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Moira Mckernan - One of the best experts on this subject based on the ideXlab platform.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.

Mary Ann Ottinger - One of the best experts on this subject based on the ideXlab platform.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.

Stacy C Dilzer - One of the best experts on this subject based on the ideXlab platform.

  • metabolism and excretion of the dipeptidyl peptidase 4 inhibitor 14c sitagliptin in humans
    2007
    Co-Authors: Stella H Vincent, Arthur J Bergman, James R Reed, Charles S Elmore, Bing Zhu, David L Ebel, Patrick J Larson, Wei Zeng, Li Chen, Stacy C Dilzer
    Abstract:

    The metabolism and excretion of [ 14 C]sitagliptin, an orally active, potent and selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a single oral Dose of 83 mg/193 μCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the Administered Dose recovered in urine. Mean fecal excretion was 13% of the Administered Dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the Dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing N -sulfate and N -carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.

  • metabolism and excretion of the dipeptidyl peptidase 4 inhibitor 14c sitagliptin in humans
    2007
    Co-Authors: Stella H Vincent, Arthur J Bergman, James R Reed, Charles S Elmore, Bing Zhu, David L Ebel, Patrick J Larson, Wei Zeng, Li Chen, Stacy C Dilzer
    Abstract:

    The metabolism and excretion of [(14)C]sitagliptin, an orally active, potent and selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a single oral Dose of 83 mg/193 muCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the Administered Dose recovered in urine. Mean fecal excretion was 13% of the Administered Dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the Dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing <1 to 7% of the radioactivity in plasma. These metabolites were the N-sulfate and N-carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.

Stella H Vincent - One of the best experts on this subject based on the ideXlab platform.

  • metabolism and excretion of the dipeptidyl peptidase 4 inhibitor 14c sitagliptin in humans
    2007
    Co-Authors: Stella H Vincent, Arthur J Bergman, James R Reed, Charles S Elmore, Bing Zhu, David L Ebel, Patrick J Larson, Wei Zeng, Li Chen, Stacy C Dilzer
    Abstract:

    The metabolism and excretion of [ 14 C]sitagliptin, an orally active, potent and selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a single oral Dose of 83 mg/193 μCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the Administered Dose recovered in urine. Mean fecal excretion was 13% of the Administered Dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the Dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing N -sulfate and N -carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.

  • metabolism and excretion of the dipeptidyl peptidase 4 inhibitor 14c sitagliptin in humans
    2007
    Co-Authors: Stella H Vincent, Arthur J Bergman, James R Reed, Charles S Elmore, Bing Zhu, David L Ebel, Patrick J Larson, Wei Zeng, Li Chen, Stacy C Dilzer
    Abstract:

    The metabolism and excretion of [(14)C]sitagliptin, an orally active, potent and selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a single oral Dose of 83 mg/193 muCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the Administered Dose recovered in urine. Mean fecal excretion was 13% of the Administered Dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the Dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing <1 to 7% of the radioactivity in plasma. These metabolites were the N-sulfate and N-carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.

Barnett A. Rattner - One of the best experts on this subject based on the ideXlab platform.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.

  • toxicity of polybrominated diphenyl ethers de 71 in chicken gallus gallus mallard anas platyrhynchos and american kestrel falco sparverius embryos and hatchlings
    2009
    Co-Authors: Moira Mckernan, Robert C Hale, Barnett A. Rattner, Mary Ann Ottinger
    Abstract:

    : Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to Administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell Administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE Administered Dose was present in the egg contents in chickens, and 18% of the Administered Dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.