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Charles M King - One of the best experts on this subject based on the ideXlab platform.

  • carcinogenicity of dinitropyrenes in the weanling female CD Rat
    Carcinogenesis, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Charles M King
    Abstract:

    The carcinogenicities of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrene were assessed in weanling female CD Rats. The animals were administered one of the compounds at 10 mumol/kg body wt through intraperitoneal or intragastric administRation three times a week for 4 weeks. The total cumulative dose averaged 16 mumol/animal. The experiment was ended 78 weeks following the first administRation. The average survival period for the animals in the 1,6- and 1,8-dinitropyrene i.p. treated groups, due to the occurrence of life-threatening peritoneal malignant fibrous histiocytomas (MFHs) in nearly all of the animals, were 19 and 38 weeks respectively. 1,3-Dinitropyrene induced only a few MFHs. 1,8-Dinitropyrene also induced a significant incidence of leukemia. A significant increase of the incidence of mammary tumors was observed in the groups of Rats treated i.p. with 1-nitropyrene, or 1,3- or 1,8-dinitropyrene, and those treated i.g. with 1,8-dinitropyrene. These results demonstRate that nitropyrenes are capable of inducing MFH, mammary tumors and leukemia in the Rat.

  • compaRative carcinogenicities of 1 2 and 4 nitropyrene and structurally related compounds in the female CD Rat
    Cancer Research, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Masao Hirose, Lee Tay, Charles M King
    Abstract:

    The compaRative carcinogenicities of N -hydroxy- N -acetyl-1-aminopyrene, N -acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weanling female CD Rats (67 µmol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene-and N -hydroxy- N -acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N -acetyl-1-aminopyrene-, N -hydroxy- N -acetyl-1-aminopyrene-, and N -hydroxy- N -acetyl-2-aminofluorene-treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N -hydroxy- N -acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administRation on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD Rats (100 µmol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstRation of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administRation used here. A further exploRation of the effect of the route of administRation involved treatment of weanling female CD Rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 µmol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide. Animals that had received 1- or 2-nitropyrene or the solvent dimethyl sulfoxide had mammary tumor incidences of only 21 to 22%. A majority of the animals that had been given 4-nitropyrene ( i.e. , 22 of 28) had tumors of the treated mammary glands as compared with only a few that developed tumors of the solvent-treated mammary glands ( i.e. , 5 of 28). These data confirm the carcinogenicity of 1-nitropyrene for Rat mammary gland and demonstRate that 4-nitropyrene is the most potent of the three isomeric mononitropyrenes for this organ. The direct carcinogenicity of 4-nitropyrene for the mammary gland establishes that this target organ possesses the enzymes necessary for the metabolic activation of this carcinogen.

Katsumi Imaida - One of the best experts on this subject based on the ideXlab platform.

  • carcinogenicity of dinitropyrenes in the weanling female CD Rat
    Carcinogenesis, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Charles M King
    Abstract:

    The carcinogenicities of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrene were assessed in weanling female CD Rats. The animals were administered one of the compounds at 10 mumol/kg body wt through intraperitoneal or intragastric administRation three times a week for 4 weeks. The total cumulative dose averaged 16 mumol/animal. The experiment was ended 78 weeks following the first administRation. The average survival period for the animals in the 1,6- and 1,8-dinitropyrene i.p. treated groups, due to the occurrence of life-threatening peritoneal malignant fibrous histiocytomas (MFHs) in nearly all of the animals, were 19 and 38 weeks respectively. 1,3-Dinitropyrene induced only a few MFHs. 1,8-Dinitropyrene also induced a significant incidence of leukemia. A significant increase of the incidence of mammary tumors was observed in the groups of Rats treated i.p. with 1-nitropyrene, or 1,3- or 1,8-dinitropyrene, and those treated i.g. with 1,8-dinitropyrene. These results demonstRate that nitropyrenes are capable of inducing MFH, mammary tumors and leukemia in the Rat.

  • compaRative carcinogenicities of 1 2 and 4 nitropyrene and structurally related compounds in the female CD Rat
    Cancer Research, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Masao Hirose, Lee Tay, Charles M King
    Abstract:

    The compaRative carcinogenicities of N -hydroxy- N -acetyl-1-aminopyrene, N -acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weanling female CD Rats (67 µmol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene-and N -hydroxy- N -acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N -acetyl-1-aminopyrene-, N -hydroxy- N -acetyl-1-aminopyrene-, and N -hydroxy- N -acetyl-2-aminofluorene-treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N -hydroxy- N -acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administRation on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD Rats (100 µmol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstRation of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administRation used here. A further exploRation of the effect of the route of administRation involved treatment of weanling female CD Rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 µmol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide. Animals that had received 1- or 2-nitropyrene or the solvent dimethyl sulfoxide had mammary tumor incidences of only 21 to 22%. A majority of the animals that had been given 4-nitropyrene ( i.e. , 22 of 28) had tumors of the treated mammary glands as compared with only a few that developed tumors of the solvent-treated mammary glands ( i.e. , 5 of 28). These data confirm the carcinogenicity of 1-nitropyrene for Rat mammary gland and demonstRate that 4-nitropyrene is the most potent of the three isomeric mononitropyrenes for this organ. The direct carcinogenicity of 4-nitropyrene for the mammary gland establishes that this target organ possesses the enzymes necessary for the metabolic activation of this carcinogen.

Ching Y Wang - One of the best experts on this subject based on the ideXlab platform.

  • carcinogenicity of dinitropyrenes in the weanling female CD Rat
    Carcinogenesis, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Charles M King
    Abstract:

    The carcinogenicities of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrene were assessed in weanling female CD Rats. The animals were administered one of the compounds at 10 mumol/kg body wt through intraperitoneal or intragastric administRation three times a week for 4 weeks. The total cumulative dose averaged 16 mumol/animal. The experiment was ended 78 weeks following the first administRation. The average survival period for the animals in the 1,6- and 1,8-dinitropyrene i.p. treated groups, due to the occurrence of life-threatening peritoneal malignant fibrous histiocytomas (MFHs) in nearly all of the animals, were 19 and 38 weeks respectively. 1,3-Dinitropyrene induced only a few MFHs. 1,8-Dinitropyrene also induced a significant incidence of leukemia. A significant increase of the incidence of mammary tumors was observed in the groups of Rats treated i.p. with 1-nitropyrene, or 1,3- or 1,8-dinitropyrene, and those treated i.g. with 1,8-dinitropyrene. These results demonstRate that nitropyrenes are capable of inducing MFH, mammary tumors and leukemia in the Rat.

  • compaRative carcinogenicities of 1 2 and 4 nitropyrene and structurally related compounds in the female CD Rat
    Cancer Research, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Masao Hirose, Lee Tay, Charles M King
    Abstract:

    The compaRative carcinogenicities of N -hydroxy- N -acetyl-1-aminopyrene, N -acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weanling female CD Rats (67 µmol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene-and N -hydroxy- N -acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N -acetyl-1-aminopyrene-, N -hydroxy- N -acetyl-1-aminopyrene-, and N -hydroxy- N -acetyl-2-aminofluorene-treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N -hydroxy- N -acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administRation on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD Rats (100 µmol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstRation of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administRation used here. A further exploRation of the effect of the route of administRation involved treatment of weanling female CD Rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 µmol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide. Animals that had received 1- or 2-nitropyrene or the solvent dimethyl sulfoxide had mammary tumor incidences of only 21 to 22%. A majority of the animals that had been given 4-nitropyrene ( i.e. , 22 of 28) had tumors of the treated mammary glands as compared with only a few that developed tumors of the solvent-treated mammary glands ( i.e. , 5 of 28). These data confirm the carcinogenicity of 1-nitropyrene for Rat mammary gland and demonstRate that 4-nitropyrene is the most potent of the three isomeric mononitropyrenes for this organ. The direct carcinogenicity of 4-nitropyrene for the mammary gland establishes that this target organ possesses the enzymes necessary for the metabolic activation of this carcinogen.

Meisie Lee - One of the best experts on this subject based on the ideXlab platform.

  • carcinogenicity of dinitropyrenes in the weanling female CD Rat
    Carcinogenesis, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Charles M King
    Abstract:

    The carcinogenicities of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrene were assessed in weanling female CD Rats. The animals were administered one of the compounds at 10 mumol/kg body wt through intraperitoneal or intragastric administRation three times a week for 4 weeks. The total cumulative dose averaged 16 mumol/animal. The experiment was ended 78 weeks following the first administRation. The average survival period for the animals in the 1,6- and 1,8-dinitropyrene i.p. treated groups, due to the occurrence of life-threatening peritoneal malignant fibrous histiocytomas (MFHs) in nearly all of the animals, were 19 and 38 weeks respectively. 1,3-Dinitropyrene induced only a few MFHs. 1,8-Dinitropyrene also induced a significant incidence of leukemia. A significant increase of the incidence of mammary tumors was observed in the groups of Rats treated i.p. with 1-nitropyrene, or 1,3- or 1,8-dinitropyrene, and those treated i.g. with 1,8-dinitropyrene. These results demonstRate that nitropyrenes are capable of inducing MFH, mammary tumors and leukemia in the Rat.

  • compaRative carcinogenicities of 1 2 and 4 nitropyrene and structurally related compounds in the female CD Rat
    Cancer Research, 1991
    Co-Authors: Katsumi Imaida, Meisie Lee, Ching Y Wang, Masao Hirose, Lee Tay, Charles M King
    Abstract:

    The compaRative carcinogenicities of N -hydroxy- N -acetyl-1-aminopyrene, N -acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weanling female CD Rats (67 µmol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene-and N -hydroxy- N -acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N -acetyl-1-aminopyrene-, N -hydroxy- N -acetyl-1-aminopyrene-, and N -hydroxy- N -acetyl-2-aminofluorene-treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N -hydroxy- N -acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administRation on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD Rats (100 µmol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstRation of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administRation used here. A further exploRation of the effect of the route of administRation involved treatment of weanling female CD Rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 µmol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide. Animals that had received 1- or 2-nitropyrene or the solvent dimethyl sulfoxide had mammary tumor incidences of only 21 to 22%. A majority of the animals that had been given 4-nitropyrene ( i.e. , 22 of 28) had tumors of the treated mammary glands as compared with only a few that developed tumors of the solvent-treated mammary glands ( i.e. , 5 of 28). These data confirm the carcinogenicity of 1-nitropyrene for Rat mammary gland and demonstRate that 4-nitropyrene is the most potent of the three isomeric mononitropyrenes for this organ. The direct carcinogenicity of 4-nitropyrene for the mammary gland establishes that this target organ possesses the enzymes necessary for the metabolic activation of this carcinogen.

I M Pritts - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of the developmental toxicity of ethylene glycol aerosol in the CD Rat and CD 1 mouse by whole body exposure
    Toxicological Sciences, 1995
    Co-Authors: R W Tyl, Bryan Ballantyne, L C Fisher, D L Fait, T A Savine, Darol E Dodd, Dennis R Klonne, I M Pritts
    Abstract:

    Ethylene glycol (EG) is a major industrial chemical, shown to be teRatogenic at high doses by gavage in rodents. Since one route of industrial exposure is to the aerosol at high concentRations, timed-pregnant CD Rats and CD-1 mice were exposed, whole-body, to a respirable aerosol of EG (mass median aerodynamic diameter, 2.3 microns) on Gestational Days (GD) 6 through 15 for 6 hr per day at target exposure concentRations of 0, 150, 1000, or 2500 mg/m3 (analytical concentRations of 0, 119 +/- 13, 888 +/- 149, and 2090 +/- 244 mg/m3, respectively), with 25 plug-positive animals per species per group. Clinical observations and maternal body weights were documented throughout gestation for both species. Maternal food and water consumption was measured in Rats only throughout gestation. At scheduled necropsy (GD 21 for Rats, GD 18 for mice), maternal animals were evaluated for body weight, liver weight, kidney weight, gravid uterine weight, number of ovarian corpora lutea, and status of implantation sites, i.e., resorptions, dead fetuses, live fetuses. Fetuses were dissected from the uterus, counted, weighed, sexed, and examined for external, visceral, and skeletal malformations and variations. All Rat dams survived to scheduled termination. Minimal maternal toxicity was indicated by a significant increase in absolute and relative liver weight at 2500 mg/m3. Food and water consumption, maternal body weights and weight gain, and maternal organ weights (other than liver) were unaffected by exposure. Gestational parameters were unaffected by exposure, including pre- and post-implantation loss, live fetuses/litter, sex Ratio, and fetal body weight/litter. There was no treatment-related increase in the incidence of any individual malformation, in the incidence of pooled external, visceral, or skeletal malformations, or in the incidence of total malformations by fetus or by litter. There were no increases in the incidence of external or visceral variations. Evidence of fetotoxicity, expressed as reduced ossification in the humerus, the zygomatic arch, and the metatarsals and proximal phalanges of the hind-limb, was observed at 1000 and 2500 mg/m3. All mouse dams survived to scheduled termination. One dam at 2500 mg/m3 was carrying a totally resorbed litter at termination. Maternal toxicity was observed at 1000 and 2500 mg/m3, expressed as reduced body weight and weight gain during and after the exposure period, and reduced gravid uterine weight. (Maternal effects may have been due, in part or whole, to effects on the conceptuses; see below.)(ABSTRACT TRUNCATED AT 400 WORDS)