Comparative carcinogenicity of ring-halogenated 3-methyl-1-phenyltriazenes and their 3,3-dimethyl analogs at equimolar dose levels in male Sprague-Dawley rats

1986 ◽  
Vol 111 (2) ◽  
pp. 129-132 ◽  
Author(s):  
Martin R. Berger ◽  
George F. Kolar
Keyword(s):  
Sprague Dawley ◽  
Equimolar Dose ◽  
Sprague Dawley Rats ◽  
Dose Levels

Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

1990 ◽  
Vol 48 (3) ◽  
pp. 830-831
Author(s):  
S.D. Barnard ◽  
S.D. Warner
Keyword(s):  
Brown Pigment ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Gelatin Capsules ◽  
Pigment Granules ◽  
Sprague Dawley Rats ◽  
Hematoxylin And Eosin ◽  
Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

Androgen-mediated sex differences of cardiovascular responses in rats

1978 ◽  
Vol 235 (2) ◽  
pp. H242-H246 ◽  
Author(s):  
P. J. Baker ◽  
E. R. Ramey ◽  
P. W. Ramwell
Keyword(s):  
Sex Differences ◽  
Arachidonic Acid ◽  
Rank Order ◽  
Cardiovascular Responses ◽  
Sprague Dawley ◽  
Similar Treatment ◽  
Depressor Response ◽  
Sprague Dawley Rats ◽  
Significant Change ◽  
Dose Levels

Sex differences in the systemic depressor response to arachidonic acid (50 or 150 microgram/kg iv) were observed in intact and castrated anesthetized Sprague-Dawley rats. The rank order of responsiveness was: castrate males, castrate females, females, males; all four groups were significantly different (P less than 0.05) at the higher dose. Castrated males pretreated with testosterone (1 mg/kg sc) 5 or 7 days previously gave a response at the higher arachidonate dose levels that was of the same order as that obtained with intact males. Similar treatment of castrate males with androgen potentiated (P less than 0.05) the vasopressor action of norepinephrine (0.25 microgram/kg) on day 7 after the testosterone pretreatment. In contrast, treatment with depot estradiol (100 microgram/kg sc) in castrate males produced no significant change in the response to either of the vasoactive compounds on both days 5 and 7 after pretreatment. These data suggest that testosterone may be a significant factor in the development of sex differences in the cardiovascular systems of rats.

scholarly journals Mechanism of Erythropoietin Production by Cobaltous Chloride

Blood ◽  
1974 ◽  
Vol 44 (3) ◽  
pp. 339-346 ◽  
Author(s):  
Marilyn E. Miller ◽  
Donald Howard ◽  
Frederick Stohlman ◽  
Patricia Flanagan
Keyword(s):  
Respiratory Alkalosis ◽  
Sprague Dawley ◽  
Acid Base Balance ◽  
Acid Base ◽  
Erythropoietin Production ◽  
Sprague Dawley Rats ◽  
Base Balance ◽  
Subsequent Effect ◽  
Significant Measure ◽  
Dose Levels

Abstract Normal and nephrectomized Sprague-Dawley rats were treated with CoCl2 at three dose levels, 10, 20, and 25 µm/ 100 g body weight. The effects of this drug on acid-base balance were related to the production of erythropoietin. Within 6 hr after the administration of CoCl2 to normal rats, a dose-related respiratory alkalosis occurred associated with an increase in the affinity of hemoglobin for oxygen. This was followed by an increase in the production of erythropoietin. Nephrectomy altered the acid-base balance of the animal such that a profound acidosis occurred after the administration of CoCl2 with an associated decrease in the affinity of hemoglobin for oxygen. Erythropoietin could not be detected in these nephrectomized rats given CoCl2. These findings demonstrate that the production of erythropoietin after the administration of CoCl2 is related in significant measure to changes in acid-base balance with its subsequent effect on the affinity of hemoglobin for oxygen.

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 Subacute Intramuscular Toxicity of the Acetylcholinesterase Reactivating Agent HI-6 in Rats and Dogs

1993 ◽  
Vol 12 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Barry S. Levine ◽  
Michael J. Tomlinson
Keyword(s):  
Injection Site ◽  
Creatine Kinase Activity ◽  
High Dose ◽  
Sprague Dawley ◽  
Hi 6 ◽  
Sprague Dawley Rats ◽  
High Doses ◽  
Hematology Parameters ◽  
Dose Levels ◽  
Dose Injection

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture, and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.

scholarly journals Subchronic toxicity of lyophilized apoaequorin protein powder in Sprague-Dawley rats

2018 ◽  
Vol 2 ◽  
pp. 239784731875690
Author(s):  
Mark R. Bauter ◽  
Odete Mendes
Keyword(s):  
Active Ingredient ◽  
Calcium Binding ◽  
Clinical Pathology ◽  
Female Rats ◽  
Test Substance ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Dose Levels

Apoaequorin is a bioluminescent calcium-binding apoprotein endogenous to the Aequorea species of jellyfish and is commercially available in a dietary supplement in support of brain and cognitive health. Results from a previous 90-day subchronic oral gavage study established the no-observed-adverse-effect-level (NOAEL) of lyophilized apoaequorin protein powder (LAPP) at 666.7 mg/kg/day. The current 90-day oral gavage study in Sprague-Dawley rats administered dose levels of 1000, 2000, and 4000 mg/kg/day of test substance as received. These doses are expressed as milligram of supplement with the amounts of apoaequorin based on the analysis of the percentage of active ingredient. The corresponding amounts of apoaequorin protein are 603, 1206, and 2412 mg/kg/day. These dose levels target approximately 4221, 8442, and 16,844 times more than the expected human oral intake. There were no mortalities, clinical observations, ophthalmological, clinical pathology, or histopathological changes attributable to LAPP administration. Changes in mean body weight and feed efficiency, without other correlating clinical or pathological or other toxicologically relevant findings, were considered to be of little toxicological significance. Therefore, the NOAEL for LAPP administered orally up to 90 days was 4000 mg/kg/day (2412 mg/kg/day based on 603 mg/g or 60.3% active ingredient, apoaequorin protein), the highest dose tested in male and female rats.

Effects of Subcutaneously Injected Graded Doses of All-Trans Retinoic Acid and All-Trans Retinoyl beta-Glucuronide on the Outcome of Pregnancy in Sprague-Dawley Rats

2002 ◽  
Vol 72 (4) ◽  
pp. 229-235 ◽  
Author(s):  
Amanda Ueltschy ◽  
Desiree Gunning ◽  
Arun Barua ◽  
James Olson
Keyword(s):  
Body Weight ◽  
Retinoic Acid ◽  
Equivalent Amount ◽  
Sprague Dawley ◽  
Subcutaneous Injections ◽  
Live Births ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Sprague Dawley Rats ◽  
Dose Levels

The effects of single subcutaneous injections (sc) of graded doses (20, 40, 80, 160, 320, and 480 mumol/kg body weight (BW) of all-trans retinoic acid (RA) and all-trans retinoyl beta-glucuronide (RAG) on day 8.5 of gestation on the outcome of pregnancy in Sprague-Dawley rats was studied. At dose levels of 20, 40, and 80 mumol/kg BW, neither RA nor RAG showed any adverse maternal or fetal effects. However, at dose levels of 160, 320, and 480 mumol/kg, RA was found to be much more toxic than RAG to both mother and fetus. Fetuses of animals receiving a 160 mumol/ kg BW dose of RA were significantly reduced in weight and length, while animals receiving the same dose of RAG had fetuses of normal size. RA doses of 320 and 480 mumol/ kg BW resulted in symptoms of maternal toxicity and even death. In contrast, RAG at these high levels produced no signs of maternal toxicity. RAG doses of 320 and 480 mumol/ kg BW were also less toxic to fetuses. RA doses of 320 mumol/kg BW resulted in only 8% live births, while animals treated with an equivalent amount of RAG experienced 95% live births. Animals receiving a dose of 480 mumol/kg BW of RA had no live births, but similar doses of RAG resulted in 28% live births and pups of normal size.

scholarly journals Safety assessment of Gossence™ (galactooligosaccharides): Genotoxicity and general toxicity studies in Sprague Dawley rats

2019 ◽  
Vol 3 ◽  
pp. 239784731986037 ◽  
Author(s):  
Manish Jain ◽  
S Narayanan ◽  
Deepika Pandey Tiwari ◽  
Bibhuti Ranjan ◽  
Avinash Jadhav ◽  
...  
Keyword(s):  
Chromosomal Aberration ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Prolonged Treatment ◽  
Sprague Dawley ◽  
Toxicity Studies ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Dose Levels

Galactooligosaccharides (GOS) used as prebiotics are one of the major constituents of the infant milk formulas. GOS (Gossence™) is produced by a patented process of biotransformation of lactose; hence toxicology studies were carried out to assess its safety. The objective of the present study was to evaluate the general and genetic toxicity of Gossence™. In 14-day and subchronic (90-day) oral toxicity studies in Sprague Dawley rats, daily administration of GOS at dose levels of 1000, 2000, or 5000 mg/kg (equivalent to 1347, 2694, and 6735 mg/kg/day of Gossence™, respectively) did not cause any mortality, or clinical signs, and changes in body weights, feed consumption, hematology, clinical chemistry, and urinalysis. In 90-day study, no changes in ophthalmological and neurological findings were observed. Significant increases in the cecum weights (with and/or without content) at dose levels of ≥2000 mg/kg were observed in both 14-day and 90-day studies. Based on the results of 90-day study, the no-observed-adverse-effect-level for GOS is 5000 mg/kg/day which is equivalent to 6735 mg Gossence™/kg/day. In the bacterial reverse mutation test, there was no significant increase in the mean numbers of revertants at the tested concentrations. Gossence™ was not mutagenic up to 5000 µg/plate. In chromosomal aberration test, there was no statistically significant increase in the number of percent aberrant metaphase for the Gossence™. Gossence™ is non-clastogenic (negative) in the in vitro chromosomal aberration test using human peripheral blood lymphocyte during short and prolonged treatment.

Effects of uranium depletion on 1α-hydroxylase in kidney of rats

2010 ◽  
Vol 30 (7) ◽  
pp. 786-790 ◽  
Author(s):  
Minfen Yan ◽  
Gaoren Zhong ◽  
Linfeng Gao ◽  
Xiqiao Xia ◽  
Lihua Wang ◽  
...  
Keyword(s):  
Active Form ◽  
Underlying Mechanism ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Sprague Dawley Rats ◽  
Dose Levels ◽  
Medium Dose

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.

Developmental Toxicity of Thiodiglycol in Sprague-Dawley Rats

2007 ◽  
Vol 26 (4) ◽  
pp. 365-371 ◽  
Author(s):  
John T. Houpt ◽  
Lee C. B. Crouse ◽  
Richard A. Angerhofer ◽  
Glenn J. Leach ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Developmental Toxicity ◽  
Female Rats ◽  
Main Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels

Thiodiglycol (TG), a hydrolysis product of sulfur mustard (HD), is a potential contaminant of soil and water at certain military sites. To establish developmental toxicity criteria for TG, an oral developmental toxicity study was conducted in Sprague-Dawley rats. Neat thiodiglycol (99.9 %) was administered orally to mated female rats from gestation days (GDs) 5 through 19. The day of positive mating was considered day 0. A pilot study was conducted with TG at dose levels 250, 500, 1000, 2000, or 5000 mg/kg to select suitable doses for the main study. In the main study, three groups of rats (25/group) received TG by gavage at dose levels of 430, 1290, or 3870 mg/kg/day. A fourth group served as a sham control. On day 20 of gestation, all females were euthanized and a cesarean section performed. Litters were examined for soft tissue and skeletal alterations. Maternal toxicity was limited to dams receiving TG at 3870 mg/kg/day. At this dose, body weights and food consumption were reduced during certain periods of gestation. Fetuses derived from those dams exhibited a nonstatistically significant increased incidence of variations when compared to controls. Fetal body weights in the 3870 mg/kg/day group were significantly lower than controls. There was no increased incidence of anomalies when thiodiglycol-treated fetuses were compared to controls. It was concluded that TG did not produce terata. Developmental toxicity (decreased fetal weights and associated delays in development) occurred only at the maternally toxic dose of 3870 mg/kg. It appears that 1290 mg/kg/day could be considered no observed adverse effect level (NOAEL) for oral developmental toxicity. The lowest observed adverse effect level (LOAEL) was 3870 mg/kg for maternal toxicity.

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