Mortality and cancer incidence among alachlor manufacturing workers 1968-99.

BACKGROUND: Alachlor is the active ingredient in pre-emergent herbicide formulations that have been used widely on corn, soybeans, and other crops. It has been found to cause nasal, stomach, and thyroid tumours in rodent feeding studies at levels that are much higher than likely human exposures. AIMS: To evaluate mortality rates from 1968 to 1999 and cancer incidence rates from 1969 to 1999 for alachlor manufacturing workers at a plant in Muscatine, Iowa. METHODS: Worker mortality and cancer incidence rates were compared to corresponding rates for the Iowa state general population. Analyses addressed potential intensity and duration of exposure. RESULTS: For workers with any period of high alachlor exposure, mortality from all causes combined was lower than expected (42 observed deaths, SMR 64, 95% CI 46 to 86) and cancer mortality was slightly lower than expected (13 observed deaths, SMR 79, 95% CI 42 to 136). Cancer incidence for workers with potential high exposure was similar to that for Iowa residents, both overall (29 observed cases, SIR 123, 95% CI 82 to 177) and for workers exposed for five or more years and with at least 15 years since first exposure (eight observed cases, SIR 113, 95% CI 49 to 224). There were no cases of nasal, stomach, or thyroid cancer. CONCLUSIONS: There were no cancers of the types found in toxicology studies and no discernible relation between cancer incidence for any site and years of alachlor exposure or time since first exposure. Despite the small size of this population, the findings are important because these workers had chronic exposure potential during extended manufacturing campaigns, while use in agriculture is typically limited to a few days or weeks each year.

A review of the epidemiology of 1,3-butadiene and chloroprene.

Butadiene epidemiologic research has focused primarily on one cohort of workers in the North American styrene-butadiene rubber (SBR) industry and on the largest cohort of workers in the United States butadiene monomer industry. The most recent studies of these populations are characterized by carefully enumerated study populations, extremely long and high quality mortality follow-up, accurate job categorizations, detailed exposure assessments, and comprehensive statistical analyses. Leukemia was clearly associated with increasing estimated butadiene exposure in the SBR study, but not in the monomer industry study. This has lead to hypotheses about exposure differences between these two industries and the presence of co-factors or confounders in the SBR industry. Research presented at this symposium should shed some light on these hypotheses. The chloroprene epidemiologic literature, on the other hand, is in an early stage of development. The existing studies are limited by poor exposure characterization, lack of control of potential confounding factors, incompleteness in cohort enumeration, short follow-up periods, and small numbers of cancer cases. The state of the science for chloroprene would be advanced by arranging more comprehensive studies than those that have been conducted to date.

Human ocular effects from self-reported exposures to Roundup herbicides.

We evaluated ocular effects from reported human exposures to Roundup herbicides based on 1513 calls to an American Association of Poison Control Centers (AAPCC) certified regional poison center during the years 1993 through 1997. The preponderance of reported exposures were judged by poison center specialists to result in either no injury (21%) or transient minor symptoms (70%). There was some temporary injury in 2% of cases; one injury took more than 2 weeks to resolve. In no instance did exposure result in permanent change to the structure or function of the eye. Since the representativeness of calls to poison control centers is unknown, several interpretations of these findings are possible. The most conservative interpretation is that there were no serious ocular effects from exposure to Roundup herbicides during a 5 year period among callers to a single regional poison center. A less conservative interpretation would be that severe ocular effects from Roundup exposures are rare among users of these products.

Review and meta-analysis of studies of acrylonitrile workers.

Twenty-five epidemiologic studies of acrylonitrile workers were reviewed and subjected to meta-analytic techniques in this study to assess the findings for 10 cancer sites. The analyses indicate that workers with acrylonitrile exposure have essentially null findings for most cancers, including lung [meta-relative risk (mRR) 0.9, 95% confidence interval (95% CI) 0.9-1.1], brain (mRR 1.2, 95% CI 0.8-1.7), and prostate (mRR 1.0, 95% CI 0.7-1.4) cancers. Bladder cancer rates were elevated (mRR 1.8, 95% CI 1.0-3.4), but the excess was not dose-related and was limited to plants with aromatic amines. Therefore, the bladder cancer excess is unlikely to be related to acrylonitrile exposure. Some evidence of publication bias was found in the examined literature, but the bias did not have a significant impact on risk estimates for individual cancers. It was concluded that the available studies do not support a causal relation between acrylonitrile exposure and cancer.

The politics of identity in epidemiology.

The predilection to doubt the objectivity of scientists based on their affiliation--particularly, but not exclusively, focused on scientists affiliated with industry-is a malignant influence in modern epidemiology. Manifestations of this "politics of identity" are widespread and include ad hominem attacks, publication restrictions, and exclusions of scientists from expert panels and advisory boards. These actions are likely to be detrimental to progress in epidemiology and are questionable from an ethical standpoint. The purpose of this commentary is to draw critical attention to the politics of identity in epidemiology and the effects it can have on individual scientists and scientific debate.

An updated meta-analysis of formaldehyde exposure and upper respiratory tract cancers.

In this study, we summarize 47 epidemiologic studies related to formaldehyde exposure and use meta-analytic techniques to assess findings for cancers of the lung, nose/nasal sinuses, and nasopharynx. Our analyses indicate that workers with formaldehyde exposure have essentially null findings for lung cancer and a slight deficit of sinonasal cancer. Nasopharyngeal cancer rates were elevated moderately in a minority of studies. Most studies, however, did not find any nasopharyngeal cancers, and many failed to report their findings. After correcting for underreporting, we found a meta relative risk of 1.0 for cohort studies. Case-control studies had a meta relative risk of 1.3. Our review of the exposure literature indicated that the nasopharyngeal cancer case-control studies represented much lower and less certain exposures than the cohort studies. We conclude that the available studies do not support a causal relation between formaldehyde exposure and nasopharyngeal cancer. This conclusion conflicts with conclusions from two previous meta-analyses, primarily because of our consideration of unreported data.

Butadiene epidemiology: a summary of results and outstanding issues.

Published epidemiologic studies of butadiene workers, individually and in aggregate, find rates similar to expected for essentially all forms of cancer, with the possible exception of lymphohematopoietic cancers. Reviewers of the literature have disagreed about whether butadiene is a cause of human lymphohematopoietic cancers. This article reviews the available butadiene epidemiologic studies and focuses on the bases for disagreement among reviewers. The disagreement seems to be due to different conventions in applying, explicitly or implicitly, Hill's causal criteria, fostered, in part, by deficiencies in the available epidemiologic studies. Many of these deficiencies will be remedied by updated studies presented at this Symposium or are remediable by other analyses of the existing data.

Evaluation of mortality and cancer incidence among alachlor manufacturing workers.

Alachlor is the active ingredient in a family of preemergence herbicides. We assessed mortality rates from 1968 to 1993 and cancer incidence rates from 1969 to 1993 for manufacturing workers with potential alachlor exposure. For workers judged to have high alachlor exposure, mortality from all causes combined was lower than expected [23 observed, standardized mortality ratio (SMR) = 0.7, 95% CI, 0.4-1.0], cancer mortality was similar to expected (6 observed, SMR = 0.7, 95% CI, 0.3-1.6), and there were no cancer deaths among workers with 5 or more years high exposure and 15 or more years since first exposure (2.3 expected, SMR = 0, 95% CI, 0-1.6). Cancer incidence for workers with high exposure potential was similar to the state rate [18 observed, standardized incidence ratio (SIR) = 1.2, 95% CI, 0.7-2.0], especially for workers exposed for 5 or more years and with at least 15 years since first exposure (4 observed, SIR = 1.0, 95% CI, 0.3-2.7). The most common cancer for these latter workers was colorectal cancer (2 observed, SIR 3.9, 95% CI, 0.5-14.2 among workers). Despite the limitations of this study with respect to small size and exposure estimating, the findings are useful for evaluating potential alachlor-related health risks because past manufacturing exposures greatly exceeded those characteristic of agricultural operations. These findings suggest no appreciable effect of alachlor exposure on worker mortality or cancer incidence rates during the study period.

Perspective on the content of worker notifications.

The concept of worker notification has evolved over the years to a prevailing view that workers should be notified of all epidemiologic studies that make use of their medical information. To adequately communicate health information to workers, epidemiologists must consider the intended audience along with its need for risk information that is scientifically valid and clearly outlines areas of uncertainty. This goal is facilitated by full disclosure to workers of information pertinent to the planning, conduct, and interpretation of research efforts. Subjectivity in choosing unanticipated research findings for inclusion in worker notifications may permit bias toward a personal viewpoint, but this can be minimized by prestudy agreement on appropriate criteria for selecting which research findings to communicate. Epidemiologic theory and principles of causal inference should guide the development of appropriate criteria. The timeliness of worker communications has received limited attention, and workers have often been the "last to know" about important studies. This may influence workers' receptivity to the risk message. Sponsoring organizations should ensure that an acceptable communications plan is included in research protocols and that the plan accords priority to notifying workers about study results.

An updated mortality study of workers in three major United States refineries and chemical plants.

A historical cohort study of refinery and chemical plant workers, originally observed from 1970 to 1977, was updated to the end of 1982. This cohort included 25,321 active, retired, and terminated workers at the Exxon refineries and chemical plants in Baton Rouge, Louisiana; Baytown, Texas; and Bayway/Bayonne, New Jersey. An emphasis was placed on the cancers previously reported to be increased in at least one petrochemical worker population. The population included a high proportion of retirees, providing adequate work experience and latency to evaluate risks associated with employment. Vital status was determined for 98.3% of the population and death certificates were obtained for 99.9% of the decedents. Mortality for "all causes of death" (standardised mortality ratio (SMR) = 89, 95% confidence interval (95% CI) 87-91) and for "all cancers" (SMR = 94, 95% CI 89-100) were lower than expected based on state rates. History of cigarette smoking collected from individual medical records and summarised work histories were used for subgroup analyses. There was no indication that cancers of primary interest were increased; however, blue collar workers at one plant had raised rates of kidney cancer (SMR = 246, 95% CI 146-390), which may require further evaluation.