J C McDonald

Prematurity and work in pregnancy.

The frequency of low birth weight (less than or equal to 2500 g) and of preterm birth (less than 37 weeks) was studied in 22,761 single live births in relation to maternal employment, taking account of 11 nonoccupational confounding factors. There was some increase of low statistical significance in both types of prematurity in service and manufacturing sectors of industry. A substantial excess of preterm births was seen in women employed in food and beverage service (O/E = 1.29, p = 0.03) and psychiatric nursing (O/E = 2.47, p less than 0.01) and of low birth weight in food and beverage service (O/E = 1.30, p = 0.02), in chambermaids and cleaners (O/E = 1.42, p = 0.03), and in those employed in the manufacture of metal and electrical and certain other goods (O/E = 1.57, p less than 0.01). Heavy lifting and long hours of work were consistently related to both outcomes, changing shift work less consistently. Noise was associated with low birth weight in the health and manufacturing sectors. The findings of this study are unlikely to have resulted from subject or observer bias but the role of unidentified factors related to selection for work are difficult to assess.

Fetal death and work in pregnancy.

The relation between spontaneous abortion (n = 5010), stillbirth without congenital defect (n = 210), and working conditions was analysed in 22,613 previous pregnancies of 56,067 women interviewed, 1982-4, immediately after termination of their most recent (current) pregnancy. The 22,613 previous pregnancies were those in which at time of conception the women were employed 30 or more hours a week. Ratios of observed (O) to expected (E) fetal deaths after allowance by logistic regression for seven non-occupational confounding variables were calculated at four stages of pregnancy in 60 occupational groups and six main sectors for women whose work entailed various physical demands, environmental conditions, and exposure to chemicals. The O/E ratios for abortion were raised in the sales sector (1.13, p less than 0.05) and services sector (1.11, p less than 0.01) and for stillbirth in the sales sector (1.50, p less than 0.1). Substantially increased O/E ratios for late but not early abortion were found in operating room nurses (2.92, p less than 0.05), radiology technicians (3.82, p less than 0.01), and employees in agriculture and horticulture (2.40, p less than 0.05); in all categories the O/E ratio for stillbirth were also raised but only significantly (5.55, p less than 0.01) in the latter group. The O/E ratio for stillbirth was also raised in leather manufacture (3.09, p less than 0.01). In both individual and grouped analysis (the latter undertaken to minimise the possible effect of recall bias) significantly increased O/E ratios for abortion were found in women exposed to various high levels of physical stress, particularly weight lifting, other physical effort, and standing (p less than 0.01). Increased ratios for stillbirth at this level of significance (p less than 0.01) were found for other physical effort and vibration. Noteworthy chemical exposure was identified only in the health, services, and manufacturing sectors; the O/E ratio for stillbirth approached two in women exposed to solvents, almost all in manufacturing (p less than 0.01). In the latter sector exposed to solvents was also associated with an approximately 20% increase in abortion ratio at similar probability level.

Cohort study of mortality of vermiculite miners exposed to tremolite.

A cohort of 406 men employed before 1963 for at least one year in a vermiculite mine in Montana was followed up until July 1983. The vermiculite ore as fed to the mill contained 4-6% of amphibole fibre in the tremolite series. Vital status was established in all but one of the 406 and death certificates were obtained and coded for 163 of the 165 men who died. Compared with white men in the United States, the cohort experienced excess mortality from all causes (SMR 1.17), respiratory cancer (SMR 2.45), non-malignant respiratory disease (SMR 2.55), and accidents (SMR 2.14). Four deaths were from malignant mesothelioma (proportional mortality 2.4%). Compared with Montana death rates, the SMR for respiratory cancer was somewhat higher (3.03). Man-year analyses of respiratory cancer and estimated cumulative exposure gave a relation that did not depart significantly from linearity. The results of this and case-referent analyses indicate an increased risk of mortality from respiratory cancer in this cohort of about 1% for each fibre year of exposure. In relation to estimated exposure the mortality experienced by the cohort from both lung cancer and mesothelial tumours was higher than in chrysotile mining.

Incidence by occupation and industry of acute work related respiratory diseases in the UK, 1992–2001

Aims: To summarise incidence rates and epidemiological characteristics of new cases of work related respiratory disease reported by specialist physicians in thoracic and occupational medicine, with particular reference to occupation, industry, and causal agents for asthma, inhalation accidents, and allergic alveolitis. Methods: Cases reported 1992–2001 to the SWORD and OPRA national surveillance schemes, in which almost all UK chest and occupational physicians participate, were analysed by age, sex, cause, occupation, and industry, with incidence rates calculated against appropriate denominators. Results: Excluding diseases of long latency, infrequently seen by occupational physicians, the distribution of diagnoses in the two specialties was similar, but with rates generally much higher in occupational than chest physicians. Occupational asthma was responsible for about 25% of cases overall, affecting mainly craft related occupations and machinists, and most often attributed to isocyanates, metals, grains, wood dusts, solders, and welding fume. These same occupations were those at highest risk from inhalation injuries, most frequently caused by irritant gases, vapours, and fume. Among medical technicians and nurses, however, glutaraldehyde and latex were the main causes of occupational asthma. Allergic alveolitis was seldom reported, with almost all cases in agriculture, forestry, and fishing. Conclusion: During the 10 year period studied, there were few changes in level of reported incidence, apart from some decline in occupational asthma and inhalation injuries. These results and their implications should be distinguished from much higher estimates of asthma made worse by work derived from population surveys, based on prevalence rather than incidence, and self-reported symptoms rather than diagnoses made by specialist physicians. Even so, the reported incidence of new cases of acute respiratory illness caused by work remains substantial.

Mortality in a cohort of vermiculite miners exposed to fibrous amphibole in Libby, Montana

Background: Fibrous tremolite is a widespread amphibole asbestiform mineral, airborne fibres of which constitute an environmental hazard in Libby, Montana, northern California, and elsewhere. Aims: To determine excess risk from lung cancer, mesothelioma, and all-cause mortality in a cohort of men exposed to tremolite, but no other form of asbestos. Methods: Mortality by certified cause and various measures of exposure to tremolite and related amphibole fibres was assessed in a cohort of 406 vermiculite mineworkers in Libby, Montana, employed before 1963 and followed until 1999. Results: Total deaths were: lung cancer 44 (SMR 2.40), non-malignant respiratory disease (NMRD) 51 (SMR 3.09), all causes 285 (SMR 1.27); included among the total were 12 deaths ascribed to mesothelioma (4.21% of all deaths). Adjusted linear increments in relative risks (per 100 f/ml.y), estimated by Poisson regression, were: lung cancer (0.36, 95% CI 0.03 to 1.20), NMRD (0.38, 95% CI 0.12 to 0.96), and all deaths (0.14, 95% CI 0.05 to 0.26). Conclusions: The all-cause linear model would imply a 14% increase in mortality for mine workers exposed occupationally to 100 f/ml.y or about 3.2% for a general population exposed for 50 years to an ambient concentration of 0.1 f/ml. Amphibole fibres, tremolite in particular, are likely to be disproportionately responsible for cancer mortality in persons exposed to commercial chrysotile, but to what extent cannot be readily assessed.

Respiratory cancer in chrysotile textile and mining industries: exposure inferences from lung analysis.

In an attempt to explain the much greater risk of respiratory cancer at the same cumulative exposure in asbestos textile workers in Charleston, South Carolina, than in Quebec miners and millers, both exposed to chrysotile from the same source, 161 lung tissue samples taken at necropsy from dead cohort members were analysed by transmission electron microscopy. Altogether 1828 chrysotile and 3270 tremolite fibres were identified; in both cohorts tremolite predominated and fibre dimensions were closely similar. Lung fibre concentrations were analysed statistically (a) in 32 paired subjects matched for duration of employment and time from last employment to death and (b) in 136 subjects stratified by the same time variables. Both analyses indicated that the Quebec/Charleston ratios for chrysotile fibre concentration in lung tissue were even higher than the corresponding ratios of estimated exposure intensity (mpcf). After allowance for the fact that regression analyses suggested that the proportion of tremolite in dust was probably 2.5 times higher in Thetford Mines, Quebec, than in Charleston, the results from both matched pair and stratification analyses of tremolite fibre concentrations in lung were almost the same as for chrysotile. It is concluded that neither fibre dimensional differences nor errors in estimation of exposure can explain the higher risks of lung cancer observed in asbestos textile workers. The possible co-carcinogenic role of mineral oil used in the past in asbestos textile plants to control dust provides an alternative hypothesis deserving consideration.

THE 1891–1920 BIRTH COHORT OF QUEBEC CHRYSOTILE MINERS AND MILLERS: DEVELOPMENT FROM 1904 AND MORTALITY TO 1992

This paper draws together the mortality experience for a cohort of some 11000 male Quebec Chrysotile miners and millers, reported at intervals since 1971 and now again updated. Of the 10918 men in the complete cohort, 1138 were lost to view, almost all never traced after employment of only a month or two before 1935; the other 9780 men were traced into 1992. Of these, 8009 (82%) are known to have died: 657 from lung cancer, 38 from mesotheliona, 1205 from other malignant disease, 108 from pneumoconiosis and 561 from other non-malignant respiratory diseases (excluding tuberculosis). After early fluctuations. SMRs (all causes) against Quebec rates have been reasonably steady since about 1945. For men first employed in Asbestos, mine or factory, they were very much what might have been expected for a blue collar population without any hazardous exposure. SMRs in the Thetford Mines area were almost 8% higher, but in line with anecdotal evidence concerning socio-economic status. At exposures below 300 (million particles per cubic foot) x years, (mpcf.y), equivalent to roughly 1000 (fibres/ml) x years-or, say, 10 years in the 1940s at 80 (fibres/ml)-findings were as follows. There were no discernible associations of degree of exposure and SMRs, whether for all causes of death or for all the specific cancer sites examined. The average SMRs were 1.07 (all causes), and 1.16, 0.93, 1.03 and 1.21, respectively, for gastric, other abdominal, laryngeal and lung cancer. Men whose exposures were less then 300 mpcf.y suffered almost one-half of the 146 deaths from pneumoconiosis or mesothelioma; the elimination of these two causes would have reduced these mens SMR (all causes) from 1.07 to approximately 1.06. Thus it is concluded from the viewpoint of mortality that exposure in this industry to less than 300 mpcf.y has been essentially innocuous, although there was a small risk or pneumoconiosis or mesothelioma. Higher exposures have, however, led to excesses, increasing with degree of exposure, of mortality from all causes, and from lung cancer and stomach cancer, but such exposures, of at least 300 mpcf.y, are several orders of magnitude more severe than any that have been seen for many years. The effects of cigarette smoking were much more deleterious than those of dust exposure, not only for lung cancer (the SMR for smokers of 20+ cigarettes a day being 4.6 times higher than that for non-smokers), but also for stomach cancer (2.0 times higher), laryngeal cancer (2.9 times higher), and-most importantly-for all causes (1.6 times higher).

The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.

A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.

Mesothelioma in Quebec chrysotile miners and millers: Epidemiology and aetiology

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

Occupation and pregnancy outcome.

Over a two year period, 1982-4, 56067 women, delivered or treated for a spontaneous abortion in 11 Montreal hospitals covering 90% of such admissions, were interviewed in detail regarding their occupational, social, and personal characteristics in their most recent and past pregnancies--104,649 in all. These data were analysed in relation to four main adverse outcomes--spontaneous abortion, stillbirth (without defect), congenital defect, and low birth weight (less than or equal to 2500 g). For comparison with observed numbers, expected figures were calculated by logistic regression using up to eight potentially confounding variables. Sixty occupational groups in six main industrial sectors were examined in current and previous pregnancies, with tests for heterogeneity between these two estimates of risk. Women in managerial, health, and clerical sectors had little evidence of excess of any of the four outcomes, by contrast with those in sales, service, and manufacturing sectors. Substantial and statistically significant excesses of spontaneous abortion were observed in nursing aides, women in sales occupations and food and beverage service; of stillbirth in agriculture and horticulture, leatherwork, and certain sales occupations; of congenital defects in women in child care, certain service occupations, and the manufacture of metal and electrical goods; and of low birth weight in chambermaids, cleaners, and janitors, and in women employed in the manufacture of food and drink, metal and electrical goods, and clothing.