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Toxicity Study (toxicity + study)
Selected AbstractsA 90-D Toxicity Study of,Monascus -Fermented Products Including High Citrinin LevelJOURNAL OF FOOD SCIENCE, Issue 5 2010Chun-Hsien Lee Abstract:,Monascus,is one of the traditional fermentation fungi and has been used in many kinds of food for thousands of years. Although,Monascus -fermented red mold rice performs cholesterol-lowering effects, blood pressure-lowing effects, and antioxidant effects, another metabolite, nephrotoxic and hepatotoxic citrinin, causes the concerns for safety. Various citrinin concentrations (1, 2, 10, 20, and 200 ppm) in the red mold rice are, respectively, estimated for safe use in animal tests. According to the results of serum biochemistry assays of liver and kidney in each group, citrinin did not reveal any nephrotoxicity and hepatotoxicity. Furthermore, the results of histopathological slices of liver and kidney in each group did not show any significant differences from control histopathological findings. As a result, we presume that citrinin concentrations in,Monascus -fermented products within 200 ppm will not affect the functions of liver and kidney or cause any nephrotoxicity and hepatotoxicity. According to safety factor, it is proposed that 2 ppm citrinin in,Monascus -fermented products may be a safe concentration. [source] Genetic damage detected in CD-1 mouse pups exposed perinatally to 3,-azido-3,-deoxythymidine and dideoxyinosine via maternal dosing, nursing, and direct gavageENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Jack B. Bishop Abstract Human immunodeficiency virus (HIV)-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug-induced chromosomal damage in neonates remains undefined. We used a mouse model to investigate this concern. In a multigeneration reproductive toxicity study, female CD-1 mice received 3,-azido-3,-deoxythymidine (AZT) and dideoxyinosine (ddI) (50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimen) began on postnatal day (PND) 4. Peripheral blood erythrocytes of male pups were screened for micronuclei, markers of chromosomal damage, on PNDs 1, 4, 8, and 21. Extraordinary increases in micronucleated cells were noted in pups for each treatment group at each sampling time; treated dams exhibited smaller yet significant increases in micronucleated erythrocytes. The frequencies of micronucleated cells in untreated pups were higher than in the untreated dams, and all pups had markedly elevated levels of circulating reticulocytes compared to dams. These observations suggest that fetal and neonatal mouse hematopoietic precursor cells have heightened sensitivity to genotoxic agents, perhaps due to rapid cell proliferation during the perinatal period of development. The amount of genetic damage observed in treated pups raises concern for the potential of similar damage in humans. Investigations of chromosomal integrity in exposed newborns and children are recommended. Environ. Mol. Mutagen. 43:3,9, 2004. © 2004 Wiley-Liss, Inc. [source] Combined repeated dose and reproductive/developmental toxicity screening test of the nitrophenolic herbicide dinoseb, 2- sec -butyl-4,6-dinitrophenol, in ratsENVIRONMENTAL TOXICOLOGY, Issue 2 2008Mariko Matsumoto Abstract In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2- sec -butyl-4,6-dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44,48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 7 2009Yuanfeng Li Abstract To investigate the neurobehavioral effects of dibutyl phthalate (DBP), an important endocrine disruptor known for reproductive toxicity, on rodent offspring following in utero and lactational exposure, pregnant Wistar rats were treated with DBP (0, 0.037, 0.111, 0.333 and 1% in the diet) from gestation day (GD) 6 to postnatal day (PND) 28, and selected developmental and neurobehavioral parameters of the offspring were measured. There were no significant effects of DBP on body weight gain of the dams during GD 6,20 or on the pups' ages of pinna detachment, incisor eruption or eye opening. Exposure to 1% DBP prolonged gestation period, decreased body weight in both male and female pups, depressed surface righting (PND 7) in male pups, shortened forepaw grip time (PND 10), enhanced spatial learning and reference memory (PND 35) in male pups. Exposure to 0.037% DBP also shortened forepaw grip time (PND 10), but inhibited spatial learning and reference memory in male pups. Sex × treatment effects were found in forepaw grip time (PND 10), spatial learning and reference memory, and the male pups appeared to be more susceptible than the females. However, all levels of DBP exposure did not significantly alter surface righting (PND 4), air righting (PND 16), negative geotaxis (PND 4 or 7), cliff avoidance (PND 7) or open field behavior (PND 28) in either sex. Overall, the dose level of DBP in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter cognitive abilities of the male rodent. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pollinex® Quattro Ragweed: safety evaluation of a new allergy vaccine adjuvanted with monophosphoryl lipid A (MPL®) for the treatment of ragweed pollen allergyJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007Paul Baldrick Abstract A novel allergy vaccine (Pollinex® Quattro Ragweed) has been developed for the prevention or relief of allergic symptoms caused by pollen from Ambrosia spp. (ragweed). An extract from the pollen (chemically modified by glutaraldehyde) is adsorbed onto l -tyrosine with addition of the immunostimulatory adjuvant, monophosphoryl lipid A (MPL®). A specific preclinical safety testing strategy was developed to support clinical use and comprised reference to preclinical data available for the marketed non-MPL® adjuvanted form of the ragweed vaccine (Pollinex® R) and a new repeat dose toxicity study in the rat. Studies with Pollinex® R comprised single dose subcutaneous toxicity studies in mice and rats, repeat dose (10 injections over 20 days) parenteral toxicity studies in rats and dogs, an in vitro gene mutation assay along with single and multiple injection local tolerance studies in rats and dogs. The repeat dose subcutaneous toxicity study with Pollinex® Quattro Ragweed involved seven injections over 3 weeks (which was more aggressive than the four weekly doses used in the clinic) with dose levels of up to 0.5 ml per animal used. Overall, the product showed no toxicological findings of significance at levels greatly in excess of those proposed for clinical use. As is a feature with vaccination, some dose site irritation was seen. Copyright © 2007 John Wiley & Sons, Ltd. [source] Two-generation reproductive toxicity study of inhaled tertiary amyl methyl ether (TAME) vapor in CD® ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2003R. W. Tyl Abstract Under Of,ce of Prevention, Pesticides and Toxic Substances draft guidelines, CD® weanling F0 rats (30 of each gender per group) inhaled tertiary amyl methyl ether vapor at 0, 250, 1500 or 3000 ppm 5 days a week and 6 h a day for 10 weeks, with vaginal cytology evaluated for weeks 8,10. The F0 animals then produced F1 offspring, with exposure 7 days a week from mating through to lactation. During the F1 prebreed exposure period, vaginal patency, preputial separation (PPS) and vaginal cytology were evaluated. The F1 animals were mated, with F2 anogenital distance measured on postnatal day zero. At F2 weaning 30 of each gender per group were selected for postwean retention, with no exposures, through vaginal patency and PPS. Body weights, feed consumption and clinical signs were recorded throughout the study. Adult F0 and F1 systemic toxicity was present at 1500 and 3000 ppm. Minor adult male reproductive toxicity was present at 3000 ppm. There were no adult effects on vaginal cyclicity, estrous cycle length, mating, fertility, pregnancy, gestational length or ovarian and uterine weights. There were no treatment-related gross or histopathologic ,ndings in parental male or female systemic or reproductive organs. The F1 and F2 offspring toxicity was present at 1500 and 3000 ppm. The no-observable-adverse-effect level for adult systemic and offspring toxicity was 250 ppm and 1500 ppm for male reproductive toxicity (females at >3000 ppm). Copyright © 2003 John Wiley & Sons, Ltd. [source] One-year dog toxicity study of D-002, a mixture of aliphatic alcoholsJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001Celia Alemán Abstract D-002 is a mixture of high-molecular-weight aliphatic alcohols, obtained from bees wax (Apis mellifera), with mild anti-inflammatory properties and effective anti-ulcer activities demonstrated in experimental models. This study investigated the oral toxicity of D-002 administered for 1 year to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in three experimental groups (four animals per group): a control and two treated groups received D-002 at 50 and 250 mg kg,1 (7 days/week) by gastric gavage. Overall, D-002 was well tolerated throughout the study. No signs or symptoms of toxicity were observed, and no mortality occurred during the study. All groups showed similar weight gain and food consumption. No hematological, blood biochemical or histopathological disturbances attributable to treatment were observed. This study shows no drug-related toxicity induced by long-term administration of up to 250 mg kg,1 D-002 to beagle dogs. Copyright © 2001 John Wiley & Sons, Ltd. [source] Renoprotective effect of Hemidesmus indicus, a herbal drug used in gentamicin-induced renal toxicityNEPHROLOGY, Issue 3 2004MANGALA S KOTNIS SUMMARY: Background and Aims: Owing to the global trend towards improved ,quality of life', there is considerable evidence of an increase in demand for medicinal plants. The WHO guidelines define basic criteria for the standardization of herbal medicines. The present work is an effort in this direction to prove the safety and efficacy of Hemidesmus indicus Linn. in the management of nephrotoxicity induced by aminoglycosides such as gentamicin. Methods and Results: Simple, quality control methods using high performance thin layer chromatographic (HPTLC) phytochemical fingerprint, proximate analysis, and the stability of the H. indicus root powder were developed. From the toxicity study using albino Swiss mice, it was observed that the drug (H. indicus) was relatively safe up to 7 g/kg bodyweight dose. Efficacy was evaluated against gentamicin-induced nephrotoxicity in albino Wister rats. The study examined animals from the following groups: no treatment, gentamicin treated, gentamicin treated recovery, and gentamicin and plant treated. Animals from all groups were killed on day 13 of the study; those from gentamicin treated group were killed on the seventh day. Assessment of the drug efficacy drug was conducted by using haematological and histological examination. Conclusion: The treatment with H. indicus helped in the management of renal impairment, which was induced by gentamicin in rats. This is evident from the results obtained for various kidney function tests for gentamicin, along with the results from the plant treated group, and is in comparison with the results found for the gentamicin recovery group. A histological examination of kidneys also supports the findings from haematological evaluations. The plant shows promise as an adjunct therapy along side aminoglycosides as it reduces nephrotoxicity caused by aminoglycosides. [source] Antiulcerogenic activity of the essential oil of Baccharis dracunculifolia on different experimental models in ratsPHYTOTHERAPY RESEARCH, Issue 10 2009Juliane Jose Massignani Abstract Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, commonly known as ,Alecrimdo-campo' is widely used in folk medicine to treat inflammation, hepatic disorders and stomach ulcers, and it is the most important botanical source of Southeastern Brazilian propolis, known as green propolis. Its essential oil is composed of non-oxygenated and oxygenated terpenes. In this work, the effects of the essential oil obtained from the aerial parts of B. dracunculifolia on gastric ulcers were evaluated. The antiulcer assays were undertaken using the following protocols in rats: nonsteroidal antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, stress-induced ulcer, and determination of gastric secretion using ligated pylorus. The treatment in the doses of 50, 250 and 500 mg/kg of B. dracunculifolia essential oil significantly diminished the lesion index, the total lesion area and the percentage of lesions in comparison with both positive and negative control groups. With regard to the model of gastric secretion a reduction of gastric juice volume and total acidity was observed, as well as an increase in the gastric pH. No sign of toxicity was observed in the acute toxicity study. Considering the results, it is suggested that the essential oil of B. dracunculifolia could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer. Copyright © 2009 John Wiley & Sons, Ltd. [source] A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiaticaPHYTOTHERAPY RESEARCH, Issue 12 2007Byung-Gyu Park Abstract Plantago asiatica is distributed widely in East Asia. Since ancient times it has been used as a diuretic to treat acute urinary infections, and as an antiinflammatory, antiasthmatic, antioxidant, antibacterial, antihyperlipidemic and antihepatitis drug. The major compound, plantamajoside from P. asiatica, which is used as a marker compound in chemotaxonomic studies, was reported to have antibacterial activity, inhibition activity against cAMP phosphodiesterase and 5-lipoxygenase and antioxidant activity. However, there are no reports on the safety of plantamajoside. This study assessed the toxic effects of plantamajoside concentrate (PC), the purity of which was above 80%, in rats following administration at dose levels of 0, 500, 1000 and 2000 mg/kg body weight/day for 13 weeks, as recommended by the OECD guidelines. The results showed that there were no differences in body weight, food intake, water consumption, relative organ weight or the hematological and serum biochemical values among the different dosage groups. No death or abnormal clinical signs were observed during the experimental period. Therefore, the results suggested that no observed adverse effect level (NOAEL) of the PC in rats after oral administration is considered to be greater than 2000 mg/kg in rats under the conditions employed in this study. Copyright © 2007 John Wiley & Sons, Ltd. [source] Association Models for Clustered Data with Binary and Continuous ResponsesBIOMETRICS, Issue 1 2010Lanjia Lin Summary We consider analysis of clustered data with mixed bivariate responses, i.e., where each member of the cluster has a binary and a continuous outcome. We propose a new bivariate random effects model that induces associations among the binary outcomes within a cluster, among the continuous outcomes within a cluster, between a binary outcome and a continuous outcome from different subjects within a cluster, as well as the direct association between the binary and continuous outcomes within the same subject. For the ease of interpretations of the regression effects, the marginal model of the binary response probability integrated over the random effects preserves the logistic form and the marginal expectation of the continuous response preserves the linear form. We implement maximum likelihood estimation of our model parameters using standard software such as PROC NLMIXED of SAS. Our simulation study demonstrates the robustness of our method with respect to the misspecification of the regression model as well as the random effects model. We illustrate our methodology by analyzing a developmental toxicity study of ethylene glycol in mice. [source] Chronic toxicity/oncogenicity study of styrene in cd-1 mice by inhalation exposure for 104 weeksJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001George Cruzan Abstract Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice. Copyright © 2001 John Wiley & Sons, Ltd. [source] | |||||||||||||