Oral Toxicity of 3-Nitro-1,2,4-triazol-5-one in Rats

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d.

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

International Journal of Toxicology ◽

10.1177/1091581812437974 ◽

2012 ◽

Vol 31 (3) ◽

pp. 250-256 ◽

Cited By ~ 4

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.

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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

International Journal of Toxicology ◽

10.1177/1091581813487564 ◽

2013 ◽

Vol 32 (4_suppl) ◽

pp. 59S-74S ◽

Cited By ~ 2

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.

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Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague–Dawley Rats

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17103404 ◽

2020 ◽

Vol 17 (10) ◽

pp. 3404

Author(s):

Zaida Zainal ◽

Augustine Ong ◽

Choo Yuen May ◽

Sui Kiat Chang ◽

Afiqah Abdul Rahim ◽

...

Keyword(s):

Lethal Dose ◽

Pharmaceutical Formulations ◽

Toxicity Study ◽

Sprague Dawley ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Organ Weights ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague–Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg−1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg−1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg−1 d−1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.

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Developmental Toxicity of Thiodiglycol in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1080/10915810701461993 ◽

2007 ◽

Vol 26 (4) ◽

pp. 365-371 ◽

Cited By ~ 2

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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Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581814547541 ◽

2014 ◽

Vol 33 (5) ◽

pp. 393-402 ◽

Cited By ~ 3

Author(s):

Richard A. Angerhofer ◽

Mark W. Michie ◽

Glenn J. Leach ◽

Mark S. Johnson ◽

Gunda Reddy

Keyword(s):

Body Weight ◽

Food Consumption ◽

Sulfur Mustard ◽

Female Rats ◽

Male Rats ◽

Control Individual ◽

Sprague Dawley ◽

Oral Toxicity ◽

Male And Female Rats ◽

Sprague Dawley Rats

Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.

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

Journal of the American College of Toxicology ◽

10.3109/10915819009078758 ◽

1990 ◽

Vol 9 (5) ◽

pp. 497-506 ◽

Cited By ~ 3

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.

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Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581815585568 ◽

2015 ◽

Vol 34 (4) ◽

pp. 336-345 ◽

Cited By ~ 3

Author(s):

Wilfred C. McCain ◽

Lee C. B. Crouse ◽

Mathew A. Bazar ◽

Laurie E. Roszell ◽

Glenn J. Leach ◽

...

Keyword(s):

Food Consumption ◽

Male Rats ◽

High Dose ◽

Histopathological Changes ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Male And Female ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

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