Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population

A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure.     

Multiple metals predict prolactin and thyrotropin (TSH) levels in men

Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.     

Azoospermia and oligospermia among a large cohort of DBCP applicators in 12 countries.

Azoospermia and oligospermia have been well demonstrated among workers exposed to 1,2-dibromo-3-chloropropane (DBCP) in manufacturing and formulation of this pesticide. After DBCP was banned in the United States in the late 1970s, two American companies continued to export it to many less developed countries. In the early to mid-1990s, attorneys assembled a cohort of approximately 26,400 male plaintiffs who, as workers on banana and pineapple plantations in 12 of these countries, had been exposed to DBCP, primarily during its application. These attorneys, for the purpose of a lawsuit against the two American companies, developed from interrogatories a database on these men that included information about stated periods of occupational DBCP exposure. Seminal fluid analysis results were also entered into the database. Analyzing information in this database, the authors found that, after a median exposure to DBCP of three years, 64.3% of these men overall, and 90.1% of men studied from the Philippines, had azoospermia or oligospermia. The mean number of children reported by the men was 2.5 overall. The percentage of men with no children was 28.5% overall. This report represents the largest cohort of DBCP-exposed workers in which adverse reproductive health effects have been described, and the first report of the adverse effects on the reproductive health of workers exposed to DBCP primarily through its application in a cohort of this size. This serious and extensive occurrence of adverse reproductive health effects due to the export of a hazardous pesticide before and after its ban in the United States illustrates a number of needs for monitoring, research, education, and policy development.     

Effects of exposure to environmental tobacco smoke on reproductive health

The scientific evidence on the effects of preconceptional and prenatal exposure to environmental tobacco smoke on reproductive health is reviewed in this article. The evidence is the most convincing for the adverse effects of environmental tobacco smoke on birthweight. In meta-analyses, exposure to environmental tobacco smoke has been estimated to reduce mean birthweight by about 25-40 grams. The majority of the studies on low birthweight also show a moderately or slightly increased risk among infants of exposed women. There is also some support for an association between high exposure to environmental tobacco smoke and preterm birth. The evidence on the effects of environmental tobacco smoke on spontaneous abortion and birth defects is weak and inconsistent. Very little is known about the impact of exposure on fertility, menstrual function, reproductive health of men, and childhood cancer. Further studies, paying attention to study design and careful exposure assessment, are therefore needed on these associations.     

Occupational and environmental exposure correlates of adverse live-birth outcomes among 1032 US Navy women

The integration of women into non-traditional military occupations raises questions concerning the impact of such jobs on women's reproductive health. This study examines the extent to which US Navy women in their reproductive years report exposures to potential occupational and environmental hazards, and the degree to which such exposures are associated with self-reported adverse live-birth outcomes. Data from a survey of pregnant Navy women provided both maternal and paternal exposure information on more than 1000 active-duty women. Self-reported exposures to heavy metals, pesticides, petroleum products, and other chemicals were associated with adverse live-birth outcomes at the bivariate level. Only a father's exposure to pesticides at work predicted an adverse live-birth outcome (preterm delivery) in multivariate models. Maternal occupational exposures may exert their influence through maternal health and/or pregnancy complications and may act as mediators of health-reproductive outcome relationships.     

消毒副产物暴露对男性生殖健康影响的研究进展

消毒副产物(disinfection by-products,DBPs)是饮用水中一类广泛存在的污染物,其来源于饮用水消毒过程中消毒剂与源水中存在的有机或者无机化学物质发生的化学反应。目前在饮用水中已鉴定的DBPs多达600多种,其中三卤甲烷类(trihalomethanes,THMs)和卤代乙酸类(haloacetic acids,HAAs)的含量最高。自20世纪70年代美国国立癌症研究所发现DBPs具有致癌性以来,有关DBPs的潜在健康危害便引起了世界各国的广泛关注,其中DBPs的生殖毒性也成为关注点之一。本文从毒理学和流行病学两方面综述了DBPs暴露对男性生殖健康影响的研究进展,并对其今后的研究展望进行了相关讨论。     

Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function.     

A review of nitrates in drinking water: maternal exposure and adverse reproductive and developmental outcomes

In this review, we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure-response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects.     

Impact of low-level exposure to organophosphates on human reproduction and survival

Despite their widespread and longstanding use for the public good, organophosphate (OP) pesticides have led to many adverse effects on human health. Environmental exposure to OPs and adverse reproductive outcomes in men and women working on or living near farms are increasingly reported worldwide. The aim of the current review is to determine whether exposure to OPs, at levels lower than that which results in clinical manifestations of acute OP poisoning, leads to an adverse impact on fertility, growth and development, and to highlight possible effects for further investigation. There is evidence of impaired fertility due to a reduction in semen quality and possibly lower testosterone levels in exposed males. There is also evidence of impairment of fetal growth and development brought about by prenatal exposure to OPs. Paraoxonase gene (PON1) activity in the fetus and during early childhood makes the fetus and child more vulnerable to OP poisoning, suggesting that OP exposure has a greater impact on fetal and infant growth and development than on adults when exposed to the same concentrations of pesticides. This review raises concerns that exposure to OP pesticides at levels currently regarded as safe adversely affect human reproductive function and survival.     

农药暴露对女性生殖健康的影响

目的：研究不同程度农药暴露对女性生殖健康的影响。方法选择长期接触农药的育龄期女性319人为观察组,其中低暴露强度104人,中暴露强度112人,高暴露强度103人;以未长期接触农药的育龄期女性109人为对照组,通过问卷调查的方式搜集资料并进行数据之间的比较。结果不同强度的农药暴露对女性的月经功能、性功能状况、乳腺疾病、阴道炎、不良妊娠结局的差异有统计学意义（P＜0.05）,且与农药暴露的相关系数分别是0.257,0.113,0.127,0.125和0.119,其中长期农药暴露对月经功能和乳腺疾病影响显著（ P＜0.01）,但不同农药暴露对子宫疾病、孕期并发症影响较小（P＞0.05）。结论长期农药暴露对女性生殖系统健康有一定影响,其中对月经功能、性功能状况、阴道炎、乳腺病、不良妊娠结局等方面影响比较显著。应增强农药使用者的安全意识,促进女性农药使用者的生殖健康。     

Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children’s neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary le vels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.     

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development

The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adverse effects at the earliest possible juncture, investigators must develop a network of biomarkers covering all stages and aspects of reproductive development and function. Biomarkers are biological indicators that can be measured repeatedly and are informative on one or more aspects of biological development or function. They can range from the anatomical level down to the molecular level and may provide information on the nature of an exposure, the effect of an exposure, or the susceptibility of individuals or populations to the toxic effects of an exposure. In theory, biomarkers can be used to monitor a wide variety of conditions and responses ranging from abnormal development to early indicators of late-onset disease. The main stumbling block with this theory has been finding appropriate biomarkers for particular conditions and exposures. Such biomarkers must be easily accessible, robust, and sensitive. Ideally, they will be expressed across a large section of the population, and can be monitored quickly, easily, conveniently, and with minimal cost. In this review, we discuss some of the current and emerging biomarkers of human pubertal development.     

An occupational reproductive research agenda for the third millennium

There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care. Many other substances are suspected of producing reproductive or developmental toxicity but lack sufficient data. Progress has been limited in identifying hazards and quantifying their potencies and in separating the contribution of these hazards from other etiologic factors. Identifying the causative agents, mechanisms by which they act, and any potential target populations, present the opportunity to intervene and protect the reproductive health of workers. The pace of laboratory studies to identify hazards and to underpin the biologic plausibility of effects in humans has not matched the pace at which new chemicals are introduced into commerce. Though many research challenges exist today, recent technologic and methodologic advances have been made that allow researchers to overcome some of these obstacles. The objective of this article is to recommend future directions in occupational reproductive health research. By bridging interdisciplinary gaps, the scientific community can work together to improve health and reduce adverse outcomes.     

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.     

Pesticide exposure and women's health

BACKGROUND: Research on pesticide-related health effects has been mostly focused in industrialized countries and in men. This paper discusses critical issues related to women's pesticide exposure and its effects on women's health. METHODS: The literature on pesticides was reviewed with emphasis on data related to women. Attention was focused on research suggesting different conditions of exposure or different response to pesticides by sex. Studies on cancer and reproductive effects were used as illustrative examples. RESULTS: Women are increasingly exposed to pesticides in developing countries, where women's poisoning and other pesticide-related injuries seem to be greatly underestimated. Many of the effects of pesticides in human health will be the same for men and women, but not always. Some organochlorine pesticides have been related to breast cancer in post-menopausal women. However, knowledge about other pesticides is much more limited. Epidemiological studies assessing maternal exposure to individual pesticides and abortion, fetal death, or congenital defects are not conclusive, although some suggestive associations have been observed. CONCLUSIONS: Gender-sensitive research is needed to properly address the study of women's pesticide exposures and related adverse outcomes. A better understanding of potential gender-environment and sex-environment interactions related to pesticide exposure and health effects in women is needed.     

A review of nitrates in drinking water: maternal exposure and adverse reproductive and developmental outcomes

In this review we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and also discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Drinking water source was related to nitrate exposure (i.e., private systems water was more likely than community system water to have nitrate levels above the maximum contaminant limit). Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure-response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. Nitrates may be just one of the contaminants in drinking water contributing to adverse outcomes. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects. Future studies incorporating individual exposure assessment about users of private wells--the population most at risk--should be considered.     

Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study

We recently reported associations between urinary 1-naphthol (1N) levels and several intermediate measures of male reproductive health, namely sperm motility, serum testosterone levels, and sperm DNA damage. However, because 1N is a major urinary metabolite of both naphthalene and the insecticide carbaryl, exposure misclassification stemming from differences in exposure source was probable and interpretation of the results was limited. As naphthalene, but not carbaryl, is also metabolized to 2-naphthol (2N), the relationship of urinary 1N to 2N within an individual may give information about source of 1N. Utilizing data from two previous studies that measured both 1N and 2N in urine of men exposed to either carbaryl or naphthalene, the present study employed several methods to differentiate urinary 1N arising from exposures to carbaryl and naphthalene among men in the reproductive health study. When re-evaluating the reproductive health data, techniques for identifying 1N source involved exploring interaction terms, stratifying the data set based on 1N/2N ratios, and performing an exposure calibration using a linear 1N to 2N relationship from a study of workers exposed to naphthalene in jet fuel. Despite some inconsistencies between the methods used to distinguish 1N source, we found that 1N from carbaryl exposure is likely responsible for the previously observed association between 1N and sperm motility, whereas 1N from naphthalene exposure is likely accountable for the association between 1N and sperm DNA damage. We demonstrate that studies of health effects associated with carbaryl should utilize a 1N/2N ratio to identify subgroups in which carbaryl is the primary source of 1N. Conversely, studies of naphthalene-related outcomes may utilize 2N levels to estimate exposure.     

Reproductive endocrine effects of acute exposure to toluene in men and women

OBJECTIVES: Despite observation of adverse reproductive effects of toluene, including alterations of serum gonadotropins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) in humans, little is known of the mechanism of toxicity. The hypothesis was tested that toluene acutely suppresses pulsatile gonadotropin secretion by measuring LH and FSH at frequent intervals during controlled exposure to toluene. METHODS: Women in the follicular and luteal phases of the menstrual cycle and men were randomised to inhale filtered air with or without 50 ppm toluene through a mouthpiece for 3 hours (19% of the OSHA permissible exposure limit). Blood was sampled by intravenous catheter at 20 minute intervals for 3 hours before, 3 hours during, and 3 hours after exposure. Plasma LH, FSH, and testosterone were measured. Pulse amplitude, pulse frequency, and mean concentrations of LH and FSH for each of the 3 hour periods before, during and after exposure to toluene versus sham exposure were calculated with the ULTRA pulse detection program and compared by analysis of variance (ANOVA) with repeated measures. RESULTS: In men mean concentrations of LH showed a significant interaction (p < 0.05) between exposure and sampling period, with a greater LH decline during exposure to toluene than sham exposure. However, there was no concomitant effect on testosterone concentrations. The LH pulse frequency of women in the luteal phase showed a trend towards a significant interaction between exposure and sampling period (p = 0.06), with a greater decline in pulse frequency during exposure to toluene than sham exposure. There were no other significant effects of exposure to toluene. CONCLUSIONS: Three hour exposure to 50 ppm toluene did not result in abnormal episodic LH or FSH secretion profiles, however, subtle effects on LH secretion in men and women in the luteal phase were found. The clinical relevance of these effects is unclear, indicating the need for further study of reproductive function in exposed workers.

 

     

Lack of allergic reactions in workers exposed to Pruteen (bacterial single-cell protein).

Men exposed to high concentrations of bacterial single-cell protein (Pruteen) dust have complained of "sticky eyes" and influenza-like symptoms. Over four years, surveillance of a work force of 70 men with a programme that included a respiratory health questionnaire, skin prick testing, serum testing for precipitating antibodies, lung function measurements, and chest radiography has shown no evidence of allergic reaction or of exposure-related deterioration in lung function. The symptoms experienced may be attributable to exposure to lipopolysaccharide. The results show that Pruteen can be produced and handled without adverse effects on health, provided that adequate measures are taken to prevent exposure to high concentrations of dust.     

Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: a cross-sectional pilot study

Background  

Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys.