生殖毒性及其危险度评价

生殖毒理学(reproductive toxicology)作为研究环境因素.特别是化学物对人类生殖影响特点和机制的毒理学分支.在过去30多年里得到了迅速发展。研究领域已从早期以致崎性观察为主.发展到生殖毒性的分子机制,生殖毒性危险度评价与管理的全面研     

邻苯二甲酸二乙基己酯生殖发育毒性及其机制

邻苯二甲酸二乙基己酯(di-2-ethylhexyl phthalate,DEHP)是一种使用广泛的邻苯二甲酸酯类增塑剂,研究表明,其是一种具有生殖毒性和发育毒性的环境雌激素,可通过消化系统、呼吸系统及皮肤接触等途径进入人体,也可通过胎盘和乳汁到达下一代体内。生殖毒性机制主要有与睾丸Leydig细胞、Sertoli细胞、germ细胞等作用干扰雄激素合成,也可通过干扰芳香酶活性及与激素合成运输有关的基因及蛋白的表达影响激素的合成、分泌及运输。DEHP主要通过影响胎盘脂质及锌代谢影响胚胎发育。由于种属之间代谢差异,把动物实验结果外推到人类还有许多问题需要考虑,但流行病调查资料显示,DEHP对人类健康产生不利影响。     

邻苯二甲酸二乙基已酯生殖发育毒性及其机制

邻苯二甲酸二乙基己酯(di-2-ethylhexyl phthalate,DEHP)是一种使用广泛的邻苯二甲酸酯类增塑剂,研究表明,其是一种具有生殖毒性和发育毒性的环境雌激素,可通过消化系统、呼吸系统及皮肤接触等途径进入人体,也可通过胎盘和乳汁到达下一代体内.生殖毒性机制主要有与睾丸Leydig细胞、Sertoli细胞、germ细胞等作用干扰雄激素合成,也可通过干扰芳香酶活性及与激素合成运输有关的基因及蛋白的表达影响激素的合成、分泌及运输.DEHP主要通过影响胎盘脂质及锌代谢影响胚胎发育.由于种属之间代谢差异.把动物实验结果外推到人类还有许多问题需要考虑,但流行病调查资料显示,DEHP对人类健康产生不利影响.     

有机磷农药的雄性生殖毒性

有机磷农药(OPPs)的广泛使用给环境和人类健康带来了严重威胁,长期接触OPPs可造成生殖毒性。本文拟从动物实验和人群研究两方面对有机磷农药生殖毒性及其可能机制作一简要介绍。     

甲醛致雌性生殖毒性的研究进展

近年来.随着居室装饰业的发展.甲醛带来的环境污染问题日益突出.其对人类健康尤其是女性生殖健康的影响引起广泛关注.该文从流行病学和毒理学两个方面,综述甲醛致女性(雌性)生殖毒性的研究进展.流行病学研究结果显示.甲醛可以导致女性月经紊乱、生育能力降低、出生儿体重减轻等生殖毒性;毒理学研究结果也显示出甲醛具有一定生殖毒性.     

甲基汞生殖毒性的研究

生殖毒理学的研究发现环境化学物、金属、激素、抗癌药物等可影响雄性动物生殖过程。甲基汞是一种重要的重金属污染物,研究证实它可通过胎盘产生胎儿性水误病[1,2]。为了解甲基汞对雄性动物的生殖毒性,我们采用不同剂量甲基汞对雄性小鼠经口慢性染毒,然后同正常处女鼠进行交配,观察其交配能力、受孕能力及胎鼠的发育情况。     

环境内分泌干扰物与女性生殖健康

人类在漫长的进化过程中，环境与生殖健康始终处于一个动态平衡。然而，自18世纪以来，人口剧增与科技发展，使人类创造的物质在数量上和潜在毒性上都大大超过了自然界的消解能力，某些有害物质通过各种途径进入人体，对人类健康，包括生殖功能，造成了潜在危害。有些化学物可通过干扰体内雌激素、雄激素、甲状腺激素和儿茶酚胺等，影响人体内分泌系统功能，被称之为“环境内分泌干扰物（environmental endocrine disruptors，EEDs）”。     

稀土元素的生殖毒性

近年来,环境化学物质引起人类的生殖危害问题日益受到重视,临床上患有性功能紊乱和不孕症的患者不断增加,男性尤其严重,而且很多原因不明确。据推测,人类生殖功能缺陷的原因有65～70%是未知的。到目前为止,对金属的生殖毒性问题已进行了广泛的研究,其中镉(Cd)、铅Pb)、汞(Hg)和镍(Ni)等金属都具有一定的生殖毒性。虽然稀土元素的一般毒性已研究的比较清楚,但是对它们的生殖毒性还没有明确的认识。为此,本文仅对稀土元素的生殖毒性进行综述,为进一步开展     

镉的雌性性腺生殖毒性研究现状

镉 (Ｃａｄｍｉｕｍ)是一种半减期很长 (19～ 30年 )的多器官、多系统毒物 ,也是一种重要的环境和工业毒物。其对生殖系统的毒性较为敏感且影响深远 ,尤其是随着妇女参加社会生产活动人数的不断递增 ,镉对接触女工的生殖健康的影响日益广泛 ,已受到国内外的普遍关注 ,并进行了一系列的动物实验和人群流行病学研究。镉是一种高度可疑的环境内分泌干扰因素 ,近来再次引起人们的关注。现对镉的雌性性腺生殖毒性及其机理的研究作一综述。1　镉在性腺、垂体中蓄积　　动物实验表明镉能在多种脏器中蓄积 ,在内分泌器官中尤为令人瞩目。给予Ｗｉｓ…     

环境雌激素对雄性生殖系统的影响及研究进展

近年来，环境化学物的内分泌干扰效应日益引起学术界的关注。具有雌激素活性或抗雄激素效应的一类化学物质称之为“环境雌激素”。大量实验表明，环境雌激素具有生殖和／或发育毒性。其作用机制非常复杂，检测方法尚需标准化。介绍环境雌激素对男性生殖系统的影响、作用机制及检测方法。重点讨论环境雌激素的作用机制和检测的研究进展。为以后的研究课题提供了方向。     

Human reproduction and environmental risk factors

Environmental pollution is a great cause of concern, in particular, growing attention is being paid to the potential of many chemicals to affect the reproductive system in humans. The key role of prevention and control of reproductive hazards is recognized world-wide. Many chemicals have been shown to impair fertility and/or prenatal and perinatal development in experimental studies. However, a sufficient evidence of an effect on human reproduction is available for some compounds only. The use of biological markers may improve the assessment of exposure to chemicals, contribute to identify mechanisms of action and put into evidence early, reversible, biological effects. Valid biological markers are also needed in epidemiological studies: without reliable data on the level of current and past exposures it is difficult to establish a causal relationship between a pollutant and the occurrence of adverse health effects. A multidisciplinary approach to risk assessment is required. Priorities for interdisciplinary research on environmental chemicals and reproduction include the identification of susceptible population subgroups and risk assessment of exposure to multiple chemicals.     

Occupational exposure associated with reproductive dysfunction

Evidence suggestive of harmful effects of occupational exposure on the reproductive system and related outcomes has gradually accumulated in recent decades, and is further compounded by persistent environmental endocrine disruptive chemicals. These chemicals have been found to interfere with the function of the endocrine system, which is responsible for growth, sexual development and many other essential physiological functions. A number of occupations are being reported to be associated with reproductive dysfunction in males as well as in females. Generally, occupations involving the manufacture/or application of some of the persistent chemicals that are not easily degradable as well as bio-accumulative chemicals, occupations involving intensive exposure to heat and radiation, occupations involving the use of toxic solvents as well as toxic fumes are reported to be associated with reproductive dysfunction. Occupational exposure of males to various persistent chemicals have been reported to have male mediated adverse reproductive outcomes in the form of abortion, reduction in fertility etc. with inconclusive or limited evidence. Nevertheless, there is a need for more well designed studies in order to implicate any individual chemical having such effects as in most occupations workers are exposed to raw, intermediate and finished products and there are also several confounding factors associated with lifestyles responsible for reproductive dysfunction. There is an urgent need to look at indiscriminate use of persistent chemicals especially pesticides and persistent organic pollutants (POP's) as these chemicals enter the food chain also and could be potential for exposure during the critical period of development. It is also necessary to impart information, and to educate about the safe use of these chemicals, as a very sensitive reproduction issue is involved with exposure to these chemicals. Occupational exposures often are higher than environmental exposures, so that epidemiological studies should be conducted on these chemicals, on a priority basis, which are reported to have adverse effects on reproduction in the experimental system.     

人体内有机物分析及邻苯二甲酸酯含量测定

目的　了解人体内有机物成分及重要有机物的污染水平 ,并评估对人群健康可能产生的危害。方法　采集 50名健康产妇静脉血 ,应用气相色谱 -质谱联用技术 (GC/MS) ,对血液中有机物进行定性检测及重要有机物的定量测定。结果　人体内共检出有机物 158种 ,检出率较高的有机物有 9-十八烯酸 (82 % )、十七烯 -(8)碳酸(66% )、邻苯二甲酸二丁酯 (62 % )、硫代 -(2 -氨基乙基 )硫酸酯 (3 4 % )、14 -β -孕激素 (2 8% )等 ,在检测出的有机物中对检出率较高、具有毒性效应的邻苯二甲酸二丁酯进行定量测定 ,其浓度为 (78 2 9± 3 4 0 1)mg/L。 结论　人体内存在有机物污染 ,部份有机物在人群体中检出率较高 ,其中检出率较高、浓度也较高的邻苯二甲酸二丁酯作为美国环境保护局 (EPA)优先控制污染物 ,具有生殖发育毒性 ,应当引起人们 (特别是育龄期妇女 )的高度重视     

全氟辛烷磺酸和全氟辛酸毒理学研究进展

全氟有机化合物,尤其是其代表性化合物全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)以及它们的盐类作为持久性有机环境污染物新成员,其所造成的全球性生态系统污染已成事实。本文以近年来国内外学者对PFOS和PFOA毒理学研究资料为依据,系统地阐述了PFOS和PFOA在实验动物和人体内的吸收、分布、排泄、代谢和毒物代谢动力学,以及它们对实验动物及人类可能造成的一般毒性、肝脏毒性、神经毒性、心血管毒性、胚胎发育与生殖毒性、遗传毒性与致癌性、免疫毒性等。同时指出,由于种属差异以及一些研究资料的尚不确定性,根据现有资料对PFOA和PFOS进行安全性评价的科学性值得商榷,进一步深入对PFOA和PFOS毒作用敏感指标及毒作用机制的探讨与研究,将成为今后环境科学和预防医学领域的研究重点。     

Significance of laboratory studies of neurobehavioral and developmental toxicities--transgenerational effects of styrene exposure

Recently, health problems caused by environmental chemical substances present in daily life have been increasing, particularly developmental toxicities, the effects of which often become apparent only after a long developmental period. It is difficult to determine adverse transgenerational effects. Therefore, we must recognize important indices to measure neurobehavioral and developmental effects. The assessment of such effects indices, is difficult and few neurobehavioral data are available compared to teratological data. Thus, through studies using laboratory animals, analyses of the mechanisms, exposure periods, doses and neurobehavioral effects are necessary. We have reviewed studies of the volatile monomer of the organic solvent styrene with regard to reproductive and developmental toxicities in laboratory animals. The styrene monomer crosses through the placenta; however, fetal excretion is less than maternal excretion. Therefore, it seems that a dose of styrene that does not affect the mother may be toxic for the fetus. We reported that exposure to low-dose styrene results in physical and neurobehavioral developmental delays, as well as decreases in enzyme activity and neurotransmitter secretion level. To prevent neurobehavioral toxicity, we need further studies to obtain precise data on chemical-biological interactions developmental toxicity and dose-response relationships. A key step towards effective prevention can also be obtained from studies in which animals are continuously exposed to chemicals for one or more generations. Thereafter, we must extrapolate developmental toxicity data from animals to humans. In this paper, we provide the information on developmental toxicity.     

Epidemiological approaches in the investigation of environmental causes of cancer: the case of dioxins and water disinfection by-products

I will refer in this paper to difficulties in research in environmental causes of cancer using as examples research on dioxins and on drinking water disinfection by-products (DBPs) that have created considerable controversy in the scientific and wider community. Dioxins are highly toxic chemicals that are animal carcinogens. For many years, evaluation of the carcinogenicity of dioxins in humans was based on case-control or registry based studies. The development of methods to measure dioxins in blood indicated that these studies suffered from extreme exposure misclassification. The conduct of large cohort studies of workers with widely contrasted exposures together with the use of biomarkers and models for exposure assessment, led to convincing evidence on the carcinogenicity of dioxins in humans. The high toxicity of a few dioxin congeners, the availability of a scheme to characterize the toxicity of a mixture of dioxins and related compounds and the long half-life of these compounds facilitated epidemiological research. Contrary to dioxins, trihalomethanes (THMs) and most of the hundreds of DBPs in drinking water are chemicals of low toxicity. For more than 15 years, the main evidence on the carcinogenicity of DBPs was through ecological or death certificate studies. More recent studies based on individual assessment confirmed increases in bladder cancer risk. However even those studies ignored the toxicological evidence on the importance of routes of exposure to DBPs other than ingestion and, probably, underestimated the risk. Persistence of weak study designs together with delays in advanced exposure assessment models led to delays in confirming early evidence on the carcinogenicity of DBPs. The evaluation of only a few chemicals when exposure is to a complex mixture remains a major problem in exposure assessment for DBPs. The success of epidemiological studies in identifying increased risks lies primarily on the wide contrast of exposure to DBPs in the general population that overcomes the significant exposure misclassification. Exposure assessment has been the Achilles heel for studies on dioxins and DBPs and cancer. The combination of powerful study designs, advanced exposure assessment together with a better understanding of mechanisms of disease and the use of biomarkers of exposure, led to the strengthening of the epidemiological evidence.     

Male reproductive health in relation to occupational exposure to endocrine disrupting and other potent chemicals, a review of the epidemiologic literature

The line of research focusing on the human, especially male, reproductive system in relation to occupational exposure has diversified since the infiltration of the concept of endocrine disrupting chemicals (EDC), early in the 1990s. The main stream, until then, was the study of reproductive toxicity caused by single albeit relatively heavy exposures to chemicals of limited range (conventional scheme). The new and increasingly important stem is the search for a wider range of chemicals with endocrine disrupting potential, and health effects due to multiple low-dose exposures of potent chemicals (new scheme). There are also studies having aspects of both the conventional and new schemes. For studies with the new scheme, progress has been made in areas such as adherence to standardized techniques in evaluating male reproductive function and more sensitive study designs. Indeed, some studies have suggested the presence of EDCs in the occupational setting. However, epidemiological findings are still constrained by difficulties in the identification of occupationally-exposed populations and evaluation of exposure. There is thus a need for convergence of knowledge and a widening of the scope of epidemiological research targeting occupationally exposed populations under a carefully-designed protocol.     

Halogenated flame retardants: do the fire safety benefits justify the risks?

Since the 1970s, an increasing number of regulations have expanded the use of brominated and chlorinated flame retardants. Many of these chemicals are now recognized as global contaminants and are associated with adverse health effects in animals and humans, including endocrine and thyroid disruption, immunotoxicity, reproductive toxicity, cancer, and adverse effects on fetal and child development and neurologic function. Some flame retardants such as polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily phased out by manufacturers because of their environmental persistence and toxicity, only to be replaced by other organohalogens of unknown toxicity. Despite restrictions on further production in some countries, consumer products previously treated with banned retardants are still in use and continue to release toxic chemicals into the environment, and the worldwide use of organohalogen retardants continues to increase. This paper examines major uses and known toxic effects of commonly-used organohalogen flame retardants, replacements for those that have been phased out, their combustion by-products, and their effectiveness at reducing fire hazard. Policy and other solutions to maintain fire safety while reducing toxicity are suggested. The major conclusions are: (1) Flammability regulations can cause greater adverse environmental and health impacts than fire safety benefits. (2) The current options for end-of-life disposal of products treated with organohalogens retardants are problematic. (3) Life-cycle analyses evaluating benefits and risks should consider the health and environmental effects of the chemicals, as well as their fire safety impacts. (4) Most fire deaths and most fire injuries result from inhaling carbon monoxide, irritant gases, and soot. The incorporation of organohalogens can increase the yield of these toxic by-products during combustion. (5) Fire-safe cigarettes, fire-safe candles, child-resistant lighters, sprinklers, and smoke detectors can prevent fires without the potential adverse effects of flame retardant chemicals. (6) Alternatives to organohalogen flame retardant chemicals include using less flammable materials, design changes, and safer chemicals. To date, before evaluating their health and environmental impacts, many flame retardant chemicals have been produced and used, resulting in high levels of human exposure. As a growing literature continues to find adverse impacts from such chemicals, a more systematic approach to their regulation is needed. Before implementing new flammability standards, decision-makers should evaluate the potential fire safety benefit versus the health and environmental impacts of the chemicals, materials, or technologies likely to be used to meet the standard. Reducing the use of toxic or untested flame retardant chemicals in consumer products can protect human and animal health and the global environment without compromising fire safety.     

Susceptibility of children to environmental toxic substances

Our understanding of toxicity of environmental substances is based mainly on investigations using adult human populations and matured animals. Therefore, the scientific community and regulatory agencies have very little knowledge regarding how children respond to insult from toxic chemicals. However, certain scientific data indicate that children are more susceptible to toxic exposure than adults because they have proportionally more intake of food contaminants, active developmental processes, multiple exposure pathways and susceptible socio-behavioral activities. More emphasis should therefore be focused on addressing the information gap for improving the health of our children.