M. Feuston, C. Mackerer, C. Schreiner, C. E. Hamilton
Two crude oils, differing in viscosity (V) and nitrogen (N) and sulfur (S) content, were evaluated for systemic toxicity. In the Crude I (low V, low N, low S) study, the material was applied to the clipped backs of rats at dose levels of 0, 30, 125, and 500 mg/kg. In the Crude II (high V, high N, moderate S) study, the oil was applied similarly at the same dose levels. The crude oils were applied for 13 wk, 5 d/wk. Exposure sites were not occluded. Mean body weight gain (wk 1-14) was significantly reduced in male rats exposed to Crude II; body weight gain of all other animals was not adversely affected by treatment. An increase in absolute (A) and relative (R) liver weights and a decrease in A and R thymus weights were observed in male and female rats exposed to Crude II at 500 mg/kg; only liver weights (A and R) were adversely affected in male and female rats exposed to Crude I. In general, there was no consistent pattern of toxicity for serum chemistry endpoints; however, more parameters were adversely affected in Crude II-exposed female rats than in the other exposed groups. A consistent pattern of toxicity for hematology endpoints was observed among male rats exposed to Crude I and male and female rats exposed to Crude II. Parameters affected included: Crudes I and II, red blood cell count, hemoglobin, and hematocrit; Crude II, platelet count. Microscopic evaluation of tissues revealed the following treatment-related findings: Crude I, treated skin, thymus, and thyroid; Crude II, bone marrow, treated skin, thymus, and thyroid. The LOEL (lowest observable effect level) for skin irritation and systemic toxicity (based on marginal effects on the thyroid) for both crude oils was 30 mg/kg; effects were more numerous and more pronounced in animals exposed to Crude II. Systemic effects are probably related to concentrations of polycyclic aromatic compounds (PAC) found in crude oil.
{"title":"Systemic toxicity of dermally applied crude oils in rats.","authors":"M. Feuston, C. Mackerer, C. Schreiner, C. E. Hamilton","doi":"10.1080/009841097160005","DOIUrl":"https://doi.org/10.1080/009841097160005","url":null,"abstract":"Two crude oils, differing in viscosity (V) and nitrogen (N) and sulfur (S) content, were evaluated for systemic toxicity. In the Crude I (low V, low N, low S) study, the material was applied to the clipped backs of rats at dose levels of 0, 30, 125, and 500 mg/kg. In the Crude II (high V, high N, moderate S) study, the oil was applied similarly at the same dose levels. The crude oils were applied for 13 wk, 5 d/wk. Exposure sites were not occluded. Mean body weight gain (wk 1-14) was significantly reduced in male rats exposed to Crude II; body weight gain of all other animals was not adversely affected by treatment. An increase in absolute (A) and relative (R) liver weights and a decrease in A and R thymus weights were observed in male and female rats exposed to Crude II at 500 mg/kg; only liver weights (A and R) were adversely affected in male and female rats exposed to Crude I. In general, there was no consistent pattern of toxicity for serum chemistry endpoints; however, more parameters were adversely affected in Crude II-exposed female rats than in the other exposed groups. A consistent pattern of toxicity for hematology endpoints was observed among male rats exposed to Crude I and male and female rats exposed to Crude II. Parameters affected included: Crudes I and II, red blood cell count, hemoglobin, and hematocrit; Crude II, platelet count. Microscopic evaluation of tissues revealed the following treatment-related findings: Crude I, treated skin, thymus, and thyroid; Crude II, bone marrow, treated skin, thymus, and thyroid. The LOEL (lowest observable effect level) for skin irritation and systemic toxicity (based on marginal effects on the thyroid) for both crude oils was 30 mg/kg; effects were more numerous and more pronounced in animals exposed to Crude II. Systemic effects are probably related to concentrations of polycyclic aromatic compounds (PAC) found in crude oil.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"18 1","pages":"387-99"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75487326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Craig C. Conrad, Christi A. Walter, Arlan Richardson, Martha A. Hanes, David T. Grabowski
To date, numerous correlative studies have implicated metallothionein in the detoxification of heavy metals and in the regulation of metal distribution within an organism. In the present study cadmium-binding proteins (metallothionein equivalents), cadmium acute toxicity, and cadmium distribution in tissues and subcellular fractions were compared in metallothionein-I and -II deficient (MT-/-) mice and the parental strain carrying intact metallothionein genes (MT+/+) to determine if the absence of metallothionein altered any of these parameters. In an uninduced state, MT-/- mice expressed lower levels of cadmium-binding proteins relative to MT+/+ mice in several tissues. Administration of zinc enhanced the levels of cadmium-binding proteins in liver, small intestine, kidney, pancreas, and male sex organs, but not in cecum or brain of MT+/+ mice compared to zinc pretreated MT-/- mice. The cadmium LD50 was similar for MT-/-, MT+/+, and zinc-pretreated MT-/- mice (15-17 mumol CdCl2/kg body weight delivered i.p.). However, zinc-pretreated MT+/+ mice had a cadmium LD50 of 58-63 mumol CdCl2/kg body weight. Over two-thirds of cadmium was found in liver, cecum, small intestine, and kidney in both MT+/+ and MT-/- mice; therefore, metallothionein levels do not appear to play a major role in the tissue distribution of cadmium. However, after zinc pretreatment, MT+/+ mice accumulated more cadmium in the liver and less in other tissues, whereas the amount of cadmium in the liver was not altered by zinc pretreatment in MT-/- mice. In general, the cytosolic/particulate ratio of cadmium was significantly higher in tissues of noninduced MT+/+ mice relative to MT-/- mice. This difference was accentuated after zinc pretreatment. Together these results indicate that basal levels of metallothionein do not protect from the acute toxicity of a single i.p. cadmium challenge. Furthermore, it does not appear that the cytosolic compartmentalization of cadmium is correlated with reduced toxicity.
{"title":"Cadmium toxicity and distribution in metallothionein-I and -II deficient transgenic mice.","authors":"Craig C. Conrad, Christi A. Walter, Arlan Richardson, Martha A. Hanes, David T. Grabowski","doi":"10.1080/009841097159502","DOIUrl":"https://doi.org/10.1080/009841097159502","url":null,"abstract":"To date, numerous correlative studies have implicated metallothionein in the detoxification of heavy metals and in the regulation of metal distribution within an organism. In the present study cadmium-binding proteins (metallothionein equivalents), cadmium acute toxicity, and cadmium distribution in tissues and subcellular fractions were compared in metallothionein-I and -II deficient (MT-/-) mice and the parental strain carrying intact metallothionein genes (MT+/+) to determine if the absence of metallothionein altered any of these parameters. In an uninduced state, MT-/- mice expressed lower levels of cadmium-binding proteins relative to MT+/+ mice in several tissues. Administration of zinc enhanced the levels of cadmium-binding proteins in liver, small intestine, kidney, pancreas, and male sex organs, but not in cecum or brain of MT+/+ mice compared to zinc pretreated MT-/- mice. The cadmium LD50 was similar for MT-/-, MT+/+, and zinc-pretreated MT-/- mice (15-17 mumol CdCl2/kg body weight delivered i.p.). However, zinc-pretreated MT+/+ mice had a cadmium LD50 of 58-63 mumol CdCl2/kg body weight. Over two-thirds of cadmium was found in liver, cecum, small intestine, and kidney in both MT+/+ and MT-/- mice; therefore, metallothionein levels do not appear to play a major role in the tissue distribution of cadmium. However, after zinc pretreatment, MT+/+ mice accumulated more cadmium in the liver and less in other tissues, whereas the amount of cadmium in the liver was not altered by zinc pretreatment in MT-/- mice. In general, the cytosolic/particulate ratio of cadmium was significantly higher in tissues of noninduced MT+/+ mice relative to MT-/- mice. This difference was accentuated after zinc pretreatment. Together these results indicate that basal levels of metallothionein do not protect from the acute toxicity of a single i.p. cadmium challenge. Furthermore, it does not appear that the cytosolic compartmentalization of cadmium is correlated with reduced toxicity.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"95 1","pages":"527-43"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73591448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Poon, H. Davis, P. Lecavalier, R. Liteplo, A. Yagminas, I. Chu, C. Bihun
The systemic toxicity of benzothiophene, a sulfur-containing heterocyclic present in petroleum, coal, and their derived products, was studied in male rats following short-term oral exposure. Male Sprague-Dawley rats (130 +/- 20 g) (n = 5 per dose group) were treated with benzothiophene by gavage at dosages of 0, 2, 20 or 200 mg/kg/d for 21 d. In another study, male rats were treated with 0, 100, or 500 ppm benzothiophene via the diet for 28 d. In the gavage study, the 200 mg/kg/d rats showed depressed weight gain, increased relative liver and kidney weights, decreased relative thymus weights, and elevated levels of serum gamma-glutamyltransferase (gamma-GT), hepatic aniline hydroxylase (AH), aminopyrine N-demethylase (APDM), pentoxyresorufin O-dealkylase (PROD), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities. A 4.5-fold increase in urine volume on d 14-21 and a transient, 4-fold increase in urinary ascorbic acid on d 1 were also detected. No treatment related changes in urinary N-acetylglucosaminidase (NAGA) activity were observed. Benzothiophene residues were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg rats, but a small quantity was detected in the urine. In the diet study, animals fed the 500 ppm diet had increased absolute and relative liver weights, elevated AH, APDM, and GST activities, decreased red blood cell count, and minor increases in serum urea nitrogen and glucose. In summary, benzothiophene produced adverse effects in male rats that included increased relative liver and kidney weights and increased urine output. Benzothiophene also caused increases in hepatic drug metabolizing enzyme activities of a phenobarbital type and a transient elevation in urinary ascorbic acid.
{"title":"Effects of benzothiophene on male rats following short-term oral exposure.","authors":"R. Poon, H. Davis, P. Lecavalier, R. Liteplo, A. Yagminas, I. Chu, C. Bihun","doi":"10.1080/009841097160609","DOIUrl":"https://doi.org/10.1080/009841097160609","url":null,"abstract":"The systemic toxicity of benzothiophene, a sulfur-containing heterocyclic present in petroleum, coal, and their derived products, was studied in male rats following short-term oral exposure. Male Sprague-Dawley rats (130 +/- 20 g) (n = 5 per dose group) were treated with benzothiophene by gavage at dosages of 0, 2, 20 or 200 mg/kg/d for 21 d. In another study, male rats were treated with 0, 100, or 500 ppm benzothiophene via the diet for 28 d. In the gavage study, the 200 mg/kg/d rats showed depressed weight gain, increased relative liver and kidney weights, decreased relative thymus weights, and elevated levels of serum gamma-glutamyltransferase (gamma-GT), hepatic aniline hydroxylase (AH), aminopyrine N-demethylase (APDM), pentoxyresorufin O-dealkylase (PROD), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities. A 4.5-fold increase in urine volume on d 14-21 and a transient, 4-fold increase in urinary ascorbic acid on d 1 were also detected. No treatment related changes in urinary N-acetylglucosaminidase (NAGA) activity were observed. Benzothiophene residues were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg rats, but a small quantity was detected in the urine. In the diet study, animals fed the 500 ppm diet had increased absolute and relative liver weights, elevated AH, APDM, and GST activities, decreased red blood cell count, and minor increases in serum urea nitrogen and glucose. In summary, benzothiophene produced adverse effects in male rats that included increased relative liver and kidney weights and increased urine output. Benzothiophene also caused increases in hepatic drug metabolizing enzyme activities of a phenobarbital type and a transient elevation in urinary ascorbic acid.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"82 1","pages":"53-65"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89017153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Occupational exposure to methyl isobutyl ketone (MiBK) or methyl n-butyl ketone (MnBK) normally occurs by inhalation. The present study reports that exposure to both ketones can potentiate cholestasis experimentally induced by taurolithocholic acid (TLC, 30 mol/kg) or by a combination of manganese (Mn, 4.5 mg/kg) and bilirubin (BR, 25 mg/kg). Male Sprague-Dawley rats were exposed for 3 d, 4 h/d, to MiBK or MnBK vapors using 0.5, 1, 1.5, or 2 times the minimal effective concentration (MEC). The estimated MiBK or MnBK MEC for potentiating TLC- or Mn-BR-induced cholestasis were 400 and 150 ppm, respectively. Eighteen hours after ketone exposure, rats were injected iv with TLC or Mn-BR. Bile flow was measured from 15 to 150 min after the cholestatic regimen. Rats exposed to MiBK or MnBK exhibited an enhanced diminution in bile flow compared to controls that was dose-dependent with the inhaled ketone dose. The dose-effect characteristics of the potentiation phenomenon were established. Results indicate that Mi...
{"title":"Ketone potentiation of intrahepatic cholestasis: effect of two aliphatic isomers.","authors":"Duguay Ab, Plaa Gl","doi":"10.1080/009841097160591","DOIUrl":"https://doi.org/10.1080/009841097160591","url":null,"abstract":"Occupational exposure to methyl isobutyl ketone (MiBK) or methyl n-butyl ketone (MnBK) normally occurs by inhalation. The present study reports that exposure to both ketones can potentiate cholestasis experimentally induced by taurolithocholic acid (TLC, 30 mol/kg) or by a combination of manganese (Mn, 4.5 mg/kg) and bilirubin (BR, 25 mg/kg). Male Sprague-Dawley rats were exposed for 3 d, 4 h/d, to MiBK or MnBK vapors using 0.5, 1, 1.5, or 2 times the minimal effective concentration (MEC). The estimated MiBK or MnBK MEC for potentiating TLC- or Mn-BR-induced cholestasis were 400 and 150 ppm, respectively. Eighteen hours after ketone exposure, rats were injected iv with TLC or Mn-BR. Bile flow was measured from 15 to 150 min after the cholestatic regimen. Rats exposed to MiBK or MnBK exhibited an enhanced diminution in bile flow compared to controls that was dose-dependent with the inhaled ketone dose. The dose-effect characteristics of the potentiation phenomenon were established. Results indicate that Mi...","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"11 1","pages":"41-52"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85133097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Kozłowska, K. Krzystyniak, N. Drela, P. Grabarczyk, K. Izdebska-Szymona
Industrial air pollutants from Upper Silesia, Poland, contain over 250 polycyclic and heterocyclic aromatic hydrocarbons and heavy metals, including mutagenic and carcinogenic chemicals that have been shown to form DNA adducts. Over 4 million habitants of Silesia are permanently exposed to the industrial pollution by pulmonary and dermal routes and by contaminated food and water. These chemicals, when examined separately in animals models, were proven immunotoxic. We studied the extrapulmonary immunotoxic potential of a typical mixture of Silesian filter-suspended matter from a selected area, over a specific season and time period. Early changes in the immune system were analyzed in BALB/c mice exposed ip to acute doses of 20-330 mg dust mixture/kg body weight (0.06-1.0 LD50). No major changes were noted for weight and the cellularity of spleen, liver and kidneys. However, dramatic decrease in thymus weight index and thymocyte cell count were noted as early as 24-72 h postexposure, which correlated with almost complete depletion of immature, double-positive CD4+CD8+ thymocytes. Changes in spleen were less profound; however, increased depletion of B cells over T cells was noted at high doses of the suspended matter. Exposure to the airborne dust also decreased cytokine production by spleen cells, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Overall, a single exposure to Silesian dust, even at the relatively low 0.06 LD50 dose, affected lymphokine production, suppressed B-cell proliferative response, and depleted thymuses of immature, double-positive CD4+CD8+ cells. A chemical synergism is suspected. To our knowledge, none of the known components of Silesian suspended matter, when examined as a single chemical, was shown to exert such a profound biological effect.
{"title":"Thymus-directed immunotoxicity of airborne dust particles from Upper Silesia (Poland) under acute extrapulmonary studies in mice.","authors":"E. Kozłowska, K. Krzystyniak, N. Drela, P. Grabarczyk, K. Izdebska-Szymona","doi":"10.1080/009841096160628","DOIUrl":"https://doi.org/10.1080/009841096160628","url":null,"abstract":"Industrial air pollutants from Upper Silesia, Poland, contain over 250 polycyclic and heterocyclic aromatic hydrocarbons and heavy metals, including mutagenic and carcinogenic chemicals that have been shown to form DNA adducts. Over 4 million habitants of Silesia are permanently exposed to the industrial pollution by pulmonary and dermal routes and by contaminated food and water. These chemicals, when examined separately in animals models, were proven immunotoxic. We studied the extrapulmonary immunotoxic potential of a typical mixture of Silesian filter-suspended matter from a selected area, over a specific season and time period. Early changes in the immune system were analyzed in BALB/c mice exposed ip to acute doses of 20-330 mg dust mixture/kg body weight (0.06-1.0 LD50). No major changes were noted for weight and the cellularity of spleen, liver and kidneys. However, dramatic decrease in thymus weight index and thymocyte cell count were noted as early as 24-72 h postexposure, which correlated with almost complete depletion of immature, double-positive CD4+CD8+ thymocytes. Changes in spleen were less profound; however, increased depletion of B cells over T cells was noted at high doses of the suspended matter. Exposure to the airborne dust also decreased cytokine production by spleen cells, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Overall, a single exposure to Silesian dust, even at the relatively low 0.06 LD50 dose, affected lymphokine production, suppressed B-cell proliferative response, and depleted thymuses of immature, double-positive CD4+CD8+ cells. A chemical synergism is suspected. To our knowledge, none of the known components of Silesian suspended matter, when examined as a single chemical, was shown to exert such a profound biological effect.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"95 1","pages":"563-79"},"PeriodicalIF":0.0,"publicationDate":"1996-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74976674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. -. Yang, C. Huang, H. Chiu, J. Chiu, S. Lan, Y. Ko
The object of this study was to assess the relationship between occupational Portland cement dust exposure and respiratory health. Respiratory symptoms and ventilatory function were studied in a group of 591 male Portland cement workers employed in four cement plants. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers. The exposed group had a significantly lower mean forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), and forced expiratory flows after exhalation of 50% and 75% of the vital capacity (FEF50, FEF75) than the control group. The data suggest that occupational exposure to Portland cement dust may lead to higher prevalence of chronic respiratory symptoms and the reduction of ventilatory capacity.
{"title":"Effects of occupational dust exposure on the respiratory health of Portland cement workers.","authors":"C. -. Yang, C. Huang, H. Chiu, J. Chiu, S. Lan, Y. Ko","doi":"10.1080/009841096160637","DOIUrl":"https://doi.org/10.1080/009841096160637","url":null,"abstract":"The object of this study was to assess the relationship between occupational Portland cement dust exposure and respiratory health. Respiratory symptoms and ventilatory function were studied in a group of 591 male Portland cement workers employed in four cement plants. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers. The exposed group had a significantly lower mean forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), and forced expiratory flows after exhalation of 50% and 75% of the vital capacity (FEF50, FEF75) than the control group. The data suggest that occupational exposure to Portland cement dust may lead to higher prevalence of chronic respiratory symptoms and the reduction of ventilatory capacity.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"32 1","pages":"581-8"},"PeriodicalIF":0.0,"publicationDate":"1996-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91285812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Siess, Mastropaolo Jp, M. Canivenc-Lavier, M. Suschetet
Effects of continuous feeding flavonoids (flavone, flavanone, and tangeretin) on drug-metabolizing enzymes in rat liver were investigated to ascertain how long feeding is required to reach maximal induction and to determine whether maximal induction is maintained for a long period of feeding. In the first experiment rats received a diet containing 10 mmol flavonoid/kg dry matter for 4, 8, 16, or 32 d. The second experiment was designed to examine the time course for induction during the first 4 d. The kinetics of induction depended on the chemical structure of the flavonoid and was different from one enzyme to another. Flavone increased P450 1A and P450 2B apoproteins and stimulated many enzyme activities. A significant increase of P450 1A1/2 proteins, ethoxyresorufin O-deethylase (EROD), and methoxyresorufin O-demethylase (MROD) activities occurred as early as 6 h after the first administration, and a gradual increase was observed up to 4 d of feeding. P450 2B1/2 proteins and pentoxyresorufin O-depentylase (PROD) activity were also increased but after a lag period when compared with P450 1A1/2 proteins. EROD and MROD activities declined after 4 d, whereas PROD activity remained steady during 32 d of flavone feeding. Glutathione transferase (GST) and p-nitrophenol UDP-glucuronosyl transferase (UGT) activities were also increased. The maximal induction was reached by 4 d of feeding for UGT and after a longer duration of feeding (16 d) for GST. Flavanone treatment induced mostly P450 2B1/2 proteins and PROD, GST, and UGT activites. After 4 d of feeding, P450 2B1/2 proteins and PROD activity declined whereas GST and UGT activities remained steady. Tangeretin treatment produced changes similar to flavone but of lesser magnitude and after a longer delay.
{"title":"Time course of induction of rat hepatic drug-metabolizing enzyme activities following dietary administration of flavonoids.","authors":"M. Siess, Mastropaolo Jp, M. Canivenc-Lavier, M. Suschetet","doi":"10.1080/009841096160709","DOIUrl":"https://doi.org/10.1080/009841096160709","url":null,"abstract":"Effects of continuous feeding flavonoids (flavone, flavanone, and tangeretin) on drug-metabolizing enzymes in rat liver were investigated to ascertain how long feeding is required to reach maximal induction and to determine whether maximal induction is maintained for a long period of feeding. In the first experiment rats received a diet containing 10 mmol flavonoid/kg dry matter for 4, 8, 16, or 32 d. The second experiment was designed to examine the time course for induction during the first 4 d. The kinetics of induction depended on the chemical structure of the flavonoid and was different from one enzyme to another. Flavone increased P450 1A and P450 2B apoproteins and stimulated many enzyme activities. A significant increase of P450 1A1/2 proteins, ethoxyresorufin O-deethylase (EROD), and methoxyresorufin O-demethylase (MROD) activities occurred as early as 6 h after the first administration, and a gradual increase was observed up to 4 d of feeding. P450 2B1/2 proteins and pentoxyresorufin O-depentylase (PROD) activity were also increased but after a lag period when compared with P450 1A1/2 proteins. EROD and MROD activities declined after 4 d, whereas PROD activity remained steady during 32 d of flavone feeding. Glutathione transferase (GST) and p-nitrophenol UDP-glucuronosyl transferase (UGT) activities were also increased. The maximal induction was reached by 4 d of feeding for UGT and after a longer duration of feeding (16 d) for GST. Flavanone treatment induced mostly P450 2B1/2 proteins and PROD, GST, and UGT activites. After 4 d of feeding, P450 2B1/2 proteins and PROD activity declined whereas GST and UGT activities remained steady. Tangeretin treatment produced changes similar to flavone but of lesser magnitude and after a longer delay.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"29 1","pages":"481-96"},"PeriodicalIF":0.0,"publicationDate":"1996-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76726693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SYMPOSIUM ON PHARMACOKINETICS PHARMACODYNAMICS IN THE DEVELOPING SYSTEM AND IMPACT ON RISK ASSESSMENT EXECUTIVE SUMMARY","authors":"John F Young Bernard A Schwetz Calv","doi":"10.1080/009841096160754","DOIUrl":"https://doi.org/10.1080/009841096160754","url":null,"abstract":"","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"7 1","pages":"339-356"},"PeriodicalIF":0.0,"publicationDate":"1996-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87219337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Castranova, W. Pailes, D. Judy, T. Blake, D. Schwegler-Berry, W. Jones
The objective of this study was to explore the use of alveolar macrophage culture to evaluate the cytotoxicity of two glass fiber materials, a building insulation fiberglass (a relatively long and thick fiber) and a glass microfiber (a short and thin fiber). Alveolar macrophages were obtained from male Sprague-Dawley rats by bronchoalveolar lavage and were cultured with varying fiber concentrations for up to 3 d. Fiber toxicity was assessed by assaying cell viability, membrane integrity, and phagocyte function. The microfibers exhibited a concentration-dependent cytotoxicity shown by the loss of cell viability and function. The building insulation fiberglass had little effect on cell viability and did not change macrophage function in this assay system. The results of this study show that short and thin glass fibers are more toxic than long and thick fibers in vitro, supporting a role of fiber dimension in toxicity.
{"title":"In vitro effects of large and small glass fibers on rat alveolar macrophages.","authors":"V. Castranova, W. Pailes, D. Judy, T. Blake, D. Schwegler-Berry, W. Jones","doi":"10.1080/009841096160763","DOIUrl":"https://doi.org/10.1080/009841096160763","url":null,"abstract":"The objective of this study was to explore the use of alveolar macrophage culture to evaluate the cytotoxicity of two glass fiber materials, a building insulation fiberglass (a relatively long and thick fiber) and a glass microfiber (a short and thin fiber). Alveolar macrophages were obtained from male Sprague-Dawley rats by bronchoalveolar lavage and were cultured with varying fiber concentrations for up to 3 d. Fiber toxicity was assessed by assaying cell viability, membrane integrity, and phagocyte function. The microfibers exhibited a concentration-dependent cytotoxicity shown by the loss of cell viability and function. The building insulation fiberglass had little effect on cell viability and did not change macrophage function in this assay system. The results of this study show that short and thin glass fibers are more toxic than long and thick fibers in vitro, supporting a role of fiber dimension in toxicity.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"1 1","pages":"357-69"},"PeriodicalIF":0.0,"publicationDate":"1996-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88538505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Summer, J. Giesy, S. Bursian, J. Render, T. Kubiak, P. Jones, D. Verbrugge, R. Aulerich
Carp from Saginaw Bay, Lake Huron, MI, was fed to White Leghorn chickens for a period of 8 wk. The diets contained 0.3 (control; 0% carp), 0.8 (3.4% carp), and 6.6 (35% carp) mg polychlorinated biphenyls (PCBs)/kg diet, by wet weight (ww). These concentrations corresponded to 3.3, 26, and 59 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents/g diet ww, respectively. Though the diets were not acutely toxic to the adult laying hens, dose- and time-dependent responses were observed in the embryos and chicks. Toxicity was manifested as a dose-dependent increase in embryo mortality and decreased hatching rates. Furthermore, embryos and chicks displayed various deformities, including (1) head and neck edema and hemorrhage, (2) abdominal edema and hemorrhage, (3) foot and leg deformities, (4) skull and brain deformities, (5) yolk-sac deformities, and (6) miscellaneous deformities. The types of deformities observed were similar to those reported for embryos and chicks of colonial waterbirds in Saginaw Bay, as well as in controlled studies where technical mixtures or individual congeners of polychlorinated diaromatic hydrocarbons (PCDAHs) were fed to chickens. Increasing concentrations of carp also significantly affected the various organ weights in 18-d embryos and hatched chicks. At 18 d of incubation, weights of the embryos' livers were directly proportional to the concentration of PCBs in the diets. The weights of the spleens and bursae were inversely proportional to the dietary PCB concentration. After 3 additional days of incubation, significant effects in body, brain, liver, heart, and bursa weights were observed in hatched chicks. The concentrations of total PCBs, as well as 2,3,7,8-TCDD equivalents (TEQs) in the diets, were in the range of those that have been shown to cause similar adverse effects in other species. This study has shown that fish, the primary food source of colonial waterbirds in Saginaw Bay, are capable of causing adverse reproductive effects in a model avian species, the chicken. However, due to differences in the relative potency to cause effects on different endpoints in different species, the results of this study should not be used to predict the threshold for effects in other species.
{"title":"Effects induced by feeding organochlorine-contaminated carp from Saginaw Bay, Lake Huron, to laying White Leghorn hens. II. Embryotoxic and teratogenic effects.","authors":"C. Summer, J. Giesy, S. Bursian, J. Render, T. Kubiak, P. Jones, D. Verbrugge, R. Aulerich","doi":"10.1080/009841096160790","DOIUrl":"https://doi.org/10.1080/009841096160790","url":null,"abstract":"Carp from Saginaw Bay, Lake Huron, MI, was fed to White Leghorn chickens for a period of 8 wk. The diets contained 0.3 (control; 0% carp), 0.8 (3.4% carp), and 6.6 (35% carp) mg polychlorinated biphenyls (PCBs)/kg diet, by wet weight (ww). These concentrations corresponded to 3.3, 26, and 59 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents/g diet ww, respectively. Though the diets were not acutely toxic to the adult laying hens, dose- and time-dependent responses were observed in the embryos and chicks. Toxicity was manifested as a dose-dependent increase in embryo mortality and decreased hatching rates. Furthermore, embryos and chicks displayed various deformities, including (1) head and neck edema and hemorrhage, (2) abdominal edema and hemorrhage, (3) foot and leg deformities, (4) skull and brain deformities, (5) yolk-sac deformities, and (6) miscellaneous deformities. The types of deformities observed were similar to those reported for embryos and chicks of colonial waterbirds in Saginaw Bay, as well as in controlled studies where technical mixtures or individual congeners of polychlorinated diaromatic hydrocarbons (PCDAHs) were fed to chickens. Increasing concentrations of carp also significantly affected the various organ weights in 18-d embryos and hatched chicks. At 18 d of incubation, weights of the embryos' livers were directly proportional to the concentration of PCBs in the diets. The weights of the spleens and bursae were inversely proportional to the dietary PCB concentration. After 3 additional days of incubation, significant effects in body, brain, liver, heart, and bursa weights were observed in hatched chicks. The concentrations of total PCBs, as well as 2,3,7,8-TCDD equivalents (TEQs) in the diets, were in the range of those that have been shown to cause similar adverse effects in other species. This study has shown that fish, the primary food source of colonial waterbirds in Saginaw Bay, are capable of causing adverse reproductive effects in a model avian species, the chicken. However, due to differences in the relative potency to cause effects on different endpoints in different species, the results of this study should not be used to predict the threshold for effects in other species.","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":"18 1","pages":"409-38"},"PeriodicalIF":0.0,"publicationDate":"1996-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74428056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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