scholarly journals Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Ray A. Matulka ◽  
Ikuo Matsuura ◽  
Tohru Uesugi ◽  
Tomomi Ueno ◽  
George Burdock
Keyword(s):  
Developmental Toxicity ◽  
Bacterial Flora ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels ◽  
Reproductive Study

Consumption of the isoflavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneficial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial flora. Research indicates that between 30–50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH) has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-effect-level (NOAEL) for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day). In the developmental toxicity phase of the study, no effects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental effects of SE5-OH is 2000 mg/kg/day (13 mg equol/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.

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

2003 ◽  
Vol 22 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Raymond G. York ◽  
Kathleen A. Funk ◽  
Michael F. Girard ◽  
David Mattie ◽  
Joan E. Strawson
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Developmental Toxicity ◽  
Thyroid Stimulating Hormone ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Maternal Thyroid

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T3, and T4 (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T4 was decreased at all levels, and T3 was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T4 was reduced at 30.0 mg/kg-day, and T3 was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T3 and T4 levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.

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.

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.

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

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.

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 A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

Developmental Toxicity of Clarified Slurry Oil Applied Dermally to Rats

1989 ◽  
Vol 5 (3) ◽  
pp. 587-599 ◽  
Author(s):  
Maureen H. Feuston ◽  
Stacy L. Kerstetter ◽  
Edward J. Singer ◽  
Myron A. Mehlman
Keyword(s):  
Body Weight Gain ◽  
Developmental Toxicity ◽  
Test Material ◽  
Residual Fraction ◽  
Pregnant Rats ◽  
Viable Offspring ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels ◽  
External Development

Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg I day. All groups received the test material on gestation days 0–19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions / deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.

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