Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic me...Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.展开更多
Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect muta...Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. Results The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P<0.05) were obtained in TA98 strain at 2000 and 3000 mg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P<0.05) appeared at 1000, 2000, and 3000 mg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P<0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P<0.05) only at the dose of 135.0 mg/kg b. w. Conclusion The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.展开更多
Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a stud...Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocylops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide prcoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products （DBPs） of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation ofMesocyclops leukorti can be inactivated effectively and safely by chlorine dioxide pre-oxidation.展开更多
The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experim...The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.展开更多
While Unleaded gasoline has the advantage of eliminating lead from automobile exhaust, its potential to reduce the exhaust gas and particles, merits further examination. In the present studies,the concentrations of hy...While Unleaded gasoline has the advantage of eliminating lead from automobile exhaust, its potential to reduce the exhaust gas and particles, merits further examination. In the present studies,the concentrations of hydrocarbons (HC) and earbon monoxides (CO) in emissions were analyzed on Santana engine Dynamometer under a standard test cycle, and total exhaust particles were collected from engines using leaded and unleaded gasoline. It was found that unleaded gasoline reduced the emissions of CO and HC, and decreased the quantity of vehicle exhaust particulate matters by 60%.With the unlead gasoline, only 23 kinds of organic substances, adsorbed in the particles, were identified by gas chromatography/mass spectrometer (GC/MS) while 32 components were detected using the leaded gasoline. The results of in vitro Salmonella/ microsomal test and micronucleus induction assay in CHL cells indicated that both types of gasoline increased the number of histidine-independent colonies and the frequencies of micronucleus induction; no significant differellce was found in their mutagenicity.展开更多
Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium ...Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.展开更多
Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutag...Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of short-term tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P>0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P > 0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1730, 1/20 and 1/15 LD50 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages.The probability of carcinogenicity of Kuianchun is 23.8%(6 = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.展开更多
Applying the micronucleus technique T.adescanlia paludosa, the mutagenicity of five pesticides, Decis, Sumicid, Cypermethrin, Trichlorphon and Diazinon were tested. The testing results showed that 0.64%, 0.32%, 0.16%,...Applying the micronucleus technique T.adescanlia paludosa, the mutagenicity of five pesticides, Decis, Sumicid, Cypermethrin, Trichlorphon and Diazinon were tested. The testing results showed that 0.64%, 0.32%, 0.16%, 0.08% of Decis, 0.64%, 0.32%, 0. 16%, 0.04% of Trichlorphon and 0.32%, 0.16%, 0.08%, 0.04% of Diazinon all had mutagenicity on Tradescantia paludosa, but Sumicid and Cypermethrin had no such characteristic.展开更多
Ibopamine(Ibo) is a new effective drug against heart failure. This paper reports the results of mutation tests of chromosome aberration of mammalian cell (Chinese hamster lung cell, CHL) in vitro and reversional mutat...Ibopamine(Ibo) is a new effective drug against heart failure. This paper reports the results of mutation tests of chromosome aberration of mammalian cell (Chinese hamster lung cell, CHL) in vitro and reversional mutation test of Salmonella typhimurium bacterium (Ames test) of ibopamine . The results of both tests were negative. Ibo did not have mutagenic effect.展开更多
Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxy...Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase (AHH) and glutathione S-transferase (GST) in rats. The extracts showed mutagenicity for Salmonella typhimurium strain TA98 and its derivatives TA98NR and TA98/1,8-DNP6 with or without S9 mix. The revertants in strains TA98NR and TA98/1,8-DNP6 were less than 40% and 50% of that in strain TA98 without S9 mix, respectively. Positive results were obtained in mouse bone marrow micronucleus assay. Intratracheal instillation of the extracts led to increase in pulmonary (but not hepatic) AHH and GST activities in rats. It was seen that AHH was more sensitive than GST to induction by the extracts展开更多
The mutngenicity of urine from individua1s exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase o...The mutngenicity of urine from individua1s exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three stralns in the presence of both rat liver S9 and β-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 μl urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the sarne samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contaln mainly arotnatic compounds as glucuronide conugates. our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic poency between the' pure' exposed (non-srnokers') and the ' pure' smokers' (unexpeed) samples was found in all three tester strains. This might mean that the exopure extent Of mutagens/carcinogens in LPG combustion products for exmped individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that sguergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.展开更多
文摘Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.
文摘Objective To evaluate the antimutagenicity of propolis in vivo and in vitro. Methods Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC. Results The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P<0.05) were obtained in TA98 strain at 2000 and 3000 mg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P<0.05) appeared at 1000, 2000, and 3000 mg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P<0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P<0.05) only at the dose of 135.0 mg/kg b. w. Conclusion The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.
基金The Hi-Tech Research and Development Program (863) of China (No. 2003AA601120)
文摘Mesocyclops leukarti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocylops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide prcoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products （DBPs） of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation ofMesocyclops leukorti can be inactivated effectively and safely by chlorine dioxide pre-oxidation.
文摘The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.
文摘While Unleaded gasoline has the advantage of eliminating lead from automobile exhaust, its potential to reduce the exhaust gas and particles, merits further examination. In the present studies,the concentrations of hydrocarbons (HC) and earbon monoxides (CO) in emissions were analyzed on Santana engine Dynamometer under a standard test cycle, and total exhaust particles were collected from engines using leaded and unleaded gasoline. It was found that unleaded gasoline reduced the emissions of CO and HC, and decreased the quantity of vehicle exhaust particulate matters by 60%.With the unlead gasoline, only 23 kinds of organic substances, adsorbed in the particles, were identified by gas chromatography/mass spectrometer (GC/MS) while 32 components were detected using the leaded gasoline. The results of in vitro Salmonella/ microsomal test and micronucleus induction assay in CHL cells indicated that both types of gasoline increased the number of histidine-independent colonies and the frequencies of micronucleus induction; no significant differellce was found in their mutagenicity.
文摘Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.
文摘Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of short-term tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P>0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P > 0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1730, 1/20 and 1/15 LD50 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages.The probability of carcinogenicity of Kuianchun is 23.8%(6 = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.
文摘Applying the micronucleus technique T.adescanlia paludosa, the mutagenicity of five pesticides, Decis, Sumicid, Cypermethrin, Trichlorphon and Diazinon were tested. The testing results showed that 0.64%, 0.32%, 0.16%, 0.08% of Decis, 0.64%, 0.32%, 0. 16%, 0.04% of Trichlorphon and 0.32%, 0.16%, 0.08%, 0.04% of Diazinon all had mutagenicity on Tradescantia paludosa, but Sumicid and Cypermethrin had no such characteristic.
文摘Ibopamine(Ibo) is a new effective drug against heart failure. This paper reports the results of mutation tests of chromosome aberration of mammalian cell (Chinese hamster lung cell, CHL) in vitro and reversional mutation test of Salmonella typhimurium bacterium (Ames test) of ibopamine . The results of both tests were negative. Ibo did not have mutagenic effect.
文摘Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase (AHH) and glutathione S-transferase (GST) in rats. The extracts showed mutagenicity for Salmonella typhimurium strain TA98 and its derivatives TA98NR and TA98/1,8-DNP6 with or without S9 mix. The revertants in strains TA98NR and TA98/1,8-DNP6 were less than 40% and 50% of that in strain TA98 without S9 mix, respectively. Positive results were obtained in mouse bone marrow micronucleus assay. Intratracheal instillation of the extracts led to increase in pulmonary (but not hepatic) AHH and GST activities in rats. It was seen that AHH was more sensitive than GST to induction by the extracts
文摘The mutngenicity of urine from individua1s exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three stralns in the presence of both rat liver S9 and β-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 μl urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the sarne samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contaln mainly arotnatic compounds as glucuronide conugates. our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic poency between the' pure' exposed (non-srnokers') and the ' pure' smokers' (unexpeed) samples was found in all three tester strains. This might mean that the exopure extent Of mutagens/carcinogens in LPG combustion products for exmped individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that sguergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.
