The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform
Devika Poddalgoda - One of the best experts on this subject based on the ideXlab platform.
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Derivation of biomonitoring equivalents (BE values) for bismuth.
Regulatory toxicology and pharmacology : RTP, 2020Co-Authors: Devika Poddalgoda, Sean M Hays, Andy NongAbstract:Bismuth (Bi) is a natural element present in the environmental media. Bismuth has been used medicinally for centuries, specifically for the treatment of gastrointestinal (GI) disorders. Although bismuth toxicity is rare in humans, an outbreak of bismuth-induced neurotoxicity was reported in France and Australia in the mid-1970s. The primary source of bismuth exposure in the general population is via food. US FDA (2019) estimated recommended daily intake (RDI) for bismuth as 848 mg bismuth/day (12.1 mg Bi/kg-d assuming a body weight of 70 kg) for GI tract disorders. Exposures to bismuth can be quantified by measuring concentrations in blood and urine. Biomonitoring equivalents (BEs) were derived based on US FDA's RDI as a tool for interpretation of population-level biomonitoring data. A regression between steady state plasma concentrations and oral intakes was used to derive plasma BEs. A whole blood: plasma partitioning coefficient of 0.6 was used to convert plasma BE into whole blood BE. A mass balance equation with a Urinary Excretion Fraction of 0.0003 was used to derive Urinary BE. The BE values associated with US FDA's RDI for plasma, whole blood and urine were 8.0, 4.8 and 0.18 μg/L, respectively. These BE values together with bismuth biomonitoring data may be used in screening and prioritization of health risk assessment of bismuth in the general population.
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Biomonitoring Equivalents for interpretation of Urinary iodine.
Regulatory toxicology and pharmacology : RTP, 2018Co-Authors: Sean M Hays, Devika Poddalgoda, Kristin Macey, Lesa Aylward, Andy NongAbstract:Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO) have established exposure guidance values for nutrition (IOM Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)). Using a Urinary Excretion Fraction of 0.9, Biomonitoring Equivalents (BE) for the EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 μg/L, respectively) and children (50, 80, 580 and 360 μg/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126 μg/L, respectively) and children (232, 189 μg/L, respectively) were above the criteria for assessing iodine nutrition, indicating that US and Canadian populations are likely to have adequate population iodine nutrition. The median UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance values for toxicity.
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Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.
Regulatory toxicology and pharmacology : RTP, 2017Co-Authors: Devika Poddalgoda, Kristin Macey, Henry Assad, Kannan KrishnanAbstract:The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of Urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL05) of 63 mg/kg bw/d. The plasma BE (9 μg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human Urinary Excretion Fraction of 0.023, a BE for Urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d.
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Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level Urinary biomonitoring data
Regulatory toxicology and pharmacology : RTP, 2016Co-Authors: Devika Poddalgoda, Kristin Macey, Innocent Jayawardene, Kannan KrishnanAbstract:Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Etude nationale nutrition sante) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a Urinary Excretion Fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for Urinary tin (26 μg/g creatinine or 20 μg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 μg/g creatinine) and France (0.51 and 2.28 μg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the Urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.
Kannan Krishnan - One of the best experts on this subject based on the ideXlab platform.
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Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.
Regulatory toxicology and pharmacology : RTP, 2017Co-Authors: Devika Poddalgoda, Kristin Macey, Henry Assad, Kannan KrishnanAbstract:The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of Urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL05) of 63 mg/kg bw/d. The plasma BE (9 μg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human Urinary Excretion Fraction of 0.023, a BE for Urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d.
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Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level Urinary biomonitoring data
Regulatory toxicology and pharmacology : RTP, 2016Co-Authors: Devika Poddalgoda, Kristin Macey, Innocent Jayawardene, Kannan KrishnanAbstract:Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Etude nationale nutrition sante) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a Urinary Excretion Fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for Urinary tin (26 μg/g creatinine or 20 μg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 μg/g creatinine) and France (0.51 and 2.28 μg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the Urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.
Holger M. Koch - One of the best experts on this subject based on the ideXlab platform.
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Metabolism and Urinary Excretion kinetics of di(2-ethylhexyl) adipate (DEHA) in four human volunteers after a single oral dose
Toxicology letters, 2019Co-Authors: Alexandra Nehring, Daniel Bury, Benedikt Ringbeck, Hans-willi Kling, Rainer Otter, Tobias Weiss, Thomas Brüning, Holger M. KochAbstract:Di(2-ethylhexyl) adipate (DEHA) is used as a substitute for the reprotoxic phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP). This study reports the first quantitative data on human in vivo DEHA metabolism and Urinary metabolite Excretion with the aim of providing tools for DEHA exposure and risk assessments. After DEHA was administered to four healthy volunteers (107-164 μg/kg body weight (bw)), urine samples were continuously and completely collected for 48 h and analyzed for the specific oxidized monoester metabolites mono-2-ethyl-5-hydroxyhexyl adipate (5OH-MEHA), mono-2-ethyl-5-oxohexyl adipate (5oxo-MEHA), and mono-5-carboxy-2-ethylpentyl adipate (5cx-MEPA), as well as for the non-specific hydrolysis product adipic acid (AA) using stable isotope dilution analysis. AA was confirmed as a major (Urinary Excretion Fraction (FUE): 10-40%), yet non-specific DEHA metabolite. 5cx-MEPA was the major specific DEHA metabolite with an FUE of 0.20% (range: 0.17-0.24%). FUEs for 5OH-MEHA and 5oxo-MEHA were 0.07% (0.03-0.10%) and 0.05% (0.01-0.06%), respectively. The three specific metabolites were excreted with two concentration maxima (tmax1 = 1.5-2.3 h, tmax2 = 3.8-6.4 h). Elimination half-lives (t1/2, calculated after the second tmax) for 5cx-MEPA were calculated between 2.1-3.8 h. The majority (98-100%) of metabolites was excreted within 24 h. The FUE of 5cx-MEPA was applied to demonstrate its applicability for calculating daily intakes based on Urinary metabolite levels from three pilot populations. Daily intakes were generally far below the tolerable daily intake (TDI) for DEHA (300 μg/kg bw/day). The highest daily intake (114 μg/kg bw/day) was calculated in individuals after consuming food that had been wrapped in DEHA containing cling film.
Sean M Hays - One of the best experts on this subject based on the ideXlab platform.
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Derivation of biomonitoring equivalents (BE values) for bismuth.
Regulatory toxicology and pharmacology : RTP, 2020Co-Authors: Devika Poddalgoda, Sean M Hays, Andy NongAbstract:Bismuth (Bi) is a natural element present in the environmental media. Bismuth has been used medicinally for centuries, specifically for the treatment of gastrointestinal (GI) disorders. Although bismuth toxicity is rare in humans, an outbreak of bismuth-induced neurotoxicity was reported in France and Australia in the mid-1970s. The primary source of bismuth exposure in the general population is via food. US FDA (2019) estimated recommended daily intake (RDI) for bismuth as 848 mg bismuth/day (12.1 mg Bi/kg-d assuming a body weight of 70 kg) for GI tract disorders. Exposures to bismuth can be quantified by measuring concentrations in blood and urine. Biomonitoring equivalents (BEs) were derived based on US FDA's RDI as a tool for interpretation of population-level biomonitoring data. A regression between steady state plasma concentrations and oral intakes was used to derive plasma BEs. A whole blood: plasma partitioning coefficient of 0.6 was used to convert plasma BE into whole blood BE. A mass balance equation with a Urinary Excretion Fraction of 0.0003 was used to derive Urinary BE. The BE values associated with US FDA's RDI for plasma, whole blood and urine were 8.0, 4.8 and 0.18 μg/L, respectively. These BE values together with bismuth biomonitoring data may be used in screening and prioritization of health risk assessment of bismuth in the general population.
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Biomonitoring Equivalents for interpretation of Urinary iodine.
Regulatory toxicology and pharmacology : RTP, 2018Co-Authors: Sean M Hays, Devika Poddalgoda, Kristin Macey, Lesa Aylward, Andy NongAbstract:Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO) have established exposure guidance values for nutrition (IOM Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)). Using a Urinary Excretion Fraction of 0.9, Biomonitoring Equivalents (BE) for the EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 μg/L, respectively) and children (50, 80, 580 and 360 μg/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126 μg/L, respectively) and children (232, 189 μg/L, respectively) were above the criteria for assessing iodine nutrition, indicating that US and Canadian populations are likely to have adequate population iodine nutrition. The median UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance values for toxicity.
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Screening-level Biomonitoring Equivalents for tiered interpretation of Urinary 3-phenoxybenzoic acid (3-PBA) in a risk assessment context
Regulatory toxicology and pharmacology : RTP, 2017Co-Authors: Lesa L. Aylward, Andy Nong, Kim Irwin, Annie St-amand, Sean M HaysAbstract:Abstract 3-Phenoxybenzoic acid (3-PBA) is a common metabolite of several pyrethroid pesticides of differing potency and also occurs as a residue in foods resulting from environmental degradation of parent pyrethroid compounds. Thus, 3-PBA in urine is not a specific biomarker of exposure to a particular pyrethroid. However, an approach derived from the use of Biomonitoring Equivalents (BEs) can be used to estimate a conservative initial screening value for a tiered assessment of population data on 3-PBA in urine. A conservative generic Urinary Excretion Fraction for 3-PBA was estimated from data for five pyrethroid compounds with human data. Estimated steady-state Urinary 3-PBA concentrations associated with reference doses and acceptable daily intakes for each of the nine compounds ranged from 1.7 μg/L for cyhalothrin and deltamethrin to 520 μg/L for permethrin. The lower value can be used as a highly conservative Tier 1 screening value for assessment of population Urinary 3-PBA data. A second tier screening value of 87 μg/L was derived based on weighting by relative exposure estimates for the different pyrethroid compounds, to be applied as part of the data evaluation process if biomonitoring data exceed the Tier 1 value. These BE values are most appropriately used to evaluate the central tendency of population biomarker concentration data in a risk assessment context. The provisional BEs were compared to available national biomonitoring data from the US and Canada.
Kristin Macey - One of the best experts on this subject based on the ideXlab platform.
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Biomonitoring Equivalents for interpretation of Urinary iodine.
Regulatory toxicology and pharmacology : RTP, 2018Co-Authors: Sean M Hays, Devika Poddalgoda, Kristin Macey, Lesa Aylward, Andy NongAbstract:Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO) have established exposure guidance values for nutrition (IOM Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)). Using a Urinary Excretion Fraction of 0.9, Biomonitoring Equivalents (BE) for the EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 μg/L, respectively) and children (50, 80, 580 and 360 μg/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126 μg/L, respectively) and children (232, 189 μg/L, respectively) were above the criteria for assessing iodine nutrition, indicating that US and Canadian populations are likely to have adequate population iodine nutrition. The median UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance values for toxicity.
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Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.
Regulatory toxicology and pharmacology : RTP, 2017Co-Authors: Devika Poddalgoda, Kristin Macey, Henry Assad, Kannan KrishnanAbstract:The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of Urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL05) of 63 mg/kg bw/d. The plasma BE (9 μg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human Urinary Excretion Fraction of 0.023, a BE for Urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d.
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Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level Urinary biomonitoring data
Regulatory toxicology and pharmacology : RTP, 2016Co-Authors: Devika Poddalgoda, Kristin Macey, Innocent Jayawardene, Kannan KrishnanAbstract:Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Etude nationale nutrition sante) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a Urinary Excretion Fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for Urinary tin (26 μg/g creatinine or 20 μg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 μg/g creatinine) and France (0.51 and 2.28 μg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the Urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.
