A normative study of levels of uranium in the urine of British Forces personnel.

OBJECTIVES: The UK Ministry of Defence (MoD) controls a biological monitoring programme that includes testing for uranium in personnel who served in the conflict in Iraq in 2003. To help interpret the results, the MoD commissioned this study to quantify a normative reference distribution of urinary uranium concentrations in military personnel who had not served in that conflict. METHODS: The study selected and visited various military establishments to recruit a representative mix of ranks, genders and occupational groups (combat, support and auxiliary). A standardised protocol and recruitment questionnaire were used. The 125 ml spot urine samples collected were analysed for uranium and creatinine concentrations and (where possible) for uranium isotope (238)U/(235)U ratio. RESULTS: Samples from 732 eligible subjects were analysed. Adjusted uranium concentrations ranged up to 556 ng.g(-1) creatinine, somewhat higher than reference values quoted for the USA but much lower than recorded in granite areas such as Finland. Isotope ratio measurements were available for 125 samples (17%) with the highest concentrations; these all had a natural isotope signature and no evidence of depleted uranium (DU). On average, urinary uranium concentrations were somewhat lower in officers than in other ranks; they differed also across the services, the Navy being lowest and the Army highest. The levels give no concern regarding health risks in the personnel studied. CONCLUSION: Since even the highest values were from natural sources, we assume the differences represent differences in ingestion of natural uranium. Definition of a reference distribution or normal values will depend on the subpopulation of interest.

A normative value pilot study: levels of uranium in urine samples from UK civilians.

A normative study of the levels of urinary uranium in the general UK population is needed for comparison with levels in UK military and ex-military personnel who served where munitions containing depleted uranium (DU) were used. As preparation, this pilot study trialled the process of collecting 24-h samples from adult male civilians, and compared the measurements from 24-h samples with those from spot samples taken over the subsequent 24h. The purpose was to assess the relative utility of the two types of samples. Twenty-five convalescent hospital in-patients were recruited as participants. Uranium concentrations in the 24-h samples ranged from 1 to 10.6 ng l(-1); in the spots, from not detectable to 38.1 ng l(-1). Normalised to creatinine, concentrations in the 24h samples ranged from approximately 100 to 800 ng mol(-1) creatinine; in the spot samples, from not detectable to approximately 4000 ng mol(-1) creatinine. The ranges appear similar to those reported for residents of the US. The distribution of spot sample results indicated that 95% of a participant's creatinine-adjusted concentrations from spot samples would be within the range 40-250% of his mean. Adjusting for creatinine almost entirely eliminated a slight indication of diurnal variation in urinary uranium concentration in spot samples. All the 24-h samples and 131 out of the 133 spot samples showed ratios of isotopes (238)U to (235)U consistent with natural uranium (i.e. neither enriched nor depleted). Slightly elevated ratios in two spot samples were not supported by other samples from the same participants, indicating that slightly elevated ratios may be recorded on very low concentration (<1 ng l(-1)) samples. In the main, quantification of this isotope ratio from spot samples was only slightly more variable than from 24-h samples. Complete 24-h urine samples gave better precision than spot samples in estimating uranium concentrations at these low levels, but presented more logistic difficulties in the collection of the samples. Clarification of the relative merits of alternative sampling strategies enables the design of a wider study to be optimised.

Dust related risks of clinically relevant lung functional deficits.

AIM: To quantify the risks of clinically important deficits of FEV1 in coal miners in relation to cumulative and average concentrations of respirable dust. METHODS: Data were studied from over 7000 men who had been surveyed in the late 1970s. Linear regression equations for the association between FEV1 and self-reported breathlessness on mild exertion were used to define clinically important levels of FEV1 deficit, and the probabilities that individuals with different dust exposures would experience these deficits were calculated. RESULTS: Levels of FEV1 were lower among breathless men than among others, with a large overlap of the distributions. The relations between standardised FEV1 and breathlessness were constant over all age and smoking groups. A decrease of 100 ml in FEV1 was associated with an increase of 1.12 in the odds of reporting breathlessness. FEV1 deficits of -0.367, -0.627, and -0.993 l (designated as "small", "medium", and "large" deficits) were, on average, associated with proportional increases of risks of breathlessness by factors of 1.5, 2.0, and 3.0 respectively. Cumulative respirable dust exposure ranged up to 726 gh/m3, mean 136 gh/m3 (British Medical Research Council measurement convention). An increase of 50 gh/m3 was associated with an increase of about 2% in the proportion of men with small deficits in FEV1. For medium deficits the increases ranged from 1.5% to 2%, depending on age. A similar pattern was seen for large deficits, but with smaller increases. CONCLUSIONS: In the unlikely event of continuous exposure at the proposed new maximum respirable dust limit for British mines of 3 mg/m3 (ISO-CEN measurement convention) for a working lifetime, the risk of a medium deficit of FEV1 for a non-smoker at age 60 would be estimated to be 34%, compared with 25% for zero dust exposure; for smokers, about 54% compared with 44%.

Dust concentrations and respiratory risks in coalminers: key risk estimates from the British Pneumoconiosis Field Research.

To help inform the setting of dust control standards in coalmines, this brief review summarises the most recent and reliable exposure-response relations, for damaging respiratory effects, derived from the Pneumoconiosis Field Research (PFR). Collecting data over 38 years in the British coal industry, this was a programme of prospective research on the respiratory health of coal miners, characterised by regular health surveys and detailed measurements of dust and silica concentrations in the workplace. Exposure-response relations are presented for coal workers' simple pneumoconiosis category II, progressive massive fibrosis, defined deficits of lung function (FEV1), and category II silicosis. This simplified overview provides a guide to the most recent and most reliable estimates from the PFR of dust-related risks of substantial pulmonary disease, and to the magnitude of the effects. Control of dust sufficient to prevent category II simple pneumoconiosis should prevent most cases of progressive massive fibrosis and most dust related large lung function deficits. Where the dust contains high proportions of silica, control to low levels is essential, and even quite brief excursions of silica to high levels must be avoided.

Quantitative relations between exposure to respirable quartz and risk of silicosis.

AIMS: To reanalyse exposure-response data from a Scottish colliery to gain a more detailed knowledge of the relations between exposure to quartz and risks of silicosis in coal miners, and hence inform the debate on an appropriate occupational standard for respirable quartz. METHODS: Detailed data on working times at different quartz concentrations were combined to produce exposure profiles for miners who had provided a full chest radiograph at a follow up survey. Logistic regression methods were used to model profusion of radiographic abnormalities category 2/1+, and a general exposure index was used to compare different quartz exposure measures in these models. RESULTS: Results in 371 men aged 50-74 indicated that cumulative quartz exposure at higher concentrations resulted in proportionally greater risks of abnormalities. One g x h x m(-3) of cumulative exposure at quartz concentrations greater than 2 mg x m(-3) was estimated to have equivalent risks to 3 g x h x m(-3) at lower concentrations. The timing of exposure relative to follow up appeared less important, although the study had limited power to compare different lag periods between exposure and effect. CONCLUSIONS: Quantification of the risks of silicosis should take account of variations in quartz exposure intensity, particularly for exposure to concentrations of greater than 1 or 2 mg.m(-3), even if exposure is for relatively short periods. The risks of silicosis over a working lifetime can rise dramatically with even brief exposure to such high quartz concentrations. Risk estimates are given, to inform choice of control limits.

An epidemiological study of the respiratory health of workers in the European refractory ceramic fibre industry.

OBJECTIVES: To investigate possible relations between respiratory health and past airborne exposure to refractory ceramic fibres (RCFs) and respirable dust in workers at six European factories, studied previously in 1987. METHODS: The target population comprised all current workers associated with RCF production, plus others who had participated in 1987 "leavers". Information was collected on personal characteristics, chest radiographs, lung function, respiratory symptoms, smoking, and full occupational history. Regression analysis was used to study relations between indices of health of individual workers and of cumulative exposure to airborne dust and fibres, and likely past exposure to asbestos. RESULTS AND DISCUSSION: 774 workers participated (90% of current workers, 37% of leavers). Profusion of small opacities in exposed workers (51% 0/1+; 8% 1/0+) was similar to that among an unexposed control group but higher than in new readings of the 1987 study films (11% 0/1+, 2% 1/0+). The large difference between 1987 and recent films may be, at least in part, a reading artefact associated with film appearance. Small opacities of International Labour Organisation (ILO) category 1/0+ were not associated with exposure. An association of borderline significance overall between 0/1+ opacities and exposure to respirable fibres was found for some exposure periods only, the time related pattern being biologically implausible. Pleural changes were related to age and exposure to asbestos, and findings were consistent with an effect of time since first exposure to RCFs. Among men, forced expired volume in 1 second (FEV(1)) and forced vital capacity (FVC) were inversely related to exposure to fibres, in current smokers only. FEV(1)/ FVC ratio and transfer factor (TL(CO)) were not related to exposures. The estimated restrictive effect was on average mild. Prevalence of respiratory symptoms was low. Chronic bronchitis and its associated symptoms (cough, phlegm) showed some association with recent exposure to respirable fibres. This could be due to an irritant effect of RCFs.

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers.

OBJECTIVES: To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy. METHODS: The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests. RESULTS: Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers. CONCLUSIONS: The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.

Epidemiological evidence on the carcinogenicity of silica: factors in scientific judgement.

In view of the extended debate and differing opinions on whether crystalline silica is a human carcinogen, we have reviewed a selection of epidemiological reports, to identify the areas of uncertainty and disagreement. We have chosen to examine the papers which in a recent review were considered to provide the least confounded examinations of an association between silica exposure and cancer risk. We also refer to a study of the mortality of coalminers very recently reported by ourselves and colleagues. We find that parts of the evidence are coherent but there are contradictions. On examination this resolves mostly into differences between types of studies. The three types of epidemiological study included are: (i) exposure-response studies, the most powerful for the confirmation of a relationship between a specific exposure and a health effect; (ii) descriptive studies in which incidence of disease in an exposed population is compared with that in a reference population; and (iii) studies of incidence of disease in subjects on silicosis case-registers. Descriptive studies frequently though not invariably suggest an excess lung cancer risk in silica-exposed workers compared with the general population, but exposure-response studies consistently fail to confirm that the cause is exposure to quartz. A single exposure-response study of cristobalite suggests a positive relation. Both sets of evidence have weaknesses. There are uncertainties on whether the excess risks in the descriptive studies are related to silica exposure or to lifestyle, including smoking habits. There are doubts on whether the exposure estimates in some of the exposure-response studies were sufficiently reliable to detect a small risk or weak association, though they are unlikely to have missed a strong effect. Studies of subjects on silicosis case registers consistently show an excess of lung cancer, but it is not clear to what extent these increased risks represent a direct effect of silica exposure, a secondary effect of the silicosis, preferential inclusion of subjects suffering from the effects of smoking, or bias in diagnostic accuracy. This not unnaturally leads to differences in opinion, exacerbated by variations in the strength of proof required by different experts. The main scientific uncertainties in the evidence are: 1. Whether, in the descriptive studies, the excess lung cancer rates in silica-exposed workers are explicable in terms of smoking habits, socio-economic class differences and inappropriate comparison populations. Better smoking information and more carefully chosen comparison populations are needed; 2. Whether the exposure-response studies could have missed a real relationship between silica exposure and lung cancer, if one exists. Many of the exposure-response studies were conducted with great care, but weaknesses, in the available data on which the exposure estimations were based, could have caused a real relationship of lung cancer and silica exposure to be missed. These studies were sufficiently powerful to demonstrate relationships of silica exposure with silicosis and silico-tuberculosis, so it is unlikely that they would have missed any but a small risk, or weak relationship, for lung cancer. Our own recent study of coalminers used uniquely detailed and reliable exposure data, and failed to demonstrate convincingly an increased risk. This negative finding, though, applies only to a dust in which the proportion of quartz in the dust is usually less than 10%. Exposure-response studies are needed, with high quality exposure estimates, in populations exposed to respirable dust of which crystalline silica comprises more than 10%; 3. Whether the excess cancer risks in subjects on silicosis registers are the result of selection and diagnostic bias. Given these difficulties, case-register studies may not be capable of giving a reliable answer to the central question, though they have been useful in pointing to the possibility of a can

Risks of respiratory disease in the heavy clay industry.

OBJECTIVES: Little information is available on the quantitative risks of respiratory disease from quartz in airborne dust in the heavy clay industry. Available evidence suggested that these risks might be low, possibly because of the presence in the dust of other minerals, such as illite and kaolinite, which may reduce the harmful effects of quartz. The aims of the present cross sectional study were to determine among workers in the industry (a) their current and cumulative exposures to respirable mixed dust and quartz; (b) the frequencies of chest radiographic abnormalities and respiratory symptoms; (c) the relations between cumulative exposure to respirable dust and quartz, and risks of radiographic abnormality and respiratory symptoms. METHODS: Factories were chosen where the type of process had changed as little as possible during recent decades. 18 were selected in England and Scotland, ranging in size from 35 to 582 employees, representing all the main types of raw material, end product, kilns, and processes in the manufacture of bricks, pipes, and tiles but excluding refractory products. Weights of respirable dust and quartz in more than 1400 personal dust samples, and site histories, were used to derive occupational groups characterised by their levels of exposure to dust and quartz. Full size chest radiographs, respiratory symptoms, smoking, and occupational history questionnaires were administered to current workers at each factory. Exposure-response relations were examined for radiographic abnormalities (dust and quartz) and respiratory symptoms (dust only). RESULTS: Respirable dust and quartz concentrations ranged from means of 0.4 and 0.04 mg.m-3 for non-process workers to 10.0 and 0.62 mg.m-3 for kiln demolition workers respectively. Although 97% of all quartz concentrations were below the maximum exposure limit of 0.4 mg.m-3, 10% were greater than this among the groups of workers exposed to most dust. Cumulative exposure calculations for dust and quartz took account of changes of occupational group, factory, and kiln type at study and non-study sites. Because of the importance of changes of kiln type additional weighting factors were applied to concentrations of dust and quartz during previous employment at factories that used certain types of kiln. 85% (1934 employees) of the identified workforce attended the medical surveys. The frequency of small opacities in the chest radiograph, category > or = 1/0, was 1.4% (median reading) and seven of these 25 men had category > or = 2/1. Chronic bronchitis was reported by 14.2% of the workforce and breathlessness, when walking with someone of their own age, by 4.4%. Risks of having category > or = 0/1 small opacities differed by site and were also influenced by age, smoking, and lifetime cumulative exposure to respirable dust and quartz. Although exposures to dust and to quartz were highly correlated, the evidence suggested that radiological abnormality was associated with quartz rather than dust. A doubling of cumulative quartz exposure increased the risk of having category > or = 0/1 by a factor of 1.33. Both chronic bronchitis and breathlessness were significantly related to dust exposure. CONCLUSIONS: Although most quartz concentrations at the time of this study were currently below regulatory limits in the heavy clay industry, high exposures regularly occurred in specific processes and occasionally among most occupational groups. However, there are small risks of pneumoconiosis and respiratory symptoms in the industry, although frequency of pneumoconiosis is low in comparison to other quartz exposed workers.

Biopersistence and durability of nine mineral fibre types in rat lungs over 12 months.

The study objectives were to assess the ability of intratracheal injection methods to discriminate between nine fibre types in respect of pulmonary biopersistence, and to provide approximate estimates of relative biopersistence and durability for a study of general relationships with biological and toxicological responses. The test fibres included six samples of size-selected fibre types specially prepared for research purposes, two commercially available fibres, and amosite. A 1 mg dose of each fibre type was administered to rats by intratracheal injection. The relative biopersistence of fibres in different size categories was assessed from the changes in mean lung burden, as determined by electron microscopy, at 3 days and 1, 6 and 12 months after injection. The ability of the test materials to resist dissolution was measured in a parallel series of simple in vitro acellular experiments at two pHs and in a continuous flow dissolution test. The observed differences in the persistence of fibres of differing length recovered from rat lungs were consistent with the current hypothesis that short fibres are cleared by cellular processes and long fibres by dissolution and disintegration. Differences in persistence of long (> 20 microns) fibres were correlated with measured rates of dissolution in vitro. Differences in persistence among those fibre types also studied by others workers were consistent with their findings after inhalation and intratracheal injection. Overall, the differences in the biopersistences of the test fibres following intratracheal injection were sufficient to enable an examination of the relationship of biopersistence with other biological and toxicological responses. Biopersistence was influenced by both fibre dimensions and solubility.

Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity.

A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses.

Influence of characteristics of inhaled fibres on development of tumours in the rat lung.

The objective was to examine and quantify the influence of fibre dimensions, persistence in the lung, and dissolution and cell toxicity in vitro, on the risks of developing lung tumours in rats. Data were brought together from the studies carried out at the IOM under the Colt Fibre Research Programme, and from studies carried out in Switzerland and the USA under the programme of the Thermal Insulation Manufacturers Association. In both studies, groups of rats were exposed by inhalation to a range of airborne fibres. At the end of their lives they were examined for the presence of benign and malignant lung tumours and mesothelioma. The studies differed in a number of details, but were combined on the basis of approximate equivalence of cumulative exposure to airborne fibres. Logistic regression models were used to relate differences in carcinogenicity to fibre characteristics; dimensions, persistence in the lung after intratracheal injection, dissolution rates from bench-top flow-through experiments, measures of inflammation, and other cell responses to fibres in vitro. Despite the small number of data points, the results suggested a primary influence of the airborne concentrations of the numbers of fibres thinner than 1 micron diameter and longer than 20 microns, and of the measured dissolution rate of the fibres. While these results are based on only a small number of fibre types, the statistical model fits the data reasonably well, and enables some cautious insights into the quantitative influences of dimensions and biopersistence. Results were broadly consistent with those from intraperitoneal injection studies of the same fibres, in that the responses were dependent on both the durability of the fibres and the numbers of long thin fibres. In vitro and in vivo cell responses did not predict significantly the risk of cancer following inhalation.

Risks of silicosis in coalworkers exposed to unusual concentrations of respirable quartz.

OBJECTIVES: To describe the radiographic changes in coalworkers exposed to unusual concentrations of respirable quartz during the 1970s, and to relate these to exposure measurements. METHODS: Men who had worked at one Scottish colliery during the 1970s were invited to a health survey. Chest radiographs were taken from 547 subjects. Classifications of these films under the International Labour Organisation (ILO) 1980 scheme were related, by logistic regression, to existing data on individual men's exposures to respirable dust and quartz. RESULTS: Taking the median of the three readers' results on profusion of small opacities, 203 men (38%) showed progression of at least one profusion category on the 12 point scale, from the various 1970s surveys to the follow up in 1990-1. A total of 158 men (29%) had a profusion of at least 1/0, and 47 (8.6%) of at least 2/1 at the follow up survey. Large opacities were recorded as present by at least two readers for 14 (2.6%) of the men. Profusion of small opacities was strongly related to exposures experienced in the 1970s, and more strongly for quartz than for the non-quartz fraction of the dust. Estimates of risk are presented over the range of quartz exposures experienced. CONCLUSIONS: The quartz exposures experienced by some men at this colliery have caused considerable progression of radiographic abnormalities since exposure ended. The data accumulated offer opportunities for further more detailed analyses to inform debate on occupational limits for quartz exposures, both in collieries and in other industries where there is exposure to quartz in mixed dust.

Respiratory health effects of opencast coalmining: a cross sectional study of current workers.

OBJECTIVE: To identify whether there is evidence of pneumoconiosis and other respiratory health effects associated with exposure to respirable mixed dust and quartz in United Kingdom opencast coalmines. METHODS: A cross sectional study of current workers (1224 men, 25 women) was carried out at nine large and medium sized opencast sites in England, Scotland, and Wales. To characterise a range of occupational groups within the industry, full shift measurements of personal exposures to respirable dust and quartz were taken. Up to three surveys were carried out at each site, covering all four seasons. For the purposes of comparisons with health indices these groups were further condensed into five broad combined occupational groups. Full sized chest radiographs, respiratory symptoms, occupational history questionnaires, and simple spirometry were used to characterise the respiratory health of the workforce. Logistic or multiple regression techniques were used to examine relations between indices of exposure and respiratory health. RESULTS: None of the group geometric mean dust concentrations, based on 626 valid dust samples, exceeded 1 mg.m-3, and 99% of all quartz concentrations were below 0.4 mg.m-3, the current maximum exposure limit. The highest quartz concentrations were experienced by the rock drilling team and drivers of bulldozers (used to move earth and stone from layers of coal). There were clear differences in mean respirable dust and quartz concentrations between occupational groups. These were consistent across the different sites, but depended in part on the day of measurement. The variations between sites were not much greater than between days, suggesting that differences between sites were at least partly explained by differences in conditions at the time of the measurements. The prevalence of radiographic small opacities profusion category > or = 1/0, based on the median of three readings, was 4.4%. Five men had category 2 pneumoconiosis and two men (including one of these five) had progressive massive fibrosis category A. From regression analyses, the relative risk of attaining a profusion of category > or = 0/1 was estimated to be doubled for every 10 years worked in the dustiest, preproduction opencast jobs, after allowing for age, smoking, and site effects. Risk was not associated with time worked in any other occupation within the industry, nor with previous employment in underground mining or other dusty jobs. Symptoms of chronic bronchitis were present in 13% of the men. Frequency of chronic bronchitis was influenced by years worked in dusty jobs outside opencast mining, but not by time spent in occupations within the industry. Asthmatic symptoms were reported by 5% of the workforce, close to the mean frequency found in adult men. No positive associations were found between asthma and occupational exposures. Lung function on average was close to predicted value and showed no relation to time worked in opencast occupations. CONCLUSIONS: Frequency of (mostly mild) chest radiographic abnormalities is associated with working in the dustier, preproduction jobs in the industry. Although some of these mild abnormalities may be non-occupational (due to aging or smoking), the association with exposure indicates a small risk of pneumoconiosis in these men, and the need to monitor and control exposures, particularly in the high risk occupations.

Assessment of human risks from exposure to low toxicity occupational dusts.

Recent animal studies have demonstrated three separate and distinct mechanisms by which low toxicity dusts can cause important chronic pulmonary effects; through overloading of clearance mechanisms, through increased toxicity associated with ultrafine particle size or by increasing the toxicity of known carcinogens in mixed exposures. The problem to be addressed is how the pathogenicity to man of various airborne dusts should be evaluated, when epidemiological evidence is often insufficient, and the reliability of extrapolation of quantitative risks from animals to man is not established. In this paper we examine the feasibility of evaluating the likely human risks of low toxicity dusts by: (1) semi-quantitative comparisons of the ability of various dusts, in animal studies, to cause overload of clearance and resulting inflammation and fibrosis; (2) postulating that these relativities apply quantitatively to human risks; and (3) estimating approximate human risks by comparisons with reference dusts for which adequate animal and human data are available. Such a decision-making framework appears feasible, provided: (1) comparable and quantitative methods are used consistently in animal studies for the measurement of impairment of clearance leading to overload and resulting inflammation and fibrosis; (2) the quantitative relationships between impairment of clearance leading to overload, and resulting inflammation and fibrosis, can be defined adequately in animals for various dusts; (3) the particle size distributions, including those in the ultrafine range, for dusts to which animals and/or humans are exposed, are taken into account (or are comparable); (4) at least two reference dusts with well-documented activities spanning the range of toxicity can be identified; and (5) the reliability of the predictions of human pathogenicity of a sample of other dusts is tested, in toxicological studies and by observation in humans. Some possible candidate reference and test dusts are identified.

Relations between upper limb soft tissue disorders and repetitive movements at work.

To make a preliminary assessment of whether upper limb soft tissue disorders might be associated with activities at work, we have conducted a case-control study of subjects attending orthopedic clinics in three cities. All subjects between the ages of 16 and 65 years, in whom defined soft tissue conditions of the upper limb were diagnosed by the participating orthopedic surgeons, were invited to take part. Controls were subjects attending the same clinics within the same age range whose clinical diagnosis did not include disease of the upper limb, cervical or thoracic spine. Information concerning repetitive movements of the upper limbs at work was elicited by questionnaire. Five hundred eighty cases and 996 controls were studied, representing 96% and 93%, respectively, of those invited to participate. The diagnoses of the cases included soft tissue conditions affecting the shoulder, elbow, forearm, wrist, thumb, hand, and fingers. The diagnoses of the controls included traumatic, degenerative, and inflammatory conditions, mostly of the legs and lower back. Women predominated among the cases (70%) and men among the controls (56%). Of 221 female cases with injury to the wrist and forearm, 32 were cleaner/domestics (14.5%) compared to 35 to 439 controls (8%), a difference statistically significant at the 2 1/2% level. Other jobs significantly overrepresented (5% level) among female cases with injuries at various anatomical sites included hairdressers, secretary/temps, assembly line workers, and machine operators (type unspecified). Among male cases, electricians were significantly overrepresented (5% level). Jobs for which there was a suggestion (p < 0.1) of overrepresentation among cases included butchers and teacher/lecturers (both males only) and the combined job groups (chosen a priori for analysis) of keyboard operators, machine operators, and music teachers (all three jobs, females only).

Questionnaire for the identification of back pain for epidemiological purposes.

OBJECTIVES: To design a questionnaire for the identification and assessment of severity of back pain for epidemiological purposes, and gain preliminary experience of its use. METHODS: A group of specialists, experienced in the epidemiology and clinical assessment of back pain, designed the questionnaire, and tested it individually. It was also given cross sectionally by interview to a population of male coal mine workers. RESULTS: The questionnaire comprised a maximum of 12 questions on the presence, radiation, frequency, and severity of back pain with reference to difficulty with specific activities, interference with normal work, and absence from work. 471 coal miners answered the questionnaire (66% of those invited). 56% (265 men) of the responders reported pain or ache in the back during the previous 12 months, and the incidence of first ever attacks during the same period was reported to be 34%. 69% reported having had back pain at some time. The responses to the questionnaire were partially validated by comparison with certified sickness absence for two days or more attributed to back pain. In men who were symptomatic in the previous 12 months, for the question relating to absence from work because of back pain, the sensitivity was 82% and specificity was 84%. CONCLUSION: The questionnaire is easy to administer and generates clear cut data that could be useful for epidemiological or screening purposes. Preliminary, limited, studies of its validity are reasonably encouraging, although further validation is required. It is hoped that researchers will find the questionnaire useful, will extend its validation, and continue to develop it.

Immune responses to colophony, an agent causing occupational asthma.

BACKGROUND: Inhalation of fumes from heated colophony (pine resin) is a recognised cause of occupational asthma, although the mechanisms by which colophony produces symptoms are unclear and specific immune responses to colophony have not been reported in sensitised workers. A study was carried out to determine whether colophony is antigenic. METHODS: The immune responses to colophony were studied in C57BL/6 mice and Dunkin Hartley guinea pigs after intraperitoneal injection of colophony conjugated to bovine serum albumin (BSA) or human IgG by a mixed anhydride procedure. Colophony and dinitrofluorobenzene were also compared in an assay of dermal sensitisation. RESULTS: Mice immunised with the colophony conjugates produced antibodies which recognised conjugates of both BSA and human IgG irrespective of which had been used as the immunogen. Solutions of unconjugated colophony inhibited the binding of antibodies to the BSA-colophony and BSA-abietic acid conjugates, confirming that the antibodies recognised one or more components in the colophony. Portuguese colophony also abrogated the antigen binding of serum from guinea pigs immunised with the BSA-colophony conjugate. Spleen cells from immunised mice proliferated in the presence of the conjugates. Although there was some cross reactivity in these responses, it was not as marked as in the antibody assays. Unconjugated colophony failed to induce an immune response when injected intraperitoneally with adjuvant. Skin sensitisation could not be induced in mice by topical application, or by subcutaneous or intradermal injection of unconjugated colophony. CONCLUSIONS: Colophony components have the potential to act as haptens and an immune component could be involved in the pathogenesis of occupational asthma in workers exposed to colophony. Colophony is not readily immunogenic unless conjugated ex vivo to proteins.

The characteristics of respiratory ill health of wool textile workers.

The relations of lung function and chest radiographic appearances with exposure to inspirable dust were examined in 634 workers in five wool textile mills in west Yorkshire, randomly selected to represent fully the range of current exposures to wool mill dust. Most of these workers could be categorised into three large sex and ethnic groups; European men, Asian men, and Asian women. Exposures to inspirable dust had been measured at a previous survey and time spent in current job, and in the industry were used as surrogates for lifetime cumulative exposures. Chest radiographs were interpreted on the International Labour Office (ILO) scale by three medically qualified readers, and the results combined. Profusions of small opacities of 0/1 on the ILO scale, or greater, were present in only 6% of the population, and were not positively associated with current exposure to wool mill dust, or duration of exposure. In general, statistically significant relations between exposure and lung function indices were not found, with the exception of an inverse relation between the forced expiratory volume/forced vital capacity ratio and dust concentration in European women. A suggestive but not statistically significant inverse relation between FVC and current dust concentration was seen in Asian men. Substantial differences were found between mills in mean values of lung function variables after adjustment for other factors but these were not apparently related to the differences in dust concentrations between these mills. Dyeworkers and wool scourers (mostly European men in relatively dust free jobs) on average experienced an FEV1 251 ml lower than other workers when age, height, smoking habits, and occupational factors had been taken into account. Twenty four per cent of the workforce responded to intracutaneous application of one or more common allergens (weal diameter at least 4 mm), only 12 (7.9%) of these responding to wool extracts. Atopic subjects did not appear to have an increased susceptibility to the effects of inspirable wool dust on lung function. These studies suggest that exposure to wool mill dust may cause functional impairment in some workers but there is little indication from these data of frequent or severe dust related functional deficits. More detailed estimates of cumulative dust exposure by reconstruction of exposure histories might clarify associations between exposure to dust and lung function. These chest radiographic findings provide no evidence that exposure to wool mill dust is related to lung fibrosis.

Inflammation in the lungs of rats after deposition of dust collected from the air of wool mills: the role of epithelial injury and complement activation.

In a previous study assessing respiratory symptoms in individuals employed in wool textile mills in the north of England relations between symptoms of chronic bronchitis, breathlessness and wheeze, and rhinitis and current exposure to airborne mass concentration of dust were shown. As preliminary steps in defining the potential hazard associated with dust from the air of wool mills the ability of inspirable dust, collected from the air of wool textile mills, to cause inflammation when injected into the lungs of rats was determined. Dusts were collected from the beginning of wool processing (opening) in one factory and from the middle (combing) and late (backwinding) stages of the process in two other factories. Ability of the dusts to cause inflammation was assessed by instillation into the lungs of rats followed by bronchoalveolar lavage. All the dusts caused some inflammation which peaked on day 1 and did not persist beyond one week. A distinctive aggregation response of mononuclear cells in the lavage, however, had a different time course, peaking at day 7. An attempt was made to determine how the wool mill dusts caused inflammation and experiments showed that the dusts themselves had no inherent chemotactic activity but that they did have a pronounced ability to generate chemotaxins in serum and so could activate complement in lung fluid. In addition, dust collected from ledges in the mills had the ability to injure epithelial cells in vitro which could also contribute to inflammation. A role for endotoxin in the inflammatory activity of the dusts was not discounted and a leachate of the dust had the ability to cause inflammation when injected into the lungs of rats. Wool mill dust is likely to be a complex mixture of materials and these experiments represent a preliminary approach to understanding the biological activity of the whole unfractionated dust and further studies are in progress to define more accurately the toxic material(s) in the dust.