MTBE: recent carcinogenicity studies

Abstract

MTBE, a gasoline oxygenate, has contaminated drinking water sources for many years. Carcinogenicity studies conducted in animals in the 1990s raised concerns of potential human health risks. Recent industry-sponsored studies have confirmed the carcinogenic effects of this agent and have identified additional sites of tumor induction (i.e., brain). However, the petroleum industry has attempted to portray these recent findings as demonstrating either no effect or no concern for humans. Our paper briefly summarizes the new findings and puts into perspective the totality of carcinogenic effects and health risks on this environmental chemical.     

A review of potential human carcinogenicity of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP.

For the purpose of assessing the human carcinogenic potential of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP, the relevant epidemiological and toxicological evidence is reviewed. These compounds have not produced tumours in animal studies conducted under current test guidelines, giving no reason to predict that they would be carcinogenic to humans. Epidemiological studies have been conducted on three continents; greater emphasis is placed on the studies reported from western Europe, however, as this has been the area of more use. Although several of these studies provide suggestive evidence of associations between exposure to chlorophenoxy compounds and increased risks for some uncommon cancers, it is inconsistent and far from conclusive. None of the evidence specifically implicates MCPA, MCPP, or 2,4-DP as human carcinogens.     

氯丁二烯对人体健康损害研究概况

近年来,针对氯丁二烯的相关毒理学研究越来越深入,动物实验表明氯丁二烯对多个靶器官(如鼻、肺、肝,皮肤)有毒作用和致癌效应,国际癌症研究机构将其定为人类可能致癌物;但我国有关氯丁二烯的诊断及其分级指标、处理原则自1988年以来未做过调整。为此,拟对20多年来氯丁二烯对人体健康损害的研究概况作一综述,作为新标准修订时的参考。     

Mortality of iron-steel workers in Anshan, China: a retrospective cohort study

Foundry workers have increased mortality and morbidity risks from numerous causes, including various cancers. A retrospective Chinese iron-steel cohort study was conducted to examine the mortality effects of exposure to foundry work. Standardized mortality ratios (SMRs) and standardized rate ratios (SRRs) were calculated to evaluate mortality risks among male workers with exposure to 15 hazardous factors, adjusting for confounders. During 14 years of follow-up, 13,363 of 121,846 male workers died. SMR analysis showed a healthy-worker effect in comparison with the general population. SRR analysis showed increased risks for all causes, all neoplasms, and others among the exposed workers compared with non-exposed blue-collar workers. Combined exposure to polycyclic aromatic hydrocarbons and two or more dusts increased the risks of lung cancer (SRR = 654; 95% CI: 113-3,780) and other malignancies. Foundry work has adverse health effects, including carcinogenic risks.     

典型重金属污染地区学龄前儿童镉暴露健康风险评价

目的 评价典型重金属污染地区学龄前儿童镉(Cadmium,Cd)暴露健康风险.方法 采集某典型重金属污染地区土壤样本和蔬菜可食用部位并检测其Cd浓度,查阅当地空气、小麦、水稻和水的Cd浓度,通过美国国家环境保护局推荐的健康风险评价模型评价当地学龄前儿童的Cd暴露健康风险,分别采用危险系数(hazard quotient...     

Implementation of the precautionary principle in standards for the workplace.

The objectives were to describe and discuss the current and proposed European occupational health policy on two categories of substances that pose serious effects: those potentially carcinogenic or genotoxic and those with toxic effects on reproduction. The precautionary principle was applied to setting standards for the workplace for those two categories of substances, to give an impression of the resulting limit values and the consequences of the implementation of this precautionary principle. A pragmatic approach was chosen as this starts with substantial indications of health risks. For the suspected carcinogenic or genotoxic substances 0.1 mg/m3 as a precautionary occupational exposure limit (precautionary OEL) is proposed. For the substances suspected of causing reproductive toxicity the precautionary OEL was derived in three ways, depending on the availability of data and of a current Dutch workplace standard (MAC, maximum accepted concentration): (a) by calculation based on available inhalatory animal data on the risks of reproductive toxicity; (b) by adding a safety factor of 10 to the current MAC, if no inhalatory animal data on reproductive toxicity are available; (c) by using 0.1 mg/m3 as precautionary OEL for substances suspected of having reproductive toxicity but without inhalatory animal data on reproductive toxicity and without a MAC.     

Administration of diethylstilbestrol during pregnancy, a public health problem

The analysis of the health risks associated with the administration of diethylstilbestrol (DES) during pregnancy (for the prevention or treatment of threatened abortions) has been largely published. Concerning mothers, a relationship between DES exposure during pregnancy and risk of cancer is unproved. However, existing studies are sufficient cause for serious concern over drug's carcinogenic potential, and further follow-up studies are required. Concerning daughters, a clear association between in utero exposure to DES and clear cell adenocarcinoma of the vagina or cervix is established (incidence between 0.14 and 1.4 per 1000 through age 24). The risk for squamous cell cancer of the vagina and cervix does not seem to be increased. Cervico-vaginal adenosis is frequent (20% to 60% of exposed subjects). This is not a pre-cancerous lesion, its spontaneous evolution is towards regression. No treatment is prescribed. Morphological changes of the genital tract have been described, their consequences on fertility and pregnancy are not clear. Concerning sons, an excess of genital abnormalities (especially of the epididymis and undescended testis) has been reported, but information on the fertility implications of these findings is not available. There is no evidence of an increased risk of testicular cancer. The analysis of all these informations should allow to bring up a policy to take into account these risks in the population.     

The IARC classification system: input, internal logic, output, and impact.

The IARC Monographs "Evaluation of Carcinogenic Risk of Chemicals to Man" elegantly condense and classify information on carcinogenic hazards. They serve as an invaluable basis for the regulation of carcinogenic exposures, yet the monographs are inadequate in several respects: 1. The monographs reflect only what is reported and published in peer-reviewed sources; they have not themselves generated support for studies on agents and processes for which information is lacking, partial, or inadequate. 2. There has been misuse of the output, which reflects varying levels of certainty as to human health hazards. Lack of absolute certainty on human carcinogenicity has been used as a basis for deferring regulations or other preventive action to restrict exposures. 3. The monographs ignore high-risk situations which may result from combined or interactive effects, because of the orientation mostly on specific agents. There is not adequate attention to frequently reported excesses of disease other than cancer in certain occupations with mixed exposures. Earlier recognition of more widespread and more reversible effects, other than cancer, needs to be emphasized to control exposures. 4. Control of carcinogenic exposures for workers has been less exacting and consistent than control of exposures for the community at large (water, air, food, and drugs). 5. The gap between knowledge of risks and action to control them is great and calls attention to the need for more aggressive professional input.     

Cancer and the Health Industry

The health industry in developed countries contributes to oneof the largest occupational groupings, yet little epidemiologicaleffort has been expended on investigating the health hazardsincluding any occupationally related neoplastic risks. Whilstradiologists in the early years of the century clearly had anincreased incidence of certain radiation-induced tumours, thishazard is now undetectable. Physicians in general have no grossneoplastic risk though the possibility of lymphoma or braintumour excesses has been raised for those exposed to radiation,as well as organic and inorganic chemigals. Nurses handlingcytostatic drugs have been shown to develop increased mutagenicactivity, whilst the risks to a wide group of staff to sterilizingagents remain unproven. Despite the fact that pharmaceuticalworkers experience a potential risk from carcinogenic agentsthey make or formulate, the meagre evidence for or against areal threat to their health remains speculative. Requests for reprints should be addressed to: J. M. Harrington, Institute of Occupational Health, The Medical School, University of Birmingham, Birmingham Bl 5 2TJ.     

Health effects of residence near hazardous waste landfill sites: a review of epidemiologic literature

This review evaluates current epidemiologic literature on health effects in relation to residence near landfill sites. Increases in risk of adverse health effects (low birth weight, birth defects, certain types of cancers) have been reported near individual landfill sites and in some multisite studies, and although biases and confounding factors cannot be excluded as explanations for these findings, they may indicate real risks associated with residence near certain landfill sites. A general weakness in the reviewed studies is the lack of direct exposure measurement. An increased prevalence of self-reported health symptoms such as fatigue, sleepiness, and headaches among residents near waste sites has consistently been reported in more than 10 of the reviewed papers. It is difficult to conclude whether these symptoms are an effect of direct toxicologic action of chemicals present in waste sites, an effect of stress and fears related to the waste site, or an effect of reporting bias. Although a substantial number of studies have been conducted, risks to health from landfill sites are hard to quantify. There is insufficient exposure information and effects of low-level environmental exposure in the general population are by their nature difficult to establish. More interdisciplinary research can improve levels of knowledge on risks to human health of waste disposal in landfill sites. Research needs include epidemiologic and toxicologic studies on individual chemicals and chemical mixtures, well-designed single- and multisite landfill studies, development of biomarkers, and research on risk perception and sociologic determinants of ill health.     

Women, work, and well-being 1950-2000: a review and methodological critique

In this research synthesis, we summarize 161 measures of the effects of women's employment on well being reported between 1950 and 2000. Variations in the conceptualization and measurement of employment and health outcomes and the difficulty in distinguishing social selection from social causation limit the inferences that can be drawn from the evidence. Therefore, we distinguish two types of studies. Longitudinal studies measuring relevant covariates at the first measurement occasion and statistically controlling them in multivariate analyses providing effect-size information are classified as Type II studies. The remaining studies are classified as Type I studies. The main findings were that (1) results from methodologically sound Type II studies confirm the cross-sectional finding that paid employment has no adverse effects on women; (2) the outcome groups psychological distress, subjective health, cardiovascular risks and disease, and mortality do not converge completely.     

Evaluation and synthesis of health effects studies of communities surrounding arsenic producing industries

Epidemiological studies designed to detect lung cancer risk and other health effects in communities surrounding arsenic-producing copper smelters were reviewed. The studies were about evenly divided in finding deleterious and 'beneficial' effects of arsenic. All of the studies had insufficient statistical power to detect the small increases in risk that may occur. Even the most powerful studies were not designed to detect relative risks less than about 1.2 and the majority of the studies had little power to detect risks under 2.0. Confidence intervals for the relative risks from these studies were not very useful in putting an upper bound on adverse effects of arsenic. Sources of bias and other difficulties with community health studies are also discussed. We argue that these studies may be a good and economical first investigation but, due to a lack of power, null findings do not rule out the possibility of excess risks that may be significant from a public health viewpoint.     

Shift work and cancer: state of science and practical consequences

In 2007, an expert Working Group convened by the IARC Monographs Programme concluded that shift work that involves circadian disruption is probably carcinogenic to humans (Group 2A). We scrutinised the epidemiological basis for this conclusion, with a focus on, but not limited to, breast and prostate cancers. We further considered practical consequences for shift workers in our industry against the background of new findings.We carried out a literature search including the epidemiological studies cited by IARC and newer available literature on shift work and cancer.Since the IARC assessment, eleven new studies have emerged, ten of which have already been published, with inconclusive results. Heterogeneity of exposure metrics and study outcomes and emphasis on positive but non-significant results make it difficult to draw general conclusions. Also, several reviews and commentaries, which have been published meanwhile, came to equivocal results. Published evidence is widely seen as suggestive but inconclusive for an adverse association between night work and breast cancer, and limited and inconsistent for cancers at other sites and all cancers combined.At this point in time it can not be ruled out that shift work including night work may increase the risk for some cancers in those who perform it. However, shift schedules can be organised in ways that minimise the associated health risks, and the risks may be further reduced through the implementation of structured and sustained health promotion programs specifically tailored to the needs of shift workers.     

Mammary gland neoplasia.

Determining how findings of chemically induced carcinogenic effects in rodents can properly be interpreted for human health poses a continuing challenge to the risk assessment community. One approach begins by comparing and contrasting carcinogenic process in rodents and humans, identifying biologically significant similarities and differences and gaps in scientific knowledge and understanding. Russo and Russo (in this issue) use just such an approach to evaluate the current state of scientific understanding of the comparative mechanisms of mammary tumorigenesis in humans and rodents, particularly the role of reproductive hormones. This commentary describes the basis for this review and suggests some of the implications the report may have for human health risk assessment and for future research.     

Effect of discounting certain tumor types/sites on evaluations of carcinogenicity in laboratory animals

It has been suggested that, for mechanistic reasons, certain tumors found in experimental animals should be discounted when evaluating carcinogenic effects. The questioned tumors are: mouse liver, rat thyroid follicular cell, bladder and kidney (male rat), forestomach (mouse and rat, gavage route), and lung (mouse and rat, inhalation of particles). We sought to determine the effects of discounting those tumors on classification of chemicals as carcinogens in animals. We looked at carcinogenicity data for chemicals studied in NCI-NTP bioassays and/or reviewed in IARC monographs and we found that deleting the questioned tumors would have significant impact on evaluations of carcinogenicity in animals. Fifty-six of 234 (24%) chemicals determined to be carcinogenic in the NCI-NTP bioassay program would no longer be considered carcinogenic; 102 (44%) would have weaker evidence of carcinogenic effects. Thirty-three of 361 (9%) chemicals determined by IARC to have “limited” or “sufficient” evidence of carcinogenicity would no longer be considered carcinogenic: 119 (33%) would have weaker evidence of carcinogenic effects. Because such a large number of chemicals currently considered carcinogenic would be affected by categorical deletion of tumors and because we are not aware of data that would justify such categorical deletion of tumors and because we are not aware of data that would justify such categorical deletions, it would be preferable to consider mechanistic justifications for discounting tumors on a case-by-case basis for each individual chemical. Deletion of tumors on a categorical basis has serious implications for regulation of toxic chemicals and for public health. Am. J. Ind. Med. 31:485–494, 1997. © 1997 Wiley-Liss, Inc.     

Prevention of work-related injuries and diseases: lessons from experience with ionizing radiation

Almost immediately after the discovery of the Roentgen ray, in 1895, radiation injuries of various kinds began to be encountered in early X-ray workers, radium handlers, radiologists, and exposed patients. The injuries, which were predominantly acute reactions resulting from the killing of cells in affected tissues, were found to be preventable merely by keeping exposures below relevant threshold levels. By the middle of the twentieth century, however, it was realized that thresholds might not exist for certain effects of ionizing radiation, such as mutagenic, carcinogenic, and teratogenic effects. The risks of such effects in workers and other populations exposed to low-level radiation have thus been of increasing concern in recent years. The scientific basis for assessing such risks and the principles that have evolved for their control have important implications for occupational and environmental health in general.     

2018年四川省江油市生活饮用水健康风险评价

目的 了解江油市生活饮用水中化学毒物的暴露水平,评估通过饮水途径对江油市不同人群健康产生的潜在危害。方法 根据江油市2018年生活饮用水的监测数据,应用美国环保局推荐的健康风险评价模型对饮用水中的17种化学污染物进行健康风险评价。结果 铬和硝酸盐分别为致癌物和非致癌物中日均暴露剂量最大的化学物,致癌及非致癌化学物通过饮水途径对不同人群所致暴露剂量大小顺序均为:成年女性＞成年男性＞儿童;致癌化学物和非致癌化学物对成年男性及女性所致健康总风险均高于儿童;致癌化学物的致癌风险大小顺序为铬＞砷＞镉＞四氯化碳＞三氯甲烷,主要的非致癌化学物的健康风险大小顺序为:铜＞铅＞氟化物＞硝酸盐;致癌物的健康风险占总健康风险的99.95%,成年男性、成年女性以及儿童的总健康风险分别为5.46×10-5a-1、5.43×10-5a-1和4.77×10-5a-1。结论 江油市饮用水中化学物的人群健康总风险低于美国环保局推荐的最大可接受风险,说明江油市生活饮用水可以安全饮用。     

Health assessment of environmental pollutants: proliferative and degenerative diseases

In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed.     

Carcinogenicity of occupational nickel exposures: an evaluation of the epidemiological evidence

The health effects documented in recent epidemiological studies of nickel-exposed workers relate to past exposures, mostly of unknown magnitude and unknown nickel speciation. Major studies have been carried out at nickel smelters and refineries. Although each study suffers from some deficiencies, as is common in such retrospective studies, the findings in concert strongly indicate that nickel emitted from the calcining and sintering operations is a potent carcinogen resulting in nasal and pulmonary cancers. Some risk appears to be present in other refinery operations, such as Orford furnace, copper and nickel sulfate, and crushing departments, and one study has suggested a risk associated with soluble nickel compounds in the electrolysis department, although this finding has not been confirmed. Only one study demonstrated an exposure-response relationship, which, however, was not statistically significant. Other studies showed a relationship between increased exposure time and augmented cancer risk. In nickel-using industries, no excess cancer related to nickel exposures has been demonstrated beyond doubt; concurrent exposures to other potential carcinogens constitute a confounding variable that makes interpretation difficult. However, the studies have not excluded that a cancer hazard may be present outside the nickel-producing facilities. Further, case-referent studies of respiratory cancers suggest that a nickel-related etiology may well exist in the nickel-using industries. As the exact identity of the carcinogenic form or forms of nickel remains unknown, exposure to all nickel compounds should be kept as low as reasonably achievable.     

Leukaemia and reproductive outcome among nurses handling antineoplastic drugs.

During the past decades conclusive evidence has accumulated that alkylating antineoplastic drugs (ADs) can cause cancer, most notably acute non-lymphocytic leukaemia, and that most ADs are reprotoxic. Studies on health workers handling ADs have shown significantly increased risks for miscarriages (two studies) and malformations (two studies). The present study monitored the risk for cancer and adverse reproductive outcome among Danish nurses handling ADs. No increased risks were found for miscarriages, malformations, low birth weight, or preterm birth among the offspring of nurses handling ADs during pregnancy. The sex ratio was normal. The relative risk (RR) for leukaemia was significantly increased (10.65) but based on only two cases, one of acute myeloblastic and one of chronic myeloid leukaemia. From the available exposure data occupational exposures to ADs were apparently higher in the studies that have reported increased risks for miscarriages and malformations than in the present one. Regarding reproductive outcome the study gives some confidence that the safety measures which were implemented in the oncology departments around 1980 can protect the health personnel against adverse effects of ADs on reproduction. As the study is as yet the only negative one in a well protected setting, it should be followed up by other studies of well protected health personnel handling ADs. The findings concerning the leukaemia risk, although based on small numbers, encourage larger studies.