A quantitative assessment of health risk induced by occupational exposure to inorganic arsenic

This article describes a series of 21 consecutive cases, each involving a solitary median maxillary central incisor; the patients were seen in the Department of Dentistry or the Victorian Clinical Genetics Unit, Murdoch Institute, at the Royal Children's Hospital, Melbourne, from 1966 to 1997. The spectrum of anomalies and associated features present in these cases--solitary median maxillary central incisor, choanal atresia, and holoprosencephaly--is described, and the literature related to the features, including genetic studies in these conditions, is reviewed. We relate our findings in these cases to current knowledge of developmental embryology. It is hoped that the findings, together with our interpretation of them, will help to clarify understanding of solitary median maxillary central incisor syndrome. This syndrome was previously considered a simple midline defect of the dental lamina, but it is now recognized as a possible predictor of holoprosencephalies of varying degrees in the proband, in members of the proband's family, and in the family's descendants.     

Brain cancer and occupational exposure to lead

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.     

Pulmonary fibrosis and occupational exposure to aluminum

Many reports of respiratory disease attributable to aluminum exposure have appeared in the European medical literature during the last 50 years. Great Britain and Germany are two major industrialized nations that acknowledge a causal relationship between occupational exposure to aluminum and respiratory impairment. For factory workers in these countries, pulmonary disease attributed to respirable aluminum particulates is compensated as a workplace disability. In North America, however, there is a lack of consensus regarding the pathogenicity of aluminum fumes and dust to the worker. This view may be based on a difference in the types of industrial usage, the updated methods of aluminum processing in this country, or the benefits of a modern workplace. It has also been proposed that the development of aluminum-induced pulmonary disease may depend on a particular host factor that has not yet been identified. We describe a patient whom we believe developed severe respiratory compromise and irreversible pulmonary fibrosis from a lifetime of industrial aluminum exposure.     

Relevance of interrater agreement to violence risk assessment.

This study considered whether assessments of violence risk in which 2 clinicians reach similar conclusions are more accurate than the conclusions of either clinician alone when their assessments disagree. One hundred ten physicians and 44 nurses estimated the probability of physical assault of 478 patients admitted to a short-term locked psychiatric inpatient unit. The level of assessed risk showed a substantial correspondence with the likelihood of later violence when the physician and nurse ratings were highly concordant. As the extent of agreement between the physician and nurse ratings decreased, the strength of the association between the risk assessments and the occurrence of violence decreased accordingly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cost-effectiveness of chemoprophylaxis after occupational exposure to HIV

OBJECTIVES: To assess the economic efficiency of recent US Public Health Service recommendations for chemoprophylaxis with a combination of antiretroviral drugs following high-risk occupational exposure to human immunodeficiency virus (HIV). To provide a framework for evaluating the relative effectiveness and costs associated with candidate postexposure prophylaxis (PEP) regimens. METHODS: Standard techniques of cost-effectiveness and cost-utility analysis were used. The analysis compares the costs and consequences of a hypothetical, voluntary combination-drug PEP program consisting of counseling for all HIV-exposed health care workers, followed by chemoprophylaxis for those who elect it vs an alternative in which PEP is not offered. A societal perspective was adopted and a 5% discount rate was used. Hospital costs of recommended treatment regimens (zidovudine alone or in combination with lamivudine and indinavir) were used, following the dosing schedules recommended by the US Public Health Service. Estimates of lifetime treatment costs for HIV and acquired immunodeficiency syndrome were obtained from the literature. Because the effectiveness of combination PEP has not been established, the effectiveness of zidovudine PEP was used in the base-case analyses. MAIN OUTCOME MEASURES: Net PEP program costs, number of HIV infections averted, cost per HIV infection averted, and cost-utility ratio (net cost per discounted quality-adjusted life-year saved) for zidovudine, lamivudine, and indinavir combination PEP. Lower bounds on the effectiveness required for combination regimens to be considered incrementally cost saving, relative to zidovudine PEP alone, were calculated. Multiple sensitivity and threshold analyses were performed to assess the impact of uncertainty in key parameters. RESULTS: Under base-case assumptions, the net cost of a combination PEP program for a hypothetical cohort of 10,000 HIV-exposed health care workers is about $4.8 million. Nearly 18 HIV infections are prevented. The net cost per averted infection is just less than $400,000, which exceeds estimated lifetime HIV and acquired immunodeficiency syndrome treatment costs. Although combination PEP is not cost saving, the cost-utility ratio (about $37,000 per quality-adjusted life-year in the base case) is within the range conventionally considered cost-effective, provided that chemoprophylaxis is delivered in accordance with Public Health Service guidelines. Small incremental improvements in the effectiveness of PEP are associated with large overall societal savings. CONCLUSIONS: Under most reasonable assumptions, chemoprophylaxis with zidovudine, lamivudine, and indinavir following moderate- to high-risk occupational exposures is cost-effective for society. If combination PEP is minimally more effective than zidovudine PEP, then the added expense of including lamivudine and indinavir in the drug regimen is clearly justified.     

Hemorheology in occupational lead exposure

OBJECTIVES: The purpose of this investigation was to study hemorheological parameters in occupationally lead exposed men. MATERIAL AND METHODS: For 15 clinically healthy lead-exposed male subjects [age 34.6 (SD 8) years] the viscous (epsilon') and elastic (epsilon") components of whole blood viscosity corrected for 45% hematocrit were measured for shear rates between 1.s-1-100.s-1 at 37 degrees C. Moreover, lead concentrations in blood and urine and the delta-aminolevulinic acid dehydrase level were determined. Fifteen unexposed age-matched men were used as referents. RESULTS: The mean lead concentration in the blood and urine of the lead-exposed men was 48.7 (SD 16.2) micrograms. dl-1 and 38.8 (SD 17.1) micrograms.g creatinine-1, respectively. While epsilon" was significantly increased only at low shear rates, epsilon' was elevated throughout the investigated shear range in comparison with the values of the unexposed referents. These results are characteristic of erythrocytes with enhanced rigidity. The aggregation and filtration index of erythrocytes were significantly elevated for the lead-exposed workers. A positive correlation existed between lead in blood and epsilon' or epsilon", whereas delta -aminolevulinic acid dehydrase and epsilon' or epsilon" were inversely correlated. No differences in plasma viscosity or in lipid status could be detected. CONCLUSION: Increased blood lead concentrations can be considered an additional risk factor for vascular diseases predisposing towards microvascular occlusion.     

Behavioral determinants of occupational exposure to chemical agents.

Used the passive-active dimension of the job demand–control model (T. Theorell and R. A. Karasek, see record 83:28881) to examine the impact of behavioral factors on the exposure to and actual uptake of airborne lead in 2 lead exposed populations of male workers (18 from an electric accumulator factors and 18 from a lead smeltery) and to ascertain work-related determinants of hygienic behavior. Environmental exposure was assessed by measurement of the concentration of lead dust in ambient air at the workplace, and the intake of lead was assessed by measurement of the lead in blood level. In the work environment of Ss in active jobs, lower concentrations of lead in air were measures, but higher levels of lead in blood were observed in these workers. The opposite was true of workers in passive jobs. Differences in hygienic behavior (e.g., use of protective equipment) at work may explain these results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Future increase of the incidence of mesothelioma due to occupational exposure to asbestos in the past

OBJECTIVE: To estimate the future course of mesothelioma mortality as a result of occupational exposure to asbestos in the past. DESIGN: Cohort age model. SETTING: Department of Public Health, Erasmus University Rotterdam, the Netherlands. METHODS: A cohort age model was developed, based upon age-specific rates of pleural mesothelioma mortality during 1969-1994. This model was linked to the future trend in mortality among Dutch men as projected by the Central Bureau for Statistics in order to predict the future course of mesothelioma mortality in the period 1995-2030. RESULTS: In the next 35 years about 20,000 cases of pleural mesothelioma among men are expected. The projection results in a peak of annual male mesothelioma deaths of approximately 700 in about the year 2018. After 2020 the annual mortality will rapidly decline to about 450 cases in 2030. It is expected that this rapid decline will continue after 2030. In the 1943-1947 birth cohort pleural mesothelioma may account for 0.87% of all deaths. Exposure to asbestos at work largely explains this particular mortality pattern. CONCLUSION: Exposure to asbestos at work has created an important public health problem among Dutch men.     

Neurobehavioral effects in occupational chemical exposure

Neurotrophic factors, such as nerve growth factor (NGF), in addition to their role in neuronal development, have protective effects on neuronal survival. Intracerebral implantation of cells genetically altered to secrete high levels of NGF is also found to promote neuronal survival in experimental lesioning models of the brain. The range of activity for such biological delivery systems has not yet been well described either spatially or temporally. Therefore, the authors chose to study the local and distant protective effects of an NGF-secreting rat fibroblast cell line implanted in an excitotoxic lesion model of Huntington's disease. They found that preimplantation of NGF-secreting fibroblasts placed within the corpus callosum reduced the maximum cross-sectional area of a subsequent excitotoxic lesion in the ipsilateral striatum by 80% when compared to the effects of a non-NGF-secreting fibroblast graft, and by 83% when compared to excitotoxic lesions in ungrafted animals (p < 0.003). However, NGF-secreting cells placed in the contralateral corpus callosum failed to affect striatal lesion size significantly when compared to contralateral or ipsilateral non-NGF-secreting cell implants. Of note, fibroblasts were clearly visible within the graft site at 7 and 18 days after implantation; however, few cells within the grafts stained positively for NGF peptide or for the messenger ribonucleic acid (mRNA) encoding the transfected NGF gene-construct at either time point. These results show that biological delivery systems for NGF appear to have a profound but local effect on neuronal excitotoxicity, which will necessitate careful neurosurgical placement for maximum effect. Furthermore, the ability of this genetically altered cell line to synthesize NGF mRNA and peptide appears to decrease spontaneously in vivo, a characteristic that will need to be addressed before this method of biological delivery can be utilized as a treatment for chronic degenerative diseases.     

On strategies for comparing occupational exposure data to limits

Although research interest in the Harderian gland (HG) has increased during the last few years, only a small amount of information exists about its organogenesis. In mouse the HG appears in the posterior part of eye region, in the form of nonluminated tubules between the sixteenth and eighteenth days of gestation. At birth it is still not differentiated histologically. In birds the HG originates from the conjunctival epithelium at a late embryonic stage. In the English sparrow, Passer domesticus (incubation period of about 13 days), it appears between the seventh and the eighth days of incubation. In the chick embryo (incubation period of about 21 days) it originates between the eleventh and the twelfth days. Among reptiles the lizard Podarcis s. sicula has proved to be a useful model to clarify the embryological origin of the orbital glands since it possesses the anterior lacrimal gland contiguous to the HG in the medial corner of the orbit. The anlage of the orbital glands appears on about the twenty-second day of development (incubation period of about 43 days) in the form of a short tubule projecting from the conjunctival epithelium, at the time of development of the nictitating membrane. At this stage the mesenchymal cells surrounding the glandular blastema form a well-defined sac, later occupied by the orbital glands. From this stage until hatching the growth of the glandular blastema continues with the formation of acini which move posteriorly into the preformed mesenchymal sac. At the thirty-sixth day of development the more lateral acini differentiate into the HG. Only at the forty-first day do the more medial acini differentiate into the anterior lacrimal gland. At hatching the HG is fully differentiated. In anuran amphibia the primordium of the HG appears during the metamorphosis at the time of development of the nictitating membrane.     

Renal cell cancer correlated with occupational exposure to trichloroethene

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).     

Best estimate of the magnitude of mortality due to occupational exposure to hazardous substances

OBJECTIVES: With a proportionate attributable risk approach, to estimate the magnitude of premature mortality induced by exposure to hazardous substances in the Australian workforce. METHODS: Estimates of the magnitude of mortality induced by exposure to hazardous substances in the Australian work-force were calculated by the proportionate attributable risk approach after careful consideration of options for methodological refinements. The main data sources used were unit mortality datasets (individual deidentified death records), and tabulations when these were unavailable. RESULTS: The estimated number of deaths that occurred in Australia each year from occupational exposure to hazardous substances was 2290; 78% of these were men. The rate of mortality attributable to occupational exposure to hazardous substances was three to four times greater in male workers than in female workers. Male (productive) person-years of life lost (PYLL) were generally eight times higher than female PYLL. Cancer was the prime cause of death, followed by renal, cardiovascular, neurological, and chronic respiratory disease. Acute toxic episodes accounted for a small proportion of mortality but yielded a much larger proportion of PYLL, reflecting the relatively young ages of those who experienced fatal effects. CONCLUSIONS: Although national estimates of the proportions of mortality attributable to occupational exposure to hazardous substances seemed to be validly derived, uncertainties remain associated with the lack of an empirical basis for derivation of proportionate risk fractions used in the calculations. The finding of an appreciable burden of mortality that is attributable to past occupational exposure to hazardous substances emphasises the necessity for occupational health and safety authorities to measure and reduce worksite exposures. There is also an incentive to encourage the construction of appropriately designed cohort studies across industries and occupational groupings so that, ultimately, risk estimates may be directly calculated and applied to total workforce data for the definitive estimation of the magnitude of harm induced by occupational exposure to hazardous substances.     

Respiratory effects of occupational exposure to an epoxy resin system

A standardized respiratory questionnaire and pulmonary function tests were used to examine thirty-four employees of a snow-ski manufacturing plant, including twenty-five workers who were exposed to an epoxy resin system containing the amine hardener 3-dimethylamino propylamine (3-DMAPA). Maximum expiratory flow-volume curves were obtained on Monday and Thursday, before and after each shift, and FVC, FEV1.0, MEF50%, and MEF25% were caculated. Environmental measurements of the total amine levels were found to range from 0.41 to 1.38 ppm. The group with the greatest exposure (0.55-1.38 ppm) showed significant decreases in lung function over Monday and over the week. Although all employees in this group showed decreases in pulmonary function, acute changes were greater in present cigarette smokers and in subjects who reported respiratory symptoms upon exposure to the epoxy resin system. There was no evidence of permanent loss of lung function in subjects with either the highest or longest exposure.     

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons

Epidemiologic evidence on the relationship between polycyclic aromatic hydrocarbons (PAH) and cancer is reviewed. High occupational exposure to PAHs occurs in several industries and occupations. Covered here are aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, shale oil extraction, wood impregnation, roofing, road paving, carbon black production, carbon electrode production, chimney sweeping, and calcium carbide production. In addition, workers exposed to diesel engine exhaust in the transport industry and in related occupations are exposed to PAHs and nitro-PAHs. Heavy exposure to PAHs entails a substantial risk of lung, skin, and bladder cancer, which is not likely to be due to other carcinogenic exposures present in the same industries. The lung seems to be the major target organ of PAH carcinogenicity and increased risk is present in most of the industries and occupations listed above. An increased risk of skin cancer follows high dermal exposure. An increase in bladder cancer risk is found mainly in industries with high exposure to PAHs from coal tars and pitches. Increased risks have been reported for other organs, namely the larynx and the kidney; the available evidence, however, is inconclusive. The results of studies addressing environmental PAH exposure are consistent with these conclusions.     

Acetone in urine as biological index of occupational exposure to isopropyl alcohol

To analyze whether HLA may be a determinant of the risk of developing cervical cancer precursor lesions, the association between HLA and cervical neoplasia among HPV16-seropositive and -negative subjects was determined in a population-based cohort in the V?sterbotten county of Northern Sweden. HLA genotyping of DR and DQ was done by PCR in 74 patients and 164 healthy controls matched for age, sex and area of residence. The presence of DQA1*0102 was weakly associated with cervical neoplasia in HPV16-seropositive patients. DQB1*0602 was weakly associated with disease in all patients, but was strongly increased among HPV16-seropositive patients compared to HPV16-seropositive controls. DR15 had an association with disease that was particularly strong among HPV16-seropositive subjects. The haplotype DQA1*0102-DQB1*0602 (DQ6) was also weakly associated with disease in all patients and significantly increased among HPV16-positive patients when compared to HPV16-positive controls. A similar association was seen when analysis was restricted to CIN 2-3 patients. DQA1*0501-DQB1*0301 (DQ7) was more common among HPV16-negative patients than among HPV16-negative controls and was also more common among HPV16-negative patients than among HPV16-positive patients. In conclusion, DQA1*0102-DQB1*0602 (DQ6) is associated with an increased risk of cervical neoplasia among HPV16-seropositive subjects and DQA1*0501-DQB1*0301 (DQ7) with an increased risk among HPV16-seronegative subjects.     

Increase in neuropsychiatric symptoms after occupational exposure to low levels of styrene

The results of this study suggest that exposure to styrene below the current Swedish permissible exposure limit of 20 ppm induces neurotoxic effects expressed as an increased number of neuropsychiatric symptoms. Twenty men exposed to styrene at a plastics factory participated. The reference group included 20 non-exposed men matched for age, working schedule, and physical work load. Exposure to styrene during one workday was assessed by personal air monitoring and biological monitoring. To evaluate the physical work load the pulse(heart) rate was measured. One week before the study each man completed a neuropsychiatric symptom questionnaire containing 16 items. Also 17 questions regarding acute symptoms of local irritation and symptoms of the central nervous system were presented after the psychometric tests were performed. The tests were simple reaction time, colour word vigilance, and symbol digit. A follow up with regard to the symptoms among the exposed men was done after their summer vacation, about two to five weeks after their last exposure. The mean eight hour time weighted average (TWA) concentration of styrene in air, measured by passive dosimetry was 8.6 ppm (range 0.04-50.4 ppm). The exposed men had significantly more symptoms than the referents although there were no significant differences for the psychometric tests. At the follow up the exposed men reported fewer symptoms. This study indicates that symptoms are earlier indicators of adverse effects than complex tests and underlines the importance of regular follow up of people exposed to styrene (and probably organic solvents in general).