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Beryllium exposure: dermal and immunological considerations.

OBJECTIVE: People exposed to beryllium compounds are at increased risk of developing beryllium sensitization and chronic beryllium disease (CBD). The purpose of this short communication is to present information regarding the potential importance of skin exposure to beryllium, an exposure and alternate immune response pathway to the respiratory tract, which has been largely overlooked in epidemiologic and exposure assessment studies. METHODS: We reviewed the published literature, including epidemiologic, immunologic, genetic, and laboratory-based studies of in vivo and in vitro models, to assess the state of knowledge concerning skin exposure to beryllium. RESULTS: Reduction in inhalation exposure to beryllium has not resulted in a concomitant reduction in the occurrence of beryllium sensitization or CBD, suggesting that continued prevalence may be due, in part, to unchecked skin exposure to beryllium-containing particles. CONCLUSIONS: Recent developments in our understanding of the multiple exposure pathways that may lead to beryllium sensitization and CBD suggest that a prudent approach to worker protection is to assess and minimize both skin and inhalation exposures to beryllium.

Berylliosis↗

Impact of microenvironmental nitrogen dioxide concentrations on personal exposures in Australia.

Indoor and outdoor NO2 concentrations were measured and compared with simultaneously measured personal exposures of 57 office workers in Brisbane, Australia. House characteristics and activity patterns were used to determine the impacts of these factors on personal exposure. Indoor NO2 levels and the presence of a gas range in the home were significantly associated with personal exposure. The time-weighted average of personal exposure was estimated using NO2 measurements in indoor home, indoor workplace, and outdoor home levels. The estimated personal exposures were closely correlated, but they significantly underestimated the measured personal exposures. Multiple regression analysis using other nonmeasured microenvironments indicated the importance of transportation in personal exposure models. The contribution of transportation to the error of prediction of personal exposure was confirmed in the regression analysis using the multinational study database.

Adult↗

Intake fraction for multimedia pollutants: a tool for life cycle analysis and comparative risk assessment.

We employ the intake fraction (iF) as an effective tool for expressing the source-to-intake relationship for pollutant emissions in life cycle analysis (LCA) or comparative risk assessment. Intake fraction is the fraction of chemical mass emitted into the environment that eventually passes into a member of the population through inhalation, ingestion, or dermal exposure. To date, this concept has been primarily applied to pollutants whose primary route of exposure is inhalation. Here we extend the use of iF to multimedia pollutants with multiple exposure pathways. We use a level III multimedia model to calculate iF for TCDD and compare the result to one calculated from measured levels of dioxin toxic equivalents in the environment. We calculate iF for emissions to air and surface water for 308 chemicals. We correlate the primary exposure route with the magnitudes of the octanol-water partition coefficient, Kow, and of the air-water partitioning coefficient (dimensionless Henry constant), Kaw. This results in value ranges of Kow and Kaw where the chemical exposure route can be classified with limited input data requirements as primarily inhalation, primarily ingestion, or multipathway. For the inhalation and ingestion dominant pollutants, we also define empirical relationships based on chemical properties for quantifying the intake fraction. The empirical relationships facilitate rapid evaluation of many chemicals in terms of the intake. By defining a theoretical upper limit for iF in a multimedia environment we find that iF calculations provide insight into the multimedia model algorithms and help identify unusual patterns of exposure and questionable exposure model results.

Algorithms↗

Time variations in the risk of cancer following irradiation in childhood.

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model.

Adolescent↗

The impact of the hepatitis B mass immunisation campaign on the incidence and risk factors of acute hepatitis B in Italy.

BACKGROUND/AIMS: This study aimed to evaluate the impact of the campaign for hepatitis B mass immunisation of children and teenagers, introduced in 1991, on the incidence of and risk factors for hepatitis B in Italy. METHODS: Hepatitis B cases reported to the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1987-1997 were used to estimate incidence. To assess the association between potential risk factors and hepatitis B cases, hepatitis A cases generated by the same surveillance system were used as controls. RESULTS: During the period 1987-1997, 8275 acute hepatitis B cases were reported to SEIEVA. Hepatitis B incidence declined from 10.4/100,000 in 1987 to 2.9/100,000 in 1997. The fall was more evident before than after the introduction of compulsory vaccination against hepatitis B. The results of multivariate analysis showed that during the years 1995-1997, blood transfusion, intravenous drug use, surgical intervention, dental therapy, other parenteral exposures, multiple sexual partners, and being in the household of a chronic HBsAg carrier were all exposures independently associated with hepatitis B. CONCLUSIONS: The strong association linking acute hepatitis B with iatrogenic exposures, which are more common in adults, suggests that the present immunisation strategy should be combined with the implementation of non-immunologic preventive measures.

Acute Disease↗

Susceptibility of children to environmental toxic substances.

Our understanding of toxicity of environmental substances is based mainly on investigations using adult human populations and matured animals. Therefore, the scientific community and regulatory agencies have very little knowledge regarding how children respond to insult from toxic chemicals. However, certain scientific data indicate that children are more susceptible to toxic exposure than adults because they have proportionally more intake of food contaminants, active developmental processes, multiple exposure pathways and susceptible socio-behavioral activities. More emphasis should therefore be focused on addressing the information gap for improving the health of our children.

Adult↗

Sulfuric acid-layered ultrafine particles potentiate ozone-induced airway injury.

Urban air pollution in the United States is composed of a complex mixture of particles and gases. Among the most prominent products of the atmospheric pollutants are sulfur oxides and ozone. In this report, we use two exposure protocols to examine the interaction between exposure to these two pollutants. In the first exposure regimen, guinea pigs were exposed to sulfuric acid (pure sulfuric acid mist or sulfuric acid layered on ZnO) for 1 h. Each exposure is followed 2 h later by another exposure to 0.15 ppm ozone for 1 h. Pulmonary function parameters were measured immediately after the ozone exposure. In guinea pigs that were exposed to 300 micrograms/m3 pure sulfuric acid mist, subsequent exposure to 0.15 ppm ozone did not produce additional change in pulmonary functions. In guinea pigs that were exposed to 84 micrograms/m3 sulfuric acid layered on ZnO, subsequent exposure to 0.15 ppm ozone produced more than additive alterations in vital capacity and diffusing capacity. In the second exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 8 and 9, animals received two additional daily 3-h exposures to 24 micrograms/m3 sulfuric acid layered on ZnO, and pulmonary functions were measured at the end of the daily exposure. Greater reductions in lung volumes and diffusing capacity were observed in animals on d 9 than would be observed in animals that received no additional exposure. In the third exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 9, animals were exposed to 0.15 ppm ozone for 1 h and pulmonary functions were measured at the end of the ozone exposure. Ozone exposure on d 9 induced reductions in lung volumes and diffusing capacity that were not observed in animals receiving exposures to either ozone or sulfuric acid layered ZnO alone. We conclude that single or multiple exposure to sulfuric acid-layered ZnO sensitizes guinea pigs to subsequent sulfuric acid or ozone exposure.

Aerosols↗

Salvage of chronically exposed Gore-Tex vascular access grafts in the hemodialysis patient.

Exposure and infection of a Gore-Tex vascular access graft often results in removal of the graft. Salvage of the graft is possible, however, with the use of well-vascularized muscle flaps. In 1982, Hodgkinson was the first to use a sublimis muscle flap to cover an exposed vascular access graft. We used the flexor carpi ulnaris and flexor digitorum superficialis to cover exposed Gore-Tex grafts in nine patients. The sublimis was used to cover distal graft exposures, and the longer flexor carpi ulnaris muscle was used to cover more proximal sites. Multiple exposures required both flaps or combinations of muscle flaps and local rotation flaps. Eight of nine chronically exposed grafts were salvaged using these techniques; a graft was removed from one patient because of diffuse unrecognized graft bed infection. Disability is minimized by using only part of the sublimis, and loss of the flexor carpi ulnaris is compensated by local muscles with similar actions. Vascular puncture can be continued during healing.

Adult↗

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

Administration, Cutaneous↗

Gulf War illnesses: causes and controversies.

Numerous studies investigating Gulf War illnesses have documented that, while Gulf War veterans are no more likely to die or be hospitalized, they complain of more symptoms than their non-Gulf War counterparts and are more likely to seek medical treatment and disability retirement. Proposed causes include exposure to chemical and microbiological agents and psychological factors. No definitive evidence has emerged to link chemical exposures to these illnesses, although epidemiological studies and animal research suggest possible synergistic effects to multiple exposures. Microbiological agents are unlikely to be etiologic. Psychological and cultural factors undoubtedly contribute to a number of illnesses, but their exact role requires further study. Based on a review of the scientific and popular literature, it is reasonable to conclude that Gulf War illnesses remain a poorly defined group of symptom clusters. Well-controlled research from independent groups is required to answer the numerous questions that have arisen from this illness outbreak.

Biological Warfare↗

Hierarchical cluster analysis applied to workers' exposures in fiberglass insulation manufacturing.

The objectives of this study were to explore the application of cluster analysis to the characterization of multiple exposures in industrial hygiene practice and to compare exposure groupings based on the result from cluster analysis with that based on non-measurement-based approaches commonly used in epidemiology. Cluster analysis was performed for 37 workers simultaneously exposed to three agents (endotoxin, phenolic compounds and formaldehyde) in fiberglass insulation manufacturing. Different clustering algorithms, including complete-linkage (or farthest-neighbor), single-linkage (or nearest-neighbor), group-average and model-based clustering approaches, were used to construct the tree structures from which clusters can be formed. Differences were observed between the exposure clusters constructed by these different clustering algorithms. When contrasting the exposure classification based on tree structures with that based on non-measurement-based information, the results indicate that the exposure clusters identified from the tree structures had little in common with the classification results from either the traditional exposure zone or the work group classification approach. In terms of the defining homogeneous exposure groups or from the standpoint of health risk, some toxicological normalization in the components of the exposure vector appears to be required in order to form meaningful exposure groupings from cluster analysis. Finally, it remains important to see if the lack of correspondence between exposure groups based on epidemiological classification and measurement data is a peculiarity of the data or a more general problem in multivariate exposure analysis.

Air Pollutants, Occupational↗

Endocardial endothelium mediates positive inotropic response to alpha 1-adrenoceptor agonist in mammalian heart.

Although the positive inotropic response to alpha 1-agonists has been well documented, the mechanism is incompletely understood. In isolated papillary muscle of cat and rabbit, low physiological concentrations of phenylephrine (PE) (10(-9)-10(-7) M; 35 degrees C) under beta-blockade (propranolol 10(-6) M) and in physiological [Ca2+]o (1.25 mM), significantly increased peak twitch tension (TT) with typical unchanged or slightly prolonged twitch contraction duration. This typical response necessitated the presence of an intact endocardial endothelium (EE) since no inotropic response was observed at or below 10(-7) M PE in muscles where the EE had been damaged by 1 s exposure to 1% Triton X-100 prior to the first PE addition. After Triton-induced EE damage prior to the first PE addition, a direct myocardial inotropic response could be demonstrated, but this response required higher concentrations of PE (10(-6)-10(-3) M) and was significantly less pronounced than in muscles with intact EE. At elevated (2.5 mM) or high (7.5 mM) Ca2+, a concentration dependent inotropic response to PE could be induced at the higher concentrations of PE (10(-6) M or higher), but the inotropic response to low concentrations of PE (10(-7) M or below) was absent even in the presence of an intact EE. In papillary muscles with intact EE at physiological [Ca2+]o of 1.25 mM, the higher concentrations of PE (10(-6) M or higher) destroyed the EE. Indeed, after washing with fresh bathing solution following prolonged exposure to these high concentrations of PE, the baseline twitches resembled twitches in muscles where the EE had been experimentally damaged. Selective destruction of the EE by PE in these conditions with no morphological damage to the subjacent myocardium was confirmed on electron microscopy. A second concentration-response curve to PE was significantly depressed, shifted to the right and with no response at or below 10(-7) M PE. Subsequent successive curves were not significantly different from the second one. At the higher Ca2+ (2.5 mM or 7.5 mM), neither functional nor morphological evidence of damage to the EE was observed regardless of the PE concentration and exposure time; in some muscles EE damage did occur at high Ca2+, however, but only after multiple exposures to high PE each followed by abundant wash. At all concentrations of PE, the alpha 1-antagonist prazosin (10(-5) M) blocked the inotropic response regardless of [Ca2+]o and prevented morphological endothelial damage at 1.25 mM Ca2+.

Adrenergic alpha-Agonists↗

Time dependence of response of transplanted mouse mammary tumors to single or split radiation doses.

The effect of single and different split radiation doses with varying rates and time intervals was investigated in an experimental system in vivo using second generation isotransplants of two mouse mammary carcinomas. The changes in the growth delay time (GDT) and tumor control rate (TCR) were analyzed, and explained by a dose dependence of the repair of sublethal radiation damage, reoxygenation and cellular repopulation in the tumors. A direct relationship was found between the size of the first of two dose fractions and the time interval between two exposures at which treatment with split doses is most effective in delaying or preventing tumor growth. Multiple exposures to unequal dose fractions are more effective than to equal fractions with the same total dose.

Animals↗

Exposure of hospital personnel to Brucella melitensis and occurrence of laboratory-acquired disease in an endemic area.

In 1997, 7 cases of laboratory-acquired Brucella melitensis infections were detected among the hospital personnel of a medical centre serving an endemic area in southern Israel. Although the onset of symptoms in 6 of the 7 patients occurred during a 2-week period, suggesting a point source exposure, biotype analysis showed that the outbreak was caused by 3 different B. melitensis serovars, indicating multiple exposures. Review of the laboratory records showed that during 1997, the microorganism was recovered from 146 blood and synovial fluid cultures, and that during the 2 months in which the laboratory-acquired cases occurred (April and June), 53 of 530 positive aerobic blood culture bottles (10.0%) grew B. melitensis. The epidemiological investigation did not reveal the source of the outbreak, and no noticeable breaches in laboratory safety practices could be demonstrated. It is concluded that in areas endemic for brucellosis, hospital personnel are frequently exposed to Brucella microorganisms. Under these circumstances, significant morbidity may occur despite observance of recommended safety practices. Biotyping of Brucella isolates may contribute to the elucidation of complex epidemiological situations.

Brucella melitensis↗

Onset of postoperative jaundice related to anaesthetic history.

A review of 182 cases from the U.S. National Halothane Study showed the interval to the onset of jaundice after one exposure to halothane (91 cases) to be slightly shorter than the interval for those having had multiple exposures to the agent. These findings are in sharp contrast to other recently published results. Thirty-three cases of jaundice after the use of other anaesthetic agents are also reported.

Anesthetics↗

Respiratory cancers and chemical exposures in the wood industry: a nested case-control study.

A cohort of 3805 men who had worked for at least one year in the particleboard, plywood, sawmill, or formaldehyde glue industries between 1944 and 1965 was followed up until 1981. From within the cohort the 57 patients with verified "respiratory" cancer (ICD 7 codes: 160-162.1, 141, 143-8) were defined as "cases," and 171 men without respiratory cancer from within the cohort were matched on birth year and used as controls. The comparison of exposures was carried out according to work histories and job exposure matrices for each plant. The odds ratio for exposure to wood dust was 1.03 (32 exposed cases) without provision for any latent period, and 0.97 (27 exposed cases) when provision for a minimum latent period of ten years was applied. The odds ratios were 1.60 and 1.68, respectively, when smoking was controlled by stratification. These results did not differ significantly from unity. The estimated average level of exposure to wood dust among the exposed was 1-2 mg/m3 and the mean duration of exposure about ten years. Significantly (one sided test, 5% level) raised odds ratios were observed for exposure to pesticides and phenol. No single pesticide could be identified as "causative" because of frequent multiple exposures. The raised odds ratios for phenol were partly explained by smoking and exposure to pesticides which confounded the observed associations for phenol exposure. Exposure to terpenes and other heating products of coniferous woods was significantly associated with a risk of respiratory cancer when the duration of exposure exceeded five years.

Adult↗

Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women.

The high incidence of lung cancer among Chinese females, despite a low smoking prevalence, remains poorly explained. Cooking fume exposure during frying could be an important risk factor. We carried out a population-based case-control study in Hong Kong. Cases were Chinese female nonsmokers with newly diagnosed primary lung cancer. Controls were female nonsmokers randomly sampled from the community, frequency matched by age groups. Face-to-face interviews were conducted using a standardized questionnaire. The "total cooking dish-years," categorized by increments of 50, was used as a surrogate of cooking fumes exposure. Multiple unconditional logistic regression was used to estimate the odds ratios (OR) for different levels of exposure after adjusting for various potential confounding factors. We interviewed 200 cases and 285 controls. The ORs of lung cancer across increasing levels of cooking dish-years were 1, 1.17, 1.92, 2.26, and 6.15. After adjusting for age and other potential confounding factors, the increasing trend of ORs with increasing exposure categories became clearer, being 1, 1.31, 4.12, 4.68, and 34. The OR of lung cancer was highest for deep-frying (2.56 per 10 dish-years) followed by that of frying (1.47), and stir-frying had the lowest OR (1.12) among the three methods. Cumulative exposure to cooking by means of any form of frying could increase the risk of lung cancer in Hong Kong nonsmoking women. Practical means to reduce exposures to cooking fumes should be given top priority in future research.

Adenocarcinoma↗

Influence of influenza viral infection on airway smooth muscle activity.

The contractility of airway smooth muscle (ASM) plays an important role in pathophysiology of several bronchial disorders. Increased contraction of ASM during asthma and respiratory viral infection has been attributed to the release of mediators acting through different receptors. In the present study, influence of influenza type A virus (H1N1) infection has been examined on ASM responsiveness to various bronchoactive agents e.g. adenosine, histamine, 5-hydroxytryptamine (5-HT) and isoproterenol in an organ bath set up for isolated tissue preparation. The contractile effect of adenosine, histamine and 5-HT was enhanced, however, relaxant response of isoproterenol was attenuated with the duration following viral exposure. The most prominent response was observed 48 to 72 hr after infection and tissues from multiple exposure to virus infected animals showed the maximum contractile response. Results demonstrated the deleterious effect of viral infection on ASM function and the findings will be helpful in understanding the mechanism of influenza virus induced bronchoconstriction.

Adenosine↗