石化企业乙烯厂环境空气中低浓度苯乙烯和三苯对男性生殖健康的影响

目的研究某石油化工企业乙烯厂区环境空气中苯乙烯和三苯有机物污染情况以及其长期低浓度对男性工作人员生殖健康的影响。方法监测某石油化工企业乙烯厂区环境空气中存在苯乙烯和三苯有机污染物的含量,利用碳管采样,气相色谱分析;对暴露组符合条件的120名23~49岁已婚男性工作人员抽血检查性激素三项:血浆的睾酮(TO)和血清促卵泡成熟激素(FSH)和促间质细胞分泌激素(LH)。对照组是符合配对条件的80名已婚男性;同时通过调查问卷(10项指标)对乙烯厂600名符合条件的已婚男性工作人员的生殖健康状况进行调查,对照组为非接触挥发性有机溶剂的港务企业600名已婚男性。结果石化乙烯厂区环境空气中检出低浓度的苯乙烯和三苯有机物污染物,监测结果均远低于国家规定限(PC-TWA);暴露组男性工作人员血性激素三项结果均显著低于对照组(P0.05);男性生殖健康调查问卷10项指标中,暴露组发病率均明显高于对照组(P0.05)。苯乙烯和三苯分别与性激素三项进行多元线性回归分析,相关系数在0.83~0.89之间,并且P值都小于0.05,苯乙烯和三苯分别与TO、FSH和LH呈线性相关。结论长期接触环境空气中低浓度苯乙烯和三苯对男性生殖健康有不良影响。     

Prolonged time to pregnancy in female workers exposed to ethylene glycol ethers in semiconductor manufacturing

BACKGROUND: Previous research on reproductive effects of working in the semiconductor industry is limited and has produced conflicting results. METHODS: This retrospective cohort study was designed to investigate the risk factors for female fertility in a wafer-manufacturing company of Taiwan in 1997. Waiting time to pregnancy and potential confounders were collected by face-to-face interview. Exposure was assessed by directors and senior engineers in manufacturing, administrative, and safety and health departments according to safety records, personnel records, and job histories from questionnaires, using a tiered exposure-assessment approach. Of a total 842 female workers, 720 (85.5%) participated. There were 292 pregnancies from 173 workers eligible for analysis. Relative fecundability (fecundability ratio, or FR) was calculated using Cox's proportional hazard models to evaluate the effect of occupational exposure to ethylene glycol ethers on female fertility. RESULTS: Waiting time to pregnancy of female workers in the photolithography area was longer than that of those in the nonfabrication area (FR = 0.77; 95% CI = 0.45-1.32), and those who were potentially exposed to ethylene glycol ethers showed longer time to pregnancy compared with those not exposed (FR = 0.59; 95% CI = 0.37-0.94). CONCLUSION: This study provides further evidence that ethylene glycol ethers may cause female subfertility.     

Glycol ethers and semen quality: a cross-sectional study among male workers in the Paris Municipality

Objectives

Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether‐based solvents have pronounced adverse effects on sperm production and male fertility in laboratory animals. The authors investigated the effects of past and current exposure to glycol ether‐containing products on semen quality and reproductive hormones among men employed by the Paris Municipality.

Methods

Between 2000 and 2001 the authors recruited 109 men who gave semen, blood and urine samples and underwent an andrological examination. Information on lifestyle, occupation, exposure and medical history was obtained by interview. According to their job and chemical products used during the period 1990–2000, men were classified as either occupationally exposed or non‐exposed. Current exposure levels to glycol ethers at the time of the study were evaluated by biological monitoring of six urinary metabolites.

Results

Previous exposure to glycol ethers was associated with an increased risk for sperm concentration, for rapid progressive motility and for morphologically normal sperm below the World Health Organization semen reference values. No effect of previous glycol ether exposure on hormones levels was observed. By contrast, current glycol ether exposure levels were low and not correlated with either seminal quality or hormone levels.

Conclusions

This study suggests that most glycol ethers currently used do not impact on human semen characteristics. Those that were more prevalent from the 1960s until recently may have long lasting negative effects on human semen quality.Male reproductive function has attracted increasing attention due to reports suggesting a recent decline in sperm production and quality in several areas of the world during recent decades.^1,2,3 These reports remain controversial and are currently the subject of intense research and debate. It is hypothesised that in utero exposure to environmental endocrine‐disrupting chemicals at critical stages of testis differentiation affects subsequent sperm production.⁴ However, there is clear evidence that exposure to some chemicals during adulthood could affect testicular and post‐testicular functions and male fertility.⁵ Studies on specific populations, exposed to well‐identified chemicals in occupational circumstances, have provided convincing evidence that some of these chemicals have adverse effects on male fertility.^6,7,8The general population has been in frequent and regular contact with glycol ether solvents since the 1960s.⁹ Their low acute toxicity and their highly miscibility in water and oils have favoured their inclusion in a range of products used professionally and domestically, including water‐based paints, cleaning products, liquid soaps, cosmetics and even some pharmaceutical products. More than 30 different glycol ethers have been produced by the chemical industry, and not all have the same toxicity. Two glycol ether families can be distinguished according to the synthesis procedure: ethylene glycol ethers and propylene glycol ethers. Numerous toxicological reports have shown that various ethylene glycol ethers, particularly the short‐chain ethylene glycol methyl ether (EGME) and ethylene glycol ethyl ether (EGEE), have pronounced adverse effects on sperm production and quality in the rat, mouse and rabbit.^9,10,11 The toxic effects of glycol ethers are thought to be mediated by their alkoxycarboxylic metabolites, which are rapidly eliminated by urines.^12,13 However, very few studies were conducted in human populations. At the end of the 1980s it was reported that shipyard painters and metal casting workers highly exposed to EGEE and EGME had low semen characteristics.^14,15 Recently, a study found no differences between the semen characteristics of 14 copper clad lamination workers exposed to EGME and 13 control workers, although the small size of this study population limited the conclusions.¹⁶ A case‐control study among infertility clinic consultants showed that urinary glycol ether metabolites were more frequently present in subjects with low semen characteristics.¹⁷ Difficulties in conceiving children have been reported in men working in the semi‐conductor industry and exposed to EGEE, EGME and perhaps other glycol ethers such as diethylene glycol dimethyl ether (DEGDME).¹⁸Considering the potential detrimental effects of glycol ethers, their uses were progressively regulated in some Western countries during the mid‐1990s.¹⁹ Short‐chain glycol ethers have been gradually replaced by long‐chain ethylene glycol ethers or by propylene glycol ethers, which are considered less toxic. Glycol ethers currently classified in the European Union as harmful for reproduction (category 2) are EGEE, EGME, DEGDME, ethylene glycol dimethyl ether (EGDME), triethylene glycol dimethyl ether (TEGDME) and 1‐propylene glycol 2‐methyl ether (1PG2ME).The objective of the present study was to determine whether past or current exposure to glycol ether‐containing products is associated with a modification of testicular function and reproductive hormones. We performed a cross‐sectional study to assess semen quality and hormones in men working for the Paris Municipality.     

The influence of occupational exposure on male reproductive function

Recently, many studies have found a decrease in semen quality which has increased the focus on male reproductive health. Occupational hazards are by far the best documented in reproductive epidemiological research. Generally, occupational exposures have been divided into physical exposures (heat and radiation), chemical exposures (solvents and pesticides), psychological exposures (distress), exposure to metals and welding. The recent and/or most important epidemiological studies exploring the effect of occupational exposures on semen quality and fecundity, the ability to conceive, are reviewed. The evidence for an adverse effect on male reproduction of several occupational and environmental exposures and toxicants, such as heat, ionizing radiation, inorganic lead, dibromochloropropane, ethylene dibromide, some ethylene glycol ethers, carbon disulfide and welding operations, is strongly supported in well-designed epidemiological studies. For other agents, the association is only suspected or suggested and needs further evaluation before conclusions can be drawn. It is also important to bear in mind that many workers in the non-Western world still are exposed to substances that are banned in the Western world, sometimes in high concentrations.     

Hepatic effects among workers exposed to ethylene glycol monoethyl ether acetate

Data about hepatic effects of ethylene glycol ethers had been limited and inconsistent. In this study, we determined whether ethylene glycol monoethyl ether acetate (EGEEA) was a hepatotoxin in exposed workers. Workers from one silk-screening shop (n=29), using EGEEA as the major cleaning solvent, were recruited as high exposure group. Another group of workers with indirect and low exposure to EGEEA (n=57) were selected as the comparison group. Air concentration of EGEEA was measured by 8-h personal sampling. The mean of air EGEEA concentration in the high exposure group was 7.41-16.5 ppm. The mean of air EGEEA concentration in the low exposure group was 0.07-3.62 ppm. Liver function profiles showed that the AST, ALT, ALP and gamma GT in both male and female EGEEA-exposed workers were not significantly different from those in the comparison group. After adjustment for potential confounders such as gender, body mass index, hepatitis B status, and duration of employment, no difference in hepatic dysfunction were found between exposed and comparison groups. In addition, a two-year follow-up study of these EGEEA-exposed workers, no significant change in hepatic function was noted either. The findings suggest that EGEEA is not a hepatotoxin in this workplace.     

汞对男工生殖功能影响的研究

本文对某荧光灯厂３７名男工的生殖功能调查研究的结果表明：工人在作业环境汞浓度超标情况下作业，导致休内汞负荷水平的增高。血汞和精汞含量（分别为０．０５８１ｍｇ／Ｌ和０．０２７０ｍｇ／Ｌ）均比对照组（分别为０．０１０９ｍｇ／Ｌ和０．１３９ｍｇ／Ｌ增高，Ｐ＜０．０１。工人的生殖功能也受到一定的影响，表现为精液量减少，液化时间延长，精子的密度减小、一次射精子数减少、活精率下降，精子畸形率增高。同时，还观察     

Urinary alkoxyacetic acids and renal effects of exposure to ethylene glycol ethers.

OBJECTIVES: Ethylene glycol ethers and their acetates are widely used in industry, because of their hydrophilic and simultaneously lipophilic properties. Ethylene glycol ethers and their acetates are mainly metabolised to alkoxyacetic acids, but there is also a minor pathway through ethylene glycol to oxalic acid. The main pathway of ethylene glycol ethers is associated with significant clinical or experimental health effects and the minor pathway is also interesting because formation of urinary stones depends principally upon the urinary concentration of oxalate and calcium. METHODS: Excretion of alkoxyacetic and oxalic acids was examined among silkscreen printers for an entire working week. The aim of the study was to evaluate alkoxyacetic acids as early indicators of exposure to glycol ethers and to evaluate their toxicity to kidneys. The load of alkoxyacetic and oxalic acids was compared with the excretion of calcium, chloride, ammonia, and glycosaminoglycans (GAG). Morning urine was chosen for the main analysis, as the overall metabolite, ethoxyacetic acid (EAA), has a long elimination time from the body. RESULTS: The excretion of calcium increased according to the urinary alkoxyacetic acid load. The excretion of ammonia and chloride was higher among the exposed workers than among the controls. The highest urinary alkoxyacetic acid load was also associated with increased excretion of GAG, which may reflect the toxicity of metabolites of ethylene glycol ether. The excretion of GAG correlated positively with that of calcium in the printers with highest exposure. The tendency to form urinary stones was 2.4-fold higher among silkscreen printers than among office workers. CONCLUSION: On the basis of renal effects our study indicates the need for establishing a new biological exposure limit before a workshift that is clearly below 100 mmol ethoxyacetic acids per mol creatinine in morning urine of people occupationally exposed to ethylene glycol ethers.     

Effect of occupational exposures on male fertility: literature review

The present review was aimed to determine the influence of working conditions, occupational exposures to potential chemical and physical reproductive toxic agents and psychological stress during work on male fertility. Significant associations were reported between impaired semen parameters and the following chemical exposures: metals (lead, mercury), pesticides (dibromochlorophane, 2,4-dichlorophenoxyacetic acid), ethylene glycol ethers and estrogens. The following physical exposures were shown to deteriorate sperm parameters: radiation (both ionized and microwaves) and heat. Psychological distress has another important contribution to infertility. Several studies indicated that stress has a negative impact on sperm parameters. Occupational parameters should be an important part of history taking among patients attending infertility clinics.     

Haematological and spermatotoxic effects of ethylene glycol monomethyl ether in copper clad laminate factories

OBJECTIVES—To investigate the effects of ethylene glycol monomethyl ether (EGME) on haematology and reproduction in exposed workers.
METHODS—53 Impregnation workers from two factories that make copper clad laminate with EGME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to EGME was recruited as the control group. Environmental monitoring of concentrations of EGME in air and biological monitoring of urinary methoxyacetic acid (MAA) concentrations were performed. Venous blood was collected for routine and biochemical analyses. Semen was collected from 14 workers exposed to EGME for sperm analysis and was compared with 13 control workers.
RESULTS—Results of haematological examination showed that the haemoglobin, packed cell volume, and red blood cell count in the male workers exposed to EGME were significantly lower than in the controls. The frequency of anaemia in the exposed group (26.1%) was significantly higher than in the control group (3.2%). However, no differences were found between the female workers exposed and not exposed to EGME. After adjustment for sex, body mass index, and duration of employment, red blood cell count was significantly negatively associated with air concentrations of EGME, and haemoglobin, packed cell volume, and red blood cell count were significantly negatively associated with urinary concentrations of MAA. The pH of semen in the exposed workers was significantly lower than in the control workers, but there were no significant differences in the sperm count or sperm morphology between the exposed and control groups.
CONCLUSION—It can be concluded that EGME is a haematological toxin, which leads to anaemia in the exposed workers. However, the data from this study did not support the theory of a spermatotoxic effect of EGME.


Keywords: ethylene glycol monomethyl ether; haematological disorders; spermatotoxicity     

Determination of urinary alkoxyacetic acids by a rapid and simple method for biological monitoring of workers exposed to glycol ethers and their acetates

Summary In control subjects and workers exposed to glycol ethers and their acetates, we determined the urinary metabolites (three alkoxyacetic acids) by a simple and rapid method. Levels of urinary metabolites were significantly higher in the solvent workers than in the nonexposed subjects. The exposure levels measured by personal monitoring of breathing zone air were far below the threshold limit value. The present results indicate that determination of urinary alkoxyacetic acids by the practical method used here is useful for evaluating excessive exposure to solvents.     

二硫化碳职业暴露对男工性功能及其配偶生殖结局的影响

[目的]探讨CS2职业暴露对男工性功能及其配偶生殖结局的影响,为制定干预对策提供科学依据。[方法]对276名CS2暴露男工（其中仅男工暴露132人为单纯组,男工及其妻子均暴露144人为混合组）和126名非CS2暴露男工的基本情况、性功能及其配偶生殖结局进行回顾性队列研究。[结果]性功能调查结果显示,年龄〈40岁或工龄≥10年的CS2暴露组男工性生活和谐及性生活频度降低,性生活厌恶增加（P〈0.05）;各组间男工妻子妊娠并发症差异无统计学意义（P〉0.05）。生殖结局调查结果表明,混合组的自然流产率与单纯组、对照组比较具有统计学意义（P〈0.05）;混合组与对照组比较,子代低出生体重率较高（P〈0.05）,子代智力发育及体格发育差异无统计学意义（P〉0.05）。[结论]长期、低浓度CS2暴露可明显影响男工性生活态度、频率并可能导致不良的生殖结局,但对子代的智力及体格发育影响不明显。     

An assessment of fertility in male workers exposed to molinate.

Molinate is a thiocarbamate herbicide used for weed control in rice fields. Since the late 1970s, findings from reproductive toxicology studies of rats have led to concern that molinate might affect human male fertility. Semen samples were collected from 272 formulation and production workers at three US plants. The samples were collected at the end of four alternate monitoring periods of either high or low exposure to molinate. In addition, 222 married workers provided reproductive-history information. Workers' mean exposures to molinate during the monitoring periods ranged from 12.7 micrograms/m3 to 210.9 micrograms/m3. There was no evidence that sperm and serum hormone levels were related to exposure to molinate before the study or exposure during the four monitoring periods. There was also no evidence of a molinate exposure-related effect on the ratio of observed to expected births.     

Evaluation of glove material resistance to ethylene glycol dimethyl ether permeation

Some glycol ethers have been reported to cause adverse reproductive effects in exposed male and female workers, and skin absorption has been determined to be an important route of entry of this class of chemicals. Because ethylene glycol dimethyl ether (EGDME) is a possible component of lithium-based primary battery electrolyte systems, a study was undertaken to determine the resistance of various commercially available gloves to permeation of this liquid. The gloves were tested by the ASTM Method F-739-81, and butyl rubber was found to be the most effective barrier to permeation. Further studies determined that the butyl gloves could be reused if they were reconditioned overnight in a vacuum oven at 50 degrees C. When a mixture of ethylene glycol dimethyl ether (30% v/v) and propylene carbonate (70% v/v) was tested, the results indicated that the propylene carbonate retards the permeation of the glycol ether by a factor of 10. This is believed to be caused by the propylene carbonate coating the surface of the butyl membrane to reduce the sorption of EGDME.     

The effect of male occupational exposure in infertile couples in Norway

The objective of the study was to assess whether reduced semen quality in infertile couples is associated with occupational exposures known to be hazardous to fertility. Results of the first semen analysis were linked to occupational exposure data from a self-administered questionnaire. Reduced semen quality was found in men exposed to electromagnetic fields (odds ratio, 3.22; confidence interval, 1.46 to 7.09). A tendency toward reduced semen quality was seen in commuters (OR, 1.52; CI, 0.89 to 2.59), shift workers (OR, 1.46; CI, 0.89 to 2.40), and men exposed to heavy metals (OR, 1.47; CI, 0.76 to 2.87). In general, the impact of occupational exposure on semen quality in infertile couples in Norway seemed to be minor. However, occupational exposure mapping is still important in individual infertility investigations.     

An epidemiologic surveillance program for evaluating occupational reproductive hazards

A noninvasive and inexpensive epidemiologic program for evaluating the possible effects of occupational exposures on fertility is proposed. This surveillance program utilizes reproductive information obtainable from a short questionnaire (1-2 pages in length) or directly from existing medical, employment, or insurance records, and results can be generated readily on a routine basis. This program examines the reproductive experience of the exposed workers in terms of live births compared with that of the US general population with the proper statistical adjustments. It calculates the standardized birth ratios (SBR), adjusting for maternal age, parity, calendar time, and race. Such an analysis will detect whether there is a significant decrease in fertility among a group of employees, and is, therefore, a useful surveillance tool. The proposed method should be viewed as a mechanism to provide an early signal for any potential hazard and to direct priority for other more in-depth epidemiologic or physiologic studies. The procedure is illustrated with data from individuals exposed to EDB, DBCP, and waste-water treatment plant processes. The method can be modified to compare the reproductive performance of an exposed group to that of an internal control group. With an internal control group, additional confounding factors can be taken into consideration. The relative merits of this approach compared to another method of fertility evaluation, semen analysis, are discussed.     

Occupational exposure to glycol ethers and human congenital malformations

Objectives This commentary reviews toxicological information and critically evaluates epidemiological information on the relationship between glycol ethers and congenital malformations.Methods The authors identified and assessed toxicological and epidemiological research on glycol ethers used in occupational settings and congenital malformations. Sensitivity analyses evaluated the possible role of methodological problems in explaining the findings of the epidemiological studies.Results Exposure to certain glycol ethers, including ethylene glycol monomethyl ether and ethylene glycol mono-ethyl ether, throughout the period of major organogenesis, has induced malformations of many organ systems in some of the animal models studied. Other glycol ethers, including ethylene glycol butyl and propyl ethers and most propylene glycol ethers, have not induced fetal malformations in the animal models studied. Four epidemiological studies have assessed the relationship between occupational exposure to glycol ethers and congenital malformations in humans. One study was uninformative because of small numbers, two found a positive association between glycol ethers and malformations of a number of different organs, and one found no association with neural-tube defects. Sensitivity analyses indicated that the results of the latter three investigations could be due to methodological problems. The positive studies, further, lack biological plausibility, in that the glycol ethers to which the subjects were exposed have not been, for the most part, teratogenic in the animal models that have been studied.Conclusions The current evidence is insufficient for one to determine whether occupational exposure to glycol ethers causes human congenital malformations. We suggest that future studies quantify the effect of methodological problems on study results, using methods such as validation studies and sensitivity analysis.     

A Cross-Sectional Study of Ethylene Glycol Monomethyl Ether Process Employees

Human exposures to ethylene glycol monomethyl ether have been associated with hematological and neurological abnormalities. Recent animal toxicology studies have also reported testicular atrophy. To determine whether employees potentially exposed to ethylene glycol monomethyl ether during manufacturing and packaging had a higher prevalence of anemia, leukopenia, or sterility than an in-plant comparison group, a crosssectional study was conducted at the Michigan Division of Dow Chemical U.S.A. Blood samples on 65 of 97 potentially exposed and control white males, and semen samples from a subset of 15 were analyzed. With the possible exception of smaller testicular size, no gross abnormalities or clinically meaningful differences in hematological or fertility indices were noted. Results of regression modeling suggested that white blood cells and hemoglobin might be decreased at higher exposure levels.     

二硫化碳作业男工性功能和精液状态的调查研究

对接触CS_2的平均浓度为35mg/m3的38名已婚纺丝男工性功能调查结果,性欲减退者36.8％,显著高于对照组。对100名纺丝男工精液检查结果,精子形态异常率高者、精子活动率低者、精子数少者和精液液化时间长者分别有64％、48％、37％和17％,均显著高于对照组。表明CS_2能损害男工性功能和精液生成。     

二硫化碳作业男工性功能和精液状态的调查研究

对接触CS_2的平均浓度为35mg/m~3的18名已婚纺丝男工性功能调查结果,性欲减退者36.8%,显著高于对照组.对100名纺丝男工精液检查结果,精子形态异常率高者、精子活动率低者、精子数少者和精液液化时间长者分别有64%、48%、37%和17%,均显著高于对照组.表明CS_2能损害男工性功能和精液生成.     

Influence of pesticides on male fertility

Several studies have shown a decline in human semen quality and increased risks of male subfertility. This paper provides an overview of the mechanisms of pesticide-induced reproductive toxicity and the effects on male fertility since exposure to pesticides may be one of the causes of these disorders. Pesticides may directly damage spermatozoa, alter Sertoli cell or Leydig cell function, or disrupt the endocrine function in any stage of hormonal regulation (hormone synthesis, release, storage, transport, and clearance; receptor recognition and binding; thyroid function; and the central nervous system). These mechanisms are described with respect to the effects of pesticide exposure in vitro and in vivo. In epidemiologic studies, effects on sperm quality and time to pregnancy are reviewed. Clear effects on male fertility have been demonstrated for some pesticides [eg, dibromochloropropane, ethylene dibromide]. But results from more recent studies are inconsistent, and no uniform conclusion can be drawn about the effects of pesticides on male reproduction.