An evaluation of the associations of leukemia and rubber industry solvent exposures

Excessive leukemia mortality has appeared consistently in epidemiological studies of British and U.S. rubber industry workers. Attempts to identify causative factors have focused on exposure to benzene and other solvents. Interpretations of findings from these studies have often been influenced by expectations of a benzene/nonlymphocytic leukemia association, seen from previous work in other settings. However, data from the rubber industry studies have not been consistent with this expectation, as lymphocytic and nonlymphocytic leukemia have shown similar mortality excesses. Data from a small case-control study of lymphocytic leukemia are presented to illustrate an approach that considers multiple solvent exposures. The associations with lymphocytic leukemia risk observed for a number of solvents, most notably carbon tetrachloride and carbon disulfide, were stronger than those detected for benzene.     

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.     

Epidemiological appraisal of studies of residential exposure to power frequency magnetic fields and adult cancers.

OBJECTIVES: To appraise epidemiological evidence of the purported association between residential exposure to power frequency magnetic fields and adult cancers. METHODS: Literature review and epidemiological evaluation. RESULTS: Seven epidemiological studies have been conducted on the risk of cancer among adults in relation to residential exposure to power frequency magnetic fields. Leukaemia was positively associated with magnetic fields in three case-control studies. The other two case-control studies and two cohort studies did not show such a link. Brain tumours and breast cancer have rarely been examined by these studies. Based on the epidemiological results, the analysis of the role of chance and bias, and the criteria for causal inferences, it seems that the evidence is not strong enough to support the putative causal relation between residential exposure to magnetic fields and adult leukaemia, brain tumours, or breast cancer. Inadequate statistical power is far more a concern than selection bias, information bias, and confounding in interpreting the results from these studies, and in explaining inconsistencies between studies. CONCLUSIONS: Our reviews suggested that the only way to answer whether residential exposure to magnetic fields is capable of increasing the risks of adult cancers is to conduct more studies carefully avoiding methodological flaws, in particular small sample size. We also suggested that the risk of female breast cancer should be the object of additional investigations, and that future studies should attempt to include information on exposure to magnetic fields from workplaces as well as residential exposure to estimate the effects of overall exposure to magnetic fields.     

Does secondhand smoke affect the development of dental caries in children? A systematic review

This review evaluated evidence of the relationship between secondhand smoke (SHS) and dental caries in children in epidemiological studies. Relevant literature was searched and screened, and the methodological quality was assessed. The search yielded 42 citations. High-quality studies including one cohort format and 14 case-control format studies were selected. Early childhood caries was examined in 11 studies. The independent association of SHS was significant in 10 studies, and the strength was mostly weak to moderate. One study did not select SHS as a significant variable. Three studies reported decreases in the risk of previous exposure, and the association was not significant. Dose-response relationships were evident in five studies. Permanent teeth were examined in seven studies. Five studies reported significant associations, which were mostly weak. The risk of previous exposure remained similar to that of current exposure, and a dose-response relationship was not evident in one study. The overall evidence for the causal association in early childhood caries is possible regarding epidemiological studies, and the evidence of permanent teeth and the effect of maternal smoking during pregnancy were insufficient. The results warrant further studies of deciduous teeth using a cohort format and basic studies regarding the underlying mechanism.     

Exposure to organic solvent mixture and hearing loss: literature overview

The chemical sector is the third largest industry in Europe. There is increasing evidence from epidemiological and clinical studies that occupational exposures to organic solvents may have detrimental effect on hearing. Most of the literature data concern one of the three following types of exposure to industrial solvents: mixed solvent exposure (the most common type); styrene-only exposure; and toluene-only exposure. This paper overviews the effects of industrial exposure to a mixture of organic solvents on hearing, with special regard to the dose-response relationship. Although the existing data make it difficult to derive a correlation between solvent concentration and hearing outcome, the current occupational exposure limits for solvents seem to be inadequate with respect to the effect that solvents may have on the auditory system.     

外源性物质对雄性生殖系统的影响

本综述基于近期的流行病学和动物实验研究，对接触外源性物质对雄性生殖系统的影响进行探讨。雄性生殖系统的损伤主要表现为精子功能、数量和雄性生育能力的改变。研究表明，很多外源性物质主要包括杀虫剂、金属、有机溶剂和药物等会抑制精子发生过程，导致雄性不育，对雄性生殖系统产生不良影响，所以必须选择性的使用外源性物质。     

Implications from epidemiologic studies on magnetic fields and the risk of childhood leukemia on protection guidelines

The objective of this review is to discuss the impact of findings in epidemiological studies on magnetic fields and the risk of childhood leukemia on the definition of exposure limits. A large number of epidemiological studies have consistently shown an association between the risk of childhood leukemia and residential extremely low-frequency magnetic field exposures. There is virtually no supportive data from experimental research and, so far, no proposed explanation has reached a level beyond speculation. The contradictory results from epidemiological and experimental research may either be due to methodological limitations creating a spurious association in the epidemiological studies or to a failure of experimental research to examine mechanisms relevant in the complex origin of childhood leukemia. Taking this together, the overall evidence is not strong enough to demand a revision of the current guidelines for public protection. Application of precautionary measures may be an option; however, decision-makers should be advised that these measures are often not straightforward and a careful evaluation of a possible benefit needs to be performed for each individual situation. Undoubtedly there are gaps in research, and no substantial contribution for clarification of the apparent inconsistencies emerges from recent studies. However, there are important lessons to learn, either with respect to the etiology of childhood leukemia or with respect to the need for improving epidemiological methods for the identification of presumably weak associations.     

Assessment of exposure in epidemiological studies: the example of silica dust

Exposure to crystalline silica ranks among the most frequent occupational exposures to an established human carcinogen. Health-based occupational exposure limits can only be derived from a reliable dose-response relationship. Although quartz dust seems to be a well-measurable agent, several uncertainties in the quantification of exposure to crystalline silica can bias the risk estimates in epidemiological studies. This review describes the silica-specific methodological issues in the assessment of exposure. The mineralogical forms of silica, the technologies applied to generate dust, protective measures, and co-existing carcinogens are important parameters to characterize the exposure condition of an occupational setting. Another methodological question concerns the measurement of the respirable dust fraction in the worker's breathing zone and the determination of the quartz content in that fraction. Personal devices have been increasingly employed over time, whereas norms for the measurement of respirable dust have been defined only recently. Several methods are available to analyse the content of crystalline silica in dust with limits of quantitation close to environmental exposure levels. For epidemiological studies, the quartz content has frequently not been measured but only calculated. To develop a silica-dust database for epidemiological purposes, historical dust concentrations sampled with different devices and measured as particle numbers have to be converted in a common exposure metric. For the development of a job-exposure matrix (JEM), missing historical data have to be estimated to complete the database over time. Unknown but frequently high-exposure levels of the past contribute largely to the cumulative exposure of a worker. Because the establishment of a JEM is crucial for risk estimates, sufficient information should be made accessible to allow an estimation of the uncertainties in the assessment of exposure to crystalline silica. The impressive number of silica dust measurements and the evaluation of methodological uncertainties allow recommendations for a best practice of exposure assessment for epidemiological studies.     

Hypotheses on the Fetal Origins of Adult Diseases: Contributions of Epidemiological Studies

Epidemiological studies have demonstrated associations between low birth weight and cardiovascular disease, type 2 diabetes and their risk factors in adult life. These findings have led to sharp debates in the literature concerning potential methodological study flaws and the effect size and causality of the associations. More recent studies seem to have overcome most methodological flaws and suggest a small effect size of low birth weight on adult diseases for the individual. However, the effect size may still be important on a population level. Various causal pathways have been hypothesized as mechanisms underlying these associations. These hypotheses have proposed central roles for (1) fetal undernutrition, (2) increased cortisol exposure, (3) genetic susceptibility and (4) accelerated post-natal growth. These hypotheses have been studied in various epidemiological study designs. Thus far, it is still not known which mechanisms underlie the associations between low birth weight and diseases in adult life. The causal pathways linking low birth weight to diseases in later life seem to be complex and may include combined environmental and genetic mechanisms in various periods of life. Well-designed epidemiological studies are necessary to estimate the population effect size and to identify the underlying mechanisms. This knowledge is needed to develop strategies for identifying groups at risk and prevention focused on early life.     

Enterolactone and breast cancer: methodological issues may contribute to conflicting results in observational studies

Lignans found in plant foods are converted by the intestinal microflora to enterolignans. The structure of enterolignans is similar to that of estrogens, which has inspired researchers to examine a potential protective association in relation to health outcomes. Numerous epidemiological studies have measured concentration of enterolignans, mainly enterolactone, in blood or urine as a biomarker of lignan exposure and studied its relation to breast cancer risk. Case-control studies have shown decreased breast cancer risk associated with high circulating enterolactone concentrations, but results demonstrated by prospective cohort studies are less clear. The purpose of this review is to discuss factors that may contribute to these contradictory findings obtained in epidemiological studies, including age distribution, enterolactone measurement error, heterogeneity of breast cancer subtypes, and genetic factors. Different sources of enterolactone precursors may also contribute to inconclusive results. In conclusion, to get robust evidence of the health effects of lignans and enterolactone, more effort has to be put on methodological problems, including reducing measurement errors in enterolactone estimation, and to identify factors that modify the effect.     

Reproductive hazards related to perchloroethylene

The literature of perchloroethylene (PER) was scrutinized to find answers to the following questions: (1) is an effect of PER on reproduction to be expected, and (2) if so, has such an effect actually been shown in animal experiments and/or in epidemiological studies? From this review it can be concluded that the first question should be answered in the affirmative, considering the various mechanisms capable of leading to defects in the reproductive processes and the information about how PER can interact (and in fact does interact) with these mechanisms. The few studies in which the effects of PER exposure on reproductive outcome have been studied are, however, not very conclusive. Some suggest an effect, others do not. In view of the incompleteness of the experimental results and the methodological shortcomings especially of the epidemiological studies, there is a need for a suitably designed epidemiological investigation on the reproductive consequences of exposure to PER. In order to avoid the methodological problems of the above-mentioned studies, the design should be a prospective one.     

Biomarkers of ambient air pollution and lung cancer: a systematic review

The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions.     

Chemical exposure during pregnancy and oral clefts in newborns

This article presents a literature review on the risk factors for oral clefts (lip and/or palate), emphasizing discussion of maternal exposure to endocrine disruptors. Several studies have identified the risk of cigarette smoking and alcohol consumption, use of anticonvulsant drugs, and exposure to organic solvents. A protective effect has been shown for supplementation with folic acid. As with other chemicals, the risk associated with exposure to sex hormones is still obscure, although some authors describe a moderate risk level. New studies addressing this hypothesis need to be conducted, while the population exposed to these endocrine disrupters is increasing.     

Lower back disorders among forklift operators: An emerging occupational health problem?

BACKGROUND: Most studies focusing on the occupational hazards associated with forklift operation have examined risks of fatalities and traumatic injuries. Few studies have examined the magnitude of risk of musculoskeletal disorders (MSDs). We review and critically appraise the epidemiological studies conducted on forklift operators in relation to MSDs, such as lower back pain and neck problems. METHODS: A comprehensive search of databases resulted in the identification of seven epidemiological studies that addressed MSDs. A critical appraisal of these studies was conducted using epidemiological principles and a meta-analysis approach that involved the use of the confidence limit method to determine an overall "meta-odds ratio." RESULTS: The methodological quality of these studies ranged from "marginal" to "average" with the exception of one study, which was considered "good." The meta-odds ratio for lower back pain among forklift operators was 2.13 (95% CI: 1.57, 2.87). CONCLUSIONS: Our results suggest that forklift operators are at increased risk of lower back pain. Additional high quality epidemiological studies are needed in the US, however, to determine the magnitude of risk for MSDs. In this regard, studies should address not only lower back pain among forklifts operators, but also neck pain. A full exposure assessment of physical and non-physical factors in these studies is needed.     

History of health studies around nuclear facilities: a methodological consideration

A brief historical review was made of low-level radiation studies for general populations living around nuclear facilities. In addition, technical and methodological problems were identified and discussed which often arise in all epidemiological studies designed to determine the possible health effects of low-level radiation released from nuclear facilities. Many of the studies reviewed were incomplete from the methodological standpoint; thus findings may be considered inconclusive. Some others presented an inadequate study design with contradictory results. Need for extremely large populations for prospective cancer studies was discussed, but accompanying ascertainment difficulties were also emphasized. More epidemiological studies are needed to provide adequate assessment of the potential health hazards of nuclear facilities.     

Residential exposure to electromagnetic fields and childhood leukaemia: a meta-analysis

Although individual epidemiological investigations have suggested associations between residential exposure to electromagnetic fields (EMFs) and childhood leukaemia, overall the findings have been inconclusive. Several of these studies do, however, lend themselves to application of the meta-analysis technique. For this purpose we carried out searches using MEDLINE and other sources, and 14 case-control studies and one cohort study were identified and evaluated for epidemiological quality and included in the meta-analysis. Relative risk estimates were extracted from each of the studies and pooled. Separate meta-analyses were performed on the basis of the assessed EMF exposure (wiring configuration codes, distance to power distribution equipment, spot and 24-h measures of magnetic field strength (magnetic flux density) and calculated magnetic field). The meta-analysis based on wiring configuration codes yielded a pooled relative risk estimate of 1.46 (95% confidence interval (CI) = 1.05-2.04, P = 0.024) and for that for exposure to 24-h measurements of magnetic fields, 1.59 (95% CI = 1.14-2.22, P = 0.006), indicating a potential effect of residential EMF exposure on childhood leukaemia. In most cases, lower risk estimates were obtained by pooling high-quality studies than pooling low-quality studies. There appears to be a clear trend for more recent studies to be of higher quality. Enough evidence exists to conclude that dismissing concerns about residential EMFs and childhood leukaemia is unwarranted. Additional high-quality epidemiological studies incorporating comparable measures for both exposure and outcomes are, however, needed to confirm these findings and, should they prove to be true, the case options for minimizing exposure should be thoroughly investigated to provide definitive answers for policy-makers.     

Review of studies on exposure to aluminum and Alzheimer's disease

A review has been made of the epidemiological studies published evaluating the role of aluminum as a risk factor for developing Alzheimer's disease. A search for published studies was conducted in the Medline database by combining the terms "Aluminum" and "Alzheimer's disease". In most of the studies reviewed, exposure to aluminum in drinking water was examined. These studies suggest that a relationship exists between aluminum (Al) and Alzheimer's disease involving relative risks of around 2 for populations exposed to Al concentrations in drinking water higher than 0.1 mg/l. Types of exposure to this metal by other means (food, medications and occupational exposure) have received little attention. These epidemiological studies entail certain methodological limitations, and their results are not consistent, so the results available to date therefore not making it possible to clearly determine that any relationship exists between exposure to aluminum and the etiology of Alzheimer's disease. Nevertheless, the toxic effect of aluminum on human health cannot be ruled out either, and thus exposure to aluminum should be monitored and limited as far as possible.     

Occupational exposures to asbestos,polycyclic aromatic hydrocarbons and solvents,and cancers of the oral cavity and pharynx: a quantitative literature review

Purpose  

The role of occupational risk factors in oral and pharyngeal cancer is not well known and is possibly underestimated. This quantitative review summarizes epidemiological findings on exposure to asbestos, polycyclic aromatic hydrocarbons and solvents, and cancers of the oral cavity and pharynx.     

Health effects of naturally radioactive water ingestion: the need for enhanced studies

Background: Radiological pollution is a potentially important aspect of water quality. However, relatively few studies have been conducted to document its possible health effects.Objective: In this commentary we discuss available epidemiological findings and related data from experimental studies concerning the health effects of naturally radioactive water ingestion.Discussion: Despite modest epidemiological evidence of uranium nephrotoxicity and radium effects on bone, available data are not sufficient to quantify the health effects of naturally occurring radionuclides in water. Methodological limitations (exposure measurement methods, control for confounding, sample size) affect most studies. Power calculations should be conducted before launching new epidemiological studies focusing on late pathological outcomes. Studies based on biomarkers of exposure and adverse effects may be helpful but should involve more specific molecules than biomarkers used in previous studies. Experimental data on ingestion of drinking water are limited to uranium studies, and there is some disagreement between these studies about the nephrotoxicity threshold.Conclusion: Further experimental and enhanced epidemiological studies should help to reduce uncertainties resulting from dose estimation to dose–response characterization.     

Health effects of phenoxy herbicides. A review

A review of epidemiological studies on the health effects of exposure to phenoxy herbicides suggests that exposure may be associated with an increased incidence of cancer and unfavorable outcomes of pregnancy. Studies on cancer have found increased risks of 5.3, 6.8 and 3.96 for soft-tissue sarcoma, 7.7 and 6.0 for stomach cancer, 2.05 for lung cancer, 4.8 for lymphoma, 2.3 for all cancers combined, and 5.2 for liver cancer after exposure to 2,4,5-T or dioxin contaminants. Several studies have suggested a possible increase in birth defects after paternal exposure. An increased risk of hydatidiform mole is suggested by Vietnamese studies on the effects of maternal exposure.