Subchronic Neurotoxicity of Vaporized Diisopropyl Ether in Rats

1997 ◽  
Vol 16 (6) ◽  
pp. 599-610 ◽  
Author(s):  
S. C. Rodriguez ◽  
W. E. Dalbey
Keyword(s):  
Nervous System ◽  
Motor Activity ◽  
Microscopic Examination ◽  
Diisopropyl Ether ◽  
Sprague Dawley ◽  
Clinical Observations ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Group Sex ◽  
The Brain

The neurotoxicity potential of diisopropyl ether (DIPE) during subchronic exposures was evaluated in rats using a functional observational battery (FOB), automated motor activity, and neuropathology. Sprague-Dawley rats were exposed 5 dl wk for 13 weeks by inhalation to either 0, 450, 3250, or 7060 ppm DIPE. Body weights were recorded weekly and clinical observations were recorded prior to each exposure. The FOB and a measurement of motor activity were performed before the first exposure. The FOB was repeated following 2, 4, 8, and 13 weeks of exposure, and motor activity was determined following 4, 8, and 13 weeks of exposure. After completion of the final evaluations, the animals were intravascularly perfused with phosphate-buffered 5% glutaraldehyde. Microscopic examination of the brain, spinal cord, gasserian and dorsal root ganglia, and sciatic nerve was performed on six animals/ group/ sex exposed to 0 or 7060 ppm DIPE. Motor activity in a figure-eight maze and unperturbed activity in the FOB were decreased at week 4 in females exposed to 7060 ppm; activity in the FOB was also decreased in females exposed to 450 ppm at week 4. Other changes in the FOB appeared to be minor, and none were observed during microscopic examination of tissues from the nervous system. In conclusion, inhalation exposures to DIPE at concentrations as high as 7060 ppm for 13 weeks resulted in few observable effects on the nervous system.

A Neurotoxicity Assessment of High Flash Aromatic Naphtha

1993 ◽  
Vol 9 (6) ◽  
pp. 1047-1058 ◽  
Author(s):  
J. Fielding Douglas ◽  
Richard H. Mckee ◽  
Stuart Z. Cagen ◽  
Susan L. Schmitt ◽  
Patrick W. Beatty ◽  
...  
Keyword(s):  
Nervous System ◽  
Body Weight ◽  
Motor Activity ◽  
Human Exposure ◽  
Refining Process ◽  
Sprague Dawley ◽  
Catalytic Reforming ◽  
Aromatic Molecules ◽  
Sprague Dawley Rats ◽  
Group Sex

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide-boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 Aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent also known as High Flash Aromatic Naphtha (HFAN). A program was initiated to assess the toxicological properties of HFAN since there may be human exposure, especially in the workplace. The current study was conducted to assess the potential for neurotoxicity in the rat. Adult male Sprague-Dawley rats of approximately 300 grams body weight, in groups of twenty, were exposed by inhalation to HFAN for 90 days at concentrations of 0, 100, 500, and 1500 ppm. During this period the animals were tested monthly for motor activity and in afunctional observation battery. After three months of exposure, for 6 hours/day, 5 days/week, 10 animals/group/sex were sacrificed and selected nervous system tissue was examined histopathologically. No signs of neurotoxicity were seen in any of the evaluated parameters, nor was there evidence of pathologic changes in any of the examined tissues.

scholarly journals Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 11902-11907 ◽  
Author(s):  
Annapurna Pamreddy ◽  
Sooraj Baijnath ◽  
Tricia Naicker ◽  
Sphamandla Ntshangase ◽  
Sipho Mdanda ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Central Nervous System ◽  
Nervous System ◽  
Mass Spectrometry Imaging ◽  
Sprague Dawley ◽  
System P ◽  
Sprague Dawley Rats ◽  
The Central Nervous System ◽  
The Brain

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.

scholarly journals Subchronic Hepatotoxicity Evaluation of 2,3,4,6-Tetrachlorophenol in Sprague Dawley Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Deborah A. Banas ◽  
Russell S. Thomas
Keyword(s):  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Serum Chemistry ◽  
Sprague Dawley ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Body Weights

Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12–22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ≥25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 μg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25 mg/kg/day.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

Ultrastructural changes of Basolateral Amygdaloid nuclei in the Sprague Dawley rats brain following exposure to naphthalene balls

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K
Keyword(s):  
Structural Changes ◽  
Corn Oil ◽  
Chromatin Condensation ◽  
Ultrastructural Changes ◽  
High Dose ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Amygdaloid Nuclei

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.

The organum vasculosum laminae terminalis in immune-to-brain febrigenic signaling: a reappraisal of lesion experiments

2003 ◽  
Vol 285 (2) ◽  
pp. R420-R428 ◽  
Author(s):  
Andrej A. Romanovsky ◽  
Naotoshi Sugimoto ◽  
Christopher T. Simons ◽  
William S. Hunter
Keyword(s):  
Side Effects ◽  
Isotonic Saline ◽  
Alternative Interpretation ◽  
Sprague Dawley ◽  
Febrile Response ◽  
Drinking Response ◽  
Organum Vasculosum Laminae Terminalis ◽  
Sprague Dawley Rats ◽  
Organum Vasculosum ◽  
The Brain

The organum vasculosum laminae terminalis (OVLT) has been proposed to serve as the interface for blood-to-brain febrigenic signaling, because ablation of this structure affects the febrile response. However, lesioning the OVLT causes many “side effects” not fully accounted for in the fever literature. By placing OVLT-lesioned rats on intensive rehydration therapy, we attempted to prevent these side effects and to evaluate the febrile response in their absence. After the OVLT of Sprague-Dawley rats was lesioned electrolytically, the rats were given access to 5% sucrose for 1 wk to stimulate drinking. Sucrose consumption and body mass were monitored. The animals were examined twice a day for signs of dehydration and treated with isotonic saline (50 ml/kg sc) when indicated. This protocol eliminated mortality but not several acute and chronic side effects stemming from the lesion. The acute effects included adipsia and gross (14% of body weight) emaciation; chronic effects included hypernatremia, hyperosmolality, a suppressed drinking response to hypertonic saline, and previously unrecognized marked (by ∼2°C) and long-lasting (>3 wk) hyperthermia. Because the hyperthermia was not accompanied by tail skin vasoconstriction, it likely reflected increased thermogenesis. After the rats recovered from the acute (but not chronic) side effects, their febrile response to IL-1β (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers (∼0.5°C), the lesioned rats did not. However, the absence of the febrile response in the OVLT-lesioned rats likely resulted from the untreatable side effects. For example, hyperthermia at the time of pyrogen injection was high enough (39–40°C) to solely prevent fever from developing. Hence, the changed febrile responsiveness of OVLT-lesioned animals is given an alternative interpretation, unrelated to febrigenic signaling to the brain.

scholarly journals Quantitative Analysis of Diffusion Tensor Imaging in Chronic Hepatitis in Rats

2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu
Keyword(s):  
Chronic Hepatitis ◽  
Diffusion Tensor Imaging ◽  
Liver Fibrosis ◽  
Diffusion Tensor ◽  
Control Group ◽  
Sprague Dawley ◽  
Subcutaneous Injections ◽  
Sprague Dawley Rats ◽  
Pathological Stages ◽  
The Brain

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.

scholarly journals Biochemical and toxicological effects of methanolic extract of Asparagus africanus Lam in Sprague-Dawley rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9138
Author(s):  
Abubakar El-Ishaq ◽  
Mohammed A. Alshawsh ◽  
Kein Seong Mun ◽  
Zamri Chik
Keyword(s):  
Methanolic Extract ◽  
Histopathological Examination ◽  
Sprague Dawley ◽  
Toxicological Effects ◽  
Methanolic Extracts ◽  
Group I ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Histopathology Result ◽  
Scanty Information

Asparagus africanus Lam. is a plant used traditionally to treat different ailments. Currently, scanty information is available on its safety. The aim of this study is to determine the acute toxicity of the methanolic extract on vital organs and its associated biochemical parameters. Fifteen female Sprague-Dawley rats were divided into five groups. Group I served as normal control, groups II, III, IV, and V were orally administered single dose of crude extract dissolved in distilled water at 5 mg/kg BW, 50 mg/kg BW, 300 mg/kg BW and 2,000 mg/kg BW. Rats were observed for 14 days and body weights were recorded. On day 15, the rats were sacrificed and blood samples were collected for biochemical and haematological analyses, while the liver and kidneys were sampled for histopathological examination. Body weight and haematology parameters results showed significance difference (p < 0.05) among means of HGB, RDW, RBC, and MCHC; likewise, (p < 0.001) for WBC and platelet among treated groups. Histopathology result showed that kidneys appeared normal while livers were congested with mildly swollen hepatocytes and occasional binucleation. Focal lobular hepatitis was observed in all treated animals. However, hepatic enzymes were not significantly affected and no histopathological harmful effects were observed in kidney. In conclusion, methanolic extracts of A. africanus are safe up to 2,000 mg/kg BW. The obtained results could be used as a justification for the traditional application of the plant for treatment of various ailments.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  
Keyword(s):  
Motor Activity ◽  
Polyacrylic Acid ◽  
Muscle Tone ◽  
Clinical Signs ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Acute Neurotoxicity ◽  
Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

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