Effects of multiple gallium arsenide exposure on some biochemical alterations in rat brain.
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Acetylcholinesterase↗
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Results for “multiple exposures”
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Effects of muscle spindle development of multiple and single exposure to x-irradiation.
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Animals↗
Hematologic and serum biochemical alterations associated with multiple halothane anesthesia exposures and minor surgical trauma in horses.
Five horses were anesthetized similarly by use of xylazine, guaifenesin, thiamylal sodium, and halothane in oxygen on 3 consecutive days, and minor surgical procedures were performed. For 1 to 10 days after the last anesthetic exposure, clinical, hematologic, and serum biochemical features were monitored, and after necropsy, histologic examination of major organ tissues was performed. Predominant hematologic changes from base-line values included leukocytosis (maximal at 27 hours, 10,500 +/- 1,750 cells/microliter), neutrophilia (maximal at 51 hours, 7,485 +/- 1,719 cells/microliter), and lymphopenia (minimal at 51 hours, 1,636 +/- 564 cells/microliter). Alterations observed in other clinicopathologic features were minor and indicative of mild renal disturbance and nonspecific cellular necrosis. Histopathologic lesions in the liver were mild.
Anesthesia, General↗
[Effect of multiple radiant heat exposures on body resistance to convection heating and total cooling].
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Acclimatization↗
Occupational exposure to glycol ethers: implications for occupational health nurses.
1. Evaluation of workplace exposure to reproductive hazards is difficult and is often confounded by occupational exposure to multiple agents and exposure to non-occupational factors. 2. A growing body of evidence from animal and human study data supports a causal association between occupational exposure to certain glycol ethers and adverse reproductive outcomes. 3. Occupational health nurses providing services to employees exposed to glycol ethers should remain knowledgeable about the results of epidemiologic studies and current trends in the regulation of glycol ethers in industry. 4. Occupational health nurses are in a key position to reduce exposure to reproductive hazards by monitoring trends in group data and by implementing training and education programs to employees exposed to reproductive hazards.
Animals↗
[Enhanced resistance to P3-X63-Ag8.653-MORS after multiple repeated stress exposures].
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Animals↗
[The evaluation of the irritating and sensitizing effects of benzalkonium chloride].
The aim of the study was to determine the threshold irritating effect of benzalkonium chloride on the rabbit's skin and eye, and its sensitizing effect on guinea pigs. The study was performed according to the OECD guidelines modified by Krysiak. As a threshold concentration of benzalkonium evoking slight inflammatory reaction on the skin in a single, closed exposure and in multiple, open exposure, the following values were adopted for its aqueous solutions: > 0.5-1%, and 05% respectively. Following the eye administration of 0.01% and 0.05% of benzalkonium aqueous solution a weak irritating and rapidly reversible effect was revealed. The study performed on guinea pigs indicated a sensitizing effect of 0.5%, 0.1% and 0.05% benzalkonium aqueous solutions. The effect differed depending on the concentration used. The evaluation covered the proportion of sensitized animals, the nature and intensity of dermal reaction, as well as peripheral blood eosinophil and basophil tests. The results showed that 0.1% benzalkonium aqueous solution is an optimum concentration for monitoring the sensitizing effect in humans being in contact with this substance.
Animals↗
Reduced cell yields of mouse cell line cultures after exposure to homogenates of multiple sclerosis tissues.
The total cell yields in cultures of a mouse cell line termed "PAM" were reduced markedly after exposure to multiple sclerosis (MS) homogenates. The reductions were noted as early as the second subcultivation. The effect was produced by eight of eight MS brain homogenates and three of three MS spleen homogenates; the samples were from 10 MS cases. The reduction in total cell yields (compared to medium-treated cultures) was not observed after exposure to homogenates, six brain and two spleen, from eight non-MS cases. The effect was produced by the 50-nm filtrate of a pool of MS brain homogenates. Five of the MS-inoculated cultures were maintained for 18 subcultivations, and the reduction in total cell yields persisted throughout the series. The capacity to induce the reduction in cell yields was present in cell-free lysates from five of five MS cultures at passage 18, as was the capacity to cause a decrease in the polymorphonuclear neutrophils in the peripheral blood of mice. Calculation of the dilution effect (at least 10(18)-fold) that had occurred by the end of the passage series proved that the factor(s) causing the cell change in culture and the polymorphonuclear neutrophil change in mice had replicated in PAM cells.
Animals↗
The cumulative probability of occupationally-acquired HIV infection: the risks of repeated exposures during a surgical career.
The cumulative risk of human immunodeficiency virus (HIV) infection over a healthcare career has rarely been estimated, but is more relevant to the description of an occupational hazard than the risk of seroconversion from a single exposure. We describe a model for assessing the individualized risk for HIV infection after multiple potential exposures over many years for surgeons and other operating room personnel, a high-risk group. For the average surgeon operating over a 30-year career on patients with an HIV seroprevalence of 0.01, the cumulative risk is estimated at 1%. The same surgeon operating on patients with a seroprevalence of 0.10 has an estimated cumulative risk of 10%. These risks may vary dramatically depending on the assumed rate of skin punctures during surgery. Healthcare workers need to be aware of the cumulative risk from multiple exposures to infectious blood and body fluids, to follow proposed suggestions for the reduction of percutaneous blood exposures and to assist in developing new technology to further reduce these risks. Failure to protect these professionals could result in the reduction of services for the approximately 1 to 1.5 million HIV-infected persons in the United States.
General Surgery↗
Hierarchical sampling of multiple strata: an innovative technique in exposure characterization.
Sampling of multiple strata, or hierarchical sampling of various exposure sources and activity areas, has been tested and is suggested as a method to sample (or to locate) areas with a high prevalence of elevated blood lead in children. Hierarchical sampling was devised to supplement traditional soil lead sampling of a single stratum, either residential or fixed point source, using a multistep strategy. Blood lead (n=1141) and soil lead (n=378) data collected under the USEPA/UCI Tijuana Lead Project (1996-1999) were analyzed to evaluate the usefulness of sampling soil lead from background sites, schools and parks, point sources, and residences. Results revealed that industrial emissions have been a contributing factor to soil lead contamination in Tijuana. At the regional level, point source soil lead was associated with mean blood lead levels and concurrent high background, and point source soil lead levels were predictive of a high percentage of subjects with blood lead equal to or greater than 10 micro g/dL (pe 10). Significant relationships were observed between mean blood lead level and fixed point source soil lead (r=0.93; P<0.05; R(2)=0.72 using a quadratic model) and between residential soil lead and fixed point source soil lead (r=0.90; P<0.05; R(2)=0.86 using a cubic model). This study suggests that point sources alone are not sufficient for predicting the relative risk of exposure to lead in the urban environment. These findings will be useful in defining regions for targeted or universal soil lead sampling by site type. Point sources have been observed to be predictive of mean blood lead at the regional level; however, this relationship alone was not sufficient to predict pe 10. It is concluded that when apparently undisturbed sites reveal high soil lead levels in addition to local point sources, dispersion of lead is widespread and will be associated with a high prevalence of elevated blood lead in children. Multiple strata sampling was shown to be useful in differentiating among sources by site-specific association to mean blood lead and the prevalence of elevated blood lead at the regional level.
Child↗
Meta-analysis of multiple myeloma and benzene exposure.
Epidemiologic studies have suggested that benzene exposure may be a risk factor of multiple myeloma (MM). We performed meta-analyses of case-control studies to assess the association between occupational exposure to benzene and the risk of MM. We divided the occupational sources of benzene exposure into 4 categories, benzene and/or organic solvents, petroleum, petroleum products, and engine exhaust, for conducting the meta-analysis. As a result, a significant positive association was indicated between exposure to engine exhaust and MM (summary odds ratio or summary OR=1.34, 95% confidence interval or 95%CI=1.14-1.57). However, no significant associations were obtained for benzene and/or organic solvents (summary OR=0.74, 95%CI=0.60-0.90), petroleum (summary OR=1.11, 95%CI=0.96-1.28) and petroleum products (summary OR=1.08, 95%CI=0.89-1.33) with risk of MM. These results suggested that benzene exposure itself was not likely to be a risk factor of MM. It is thought that several harmful chemical agents in engine exhaust, other than benzene, could be etiologically related to the risk of MM. Further case-control studies on MM are needed to obtain more information about detailed occupational exposure to toxic substances.
Air Pollutants, Occupational↗
Dose rate and mode of exposure are key factors in JNK activation by UV irradiation.
Single exposure of cells to UVC (254 nm for 30 s) or to UVB (300 nm for 10 min) was shown to activate jun-NH2 kinases which, in turn, phosphorylate their substrates ELK-1, c-jun and ATF-2. While UVC (40-80 J/m2) activates JNK up to 4 h, with maximal induction after 30 min, UVB (150-300 J/m2) activates JNK over a prolonged period, up to 24 h, with maximal induction after 6 h. UV-mediated activation of src-related tyrosine kinases and MAPK revealed different kinetics, with maximal induction after 24 h. As recent studies had indicated a role of a UVC component in mediating the ability of UVB to activate JNK, we have examined the effect of dose rate as well as of multiplicity of exposures on the activation of these kinases. The UVC portion found in 300 J/m2 UVB (5%, corresponding to 15 J/m2, administered within 10 s) did not activate JNK. However, when the same dose was administered at a lower rate (i.e. over 10 min, as needed for UVB irradiation) it was found capable of activating JNK, MAPK and src kinases, but to a lower degree and with different kinetics than found for UVB. Such differences point to cellular changes which are elicited by UVB, but not UVC. Although a single UVB exposure using a filter that blocks wavelengths below 300 nm prevented activation of JNK, multiple exposures of filtered UVB wavelengths (mimicking chronic exposure) were able to activate JNK. We conclude that the mode of UVB exposure (dose rate and multiplicity) is a crucial determinant for physiologically relevant activation of JNK.
3T3 Cells↗
Occupational risk of acquiring HIV infection through needlestick injuries.
Accidental needlestick exposures occur frequently among hospital personnel and account for most incidents of percutaneous injuries. Even if universal precautions were followed routinely, it is unlikely that multiple needlestick exposures could be avoided completely. Despite the likelihood of persons incurring multiple needlestick exposures, relatively little information is available on the cumulative risk of human immunodeficiency virus (HIV) infection for health care workers attending unrecognized HIV-infected patients. A quantitative method to estimate annual cumulative risk from multiple exposures is offered, and the risk of HIV infection is estimated by use of a probability model for health care workers in both hospital and emergency department settings.
HIV Infections↗
Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.
A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.
Animals↗
Diagnostic x-ray procedures and risk of leukemia, lymphoma, and multiple myeloma.
Exposure to diagnostic x-rays and the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma were studied within two prepaid health plans. Adult patients with leukemia (n = 565), NHL (n = 318), and multiple myeloma (n = 208) were matched to controls (n = 1390), and over 25,000 x-ray procedures were abstracted from medical records. Dose response was evaluated by assigning each x-ray procedure a score based on estimated bone marrow dose. X-ray exposure was not associated with chronic lymphocytic leukemia, one of the few malignant conditions never linked to radiation (relative risk [RR], 0.66). For all other forms of leukemia combined (n = 358), there was a slight elevation in risk (RR, 1.17) but no evidence of a dose-response relationship when x-ray procedures near the time of diagnosis were excluded. Similarly, patients with NHL were exposed to diagnostic x-ray procedures more often than controls (RR, 1.32), but the RR fell to 0.99 when the exposure to diagnostic x-ray procedures within 2 years of diagnosis was ignored. For multiple myeloma, overall risk was not significantly high (RR, 1.14), but there was consistent evidence of increasing risk with increasing numbers of diagnostic x-ray procedures. These data suggest that persons with leukemia and NHL undergo x-ray procedures frequently just prior to diagnosis for conditions related to the development or natural history of their disease. There was little evidence that diagnostic x-ray procedures were causally associated with leukemia or NHL. The risk for multiple myeloma, however, was increased among those patients who were frequently exposed to x-rays.
Adult↗
Effects of multiple routes of cadmium exposure on the hibernation success of the American toad (Bufo americanus).
The effects of multiple routes of cadmium exposure on juvenile American toads (Bufo americanus) were evaluated using environmentally relevant concentrations. During or after exposure, toads were individually hibernated for 172 days at approximately 4degreesC. The following experiments were conducted: (1) dermal exposure (hibernation in soil contaminated with up to 120 microg Cd/g (dry weight)); (2) injection exposure (single injection with cadmium to achieve a maximum whole-body nominal concentration of 3 microg Cd/g (wet weight) 12 days before hibernation in uncontaminated soil); and, (3) oral exposure (feeding with mealworms containing < or =16 microg Cd/g (dry weight) for 50 days before hibernation in uncontaminated soil). We hypothesized that sublethal levels of cadmium would become lethal during hibernation because of combined chemical and cold stress. No prehibernation mortality occurred in the injection and oral exposure studies. There was a significant treatment effect on whole-body cadmium concentration in toads orally or dermally exposed and on percent of cadmium retention in toads orally exposed. There was also a trend of increased time-to-burrowing and more toads partially buried with greater cadmium concentration in the dermal study, which indicated avoidance. In all 3 experiments, no significant differences were found among cadmium treatments in hibernation survival, percent of mass loss, or locomotor performance. However, toads fed mealworms averaging 4.7 microg Cd/g (dry weight) had only 56% survival compared with 100% survival for controls. Although our results suggest that environmentally relevant levels of cadmium do not pose a great risk to American toads, factors such as soil type or prey species may increase cadmium bioavailability, and other amphibian species may be more sensitive to cadmium than B. americanus.
Administration, Oral↗
Planning and using PB-PK models: an integrated inhalation and distribution model for nickel.
A general method is presented for the use of mathematical modeling in the design, execution, and interpretation of toxicology experiments. To illustrate the use of mathematical modeling toxicology, a case study is presented of how a dosimetry model for inhaled nickel was developed for use in cancer risk estimation. A physiologically based pharmacokinetic (PB-PK) dosimetry model is used to plan animal experiments and to extrapolate nickel kinetics from animals to humans. These data are then used to estimate human lung cancer risks from human exposure to nickel aerosols. To achieve this goal, a PB-PK dosimetry model for the lung was integrated with a PB-PK dosimetry model for the internal organs. Nickel removal from the lung was found to be saturable and to follow Michaelis-Menten kinetics. The PB-PK lung dosimetry model was used to design both short-term (single exposures) and long-term (multiple intermittent exposures) needed to validate the parameters (Km and Vmax) of the lung dosimetry model. A constant infusion experiment was planned using the PB-PK modeling approach to measure the distribution and elimination of intravenously administered nickel. The two PB-PK models were integrated to estimate the fate of nickel after inhalation and are being used to plan experiments for other routes of exposure such as ingestion of drinking water and dermal contact. The integrated model has been used to calculate a human cancer risk estimate in combination with short-term genotoxic experiments. Using PB-PK models in toxicology, as illustrated here, conserves experimental animals, aids in understanding new physiological phenomena (such as saturable clearance from the lung), incorporates in vitro tests with in vivo experiments, and provides a means of extrapolation to human health risks from multiple routes of exposure. Introducing the concepts of mathematical modeling into toxicity experiments at the beginning of the experiment improves the usefulness of the experiments in risk estimation. PB-PK models are suggested as a new basis for experimental design in toxicology.
Administration, Inhalation↗
Endurance and performance during multiple intense high +Gz exposures with effective anti-G protection.
BACKGROUND: In many high-intensity wartime scenarios, pilots may be required to fly multiple, strenuous missions during the same day. HYPOTHESIS: New anti-G protection allows fighter pilots to endure multiple high +G, exposures during several sorties in a limited time interval. METHODS: Nine well-trained centrifuge subjects were exposed to tactical aerial combat maneuvers using balanced pressure breathing during G (PBG) and an extended coverage anti-G suit. The centrifuge exposures consisted of five simulated sorties during a 4-h period, each consisting of four engagements with rapid onset cycles (6 G x s(-1)) varying between +4 G, and -9 GC. The subjects executed a tracking task before, during, and after each engagement and verbally indicated their effort level. Neck muscle strength was measured before and after the test. RESULTS: Seven of the nine subjects could endure all five sorties during the 4-h period. On a scale from 0 (no effort) to 11 (maximum possible effort), highest effort level during runs varied from 5.5 to 11 units (mean 8.7). Maximal heart rate varied from 140-173 bpm (mean 159) and minimum finger oxygen saturation from 75-93% (mean 88). Maximal peripheral and central light-loss varied from 0 to 100% (mean 71 and 40, respeclively). Three G-LOCs (two in the same subject) and four cases of near loss of consciousness occurred. The general fatigue recovery time varied from 9 to 48 h (mean 21). The tracking tests showed that performance deteriorated significantly during all G exposures; the neck muscle contraction was impaired by 12% (p = 0.035) after the C exposures. CONCLUSION: It is possible to train subjects to withstand five simulated flight sorties during a 4-h period with a total of up to 80 peaks to +9 Gz and 80 peaks to +8 Gz using PBCG and an extended coverage anti-G suit.
Aerospace Medicine↗