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At least 415 records · Page 23Linked to original sources
PubMed1990

Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: system organ studies and comparison of clinical indices of exposure.

In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats.

Administration, Inhalation↗
PubMedDate not supplied

Neurobehavioral effects of occupational exposure to low-level styrene.

Eighty-six workers in six fiberglass-reinforced plastics manufacturing plants in Taiwan were given a detailed evaluation including medical and occupational questionnaires, symptom questionnaires, blood sampling, and neurobehavioral tests, including cognitive performance, vibratory perception threshold, and thermal perception threshold. A Chinese version of cognitive tests modified from the Neurobehavioral Evaluation System 2 was applied. Forty-one workers directly exposed to styrene at the mean concentration of 22 ppm are compared with 45 workers not subject to styrene exposure. Multiple linear regression analysis controlling for age, sex, education, and alcohol intake revealed significant associations between styrene exposure and responses in some neuropsychologic measurements. No acute or chronic symptom had significant correlation with styrene exposure. Among the neurobehavioral tests, only the continuous performance test and vibration threshold were significantly and adversely affected in workers exposed to styrene. Significant changes in the central and peripheral nervous system were thus detected at a mean styrene exposure of 22 ppm.

Adolescent↗
PubMedDate not supplied

Occupational exposure to noise and ototoxic organic solvents.

The objectives of this study were to review the literature on the effects of occupational exposure to organic solvents on the auditory system and to identify work settings in which exposure to these agents and to noise might occur. The criteria for selecting the chemicals were (a) evidence available that indicated that the chemicals may affect the auditory system and enhance noise effects, and (b) the ubiquity of their use. References to ototoxicity were noted for three proven neurotoxicants, i.e., carbon disulfide, toluene, and trichloroethylene, and for two probable human neurotoxicants--styrene and xylene. The percentages of workers (estimated by NIOSH National Occupational Exposure Survey) exposed to these solvents in each economic sector are shown. Work settings are identified where multiple exposures occur to solvents and noise. The need for future research is discussed.

Animals↗
PubMed1991

Further evidence that glycoprotein IIb-IIIa mediates platelet spreading on subendothelium.

In order to explore further the mechanism by which glycoprotein GPIIb-IIIa promotes platelet vessel wall interaction, platelet adhesion to subendothelium was studied in an annular chamber in which subendothelium from rabbit aorta was exposed at a shear rate of 2,600 s-1 to blood from patients with thrombasthenia. Perfusions were conducted for each of 5 exposure times (1, 2, 3, 5 and 10 min), and the percent surface coverage of the vessel segment with platelets in the contact (C) and spread (S) stage was determined. Increased values of platelet contact (C) were obtained in thrombasthenia at all exposure times; this finding is consistent with a defect in platelet spreading, based on a previously described kinetic model of platelet attachment to subendothelium. According to this model of attachment, increased values of platelet contact (C) at a single exposure time may be indicative of either a defect in spreading (S) or initial contact (C), but multiple exposures will result in increased contact only for defects which are related to defective platelet spreading (S). The results obtained over a broad range of exposure times provide more conclusive evidence that GPIIb-IIIa mediates platelet spreading than those previously obtained at single exposure times.

Animals↗
PubMed1988

The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice. II. Strain comparisons involving B6C3F1, C57B1/6 and DBA/2 male mice.

In a companion paper (Luke et al., 1988), the effect of exposure duration and regimen on benzene induced-bone marrow damage was evaluated in male and female DBA/2 mice using the peripheral blood micronucleus assay. To assess the general applicability of the findings obtained for DBA/2 mice to other strains, similar studies were conducted using B6C3F1 and C57B1/6 male mice. An analysis of peripheral blood smears taken weekly from these mice exposed to 300 ppm benzene for 13 weeks (6 h per day) for either 5 days per week (Regimen 1) or for 3 days per week (Regimen 2) revealed: (i) a highly significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE), the magnitude of which was strain specific (DBA/2 greater than C57B1/6 = B6C3F1), but independent of exposure regimen and, except for Regimen 2 B6C3F1 mice, of exposure duration. In male B6C3F1 mice, MN-PCE frequencies increased slightly with increasing exposure duration; (ii) a strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent increase across time in the frequency of micronucleated normochromatic erythrocytes (MN-NCE). Apparent steady-state conditions for MN-NCE frequencies were attained by about 5 weeks of exposure in male mice of all three strains exposed to benzene by Regimen 2. Steady-state conditions for MN-NCE frequencies in male mice exposed to benzene by Regimen 1 did not occur during the duration of the study, with strain-dependent differences in the kinetics of MN-NCE accumulation being present; and (iii) in all 3 strains, an initial severe depression in the rate of erythropoiesis, the return of which to normal levels was both strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent. These data indicate that the induction of genotoxic and cytotoxic damage in the bone marrow of male mice exposed to benzene for 13 weeks can be highly dependent on strain, exposure regimen and exposure duration but that under no circumstance did the level of genotoxic damage induced by benzene decrease under multiple exposure conditions.

Animals↗
PubMed1994

Airway hyper-responsiveness and the prevalence of work-related symptoms in workers exposed to irritants.

The association between exposure to airway irritants and the presence of work-related symptoms and whether this association was modified by airway hyper-responsiveness, smoking, and allergy by history was studied in 668 workers of synthetic fiber plants. A Dutch version of the British Medical Research Council (BMRC) questionnaire with additional questions on allergy and work-related symptoms was used to assess symptoms, and a standardized histamine challenge test of airway hyper-responsiveness (AHR) was employed. Work-related symptoms were defined as having more than usual eye and respiratory symptoms during work. On the basis of job titles and working department, the exposure status of all workers was characterized into seven groups: (1) reference group; (2) white collars; (3) SO2, HCl, SO4(2-); (4) polyester vapor; (5) oil mist and oil vapor; (6) polyamide and polyester vapor; and (7) multiple exposure. The association between exposure groups and work-related symptom prevalence was estimated by means of multiple logistic regression. The overall prevalence of the work-related symptoms were: cough 9%; phlegm 6%; dyspnea 7%; wheeze 2%; eye symptoms 16%; nasal symptoms 15%. Exposure to airway irritants was significantly associated with work-related symptoms, independent of AHR, smoking, allergy by history, and chronic respiratory symptoms. The association of exposure group with work-related symptoms was stronger for subjects with AHR than for subjects with no AHR. The association with dyspnea and/or wheeze was also stronger for smokers than for nonsmokers and ex-smokers. In contrast, the association between exposure and a higher prevalence of work-related symptoms was stronger in subjects with no history of allergy than in subjects with history of allergy. This is most likely due to the relatively high prevalence of background symptoms in (nonexposed) allergic subjects. It is concluded that exposure to irritants in the working environment might lead to respiratory symptoms, even if exposure levels are relatively low.

Adult↗
PubMed2006

Estimation of the benchmark dose by structural equation models.

While epidemiological data typically contain a multivariate response and often also multiple exposure parameters, current methods for safe dose calculations, including the widely used benchmark approach, rely on standard regression techniques. In practice, dose-response modeling and calculation of the exposure limit are often based on the seemingly most sensitive outcome. However, this procedure ignores other available data, is inefficient, and fails to account for multiple testing. Instead, risk assessment could be based on structural equation models, which can accommodate both a multivariate exposure and a multivariate response function. Furthermore, such models will allow for measurement error in the observed variables, which is a requirement for unbiased estimation of the benchmark dose. This methodology is illustrated with the data on neurobehavioral effects in children prenatally exposed to methylmercury, where results based on standard regression models cause an underestimation of the true risk.

Biometry↗
PubMed1991

Active oxygen transforms murine myeloid progenitor cells in vitro.

Active oxygen (AO) is ubiquitous in nature and its many forms can act as natural carcinogens. Their effect on the transformation of a mouse myeloid progenitor cell line was studied using anchorage-independent colony formation in methylcellulose as the primary assay. Both cytotoxic and non-toxic concentrations of t-butylhydroperoxide, hydrogen peroxide and menadione were examined. At non-cytotoxic concentrations, no AO transformation of these cells from interleukin-3 dependence to factor independence (FI) was observed, even after as many as 25 treatments. At cytotoxic concentrations, however, all 3 classes of AO transformed the cells to FI growth. The most potent agent was t-butyl hydroperoxide (43-fold induction), followed by hydrogen peroxide and then menadione. As little as one exposure to cytotoxic levels of these oxidants induced significant transformation, with relative potencies the same as those observed for multiple exposures. These inductions were not due to general cytotoxic effects, since sodium fluoride and heat-shock treatment gave minimal inductions. AO-induced colonies in methylcellulose that were removed, examined and then injected into pre-irradiated mice uniformly produced tumors. Control, non-treated cells did not form tumors. Tumorigenic cells did not form colonies in methylcellulose at lower plating densities. Furthermore, low numbers of transformed cells supplemented to high density with normal cells showed a small but insufficient increase in colony number as compared with high-density cultures of transformed cells. Our results suggest that the transformants depend upon a paracrine mechanism of growth that is mediated by the transformed cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Causal thinking, biomarkers, and mechanisms of carcinogenesis.

The use of biomarkers is increasing both in acute and chronic disease epidemiology, but the rationale for their introduction is not always firmly established (e.g., when and how their use is scientifically justifiable and cost effective). The use of biomarkers should be considered within the context of causal models in epidemiology, and of the intertwining of causation and pathogenesis. Unlike infectious diseases, for cancer and cardiovascular disease external "necessary" causes have not been identified. Thus, the classification of cancer and other chronic diseases cannot be based on unequivocal criteria such as the "etiologic" classification of infectious diseases. As far as morphology is concerned, "neoplasia" and "anaplasia" are attributes of cancer that cannot be defined in a straightforward way. Tissue pathologies are minimal and difficult to differentiate from normal tissue in some cancers but are obvious in others. From a mechanistic point of view, unless molecular biology discovers specific mechanistic steps in carcinogenesis, which indicate the existence of "necessary" events in carcinogenesis, we cannot adopt an unequivocal definition of cancer. The potential contribution of biomarkers to the elucidation of the pathogenetic process should be considered in the light of such uncertainties. There is a range of indications for biomarkers, from the use of very specific measurements aimed at single molecules, to measurements indicating cumulative exposure to agents with the same mechanism of action. The potential uses of markers in chronic disease epidemiology include (1) exposure assessment in cases in which traditional epidemiologic tools are insufficient (particularly for low doses and low risks); (2) multiple exposures or mixtures, in which the aim is to disentangle the etiologic role of single agents; (3) estimation of the total burden of exposure to chemicals having the same mechanistic target; (4) investigation of pathogenetic mechanisms, and (5) study of individual susceptibility (e.g., metabolic polymorphism, DNA repair).

Animals↗
PubMed2002

Risk factors for waterborne enteric infections.

Risk factors for waterborne enteric infections are deduced primarily from outbreak surveillance data; however, in the United States, only a fraction of the estimated water-related outbreaks are reported through passive surveillance. In the past several years, advances in molecular detection techniques have furthered our knowledge about foodborne and waterborne causes of gastroenteritis, allowing the association of certain pathogens with biologic and exposure-related susceptibilities in their hosts. This article summarizes some of the recent data characterizing susceptibility to three common waterborne pathogens:Cryptosporidium, a protozoan; Norwalk-like virus; and the bacterium Escherichia coli O157:H7. The infectious dose of Cryptosporidium varies by several orders of magnitude by strain, and repeated low-level exposure in drinking water may be protective. Some people may be innately immune to Norwalk-like virus, despite multiple exposures. A major risk factor for E. coli O157:H7 infection is exposure to shallow groundwater sources contaminated with animal waste.

Journal Article↗
PubMed1992

Uses of biochemical and biological markers in occupational epidemiology.

The use of biochemical or biological markers is increasing in cancer epidemiology, but the rationale for their introduction is not always clear, i.e. it has not been established when and how their use is scientifically justifiable, ethically correct and cost-effective. There is an entire range of indications for biomarkers, from the use of very specific measurements aimed at single molecules, to measurements indicating cumulative exposure to agents with the same mechanism of action. The following are some potential uses of markers in occupational epidemiology: 1) exposure assessment in cases in which traditional epidemiologic tools are insufficient (particularly for low doses and low risks; 2) multiple exposures or mixtures, in which the aim is to disentangle the etiologic role of single agents; 3) estimation of the total burden of exposure to chemicals having the same mechanistic target; 4) investigation of pathogenetic mechanisms; 5) study of individual susceptibility (e.g. metabolic polymorphism, DNA repair). Examples are discussed together with methodological limitations.

Biomarkers↗
PubMed1989

[Progress report. Factors influencing nutritional toxic effects].

The basis of the requirement for nutrio-toxicological model investigations is the result of many years of international experience. They are, however, limited for pragmatic reasons to standardized one-dimensional test conditions and can only be partially compared with the variable exposure conditions of man. Therefore, we have tried to review the practical significance of factors influencing nutrio-toxic effects. It has been shown that due to physiological and genetic differences, different lifestyle, biogeochemical and nutritional factors, additional occupational exposure as well as spontaneous diseases individual sensitivity shows a great variation range in man and laboratory animals. The multiple exposure which is common practice makes it difficult to provide proven evidence. The safety factor used for the extrapolation of results obtained in animal experiments as compared with man is a suitable pragmatic safety measure, but in the case of 1:100 as to the order of magnitude it is not always in accordance with the range of response to xenobiotics in a human population. This fact raises the necessity of searching for so-called "risk-groups" in the population. Additionally, the possible acceleration of spontaneous diseases by exposure to xenobiotics has to be taken into consideration.

Animals↗
PubMed1981

A documented episode of pulmonary vasoconstriction in systemic sclerosis.

Severe paroxysmal pulmonary hypertension with increased pulmonary vascular resistance precipitated by exposure to cold is postulated as the mechanism causing dyspnea and cardiopulmonary arrest in a patient with systemic sclerosis. Multiple exposures to cold air and a 0 degree C saline infusion resulted in the acute onset of dyspnea and peripheral vasoconstriction. Pressure readings from a Swann-Ganz catheter in place during the saline-induced dyspneic attack showed significant elevation of pulmonary arterial pressure and vascular resistance, suggesting that pulmonary vasospasm caused the attack.

Blood Pressure↗
PubMed2006

Atypical warfarin-induced skin necrosis.

Warfarin-induced skin necrosis (WISN) is a disorder of unclear etiology that predominantly affects obese women. Although WISN typically occurs within the first 10 days of warfarin therapy, some patients develop the complication several years after warfarin exposure. We describe the case of a 43-year-old Caucasian woman with a history of recurrent thromboembolic disorders, protein S deficiency, and multiple exposures to warfarin who came to the emergency room with complaints of worsening dermatitis that had progressed over a 15-hour period. Examination revealed multiple, diffuse "lace-like" erythematous eruptions with superimposed lesions that were tender, ulcerated, and crusted. A biopsy was performed, and histopathologic findings were consistent with WISN. Based on the Naranjo adverse drug reaction probability scale, a probable causal relationship existed between warfarin and skin necrosis in this patient. Since treatment is generally supportive, prompt and prudent evaluation of suspicious skin lesions is necessary to prevent the serious sequelae associated with WISN.

Adult↗
PubMed1989

[Evaluation of primary multiple cancer manifesting exposure to asbestos].

Twenty five cases (71%) of 35 primary multiple cancer, confirmed by autopsy, were proved to have been exposed to asbestos. Of these cases, lung and stomach cancers, which were related to the asbestos exposure, were main component of the multiple cancers. Thirteen of these cases had definite occupational histories of asbestos exposure and the number of asbestos bodies in five grams of autopsied wet lung tissue amounted to more than 1000. This result suggests that asbestos exposure might possibly induce a high incidence of multiple cancers.

Aged↗
PubMed1999

Nurses failure to appreciate the risks of infection due to needle stick accidents: a hospital based survey.

One of the most important occupational risks to healthcare workers is exposure is to blood-borne viruses. This study examined nurses' perceptions of risk of contracting infection following single or multiple exposure to blood or body fluids. Two hundred and ninety nurses were surveyed using a questionnaire. One hundred and thirty-three responded; 85 worked in higher risk areas (ITU, Haematology, Haemodialysis and Neonatal Surgical Units) (Group A) and 48 worked in lower risk areas (medical wards, an orthopaedic and an ENT ward) (Group B). Forty-nine percent of subjects from group A and 60% of subjects from Group B believed that a needle stick injury with a needle contaminated with infected blood was an unlikely source of infection. Fifteen percent from group A and 20% from group B thought that infection with a blood-borne virus following a needle stick injury contaminated with Human Immunodeficiency Virus (HIV) infected blood was very unlikely. Twelve percent from group A and 10% from Group B did not know whether resheathing needles between use can provide protection against HIV. Sixty-seven percent from group A and 71% from group B disagreed with the statement that nurses are at higher risk of exposure to HIV/HBV than the other healthcare workers. Thirteen percent from group A and 5% from group B agreed with the statement, whereas 8% from group A and 5% from group B thought that nurses are at less risk. Only 22% from group A and 23% from group B would take more precautions if they knew that the patient had HIV/HBV infection, whilst 11% and 8% respectively admitted that they would take special precautions only when the patient has clinical symptoms of HIV/HBV infection. The findings suggest that these nurses would benefit from further education regarding infection from blood-borne viruses.

Attitude of Health Personnel↗
PubMed1986

Epidemiology of emergence and spread of drug-resistant falciparum malaria in Southeast Asia.

In Southeast Asia the medicated salt project of Pailin, on the Kampuchea-Thai border, demonstrated that drug resistance, especially chloroquine resistance, can develop when a large population of P. falciparum parasites is exposed to intense transmission under intense drug pressure. The selection of resistant parasites being activated by the introduction of non-immune groups. Emergence of drug resistance was the result of continuous and prolonged mass exposure of P. falciparum to pyrimethamine and chloroquine resulting in the selection of resistant mutants. This selection was associated with multiple exposures of the parasites to much higher drug doses, during repeated passages through the non-immune hosts, increasing the degree of resistance. Resistances spread to the receptive areas of Kampuchea and other neighbouring countries through the movements of the temporary migrants who, by then, had become carriers infected with drug resistant falciparum parasites. The rapid and early spread of chloroquine resistance in A. balabacensis areas was not a coincidence but the result of the biological advantages of this species complex in relation to malaria transmission. In Australasia the medicated salt project carried out in Irian Jaya, on the border with Papua New Guinea, also resulted in the development of drug resistance in P. falciparum.

Anopheles↗
PubMed2002

Mixture toxicity of priority pollutants at no observed effect concentrations (NOECs).

Environmental exposure situations are often characterised by a multitude of heterogeneous chemicals with ambiguous or unknown modes of action present at low concentrations. While multiple exposure is widely acknowledged, arguments are raised that adverse combined effects might not be evoked by mixtures of substances with dissimilar modes of action and being present at only low concentrations. In this study the combined effect of a multiple mixture composed of structurally dissimilar priority pollutants with mostly unknown modes of action has been investigated using an algal biotest. The concentrations of the components in the mixture equalled statistically estimated, individual no observed effect concentrations (NOECs). The observed mixture toxicity was not only clearly higher than expected for any single substance alone, but also well predictable using the concept of independent action.

Atrazine↗