Exposure to widespread environmental toxicants and children’s cognitive development and behavioral problems

Nowadays a special attention is focused on prenatal and childhood exposures to a variety of contaminants in the environment, especially toxicants widely present in the environment and their impact on children’s health and neurodevelopment. This article aims at evaluating the impact of exposure to several widespread toxicants including: polycyclic aromatic hydrocarbons (PAHs), phthalates, bisphenol A, brominated flame retardants and gas cooking on children’s cognitive development and behavioral problems by reviewing most recent published literature. Epidemiological studies focusing on exposure to widespread toxicants and children’s development for the last eleven years were identified by a search of the PubMed, Medline, Ebsco and Toxnet literature bases. The combination of following key words was used: 1) referring to the exposure: pregnancy, prenatal exposure, postnatal exposure, gas cooking, exposure to phthalates, bisphenol A, brominated flame retardants, PAHs and 2) referring to outcome: neurodevelopment, neurobehavior, psychomotor development, behavioral problems, cognitive development, mental health, school achievements, learning abilities. The results from the presented studies suggest that there are strong and rather consistent indications that the developing nervous system is particularly vulnerable to insult from low levels of exposure to widespread environmental contaminants such as: phthalates, bisphenol A, brominated flame retardants, polycyclic aromatic hydrocarbons, gas cooking. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.     

邻苯二甲酸酯雌性生殖毒性研究进展

邻苯二甲酸酯是一类产量大、用途广而且严重污染环境的化合物,流行病学调查证实了邻苯二甲酸酯的暴露与女性生殖功能损害的关系。本文就邻苯二甲酸酯对雌性生殖功能损害的体内、体外实验及毒性的机制进行了回顾。     

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.     

Phthalates: toxicology and exposure

Phthalates are used as plasticizers in PVC plastics. As the phthalate plasticizers are not chemically bound to PVC, they can leach, migrate or evaporate into indoor air and atmosphere, foodstuff, other materials, etc. Consumer products containing phthalates can result in human exposure through direct contact and use, indirectly through leaching into other products, or general environmental contamination. Humans are exposed through ingestion, inhalation, and dermal exposure during their whole lifetime, including intrauterine development. This paper presents an overview on current risk assessments done by expert panels as well as on exposure assessment data, based on ambient and on current human biomonitoring results. Some phthalates are reproductive and developmental toxicants in animals and suspected endocrine disruptors in humans. Exposure assessment via modelling ambient data give hints that the exposure of children to phthalates exceeds that in adults. Current human biomonitoring data prove that the tolerable intake of children is exceeded to a considerable degree, in some instances up to 20-fold. Very high exposures to phthalates can occur via medical treatment, i.e. via use of medical devices containing DEHP or medicaments containing DBP phthalate in their coating. Because of their chemical properties exposure to phthalates does not result in bioaccumulation. However, health concern is raised regarding the developmental and/or reproductive toxicity of phthalates, even in environmental concentrations.     

饮食与儿童性早熟的研究进展

儿童性早熟是指男童在9岁前,女童在8岁以前呈现第二性征的现象。儿童性早熟可导致生理与心理的双重损害,亦对成人时期的健康产生影响。近年来,儿童性早熟的发病率呈上升的趋势。现有研究提示,饮食与儿童性早熟之间有着密切关系,肉类、含糖饮料、保健品可能是儿童性早熟饮食的危险因素、富含膳食纤维的食物可能是保护因素,而奶制品、豆类及其制品与儿童性早熟的关系尚有争议。本文就饮食与儿童性早熟的研究进展进行综述。     

镇江市城区4~10岁儿童性早熟发育的现状调查及其危险因素分析

目的 调查镇江市区4~10岁儿童性早熟发育现状及其诱发引起性早熟的相关风险因素,为防治儿童性早熟发育提供科学理论依据。方法 2016年3月-2017年3月对镇江市区9个街道共3 442名4~10岁儿童进行问卷调查和体格检查。确诊性早熟发育儿童42例,其中女童35例,男童7例,检出率为1.22%,女童性早熟检出率是男童的5倍,且检出率随着年龄增长而提高;肥胖和超重儿童性早熟检出率高于正常体重组;常服用保健滋补品、儿童饮料和人工饲养水产及动物肉类的儿童性早熟检出率明显高于对照组,且差异具有统计学意义(P< 0.05)。结论 性早熟发育的检出率较高,与日常饮食习惯及体重变化等存在一定的相关性,应当引起重视,并采取相关措施进行儿童性早熟发育的预防保健。     

上海市女童血清中邻苯二甲酸二丁酯和邻苯二甲酸-2-乙基己酯水平与性早熟关系研究

目的通过对上海市性早熟女童血清中邻苯二甲酸二丁酯(DBP)和邻苯二甲酸-2-乙基己酯(DEHP)水平变化研究,探讨DBP、DEHP与性早熟女童发病的关系。方法运用气相色谱法测定110例性早熟女童和100例正常儿童血清中DBP和DEHP的含量,同时运用B型超声仪测定性早熟女童与正常儿童的子宫与卵巢体积,然后做性早熟女童血清中DBP和DEHP含量水平与子宫、卵巢体积之间的相关性分析。结果27.3%和22.7%的性早熟女童血清中分别检测出DBP和DEHP,而正常儿童仅4%和3%分别检测出DBP和DEHP。从血清中DBP和DEHP的含量构成比来看,性早熟女童血清中DBP和DEHP的含量构成比均高于正常儿童;性早熟女童子宫、卵巢体积均大于正常儿童子宫、卵巢体积(P<0.05,P<0.05);性早熟女童血清中DBP与子宫呈正相关(r=0.456,P<0.05),与卵巢也呈正相关(r=0.378,P<0.01),性早熟女童血清中DEHP与子宫呈正相关(r=0.382,P<0.05,),与卵巢呈正相关(r=0.689,P<0.01)。结论性早熟女童受DBP和DEHP污染的程度均比正常儿童严重得多,而且DBP和DEHP对子宫、卵巢的体积有影响。     

儿童性早熟192例临床分析

目的:探讨儿童性早熟的年龄、病因及临床特征,提高对本病的认识。方法:对2007年4月～2010年5月在九江市妇幼保健院诊治的192例(男5例,女187例)性早熟儿童的年龄、临床特征、病因、实验室数据进行回顾性分析。结果:儿童性早熟中以女性为主,占97.4%,年龄以8月～1岁占2.08%,～3岁占28.12%,～9岁7月占69.79%。临床表现最常见的是乳房增大占92.9%,其次为乳房色素沉着占65.5%,外阴分泌物增多占12.3%,阴毛早现占4.3%和阴蒂(阴茎)、睾丸增大占4.6%,阴道出血占0.01%。病因:促性腺素依赖性性早熟(CPP)占26.4%,同性性早熟中女性除垂体肿瘤2例、先天性甲状腺功能减低症1例、Williams综合征1例外,余均为特发性性早熟,男性先天性肾上腺皮质增生症2例。非促性腺素依赖性性早熟(GIPP)占73.6%。女性均表现为同性性早熟,男性则因外源性摄入雌激素(避孕药)表现为异性性早熟3例。<3岁的婴幼儿发病率达28.12%,除1例CAH及1例垂体肿瘤外,均为GIPP,发病人群以农村儿童多见占87%,尤以留守儿童为主,以酸奶饮料代替牛奶,不加节制的喝饮料和吃油炸小零食以及误服避孕药是发病的主要原因。结论:儿童性早熟病因复杂,须仔细询问病史、体格检查,及相应的实验室检查。特别关注农村婴幼儿饮食安全,提高家长认知能力,应引起社会的关注。     

反季节水果摄入与女童性早熟的关联性研究

目的:探讨反季节水果摄入与女童性早熟之间的相关关系,为进一步评价反季节水果的安全性提供线索。方法:采用以医院为基础的1∶1配对病例-对照研究方法,按同性别、年龄相差不超过1岁进行配对,收集性早熟女童及其他疾病患儿各105例。采用膳食频率问卷调查方法调查主要反季节水果的摄入量,进行单因素及多因素Logistic回归分析。结果:反季节水果暴露的总体情况病例组与对照组无统计学差异(P>0.05)。进一步按季节划分,经多因素分析发现水果因素中摄入春季的芒果、草莓、樱桃、甜橙,夏季的桃子过多,与女童发生性早熟正关联(P<0.05),而经常摄入夏季、冬季的葡萄,夏季的草莓和秋季的桃子、甜橙与其负关联(P<0.05)。非水果因素中禽畜肉类摄入情况与发生性早熟呈负相关(P<0.05),营养保健品服用史与其呈正相关(P<0.05),洋快餐及油炸食品摄入未见统计学差异(P>0.05)。结论:本研究未发现反季节水果的总体摄入与女童性早熟的关联性。但部分反季节水果过多摄入在女童性早熟发病中可能起促进作用,仍需进一步研究。     

沙颍河水邻苯二甲酸酯污染对儿童甲状腺功能及智力的影响

目的探索淮河流域沙颍河水邻苯二甲酸酯类物质(PAEs)污染现状及其对儿童智力发育和甲状腺相关激素的影响。方法在沙颍河出河南省的S县段内,分别距河床2km以内和20km以外,各选取1个村庄作为污染区和对照区,分别采集河水和居民生活饮用水。高效液相色谱法检测河水和饮用水水中4种PAEs(DEP、DBP、DMP、DEHP)水平;整群抽取两区8～13岁在校学生作为观察对象进行问卷调查;采用联合型瑞文测验方法对两区学生进行智力测验,化学发光法测定促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT3)和游离四碘甲腺原氨酸(FT4)含量。结果沙颍河S段各断面DEP、DBP水平均超过国家地表水环境质量标准;同对照区相比,污染区饮用水中DEP、DBP均明显高于对照区,差异有统计学意义(P<0.05)。污染区儿童血清中FT4明显高于对照区儿童(P<0.05)。污染区儿童智力低于对照区儿童(P<0.05)。结论污染区儿童体内甲状腺相关激素及智力发育受到一定影响,是否与水质PAEs污染有关,尚需进一步调查。     

Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany

Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.     

Diet-Induced Hypothalamic Inflammation,Phoenixin, and Subsequent Precocious Puberty

Recent studies have shown a rise in precocious puberty, especially in girls. At the same time, childhood obesity due to overnutrition and energy imbalance is rising too. Nutrition and fertility are currently facing major challenges in our societies, and are interconnected. Studies have shown that high-fat and/or high-glycaemic-index diet can cause hypothalamic inflammation and microglial activation. Molecular and animal studies reveal that microglial activation seems to produce and activate prostaglandins, neurotrophic factors activating GnRH (gonadotropin-releasing hormone expressing neurons), thus initiating precocious puberty. GnRH neurons’ mechanisms of excitability are not well understood. In this review, we study the phenomenon of the rise of precocious puberty, we examine the physiology of GnRH neurons, and we review the recent literature regarding the pathophysiological mechanisms that connect diet-induced hypothalamic inflammation and diet-induced phoenixin regulation with precocious puberty.     

安徽阜阳地区性早熟女童的环境激素暴露研究

目的 调查常见的环境激素在女童性早熟的发病机制中可能起到的作用,为阜阳地区儿童环境激素的暴露情况积累基础数据。方法 随机选取2020年10月—2021年4月在阜阳市人民医院生长发育专科门诊就诊的初诊为性早熟的女童,包括中枢性(CPP组)、外周性(PPP组)性早熟各30例,以及23例健康女童(正常对照组)作为研究对象,并就日常生活中可能接触到环境激素的途径填写相关内容调查问卷。应用超高效液相色谱串联质谱法测定3组女童尿液中15种环境激素的暴露水平,以及测定CPP组及PPP组女童的血清基础性激素、甲状腺激素水平,并完善性腺彩超等检查,进行3组女童尿液中环境激素暴露水平研究及相关性分析。结果 正常组、CPP及PPP 3组女童在使用塑料水杯方面、尿液中邻苯二甲酸单乙基己酯(MEHP)、邻苯二甲酸单丁基酯(MBP)的暴露水平分布差异具有统计学意义(χ²=8.111,F=3.741、5.672,P<0.05);CPP组与正常组女童尿MEHP、MBP暴露水平差异无统计学意义(P＞0.05),但PPP与CPP组、PPP与正常组女童的尿MEHP、MBP暴露水平分布差异有统计学意义(P＜0.05);PPP组内MEHP的分布水平与E₂呈正相关关系(r=0.688,P＜0.05)。结论 频繁使用塑料制品可能促进性早熟的发病;安徽阜阳地区女童普遍受到环境激素的污染;邻苯二甲酸单乙基己酯、邻苯二甲酸单丁基酯的暴露可能在外周性性早熟的病因中发挥着重要的作用,并且干扰体内性激素的分泌。     

Childhood Exposure to Phthalates: Associations with Thyroid Function,Insulin-like Growth Factor I,and Growth

Background

Phthalates are widely used chemicals, and human exposure is extensive. Recent studies have indicated that phthalates may have thyroid-disrupting properties.

Objective

We aimed to assess concentrations of phthalate metabolites in urine samples from Danish children and to investigate the associations with thyroid function, insulin-like growth factor I (IGF-I), and growth.

Methods

In 845 children 4–9 years of age, we determined urinary concentrations of 12 phthalate metabolites and serum levels of thyroid-stimulating hormone, thyroid hormones, and IGF-I.

Results

Phthalate metabolites were detected in all urine samples, of which monobutyl phthalate was present in highest concentration. Phthalate metabolites were negatively associated with serum levels of free and total triiodothyronine, although statistically significant primarily in girls. Metabolites of di(2-ethylhexyl) phthalate and diisononyl phthalate were negatively associated with IGF-I in boys. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes.

Conclusions

Our study showed negative associations between urinary phthalate concentrations and thyroid hormones, IGF-I, and growth in children. Although our study was not designed to reveal the mechanism of action, the overall coherent negative associations between urine phthalate and thyroid and growth parameters may suggest causative negative roles of phthalate exposures for child health.     

尿液双酚A浓度及生活习惯与女童性早熟关系的研究

目的 探讨双酚A与女童性早熟发病的关系;首次尝试了解生活习惯与双酚A暴露及性早熟的关系。方法 收集2011年7-12月于本院门诊就诊的性早熟病例组和正常对照组女童各44例;采用高效液相色谱法分别检测两组女童尿液双酚A浓度;通过自编问卷了解日常生活中可能存在双酚A暴露的生活习惯。结果 病例组和对照组尿液双酚A检出率分别为70.45%和43.18%,差异有统计学意义(χ²=6.67,P<0.05);病例组尿液双酚A浓度高于对照组(Z=3.49,P<0.01);是否饮用桶装水热水可能是女童患有性早熟的弱危险因素(β=0.967 8,χ²=3.870 3,P=0.049 1,OR=2.632,95%CI:1.004~6.903)。 结论 双酚A暴露可能与女童性早熟发病有关;正常对照组女童亦有较高的双酚A暴露率;尿样更适合用来评估人体双酚A暴露情况;常饮用桶装水热水可能增加女童患性早熟的风险;正确合理地使用塑料制品十分重要。     

Environmental exposure and children's health in China

Concerns regarding adverse health effects of exposure to environmental pollutants among children are increasing. This subject area is particularly important in China because of environmental pollution problems associated with rapid development and a large population. The authors provide what is, to their knowledge, the first review in China of English- and Chinese-language literature regarding the current status of environmental exposures to children in China and the impact of these exposures on the health of children. Children in China are exposed to diverse environmental pollutants, including traditional pollutants such as lead and mercury and emerging pollutants such as phthalates and perfluorinated compounds. Incidence and prevalence of certain childhood diseases have increased in last decades. In China, a limited number of data on environmental exposure and children's health are available, and further high-quality studies are needed.     

Effects on Puberty of Nutrition-Mediated Endocrine Disruptors Employed in Agriculture

Pesticide residues are largely found in daily consumed food because of their extensive use in farming and their long half-life, which prolongs their presence in the environment. Many of these pesticides act as endocrine-disrupting chemicals after pre- or postnatal exposure, significantly affecting, among other things, the time of puberty onset, progression, and completion. In humans, precocious or delayed puberty, and early or delayed sexual maturation, may entail several negative long-term health implications. In this review, we summarize the current evidence on the impact of endocrine-disrupting pesticides upon the timing of the landmarks of female and male puberty in both animals (vaginal opening, first estrus, and balanopreputial separation) and humans (thelarche, menarche, gonadarche). Moreover, we explore the possible mechanisms of action of the reviewed endocrine-disrupting pesticides on the human reproductive system. Access to safe, healthy, and nutritious food is fundamental for the maintenance of health and wellbeing. Eliminating the presence of hazardous chemicals in largely consumed food products may increase their nutritional value and be proven beneficial for overall health. Consequently, understanding the effects of human exposure to hazardous endocrine-disrupting pesticides, and legislating against their circulation, are of major importance for the protection of health in vulnerable populations, such as children and adolescents.     

Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: estimation of daily phthalate intake

Background

Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and asthma.

Objectives

To study the urinary excretion of phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of phthalates in this segment of the population.

Method

One 24 h urine sample and to consecutive first morning urine samples were collected from 129 healthy Danish children and adolescents (range 6–21 yrs). The concentrations of 11 phthalate metabolites of 5 different phthalate diesters were analyzed by liquid chromatography–tandem mass spectrometry.

Results

The analyzed metabolites were detectable in almost all 24 h urine samples. The median concentrations of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and the sums of the two monobutyl phthalate isoforms (∑MBP(i+n)), metabolites of di-(2-ethylhexyl) phthalate (∑DEHPm) and of di-iso-nonyl phthalate (∑DiNPm) were 29, 17, 111, 107 and 31 ng/mL, respectively. The youngest children were generally more exposed to phthalates than older children and adolescents (except diethyl phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of phthalate diesters was: 4.29 (dibutyl phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0.62 (butylbenzyl phthalate (BBzP)), all calculated as μg/kg body weight/24 h. Between 40% and 48% of the absolute amount of phthalate metabolites excreted over 24 h were excreted in first morning urine voids.

Conclusion

Danish children are exposed simultaneously to multiple phthalates. The highest exposure levels were found for DBP(i+n) and DEHP, which in animal models are the known most potent anti-androgenic phthalates. The combined exposure to the two isoforms of DBP, which have similar endocrine-disrupting potencies in animal models, exceeded the TDI for di-n-butyl phthalate (DnBP) in several of the younger children.     

女童性早熟的超声诊断应用研究

目的 研究女童不同类型性早熟敏感性及特异性较高的超声参数,寻求超声在女童性早熟诊断中的应用价值。方法 2016 年2 月-2018 年 2 月,收集性早熟女童263例,其中,中枢性性早熟组 (CPP组)146例,外周性性早熟组(PPP组)117例。另选择正常女童 146 例,均检测子宫、卵巢及乳腺腺体情况,超声多参数测量数据进行比较,观察不同类型性早熟患儿组之间及其与正常女童各项超声参数的差异与特征。结果 宫颈厚是诊断CPP的最佳诊断指标,临界值为0.75 cm,乳腺腺体厚是特异度最高的指标,临界值为1.03 cm,二者联合,诊断的灵敏度为92.1%,特异度为96.3%;宫颈长度是PPP的最佳诊断指标,临界值为1.51 cm,宫体体积是特异度最高的指标,临界值为2.87 cm³,二者联合,诊断的灵敏度为90.1%,特异度为95.4%;卵巢体积是区分CPP与PPP的最佳诊断指标,临界值为2.25 cm³,乳腺腺体长度是特异度最高的指标,临界值为3.67 cm,二者联合,诊断的灵敏度为93.5%,特异度为89.2%。结论 超声检查无创、可靠,其超声测量参数在女童性早熟的临床诊断与鉴别中有者较高的应用价值。     

生命早期邻苯二甲酸酯暴露与儿童青春发动时相提前关联研究进展

儿童青春发动时相提前对儿童身心健康造成了不小的影响, 也与成年时期多种慢性非传染性疾病有关, 其病因复杂, 主要包括环境因素及遗传学因素。邻苯二甲酸酯(PAEs)作为一类常见环境污染物, 暴露于人体后其代谢物可作为内分泌干扰物影响身体的内分泌系统稳态。生命早期更是疾病易感时期, 很多研究发现, 围生期及发育关键时期暴露于PAEs可促进青春期发展。本文从PAEs暴露与青春发动时相提前关联的流行病学研究和相关机制方面进行阐述。