Influence of varions mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats

1992 ◽  
Vol 70 (3) ◽  
pp. 385-393 ◽  
Author(s):  
R. Tardif ◽  
G. L. Plaa ◽  
J. Brodeur
Keyword(s):  
Biological Monitoring ◽  
Urinary Metabolites ◽  
Exposure Period ◽  
Male Rats ◽  
Single Exposure ◽  
Simultaneous Exposure ◽  
Metabolic Interaction ◽  
Metabolic Interactions ◽  
Blood Toluene ◽  
Metabolic Disposition

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20–30%) and methylhippuric acids (4–40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190–240%; xylene, 340–650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.Key words: toluene, xylene, simultaneous exposure, biological monitoring, metabolic interaction, inhalation.

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

Endotoxin-Induced Uveitis Causes Long-Term Changes in Trigeminal Subnucleus Caudalis Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 3815-3825 ◽  
Author(s):  
David A. Bereiter ◽  
Keiichiro Okamoto ◽  
Akimasa Tashiro ◽  
Harumitsu Hirata
Keyword(s):  
Ocular Surface ◽  
Receptive Fields ◽  
Male Rats ◽  
Cervical Cord ◽  
Single Exposure ◽  
Eye Blinks ◽  
Long Term Changes ◽  
Trigeminal Subnucleus Caudalis ◽  
Stimulation Of

Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin or lipopolysaccharide (LPS, 1 mg/kg ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS, Vc/C1 units had reduced responses to histamine, nicotine, and CO2 gas applied to the ocular surface, whereas unit responses were increased 7 days after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7 days after LPS. Units at the Vi/Vc transition also had reduced responses to histamine and CO2 2 days after LPS but no enhancement was seen at 7 days. Tear volume evoked by CO2 was reduced 2 days after LPS and returned toward control values by 7 days, whereas CO2-evoked eye blinks were normal at 2 days and increased 7 days after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.

Biological monitoring of workers exposed toN,N-dimethylformamide by determination of the urinary metabolites,N-methylformamide andN-acetyl-S-(N-methylcarbamoyl) cysteine

1995 ◽  
Vol 67 (2) ◽  
pp. 125-129 ◽  
Author(s):  
Tadashi Sakai ◽  
Hiroshi Kageyama ◽  
Takaharu Araki ◽  
Takayuki Yosida ◽  
Takeshi Kuribayashi ◽  
...  
Keyword(s):  
Biological Monitoring ◽  
Urinary Metabolites

scholarly journals Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats

Xenobiotica ◽  
2015 ◽  
Vol 45 (8) ◽  
pp. 711-721 ◽  
Author(s):  
Ala F. Nassar ◽  
Adam Wisnewski ◽  
Ivan King
Keyword(s):  
Male Rats ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Metabolic Disposition

scholarly journals An integrated text mining framework for metabolic interaction network reconstruction

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1811 ◽  
Author(s):  
Preecha Patumcharoenpol ◽  
Narumol Doungpan ◽  
Asawin Meechai ◽  
Bairong Shen ◽  
Jonathan H. Chan ◽  
...  
Keyword(s):  
Text Mining ◽  
Interaction Network ◽  
Network Reconstruction ◽  
Event Extraction ◽  
Metabolic Interaction ◽  
Test Corpus ◽  
Metabolic Event ◽  
Metabolic Interactions ◽  
Complex Relationships ◽  
Biological Entities

Text mining (TM) in the field of biology is fast becoming a routine analysis for the extraction and curation of biological entities (e.g., genes, proteins, simple chemicals) as well as their relationships. Due to the wide applicability of TM in situations involving complex relationships, it is valuable to apply TM to the extraction of metabolic interactions (i.e., enzyme and metabolite interactions) through metabolic events. Here we present an integrated TM framework containing two modules for the extraction of metabolic events (Metabolic Event Extraction module—MEE) and for the construction of a metabolic interaction network (Metabolic Interaction Network Reconstruction module—MINR). The proposed integrated TM framework performed well based on standard measures of recall, precision and F-score. Evaluation of the MEE module using the constructed Metabolic Entities (ME) corpus yielded F-scores of 59.15% and 48.59% for the detection of metabolic events for production and consumption, respectively. As for the testing of the entity tagger for Gene and Protein (GP) and metabolite with the test corpus, the obtained F-score was greater than 80% for the Superpathway of leucine, valine, and isoleucine biosynthesis. Mapping of enzyme and metabolite interactions through network reconstruction showed a fair performance for the MINR module on the test corpus with F-score >70%. Finally, an application of our integrated TM framework on a big-scale data (i.e., EcoCyc extraction data) for reconstructing a metabolic interaction network showed reasonable precisions at 69.93%, 70.63% and 46.71% for enzyme, metabolite and enzyme–metabolite interaction, respectively. This study presents the first open-source integrated TM framework for reconstructing a metabolic interaction network. This framework can be a powerful tool that helps biologists to extract metabolic events for further reconstruction of a metabolic interaction network. The ME corpus, test corpus, source code, and virtual machine image with pre-configured software are available atwww.sbi.kmutt.ac.th/ preecha/metrecon.

scholarly journals Current Research Trends on the Effects of Microplastics in Soil Environment Using Earthworms: Mini-Review

2021 ◽  
Vol 43 (4) ◽  
pp. 299-306
Author(s):  
Jaeryung Hur ◽  
Eun Hea Jho
Keyword(s):  
Marine Environment ◽  
Human Life ◽  
Exposure Period ◽  
Soil Environment ◽  
Single Exposure ◽  
Experimental Conditions ◽  
Test Species ◽  
Oxidation Stress ◽  
Induced Changes ◽  
The Impact

Objectives : The increase in the amount of plastics used has brought convenience to human life, but has also caused various environmental problems such as problems related to microplastics. Microplastics are defined as small plastic particles with a size of under 5 mm. As of now, research on microplastics has been largely focusing on the marine environment, and studies on microplastics in soil environment are on the rise in very recent years. Thus, the environmental impact of microplastics on the soil environment are insufficient than those on the marine environment, and there is a need for more studies. Therefore, this mini-review attempts to examine the studies on microplastics in soil environment focusing on the studies using earthworms as a test species.Methods : Published studies on microplastics in soil environment were identified by searching Web of Science. The focus of this mini-review was to gather the published articles reporting the effect of microplastics on earthworms in the absence and presence of other chemical contaminants.Results and Discussions : The number of studies evaluating the effect of microplastics in soil are significantly increasing, and earthworms are being mostly used as the test species. Experimental conditions were divided into two types: Single exposure to microplastics and combined exposure to microplastics and other chemicals. In most studies, changes in the biomarkers which are related to oxidation stress of earthworms were confirmed, and direct damage to intestinal tissues of earthworms was also observed. However, in the case of the changes of the biomarkers of earthworms, their patterns were different depending on the experimental conditions (i.e., concentrations of microplastics and chemicals, microplastics size and type, exposure period, etc.). Also, the avoidance behavior of earthworms and the internal accumulation of microplastics and co-existing chemicals were not consistent among the studies. Thus, the effects of microplastics on earthworms are not clear yet, although they seem to have some adverse effects.Conclusions : This study showed that the interest in the impact of microplastics in the soil environment has been increased recently, and earthworms are being used mostly in the studies. Yet, there is no standardized method to study the effect of microplastics on earthworms. Studies so far confirmed that microplastics induced changes in and outside of earthworm bodies. However, due to various experimental conditions, it seemed that consistent results could not be confirmed in those researches. For that reason, this study suggests that standardized research methods for microplastics researches using earthworms as a test species need to be established and need to be applied to further studies.

scholarly journals Role of Insulin/Glucagon Ratio and Cell Redox State in the Hyperglycaemia Induced by Exposure to Electromagnetic Fields in Rats.

2021 ◽  
Author(s):  
Gabriel Martiñón-Gutiérrez ◽  
María Luna-Castro ◽  
Rolando Hernández-Muñoz
Keyword(s):  
Glucose Metabolism ◽  
Electromagnetic Fields ◽  
Redox State ◽  
Serum Insulin ◽  
Glucagon Secretion ◽  
Serum Levels ◽  
Male Rats ◽  
Single Exposure ◽  
Cellular Redox ◽  
Cellular Redox State

Abstract The exposure to extremely low-frequency electromagnetic fields (EMFs) with a might adversely affect the endocrine system and reproductive functions. Nonetheless, the use of EMFs in the form of magneto-therapy exerts beneficial actions in human medicine, but also affecting glucose and lipids metabolism, inducing hyperglycaemia and a “diabetic” response. Therefore, we used fed or fasted male rats for a single exposure to 60-Hz EMFs, determining serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to EMFs induced hyperglycaemia in both, fed and fasted rats, accompanied by an attenuated second serum insulin peak. In addition, EMFs also decreased serum levels of free fatty acids and lactate, while they increased those of pyruvate and acetoacetate. Changes in blood glucose level were related with a more oxidized cellular redox state and with the insulin/glucagon ratio. Moreover, rat’s glucose metabolism also coincided with variations in insulin and glucagon secretion, probably depending on cell redox state. The EMFs effects were not modified in animals previously subjected to a chronic exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by EMFs exposure were closely related with the cellular redox state and with the insulin/glucagon ratio.

scholarly journals Development, Testing, Parameterisation and Calibration of a Human PBPK Model for the Plasticiser, Di-(2-propylheptyl) Phthalate (DPHP) Using in Silico, in vitro and Human Biomonitoring Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Kevin McNally ◽  
Craig Sams ◽  
Alex Hogg ◽  
Annie Lumen ◽  
George Loizou
Keyword(s):  
Sensitivity Analysis ◽  
Biological Monitoring ◽  
In Silico ◽  
Model Development ◽  
Human Biomonitoring ◽  
Urinary Metabolites ◽  
Monitoring Data ◽  
Pbpk Models ◽  
Lymphatic Uptake

A physiologically based pharmacokinetic model for Di-(2-propylheptyl) phthalate (DPHP) was developed to interpret the biokinetics in humans after single oral doses. The model was parameterized with in vitro and in silico derived parameters and uncertainty and sensitivity analysis was used during the model development process to assess structure, biological plausibility and behaviour prior to simulation and analysis of human biological monitoring data. To provide possible explanations for some of the counter-intuitive behaviour of the biological monitoring data the model included a simple lymphatic uptake process for DPHP and enterohepatic recirculation (EHR) for DPHP and the mono ester metabolite mono-(2-propylheptyl) phthalate (MPHP). The model was used to simultaneously simulate the concentration-time profiles of blood DPHP, MPHP and the urinary excretion of two metabolites, mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP) and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). The availability of blood and urine measurements permitted a more robust qualitative and quantitative investigation of the importance of EHR and lymphatic uptake. Satisfactory prediction of blood DPHP and urinary metabolites was obtained whereas blood MPHP was less satisfactory. However, the delayed peak of DPHP concentration relative to MPHP in blood and second order metabolites in urine could be explained as a result of three processes: 1) DPHP entering the systemic circulation from the lymph, 2) rapid and very high protein binding and 3) the efficiency of the liver in removing DPHP absorbed via the hepatic route. The use of sensitivity analysis is considered important in the evaluation of uncertainty around in vitro and in silico derived parameters. By quantifying their impact on model output sufficient confidence in the use of a model should be afforded. This approach could expand the use of PBPK models since parameterization with in silico techniques allows for rapid model development. This in turn could assist in reducing the use of animals in toxicological evaluations by enhancing the utility of “read across” techniques.

scholarly journals Combined Subchronic Toxicity of Aluminum (III), Titanium (IV) and Silicon (IV) Oxide Nanoparticles and Its Alleviation with a Complex of Bioprotectors

2018 ◽  
Author(s):  
Ilzira A. Minigalieva ◽  
Boris A. Katsnelson ◽  
Larisa I. Privalova ◽  
Marina P. Sutunkova ◽  
Vladimir B. Gurvich ◽  
...  
Keyword(s):  
Exposure Period ◽  
Complex Interaction ◽  
Oxide Nanoparticles ◽  
Combined Toxicity ◽  
Subchronic Toxicity ◽  
Bioactive Substances ◽  
Simultaneous Exposure ◽  
Toxic Species ◽  
Dose Levels ◽  
Harmful Effects

Stable suspensions of metal/metalloid oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism’s status. In many respects, the Al2O3-NP was found to be the most toxic species alone and the most dangerous component of the combinations studied. Mathematical modeling with the help of the Response Surface Methodology showed that, as well as in the case of any other binary toxic combinations previously investigated by us, the organism’s response to a simultaneous exposure to any two of the Me-NP species under study was characterized by a complex interaction between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which outcome a given type was estimated for and on effect and dose levels. With any third MeO-NP species acting in the background, the type of combined toxicity displayed by the other two remained virtually the same or changed significantly, becoming either more or less unfavorable. Various harmful effects produced by the [Al2O3-NP+TiO2-NP+SiO2-NP]-combination, including its genotoxicity, were substantially attenuated by giving the rats per os during the entire exposure period a complex of innocuous bioactive substances expected to increase the organism’s antitoxic resistance.

Gas chromatographic/mass spectrometric studies of the urinary metabolites of male rats given indan

1987 ◽  
Vol 14 (11) ◽  
pp. 649-651
Author(s):  
Kyung O. Yu ◽  
Carl T. Olson ◽  
Michelle J. Ferry ◽  
M. P. Serve
Keyword(s):  
Urinary Metabolites ◽  
Mass Spectrometric ◽  
Male Rats ◽  
Chromatographic Mass
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