Safety Evaluation of Zinc Threoninate Chelate

2010 ◽  
Vol 29 (4) ◽  
pp. 372-379 ◽  
Author(s):  
Xiao-bo Hu ◽  
Yi Gong ◽  
Lei Li ◽  
Shao-ping Nie ◽  
Yuan-xing Wang ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Organ Weight ◽  
Female Rats ◽  
Male Rats ◽  
Repeat Dose ◽  
Pregnant Rats ◽  
Sperm Abnormality ◽  
Daily Dose

The acute toxicity of zinc threoninate chelate was assessed. The oral lethal dose 50% (LD50) was 2710 mg/kg in female rats and 3160 mg/kg in male rats. Genotoxicity was assessed by Ames test in Salmonella typhimurium strains TA97, TA98, TA100, and TA102, by bone marrow mouse micronucleus test and a sperm abnormality test with mice. Thirty-day repeat dose toxicity study was conducted at oral daily doses of 0, 42, 169, and 675 mg/kg in rats. Teratogenicity was assessed at the same daily dose in pregnant rats by gavage. No significant changes in body weight, food consumption, organ weight, relative organ weight, hematology, blood biochemistry, histopathology, behavior, mortality, sperm abnormality, mutagenicity, and micronucleus formation were observed and no clinical signs or adverse effects were detected. Zinc threoninate chelate had no significant teratogenic effect at a daily dose of 42 mg/kg.

The Effect of Sodium Nitrite on Experimental Animals

1942 ◽  
Vol 6a (1) ◽  
pp. 63-73 ◽  
Author(s):  
H. L. A. Tarr ◽  
N. M. Carter
Keyword(s):  
Sodium Nitrite ◽  
Lethal Dose ◽  
Oral Route ◽  
Female Rats ◽  
Male Rats ◽  
Subcutaneous Route ◽  
Healthy Male ◽  
Experimental Animals ◽  
White Rats ◽  
Healthy Female

Incorporation of sodium nitrite in the diet of cats and white rats on the basis of an average sized man consuming 1 lb. (454 g.) of fish containing 0.2 per cent (908 mg.) of this salt daily for six days each week does not appear to affect their growth rate nor the development (weight) of their thyroid, heart, lungs, spleen, liver, kidneys or adrenals. The fecundity of white rats as judged by their ability to breed and raise normal litters is apparently not affected thereby. The lethal dose of sodium nitrite by oral route is about 1.1 to 2.0 g./kg. for healthy male rats, 0.46 to 1.2 g./kg. for healthy female rats and 0.073 g./kg. for cats (one animal). The lethal dose by subcutaneous route is about 0.19 to 0.20 g./kg. for healthy male rats and 0.057 to 0.13 g./kg. for healthy female rats.

scholarly journals Acute Toxicity of the Recombinant and Native Phα1β Toxin: New Analgesic from Phoneutria nigriventer Spider Venom

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 531 ◽  
Author(s):  
Eliane Dallegrave ◽  
Eliane Taschetto ◽  
Mirna Bainy Leal ◽  
Flavia Techera Antunes ◽  
Marcus Gomez ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Relative Weight ◽  
Serum Biochemistry ◽  
Renal Tissue ◽  
Organ Weight ◽  
Female Rats ◽  
Mild Degree ◽  
Physiological Limits ◽  
Voltage Dependent ◽  
Phoneutria Nigriventer

Phα1β, a purified peptide from the venom of the spider Phoneutria nigriventer, and its recombinant form CTK 01512-2 are voltage-dependent calcium channel (CaV) blockers of types N, R, P/Q, and L with a preference for type N. These peptides show analgesic action in different pain models in rats. The aim of this study was to evaluate the acute intrathecal toxicity of the native and recombinant Phα1β toxin in Wistar rats. Clinical signs, serum biochemistry, organ weight, and histopathological alterations were evaluated in male and/or female rats. Dyspnea was observed in males, hyporesponsiveness in females, and Straub tail and tremors in both genders. There were no significant differences in male organ weight, although significant differences in the female relative weight of the adrenal glands and spleen have been observed; these values are within the normal range. Serum biochemical data revealed a significant reduction within the physiological limits of species related to urea, ALT, AST, and FA. Hepatic and renal congestion were observed for toxin groups. In renal tissue, glomerular infiltrates were observed with increased glomerular space. These histological alterations were presented in focal areas and in mild degree. Therefore, Phα1β and CTK 01512-2 presented a good safety profile with transient toxicity clinical signals in doses higher than used to obtain the analgesic effect.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Chronic Toxicity ◽  
Hematological Parameters ◽  
Lethal Dose ◽  
Relative Weight ◽  
Stem Bark ◽  
The Body ◽  
Female Rats ◽  
Male Rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

Final Report on the Safety Assessment of HC Blue No. 1

1994 ◽  
Vol 13 (5) ◽  
pp. 344-360
Keyword(s):  
Animal Studies ◽  
Current Data ◽  
Female Rats ◽  
Male Rats ◽  
Final Report ◽  
Positive Trend ◽  
Hair Dyes ◽  
Pregnant Rats ◽  
Hepatocellular Carcinomas ◽  
Dose Dependent

The aromatic amine HC Blue No. 1 is a hair colorant intended exclusively for use in hair dyes. While this colorant had previously been used in concentrations up to 1.6%, current information indicates it is not presently used in any hair dyes. Animal studies indicate this ingredient is absorbed slowly through the skin. Short-term and subchronic animal toxicity studies show a dose-dependent reduction in weight gain. HC Blue No. 1 was mutagenic in some, but not all, test systems, and was associated with fetal bone malformations when given orally to pregnant rats at levels that were maternally toxic. In a National Toxicology Program feeding study, dosed male rats had a positive trend in incidence of hepatic neoplastic nodules, but not in hepatic carcinomas; dosed female rats showed a positive trend in the incidence of alveolar/bronchiolar neoplasms; and mice of both sexes showed an increase in hepatocellular carcinomas. Although it is recognized that further dermal carcinogenicity data would help clarify the different findings in the current data, such information is not expected, and it is concluded on the basis of the data that are available in this report that HC Blue No. 1 is unsafe for use in cosmetic formulations (hair dyes).

Modest maternal protein restriction fails to program adult hypertension in female rats

2005 ◽  
Vol 289 (4) ◽  
pp. R1131-R1136 ◽  
Author(s):  
Lori L. Woods ◽  
Julie R. Ingelfinger ◽  
Ruth Rasch
Keyword(s):  
Renin Angiotensin System ◽  
Female Gender ◽  
Female Offspring ◽  
Protein Restriction ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Angiotensin System ◽  
Low Protein ◽  
Maternal Protein Restriction

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50–65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 ± 3 mmHg vs. NP: 121 ± 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 ± 2,071 vs. NP: 26,248 ± 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 ± 0.11 106μm3, LP vs. NP: 1.07 ± 0.11 106μm3); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender.

Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 101-118 ◽  
Author(s):  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Food Consumption ◽  
Water Intake ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Organ Weights

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100,300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses ≤300 mg/kg or in females at any of the doses tested (≤1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

scholarly journals Acute toxicity assessment for TiO2 photocatalyst (GST) made from wastewater using TiCl4 in rat

2021 ◽  
Vol 36 (3) ◽  
pp. e2021019
Author(s):  
Ja Kyung Seol ◽  
Myeongkyu Park ◽  
Jae Min Im ◽  
Heung Sik Seo ◽  
Hee Ju Park ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
High Efficiency ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Body Weight Loss ◽  
Toxicity Assessment ◽  
Female Rats ◽  
Sprague Dawley ◽  
Weight Changes

TiO2 was a photocatalyst that used to the most common product because of the high efficiency. TiO2 (P-25, commercial nanomaterial product) is the most typical photocatalyst product and TiO2 (GST) was a sludge recycling product. This study was reported to evaluate an acute toxicity of TiO2 (P-25 and GST) according to OECD test guideline 402 and 423 in Sprague-Dawley (SD) female rats via route of oral and dermal. There was investigated the lethal dose (LD50), and mortality, clinical signs, body weight changes and gross findings were continually monitored for 14 days following the single administration. After administration, TiO2 (P-25) was calculated that LD50 was considered to be a dose of over 2000 mg/kg body weight for both different route of exposure, and TiO2 (GST) was the same. Other items were no observed an adverse effect between P-25 and GST; no mortality and clinical signs, accidental body weight loss, no gross findings. On the basis of the above results, the toxicity of the GST was almost equal to that of the commercial product, P-25 and there was no toxicological evidence.

scholarly journals Acute and 30-day oral toxicity studies of a novel coccidiostat – ethanamizuril

2019 ◽  
Vol 8 (5) ◽  
pp. 686-695 ◽  
Author(s):  
Wenlong Xiao ◽  
Xiaoyang Wang ◽  
Chunmei Wang ◽  
Mi Wang ◽  
Chenzhong Fei ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Wall Thickening ◽  
High Dose ◽  
Alveolar Wall ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Ld50 Value

Abstract Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg−1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg−1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg−1 groups. Histopathological observations revealed that 60 and 120 mg kg−1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg−1 feed.

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