scholarly journals Subchronic Toxicity Studies of 2,4,6-Trichlorophenol in Sprague-Dawley Rats

1990 ◽  
Vol 9 (5) ◽  
pp. 497-506 ◽  
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lillian Jones ◽  
Norbert P. Page ◽  
Michael J. Parnell ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Adrenal Glands ◽  
Corn Oil ◽  
Clinical Chemistry ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

2,4,6-Trichlorophenol (TCP) has been found in drinking water as a result of its use as a fungicide and due to its inadvertent production in the water purification process. This study was conducted since information on the toxicity from repeated ingestion was inadequate. Male and female Sprague-Dawley rats were gavaged with TCP administered in corn oil (2 ml/kg body weight) for 90 consecutive days at dose levels of 0, 80, 240, and 720 mg/kg per day. Treatment-related effects were observed at the highest dose (720 mg/kg/day) and consisted of salivation, urine stains on the fur, increase in absolute and relative weights of the kidneys, liver, adrenal glands, and testes. At this dose, increases were seen in serum protein, albumin, and alanine aminotransferase (ALT), with a decrease in urinary pH. Some effects observed at 240 mg/kg per day were an increase in the absolute and relative weights of the liver and adrenal glands in females, relative liver weights in males, and an increase in serum albumin in males. No treatment-related effects were observed at 80 mg/kg per day. No mortality or significant effects were observed at any dose level for body weight, food consumption, ophthalmic lesions, hematology, gross pathology, or histopathology. Based on clinical chemistry and organ weight changes, it appears that the liver, kidney, and adrenal glands were target organs for systemic toxicity to TCP in this study, although this was not correlated with histopathology lesions. It was concluded that 240 mg/kg/day represents a lowest observed adverse effect level (LOAEL), although the toxic effects were minimal. The no observed adverse effect level (NOAEL) for subchronic exposure to TCP by the oral route was 80 mg/kg per day.

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

2012 ◽  
Vol 31 (3) ◽  
pp. 250-256 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Kathleen A. Funk ◽  
Russell S. Thomas
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Sprague Dawley ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

scholarly journals Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sittichai Koontongkaew ◽  
Orapan Poachanukoon ◽  
Seewaboon Sireeratawong ◽  
Thaweephol Dechatiwongse Na Ayudhya ◽  
Parirat Khonsung ◽  
...  
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Hematological Parameters ◽  
Safety Evaluation ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Zingiber Cassumunar

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P<0.05). The weights of lung and kidney of treated females were increased (P<0.05). Treated males were increased in spleen and epididymis weights (P<0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

Comparative Toxicology Studies in Sprague-Dawley Rats, Rhesus Monkeys, and New Zealand White Rabbits to Determine a No Observed Adverse Effect Level for 1,1′-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] Dimethanesulfonate

2013 ◽  
Vol 32 (4_suppl) ◽  
pp. 59S-74S ◽  
Author(s):  
Merrill R. Osheroff ◽  
Dean J. Kobs ◽  
Matthew Buccellato ◽  
Claire R. Croutch ◽  
Laura E. Elcock ◽  
...  
Keyword(s):  
Adverse Effect ◽  
New Zealand ◽  
Rhesus Monkeys ◽  
Clinical Pathology ◽  
Intramuscular Administration ◽  
Sprague Dawley ◽  
Single Dose Study ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Studies were conducted in Sprague-Dawley rats, New Zealand White (NZW) rabbits, and rhesus monkeys to characterize the toxicity of 1,1′-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) following intramuscular administration. Rats received MMB4 DMS once daily for 7 days at 100, 200, 400, and 800 mg/kg/d; rabbits received a range of dose levels in 3 separate 7-day studies from 3 to 800 mg/kg/d and in a single-dose study from 50 to 200 mg/kg; and monkeys received MMB4 DMS at 150 to 600 mg/kg/d. Mortality was noted in rats and rabbits administered ≥200 mg/kg. All monkeys survived until scheduled termination. Adverse clinical observations were noted in the rats at ≥400 mg/kg/d and in rabbits administered ≥200 mg/kg; no adverse findings were noted in the monkeys. Clinical pathology changes were noted in the rabbit related to cardiac and renal function. In the rabbit and monkey, elevations in myoglobin, alanine aminotransferase/aspartate aminotransferase, platelets, creatine kinase, and coagulation factors were related to local inflammation at the intramuscular administration site. Light microscopic examination at the injection sites revealed acute skeletal muscle necrosis in vehicle control and treated groups. Target tissues in the rabbit studies were identified as kidney, heart, and lungs at ≥100 mg/kg/d. All changes noted in all the species demonstrated partial to complete recovery comparable to control values or to a clinically irrelevant level of effect. The NZW rabbit was the most sensitive species, and the no observed adverse effect level (NOAEL) was determined as 50 mg/kg/d; the NOAEL in the rat was 100 mg/kg/d; and the NOAEL in rhesus monkeys was >600 mg/kg/d.

A Study of the Developmental Toxicity Potential of Pentachlorophenol in the Rat

2001 ◽  
Vol 20 (6) ◽  
pp. 353-362 ◽  
Author(s):  
Bruce K. Bernard ◽  
Alan M. Hoberman
Keyword(s):  
Adverse Effect ◽  
Corn Oil ◽  
Developmental Toxicity ◽  
Wood Preservative ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Fetal Toxicity ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Effect Level

Pentachlorophenol (penta, CAS #87–86–5) is primarily used as a wood preservative. As part of the USEPA pesticide reregistration process, the developmental toxicity (embryo-fetal toxicity and teratogenic potential) of commercially available penta was studied following oral gavage to presumed pregnant female Sprague-Dawley rats (Crl:CD BR VAF/Plus Subdivision F, 83–3). Both study design and penta purity met the requirements of the USEPA. Doses of 0 (corn oil), 10, 30, and 80 mg/kg/day were administered to the rats at concentrations of 0, 2, 6, and 16 mg/ml, respectively from day 6 to day 15 of presumed gestation. The dosage volume was 5 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before intubation. The rats were sacrificed on day 20 of presumed gestation and necropsied. The number of corpora lutea in each ovary was recorded. The uterus was examined for pregnancy, number and distribution of implantations, early and late resorptions and live and dead fetuses. Each fetus was weighed, sexed, and examined for gross external, soft tissue and skeletal alterations. The no-observable-adverse-effect-level (NOAEL) for maternal toxicity in rats was determined to be 30 mg/kg/day of penta. The developmental NOAEL for penta in rats was also found to be 30 mg/kg/day. The lowest-observable-adverse-effect-level (LOAEL) for penta developmental toxicity (80 mg/kg/day) was associated with increased resorptions, reduced live litter size and fetal body weights, and caused increased malformations and variations. These NOAELs, derived using USEPA approved study designs, are higher than those previously reported using penta that is no longer commercially available in studies with non-approved experimental designs. Penta should not be identified as a selective developmental toxicant in the rat because adverse effects on development of rat conceptuses occurred only at maternally toxic dosages.

scholarly journals Toxicological evaluation of alpha-galacto-oligosaccharides shows no adverse effects over a 90-day study in rats

2017 ◽  
Vol 1 ◽  
pp. 239784731771640
Author(s):  
Claire Kruger ◽  
Nicole Beauchamp ◽  
Virginie Modeste ◽  
Fanny Morel-Despeisse ◽  
Eric Chappuis
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Toxicological Evaluation ◽  
Organ Weights ◽  
Naturally Occurring ◽  
Adverse Effect Level ◽  
Effect Level

AlphaGOS®, an alpha-galacto-oligosaccharides product, is a mixture of bi-, tri- and tetrasaccharides derived from oligosaccharides in the raffinose family of oligosaccharides (RFOs), naturally occurring plant-derived sugars. RFOs are alpha α-1,6-linked chains of D-galactose attached to the 6-position of D-glucose and differ from the currently commercially available beta-galacto-oligosaccharides products in the chirality and glyosidic bonds. In order to determine the safety of AlphaGOS, rats were given 2000 mg AlphaGOS/kg/day daily via gavage over 90 days. Daily assessments of the animals showed no adverse clinical signs. No adverse treatment-related changes in feed consumption, body weight, clinical chemistry or hematology were noted. There were no adverse treatment-related changes in organ weights, gross or histopathology. Given these findings, it can be concluded that the no observed adverse effect level for AlphaGOS is greater than 2000 mg/kg/day.

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.

Evaluation of the Developmental Toxicity of Linalool in Rats

2008 ◽  
Vol 27 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Valerie T Politano ◽  
Elise M Lewis ◽  
Alan M Hoberman ◽  
Mildred S Christian ◽  
Robert M Diener ◽  
...  
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Weight Gains ◽  
Adverse Effect Level ◽  
Effect Level

The developmental toxicity of linalool, a widely used fragrance ingredient, was evaluated in presumed pregnant Sprague-Dawley rats (25/group). Oral dosages of 0, 250, 500, or 1000 mg/kg/day linalool were administered by gavage on gestational days 7 to 17. The presence of spermatozoa and/or a copulatory plug in situ was designated as gestational day 0. Rats were observed for viability, clinical signs, body weights, and feed consumption. Caesarean sectioning and necropsy occurred on gestational day 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. There were no maternal deaths, clinical signs, or gross lesions that were considered related to linalool. During the dosage period, mean relative feed consumption was significantly reduced by 7% and mean body weight gains were reduced by 11% at 1000 mg/kg/day. During the postdosage period, feed consumption values at 1000 mg/kg/day were significantly higher than vehicle control values, which corresponded to the increase in body weight gains during this period. Caesarean section and litter parameters, as well as fetal alterations, were not affected by linalool at any of the three dosages tested. On the basis of these data, the maternal no observed adverse effect level (NOAEL) of linalool is 500 mg/kg/day, whereas the developmental NOAEL is ≥ 1000 mg/kg/day. It is concluded that linalool is not a developmental toxicant in rats at maternal doses of up to 1000 mg/kg/day.

Effect of Gasohol on The Rat Liver

1997 ◽  
Vol 3 (S2) ◽  
pp. 49-50
Author(s):  
B.A. MacDuff ◽  
A. Singh ◽  
I. Chu
Keyword(s):  
United States ◽  
Body Weight ◽  
Adverse Effects ◽  
Rat Liver ◽  
Corn Oil ◽  
The United States ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Although there are a variety of gasoline ethanol mixtures proposed as neat fuels (ethanol 85% + gasoline 15% = E85; E95) for automobiles, gasohol (gasoline 90% + ethanol 10%) is presently used as a fuel in the United States. The adverse effects, if any, of gasohol ingestion are unknown; effects on the liver of rats administered gasohol are examined in this study.Twenty-four female Sprague-Dawley rats received daily, via gavage, one of the three concentrations of gasohol for 28 days; LD50/20, LD50/100 and LD50/1000, where LD50 = 1.5g ethanol / kg body weight (bw) and 14g gasoline / kg bw. The LD50 was based on that of gasoline, which was obtained from literature value.1 The amount of ethanol added to stock gasohol was only 1/10 its LD50, required to maintain the gasoline ethanol proportion of 9:1. Gasohol was administered in corn oil with total volume 10 ml. Animals that received only corn oil served as controls.

scholarly journals A 4-Week Repeated Oral Dose Toxicity Study of Ssanghwa-Tang in Crl:CD Sprague Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Safety Information ◽  
Experimental Period ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Herbal Formula ◽  
Sprague Dawley ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Ssanghwa-tang (SHT), a traditional herbal formula, has been widely used to recover fatigue or consumptive disease after an illness. Along with much attention to herbal formula, the concerns about the safety and toxicity have arisen. To establish the safety information, SHT was administrated in Crl:CD Sprague Dawley rats at a daily dose of 0, 1000, 2000, and 5000 mg/kg for 4 weeks. During the test periods, we examined the mortality, clinical observation, body weight change, food consumption, organ weights, hematology, serum biochemistry, and urinalysis parameters. No changes of mortality and necropsy findings occurred in any of the groups during the experimental period. In either sex of rats treated with SHT at 5000 mg/kg/day, changes were observed in food intake, reticulocyte, total bilirubin, some urinalysis parameters, and relative organ weights. The results indicated that SHT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. This dosage was considered no observed adverse effect level (NOAEL) and was appropriate for a 13-week subchronic toxicity study.

scholarly journals Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-25
Author(s):  
Gajanan Deshmukh ◽  
Suresh B. Venkataramaiah ◽  
Chandrashekar M. Doreswamy ◽  
Mohan C. Umesh ◽  
Rajesh B. Subbanna ◽  
...  
Keyword(s):  
Biologically Active ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Endogenous Antioxidant ◽  
In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

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