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PubMed1979

Cytochemical bioassay and radioimmunoassay of ACTH in noise stressed rats.

Serum corticosterone and ACTH levels were measured in rats subjected to one and two 30 min intervals of noise (100 dB, 250--20,000 Hz). Both hormones were elevated immediately after noise exposure, dropped below pre-exposure levels after a 2 hr recovery interval and were again elevated with a second exposure. The ratio of immunoactive to bioactive ACTH was slightly depressed after one exposure and markedly depressed after two successive noise exposures (relative to controls) indicating that multiple exposure to auditory stimulation effects a proportionally greater output of bioactive ACTH.

Acoustic Stimulation↗
PubMedDate not supplied

[The risk from mixtures in the indoor air].

Indoor air is typically contaminated by complex mixtures of several pollutants at low concentrations. As a consequence, the application of methods for evaluating the effects of multiple exposure should be recommended for risk assessment of indoor air pollutants. For this purpose, criteria recommended by scientific and governmental Institutions for risk assessment of multiple indoor exposure are reported.

Air Pollutants↗
PubMed1994

Influence of carbon dioxide anesthesia on chlorpyrifos toxicity in the German cockroach (Dictyoptera: Blattellidae).

Insecticide-susceptible (Orlando normal) and multi-insecticide-resistant (Village Green) adult male German cockroaches, Blattella germanica (L.), were exposed to carbon dioxide (CO2) gas in either varying durations or multiple exposures of fixed duration followed by topical treatment with acetone or chlorpyrifos (LD25) to evaluate the effect of CO2 anesthesia on chlorpyrifos toxicity. CO2 anesthesia did not increase chlorpyrifos toxicity in either strain regardless of exposure duration up to 1 h. However, multiple CO2-induced knockdowns alone caused mortality and increased chlorpyrifos toxicity. Twenty-four-hour weight loss was independent of CO2 duration exposure by strain. Village Green and Orlando cockroaches lost 5.3 and 7.6% of their weight in 24 h when treated with acetone and 10.5 and 12.8% when treated with chlorpyrifos, respectively. Conversely, 0- and 24-h weight loss increased with increasing CO2-induced knockdowns regardless of strain or topical treatment. Based on these results, CO2 used either once of limited duration (< or = 15 min) or multiple times of short duration, not to exceed four total knockdowns, does not increase chlorpyrifos toxicity in the adult male German cockroach.

Anesthesia↗
PubMed1988

Halothane hepatitis.

Hepatitis following halothane anaesthesia may take two forms: a mild self-limiting disease or a more severe hepatitis with a high mortality. Whether these two forms represent two distinct entities or ends of a spectrum is unclear. Severe hepatitis is commoner after multiple exposures and has many of the characteristics of an immune-mediated hypersensitivity reaction. The incidence is very low; the best, albeit unsatisfactory, estimate of the incidence is about 1 in 3,700 patients with multiple halothane exposures. The mechanism of liver damage is uncertain: in some circumstances halothane may be directly hepatotoxic, but it remains to be conclusively proved that immune mechanisms are responsible. Studies from our unit have suggested that halothane hepatitis can positively be diagnosed by demonstration of antibodies reacting with halothane-altered liver cell determinants. The incidence of the condition can be reduced by taking a full anaesthetic history and avoiding the use of halothane in the high-risk patients, namely those who have had recent previous halothane anaesthesia and those who have had jaundice or unexplained post-operative pyrexia following earlier halothane anaesthetics. When halothane hepatitis has occurred, treatment is purely supportive with the possibility of transplantation for those in grade IV encephalopathy.

Adult↗
PubMed2003

Role of repeated lung injury and genetic background in bleomycin-induced fibrosis.

Current hypotheses of the pathogenesis of many forms of pulmonary fibrosis suggest that (i) a stimulus results in repeated or prolonged episodes of lung injury, and (ii) genetic factors modulate the outcome of the injury. The commonly employed single-exposure bleomycin model results in only temporary fibrosis. Therefore, we evaluated whether repeated bleomycin exposures, in the setting of a genetic background more likely to develop a T helper 2 (Th2) response, would induce prolonged fibrosis. Lung fibrosis was induced by intratracheal bleomycin injection, either as a single exposure or as three consecutive exposures. We found that bleomycin induced a Th2-like environment in both Th1-biased C57BL/6J and Th2-biased DBA/2 mice. We also found histologic changes and collagen increases consistent with lung injury/fibrosis at early time points, but prolonged fibrosis only after multiple exposures in the Th2-biased DBA/2 mice. We also determined if impaired healing of bleomycin-induced injury would prolong fibrosis in the C57BL/6J mice. Endothelial nitric oxide (which protects endothelial cells from oxidant-induced injury) synthase knockout animals on a C57BL/6J background also had prolonged fibrosis, similar to DBA/2 mice, after multiple bleomycin exposures. This was specific to eNOS, as inducible nitric oxide synthase knockout animals cleared the fibrosis as effectively as wild-type C57BL/6J mice. This data indicate that healing of injury/fibrosis after bleomycin is complex and can be determined by a number of genetic and environmental factors.

Animals↗
PubMedDate not supplied

Cancer incidence and risks in selected agricultural settlements in the Negev of Israel.

Medical staff of two Negev kibbutzim invited epidemiologists to help them investigate cancer rates among their members. Our objectives were (a) to determine whether the cancer rate in the kibbutzim was elevated or abnormal and (b) to determine the role of agricultural and other relevant exposures if cancer incidence was elevated. We validated cases of cancer by kibbutz records and by surveying other information; we computed expected values on the basis of the age-sex-calendar period and site-specific cancer incidence rates reported by the Israel Cancer Registry for the entire population; and we compared the data for the 2 kibbutzim with data derived for similar age and sex groups in 2 other kibbutzim, which were assumed not to have increased cancer rates. In addition, we planned and conducted a case-referent study, including the design, pretest, and use of questionnaires, including data about lifetime exposures (i.e., type of work and its duration, agricultural and industrial chemicals, smoking and alcohol use, demographic variables, health experiences, and family history). In only one of the kibbutzim, for which high cancer rates were suspected, was there significant excess for all sites in persons who were less than 40 y of age. In one of the "comparison" kibbutzim, we found increased cancer rates overall. Much of the excess in the high cancer kibbutzim was in hematological cancer (i.e., leukemia and lymphoma). Multiple years of work in fields, orchards, and landscape, as well as orchard work that commenced before 1960, were associated with increased risk of cancer (p < .08). We also found an association between cancer rate and numbers of industrial chemicals used (p < .08). Pipe and cigarette smoking were also associated with increased cancer incidence. In the multivariate analysis, the association with calendar year in which orchard work was started and multiple exposures to industrial chemicals was stronger than associations noted in the univariate analyses. Although duration of agricultural work or multiple industrial exposures were clearly associated with increase in cancer risk, we were unable to identify the causal role of specific agent(s). Nonetheless, educational programs for cancer prevention can be based, in part, on the results of such a study.

Adolescent↗
PubMed1990

Inhalation carcinogenesis of repeated exposures to high-fired 244CmO2 in rats.

Rats were given single or multiple (10 exposures at about 21-d intervals) inhalation exposures to 244CmO2 starting at 70 d of age. Mean lung and bone doses (+/- standard deviation) were 1.4 +/- 1.3 and 0.74 +/- 1.1 Gy, respectively, in the single exposure group, and 1.8 +/- 2.9 and 0.53 +/- 0.74 Gy, respectively, in the multiple exposure group. After cessation of exposure in the multiple exposure group, mean cumulative lifetime radiation doses to lung and skeleton were not significantly different in the two groups. The percentages of rats with lung and bone tumors were 9.1 and 12%, respectively, in the single exposure group, and 20 and 24%, respectively, in the multiple exposure group. However, the multiple exposure regimen did not significantly alter survival times or tumor incidences in lung or bone from a single inhalation exposure to 244CmO2 when survival patterns were taken into account.

Administration, Inhalation↗
PubMed2005

Non-Hodgkin lymphoma and benzene exposure: a systematic literature review.

Epidemiological papers that address an association between benzene exposure and non-Hodgkin lymphoma (NHL) were identified and separated by study design. Eighteen studies contained 21 study groups-11 population-based case-control study groups, 3 nested occupation-based case-control study groups and 7 occupational benzene cohort study groups. Petroleum industry studies were not included. Only two of these 21 study groups showed statistically significant associations. However, these were among workers with multiple exposures across industries. Eleven of the 21 study groups presented ratios less than one, two equaled one, and eight were greater than one. Over all, about as many cases were observed (404) as expected (390.0) for an observed to expected ratio of 1.04 (0.94-1.14). After removal of the studies with multiple chemical exposures problems, the observed was 359 cases with 373.2 cases expected, yielding an odds ratio of 0.96 (0.86-1.06). Further assessment of an association with NHL should document the benzene exposure and separate out the contribution of non-benzene exposures.

Air Pollutants, Occupational↗
PubMed2003

Toxic effects of profenofos on tissue acetylcholinesterase and gill morphology in a euryhaline fish, Oreochromis mossambicus.

Acute and sub-acute studies of profenofos [ O-(4-bromo-2-chlorophenyl)- O-ethyl- S-propyl phosphorothioate] on fish, Oreochromis (Tilapia) mossambicus, were carried out to assess the toxicity in relation to behaviour, morphology, and interactions with the targeted enzyme acetylcholinesterase (AChE, EC 3.1.1.7). Profenofos can be rated as highly toxic to O. mossambicus, with a median lethal concentration (LC(50)) of 0.272+/-0.0177 mg/l. The inhibitory and recovery pattern of brain and gill AChE was studied in vivo after exposure to a single LC(50) and multiple exposures to sub-lethal concentrations (0.108 mg/l) for 28 days, respectively. The LC(50)-exposed fish exhibited 90% inhibition of AChE activity in brain and gill in 24 h, and completely recovered within 23 days. Electron microscopy studies revealed an abnormal gill morphology, with distinct breakages in gill arches and rakers, along with deep lesions and erosions in the epithelium. Prolonged exposure at 0.108 mg/l also had similar effects, such as gill damage and AChE inhibition. The in vitro AChE study indicated that profenofos is neurotoxic and that it alters the apparent K(m) values widely in a concentration-dependent manner, resulting in a competitive type of inhibition. Based on the K(i) values, the sensitivity of AChE in brain was greater than that in gill tissue, at 2.38 x 10(-5) and 4.62 x 10(-5) M, respectively. The bioaccumulation values in head, body and viscera were estimated at regular intervals by gas chromatography method. The results indicated that the accumulation of profenofos was the highest in viscera followed by head and body, with depuration rates of 6.14, 0.16 and 0.12 micro g/h, respectively.

Acetylcholinesterase↗
PubMed1991

Recovery of vascular smooth muscle relaxation from nitroglycerin-induced tolerance following a drug-free interval. A time-course in vitro study.

Hemodynamic tolerance occurs upon continuous exposure of vascular tissues to nitroglycerin (NTG). This phenomenon is believed to be due to the depletion of the tissue sulfhydryl (SH) group, which is essential for NTG-induced increase in tissue cyclic GMP and vasorelaxation. To determine the effect of an NTG-free interval on recovery of tissue cyclic GMP accumulation and vasorelaxation following development of NTG tolerance, isolated rat aortic rings were kept in Krebs physiologic buffer at 37 degrees, precontracted with epinephrine, and exposed to NTG. The mean concentration of NTG, which relaxed the rings by 50% (EC50) upon first exposure, was 1.1 x 10(-7) M (N = 20), and vascular cyclic GMP levels after NTG increased from 21 to 46 fmol/mg (P less than 0.02). A second exposure to NTG 15 min later increased the EC50 to 1.3 x 10(-4) M and cyclic GMP levels did not change (P less than 0.001 vs first NTG exposure), indicating tolerance to NTG. However, acetylcholine-mediated relaxation of aortic rings was preserved even in NTG-tolerant rings. A second exposure of tissues to NTG separated by 30, 60, and 120 min from the first exposure progressively decreased the EC50, such that at 120 min the EC50 of NTG was 0.4 x 10(-7) M (P = NS vs first NTG exposure). Tissue cyclic GMP levels increased from 14 to 71 fmol/mg (P = NS vs first NTG exposure). These data confirm development of tolerance to the vasorelaxant effects of NTG following initial exposure. An interval of 2 hr between multiple exposures of tissues to NTG results in preservation of the smooth muscle relaxation and an increase in tissue cyclic GMP in response to NTG.

Acetylcholine↗
PubMed2001

Pet dogs as sentinels for environmental contamination.

The presence of environmental contaminants in air, water and food may pose significant health risks to the exposed human population. However, problems associated with assessing chronic exposure to low doses of environmental chemicals, multiple exposure routes, diseases with long latency periods, and non-specific health outcomes make it difficult to conduct the appropriate human epidemiologic studies. It may be useful to complement human epidemiology with animal studies. Animals monitored or evaluated in situ for the appropriate suite of endpoints can provide information about both exposure levels and potential adverse health effects. Animals have served as sentinel indicators for health effects associated with a number of environmental exposures, including pesticides and asbestos. Pet dogs may be particularly valuable sentinels because they share the human environment. In addition, dogs respond to many toxic insults in ways analogous to humans, they have physiologically compressed life spans, and they are free from some important lifestyle risk factors for disease. An example of how pet dogs may be used as sentinels for potential human health hazards involves a study of the genotoxic effects resulting from exposure to a mixture of chemicals from nearby Superfund sites. We conducted a cross-sectional study of exposed dogs (living in the community with the Superfund sites) and controls (living in a nearby community). The pet owners completed a questionnaire, and we collected a blood sample from each dog. The blood samples were analyzed for standard clinical parameters and assays for possible genotoxic effects (peripheral blood lymphocyte micronucleus frequency and lymphocyte subtyping). Pet dogs living near the Superfund sites had a higher micronucleus frequency than control animals, suggesting that the dogs may have been exposed to environmental contaminants from these sites.

Alanine Transaminase↗
PubMed2003

Assessment of exposure to a flood disaster in a mental-health study.

The lasting psychological consequences of disasters are an important public health issue, especially for determining the support needed by victims. One important question in evaluating psychological consequences remains the assessment of individual disaster-related experiences or stressors. This article proposes two approaches towards the construction of cumulative exposure indicators (CEIs) for a disaster and discusses their relevance for other disasters. In 1997, we carried out a cross-sectional study of the association between the severity of exposure to a 1992 flood in southeastern France and the prevalence of psychological symptoms 5 years later. We interviewed 500 randomly selected subjects residing in one of the most affected municipalities and constructed two CEIs: one based on relevant articles in the literature and the second based on the results of a principal component analysis (PCA) of all the items exploring exposure to the flood. We compared these CEIs with a map of flood damage and tested the association between these indicators and a score of post-traumatic stress symptoms. Most of the subjects (79.1%) had been exposed to at least one stressor besides physical presence. The two CEIs were significantly correlated with one another; comparisons with the map showed that both had good ability to discriminate between mild and severe exposure. Multiple regression analyses showed a significant exposure-effect relation, of the same level of magnitude and significance, between the post-traumatic stress disorder score and each CEI. Our results show the appropriateness of such indicators in assessing the effect of cumulative stress from natural disasters. Guidelines should be developed to improve the comparability of instruments and help standardize methods for evaluating cumulative stress from disasters insofar as possible. Further research is nonetheless necessary to assess the consistency and reproducibility of the data collected.

Adult↗
PubMed2003

Stretch-activated ion channels and c-fos expression remain active after repeated eccentric bouts.

This study was undertaken to measure the response of stretch-activated ion channels (SAC) and transcript levels of the oncogene c-fos to separate bouts of eccentric contractions (EC). It was hypothesized that SAC in rat skeletal muscle would contribute to resting membrane potential depolarization after separate repeated bouts of EC. Blockage of SAC during an EC training regime also tested the necessity of SAC for a training response. It was also hypothesized that transcript levels of c-fos would be maximally elevated after the first exposure to EC and diminish with repeated exposures. The results indicate less depolarization after multiple bouts of EC, which could be reversed by blocking the SAC. Transcript levels of c-fos were elevated to a similar degree after either a single or multiple exposures to EC. EC training resulted in significant increases in contractile force and muscle wet and dry weights in nontreated animals. Training in the presence of the SAC-blocker streptomycin produced similar changes in contractile force without changes in muscle weight. SAC and c-fos are activated after several exposures to EC and therefore remain as possible signals in EC training responses.

Animals↗
PubMed1985

The case-referent study--some comments on its structure, merits and limitations.

Case-referent (case-control) studies have become increasingly important in occupational health epidemiology. The concept of study base [Miettinen, Scand J Work Environ Health 8 (1982):suppl 1, 7-14] as referring to the health experience of the study population over time, and a clear recognition of open and closed populations, ie, with or without turnover, make the structure of the case-referent study clearer. The referents should represent the study base in terms of exposure and nonexposure and even with regard to other determinants of the disease under study. Case-referent studies refer to open populations unless nested in cohorts. Matching in cohort studies is straight-forward and creates a symmetrical situation among the exposed and unexposed with regard to the matching factor, but this symmetry is not achieved in case-referent studies, in which matching tends to distort the representativeness of the referents with regard to the study base. This circumstance suggests that matching on determinants of the disease should be maintained in the analysis. However, since the referents are a sample of the base, there might be confounding in the data, which does not exist in the base and vice versa, ie, full control of confounding in case-referent studies is not achievable either through matching or through any other procedure, but a large sample of referents would more properly reflect the distribution of confounders in the base. Using hospital referents, one has to consider possible relations between the referent diseases and the exposure under study, and therefore evaluation of multiple exposures may even require different sets of hospital referents.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiologic Methods↗
PubMed1994

Vibration-induced white finger as a risk factor for hearing loss and postural instability.

Effect of vibration-induced white finger (VWF) on the hearing was examined in 289 Japanese forest workers. From 51 subjects suffering from VWF and 228 with no history of VWF, 37 pairs were formed, matched for age and hours of noise exposure. The cases with VWF had a significantly higher hearing threshold at 4 and 8 kHz than their matched controls. This result was corroborated by the follow-up study which showed significant deterioration of hearing at 2 and 4 kHz only in subjects with VWF during five-year follow-up period. The possible effects of VWF on the postural stability were investigated in 71 Finnish forest workers. Postural stability was evaluated by an average velocity of the body-sway (ASV) measured with a force platform technique. Neither age nor exposure duration to chain saw noise and vibration correlated with ASV. A significant positive correlation was found between ASV and hearing level at 4 kHz after allowing for the effects of the exposure. Multiple regression analysis of ASV on age, exposure hours, hearing level at 4 kHz and prevalence of VWF showed that the hearing level and VWF had significant and almost significant effects on ASV, respectively. Thus, the workers suffering from VWF developed greater hearing loss and the hearing loss correlated with ASV. VWF explained some variance of ASV in the regression analysis. VWF seemed to play some role in hearing deterioration and possibly in genesis of balance disorder.

Adult↗
PubMed1992

Biomarkers of pesticide exposure.

Incorporation of biomarkers in studies of occupational exposure hazards is now recognized as a highly useful adjunct to the surrogate measures employed in the past, for example, time worked, ambient air data, interview responses. Application to studies of workers potentially exposed to pesticides has barely begun and provides many challenges to chemist/epidemiologist teams. This review indicates several excellent studies employing multiple-exposure measures to document the validity of specific biomarkers for particular exposure situations. In general, exposure reflected by urinary assays of specific pesticides is a low percentage of that indicated by dermal or breathing zone measures. Markers for many of the pesticides in current usage have yet to be developed and validated, and information on population variability is generally lacking for existing markers. The challenge provided by the complexity of multiple, and often unknown, exposures to individuals in pesticide environments has begun to be addressed employing cytogenetic or urinary measures that attempt to integrate these complex exposures. The lack of data regarding sensitivity and specificity of biomarkers, especially in complex exposure situations, is a major problem that perhaps will best be addressed by studies combining nonspecific measures with specific ones, utilizing stored sample banks created for that purpose. Expanding the repertoire of available biomarkers of pesticide exposure and employing multiple ones in well-designed study protocols will provide critical tools in the evaluation of pesticide safety and design of appropriate measures to minimize adverse exposures. Ironically, one of the problems that biological markers of exposure can help overcome, reliance on poorly measured ambient exposure data, hampers the evaluation of the markers themselves. Therefore, the combination of in vitro, animal, and human data will give the best picture of a marker's performance. (Wilcosky 1990).

Biomarkers↗
PubMed2007

Determinants of allergen concentrations in apartments of asthmatic children living in public housing.

There is growing evidence linking poor housing conditions and respiratory diseases, including asthma. The association between housing conditions and asthma in the inner city has been attributed in part to cockroach and mouse infestation and the resulting allergen exposures. Multiple social and behavioral factors can influence environmental exposures and health conditions, necessitating a thorough examination of such factors. As part of the Healthy Public Housing Initiative, we evaluated the association between physical and household characteristics and pest-related allergen levels in three public housing developments in Boston, MA. We detected cockroach allergens (Bla g 1 and Bla g 2) in bedroom air, bed, and especially high concentrations in kitchen samples. In multivariate Tobit regressions controlling for development and season, clutter and lack of cleanliness in the apartment were associated with a tenfold increase in Bla g 1 concentration in the air, a sevenfold increase in Bla g 1 and an eightfold increase in Bla g 2 concentrations in the bed, and an 11-fold increase in Bla g 2 in the kitchen (p<0.05 for all). Holes in the wall/ceiling were associated with a six- to 11-fold increase in kitchen cockroach allergen concentrations (p<0.05). Occupancy in an apartment unit of 2 years or more was also associated with increased cockroach allergen concentrations. In contrast, there were low concentrations of mouse urinary protein in this population. In conclusion, these results suggest that interventions in these homes should focus on reducing cockroach allergen concentrations and that building-wide interventions should be supplemented with targeted efforts focused on high-risk units.

Adolescent↗
PubMed2000

Characterization of metalworking fluid exposure indices for a study of acute respiratory effects.

Although metalworking fluids have been widely used throughout industry for decades, occupational exposures to metalworking fluid aerosols and their constituents have not been well characterized. This article describes an exposure assessment for a study of metalworking fluid aerosols and acute respiratory effects. This exposure assessment was unique in its inclusion of multiple exposure measures relevant to a complex environment, and extensive personal sampling for bacteria and endotoxin. The specific objectives were to: (1) obtain indices of personal exposure to metalworking fluid aerosols in an automotive transmission plant, either directly (by sampling) or indirectly (by estimation), and (2) identify and adjust for sources of error in exposure/dose measures, where possible. No prior studies have characterized personal exposures to metalworking fluid aerosols so extensively. Exposure data were obtained during a pilot phase and three principal rounds of data collection over a 15-month period in conjunction with spirometric testing. Subjects worked in one of two machining departments, Case and Valve Body, or in a comparison department, Final Assembly. The primary exposure measures for this study were thoracic fraction particulate, thoracic fraction bacteria (viable plus non-viable), and total endotoxin. Mean personal air concentrations of thoracic particulate across all study rounds were 0.13 mg/m3 in Final Assembly, 0.32 mg/m3 in Valve Body, and 0.56 mg/m3 in Case. Average personal exposures to thoracic fraction bacteria were 0.38 bacteria/cc in Final Assembly, 0.87 bacteria/cc in Valve Body, and 2.66 bacteria/cc in Case. Average personal endotoxin measurements, collected in Round 3 of the study, were 16.4 endotoxin units (EU)/m3 in Assembly, 34.7 EU/m3 in Valve Body, and 234 EU/m3 in Case. Sump fluid contained on the order of 10(8) bacteria/ml, and 10(4)-10(5) EU/ml. Air concentrations of thoracic particulate, thoracic bacteria, and total endotoxin were highly correlated in metalworking operations. Thus, reducing airborne particulate levels should also reduce ambient bacteria and endotoxin, which are suspect agents of respiratory impairment. The elevated endotoxin levels in Final Assembly were unexpected, and suggest an independent source of endotoxin contamination in this department.

Acute Disease↗