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Individual and joint effects of organophosphate esters and hypertension or diabetes on renal injury among Chinese adults 有机磷酸酯与高血压或糖尿病对中国成年人肾损伤的单独和联合影响
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-16 DOI: 10.1016/j.ijheh.2024.114424

Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 μg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, −0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, −0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, −0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 μg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend > 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P<0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations.

接触环境污染物以及高血压和糖尿病的发生是慢性肾脏病(CKD)的重要风险因素。毒理学研究表明,有机磷酸酯(OPE)会损害肾功能。然而,暴露于 OPE 对肾损伤的共同影响以及暴露于 OPE 与高血压或糖尿病对肾损伤的相互作用仍不清楚。我们的研究旨在调查暴露于 OPE 对肾损伤的个体和联合影响,以及暴露于 OPE 与高血压或糖尿病对肾损伤的潜在相互作用。该研究在中国武汉市招募了 1938 名参与者。为探讨暴露于 OPE 与肾损伤之间的关系,我们进行了多变量线性回归分析和逻辑回归分析。结果表明,4-羟基苯基二苯基磷酸酯 (4-HO-DPHP)、双(2-丁氧基乙基)磷酸酯 (BBOEP) 和三(2-氯乙基)磷酸酯 (TCEP) 每增加一个单位(1 μg/L-ln 转化),就会导致 0.57 mL/min/1.73 m2 (95%CI:-1.05, -0.09)、0.85 mL/min/1.而4-HO-DPHP和BBOEP(1 μg/L-ln转化)每增加一个单位,就会导致肾功能受损(IRF)风险分别增加14%和20%。值得注意的是,BCIPHIPP 的最高三分位数与 eGFR 呈正相关,但趋势 p > 0.05。我们采用贝叶斯核机器回归(BKMR)和基于四分位数的 g 计算(qgcomp)模型来探讨 OPE 混合物对 eGFR 和 IRF 的共同影响。BKMR 和 qgcomp 模型的结果一致表明,OPE 混合物与 eGFR 之间存在负相关,TCEP 和 4-HO-DPHP 是主要的影响因素。此外,我们还观察到磷酸二苯酯(DPHP)、BBOEP、磷酸二对甲酚酯(DoCP)&amp、磷酸二对甲酚酯(DpCP)、1-羟基-2-丙基双(1-氯-2-丙基)磷酸酯(BCIPHIPP)与高血压或糖尿病对肾损伤的乘法相互作用(均为 P<0.05)。与没有糖尿病或高血压的人相比,患有糖尿病或高血压且 OPE 代谢物浓度较高的人肾功能受损的风险更高。这些研究结果表明,特定的 OPE 暴露可能会增加肾损伤的风险,尤其是在高血压和糖尿病人群中。
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引用次数: 0
Phthalate exposure during pregnancy and its association with thyroid hormones: A prospective cohort study 孕期接触邻苯二甲酸盐及其与甲状腺激素的关系:一项前瞻性队列研究。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-13 DOI: 10.1016/j.ijheh.2024.114421
Iman Al-Saleh , Rola Elkhatib , Reem Alghamdi , Nujud Alrushud , Hissah Alnuwaysir , Maha Alnemer , Hesham Aldhalaan , Mohamed Shoukri

Phthalate esters (PAEs) possess endocrine-disrupting properties. Studies in humans have indicated that in utero phthalate exposure affects maternal thyroid hormones, which are essential for fetal growth and development. However, these studies also reported inconsistent results on the relationship between phthalates and thyroid hormones. This prospective cohort study aimed to assess phthalate exposure across the three trimesters of pregnancy and its association with thyroid hormone levels. From 2019 to 2022, we recruited 672 pregnant women, and two urine samples and one blood sample were collected from each participant during the pregnancy. We examined the urine samples from 663, 335, and 294 women in the first, second, and third trimester, respectively, for the following seven phthalate metabolites: monoethyl phthalate (MEP) from diethyl phthalate (DEP); mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP) from dibutyl phthalate (DBP); monobenzyl phthalate (MBzP) from butyl benzyl phthalate; and three di(2-ethylhexyl) phthalate (DEHP) metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP). Additionally, we examined the levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH), and total triiodothyronine (TT3) in the serum samples of the following participants: 596, 627, and 576 in the first trimester; 292, 293, and 282 in the second trimester; and 250, 250, and 248 in the third trimester, respectively. Other than MBzP, which was detected in 25%–33% of the samples, other metabolites were detectable in >86% of urine samples, indicating widespread exposure to DEP, DBP, and DEHP. The detected phthalate exposure levels in our cohort were significantly higher than those reported in other countries. Metabolite levels varied across the trimesters, implying changes in exposure and metabolism throughout pregnancy. The observed variability in urinary concentrations of phthalate metabolites, which ranged from poor to moderate, underscores the importance of taking multiple measurements during pregnancy for precise exposure assessment. Using a linear mixed model, we analyzed the effects of repeated phthalate exposure on thyroid hormone levels while adjusting for potential confounders. We observed significant linear trends in FT4, TSH, and, to a lesser extent, TT3 across quartiles of specific phthalate metabolites. Comparing the highest to the lowest quartiles, we found a significant increase in FT4 levels, ranging from 2 to 3.7%, associated with MEP; MECPP; MEHHP; and the sum of seven metabolites (∑7PAE), three DEHP metabolites (∑3DEHP), two DBP metabolites (∑DBP), and both low molecular weight (∑LMW) and high molecular weight metabolites. Increased TSH levels (5%–16%) were observed for all phthalate metabolites (except MEHHP) and their molar sums, including ∑7

邻苯二甲酸酯(PAEs)具有干扰内分泌的特性。对人类的研究表明,子宫内接触邻苯二甲酸酯会影响母体的甲状腺激素,而甲状腺激素对胎儿的生长和发育至关重要。然而,这些研究对邻苯二甲酸盐与甲状腺激素之间关系的研究结果并不一致。这项前瞻性队列研究旨在评估孕期三个月的邻苯二甲酸盐暴露及其与甲状腺激素水平的关系。从2019年到2022年,我们招募了672名孕妇,并为每位参与者收集了孕期的两份尿样和一份血样。我们分别对 663 名、335 名和 294 名孕妇在第一、第二和第三孕期的尿样进行了检测,以检测以下七种邻苯二甲酸酯代谢物:来自邻苯二甲酸二乙酯(DEP)的邻苯二甲酸单乙酯(MEP);来自邻苯二甲酸二丁酯(DBP)的邻苯二甲酸单正丁酯(MnBP)和邻苯二甲酸单异丁酯(MiBP);来自邻苯二甲酸丁苄酯的邻苯二甲酸单苄酯(MBzP);以及三种邻苯二甲酸二(2-乙基己基)酯(DEHP)代谢物:邻苯二甲酸单(2-乙基-5-羟基己基)酯(MEHHP)、邻苯二甲酸单(2-乙基-5-氧代己基)酯(MEOHP)和邻苯二甲酸单(2-乙基-5-羧基戊基)酯(MECPP)。此外,我们还检测了以下参与者血清样本中游离甲状腺素(FT4)、促甲状腺激素(TSH)和总三碘甲状腺原氨酸(TT3)的水平:第一孕期分别为 596、627 和 576;第二孕期分别为 292、293 和 282;第三孕期分别为 250、250 和 248。除了在 25%-33% 的样本中检测到 MBzP 外,在大于 86% 的尿液样本中检测到了其他代谢物,这表明 DEP、DBP 和 DEHP 的暴露范围很广。我们队列中检测到的邻苯二甲酸酯暴露水平明显高于其他国家的报告水平。不同孕期的代谢物水平各不相同,这意味着整个孕期的接触和代谢情况都会发生变化。观察到的尿液中邻苯二甲酸酯代谢物浓度的变化从低到高不等,这凸显了在孕期进行多次测量以精确评估暴露量的重要性。我们使用线性混合模型分析了重复接触邻苯二甲酸盐对甲状腺激素水平的影响,同时调整了潜在的混杂因素。我们观察到,在特定邻苯二甲酸酯代谢物的四分位数中,FT4、促甲状腺激素呈明显的线性趋势,其次是TT3。将最高四分位数与最低四分位数进行比较,我们发现 FT4 水平的显著增加(2%-3.7%)与 MEP、MECPP、MEHHP 以及七种代谢物之和(∑7PAE)、三种 DEHP 代谢物(∑3DEHP)、两种 DBP 代谢物(∑DBP)以及低分子量(∑LMW)和高分子量代谢物有关。所有邻苯二甲酸酯代谢物(MEHHP 除外)及其摩尔总和(包括 ∑7PAE)的 TSH 水平均出现升高(5%-16%)。就 TT3 而言,观察到 MEP 显著增加(2.2%),而 ∑DBP 则下降(-2.7%)。在几种邻苯二甲酸酯代谢物的最高四分位数(第三或第四位)中观察到较高的 TSH/FT4 比率:MEP(8.8%)、MiBP(8.7%)、MnBP(22.2%)、∑7PAE(15.3%)、∑DBP(16.4%)和∑LMW(18.6%)。这些激素变化(尤其是在第二和第三孕期)表明,接触邻苯二甲酸盐可能会通过影响母体甲状腺功能来影响胎儿的生长发育。
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引用次数: 0
Impact of antenatal exposure to a mixture of persistent organic pollutants on intellectual development 产前接触持久性有机污染物混合物对智力发育的影响。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-08 DOI: 10.1016/j.ijheh.2024.114422
Christophe Barrea , Patrice Dufour , Pirard Catherine , Corinne Charlier , Fanny Brevers , Laurence Rousselle , Anne-Simone Parent

Objective

Strong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child's cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects. We examined here the impact of a prenatal exposure to a mixture of persistent organic pollutants (POPs) on intellectual abilities in preschool children, and compared their effects to those described in the literature.

Methods

Sixty-two children were included in a longitudinal cohort. Four organochlorine pesticides, four polychlorinated biphenyls (PCBs) and seven perfluorinated compounds (PFCs) were measured in cord blood. Intellectual abilities were assessed at 6 years of age using the Wechsler Preschool and Primary Scale of Intelligence 4th ed. (WPPSI-IV). We examined the associations between a mixture of POPs and cognitive performances using principal components approach (PCA) and weighted quantile sum (WQS) regression taking sex difference into account.

Results

No negative correlation was found when analyses were performed on boys and girls together. In sex-stratified analyses, lower scores in full scale intelligence quotient (FSIQ) and fluid reasoning index (FRI) were observed in boys most exposed to a mixture of POPs. Increase of the WQS index was also associated with lower verbal comprehension index (VCI) scores in girls only. No other negative correlation was found using both WQS and PCA models.

Conclusion

Our study suggests deleterious associations between antenatal exposure to a mixture of POPs and sex-specific cognitive level, clarifying some trends described in the literature.

目的:有确凿的实验证据表明,几种干扰内分泌的化学品(EDCs)具有神经行为毒性。然而,产前暴露与儿童认知发展之间的关联证据并不一致。此外,人们通常对有毒物质进行逐一分析,而不考虑其综合影响。我们在此研究了产前接触持久性有机污染物(POPs)混合物对学龄前儿童智力的影响,并将其影响与文献中描述的影响进行了比较:方法:在一个纵向队列中纳入了 62 名儿童。测量了脐带血中的四种有机氯农药、四种多氯联苯和七种全氟化合物。我们使用韦氏学前和小学智力量表第四版(WPPSI-IV)对 6 岁儿童的智力进行了评估。我们使用主成分法(PCA)和加权量子和(WQS)回归法研究了持久性有机污染物混合物与认知能力之间的关联,并将性别差异考虑在内:对男孩和女孩一起进行分析时未发现负相关。在性别分层分析中,观察到接触持久性有机污染物混合物最多的男孩的全量表智商(FSIQ)和流体推理指数(FRI)较低。只有女孩的 WQS 指数的增加与言语理解指数(VCI)的降低有关。使用 WQS 和 PCA 模型没有发现其他负相关关系:我们的研究表明,产前暴露于持久性有机污染物混合物与特定性别的认知水平之间存在有害关联,从而澄清了文献中描述的一些趋势。
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引用次数: 0
Inflammation as a pathway for heavy metal-induced liver damage—Insights from a repeated-measures study in residents exposed to metals and bioinformatics analysis 炎症是重金属诱发肝损伤的途径--对接触金属的居民进行的重复测量研究和生物信息学分析的启示。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-04 DOI: 10.1016/j.ijheh.2024.114417
Shuanzheng Zhao , Guohuan Yin , Meiduo Zhao , Jingtao Wu , Xiaolin Liu , Lanping Wei , Qun Xu , Jing Xu

Background

Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms.

Method

We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage.

Result

We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (β = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (β = −0.21; 95% CI: −0.39, −0.03), Mn and the annual increase rate of GLB (β = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (β = −1.15; 95% CI: −2.00, −0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways.

Conclusion

Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.

背景:有关重金属暴露和肝损伤的流行病学研究主要是横断面研究,缺乏纵向数据和对潜在机制的探索:我们于 2016 年至 2019 年在中国东北地区开展了一项重复测量研究,共有 322 人参与。采用线性混合模型(LMM)和贝叶斯核机器回归(BKMR)探讨个体和混合血液金属浓度[铬(Cr)、镉(Cd)、钒(V)、锰(Mn)、铅(Pb)]与肝功能生物标志物[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(ALB)、球蛋白(GLB)、总蛋白(TP)]之间的关联。通过中介分析和富集分析,确定炎症反应是否是重金属诱发肝损伤的关键途径:结果:我们共获得 958 个观察结果。LMM和BKMR的结果表明,单个重金属和混合重金属与肝功能生物标志物之间存在显著关联。纵向分析显示,镉与谷丙转氨酶的年升高率(β = 2.61; 95% CI: 0.97, 4.26)、谷草转氨酶的年降低率(β = -0.21; 95% CI: -0.39, -0.03)、锰与谷草转氨酶的年升高率(β = 0.38; 95% CI: 0.05, 0.72)、钒与谷草转氨酶/谷草转氨酶的年降低率(β = -1.15; 95% CI: -2.00, -0.31)之间存在关联。中介分析表明,高敏 C 反应蛋白(hsCRP)在镉与谷草转氨酶、谷丙转氨酶之间的关系中起中介作用,中介效应分别为 27.7% 和 13.4%。此外,基因本体和京都基因和基因组百科全书的富集分析结果也支持炎症反应通路的作用:我们的研究结果表明,重金属暴露会导致肝损伤,而炎症反应可能是这一过程中的关键途径。这项研究为理解重金属诱导的肝损伤提供了一个新的视角,并为预防重金属对健康造成的损害提供了启示。
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引用次数: 0
Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study 产前接触多环芳烃和邻苯二甲酸酯与妊娠糖尿病:一项前瞻性队列研究。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-04 DOI: 10.1016/j.ijheh.2024.114419
Minghao Guo , Yiwei Fang , Meilin Peng , Chao He , Jin Chen , Borui Sun , Chunyan Liu , Yuanzhong Zhou , Huiping Zhang , Kai Zhao

Background

Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited.

Objective

To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women.

Methods

The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models.

Results

A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02–1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02–1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk.

Conclusions

Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

背景:多环芳烃和邻苯二甲酸酯(PAHs & PAEs)被称为内分泌干扰化学品(EDCs),广泛存在于日常生活和工业生产中。以往的研究表明,PAHs 和 PAEs 可能会改变胎儿宫内的稳态,对胎儿发育产生不利影响。然而,有关 PAHs 和 PAEs 与妊娠糖尿病(GDM)之间关系的流行病学证据仍然有限:调查产前多环芳烃和多环芳烃暴露对孕妇妊娠糖尿病和高血糖风险的影响:研究对象为2019年12月至2021年12月进行的一项前瞻性出生队列研究中的725名孕妇。血糖水平由医院信息系统收集。通过气相色谱串联质谱法测定尿液中 PAHs 和 PAEs 的浓度。应用广义线性模型泊松回归法(GLM)、多元线性回归法、基于量级的g计算法(qgcomp)和贝叶斯核机回归法(BKMR)来探讨和验证PAHs和PAEs对葡萄糖稳态的个体和整体影响。所有统计模型均调整了潜在的混杂因素:共有 179 名妇女(24.69%)被确诊为 GDM。泊松回归表明,4-OHPHE(4-羟基菲)的ln-单位增量(调整风险比(aRR)=1.13;1.02-1.26)与GDM风险的增加有关。混合暴露模型显示了类似的结果。我们还发现,在 qgcomp 模型中,MBZP(邻苯二甲酸单苄酯)(aRR = 1.19;1.02-1.39)与 GDM 风险呈正相关。虽然这两个模型都没有证明 2-OHNAP(2-羟基萘)和 9-OHFLU(9-羟基芴)会增加 GDM 风险,但 2-OHNAP 和 9-OHFLU 暴露会显著增加血糖水平。BKMR模型进一步证实,PAHs和PAEs的总体效应与妊娠高血糖和GDM风险密切相关:我们的研究表明,环境中暴露于 PAHs 和 PAEs 与妊娠期血糖水平和患 GDM 的风险呈正相关。其中,2-OHNAP、9-OHFLU、4-OHPHE 和 MBZP 可作为预防 GDM 发生的重要监测指标。
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引用次数: 0
Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts 三个欧洲队列中产前接触邻苯二甲酸盐和合成酚与青春期发育的关系。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-04 DOI: 10.1016/j.ijheh.2024.114418
Carmen Freire , Francesca Castiello , Izaro Babarro , Augusto Anguita-Ruiz , Maribel Casas , Martine Vrijheid , Blanca Sarzo , Andrea Beneito , Manik Kadawathagedara , Claire Philippat , Cathrine Thomsen , Amrit Kaur Sakhi , Maria-Jose Lopez-Espinosa

Background

There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing.

Objective

To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts.

Methods

Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999–2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7–12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed.

Results

Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98–1.30] and 1.20 [1.06–1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85–1.01] and BuPB: 0.95 [0.90–1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77–0.95] and 0.90 [0.84–0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls.

Conclusions

Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.

背景:关于产前暴露于邻苯二甲酸盐和合成酚与青春期时间改变之间的关系,流行病学证据有限:目的:研究三个欧洲队列中女孩和男孩产前接触邻苯二甲酸盐、双酚 A (BPA)、对羟基苯甲酸酯、二苯甲酮 3 (BP-3) 和三氯生 (TCS) 与青春期发育的关系:方法:从三个出生队列的母亲怀孕期间(1999-2008 年)采集的一份或两份(孕期第一和第三季度)尿液样本中,对六种不同邻苯二甲酸酯二聚体(DEP、DiBP、DnBP、BBzP、DEHP 和 DiNP)、双酚 A、甲基对羟基苯甲酸酯 (MePB)、乙基对羟基苯甲酸酯 (EtPB)、丙基对羟基苯甲酸酯 (PrPB) 和丁基对羟基苯甲酸酯 (BuPB)、BP-3 和三氯生 (TCS) 的尿液代谢物进行了定量分析:INMA(西班牙)、EDEN(法国)和 MoBa(挪威)。采用家长报告的青春期发育量表(PDS)对其子女(579 名女孩,644 名男孩)在 7-12 岁时的青春期发育情况进行了一次评估。采用混合效应泊松计算、g计算和贝叶斯核机器回归(BKMR)分别考察了单个和综合产前化学品暴露与女孩和男孩总体青春期发育、肾上腺发育和性腺发育(2+期)概率的关系。此外,还评估了儿童体重指数(BMI)对影响的修正作用:结果:母体中 DEHP 和 DiNP 代谢物摩尔总和的浓度与男童开始青春期的概率略高有关(浓度增加两倍,相对风险,RR [95% CI] = 1.13 [0.98-1.30] 和 1.20 [1.06-1.34]),在超重或肥胖的男童中,DiNP 的相关性更强。相比之下,BPA、BuPB、EtPB 和 PrPB 与所有男孩青春期开始、肾上腺皮质发育期和/或性腺发育期的概率较低有关(如整体青春期,BPA:RR[95%CI]=0.93[0.85-1.01],BuPB:0.95[0.90-1.00]),在体重不足/体重正常的男孩中,BPA 的相关性更强。在体重不足/体重正常的女孩中,MEHP 和 BPA 与性腺初潮延迟有关(RR [95% CI] 分别为 0.86 [0.77-0.95] 和 0.90 [0.84-0.97])。这些关联大多与孕期有关。然而,化学混合物与男孩或女孩的任何青春期结果都无关:结论:产前暴露于某些邻苯二甲酸盐和合成酚(如双酚 A)可能会影响男孩的青春期发育,而体重状况可能会改变这种影响。双酚 A 也可能会改变女孩的青春期发育。
{"title":"Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts","authors":"Carmen Freire ,&nbsp;Francesca Castiello ,&nbsp;Izaro Babarro ,&nbsp;Augusto Anguita-Ruiz ,&nbsp;Maribel Casas ,&nbsp;Martine Vrijheid ,&nbsp;Blanca Sarzo ,&nbsp;Andrea Beneito ,&nbsp;Manik Kadawathagedara ,&nbsp;Claire Philippat ,&nbsp;Cathrine Thomsen ,&nbsp;Amrit Kaur Sakhi ,&nbsp;Maria-Jose Lopez-Espinosa","doi":"10.1016/j.ijheh.2024.114418","DOIUrl":"10.1016/j.ijheh.2024.114418","url":null,"abstract":"<div><h3>Background</h3><p>There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing.</p></div><div><h3>Objective</h3><p>To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts.</p></div><div><h3>Methods</h3><p>Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999–2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7–12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed.</p></div><div><h3>Results</h3><p>Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98–1.30] and 1.20 [1.06–1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (<em>e.g.</em> overall puberty, BPA: RR [95% CI] = 0.93 [0.85–1.01] and BuPB: 0.95 [0.90–1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77–0.95] and 0.90 [0.84–0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls.</p></div><div><h3>Conclusions</h3><p>Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.</p></div>","PeriodicalId":13994,"journal":{"name":"International journal of hygiene and environmental health","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438463924000993/pdfft?md5=ac171343a92a8e90deda08695602e71b&pid=1-s2.0-S1438463924000993-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141539132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer incidence in Swedish oil refinery workers exposed to benzene 接触苯的瑞典炼油厂工人的癌症发病率。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-07-04 DOI: 10.1016/j.ijheh.2024.114420
E.M. Andersson , L. Barregard , M. Akerstrom , G. Sallsten , B. Järvholm , R.I. Nilsson

Background

Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers’ exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma.

Aim

The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries.

Methods

Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35–47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated.

Results

In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95–1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18–4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1–31.1).

Discussion

The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure.

Conclusion

The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.

背景:炼油厂工人接触苯,而苯是众所周知的白血病病因,但炼油厂工人白血病的研究结果不一,有关工人接触苯的数据也很有限。炼油厂工人也会接触石棉,一些研究显示间皮瘤的风险会增加。目的:研究目的是调查中低度接触苯的癌症发病率,尤其是白血病,这是对之前对瑞典三家炼油厂的员工进行的研究的更新:对在瑞典三家炼油厂工作至少一年的 2264 名男性(1548 名炼油厂操作工)的癌症发病率进行了跟踪调查。从完整的公司档案中收集了工作类型和工作时间。职业卫生学家与炼油厂合作,利用历史测量数据以及有关工业卫生和技术发展变化的详细信息,对苯接触情况进行了回顾性评估。通过与瑞典癌症登记册的连接,对 35-47 年的跟踪调查结果进行了癌症病例检索,并计算了标准化发病率(SIR)和 95% 的置信区间(CI):总共有 258 例肿瘤发生,而预期为 240 例(SIR 1.07;95% CI 0.95-1.21)。白血病病例有 10 例,均为炼油厂操作工(SIR 2.4;95% CI 1.18-4.51)。胸膜间皮瘤有 3 例,其中 2 例为炼油厂操作工。据估计,白血病病例的平均累积苯暴露量为 7.9 ppm-年(中位数为 4.9,范围为 0.1-31.1):讨论:这项研究表明,中低水平的平均累积苯暴露量会增加白血病的风险。结论:本研究表明,中低浓度的平均累积苯暴露会增加患白血病的风险:本研究表明,男性炼油厂工人接触中低浓度苯会增加患白血病的风险。
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引用次数: 0
Outbreak of cholera due to contaminated pond water utilisation in a rural area of West Bengal, India, 2021 2021 年,印度西孟加拉邦农村地区因使用受污染的池塘水而爆发霍乱。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-06-28 DOI: 10.1016/j.ijheh.2024.114409
Dhiraj Roy , Tanima Roy Mondal , Pallavi Indwar

Background

On March 31, 2021, an outbreak of diarrhoeal disease was reported in Dangapara village of Purba Bardhaman district, West Bengal, India. The outbreak was investigated to estimate the magnitude, identify aetiological agents and source of infection, and guide prevention control measures.

Methods

We did an active search for case patients at Dangapara village. We excluded children under five years of age from the epidemiological analysis. We described the outbreak by time, place, and person. We conducted a case control study with 133 controls and 65 cases. Water samples from different sources and rectal swabs from case patients were collected and sent for laboratory investigations.

Results

We identified 95 case patients among 330 residents of Dangapara village (attack rate 29 %). Three stool samples were positive for Vibrio cholerae, and two pond water samples were contaminated with coliform organisms. Washing utensils [adjusted odds ratio (AOR): 69.8, (95% confidence interval (CI) 6.5–749.5)] and taking a bath in pond water [AOR: 3.4, (95% CI 1.2–9)] were associated with increased risk of illness. About 97% of cases were attributed to washing utensils in pond water. Washing hands before taking food was associated with a lower risk of developing disease with AOR: 0.1 (95% CI 0.03–0.33).

Conclusion

A cholera outbreak occurred among residents of Dangapara village due to theuse of contaminated pond water for washing utensils and bathing. Prompt management of cases and immediate discontinuation of pond water use stopped the outbreak.

背景:2021 年 3 月 31 日,印度西孟加拉邦 Purba Bardhaman 区 Dangapara 村爆发了腹泻病。我们对疫情进行了调查,以估计疫情的严重程度,确定病原体和感染源,并指导预防控制措施:我们在 Dangapara 村积极寻找病例患者。我们在流行病学分析中排除了五岁以下儿童。我们按时间、地点和人员对疫情进行了描述。我们进行了病例对照研究,其中有 133 名对照者和 65 名病例。我们收集了不同来源的水样和病例患者的直肠拭子,并将其送往实验室进行化验:我们在 Dangapara 村的 330 名居民中发现了 95 名病例患者(发病率为 29%)。三份粪便样本霍乱弧菌呈阳性,两份池塘水样本受到大肠菌群污染。清洗餐具[调整后的几率比(AOR):69.8,(95% 置信区间(CI)6.5-749.5)]和在池塘水中洗澡[AOR:3.4,(95% 置信区间(CI)1.2-9)]与患病风险增加有关。约 97% 的病例与在池塘水中清洗餐具有关。结论:结论:由于使用受污染的池塘水清洗餐具和洗澡,Dangapara 村居民中爆发了霍乱。对病例的及时处理和立即停止使用池塘水阻止了疫情的爆发。
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引用次数: 0
Association of metals with early postnatal gut microbiota among infants admitted to the neonatal intensive care unit 新生儿重症监护室收治的婴儿中金属与产后早期肠道微生物群的关系。
IF 4.5 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-06-25 DOI: 10.1016/j.ijheh.2024.114410
Shi-ting Xiang , Changci Zhou , Kunyan Zhao , Ye Ma , Ruiwen Huang , Yunlong Peng , Yan Tang , Fei Yang , Jun Qiu

The gut microbiota is closely related to infant health. However, the impact of environmental factors on the gut microbiota has not been widely investigated, particularly in vulnerable populations such as infants admitted to the neonatal intensive care unit (NICU). This study investigated the association between exposure to 12 metals and the composition of the gut microbiota in infants admitted to the NICU. Metal concentrations were determined in serum samples obtained from 107 infants admitted to the NICU at Hunan Children's hospital, China. Gut microbiota data were derived from 16S rRNA sequencing using stool samples. Generalized linear regression (GLR) models and Bayesian kernel machine regression (BKMR) analyses were used to estimate the associations between metals and both alpha-diversity indices and bacterial taxa. The GLR models showed that tin correlated negatively with the Shannon index (β = −0.55, 95% conficence interval [CI]: −0.79, −0.30, PFDR< 0.001) and positively with the Simpson index (β = 0.26, 95% CI: 0.13, 0.39, PFDR< 0.001). The BKMR analysis yielded similar results, showing that tin had the largest posterior inclusion probability for both the Shannon (0.986) and the Simpson (0.796) indices. Tin, cadmium, mercury, lead, and thallium were associated with changes in one or more taxa at the genus level. The BKMR analysis also revealed a negative correlation between metal mixtures and Clostridium_sensu_stricto, and tin contibuted mostly to the negative correlation. Early postnatal exposure to metals were associated with differences in the microbiome among infants admitted to the NICU. However, as the study was cross-sectional, these relationships must be confirmed in further studies.

肠道微生物群与婴儿健康密切相关。然而,环境因素对肠道微生物群的影响尚未得到广泛研究,尤其是在易感人群中,如新生儿重症监护室(NICU)收治的婴儿。本研究调查了新生儿重症监护室婴儿接触 12 种金属与肠道微生物群组成之间的关系。研究人员测定了中国湖南省儿童医院新生儿重症监护室 107 名婴儿血清样本中的金属浓度。肠道微生物群数据来自粪便样本的 16S rRNA 测序。使用广义线性回归(GLR)模型和贝叶斯核机器回归(BKMR)分析来估计金属与α-多样性指数和细菌分类群之间的关系。GLR 模型显示,锡与香农指数呈负相关(β = -0.55,95% 置信区间 [CI]:-0.79,-0.30,PFDR< 0.001),与辛普森指数呈正相关(β = 0.26,95% 置信区间:0.13,0.39,PFDR< 0.001)。BKMR 分析也得出了类似的结果,显示锡在香农指数(0.986)和辛普森指数(0.796)中的后纳入概率最大。锡、镉、汞、铅和铊与一个或多个类群在属一级的变化有关。BKMR 分析还显示,金属混合物与梭状芽孢杆菌之间存在负相关关系,而锡在负相关关系中占绝大部分。产后早期接触金属与新生儿重症监护室婴儿微生物组的差异有关。然而,由于该研究是横断面研究,这些关系必须在进一步的研究中得到证实。
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引用次数: 0
Prenatal and childhood exposure to bisphenols and bone mineral density in 7-year-old children from the Odense Child Cohort 欧登塞儿童队列中 7 岁儿童的产前和童年双酚暴露与骨矿物质密度
IF 6 2区 医学 Q1 Medicine Pub Date : 2024-06-18 DOI: 10.1016/j.ijheh.2024.114408
Annika Sigvaldsen , Hanne Frederiksen , Frederik Damsgaard Højsager , Anna-Maria Andersson , Anders Juul , Henriette Boye , Marianne Skovsager Andersen , Tina Kold Jensen

Background

Bisphenol A (BPA) is a well-known endocrine disrupter used in several consumer products. Restricted use of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). While previous studies found no associations between prenatal BPA and BPF exposure and bone mineral density (BMD), two recent cohort studies found that prenatal BPS exposure was negatively associated with bone mineral density in the offspring.

Aim

To determine possible associations between maternal and child urinary bisphenol concentrations, BMD and bone mineral content (BMC) in 7-year-old healthy children.

Methods

Pregnant women were recruited in 2010–2012 to participate in the Odense Child Cohort (OCC), Denmark. Maternal urine samples were collected in gestational week 28 and urinary BPA concentration was measured by isotope diluted LC-MS/MS. The children delivered a urine sample at age 7 years in which BPA, BPF and BPS were measured by an extended LS-MS/MS method based on the original method. At age 7 years DXA scans were performed and BMC and Z-score for BMD calculated. Associations between osmolality adjusted urinary maternal BPA and child BPA, BPF and BPS concentrations and BMC and BMD Z-score were examined by multiple linear regression analysis adjusted for potential confounders. Additionally, a combined effect of the bisphenols were evaluated by including the sum of child urinary BPA, BPF and BPS concentrations in the statistical analyses.

Results

A total of 546 mothers and 453 children aged 7 years participated. BPA was detected in 84% and 96% of the maternal and child urine samples, respectively. We found no significant association between maternal urinary BPA concentration during pregnancy and BMC and BMD Z-score in 7-year-old children. In addition, no association between current bisphenol exposure in tertiles and bone density was found, interestingly, current BPA and summed bisphenol exposure in the highest 10% was associated with lower BMD Z-score at age 7-years, statistically significant for boys.

Conclusion

In these low exposed children we found no association between prenatal or current bisphenol exposure in tertiles and BMD in healthy children, however, the highest 10% exposed children had lower BMD, significant for boys, suggesting a negative impact with high bisphenol exposure. The short half-lives of bisphenols and the cross-sectional nature of the child exposure prompt more longitudinal studies to further clarify this topic.

背景双酚 A(BPA)是一种众所周知的内分泌干扰物,被用于多种消费品中。限制双酚 A 的使用导致双酚 F(BPF)和双酚 S(BPS)的使用增加。尽管之前的研究发现产前双酚 A 和双酚 F 暴露与骨矿物质密度 (BMD) 之间没有关联,但最近的两项队列研究发现产前双酚 S 暴露与后代的骨矿物质密度呈负相关。在孕 28 周时收集母体尿样,并通过同位素稀释 LC-MS/MS 方法测量尿液中的双酚 A 浓度。孩子们在 7 岁时采集尿样,在原有方法的基础上采用扩展的 LS-MS/MS 方法测量双酚 A、双酚 F 和双酚 S。7 岁时进行 DXA 扫描,并计算 BMC 和 BMD 的 Z 值。经渗透压调整的母体双酚 A 和儿童双酚 A、BPF 和 BPS 尿液浓度与 BMC 和 BMD Z 评分之间的关系通过多元线性回归分析进行了研究,并对潜在的混杂因素进行了调整。此外,通过将儿童尿液中双酚 A、双酚 F 和双酚 S 的浓度总和纳入统计分析,评估了双酚的综合影响。分别有 84% 和 96% 的母亲和儿童尿液样本中检测到双酚 A。我们发现,孕期母体尿液中的双酚 A 浓度与 7 岁儿童的 BMC 和 BMD Z 分数之间没有明显关联。结论 在这些低暴露儿童中,我们没有发现产前或当前双酚暴露量级与健康儿童的骨密度之间有任何关联,但是,暴露量最高的 10%儿童的骨密度较低,男孩的骨密度较低,这表明高双酚暴露量会产生负面影响。由于双酚的半衰期较短,而且儿童接触双酚的情况是横断面的,因此需要进行更多的纵向研究来进一步澄清这一问题。
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引用次数: 0
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International journal of hygiene and environmental health
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