bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer mortality among workers in the German rubber industry: 1981-91.
Authors: Weiland S K , Mundt K A , Keil U , Kraemer B , Birk T , Person M , Bucher A M , Straif K , Schumann J , Chambless L
Published: December 2008

OBJECTIVES: To determine the cancer specific mortality of active and retired workers of the German rubber industry with emphasis on cancer sites which have been associated with the rubber industry in previous studies. METHODS: A cohort of 11,663 German men was followed up for mortality from 1 January 1981 to 31 December 1991. Cohort members were active (n = 7536) or retired (n = 4127) at the beginning of the study, and had been employed for at least one year in one of five study plants producing types or general rubber goods. Vital status was ascertained for 99.7% of the cohort members, and cause of death found for 96.8% of the 2719 decedents. Age and calendar year adjusted standardised mortality ratios (SMR) and 95% confidence intervals (95% CI) were calculated overall from national reference rates and stratified by year of hire and by years since hire. RESULTS: Mortalities from all causes (SMR 108; 95% CI 104-112) and all cancers (SMR 111; 95% CI 103-119) were significantly increased in the study cohort. Significant excesses in the mortalities from lung cancer (SMR 130; 95% CI 115-147) and pleural cancer (SMR 401; 95% CI 234-642) were identified. SMRs higher than 100 were found for cancers of the pharynx (SMR 144; 95% CI 76-246), oesophagus (SMR 120; 95% CI 74-183), stomach (SMR 110; 95% CI 86-139), rectum (SMR 123; 95% CI 86-170), larynx (SMR 129; 95% CI 69-221), prostate (SMR 108; 95% CI 84-136), and bladder (SMR 124; 95% CI 86-172), as well as for leukaemia (SMR 148; 95% CI 99-213). Mortalities from liver cancer, brain cancer, and lymphoma were lower than expected. CONCLUSIONS: Mortalities from cancer of several sites previously associated with the rubber industry were also increased among workers of the German rubber industry. Results of the stratified analyses are consistent with a role of occupational exposure in the aetiology of some of these cancers.
Mortality study of employees with potential exposure to epichlorohydrin: a 10 year update.
Authors: Tsai S P , Gilstrap E L , Ross C E
Published: December 2008

OBJECTIVES: A 10 year extension of follow up (up to 1993) of 863 employees who had potential exposure to epichlorohydrin at two chemical plants between May 1948 and December 1965 was conducted to further evaluate the previously reported potential association between exposure to epichlorohydrin and heart disease. METHODS: The mortality observed was compared with that expected from the death rates from the local male population where these chemical plants are located. Workers were assigned to one of five exposure categories based on their job with the highest level of potential exposure. Vital status was ascertained to the end of 1993. RESULTS: Among diseases of particular interest, there were no excess deaths from heart disease (standardised mortality ratio (SMR) 63.3), lung cancer (SMR 63.8), or non-malignant respiratory disease (SMR 37.7) for employees with 20 or more years after first exposure. Based on the level of potential exposure to epichlorohydrin, mortality for heart disease was slightly higher (SMR 75.7, 95% confidence interval (95% CI) 51.8-106.7) in the moderate to heavy exposure group than in the none to light exposure group (SMR 59.5, 95% CI 37.7-89.3); this difference is well within the range of random variation. The SMR for heart disease was 90.4 among employees who had both probable exposure to allyl chloride and moderate to heavy exposure to epichlorohydrin, although it was 88.1 among employees who had moderate to heavy potential exposure to epichlorohydrin but no exposure to allyl chloride. CONCLUSIONS: This study does not support an association between exposure to epichlorohydrin and heart disease or lung cancer. There were no additional deaths from leukaemia in this update; the raised SMR for leukaemia noted in the previous study has substantially decreased from 500.0 to 161.3 (95% CI 33.2-471.0) and is not significant. The overall mortality and cancer mortality of employees potentially exposed to epichlorohydrin continued to be lower than that of the local population.
Radium in drinking water and risk of bone cancer in Ontario youths: a second study and combined analysis.
Authors: Finkelstein M M , Kreiger N
Published: December 2008

OBJECTIVES: Radium induces bone sarcomas at high doses, but there is controversy about risk at low doses. A previous study in Ontario found an association between the presence of radium in birthplace water supplies and an increased risk of death from bone cancer in young people. An investigation was performed to test the findings of the previous study with an independent group of subjects for whom complete information on radium exposure would be obtained. METHODS: A population based case-control study (238 cases; 432 controls) was conducted with incident cases of bone sarcoma identified from the Ontario cancer registry. Residential histories were collected by questionnaire and water samples were obtained and analysed for radium content. RESULTS: There was an association between risk of osteosarcoma and birthplace exposures (odds ratios (ORs) and 90% confidence intervals (90% CIs) 1.77 (1.03-3.00) but not with lifetime measures of exposure. When lifetime exposure was dichotomised, the OR was 1.31 (0.76-2.24) for osteosarcoma. There was no trend with increasing exposure. Bootstrap resampling was used to simulate lifetime doses in a pooled analysis of 1293 subjects from the two Ontario studies. The ORs were 1.38 (1.08-1.73) for all sarcomas, and 1.44 (1.01-1.87) for osteosarcoma. Geometric mean doses in bone were about 26 mRad. CONCLUSIONS: An association was found between the presence of radium in birthplace water supplies and increased risk of bone sarcoma in two studies. Increased risk was present for lifetime measures of exposure, but the association was not significant, and there was no dose-response trend. Our findings are compatible with the absence of risk at low doses, but they might also reflect inadequate statistical power to measure a true risk at environmental exposure levels. If the increased risk at environmental doses is causal, risk of bone sarcoma is effectively linearly related to dose over five orders of magnitude.
Biomarkers of exposure to low concentrations of benzene: a field assessment.
Authors: Ong C N , Kok P W , Ong H Y , Shi C Y , Lee B L , Phoon W H , Tan K T
Published: December 2008

OBJECTIVE: To carry out a comprehensive field investigation to evaluate various conventional and recently developed biomarkers for exposure to low concentrations of benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in blood and urine, urinary trans, transmuconic acid, and three major phenolic metabolites of benzene: phenol, catechol, and hydroquinone. Validations of these biomarkers were performed on 131 never smokers occupationally exposed to the time weighed average benzene concentration of 0.25 ppm (range, 0.01 to 3.5 ppm). RESULTS: Among the six biomarkers studied, unmetabolised benzene in urine correlated best with environmental benzene concentration (correlation coefficient, r = 0.76), followed by benzene in blood (r = 0.64). When urinary metabolites were compared with environmental benzene, trans, trans-muconic acid showed a close correlation (r = 0.53) followed by hydroquinone (r = 0.44), and to a lesser extent with urinary phenol (r = 0.38). No correlation was found between catechol and environmental benzene concentrations. Although unmetabolised benzene in urine correlates best with benzene exposure, owing to serious technical drawbacks, its use is limited. Among the metabolites, trans, trans-muconic acid seems to be more reliable than other phenolic compounds. Nevertheless, detailed analyses failed to show that it is specific for monitoring benzene exposures below 0.25 ppm. CONCLUSION: The overall results suggest that most of the currently available biomarkers are unable to provide sufficient specificity for monitoring of low concentrations of benzene exposure. If a lower occupational exposure limit for benzene is to be considered, the reliability of the biomarker and the technical limitations of measurements have to be carefully validated.
Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.
Authors: Chitano P , Rado V , Di Stefano A , Papi A , Boniotti A , Zancuoghi G , Boschetto P , Romano M , Salmona M , Ciaccia A , Fabbri L M , Mapp C E
Published: December 2008

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.
Wool and grain dusts stimulate TNF secretion by alveolar macrophages in vitro.
Authors: Brown D M , Donaldson K
Published: December 2008

OBJECTIVE: The aim of the study was to investigate the ability of two organic dusts, wool and grain, and their soluble leachates to stimulate secretion of tumour necrosis factor (TNF) by rat alveolar macrophages with special reference to the role of lipopolysaccharide (LPS). METHODS: Rat alveolar macrophages were isolated by bronchoalveolar lavage (BAL) and treated in vitro with whole dust, dust leachates, and a standard LPS preparation. TNF production was measured in supernatants with the L929 cell line bioassay. RESULTS: Both wool and grain dust samples were capable of stimulating TNF release from rat alveolar macrophages in a dose-dependent manner. The standard LPS preparation caused a dose-dependent secretion of TNF. Leachates prepared from the dusts contained LPS and also caused TNF release but leachable LPS could not account for the TNF release and it was clear that non-LPS leachable activity was present in the grain dust and that wool dust particles themselves were capable of causing release of TNF. The role of LPS in wool dust leachates was further investigated by treating peritoneal macrophages from two strains of mice, LPS responders (C3H) and LPS non-responders (C3H/HEJ), with LPS. The non-responder mouse macrophages produced very low concentrations of TNF in response to the wool dust leachates compared with the responders. CONCLUSIONS: LPS and other unidentified leachable substances present on the surface of grain dust, and to a lesser extent on wool dust, are a trigger for TNF release by lung macrophages. Wool dust particles themselves stimulate TNF. TNF release from macrophages could contribute to enhancement of inflammatory responses and symptoms of bronchitis and breathlessness in workers exposed to organic dusts such as wool and grain.
Semen quality of men employed at a lead smelter.
Authors: Alexander B H , Checkoway H , van Netten C , Muller C H , Ewers T G , Kaufman J D , Mueller B A , Vaughan T L , Faustman E M
Published: December 2008

OBJECTIVE: To evaluate the effects of recent and long term occupational lead exposure on indicators of male reproductive health. METHODS: In a cross sectional study of male employees of a lead smelter (n = 2469), blood samples were obtained from 152 workers including 119 who also provided semen samples. Semen analysis and serum concentrations of testosterone, follicle stimulating hormone, and luteinising hormone were used as indicators of reproductive health. Semen and hormone variables were examined in relation to measures of current and long term body lead burden estimated from current blood lead concentrations and historical blood lead monitoring data. RESULTS: For current blood lead concentration groups of < 15, 15-24, 25-39, > 40 micrograms/dl, the geometric mean sperm concentrations were, respectively, 79.1, 56.5, 62.7, and 44.4 million cells/ml and geometric mean total sperm counts were 186, 153, 137, and 89 million cells (P for trend 0.04). Compared with workers with blood lead concentrations less than 15 micrograms/dl, workers with current blood lead concentrations of 40 micrograms/dl or more had an increased risk of below normal sperm concentration (odds ratio (OR) 8.2, 95% confidence interval (95% CI) 1.2-57.9) and total sperm count (OR 2.6, 95% CI 0.4-15.7), based on World Health Organisation standards. Independent of current lead exposure, sperm concentration, total sperm count, and total motile sperm count were inversely related to measures of long term lead exposure. No association was found between lead exposure and measures of sperm motility, sperm morphology, or serum concentrations of reproductive hormones. CONCLUSIONS: Blood lead concentrations below the currently accepted worker protection criteria seem to adversely affect spermatogenesis.
Biological indicators of exposure to total and respirable aluminium dust fractions in a primary aluminium smelter.
Authors: Röllin H B , Theodorou P , Cantrell A C
Published: December 2008

OBJECTIVES: The study attempts to define biological indicators of aluminium uptake and excretion in workers exposed to airborne aluminium compounds in a primary aluminium smelter. Also, this study defines the total and respirable aluminium dust fractions in two different potrooms, and correlates their concentrations with biological indicators in this group of workers. METHODS: Air was sampled at defined work sites. Non-destructive and conventional techniques were used to find total and respirable aluminium content of the dust. Blood and urine was collected from 84 volunteers employed at various work stations throughout the smelter and from two different cohorts of controls matched for sex, age, and socioeconomic status. Aluminium in serum samples and urine specimens was measured by flameless atomic absorption with a PE 4100 ZL spectrometer. RESULTS: The correlation of aluminium concentrations in serum and urine samples with the degree of exposure was assessed for three arbitrary exposure categories; low (0.036 mg Al/m3), medium (0.35 mg Al/m3) and high (1.47 mg Al/m3) as found in different areas of the smelter. At medium and high exposure, the ratio of respirable to total aluminium in the dust samples varied significantly. At high exposure, serum aluminium, although significantly raised, was still within the normal range of an unexposed population. The workers with low exposure excreted aluminium in urine at levels significantly higher than the controls, but still within the normal range of the population. However, potroom workers with medium and high exposure had significantly higher urinary aluminium than the normal range. CONCLUSIONS: It is concluded that only urinary aluminium constitutes a practical index of occupational exposure at or above 0.35 mg Al/m3, and that the respirable fraction of the dust may play a major role in the biological response to exposure to aluminium in a smelter environment.
Mutation rates at the glycophorin A and HPRT loci in uranium miners exposed to radon progeny.
Authors: Shanahan E M , Peterson D , Roxby D , Quintana J , Morely A A , Woodward A
Published: December 2008

OBJECTIVES--To find whether a relation exists between estimated levels of exposure to radon and its progeny and mutations in hypoxanthine phosphoribosyl transferase (HPRT) and glycophorin A in a cohort of former uranium miners. METHODS--A cohort study involving a sample of miners from the Radium Hill uranium mine in South Australia, which operated from 1952 to 1961. Radiation exposures underground at Radium Hill were estimated from historical radon gas measures with a job exposure matrix. Workers from the mine who worked exclusively above ground according to mine records were selected as controls. In 1991-2 miners were interviewed and blood taken for measurement of somatic mutations. Mutation rates for HPRT and glycophorin A were estimated with standard assay techniques. RESULTS--Homozygous mutations of glycophorin A were increased in underground miners (P = 0.0027) and the mutation rate tended to rise with increasing exposure with the exception of the highest exposure (> 10 working level months). However, there was no association between place of work and either the hemizygous mutations of glycophorin A or the HPRT mutation. CONCLUSIONS--There may be an association between glycophorin A mutations and previous occupational exposure to ionising radiation. However, not enough is known at present to use these assays as biomarkers for historical exposure in underground mining cohorts.
Controlling the healthy worker survivor effect: an example of arsenic exposure and respiratory cancer.
Authors: Arrighi H M , Hertz-Picciotto I
Published: December 2008

OBJECTIVE--This investigation sought to examine whether methods proposed to control the healthy worker survivor effect would influence the shape or magnitude of the dose-response curve for respiratory cancer induced by arsenic. METHODS--Results from an unadjusted analysis are compared with results obtained by applying four different methods for control of the healthy worker survivor effect to data on arsenic exposure and respiratory cancer. The four methods are: exposure lag, adjustment for work status, cohort restriction, and the G null test. RESULTS--Cohort restriction gave erratic results depending upon the minimum years of follow up used. Exposure lag substantially increased the rate ratios and a non-linear shape (decreasing slope) compared with an unlagged analysis. Adjusting for work status (currently employed upsilon retired or otherwise not employed) yielded slightly higher rate ratios than an unadjusted analysis, with an overall shape similar to the baseline analysis. Results from the G null test procedure of Robins (1986), although not directly comparable with the baseline analysis, did show an adverse effect of exposure that seemed to reach a maximum when exposure was lagged between 10 and 20 years. CONCLUSIONS--All results confirm an adverse effect of arsenic exposure on respiratory cancer. In these data, it seems that the healthy worker survivor effect was not strong enough to mask the strong effect of arsenic exposure on respiratory cancer. Nevertheless, several methods show a stronger association between arsenic exposure and respiratory cancer after adjustment for the healthy worker survivor effect, suggesting that for weaker causal associations, studies not controlling for this source of bias will have low power to detect results. Although the G methods are theoretically the most unbiased, further work elucidating the validity of the assumptions underlying lagging, adjustment for work status, and the G methods are needed before clear recommendations can be made.
Cancer incidence and specific occupational exposures in the Swedish leather tanning industry: a cohort based case-control study.
Authors: Mikoczy Z , Schütz A , Strömberg U , Hagmar L
Published: December 2008

OBJECTIVE--To study the effect on the incidence of cancer of exposure to chemicals handled in the leather tanning industry. MATERIALS AND METHODS--A case-control study was performed within a cohort of 2487 workers employed for at least six months during the period 1900-89 in three Swedish leather tanneries. 68 cancer cases (lung, stomach, bladder, kidney, nasal, and pancreatic cancers and soft tissue sarcomas) and 178 matched controls were studied. Effects of chemical exposures on cancer incidence, adjusted for age at risk, sex, and plant were estimated with a conditional logistic regression model. RESULTS--A significant association was found between exposure to leather dust and pancreatic cancer (odds ratio (OR) 7.19, 95% confidence interval (95% CI) 1.44 to 35-89). An association was indicated between leather dust from vegetable tanning and lung cancer. After adjustment for smoking habits a tentative association between organic solvents and lung cancer lost its significance. No association was found between exposure to chlorophenols and soft tissue sarcomas. CONCLUSIONS--The significant association between leather tanning and soft tissue sarcomas that was found in our previous cohort analysis could not be explained by exposure to chlorophenols. On the other hand a significant association was found between exposure to leather dust and pancreatic cancer, and exposure to leather dust from vegetable tanning was often present in cases with lung cancer. Due to the small numbers of cases, the results can, however, only lead to tentative conclusions.
Neuropsychological verbal tests may lack "hold" properties in occupational studies of neurotoxic effects.
Authors: Michélsen H , Lundberg I
Published: December 2008

OBJECTIVES--In epidemiological studies of neurotoxic effects neuropsychological tests are often applied to assess possible functional changes. In these studies tests presumed to be resistant to neurotoxic effects, "hold tests", are often used to adjust performance in tests presumed to be sensitive to neurotoxic effects, "nonhold tests", in assessment of pre-exposure ability. This conception is based on experience from the examination of patients with organic brain disorders. For this adjustment to be valid hold tests should change comparatively little over time and should not change differently in groups of people with different exposures to neurotoxic agents. METHODS--These assumptions were examined in 71 carpenters and 135 painters divided in three subgroups according to level of cumulative exposure to organic solvents. The results were noted from two verbal tests (test A, which involved following verbal instructions and test C, word comprehension), which were performed at conscription (age 18-20). The tests resemble hold tests used in occupational studies. The same tests were performed again at the age of 45-60 together with a conventional synonym test (SRB 1), often used in occupational studies. RESULTS--In the three tests given at the time of the investigation some differences were found between the carpenters and the subgroups of painters. The painters with low exposure tended to perform better than the carpenters in all three tests and the heavily exposed painters tended to perform less well in the tests. These differences were not present at the age of 18-20. In one of the conscription tests painters with different cumulative exposure to organic solvents developed differently over time. There was little improvement among painters with heavy and intermediate exposure and obvious improvement among painters with low exposure. The results in the other conscription test showed similar tendencies. CONCLUSIONS--The results indicate that the hold tests examined do not meet basic criteria for hold tests used in occupational studies. Thus adjustments for conventional verbal tests seem inappropriate in such studies. It is possible that other presumed hold tests may meet the criteria but our results suggest that such tests also should be evaluated before being used as hold tests in working populations.
Prognostic factors for return to work after a first compensated episode of back pain.
Authors: Infante-Rivard C , Lortie M
Published: December 2008

OBJECTIVES--To determine which factors measured at baseline and during the course of treatment influence time to return to work after a first compensated episode of back pain. METHODS--The design is a treatment inception cohort including 305 compensated workers out of 402 eligible ones presenting at two rehabilitation centres for conventional treatment. Crude and adjusted rate ratios (RRs) along with 95% confidence intervals (95% CIs) were estimated with the Cox's proportional hazards regression. RESULTS--50% of workers had not returned to work after 112 days of follow up, and 11.3% still had not after 270 days. At the end of the study period (maximum follow up time was 1228 days), 230 workers (75.4%) had returned to work, 6.5% had not, and a similar percentage had retired, gone into vocational training, or returned to school. In the final model stratified for radiating pain during treatment, which was an important prognostic variable, workers between 21 to 30 years of age had a greater chance of returning to work (RR (95% CI) 1.43 (1.04 to 1.98) than those > or = 30. The other factors associated with a greater chance of returning to work were: a diagnosis of sprain or pain upsilon a diagnosis of intervertebral disc disorder (2.20 (1.23-3.91)), < 30 days of waiting between the accident and the beginning of treatment (1.30 (0.96 to 1.77)), a good flexion at baseline (1.52 (1.04 to 2.23)), absence of neurological symptoms during treatment (1.40 (0.98-2.00)), > 24 months of employment in the industry (1.49 (1.10 to 2.03)), working for a public industry upsilon a private one (1.63 (1.21 to 2.19)), and the ability to take unscheduled breaks (1.45 (1.06 to 1.97)). CONCLUSIONS--Even with a first episode of back pain, time to return to work is long and the proportion not returning is high. Return to work as expected is influenced by disease and host characteristics but also by social and work factors. Reinstatement programmes should account for all these factors.
Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.
Authors: Bonde J P , Giwercman A , Ernst E
Published: December 2008

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function.
Abnormalities on neurological examination among sheep farmers exposed to organophosphorous pesticides.
Authors: Beach J R , Spurgeon A , Stephens R , Heafield T , Calvert I A , Levy L S , Harrington J M
Published: December 2008

OBJECTIVES: Organophosphates are effective pesticides which are frequently used in several agricultural settings. Although their acute effects are well characterised, it remains unclear whether long term exposure can damage the human nervous system. This study sought to investigate their long term effects by comparing abnormalities on neurological examination between groups of workers exposed to organophosphates and an unexposed group. METHODS: 146 exposed sheep farmers and 143 unexposed quarry workers were recruited into a cross sectional study of symptoms and neuropsychological effects of long term exposure to organophosphates in sheep dip. From a symptom questionnaire given immediately after dipping the 10 most symptomatic and 10 least symptomatic farmers were selected. Several months later each of these, along with 10 of the unexposed quarry workers, underwent a standardised neurological examination similar to that which might be used in clinical practice, at at time as remote as possible from recent exposure to organophosphates so as to exclude any acute effects. RESULTS: All 30 selected subjects agreed to participate. The components of the examination which showed a significant difference were two point discrimination on the dorsum of the hand (symptomatic farmers 22 mm; asymptomatic farmers 13 mm; quarry workers 8 mm) and the dorsum of the foot (symptomatic farmers 34 mm; asymptomatic farmers 10 mm; quarry workers 11 mm), and mean calf circumference (symptomatic farmers 35.0 cm; asymptomatic farmers 36.3 cm; quarry workers 38.6 cm). Overall the prevalence of neurological abnormalities was low. CONCLUSIONS: The differences in neurological examination detected between groups were subtle and their clinical significance was unclear. However, they do suggest evidence of an adverse neurological effect from exposure to organophosphates. Further, larger scale studies will be required before it is possible to confirm or refute the differences detected.
Carinal and tubular airway particle concentrations in the large airways of non-smokers in the general population: evidence for high particle concentration at airway carinas.
Authors: Churg A , Vedal S
Published: December 2008

OBJECTIVE: To evaluate the extent to which human airway carinas accumulate ambient atmospheric particles, a newly developed technique was used to micro-dissect and analyse particle concentration in tubular segments and carinas of the large airways of 10 necropsy lungs from non-smokers from the general population of Vancouver. METHODS: Ratios of the particle concentrations on the carinas to the tubular segment immediately preceding it were measured with analytical electron microscopy for the mainstem bronchus, upper and lower lobe bronchi, and four different segmental or subsegmental bronchi--that is, Weibel generations 1 to about 5. A total of 119 carinal-tubular pairs was evaluated. RESULTS: Over all cases, both carinal and tubular particle concentrations increased with increasing airway generation; the median ratio of carinal to tubular particle concentration was 9:1 and did not show any trend with airway generation. The ratio was > 5 in 71% of carinal-tubular pairs, > 10 in 42% of pairs, > 20 in 31% of pairs, and > 100 in 9% of pairs. Some subjects showed a notable tendency to high ratios, with many ratios > 100, and other subjects had a tendency toward low ratios. The predominant mineral species in both carinas and tubular airway segments was crystalline silica and the relative proportion was similar in both sites; however, mean particle diameter was consistently less in the carinal tissues. CONCLUSIONS: These findings suggest that the ratio of carinal to tubular retained particles in the large airways in non-smokers is higher than might be supposed from data generated in airway casts, and that there is considerable variation in this ratio between subjects. This finding is of potential interest in models of carcinogen, toxin, and dose of fibrogenic agent to the large airways as it suggests high and sometimes extreme concentrations of toxic particles at carinas, and thus reinforces the notion that carinas may be sites of initiation of disease.
Immunological changes among farmers exposed to phenoxy herbicides: preliminary observations.
Authors: Faustini A , Settimi L , Pacifici R , Fano V , Zuccaro P , Forastiere F
Published: December 2008

OBJECTIVES: To evaluate short term immunological changes after agricultural exposure to commercial formulations of chlorophenoxy herbicides. METHODS: Blood samples were collected from 10 farmers within seven days before exposure, one to 12 days after exposure, and again 50 to 70 days after exposure. Whole blood was used to count lymphocyte subsets with monoclonal antibodies. Peripheral blood mononuclear (PBM) cells were used to measure natural killer (NK) cell activity and lymphocyte response to mitogenic stimulations. Values before exposure were used as reference. RESULTS: In comparison with concentrations before exposure, a significant reduction was found one to 12 days after exposure in the following variables (P < 0.05): circulating helper (CD4) and suppressor T cells (CD8), CD8 dim, cytotoxic T lymphocytes (CTL), natural killer cells (NK), and CD8 cells expressing the surface antigens HLA-DR (CD8-DR), and lymphoproliferative response to mitogen stimulations. All immunological values found 50-70 days after exposure were comparable with concentrations before exposure, but mitogenic proliferative responses of lymphocytes were still significantly decreased. CONCLUSIONS: According to our data agricultural exposure to commercial 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) formulations may exert short term immunosuppressive effects. Further studies should clarify whether the immunological changes found may have health implications and can specifically contribute to cancer aetiology.
Acute effects of exposure to air contaminants in a sawmill on healthy volunteers.
Authors: Dahlqvist M , Palmberg L , Malmberg P , Sundblad B M , Ulfvarson U , Zhiping W
Published: December 2008

OBJECTIVES: To study whether air contaminants in sawmills can induce acute changes in the upper and lower airways of previously non-exposed subjects. METHODS: Nineteen healthy volunteers were examined to find the concentration of interleukin 6 (IL-6) in nasal lavage fluid and lung function before and after five hour exposure to dusts and fumes generated in a sawmill where timber from Scots pine was sawed. When exposed, the subjects had respirators with and without a particle filter. RESULTS: The median for daily time weighted average concentration of total dust for subjects with respirators without a filter was 0.13 mg/m3, which was significantly higher than the median of 0.04 mg/m3 for subjects who had respirators with a filter. The median for the concentration of IL-6 in the nasal lavage fluid increased after exposure from 0.5 to 5.9 pg/ml in subjects with respirators without a particle filter (P < 0.05). The increase of the concentration of IL-6 was significantly correlated with the dust concentration. A decrease in transfer factor of the lung was significantly correlated with daily time weighted average concentrations of terpenes. CONCLUSION: The findings suggest that healthy volunteers, exposed to air contaminants in a sawmill, show a slight inflammatory reaction. Also, the results of the study indicate the importance of decreasing the concentrations of wood dust in the work environment.
Comparison of average estimated metabolic rates for styrene in previously exposed and unexposed groups with pharmacokinetic modelling.
Authors: Wang Y , Kupper L L , Löf A , Rappaport S M
Published: December 2008

OBJECTIVE: To understand whether previous styrene exposure increases the human liver's ability to convert styrene into styrene oxide. METHODS: The hypothesis was tested that the average linear metabolic rate constant kappa was the same in both exposed and unexposed groups, when the exposed group comprised people with a history of styrene exposure and the unexposed group had no exposure. In an experimental chamber, these two groups of subjects were exposed to a concentration of 80 ppm styrene for two hours. A three compartment pharmacokinetic model was used to define kappa. Based on large sample theory, the comparison of estimated mean values of kappa in the exposed and unexposed groups was shown to be equivalent to a comparison of the estimated mean values of the hepatic clearance X in the two groups. A method was developed to estimate X for each subject in both groups from the subject's height, weight, and estimated asymptotic styrene decay constant alpha. Here, alpha was estimated individually from observed blood concentrations over time when sufficient time had elapsed after the controlled exposure. RESULTS: The proposed methodology of comparing the estimated mean values of kappa in exposed and unexposed groups reduced the number of specific physiological variables involved to three, all of which were estimable from data based on simple direct measurements. In contrast, other methods based on pharmacokinetic models usually involved many variables that were non-estimable on an individual basis. Consequently, statistical comparisons were impossible. These methods were applied to analyse previously published data on the time course of styrene concentrations in arterial blood of subjects in both exposed and unexposed groups. A Wilcoxon non-parametric rank sum test with the individually estimated X values was used, and no significant difference in the means of X in the two groups was found. CONCLUSION: The linear metabolic rate constant kappa for humans is probably not altered by previous exposure to styrene. This result is in agreement with some experimental studies on animals. However, in the data analysis, it was noted that the number of subjects in each group was small (6-7) and that the styrene concentration data did not exactly reflect true behaviour of asymptotic decay. Further studies are still needed to draw more definitive conclusions.
Mortality among chemical workers in a factory where formaldehyde was used.
Authors: Marsh G M , Stone R A , Esmen N A , Henderson V L , Lee K Y
Published: December 2008

OBJECTIVES: An independent and updated historical cohort mortality study was conducted among chemical plant workers to investigate further an association between exposures to formaldehyde and particulates and cancers of the nasopharynx and lung reported in an earlier National Cancer Institute study of the same plant. METHODS: Subjects were 7359 workers who were first employed between 1941 and 1984 in a factory in Wallingford, Connecticut where formaldehyde was used. Vital status was determined on 31 December 1984 for 96% of the cohort and death certificates were obtained for 93% of 1531 known deaths. Exposures of individual workers were estimated quantitatively for formaldehyde, product particulates, and non-product particulates, and qualitatively for pigment. Statistical analyses focused on 6039 white men in 1945-84. Cohort data that could not have been included in the National Cancer Institute study were also analysed separately. RESULTS: Mortality among long term workers (employed > or = 1 y) was generally similar to or more favourable than that of the general population, and there was little evidence of a relation between either rates of lung cancer or standardised mortality ratios (SMRs) and several measures of exposure to formaldehyde, particulates, and pigment. For several causes including lung cancer, death rates among short term workers (employed < 1 y) were significantly increased. Short term workers did not seem to differ from long term workers for the exposures considered. Among all white men, a significant SMR of 550 (local comparison) for nasopharyngeal cancer (NPC) was based on the same four index cases identified in the earlier study of this plant. Only one case of nasopharyngeal cancer had any appreciable exposure to formaldehyde. No new cases of nasopharyngeal cancers were found among the cohort data that could not have been included in the National Cancer Institute study--that is, extended observation time and additional study members. CONCLUSIONS: Among workers employed for at least one year, this study provides little evidence that the risk of lung cancer is associated with exposure to formaldehyde alone or in combination with particulates or pigment. The significant increases in both the rates and SMRs for lung cancer seem to be primarily a phenomenon of short term workers, but the possibility remains that unmeasured occupational or non-occupational factors may have played a part.
Preventive effectiveness of pre-employment medical assessments.
Authors: de Kort W , van Dijk F
Published: December 2008

OBJECTIVE AND METHODS: Health gain, prevention of health loss, and avoidance of financial risk all seem to be driving forces for the use of pre-employment medical assessment. An attempt is made to measure the effect of implementing the pre-employment medical assessment on these end points. The anticipated maximum preventive effect (preventive effectiveness) of selection by means of pre-employment medical assessments for work related risks and the potential for disablement in individual workers can be calculated or estimated. Necessary parameters include test validity characteristics and epidemiological data for both the adverse outcome to be prevented, and risk factors of concern. RESULTS: The preventive effectiveness can be expressed as the effort (number of actions) needed to prevent one adverse event-for example, one case of occupational disease or one case of long term disablement. Actions include: a pre-employment health assessment, rejection of the candidate, individual precautions, adjustments of the job, and adjustments of the job environment. It seems that the preventive effectiveness of many actions can be low, implying that large numbers of actions are needed to prevent one adverse outcome. DISCUSSION: The medical assessment should consist of no more questions and tests than are required relevant to the stated aim. Particularly, when the pre-employment medical assessment is used to reject candidates at risk, the use of tests should be carefully weighed. If the preventive effectiveness is considered to be too low, then the question or test should not be incorporated for selection purposes. The application of a so called "expert judgment" should be based on professional guidelines wherever possible and should be made clear. The benefit of reducing the incidence of a serious adverse event by one may outweigh the costs of rejecting many candidates. CONCLUSIONS: The concept of preventive effectiveness may help to reach evidence based occupational medicine, which starts at the pre-employment medical assessment.
Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites.
Authors: Elliott P , Kleinschmidt I
Published: December 2008

OBJECTIVES: To study the incidence of angiosarcoma of the liver in England and Wales 1979-86 and Scotland 1975-87. To investigate whether any non-occupational neighbourhood cases occurred near a vinyl chloride site. METHODS: This is a geographical study of incident cases among the general population of Great Britain. Diagnosis of angiosarcoma of the liver was based mainly on the national cancer registry, the world register of cases among vinyl chloride workers, and the register of cases (including histological review) maintained by the Health and Safety Executive. Proximity (< 10 km) of residence to a vinyl chloride site was based on postcode of address at the time of diagnosis. RESULTS: 55 cases were ascribed to angiosarcoma of the liver in England and Wales with a further six cases in Scotland (annual incidence in Great Britain from all sources of around 1.4 cases per 10 million population). There were two cases with documented exposure to Thorotrast, and 10 cases among vinyl chloride workers. There were no vinyl chloride sites in Scotland. Among the 25 cases in England and Wales with histological diagnosis after review by a panel of pathologists, only 15 were confirmed as angiosarcoma, and one of the two Scottish cases after histological review was also confirmed. Overall, 11 cases ascribed to angiosarcoma were resident within 10 km of a vinyl chloride site; nine were vinyl chloride workers, one further case on histological review was not considered to have been correctly diagnosed as angiosarcoma, and the remaining case, confirmed as angiosarcoma, was employed at a vinyl chloride factory during the late 1950s, although not as a vinyl chloride worker. CONCLUSION: The incidence of angiosarcoma of the liver in Great Britain remains extremely rare. The one confirmed case in a non-vinyl chloride worker within 10 km of a site must nevertheless be presumed to have been exposed to vinyl chloride in the workplace. In the period of study, there were no confirmed non-occupationally exposed cases of angiosarcoma among residents living near a vinyl chloride site in Great Britain.
Relation between decline in FEV1 and exposure to dust and tobacco smoke in aluminium potroom workers.
Authors: Søyseth V , Boe J , Kongerud J
Published: December 2008

OBJECTIVES: To investigate the relation between pulmonary function and occupational exposure in aluminium pot operators. METHODS: 2795 observations were obtained in 630 workers over six years of follow up. An autoregressive method of analysis was used. RESULTS: After adjustment for FEV1 in the three previous years, the effect of smoking v no smoking on FEV1 was -43.1 ml, 95% confidence interval (95% CI) -72.3 to -13.9. Similarly, an increase in the exposure to particulates by 1 mg/m3 corresponded to a decrease in FEV1 of -11.9 ml, 95% CI -19.9 to -3.9. Age was a significant predictor of both FEV1 and FVC. CONCLUSION: Exposure to particulates in aluminium potrooms seems to increase the decline in FEV15 thereby increasing the risk of development of chronic obstructive lung disease in pot operators.