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Manjeong Paik - One of the best experts on this subject based on the ideXlab platform.
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Inflammatory and tumorigenic effects of environmental pollutants found in particulate matter on lung epithelial cells
Toxicology in Vitro, 2019Co-Authors: Rui Zhou, So-yeon Park, Yi Yang, Chathurika D. B. Gamage, Manjeong PaikAbstract:Abstract Exposure to environmental pollutants is a major public health concern. This study investigated the inflammatory and tumorigenic effects of environmental pollutants (benzene, benzo[a]pyrene, cadmium, and Diisononyl Phthalate) on transformed A549 and H292 lung alveolar epithelial cells and non-transformed BEAS-2B lung bronchial epithelial cells. The cytotoxic effects of the pollutants were analyzed by the methyl thiazolyl tetrazolium assay. The anchorage-independent soft agar assay demonstrated that treatment with benzene, cadmium, and Diisononyl Phthalate for 4 weeks induced malignant transformation of BEAS-2B cells and tumorigenesis of A549 and H292 cells. mRNA expression of the inflammation-related genes tenascin-C, matrix metalloproteinase (MMP)-9, and MMP-2, as well as inhibitors of MMPs (TIMP-1 and TIMP-2), was analyzed by RT-PCR. The pollutants largely upregulated expression of MMP-9 and MMP-2, but suppressed expression of their inhibitors TIMP-1 and TIMP-2. Measurement of transepithelial electrical resistance revealed that cadmium and Diisononyl Phthalate significantly increased cell permeability. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor of inflammatory genes, including MMP-9 and MMP-2, while signal transducer and activator of transcription (STAT) 3 is a key regulator of malignant transformation. All the pollutants activated the NF-κB promoter, while only cadmium induced activation of the STAT3 promoter in HEK293T cells. Moreover, all the pollutants increased the phospho-NF-κB level, but only cadmium and Diisononyl Phthalate increased the phospho-STAT3 level in A549 and BEAS-2B cells. These findings suggest that specific environmental pollutants enhance inflammation, cell permeability, and malignant transformation in lung epithelial cells by activating the oncogenic transcription factors STAT3 and NF-κB.
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effects of Diisononyl Phthalate on osteopenia in intact mice
Toxicology and Applied Pharmacology, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Osteopenia is characterized by bone loss and deterioration of trabecular bone, which leads to osteoporotic fractures. This disease is highly prevalent in industrialized areas and is associated with exposure to endocrine disrupting chemicals (EDCs). Diisononyl Phthalate (DINP) is one of these EDCs and is mainly used as a plasticizer in flexible polyvinyl chloride (PVC) products. Although it is well known that exposure to DINP is harmful to humans, no studies have been reported concerning its contribution to osteopenia. Therefore, in this study, we injected DINP (2, 20, and 200 mg/kg) into C3H/HeN mice for 6 weeks and found that the uterus weight, bone (femur and tibia) weight, and bone length of the DINP-exposed mice were reduced compared to those of the SHAM group. On the other hand, body weight, the serum alkaline phosphatase (ALP) and inorganic phosphorus (IP) levels in the DINP treated mice were increased compared with those of the SHAM group. The tartrate-resistant acid phosphatase (TRAP) activity (bone resorption marker) was increased and the bone alkaline phosphatase (BALP) activity was lowered by the treatment with DINP as compared with the SHAM group. Furthermore, the microarchitecture of the femur and tibia in the intact mice was destroyed by the DINP injection. The tissue volume (TV), bone volume (BV), BV/TV, bone surface (BS), BS/TV, trabecular thickness (Tb.Th), and trabecular number (Tb.N) were reduced and the trabecular pattern factor (Tb.Pf), structure model index (SMI), and trabecular separation (Tb.Sp) were increased by the DINP injection. The bone mineral density (BMD) of the femur and tibia was lower in the DINP group than in the SHAM group. These results indicate that DINP contributes to an increased risk of osteopenia via destruction of the microarchitecture and enhancement of osteoclast activity.
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Diisononyl Phthalate induces asthma via modulation of th1 th2 equilibrium
Toxicology Letters, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Diisononyl Phthalate (DINP), a member of the Phthalate family, is used to plasticize polyvinyl chloride (PVC). This chemical is known to enhance airway inflammation in the OVA-induced asthma model (adjuvant effects) and aggravate allergic dermatitis. Moreover, DINP enhances the production of interleukin-4 in activated CD4+ T cells. However, the effect of DINP itself on the differentiation of naive CD4+ T cells into T helper cells (Th1/Th2) in vitro and allergic asthma in vivo has not yet been studied. In this study, DINP was shown to suppress the polarization of Th1 and enhance the polarization of Th2 from naive CD4+ T cells in vitro. Also, DINP induced allergic asthma via the production of IL-4, IL-5, IgE and IgG1 and the reduction of IFN-γ and IgG2a. Finally, we confirmed that exposure to DINP induces the infiltration of inflammatory cells and PAS positive cells and increases the expression of caspase-1 and caspase-3 in asthmatic mice. In conclusion, we suggest that DINP as an environmental pollutant or endocrine disruptor (ECD) induces asthma via the modulation of the Th1/Th2 equilibrium and production of Th2 mediated cytokines and immunoglobulin.
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Diisononyl Phthalate induces asthma via modulation of Th1/Th2 equilibrium.
Toxicology Letters, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Diisononyl Phthalate (DINP), a member of the Phthalate family, is used to plasticize polyvinyl chloride (PVC). This chemical is known to enhance airway inflammation in the OVA-induced asthma model (adjuvant effects) and aggravate allergic dermatitis. Moreover, DINP enhances the production of interleukin-4 in activated CD4+ T cells. However, the effect of DINP itself on the differentiation of naive CD4+ T cells into T helper cells (Th1/Th2) in vitro and allergic asthma in vivo has not yet been studied. In this study, DINP was shown to suppress the polarization of Th1 and enhance the polarization of Th2 from naive CD4+ T cells in vitro. Also, DINP induced allergic asthma via the production of IL-4, IL-5, IgE and IgG1 and the reduction of IFN-γ and IgG2a. Finally, we confirmed that exposure to DINP induces the infiltration of inflammatory cells and PAS positive cells and increases the expression of caspase-1 and caspase-3 in asthmatic mice. In conclusion, we suggest that DINP as an environmental pollutant or endocrine disruptor (ECD) induces asthma via the modulation of the Th1/Th2 equilibrium and production of Th2 mediated cytokines and immunoglobulin.
Antonia M Calafat - One of the best experts on this subject based on the ideXlab platform.
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occupational exposure to Diisononyl Phthalate dinp in polyvinyl chloride processing operations
International Archives of Occupational and Environmental Health, 2012Co-Authors: Cynthia J Hines, Manori J Silva, Nancy B Hopf, James A Deddens, Antonia M CalafatAbstract:Purpose Diisononyl Phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations.
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Occupational exposure to Diisononyl Phthalate (DiNP) in polyvinyl chloride processing operations
International Archives of Occupational and Environmental Health, 2012Co-Authors: Cynthia J Hines, Manori J Silva, Nancy B Hopf, James A Deddens, Antonia M CalafatAbstract:Purpose Diisononyl Phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations. Methods We assessed DiNP exposure in participants from two companies that manufactured PVC materials, a PVC film manufacturer ( n = 25) and a PVC custom compounder ( n = 12). A mid-shift and end-shift urine sample was collected from each participant and analyzed for the DiNP metabolite mono(carboxy-isooctyl) Phthalate (MCiOP). Mixed models were used to assess the effect on MCiOP concentrations of a worker being assigned to (1) a task using DiNP and (2) a shift where DiNP was used. A simple pharmacokinetic model was used to estimate DiNP daily intake from the MCiOP concentrations. Results Creatinine-adjusted MCiOP urinary concentrations ranged from 0.42–80 μg/g in PVC film and from 1.11–13.4 μg/g in PVC compounding. PVC film participants who worked on a task using DiNP ( n = 7) had the highest MCiOP geometric mean (GM) end-shift concentration (25.2 μg/g), followed by participants who worked on a shift where DiNP was used ( n = 11) (17.7 μg/g) as compared to participants with no task (2.92 μg/g) or shift (2.08 μg/g) exposure to DiNP. The GM end-shift MCiOP concentration in PVC compounding participants (4.80 μg/g) was comparable to PVC film participants with no task or shift exposure to DiNP. Because no PVC compounding participants were assigned to tasks using DINP on the day sampled, DiNP exposure in this company may be underestimated. The highest DiNP intake estimate was 26 μg/kg/day. Conclusion Occupational exposure to DiNP associated with PVC film manufacturing tasks were substantially higher (sixfold to tenfold) than adult general population exposures; however, all daily intake estimates were less than 25% of current United States or European acceptable or tolerable daily intake estimates. Further characterization of DiNP occupational exposures in other industries is recommended.
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Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey
Environmental Health Perspectives, 2010Co-Authors: Antonia M Calafat, Lee Yang Wong, Manori J Silva, James L Preau, Ella Samandar, Larry L. NeedhamAbstract:BackgroundHigh-molecular-weight Phthalates, such as Diisononyl Phthalate (DINP) and diisodecyl Phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.ObjectivesWe assessed exposure...
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Selecting adequate exposure biomarkers of Diisononyl and diisodecyl Phthalates: data from the 2005-2006 National Health and Nutrition Examination Survey.
Environmental Health Perspectives, 2010Co-Authors: Antonia M Calafat, Lee Yang Wong, Manori J Silva, James L Preau, Ella Samandar, Larry L. NeedhamAbstract:BackgroundHigh-molecular-weight Phthalates, such as Diisononyl Phthalate (DINP) and diisodecyl Phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.ObjectivesWe assessed exposure...
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oxidative metabolites of Diisononyl Phthalate as biomarkers for human exposure assessment
Environmental Health Perspectives, 2006Co-Authors: Manori J Silva, James L Preau, Larry L. Needham, John A Reidy, Antonia M CalafatAbstract:Diisononyl Phthalate (DINP) is a complex mixture of predominantly nine-carbon branched-chain dialkyl Phthalate isomers. Similar to di(2-ethylhexyl) Phthalate, a widely used Phthalate, DINP causes antiandrogenic effects on developing rodent male fetuses. Traditionally, assessment of human exposure to DINP has been done using monoisononyl Phthalate (MINP), the hydrolytic metabolite of DINP, as a biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative metabolites, including mono(carboxyisooctyl) Phthalate (MCIOP), mono(oxoisononyl) Phthalate (MOINP), and mono(hydroxyisononyl) Phthalate (MHINP) are the major urinary metabolites in DINP-dosed rats. The urinary concentrations of MINP, MCIOP, MOINP, and MHINP were measured in 129 adult anonymous human volunteers with no known exposure to DINP. Although MINP was not present at detectable levels in any of the samples analyzed, MCIOP, MHINP, and MOINP were detected in 97, 100, and 87% of the urine samples at geometric mean levels equal to 8.6, 11.4, and 1.2 ng/mL, respectively. The concentrations of all three oxidative metabolites were highly correlated with each other (p < 0.0001), which confirms a common precursor. MCIOP was excreted predominantly as a free species, whereas MOINP was excreted mostly in its glucuronidated form. The percentage of MHINP excreted either glucuronidated or in its free form was similar. The significantly higher frequency of detection and urinary concentrations of oxidative metabolites than of MINP suggest that these oxidative metabolites are better biomarkers of exposure assessment of DINP than is MINP. Therefore, we concluded that the prevalence of human exposure to DINP is underestimated by using MINP as the sole DINP urinary biomarker.
Yunho Hwang - One of the best experts on this subject based on the ideXlab platform.
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effects of Diisononyl Phthalate on osteopenia in intact mice
Toxicology and Applied Pharmacology, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Osteopenia is characterized by bone loss and deterioration of trabecular bone, which leads to osteoporotic fractures. This disease is highly prevalent in industrialized areas and is associated with exposure to endocrine disrupting chemicals (EDCs). Diisononyl Phthalate (DINP) is one of these EDCs and is mainly used as a plasticizer in flexible polyvinyl chloride (PVC) products. Although it is well known that exposure to DINP is harmful to humans, no studies have been reported concerning its contribution to osteopenia. Therefore, in this study, we injected DINP (2, 20, and 200 mg/kg) into C3H/HeN mice for 6 weeks and found that the uterus weight, bone (femur and tibia) weight, and bone length of the DINP-exposed mice were reduced compared to those of the SHAM group. On the other hand, body weight, the serum alkaline phosphatase (ALP) and inorganic phosphorus (IP) levels in the DINP treated mice were increased compared with those of the SHAM group. The tartrate-resistant acid phosphatase (TRAP) activity (bone resorption marker) was increased and the bone alkaline phosphatase (BALP) activity was lowered by the treatment with DINP as compared with the SHAM group. Furthermore, the microarchitecture of the femur and tibia in the intact mice was destroyed by the DINP injection. The tissue volume (TV), bone volume (BV), BV/TV, bone surface (BS), BS/TV, trabecular thickness (Tb.Th), and trabecular number (Tb.N) were reduced and the trabecular pattern factor (Tb.Pf), structure model index (SMI), and trabecular separation (Tb.Sp) were increased by the DINP injection. The bone mineral density (BMD) of the femur and tibia was lower in the DINP group than in the SHAM group. These results indicate that DINP contributes to an increased risk of osteopenia via destruction of the microarchitecture and enhancement of osteoclast activity.
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Diisononyl Phthalate induces asthma via modulation of th1 th2 equilibrium
Toxicology Letters, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Diisononyl Phthalate (DINP), a member of the Phthalate family, is used to plasticize polyvinyl chloride (PVC). This chemical is known to enhance airway inflammation in the OVA-induced asthma model (adjuvant effects) and aggravate allergic dermatitis. Moreover, DINP enhances the production of interleukin-4 in activated CD4+ T cells. However, the effect of DINP itself on the differentiation of naive CD4+ T cells into T helper cells (Th1/Th2) in vitro and allergic asthma in vivo has not yet been studied. In this study, DINP was shown to suppress the polarization of Th1 and enhance the polarization of Th2 from naive CD4+ T cells in vitro. Also, DINP induced allergic asthma via the production of IL-4, IL-5, IgE and IgG1 and the reduction of IFN-γ and IgG2a. Finally, we confirmed that exposure to DINP induces the infiltration of inflammatory cells and PAS positive cells and increases the expression of caspase-1 and caspase-3 in asthmatic mice. In conclusion, we suggest that DINP as an environmental pollutant or endocrine disruptor (ECD) induces asthma via the modulation of the Th1/Th2 equilibrium and production of Th2 mediated cytokines and immunoglobulin.
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Diisononyl Phthalate induces asthma via modulation of Th1/Th2 equilibrium.
Toxicology Letters, 2017Co-Authors: Yunho Hwang, Manjeong PaikAbstract:Abstract Diisononyl Phthalate (DINP), a member of the Phthalate family, is used to plasticize polyvinyl chloride (PVC). This chemical is known to enhance airway inflammation in the OVA-induced asthma model (adjuvant effects) and aggravate allergic dermatitis. Moreover, DINP enhances the production of interleukin-4 in activated CD4+ T cells. However, the effect of DINP itself on the differentiation of naive CD4+ T cells into T helper cells (Th1/Th2) in vitro and allergic asthma in vivo has not yet been studied. In this study, DINP was shown to suppress the polarization of Th1 and enhance the polarization of Th2 from naive CD4+ T cells in vitro. Also, DINP induced allergic asthma via the production of IL-4, IL-5, IgE and IgG1 and the reduction of IFN-γ and IgG2a. Finally, we confirmed that exposure to DINP induces the infiltration of inflammatory cells and PAS positive cells and increases the expression of caspase-1 and caspase-3 in asthmatic mice. In conclusion, we suggest that DINP as an environmental pollutant or endocrine disruptor (ECD) induces asthma via the modulation of the Th1/Th2 equilibrium and production of Th2 mediated cytokines and immunoglobulin.
Manori J Silva - One of the best experts on this subject based on the ideXlab platform.
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occupational exposure to Diisononyl Phthalate dinp in polyvinyl chloride processing operations
International Archives of Occupational and Environmental Health, 2012Co-Authors: Cynthia J Hines, Manori J Silva, Nancy B Hopf, James A Deddens, Antonia M CalafatAbstract:Purpose Diisononyl Phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations.
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Occupational exposure to Diisononyl Phthalate (DiNP) in polyvinyl chloride processing operations
International Archives of Occupational and Environmental Health, 2012Co-Authors: Cynthia J Hines, Manori J Silva, Nancy B Hopf, James A Deddens, Antonia M CalafatAbstract:Purpose Diisononyl Phthalate (DiNP) is primarily used as a plasticizer in polyvinyl chloride (PVC) materials. While information is available on general population exposure to DiNP, occupational exposure data are lacking. We present DiNP metabolite urinary concentrations in PVC processing workers, estimate DiNP daily intake for these workers, and compare worker estimates to other populations. Methods We assessed DiNP exposure in participants from two companies that manufactured PVC materials, a PVC film manufacturer ( n = 25) and a PVC custom compounder ( n = 12). A mid-shift and end-shift urine sample was collected from each participant and analyzed for the DiNP metabolite mono(carboxy-isooctyl) Phthalate (MCiOP). Mixed models were used to assess the effect on MCiOP concentrations of a worker being assigned to (1) a task using DiNP and (2) a shift where DiNP was used. A simple pharmacokinetic model was used to estimate DiNP daily intake from the MCiOP concentrations. Results Creatinine-adjusted MCiOP urinary concentrations ranged from 0.42–80 μg/g in PVC film and from 1.11–13.4 μg/g in PVC compounding. PVC film participants who worked on a task using DiNP ( n = 7) had the highest MCiOP geometric mean (GM) end-shift concentration (25.2 μg/g), followed by participants who worked on a shift where DiNP was used ( n = 11) (17.7 μg/g) as compared to participants with no task (2.92 μg/g) or shift (2.08 μg/g) exposure to DiNP. The GM end-shift MCiOP concentration in PVC compounding participants (4.80 μg/g) was comparable to PVC film participants with no task or shift exposure to DiNP. Because no PVC compounding participants were assigned to tasks using DINP on the day sampled, DiNP exposure in this company may be underestimated. The highest DiNP intake estimate was 26 μg/kg/day. Conclusion Occupational exposure to DiNP associated with PVC film manufacturing tasks were substantially higher (sixfold to tenfold) than adult general population exposures; however, all daily intake estimates were less than 25% of current United States or European acceptable or tolerable daily intake estimates. Further characterization of DiNP occupational exposures in other industries is recommended.
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Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey
Environmental Health Perspectives, 2010Co-Authors: Antonia M Calafat, Lee Yang Wong, Manori J Silva, James L Preau, Ella Samandar, Larry L. NeedhamAbstract:BackgroundHigh-molecular-weight Phthalates, such as Diisononyl Phthalate (DINP) and diisodecyl Phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.ObjectivesWe assessed exposure...
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Selecting adequate exposure biomarkers of Diisononyl and diisodecyl Phthalates: data from the 2005-2006 National Health and Nutrition Examination Survey.
Environmental Health Perspectives, 2010Co-Authors: Antonia M Calafat, Lee Yang Wong, Manori J Silva, James L Preau, Ella Samandar, Larry L. NeedhamAbstract:BackgroundHigh-molecular-weight Phthalates, such as Diisononyl Phthalate (DINP) and diisodecyl Phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.ObjectivesWe assessed exposure...
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oxidative metabolites of Diisononyl Phthalate as biomarkers for human exposure assessment
Environmental Health Perspectives, 2006Co-Authors: Manori J Silva, James L Preau, Larry L. Needham, John A Reidy, Antonia M CalafatAbstract:Diisononyl Phthalate (DINP) is a complex mixture of predominantly nine-carbon branched-chain dialkyl Phthalate isomers. Similar to di(2-ethylhexyl) Phthalate, a widely used Phthalate, DINP causes antiandrogenic effects on developing rodent male fetuses. Traditionally, assessment of human exposure to DINP has been done using monoisononyl Phthalate (MINP), the hydrolytic metabolite of DINP, as a biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative metabolites, including mono(carboxyisooctyl) Phthalate (MCIOP), mono(oxoisononyl) Phthalate (MOINP), and mono(hydroxyisononyl) Phthalate (MHINP) are the major urinary metabolites in DINP-dosed rats. The urinary concentrations of MINP, MCIOP, MOINP, and MHINP were measured in 129 adult anonymous human volunteers with no known exposure to DINP. Although MINP was not present at detectable levels in any of the samples analyzed, MCIOP, MHINP, and MOINP were detected in 97, 100, and 87% of the urine samples at geometric mean levels equal to 8.6, 11.4, and 1.2 ng/mL, respectively. The concentrations of all three oxidative metabolites were highly correlated with each other (p < 0.0001), which confirms a common precursor. MCIOP was excreted predominantly as a free species, whereas MOINP was excreted mostly in its glucuronidated form. The percentage of MHINP excreted either glucuronidated or in its free form was similar. The significantly higher frequency of detection and urinary concentrations of oxidative metabolites than of MINP suggest that these oxidative metabolites are better biomarkers of exposure assessment of DINP than is MINP. Therefore, we concluded that the prevalence of human exposure to DINP is underestimated by using MINP as the sole DINP urinary biomarker.
Jodi A Flaws - One of the best experts on this subject based on the ideXlab platform.
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exposure to di 2 ethylhexyl Phthalate and Diisononyl Phthalate during adulthood disrupts hormones and ovarian folliculogenesis throughout the prime reproductive life of the mouse
Toxicology and Applied Pharmacology, 2020Co-Authors: Catheryne Chiang, Lily R Lewis, Grace Borkowski, Jodi A FlawsAbstract:Abstract Di(2-ethylhexyl) Phthalate (DEHP) is a Phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl Phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these Phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39–40 days were orally dosed with either vehicle control (corn oil), DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days. Ovarian follicle populations, estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), and inhibin B were analyzed at time points immediately post-dosing and 3, 6, and 9 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones at multiple time points, including the last time point, 9 months post-dosing. Further, FSH was increased at multiple doses up to 6 months post-dosing. Inhibin B was not affected by treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure.
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late life consequences of short term exposure to di 2 ethylhexyl Phthalate and Diisononyl Phthalate during adulthood in female mice
Reproductive Toxicology, 2020Co-Authors: Catheryne Chiang, Lily R Lewis, Grace Borkowski, Jodi A FlawsAbstract:Abstract Di(2-ethylhexyl) Phthalate (DEHP) is a known endocrine disruptor and Diisononyl Phthalate (DiNP) is a common DEHP replacement chemical. However, little is known about late-life consequences due to DEHP or DiNP exposure during adulthood. Thus, this study tested the hypothesis that adult exposure to DEHP or DiNP affects female reproductive parameters during late-life in female mice. Female CD-1 mice (age 39–40 days) were dosed with either vehicle control, DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days and breeding trials were conducted at 12 and 15 months post-dosing. Further, ovaries and sera were collected at 12, 15, and 18 months post-dosing. DEHP and DiNP disrupted estrous cyclicity, increased pregnancy loss, decreased fertility, altered the sex ratio of pups, altered ovarian follicle populations, and disrupted hormone levels. Collectively, these data show that short-term exposure to DEHP or DiNP during adulthood has long-term consequences in late-life.
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subchronic exposure to di 2 ethylhexyl Phthalate and Diisononyl Phthalate during adulthood has immediate and long term reproductive consequences in female mice
Toxicological Sciences, 2019Co-Authors: Catheryne Chiang, Jodi A FlawsAbstract:: Di(2-ethylhexyl) Phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl Phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on female reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for female reproduction in mice. Adult female CD-1 mice (39-40 days) were orally dosed with vehicle control (corn oil), DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 µg/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 µg/kg/day) significantly reduced the ability of females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 µg/kg/day), reduced time to mating (100 µg/kg/day-200 mg/kg/day), and borderline reduced percent of females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 µg/kg/day and 200 mg/kg/day) and DiNP (100 µg/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for female reproduction, even long after cessation of exposure.