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PubMed2006

Occupational exposures and risk of systemic lupus erythematosus: a review of the evidence and exposure assessment methods in population- and clinic-based studies.

Epidemiologic and experimental research suggests a potential role of occupational exposures in the development of systemic lupus erythematosus (SLE). A plausible association has been identified in studies of occupational silica exposure and SLE, complemented by experimental studies in lupus-prone mice exploring potential mechanisms related to apoptosis and immune dysregulation. Experimental studies of the solvent trichloroethylene in lupus-prone mice provide evidence of effects on immune function, including increased production of autoantibodies and activation of CD4+ T cells. However, few studies of occupational solvent exposure and SLE have been conducted, and those that are available show little evidence of an association. There is some suggestion from the available studies of the potential influence of pesticides on SLE, but as with solvents, the specific type of pesticides that may be implicated is not known. Our understanding of the role of occupational exposures in SLE could be advanced by the development of larger, multisite or parallel studies that utilize similar questionnaire and exposure evaluation methods. Multiple studies using comparable exposure measures are needed to provide sufficient sample size for examining gene-environment interactions. We provide a general overview of data requirements and methods available for the assessment and evaluation of occupational exposures in clinical and population-based studies of SLE.

Animals↗
PubMed2004

Temporal variability of urinary phthalate metabolite levels in men of reproductive age.

Phthalates are a family of multifunctional chemicals widely used in personal care and other consumer products. The ubiquitous use of phthalates results in human exposure through multiple sources and routes, including dietary ingestion, dermal absorption, inhalation, and parenteral exposure from medical devices containing phthalates. We explored the temporal variability over 3 months in urinary phthalate metabolite levels among 11 men who collected up to nine urine samples each during this time period. Eight phthalate metabolites were measured by solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry. Statistical analyses were performed to determine the between- and within-subject variance apportionment, and the sensitivity and specificity of a single urine sample to classify a subject's 3-month average exposure. Five of the eight phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in 100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples. Although we found both substantial day-to-day and month-to-month variability in each individual's urinary phthalate metabolite levels, a single urine sample was moderately predictive of each subject's exposure over 3 months. The sensitivities ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance and the predictive ability of a single urine sample differed among phthalate metabolites. In particular, a single urine sample was most predictive for MEP and least predictive for MEHP. These results suggest that the most efficient exposure assessment strategy for a particular study may depend on the phthalates of interest.

Adult↗
PubMedDate not supplied

Challenges in addressing community concerns regarding clusters of multiple sclerosis and potential environmental exposures.

Citizens living around hazardous waste sites in the USA have expressed concern to public health officials at the local, state and federal level about a perceived high prevalence of multiple sclerosis (MS) in their communities. Many believe the occurrence of the disease is directly linked to exposure to chemical agents from the nearby hazardous waste site. Although the public's concern regarding these clusters should be addressed, epidemiologists have long known that evaluating perceived clusters is rarely fruitful for identifying an etiologic agent. In order to adequately address concerns regarding clusters of MS, as well as examining the role of environmental exposures and genetic susceptibility in the causal mechanism of disease, several activities need to be conducted including characterizing the occurrence of disease, developing a standardized case definition and establishing partnerships to develop innovative research techniques. Only with collaboration across disciplines and lessons learned from past research will we be able to effectively guide research efforts directed at determining the etiology of this disease.

Cluster Analysis↗
PubMed1996

Influence of exposure to fluoridated water on socioeconomic inequalities in children's caries experience.

This study aimed to evaluate inequalities in children's dental caries experience among socioeconomic status (SES) groups and to investigate effects of exposure to fluoride in water on those inequalities. Cross-sectional data were obtained from 6704 Queensland children aged 5-12 years and 6814 South Australian children aged 5-15 years. School dental therapists and dentists recorded dmfs and DMFS data. A questionnaire to parents sought information about household SES and each child's lifetime exposure to fluoridated drinking water. SES fluoride exposure and multiplicative interactions between the two were used as explanatory variables in least squares models in which dmfs and DMFs were dependent variables. Additive interactions were evaluated by calculating the excess rate of disease. In both states, children from low SES groups (categorized by household income or parental education) had higher mean dmfs and DMFS values than children from high SES groups (P < 0.01). Independent effects of income and education remained significant (P < 0.01) after controlling for exposure to fluoride in drinking water. In Queensland, there was a significant multiplicative interaction whereby SES inequalities were lower among children exposed to fluoride: dmfs ratios between low- and high-income groups ranged among ages from 1.54 to 3.56 for children with no exposure to fluoride and from 0.84 to 2.07 for children with lifetime exposure to fluoride. Multiplicative interactions were not statistically significant in South Australia or when DMFS was the dependent variable. However, additive interactions were consistent and most pronounced for deciduous teeth in both States. Absolute differences in caries experience between low and high SES children were greater among non-exposed groups due to the higher underlying levels of caries experience of children with no exposure to fluoride in water.

Adolescent↗
PubMed2004

[Wegener's disease and exposure to silica. Study of the physiopathological mechanisms].

CRYSTALLINE SILICA: Crystalline silica is an abundant mineral found in multiple occupational exposures. It is a recognised occupational risk factor for some systemic auto-immune diseases such as progressive systemic scleroderma and Caplan-Colinet's syndrome, or just suspected in Goujerot-Sjögren's syndrome, periarteritis nodosa and systemic lupus erythematosus. WEGENER'S GRANULOMATOSIS: A rare disease of unknown of unknown aetiology, the disease is characterised by granulomatous vasculitis affecting the upper respiratory tracks, lungs and kidneys, associated with glomerulonephropathy. THE ROLE OF SILICA PARTICLES: Studies have shown that crystalline silica may be implied in Wegener's disease. Associated with other factors, notably with a genetic predisposal, silica particles might, through the release of reactive oxygen radicals and inflammatory cytokines, trigger-off immunopathological mechanisms. The latter would be manifested by exocytosis of the proteinase 3 and myeloperoxidase antigens on the surface of the polynuclear neutrophils.

Cytokines↗
PubMed1991

Use of "time windows" to investigate lung cancer latency intervals at an Ontario steel plant.

This paper describes an application of the time windows method to an examination of the temporal pattern of lung cancer risk among steel workers. Case-control methodology was utilized. The cases were 36 men who had died of lung cancer and the controls were 289 men who had died of any other cause. The number of years of employment in the steel pouring area was used as a surrogate measure of exposure. The data were examined by contingency table analysis and by logistic regression, which permitted adjustment for exposures in multiple time windows and the use of continuous, rather than categorical, measures of exposure. It was found that lung cancer risk was associated with exposures occurring between 18 and 30 years before death. It cannot yet be determined whether this time course reflects a biological response or the temporal pattern of exposure to an as yet unidentified toxic agent.

Case-Control Studies↗
PubMed1994

Empirical test of an ion parametric resonance model for magnetic field interactions with PC-12 cells.

A companion paper describes a predictive ion parametric resonance (IPR) model of magnetic field interactions with biological systems based on a selective relation between the ratio of the flux density of the static magnetic field to the AC magnetic field and the charge-to-mass ratio of ions of biological relevance. Previous studies demonstrated that nerve growth factor (NGF)-stimulated neurite outgrowth (NO) in PC-12 cells can be inhibited by exposure to magnetic fields as a function of either magnetic field flux density or AC magnetic field frequency. The present work examines whether the PC-12 cell response to magnetic fields is consistent with the quasi-periodic, resonance-based predictions of the IPR model. We tested changes in each of the experimentally controllable variables [flux densities of the parallel components of the AC magnetic field (Bac) and the static magnetic field (Bdc) and the frequency of the AC magnetic field] over a range of exposure conditions sufficient to determine whether the IPR model is applicable. A multiple-coil exposure system independently controlled each of these critical quantities. The perpendicular static magnetic field was controlled to less than 2 mG for all tests. The first set of tests examined the NO response in cells exposed to 45 Hz Bac from 77 to 468 mG(rms) at a Bdc of 366 mG. Next, we examined an off-resonance condition using 20 mG Bdc with a 45 Hz AC field across a range of Bac between 7.9 and 21 mG(rms). Finally, we changed the AC frequency to 25 Hz, with a corresponding change in Bdc to 203 mG (to tune for the same set of ions as in the first test) and a Bac range from 78 to 181 mG(rms). In all cases the observed responses were consistent with predictions of the IPR model. These experimental results are the first to support in detail the validity of the fundamental relationships embodied in the IPR model.

Animals↗
PubMed1998

Nonlinearities in 2-acetylaminofluorene exposure responses for genotoxic and epigenetic effects leading to initiation of carcinogenesis in rat liver.

The dose responses for several effects of low-level limited exposures to 2-acetylaminofluorene (AAF) in the livers of male Fischer 344 rats were measured and a subsequent phenobarbital tumor promotion regimen was used to manifest initiation of carcinogenesis. Three doses over a 10-fold range yielding cumulative total exposures of 0.126, 0.42, and 1.26 mmol AAF/kg body weight were achieved by daily intragastric instillation for up to 12 weeks with interim terminations. This was followed by 24 weeks administration of 500 ppm phenobarbital (PB) in the diet to promote liver tumor development. At 12 weeks at the end of AAF administration, all exposures produced adducts in liver DNA, measured by 32P postlabeling, and the level of adducts increased with exposure, except that the high exposure did not produce a dose proportional increase. Measurement of arylsulfotransferase activity, a key enzyme in the metabolic activation of AAF, revealed that in livers from the high exposure animals, the enzyme was inhibited. To assess for toxicity, the centrilobular zone of glutamine synthetase-positive hepatocytes was quantified immunohistochemically at 12 weeks. The area of the zone was reduced in the high exposure group and there was a trend to reduction in relationship to exposure. The two lower exposures to AAF produced no increase in cell proliferation, whereas the high exposure resulted in a marked increase, about 8-fold over controls. Initiation was assessed by induction of hepatocellular altered foci (HAF) that expressed the placental form of glutathione S-transferase. AAF induced HAF in the high exposure group, 9-fold at 8 weeks and 170-fold at 12 weeks compared to controls. In rats maintained on PB for 24 weeks after exposure, the multiplicity of HAF increased in controls and comparably in the low and mid exposure groups, but remained at the about the same high level in the high exposure group. The high exposure produced a substantial incidence of benign neoplasms by 12 weeks, and with promotion by 36 weeks, all rats developed hepatocellular neoplasia. In the mid exposure group, only one adenoma occurred at 36 weeks in 17 rats, while in the low exposure group, no liver tumor occurred in 23 rats. Thus, these findings document nonlinearities for some of the effects of AAF, with supralinear effects at the high exposure for cell proliferation and induction of HAF, and a no-observed-effect level for induction of promotable liver neoplasms at the lowest cumulative exposure of 0.126 mmol/kg, in spite of the formation of DNA adducts. We conclude that the effects of this DNA-reactive hepatocarcinogen leading to initiation exhibit nonlinearities and possible thresholds.

2-Acetylaminofluorene↗
PubMed2004

Lack of association of delta-aminolevulinic acid dehydratase genotype with cytogenetic damage in lead workers.

OBJECTIVE: The objective of this study was to evaluate the correlations of genetic polymorphism of genotypes delta-aminolevulinic acid dehydratase (ALAD), blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges (SCEs), and high SCE frequency cells (HFCs) in lead workers. METHODS: Three groups of lead workers were included in the study: high lead exposure group (26 workers), low lead exposure group (31 workers) and control group (30 controls who lived in an area uncontaminated by lead). Blood samples were taken from all subjects and analyzed for lead levels, ALAD genotype and SCE levels. RESULTS: Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin levels than the controls. There were no differences among the three groups regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2 genotype was not detected in any of the three groups. There were no significant differences among the three groups for BLLs, ZPP and hemoglobin levels based on ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P < 0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the high lead exposure group than in the low lead exposure group (16.1%) and the control group (10%). There appeared to be an interaction effect on HFC percentages between smoking and lead exposure. When multiple regression analysis was used, the factors that affected SCE levels were lead exposure and smoking, but ALAD genotypes did not have any significant effect. CONCLUSIONS: A significant association existed between both SCE and HFC levels and lead exposure. However, different ALAD genotypes were not found to be associated with levels of blood lead and ZPP in the three groups.

Adult↗
PubMed2005

Assessment of human exposure to copper: a case study using the NHEXAS database.

Copper is an essential trace element and adverse health effects can potentially be associated with both very low and very high intakes. Accurate estimates of inhalation and ingestion (food and drinking water) exposures are therefore needed in order to realistically assess any effects of the distribution of copper intakes within the general population. The work presented here demonstrates an application of a customized subset of the MENTOR/SHEDS-4M computational system (Modeling ENvironment for TOtal Risk studies, employing the Stochastic Human Exposure and Dose Simulation approach, for Multimedia, Multipathway, Multiroute exposures to Multiple co-occurring contaminants. The application utilized data from the National Human Exposure Assessment Survey (NHEXAS) for USEPA Region V as well as from a variety of other available databases. The case study, using a statistical population-based modeling framework, was performed for Eaton County, MI. The results of the simulations, aggregated for six age subgroups of the general population, suggest that food intake is the major pathway for total copper exposure, while drinking water can have significant contributions at the tail of the distribution of intakes. Specifically, it was estimated that over 80% of the county population received potential doses of copper from food that were lower than the Institute of Medicine (IOM) Recommended Dietary Allowance (RDA) value of 900 microg/day. Furthermore, the total combined potential dose from food and water was only about two times greater than the recommended value only for individuals with intakes in the range above the 99th percentile of both food and water intakes. The values were well below the upper tolerable intake value of 10,000 microg/day. The inhalation route consistently acted as only a minor contributor to the total exposure.

Adolescent↗
PubMedDate not supplied

Environmental copper: its dynamics and human exposure issues.

This article provides an overview of the environmental patterns and dynamics of copper from the perspective of issues that affect our ability to examine current human exposures. It presents selected summary information on the levels of copper found in various media and exposure pathways from a variety of information sources, and discusses the breadth and the limitations of this information. The analysis presented focuses on the ability to provide quantitative values for both external metrics of exposures (microenvironmental levels) and internal biological markers of exposure. The status of the current information on environmental copper is placed within a conceptual framework that can be used to identify data gaps, assess the utility of current biological markers of exposure, and examine the need for systematic and consistent data-gathering studies to improve our ability to complete exposure assessments. A primary concern is the exposure to copper through potable water supplies; this is considered within a framework that examines copper levels and distribution in food, soil, air and sediments, as well as the levels found in biological media such as urine, blood, and hair. An existing water consumption model for copper and associated exposure factors is briefly discussed. This type of model will eventually be valuable within a total exposure analysis modeling framework that can consider and prioritize exposures from multiple routes and differentiate levels of concern for both excesses and deficiencies in exposure, an important issue, since copper is an essential nutrient. Finally, this review attempts to examine the needs for better information using as a basis the concerns briefly mentioned in the recent NRC report "Copper in Drinking Water" (National Research Council, 2000).

Copper↗
PubMed2005

Neonatal morbidity and growth in very low birth-weight infants after multiple courses of antenatal steroids.

OBJECTIVE: To evaluate the neonatal morbidity and the growth in very low birth-weight (VLBW) infants after exposure to multiple courses of antenatal steroids. STUDY DESIGN: A total of 319 VLBW infants were placed in one of the two groups based on exposure to antenatal steroids: Group 1: less than two complete courses; Group 2: two complete courses or more. Anthropometric measurements at birth and discharge and neonatal morbidity were recorded. Composite morbidity was defined as presence of any of the following: death, chronic lung disease, major intraventricular hemorrhage and periventricular leukomalacia. RESULTS: The composite morbidity was not significantly different between the two groups (p=0.26). A significantly higher percentage of infants born after multiple courses of antenatal steroids had head circumference below 10th percentile at discharge (23 vs 9%, adjusted OR, 3.25, (95% CI, 1.4, 7.3); p=0.015). CONCLUSIONS: Multiple courses of antenatal steroids may predispose VLBW infants to impairment of postnatal somatic growth without providing any additional benefit for immediate neonatal outcome.

Anthropometry↗
PubMed1995

Hierarchical cluster analysis for exposure assessment of workers in the Semiconductor Health Study.

The fabrication of integrated circuits in the semiconductor industry involves worker exposures to multiple chemical and physical agents. The potential for a high degree of correlation among exposure variables was of concern in the Semiconductor Health Study. Hierarchical cluster analysis was used to identify groups or "clusters" of correlated variables. Several variations of hierarchical cluster analysis were performed on 14 chemical and physical agents, using exposure data on 882 subjects from the historical cohort of the epidemiological studies. Similarity between agent pairs was determined by calculating two metrics of dissimilarity, and hierarchical trees were constructed using three clustering methods. Among subjects exposed to ethylene-based glycol ethers (EGE), xylene, or n-butyl acetate (nBA), 83% were exposed to EGE and xylene, 86% to EGE and nBA, and 94% to xylene and nBA, suggesting that exposures to EGE, xylene, and nBA were highly correlated. A high correlation was also found for subjects exposed to boron and phosphorus (80%). The trees also revealed cluster groups containing agents associated with work-group exposure categories developed for the epidemiologic analyses.

Cluster Analysis↗
PubMed1994

The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure.

Our trauma research center program entitled, "Trauma Primes Cells" is based on the fundamental hypothesis that prior exposure to multiple, sequential, sublethal cellular insults primes constructive or destructive pathways of cellular responses of subsequent injury. A major objective is to design therapy that will reduce the incidence of multiple organ failure. Although a number of inflammatory cascades have been incriminated in the pathogenesis of multiple organ failure (MOF), diffuse PMN-mediated tissue injury remains an attractive unifying concept. We have developed a sequential insult rodent model in which the priming event consisted of superior mesenteric arterial (SMA) clamping for 45 minutes followed by 6 hours of reperfusion. Following this priming event, activation was induced with a low dose of endotoxin (2.5 mg/kg). We believe that these studies support our hypothesis: mesenteric ischemic/reperfusion primes circulating PMNs. When these have been activated they can then be provoked by endotoxin to provoke distant organ injury. Primed PMNs are released from the postischemic mesenteric bed and enter the systemic circulation. They subsequently sequester in the pulmonary vascular bed where they are relatively harmless until they are activated by low dose endotoxin. These activated PMNs then migrate across the endothelium cell and release reactive oxygen metabolites.

Animals↗
PubMed1995

An improved aetiologic fraction for alcohol-caused mortality.

A method is proposed for estimation of alcohol-caused mortality in which the aetiologic fraction of deaths is derived from an exposure contrast between the 'unsafe' drinker and 'safe' drinker; not between the drinker and the nondrinker. The method is consistent with the objectives of public health intervention in the alcohol education field. The 'safe' drinker is the reference exposure category and aetiologic fractions are obtained for the single categories of a multiple-level exposure scale, using separate relative risks for the 'unsafe' drinker and the nondrinker. Preliminary application of the method to Australian data yields an estimate of the number of deaths caused by misuse of alcohol that is larger than those obtained under the old conceptual model. Thus, the public health importance of unsafe alcohol consumption has been underrepresented.

Alcohol Drinking↗
PubMed2004

Jimson weed extract as a protective agent in severe organophosphate toxicity.

UNLABELLED: Treatment of patients following an organophosphate (OP) exposure can deplete a hospital's entire supply of atropine. Given the possibility of multiple severe exposures after a terrorist attack using OP nerve agents, there exists a need for either greater atropine stores or the development of alternative antidotes. Jimson weed (Datura stramonium) contains atropine and other anticholinergic compounds and is common and readily available. It is used recreationally for its central anticholinergic effects and is made easily into an extract by boiling the crushed seeds. The extract has rapid onset of effects and may be useful for treatment of OP poisoning. OBJECTIVES: To determine whether pretreatment with an easily stored and prepared Datura seed extract (DSE) will increase survival following a severe OP poisoning. METHODS: Datura stramonium seeds were collected, crushed, and then heated in water to make a 2-mg/mL atropine solution (100 seeds contain approximately 6 mg of atropine or 0.007 mg/seed). Male rats were randomized to pretreatment with either saline (n = 10) or 7.5 mg/kg DSE (n = 10) given as a single intraperitoneal injection 5 minutes prior to a subcutaneous injection of 25 mg/kg of dichlorvos. The endpoint was time to death recorded by a blinded observer. RESULTS: The Kaplan-Meier estimates of the 24-hour survival rate was 90% (95% CI = 56% to 100%) for the DSE-pretreated group and 10% (95% CI = 0% to 45%) for the control group. The log-rank test revealed a statistically significant longer survival for the Datura-treated animals (p = 0.0002). Median survival time was 22 minutes 30 seconds for the control group and greater than 24 hours for the DSE-pretreated group. CONCLUSIONS: Pretreatment with DSE significantly increases survival following severe dichlorvos exposure.

Animals↗
PubMed1998

Lifetime exposure to traumatic events among a sample of city bus drivers.

Lifetime exposure to traumatic events was assessed retrospectively among a representative sample of city bus drivers (228 men and 54 women) from Montréal, Canada. Among them, 68.1% reported at least one exposure to a traumatic event of any type. Among the 68% exposed. 70.4% reported multiple traumatic exposures (M = 2.6, SD = 1.67), with ratings ranging from 0 to 12. This report underlines the fact that the prevalence of traumatic events is not yet well known. Epidemiological research should devote more effort to assess fully the lifetime prevalence of traumatic events and not only cases of PTSD.

Adult↗
PubMed1998

Relative activities of methyl methanesulphonate (MMS) as a genotoxin, clastogen and gene mutagen to the liver and bone marrow of MutaMouse mice.

The mutagenicity of the rodent carcinogen methyl methanesulphonate (MMS) to the liver and bone marrow of MutaMouse lacZ- transgenic mice was evaluated. A single intraperitoneal (i.p.) dose of 100 mg/kg MMS gave a strong positive response in the liver UDS and bone marrow micronucleus assays conducted 2 hr and 30 hr, respectively, after dosing. A single i.p. administration of 100 mg/kg of MMS, or five daily administrations of 20 mg/kg MMS, failed to increase significantly the lacZ- --> lacZ+ mutation frequency (MF) in either the liver or the bone marrow, albeit some evidence of weak mutagenicity was observed for the liver. The gene mutation analyses were undertaken 14 days after the final chemical exposure. Administration of the liver mitogens dimethylnitrosamine (DMN), or 4-acetylaminofluorene (4AAF), subsequent to multiple (five) exposures of 20 mg/kg MMS, foiled to enhance the mutagenicity of MMS to the liver, thereby eliminating the possibility that MMS produced promutagenic lesions in the liver that were not transformed to mutations because of the absence of MMS-induced cell division. In the latter experiments, DMN gave a strong mutagenic response and 4AAF a weak mutagenic response. Possible reasons for this selective mutagenicity of MMS (DNA damage and micronuclei induction in the absence of gene mutations) are discussed, but no clear outcome emerges. It is concluded that transgenic mutation assays should not be employed for defining genetic toxicity in vivo, but rather should be reserved for mechanistic studies on previously established rodent genotoxins and/or carcinogens.

2-Acetylaminofluorene↗