scholarly journals Thirteen-week nose-only inhalation exposures of propylene glycol aerosols in Sprague Dawley rats with a lung systems toxicology analysis

2021 ◽  
Vol 5 ◽  
pp. 239784732110210
Author(s):  
T Langston ◽  
J Randazzo ◽  
U Kogel ◽  
J Hoeng ◽  
F Martin ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Lung Tissue ◽  
Reference Group ◽  
Clinical Chemistry ◽  
Mucous Cell ◽  
High Dose ◽  
Sprague Dawley ◽  
Systems Toxicology ◽  
Terminal Organ ◽  
Sprague Dawley Rats

The objectives of this study were to increase PG exposure above concentrations tested by Suber et al. and use systems toxicology analysis of lung tissue to understand molecular events. Sprague Dawley rats were exposed to filtered air (sham), propylene glycol/water (PG/W; 90:10) or a propylene glycol/vegetable glycerin/water (PG/VG/W; 50:40:10) reference. The reference group was added at the high dose to observe any changes that might be associated with a carrier more in line with e-vapor products. Macroscopic examinations and terminal organ weights revealed no observations associated with exposure to PG/W or reference. Food consumption and body weights were unaffected by PG/W or reference when compared to sham. No exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or BALF cytology and clinical chemistry. Although clinical observations of dried red material around the nose in the high dose PG/W group were reported, histopathology showed no nasal hemorrhaging which was previously reported by Suber et al. Non-adverse PG/W and reference related findings of minimal mucous cell hyperplasia were noted in nasal cavity section II. No other exposure-related findings were noted in the primary or recovery necropsies. A systems toxicology analysis on lung tissue showed no statistically significant differentially expressed transcripts or proteins compared to the sham group. The endpoints measured from the PG/W high dose group did not differ significantly from those in the more common carrier PG/VG/W. As anticipated, exposure to PG aerosols was slightly irritating but well tolerated. Accordingly, the highest PG exposure (5 mg/L, 6 hrs/day) was regarded as the NOAEC, corresponding to a PG delivered dose of 1,152 mg/kg/day in rats.

Repeated-Dose and Subchronic Toxicity Studies of 2,2,2-Trichloroethanol in Sprague-Dawley Rats

1991 ◽  
Vol 10 (2) ◽  
pp. 223-232
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lucille M. Garner ◽  
Norbert P. Page ◽  
Greg R. Olson
Keyword(s):  
Toxic Effect ◽  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Lactic Dehydrogenase ◽  
Target Organ ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Levels

Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.

scholarly journals Juvenile toxicity study of Gossence™ (galactooligosaccharides) in Sprague Dawley rats

2020 ◽  
Vol 4 ◽  
pp. 239784732091321
Author(s):  
Manish Jain ◽  
Moninder Kaur ◽  
Deepika Pandey Tiwari ◽  
Chandrashekara Vishwanath ◽  
Nataraju Javaregowda ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Pediatric Population ◽  
Recovery Period ◽  
Clinical Signs ◽  
Weighted Average ◽  
Organ Weight ◽  
High Dose ◽  
Average Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Gossence™ (galactooligosaccharide; GOS) is a prebiotics and used as one of the major constituents in infant milk formulas that act as a functional food. Gossence is manufactured by Tata Chemicals Ltd, India, through a patented process of biotransformation of lactose. A toxicology study in juvenile rats was carried out to assess the safety profile of Gossence intended for pediatric population. The objective of this study is to assess the potential systemic toxicity of Gossence when administered through gavage at dose levels of 1000, 2000, or 5000/3000 mg/kg/day (equivalent to 1347, 2694, and 6735/4041 mg/kg/day of GOS, respectively) to juvenile Sprague Dawley rats from postnatal day (PND) 4 to PND 52 (i.e. total 49 days of dosing period). A separate group of animals were treated with vehicle (purified Milli Q water) for a similar duration. The following parameters were evaluated during the study period: morbidity/mortality check, clinical signs, body weights, body weight changes, food consumption, functional observational battery, motor activity, postnatal developmental observations, hematology, clinical chemistry, urinalysis, organ weight, gross pathology, and histopathology. During dosing phase, the high-dose group, 5000 mg/kg/day, was reduced to 3000 mg/kg/day (equivalent to 4041 mg/kg/day dose of GOS) from day 16 (PND 19) onward, due to clinical signs of watery feces and yellow color stains at urogenital region and mortality in two animals on day 15 (PND 18) of the study. Time-weighted average dose for 5000 mg/kg/day was equivalent to 3600 mg/kg/day. No further deaths or clinical signs were noticed in animals at 3000 mg/kg/day from day 18 (PND 21) of dosing phase to until terminal euthanization. At the terminal euthanization, there were no test item-related gross changes observed in all surviving rats except for, an increased cecum size in some of the rats at 5000/3000 mg/kg/day, which correlated with the increased weights of cecum with contents during organ weight recording, but this had no correlating light microscopic changes during histological examination. The cecal enlargement was completely recovered following the 14-day recovery period. The no-observedadverse-effect level is 3000 mg/kg/day for Gossence, which is equivalent to 4041 mg/kg/day of GOS in both sexes.

A Subchronic Toxicity Study of Phosflex 51B in Sprague-Dawley Rats

2001 ◽  
Vol 20 (5) ◽  
pp. 269-274 ◽  
Author(s):  
Ralph I. Freudenthal ◽  
David Brandwene ◽  
Welmoed Clous
Keyword(s):  
Food Consumption ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Significant Treatment ◽  
Sprague Dawley Rats ◽  
The Mean ◽  
Microscopic Pathology

Phosflex 51B is a flame retardant plasticizer that is blended with polyvinyl chloride films to effectively control product flammability. Its composition places it in the butylated triphenyl phosphate category. Previous studies have shown Phosflex 51B to have low acute toxicity, to lack teratogenic and mutagenic activity, and to not induce delayed peripheral neuropathy. The present study was conducted to determine the toxicity of Phosflex 51B after repeated dietary exposure. Four groups, each consisting of 20 male and 20 female Sprague-Dawley rats, received rodent diet containing either 0, 100, 400, or 1600 ppm for 90 days. Parameters measured include body weight, food consumption, clinical observations, hematology, clinical chemistry, and cholinesterase activity. Tissues were examined at necropsy for gross changes and were processed for microscopic pathology. There were no significant treatment-related effects on body weights, food consumption, hematology and clinical chemistry, or cholinesterase values. A significant increase was observed in the absolute and relative mean weights of livers in high-dose male rats, the mean relative fiver weights of the high-dose female animals, the mean relative kidney weights of the high-dose male rats, and the mean absolute weights of the adrenal glands from high-dose female rats. Neither gross nor microscopic pathology examinations revealed tissue changes in these organs or in any other organs. Although increases in fiver, kidney, and adrenal weights were observed in certain animals in the 1600-ppm high-dose group, the administration of Phosflex 51B did not result in significant treatment-related adverse effects at dietary dose levels of 100 and 400 ppm. The no-observable-effect level (NOEL) in this study is 400 ppm.

A Subchronic Toxicity Study of Fyrol PCF in Sprague-Dawley Rats

1999 ◽  
Vol 18 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Ralph I. Freudenthal ◽  
Richard T. Henrich
Keyword(s):  
Cholinesterase Activity ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Brain Cholinesterase ◽  
Sprague Dawley Rats

Fyrol PCF is a flame retardant chemical widely used to control the flam mability of rigid polyurethane foams and polyester foam systems. It has moderate acute toxicity and was shown to lack mu-tagenic activity. The present study was conducted to determine the toxicity of Fyrol PCF after repeated dietary exposure. Five groups, each consisting of 20 male and 20 female Sprague-Dawley rats, a diet containing either 0, 800, 2500, 7500, or 20,000 ppm Fyrol PCF for 90 days. Data collected include clinical observations, food consumption, body weights, organ weights, urinalysis, hematology, clinical chemistry, brain cholinesterase activity, and gross and microscopic pathology. The mean body weight of animals receiving 20,000 ppm was significantly lower than control values for most study weeks. No clinical signs were noted during cage-side observations. Liver weights were increased in male rats in all treatment groups, and in female rats in both the mid-and high-dose groups. No treatment-related histopathologic changes were observed in the livers of animals that 800, 2500, or 7500 ppm Fyrol PCF; however very mild periportal hepato-cellular swelling was seen in certain of the 20,000 ppm animals. Mean kidney weights were significantly greater in the male animals given 2500, 7500, and 20,000 ppm. Very mild cortical tubular degenerative changes were found in kidneys of male rats that 7500 ppm or 20,000 ppm and in female animals that ingested 20,000 ppm Fyrol PCF. An increase in the incidence of very mild thyroid follicular changes was found in the two highest dose groups. Fyrol PCF did not affect hematology or clinical chemistry parameters, nor did it significantly inhibit brain cholinesterase activity. None of the observed minimal treatment-related changes appear to have human relevance, because they occurred only at the highest doses used in the study. The no observable effect level in this study is 2500 ppm. Fyrol PCF demonstrated low subchronic toxicity in this study.

scholarly journals Antidepressant-Like Effect of Lipid Extract ofChanna striatusin Postpartum Model of Depression in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Mohamed Saleem Abdul Shukkoor ◽  
Mohamad Taufik Hidayat Bin Baharuldin ◽  
Abdul Manan Mat Jais ◽  
Mohamad Aris Mohamad Moklas ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Postpartum Period ◽  
Estradiol Benzoate ◽  
Plasma Corticosterone ◽  
Positive Control ◽  
Lipid Extract ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malay Population ◽  
Swimming Test

Postpartum depression affects 15% of women.Channa striatus, a freshwater fish, is consumed in local Malay population as a rejuvenating diet during postpartum period. This study evaluated the antidepressant-like effect of lipid extract ofC. striatusfillet and its mechanism of action in female Sprague-Dawley rats in postpartum model of depression. The rats were ovariectomized and treated with high dose of progesterone and estradiol benzoate for 23 days to have hormone-simulated pregnancy. The day 24 and afterwards were considered as the postpartum period. During the postpartum period, lipid extract was administered at 125, 250, and 500 mg/kg through intraperitoneal route for 15 days. Fluoxetine (10 mg/kg) was used as the positive control. On postpartum day 15, the animals were tested in forced swimming test (FST) and open field test (OFT) followed by biochemical analysis. Withdrawal of hormone administration during the postpartum period induced depressive-like behavior in FST. Administration of lipid extract reversed that depressive-like behavior at 125, 250, and 500 mg/kg in FST. In OFT, it decreased the exploratory activity. The mechanism of the antidepressant-like effect may be mediated through the decrease in plasma corticosterone, increase in plasma oxytocin, and decrease in nuclear factor-kappa B in prefrontal cortex of rats.

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.

Toxicity of aerosols of propylene glycol, vegetable glycerin and nicotine in Sprague-Dawley rats in a 90-d OECD 413 sub-chronic inhalation study

2016 ◽  
Vol 258 ◽  
pp. S201
Author(s):  
B. Phillips ◽  
D. Sharma ◽  
D. Sciuscio ◽  
E. Veljkovic ◽  
S. Lebrun ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Sprague Dawley ◽  
Inhalation Study ◽  
Sprague Dawley Rats

scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

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.

Impaired follicular development and endocrine disorders in female rats by prepubertal exposure to toxic doses of cadmium

2020 ◽  
Vol 36 (2) ◽  
pp. 63-75
Author(s):  
Saman Saedi ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Mehdi Totonchi ◽  
Mohammad Dadpasand ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Endocrine System ◽  
Follicular Development ◽  
Female Rats ◽  
High Dose ◽  
Endocrine Disorders ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Puberty Onset ◽  
Different Doses

Cadmium (Cd) has been associated with several physiological problems including reproductive and endocrine system dysfunction resulting in temporary infertility. The principal objective of this project was to investigate the effects of prepubertal exposure to toxic doses of Cd on puberty onset, the endocrine system, and follicular development. For this purpose, 16 female Sprague-Dawley rats weaned on postnatal day (PND) 21 were randomly divided into 4 groups ( n = 4 per group). The treatments were as follows: 0, 25, 50, and 75 mg/kg/day of cadmium chloride (CdCl2) by oral gavage from PND 21 to observation of first vaginal opening (VO). The results demonstrated that prepubertal exposure to different doses of CdCl2 delays the age of VO, first diestrus, and first proestrus via altering the concentrations of estradiol and progesterone. The low level of these steroid hormones contributed to lower differentiation and maturation of follicles and it finally led to reduced ovarian reservoir of follicles and impaired follicular development. The number of atretic follicles and secondary follicles with premature cavity increased in rats that received a high dose of CdCl2, whereas the number of secondary follicles and corpora luteum decreased in the same circumstances. Taken together, these data suggest that prepubertal exposure to toxic doses of Cd delays the onset of puberty via disorderliness in the concentration of steroid hormones and reduces the ovarian reservoir of follicles, as well as folliculogenesis.

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