Mouse Bone Marrow Micronucleus Test Research Articles

A study of the genotoxicity, fertility and early embryonic development toxicity of rotigotine behenate extended-release microspheres.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson's disease (PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represent a new treatment regime for CDS and are undergoing clinical trials. In this study, we aimed to investigate the effect of RBEM on genotoxicity, fertility and early embryonic development. We used the Ames test, Chinese hamster lung (CHL) cell chromosome aberration test and the mouse bone marrow micronucleus test, to evaluate the genotoxicity of RBEM. These tests were all negative, thus indicating that RBEM did not induce genotoxicity. In reproduction toxicity testing in male rats on obvious findings following intramuscular administration (i.m.) of RBEM at up to 540 mg/kg (P > 0.5), when female rats were administered with RBEM in the dose range of 60 to 540 mg/kg given (i.m.), there were clear effects on fertility and early embryonic development. These results indicated that RBEM could induce toxicity in female rats and exert effect on fertility and early embryonic development stage.

Acute toxicity and genotoxicity studies on new melatonergic antidepressant GW117

GW117, a novel derivate compound of agomelatine that acts as both a 5-HT2C receptor antagonist and a MT1/MT2 receptor agonist, likely underlines the potent antidepressant action with less hepatotoxicity than agomelatine. We evaluated the acute toxicity of GW117, and the genotoxicity of GW117 using bacterial reverse mutation test, mammalian chromosomal aberration test in Chinese hamster lung cells (CHL) and mouse bone marrow micronucleus test. The acute toxicity test results showed that maximum tolerated dose (MTD) of GW117 was 2000 mg/kg, under which mean Cmax and AUC0→t was 10,782 ng/mL and 81,046 ng/mL × h, respectively. The result of bacterial reverse mutation test showed that the number of bacterial colonies in each dose group of GW117 did not increase significantly compared with that in the solvent control group with or without S9 metabolic activation system. In vitro chromosome aberration test of CHL cells, the chromosome aberration rate of each dose group of GW117 did not increase with or without S9 metabolic activation system. In mouse micronucleus test, the highest dose was 2000 mg/kg, the micronucleus rate did not increase significantly. Under the conditions of this study, the MTD of a single GW117 administration was 2000 mg/kg, there was no genotoxicity effect of GW117.

In Vitro Genotoxicity Assessment from the Glycyrrhiza New Variety Extract

The various species that comprise the genus Glycyrrhiza (Licorice) have long been used as oriental herbal medicines in Asian countries. Wongam (WG), which is a new variety of Glycyrrhiza, was developed in Korea to overcome the limitations of low productivity, environmental restrictions, and an insufficient presence of glycyrrhizic acid and liquiritigenin. In this study, we evaluated WG extract’s genotoxicity through an in vitro bacterial reverse mutation (AMES) test, an in vitro chromosome aberration test, and an in vivo mouse bone marrow micronucleus test. In the AMES test, WG extract at concentrations of up to 5000 µg/plate showed no genotoxicity regardless of S9 mix. No chromosome aberrations appeared after 6 h in 1400 µg/mL WG extract regardless of S9 mix or in 1100 µg/mL WG extract after 24 h without S9 mix. Nor was there a significant increase in the number of micronucleated polychromatic erythrocytes to total erythrocytes up to 5000 mg/kg/day for 2 days detected in the micronucleus test. These results confirm that WG extract is safe for use as an herbal medicine, as it precipitates no detectable genotoxic effects.

Evaluation of oral toxicity and genotoxicity of Achyranthis Radix extract

Ethnopharmacological relevanceThe root of Achyranthes bidentata Blume, Achyranthis Radix (AR), is used as a traditional medicine ingredient in East Asia. It has anti-inflammatory, anti-oxidative, and anti-diabetic activities. Aim of the studyIn the present study, we aimed to evaluate the oral toxicity and genotoxicity of single-dose and 4-week repeated-doses of AR hot water extract (ARE), under the good laboratory practice principles. Materials and methodsFor oral toxicity studies, SD rats (n = 5 per sex and group) were administered ARE at concentrations of 500, 1000, and 2000 mg/kg/day once (single dose) or once per day for 4 weeks (repeated dose). The non-clinical genotoxicity study consisted of bacterial reverse mutation using Escherichia coli (WP2 uvrA) and Salmonella typhimurium (TA98, TA100, TA1535, and TA1537), in vitro chromosomal aberration test with Chinese hamster lung cells (CHL/IU), and in vivo mouse bone marrow micronucleus test using bone marrow cells collected from male ICR mice (n = 5) that were orally administered ARE. ResultsIn the single-dose oral toxicity study, mortality and treatment-related changes in body weight were not observed throughout the study, and the lethal dose was estimated to be > 2000 mg/kg in rats. In the 4-week repeated-dose oral toxicity study, ARE did not induce significant changes in body weight, organ weight, food intake, or hematological and serum biochemical parameters in any group. In the bacterial reverse mutation test, ARE did not induce gene mutations in any tested strain. In the chromosomal aberration test, ARE did not cause chromosomal aberrations. The micronucleus test showed no significant increase in the number of micronucleated polychromatic erythrocytes or the mean ratio of polychromatic to total erythrocytes. ConclusionsThese results showed that ARE does not induce oral toxicity and genotoxicity in the in vivo and in vitro test systems.

Evaluation of the in vitro and in vivo genotoxicity of a Dioscorea Rhizome water extract.

Dioscorea Rhizome is commonly used in traditional herbal medicines for the treatment of diabetes, hyperthyroidism, liver damage, neuropathy, and asthma. Here, we investigated the genotoxicity potential of D. Rhizome water extract (DRWE) using three standard battery systems in accordance with the test guidelines of the Organisation for Economic Cooperation and Development and Ministry of Food and Drug Safety as well as the principles of Good Laboratory Practice. A bacterial reverse mutation test (Ames test) was performed using the direct plate incorporation method in the presence or absence of a metabolic activation system (S9 mixture). The tester strains used included four histidine auxotrophic strains of Salmonella typhimurium, TA100, TA1535, TA98, and TA1537, along with a tryptophan auxotrophic strain of Escherichia coli, WP2 uvrA. An in vitro chromosome aberration test was performed using CHL/IU cells originally derived from the lung of a female Chinese hamster in the presence or absence of the S9 mixture. An in vivo mouse bone marrow micronucleus test was performed using male ICR mice. The micronucleus was confirmed after observation of the micro-nucleated polychromatic. The Ames test showed that DRWE did not induce gene mutations at any dose level in any of the tested strains. Additionally, DRWE did not result in any chromosomal aberrations specified in the in vitro chromosomal aberration and in vivo micronucleus tests. These results showed that DRWE exhibited neither mutagenic nor clastogenic potential in either the in vitro or in vivo test systems.

Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice

Natural astaxanthin is the strongest antioxidant ever discovered, with many biological functions, and it is widely used in the fields of health food and biomedical research. In the present study, we aimed to investigate the plasma concentration, distribution and safety of astaxanthin from Haematococcus pluvialis in pregnant mice. In the acute studies, the oral LD50 of astaxanthin was greater than 20 g/kg·bw. In mouse bone marrow micronucleus test, 10 g/kg·bw astaxanthin did not cause damage to chromosomes and mitotic apparatus of pregnant mice. After treatment with a single dose of 500 mg/kg·bw astaxanthin, the concentration of astaxanthin in plasma reached the maximum at 8 h (55.7 μg/L), which was completely metabolized after 48 h. In the repeat-dose toxicity test, 100, 250 and 500 mg/kg·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.

Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42–46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non‐clinical safety testing comprised a single‐dose oral toxicity study and a 28‐day repeated‐dose oral toxicity study with a 14‐day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single‐dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28‐day repeated‐dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single‐dose study. The no‐observed‐adverse‐effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague‐Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

STUDIES OF THE GENOTOXICITY OF TECHNICAL PRODUCTS OF THE BENZOYLCYCLOHEXANE-1,3-DIONE DERIVATIVE PESTICIDE

Introduction. Currently, a large number of pesticide analogues manufactured past the expiration date of the patent protection of the original active ingredients are imported in the Russian Federation. The toxicological-hygienic examinations based on numerous trials, including mutagenicity (genotoxicity) studies, is necessary to confirm their safety. Material and methods. The study of the genotoxic activity of three technical products of the pesticide active ingredient, a benzoylcyclohexane-1,3-dione derivative, produced in the various factories was carried out. research was performed using the bacterial reverse mutation method (Ames test) and the in vivo mouse bone marrow micronucleus test. Results. Statistically significant and dose-dependent genotoxic effects of the test samples were observed in the strains of Salmonella typhimurium of TA 97, TA 102, TA 100. However, the increase in the number of revertants in the experiment versus the negative control was less than two in all cases, with the exception of strain TA 97. Weak but biologically significant outcomes were found in TA 97 culture (the increase in the number of revertants in comparison to spontaneous level was ≥ 2. In the micronucleus test only two of the three samples produced a statistically significant increase in the incidence of micronucleated polychromatophilic erythrocytes. One of the samples induced the significant genotoxic effect only at the high dose (2000 mg/kg b.w.), and another one (with the lowest active substance content) at all dose levels. In both cases, a linear dose-effect dependence was found. The cytogenetic effects were low, at the level of the upper limit of the laboratory's historical negative control Conclusion. The obtained data indicate that the ability of the tested technical products of the benzoylcyclohexane-1,3-dione derivative to induce the gene and chromosomal damages increases with decreasing concentration of the active ingredient in technical products, probably due to the enhancement of the genotoxic impurity level. Thus, the technical products of analogue pesticides are not always equivalent to the original active substances in terms of their biological activity. That confirms the necessity for toxicological-hygienic testing, in particular genotoxicity assessments of all generic pesticides entering the market.

Assessment of genotoxic activity of oleoresins and leaves extracts of six Copaifera species for prediction of potential human risks

Ethnopharmacological relevanceCopaifera species are used in folk medicine for a wide variety of pharmacological properties. This paper reports the cytotoxic and genotoxic analyses of oleoresins and leaves extracts of Copaifera species: C. duckei, C. multijuga, C. paupera, C. pubiflora, C. reticulata and C. trapezifolia. Materials and methodsIn vitro assays were performed using Chinese hamster lung fibroblasts (V79 cells). The clonogenic efficiency and cytokinesis-block micronucleus assays were employed for the cytotoxicity and genotoxicity assessment, respectively. The mouse bone marrow micronucleus test was used for in vivo studies. ResultsThe cytotoxicity results using the clonogenic efficiency assay showed IC50 values ranging from 9.8 to 99.2 µg/mL for oleoresins and 66.4–721.5 for leaves extracts. However, no cytotoxic effect was observed in the in vivo studies. Additionally, the treatments with oleoresins and leaves extracts did not significantly increase the frequency of micronuclei in both in vitro and in vivo mammalian cells. The UPLC-MS/MS and CG/MS analyses of Copaifera oleoresins allowed the identification of 10 acid diterpenes and 11 major volatile sesquiterpenes. Leaves are rich in phenolic compounds including two flavonoid heterosides and 16 galloylquinic acid derivatives. ConclusionsThe oleoresins and leaves extracts of studied Copaifera species were not cytotoxic in vivo, as well as not genotoxic in both in vitro and vivo assays, under the experimental conditions used. Therefore, the obtained results should be sufficient to demonstrate the absence of significant genotoxic risk of these Copaifera products for human use in the evaluated concentrations range.

Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays.

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention.

Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow.

Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.

Antimutagenic, Antigenotoxic, and Anticytotoxic Activities of Silybum Marianum [L.] Gaertn Assessed by the Salmonella Mutagenicity Assay (Ames Test) and the Micronucleus Test in Mice Bone Marrow

ABSTRACTSilymarin (SM), a standardized extract from Silybum marianum (L.) Gaertn., is composed mainly of flavonolignans, and silibinin (SB) is its major active constituent. The present study aimed to evaluate the antimutagenic activities of SM and SB using the Ames mutagenicity test in Salmonella Typhimurium, as well as their anticytotoxic and antigenotoxic activities using the mouse bone marrow micronucleus test. To assess antimutagenicity, Salmonella Typhimurium strains were treated with different concentrations of SM or SB and the appropriate positive control for each strain. To assess antigenotoxicity and anticytotoxicity, Swiss mice were treated with different concentrations of SM or SB and mitomycin C (MMC). The results showed that SM was not significantly effective in reducing the number of frameshift mutations in strain TA98, while SB demonstrated significant protection at higher doses (P < 0.05). Regarding strain TA 100, SM and SB significantly decreased mutagenicity (point mutations) (P < 0.05). The results of the antigenotoxic evaluation demonstrated that SM and SB significantly reduced the frequency of micronucleated polychromatic erythrocytes (MNPCE) (P < 0.05). The results also indicated that SM and SB significantly attenuated MMC-induced cytotoxicity (P < 0.05). Based on these results, both SM and SB presented antimutagenic, antigenotoxic, and anticytotoxic actions.

Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage.

Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities.

Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

Assessment of the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus).

The present study aimed to assess the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus), which is commonly used as an anti-rheumatic, analgesic, antimicrobial, anticercariae, and anti-inflammatory. We used the mouse bone marrow micronucleus test as an experimental model. The experimental groups, which consisted of 5 animals, was administered sucupira oil (100 mg/kg body weight) intraperitoneally and evaluated 24 h after the treatment. The negative control group was treated with sterile distilled water, and the positive control group received an intraperitoneal dose of 4 mg/kg mitomycin C, a dose that corresponds to 80% of its median lethal dose. Cytotoxicity was determined by the polychromatic to normochromatic erythrocytes ratio (PCE/NCE). Sucupira oil had no significant effects (P > 0.05) on the frequency of micronucleated polychromatic erythrocytes as compared to the negative control group. However, the difference was significant (P < 0.005) as compared to the positive control group. The PCE/NCE (100 mg/kg oil and 4 mg/kg mitomycin) ratio did not differ between the experimental group and the positive control group, but it differed significantly when compared to the negative control group (P < 0.05). Thus, these findings suggested that the P. emarginatus oil showed no cytotoxic, mutagenic, or antimutagenic activities at a dose of 100 mg/kg.

Evaluación preclínica y estudio de estabilidad de extractos a partir del follaje de Momordica charantia Lin

El objetivo del presente trabajo fue la evaluación preclínica y el estudio de estabilidad de extractos a partir del follaje de Momordica charantia Lin. Se obtuvieron extractos acuoso e hidroalcohólico para los cuales se establecieron las especificaciones de calidad mediante la evaluación de tres lotes y se estudió su estabilidad por el método de vida de estante durante 12 meses. A los extractos se le evaluó el potencial genotóxico mediante ensayos de micronúcleos en médula ósea de ratón y aberraciones cromosómicas en linfocitos de sangre periférica. La actividad hipoglicemiante oral fue evaluada en animales con hiperglicemia temporal inducida por carga de glucosa. Como resultados se establecieron las especificaciones de calidad de los extractos acuoso e hidroalcohólico, los mismos mostraron estabilidad por 6 meses para el extracto acuoso y 12 meses para el extracto hidroalcohólico. No mostraron efecto genotóxico en los ensayos evaluados y mostraron efecto hipoglicemiante oral a la dosis de 450 mg/kg.

Evaluation of vinyl laurate in a battery of in vitro and in vivo tests for genotoxicity

Vinyl laurate is a potential residual monomer in chewing gum base formulated with polyvinyl acetate vinyl laurate copolymer (PVAcVL). The genotoxic potential of vinyl laurate was examined in a battery of in vitro and in vivo genotoxicity tests. Vinyl laurate was not mutagenic in Ames tests. In addition, it was not mutagenic in the HPRT mutation assay in L5178Y cells. An in vitro mammalian chromosome aberration assay performed in CHO cells was equivocal. Vinyl laurate and/or its metabolites were not clastogenic in the mouse bone marrow micronucleus test. Kinetic data indicate that VL is metabolised to acetaldehyde and lauric acid. Both metabolites are well known and have been studied previously. Model calculations show, that any exposure to acetaldehyde from the consumption of PVAcVL containing chewing gum will remain far below levels of acetaldehyde exposure from food in which acetaldehyde occurs naturally. Direct exposure to VL will primarily be at the site of entry. The lack of toxicity in a 90-day repeated dose toxicity test, performed with VL doses up to approximately 3000 times higher than the maximal VL intake from the consumption of a typical piece of chewing gum, demonstrates a high safety margin.

Preliminary Toxicology Evaluation of Silymarin

Research silymarin food security through animal experiments. Acute toxicity test, mouse bone marrow micronucleus test, mice sperm abnormality test results were evaluated. Male and female mice by oral maximum tolerated dose (MTD) are more than 20.0g/kg body weight, according to the acute toxicity grading standards, which are non-toxic level. Mouse bone marrow micronucleus test, mice sperm abnormality test and genotoxicity test were negative. Showed that silymarin is a food safety component.

Genotoxicity and subacute toxicity studies of a new astaxanthin-containing &lt;i&gt;Phaffia rhodozyma&lt;/i&gt; extract

Experimental and clinical studies demonstrate that astaxanthin (AXN), a xanthophyll carotenoid, has protective effects against oxidative damage. Because most of these studies assessed AXN derived fromHaematococcus pluvialisthat were cultivated at industrial scales, few studies have examined the toxicity of AXN derived fromPhaffia rhodozyma. To evaluate the safety of astaxanthin-containingP. rhodozymaextract (AXN-PRE), genotoxicity was assessed in bacterial reverse mutation test and mouse bone marrow micronucleus test, and general toxicity was assessed in 4-week repeated oral toxicity study in rats. AXN-PRE did not induce reverse mutations in theSalmonella typhimuriumstrains TA98 or TA100 at concentrations of 5,000 µg/plate with or without S9 mix, and no chromosome damage was observed at a dose of 2,000 mg/kg in mouse micronucleus test. In the subacute toxicity study, male and female Sprague-Dawley rats were given AXN-PRE at doses of 0, 500, and 1,000 mg/kg by gavage for 4 weeks. Body weights, urinalysis, hematology, serum biochemistry, organ weights, or histopathological lesions indicated no distinct toxicity. In conclusion, AXN-PRE had no effect in bacterial reverse mutation test and mouse bone marrow micronucleus test. The no-observed-adverse-effect level for AXN-PRE in 4-week repeated oral toxicity study in rats was determined to be greater than 1,000 mg/kg (corresponding to dose of 50 mg/kg AXN) regardless of gender.