A 17-year epidemiological study on changes in lung function in toluene diisocyanate foam workers.

OBJECTIVE: To determine whether longitudinal declines in ventilatory capacity and the occurrence of respiratory symptoms in workers manufacturing polyurethane foam were related to toluene diisocyanate (TDI) exposure. METHODS: A population of workers from 12 UK factories was studied between 1981 and 1986 [8]. A survivor cohort of 251, of whom 217 were in the 1981-1986 study, was examined again in 1997-1998. Modified British Medical Research Council respiratory questionnaires and lung function measurements were completed for each of the 251 subjects at the beginning and end of the 17-year study period. Mean TDI exposures for all jobs in which subjects were employed were assessed and related to their occupational histories. RESULTS: The annual declines in 1-second forced expiratory volume (FEV(1)) and forced vital capacity (FVC) were not related to TDI exposure, and were typical of those measured in other populations not exposed to TDI. Over the study period the cold-foam handling group ( n=26) showed an increase in breathlessness and a significant excess decline in FVC; the exposed group ( n=175) showed an increase in wheezing (mainly smokers), whilst the low-exposure group ( n=50) showed a decrease in chest illness. Smoking and an increase in body weight both caused excess declines in FEV(1). CONCLUSIONS: This study does not provide evidence that there was any TDI-related decline in FEV(1) or in FVC over a 17-year period in workers exposed to TDI at the levels prevailing in the UK factories that manufactured flexible polyurethane foam.

Study of two cohorts of workers exposed to methyl methacrylate in acrylic sheet production.

OBJECTIVES: To study mortality among 4324 workers at two United Kingdom factories, Darwen, Lancashire and Wilton, Cleveland, producing polymethyl methacrylate (PMMA) sheet. The Darwen factory is still active, but the Wilton one was closed in 1970. Also, to investigate patterns of mortality after exposure to methyl methacrylate; in particular, mortality from colon and rectal cancer. METHODS: All male employees at the Darwen factory with a record of employment in 1949-88 and all men ever employed at the Wilton factory (1949-70) were investigated. The vital status of both cohorts was ascertained on 31 December 1995. The exposure of 1526 subjects at the Darwen plant who were engaged from 1949 onwards could be characterised. The mean duration of exposure was 7.6 years at 13.2 ppm (8 hour time weighted average), although exposures in some work groups were as high as 100 ppm. It was not possible to calculate the cumulative exposure of workers first employed at the Darwen plant before 1949 or workers at the Wilton factory. RESULTS: In the Darwen cohort, 622 deaths were identified and a further 700 deaths in the Wilton cohort. Mortalities for the cohort were compared with national and local rates and expressed as standardised mortality ratios (SMRs). In the subcohort of Darwen workers with more than minimal exposure to MMA, reduced mortalities compared with national and local rates, were found for all causes (SMR 94), and colorectal cancer (SMR 92), but mortality from all cancers was slightly increased (SMR 104). No relations were found with cumulative exposure to MMA. In the subcohort of Wilton workers, mortality from all causes of death was significantly reduced (SMR 89), but mortality from all cancers (SMR 103) and colorectal cancer (SMR 124) were increased. The excess of colorectal cancer was confined to employees with less than 1 year of employment. CONCLUSION: The study provided no clear evidence that employment at the factories or exposure to MMA had adversely affected the mortalities of workers.

Respiratory symptoms and ventilatory performance in workers exposed to grain and grain based food dusts.

A health surveillance study of male grain food manufacturing workers used a respiratory health questionnaire and spirometry to assess the prevalence of work-related respiratory symptoms and impaired ventilatory performance. The prevalence of cough, breathlessness, wheeze and chest tightness was between 8-13% but was 20% for rhinitis. Rhinitis was the most common symptom with 37% of those reporting rhinitis describing this as work-related. A case-control analysis of workers reporting rhinitis did not identify any specific occupational activities associated with increased risk of rhinitis. Smoking habit and all respiratory symptoms apart from rhinitis had a significant effect upon ventilatory performance. Occupational exposure to raw grains, flour, ingredients and finished food was categorized as high, medium or low in either continuous or intermediate patterns. Multiple regression analysis confirmed the effects of height, age and smoking upon ventilatory performance. However, occupational exposure to grain, flour, food ingredients and cooked food dusts had no effect upon ventilatory performance. It is concluded that smoking habit is the major determinant of respiratory symptoms and impaired ventilatory function. The excess complaints of rhinitis warrant further study but it would appear that the current occupational exposure limits for grain, flour, food ingredients and cooked food dusts are adequate to protect workers against impairment of ventilatory performance.

Metaanalysis as an epidemiological tool and its application to studies of chromium.

Metaanalysis is a technique for combining the results of similar studies to arrive at a single estimate of effect or risk. It is of proven value in the field of clinical trials but its use as an epidemiological tool is less well established. The principal obstacles to the valid use of metaanalysis are lack of consistency in the design, conduct and analysis of studies, publication bias, and reporting bias. Metaanalysis has been used to question whether an excess of lung cancer is associated with postmodification production of chromates and whether tumors of any site other than the lung are associated with any level of chromium exposure. The metaanalysis of lung cancer postmodification did not show a statistically significant excess, but the combined studies lacked the statistical power to exclude the possibility of a continuing risk of moderate size. The data in the literature for tumors at sites other than the lung were too impaired by heterogeneity of reporting and reporting bias for metaanalysis to be applied with any validity. A more uniform approach to the planning and reporting of studies is essential if metaanalysis is to gain credibility as an epidemiological tool.

Occupational exposure to magnetic fields in relation to mortality from brain cancer among electricity generation and transmission workers.

OBJECTIVE: To investigate whether the risks of mortality from brain cancer are related to occupational exposure to magnetic fields. METHODS: A total of 112 cases of primary brain cancer (1972-91) were identified from a cohort of 84,018 male and female employees of the (then) Central Electricity Generating Board and its privatised successor companies. Individual cumulative occupational exposures to magnetic fields were estimated by linking available computerised job history data with magnetic field measurements collected over 675 person-workshifts. Estimated exposure histories of the case workers were compared with those of 654 control workers drawn from the cohort (nested case-control study), by means of conditional logistic regression. RESULTS: For exposure assessments based on arithmetic means, the risk of mortality from brain cancer for subjects with an estimated cumulative exposure to magnetic fields of 5.4-13.4 microT.y v subjects with lower exposures (0.0-5.3 microT.y) was 1.04 (95% confidence interval (95% CI) 0.60 to 1.80). The corresponding relative risk in subjects with higher exposures (> or = 13.5 microT.y) was 0.95 (95% CI 0.54 to 1.69). There was no indication of a positive trend for cumulative exposure and risk of mortality from brain cancer either when the analysis used exposure assessments based on geometric means or when the analysis was restricted to exposures received within five years of the case diagnosis (or corresponding period for controls). CONCLUSIONS: Although the exposure categorisation was based solely on recent observations, the study findings do not support the hypothesis that the risk of brain cancer is associated with occupational exposure to magnetic fields.

The evaluation of carcinogenic risk to humans: occupational exposures in the spraying and application of insecticides.

The International Agency for Research on Cancer (IARC) has reviewed the carcinogenic risk to man of the occupation of spraying or applying insecticides. IARC was unable to conclude that a causal relationship had been established (category 1), but there was some evidence which led them to consider the occupation to be probably carcinogenic (in category 2A). These conclusions have been reviewed by a working group of the International Group of National Associations of Manufacturers of Agrochemical Products (GIFAP) to determine what steps needed to be taken which might improve safety for those working with insecticides. The working group reinforced the view that a causal relationship could not be established. In addition, the usage rate of insecticides has decreased since the time of the studies that IARC considered, their general toxicity has decreased, and the products themselves have been the subject of close regulatory scrutiny. It is considered that these changes are addressing any concerns that may be raised by the IARC report.

Better quality studies through review of protocols.

The importance of a protocol is well recognized by scientists whose work is governed by good laboratory practices. Epidemiologists have used protocols for many years but have not always reaped the full benefits. Until relatively recently, there has been little consensus among epidemiologists about what constitutes a good protocol and, consequently, expectations of the pre-study review process may not be fulfilled. This paper examines some of the benefits to be derived from a good protocol and the importance of prestudy review. Our experience suggests that peer review cannot substitute for a competent principal investigator supported by a strong study management team. If such a study management team exists, the most important contribution of the external peer reviewer should be to ensure the impartiality of the study.

Mortality of employees in plants manufacturing 4,4'-bipyridyl.

A historical-prospective cohort study was conducted of 729 male employees of plants manufacturing 4,4'-bipyridyl. The cohort was studied because employment in some of the plants had been linked to malignant and nonmalignant skin lesions attributed to exposure to tarry by-products. The overall mortality experience of the cohort did not show any statistically significant findings. More-detailed analysis of subdivision of the cohort gave results that justified further inquiry into lung cancer incidence. A nested case-referent study did not indicate that any occupational factor other than employment in a bipyridyl plant was related to the incidence of lung cancer. The epidemiologic, toxicologic, and industrial hygiene information was assessed, and it was concluded that there was no evidence of a plausible occupational hazard of lung cancer to the bipyridyl workers, but that a follow-up of the cohort after an interval of five years should be undertaken.

Does formaldehyde cause nasopharyngeal cancer in man?

Formaldehyde is a widely used industrial chemical, which also has uses in consumer products, and hence large numbers of people are exposed to it. It is also an endogenous metabolite with measurable levels in body fluids and tissues. The reports of its carcinogenicity to rats have raised concern about its potential to cause a carcinogenic response in exposed populations. This letter reviews the information on the carcinogenicity of formaldehyde, particularly to the upper respiratory tract, in animals and man.

Vinyl chloride: an assessment of the risk of occupational exposure.

There is little doubt that exposure to high levels of VCM as a consequence of occupation can result in an increased incidence of ASL. A review of 20 epidemiological studies involving about 45,000 workers occupationally exposed to VCM showed that neoplasms of the liver showed an increase in incidence in the majority of studies. For brain cancer the association between exposure to VCM and an increased incidence was less clear because of the lower relative risk. Neoplasms of the respiratory tract, digestive system, lymphatic and haemopoietic system, buccal cavity, and pharynx, cardiovascular system and colon/stomach were reported to show an increased incidence in one or more studies, but to show no increase, or in some cases a decrease, in incidence in other studies. In view of the increased incidence of breast neoplasms in rodents exposed to VCM, the studies of Chaizze et al. (1980), who did not confirm these findings in humans, are of importance. The register of ASL cases now contains records of 99 persons with confirmed ASL and occupational exposure to VCM. The average latent period between first exposure to VCM and death from ASL is 21.9 years. The majority of cases occurred in autoclave workers, who are recognized as having been exposed to extremely high levels. Although precise estimates of exposure are not available for the periods of most interest, the pattern of cases roughly suggests that extremely high exposures were necessary for the induction of ASL. For example, ASL cases tended to occur in larger numbers in some plants than in others, a finding that can be explained most easily by differences in exposure patterns. There is an extensive series of animal studies on the carcinogenicity of VCM. Some of these precede the epidemiological studies confirming the association between VCM exposure and ASL in man. ASL and neoplasms of a number of other organs have been induced in laboratory rodents by VCM. Estimation of the exposure levels likely to cause a lifetime risk of ASL of 10(-6) on the basis of these data give extremely low levels (down to 3.9 X 10(-7) ppb) which appear to be unrealistic estimates for man. Part of the reason for this is that laboratory studies have shown that VCM is metabolized in the liver (and elsewhere in the body) to the reactive metabolites chloroethylene oxide and chloroacetaldehyde. The rate of conversion is limited at high levels of exposure giving inaccurate estimates of the slope of the dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

An investigation of an excess incidence of heart disease.

In a large complex chemical company, it is difficult to distinguish clusters of disease of occupational origin from those due to non-occupational factors and those that have arisen by chance. The mechanical application of statistical procedures to health data to detect occupational hazards will produce many false positives. More refined techniques were used to demonstrate that the incidence of coronary disease at a small site was too high to be attributed to chance alone. An intensive search for a causative factor proved abortive.

Lung function in workers exposed to polyvinyl chloride dust.

Several reported studies on the effects of polyvinyl chloride (PVC) dust in animals and man have been conflicting. The present study of the ventilatory function of 509 male workers exposed to PVC dust was made in 1977. Altogether 104 men exposed to PVC dust only, 112 men exposed to non-chlorinated solvents only, and 293 men exposed to a mixture of both completed the MRC questionnaire on respiratory function and performed simple spirometric tests (forced expiratory volume in one second and forced vital capacity). No differences were found between the three groups after allowance was made for age, height, and smoking. When exposure and smoking effects were considered separately, the latter was shown to be the dominant cause of reduced lung function. In this study work with PVC dust has not produced deleterious effects on ventilatory function.

Epidemiological and animal data as a basis for risk assessment.

The assessment of the cancer risk inherent in a chemical compound with a lengthy manufacturing history should involve the allocation of suitable weights to the various pieces of evidence. These pieces of evidence will always conflict quantitatively or even qualitatively. Data derived from animal experiments have many advantages over epidemiological material. The two major advantages of epidemiology are the relevance of the species, and the relevance of the dose to that species. The high weight to be attached to the animal data for the categorisation of carcinogens has to be severely depreciated when attempting to assess risk.

Chromosomal analyses in vinyl chloride-exposed workers.

Chromosomal morphology from cultured peripheral lymphocytes was studied in 81 men; 57 of the men were employed on plants manufacturing vinyl chloride or polyvinylchloride, 19 were on-site controls and 5 were off-site controls. There was a significant increase in chromosomal abnormalities in the exposed workers when compared with the controls. The greatest statistically significant increase in total B and total C cells occurred in autoclave operators, with smaller increases in other job categories. The increase in chromosomal aberrations was correlated with the length of exposure and with a history during the year prior to sampling (1973--1974) of exposure to excursion levels of vinyl chloride. Information on smoking habits was obtained 18 months after blood sampling and a positive correlation between these and total C cell abnormalities was found. There was no positive correlation with various other parameters (bilirubin, platelets, gamma-glutamyltranspeptidase, alkaline phosphatase, alanine transaminase and aspartate transaminase). It was not possible to estimate which of the three parameters (smoking history, length of employment or exposure to excursion levels) was the most important.