺Clothianidin 75.50 0.41 3.49 77.78 0.38 2.46 N-去甲基噻虫胺N-desmethyl-clothianidin 44.37 — 3.59 50.00 0.26 4.25 吡虫啉及5-羟基-吡虫啉Imidacloprid and 5-hydroxy-imidacloprid 12.58 — 0.71 9.26 — 0.26 吡虫啉Imidacloprid 12.58 — 0.71 9.26 — 0.26 5-羟基-吡虫啉5-hydroxy-imidacloprid — — — — — — 啶虫脒及N-去甲基-啶虫脒Acetamiprid and N-desmethyl-acetamiprid 78.15 1.04 9.51 74.07 0.76 7.64 啶虫脒Acetamiprid 2.65 — — 3.70 — 0.10 N-去甲基-啶虫脒N-desmethyl-acetamiprid 78.15 1.04 9.41 74.07 0.76 7.64 其他Other 13.91 — 2.10 11.11 — 1.61 氯噻啉Midaclothiz - — — — — — 呋虫胺Dinotefuran 2.65 — — 3.70 — — 烯啶虫胺Nitenpyram 11.92 — 1.39 7.40 — 0.94 噻虫啉Thiacloprid - — — — — 0.52 全部All 93.38 2.66 19.99 90.74 2.06 12.93 新烟碱杀虫剂Neonicotinoids 孕中期(13~27周) Second trimester (13-27 weeks) (n=52) 孕晚期(≥28周) Third trimester (≥28 weeks) (n=45) 检出率/% Detection rate/% 浓度百分位数① Concentration percentile ① 检出率/% Detection rate/% 浓度百分位数① Concentration percentile ① 50 th 95 th 50 th 95 th 噻虫嗪及N-去甲基-噻虫嗪Thiamethoxam and N-desmethyl-thiamethoxam 69.23 0.47 4.96 71.11 0.47 4.15 噻虫嗪Thiamethoxam 69.23 0.47 4.96 71.11 0.47 4.15 N-去甲基-噻虫嗪N-desmethyl-thiamethoxam — — — — — — 噻虫胺及N-去甲基-噻虫胺Clothianidin and N-desmethyl-clothianidin 75.00 0.82 9.29 75.56 0.47 8.00 噻虫胺Clothianidin 75.00 0.54 3.84 73.33 0.40 4.39 N-去甲基噻虫胺N-desmethyl-clothianidin 44.23 — 3.96 37.78 — 3.61 吡虫啉及5-羟基-吡虫啉Imidacloprid and 5-hydroxy-imidacloprid 13.46 — 1.16 15.56 — 1.99 吡虫啉Imidacloprid 13.46 — 1.16 15.56 — 1.99 5-羟基-吡虫啉5-hydroxy-imidacloprid — — — — — — 啶虫脒及N-去甲基-啶虫脒Acetamiprid and N-desmethyl-acetamiprid 80.77 1.12 11.10 80.00 1.05 9.15 啶虫脒Acetamiprid 1.92 — — 2.22 — — N-去甲基-啶虫脒N-desmethyl-acetamiprid 80.77 1.12 11.10 80.00 1.05 9.15 其他Other 13.46 — 2.49 17.78 — 4.14 氯噻啉Midaclothiz — — — — — — 呋虫胺Dinotefuran 1.92 — — 2.22 — — 烯啶虫胺Nitenpyram 11.54 — 2.39 17.78 — 4.14 噻虫啉Thiacloprid — — — — — — 全部All 94.23 3.28 21.89 95.56 3.25 20.23 注:—,低于检出限。
①表示肌酐校正浓度/(μg·g-1)。
Note: —, below the limit of detection.
①indicates creatinine-adjusted concentration/(μg·g-1).表 2 孕妇尿液中新烟碱类杀虫剂与尿液雌激素水平的方差分析
Table 2. ANOVA of urinary neonicotinoids exposure levels and urinary estrogen levels in pregnant women
新烟碱类杀虫剂Neonicotinoids 模型Model 占比/% Proportion/% 雌酮Estrone 雌二醇Estradiol 雌三醇Estriol 浓度Concentration [M(P25, P75)] P值① value P‘值② value 浓度Concentration [M(P25, P75)] P值① value P‘值② value 浓度Concentration [M(P25, P75)] P值① value P‘值② value 噻虫嗪及N-去甲基-噻虫嗪Thiamethoxam and N-desmethyl-thiamethoxam 检出Detected 68.87 41.14 (15.06, 118.46) 0.049 0.008 22.02 (8.56, 40.39) 0.487 0.271 150.84 (30.38, 551.49) 0.793 0.825 未检出Undetected 31.13 30.55 (5.79, 100.71) 17.27 (7.09, 39.27) 122.88 (35.99, 569.65) 噻虫胺及N-去甲基-噻虫胺Clothianidin and N-desmethyl-clothianidin 检出Detected 76.16 30.58 (11.67, 98.65) 0.548 0.756 16.68 (7.46, 38.69) 0.054 0.043 96.64 (29.55, 517.89) 0.029 0.008 未检出Undetected 23.84 63.34 (13.29, 120.58) 31.33 (16.33, 39.97) 354.20 (69.55, 709.17) 吡虫啉及5-羟基-吡虫啉Imidacloprid and 5-hydroxy-imidacloprid 检出Detected 12.58 92.34 (22.90, 160.99) 0.137 0.543 36.69 (7.77, 43.04) 0.204 0.727 457.20 (44.84, 893.71) 0.059 0.108 未检出Undetected 87.42 34.30 (11.20, 102.62) 17.42 (8.43, 37.76) 119.34 (29.93, 527.38) 啶虫脒及N-去甲基-啶虫脒Acetamiprid and N-desmethyl-acetamiprid 检出Detected 78.15 40.82 (13.33, 107.78) 0.143 0.110 22.02 (8.46, 40.95) 0.118 0.092 166.75 (31.20, 576.43) 0.702 0.747 未检出Undetected 21.85 28.95 (7.80, 104.04) 16.89 (6.56, 36.88) 107.24 (40.66, 507.50) 其他③ Other ③ 检出Detected 13.91 51.49 (13.97, 148.03) 0.487 0.407 23.10 (7.94, 49.33) 0.572 0.627 306.42 (37.14, 778.04) 0.418 0.483 未检出Undetected 86.75 38.41 (11.58, 101.81) 18.89 (9.28, 38.84) 127.08 (31.20, 532.84) 全部All 检出Detected 93.38 39.66 (13.18, 105.39) 0.204 0.237 20.52 (8.51, 39.46) 0.506 0.690 143.03 (31.84, 562.86) 0.800 0.847 未检出Undetected 6.62 22.82 (5.35, 119.88) 13.97 (5.31, 50.30) 92.15 (32.81, 612.58) 注:①单因素方差分析。②校正年龄(年)、孕周(周)、受教育水平和家庭年总收入后的多因素方差分析。③包始氯噻啉、呋虫胺、烯啶虫胺和噻虫啉。
Note: ① analysis of Variance (ANOVA); ②ANOVA adjusted for age (years), gestational weeks, education level, and total annual household income; ③ includes midaclothiz, dinotefuran, nitenpyram and thiacloprid.表 3 孕妇尿液中新烟碱类杀虫剂与尿液雌激素水平的多元线性回归
Table 3. Multiple linear regression of urinary neonicotinoids exposure levels and urinary estrogen levels in pregnant women
新烟碱类杀虫剂Neonicotinoids 模型Model 雌酮Estrone 雌二醇Estradiol 雌三醇Estriol β值(95% CI) β value(95% CI) P值value 浓β值(95% CI) β value(95% CI) P值value β值(95% CI) β value(95% CI) P值value 噻虫嗪及N-去甲基-噻虫嗪Thiamethoxam and N-desmethyl-thiamethoxam 未校正Unadjusted 0.200(0.055, 0.346) ② 0.007 0.116(0.000, 0.231) 0.049 0.165(-0.003, 0.333) 0.054 校正Adjusted 0.154(0.032, 0.275) ③ 0.013 0.084(-0.015, 0.182) 0.096 0.063(-0.041, 0.168) 0.232 噻虫胺及N-去甲基-噻虫胺Clothianidin and N-desmethyl-clothianidin 未校正Unadjusted 0.018(-0.117, 0.153) 0.793 -0.056(-0.161, 0.049) 0.293 -0.077(-0.230, 0.075) 0.318 校正Adjusted 0.048(-0.063, 0.160) 0.393 -0.040(-0.130, 0.049) 0.375 -0.052(-0.146, 0.041) 0.270 吡虫啉及5-羟基-吡虫啉Imidacloprid and 5-hydroxy-imidacloprid 未校正Unadjusted 0.329(0.081, 0.577) 0.010 0.205(0.010, 0.401) 0.040 0.401(0.119, 0.682) 0.006 校正Adjusted 0.164(-0.049, 0.377) 0.130 0.079(-0.092, 0.250) 0.362 0.174(-0.004, 0.353) 0.056 啶虫脒及N-去甲基-啶虫脒Acetamiprid and N-desmethyl-acetamiprid 未校正Unadjusted 0.157 (0.028, 0.286) 0.017 0.119(0.018, 0.219) 0.021 0.095(-0.051, 0.240) 0.201 校正Adjusted 0.114(0.006, 0.221) 0.038 0.086(0.000, 0.171) 0.051 -0.009(-0.099, 0.081) 0.848 其他① Other ① 未校正Unadjusted 0.072(-0.119, 0.263) 0.457 0.057(-0.093, 0.206) 0.455 0.111(-0.106, 0.327) 0.314 校正Adjusted 0.044(-0.114, 0.202) 0.585 0.039(-0.087, 0.165) 0.542 0.053(-0.080, 0.185) 0.433 全部All 未校正Unadjusted 0.162(0.019, 0.306) 0.027 0.070(-0.043, 0.183) 0.220 0.054(-0.109, 0.217) 0.515 校正Adjusted 0.137(0.019, 0.256) 0.023 0.049(-0.047, 0.145) 0.315 -0.016(-0.116, 0.084) 0.751 注:①包括氯噻啉、呋虫胺、烯啶虫胺和噻虫啉; ②表示未校正回归系数(95% CI);③表示校正年龄(年)、孕周(周)、受教育水平、家庭年总收入的回归系数(95% CI)。
Notes: ① includes midaclothiz, dinotefuran, nitenpyram and thiacloprid; ② indicates unadjusted regression coefficients (95% CI); ③ indicates regression coefficients (95% CI) adjusted for age (years), gestational weeks, education level, and total annual household income. -
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