Urinary Biomonitoring Research Articles

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio.

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20-49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4-6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥ 89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults' ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults' ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults' ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0.056) of the adults' ln(urinary PCP) concentrations. In conclusion, specific sociodemographic and lifestyle factors were identified that increased the exposures of these adults to several different pesticides in their daily environments.

Urinary Biomarkers as Exposure Surrogates: Controlling for Possible Bias

Biomonitoring, or measuring levels of contaminants and their metabolites in human biological samples, can tell researchers a good deal about the environmental agents to which populations are exposed.1 This information can help identify human health risks associated with environmental exposures, but the accuracy of conclusions hinges on the correct interpretation of the data.2,3,4 A new study in EHP highlights a potential source of bias in estimating exposures on the basis of urine samples and suggests a possible means to control for it.2 The study used data collected through the National Health and Nutrition Examination Survey (NHANES), an ongoing program that includes biomonitoring of a nationally representative segment of the U.S. general population.5 Participants undergo physical examination, provide biological samples such as blood and urine for laboratory testing, and complete interviews regarding health, lifestyle, socioeconomic status, and other variables. NHANES data are then available for analysis by various research groups for the general purpose of evaluating and improving public health. The findings from a new study may enable researchers to more accurately assess the significance of chemical concentrations in biological samples. In NHANES, as well as in biomonitoring studies in general, urine is one of the most commonly used biological specimens.4 Sample collection is noninvasive, and laboratory analysis can quantify specific environmental contaminants in the sample. However, various factors such as hydration status and physiological differences among individuals can introduce uncertainty when estimating actual exposures from these measurements. For instance, as a result of variables such as these, the same exposure could result in different concentrations of metabolite in two different people’s urine. Linking estimated exposures to specific health outcomes represents an additional layer of uncertainty.2,3 The authors of the current study used data from the 2009–2010 and 2011–2012 NHANES cycles to assess patterns in the relationship between urinary flow rate (UFR) and body weight–adjusted urinary flow rate (UFRBW). These NHANES cycles differed from previous ones in that they collected data on the time between last and current urination and on urine volume, details that provide a more in-depth understanding of what urinary concentrations of environmental contaminants and their metabolites actually mean. “The issue of adjusting for hydration status in general—how much urine someone is producing over a period of time—is something that people in the biomonitoring community always struggle with in terms of correcting for it,” says coauthor Lesa Aylward, principal at Summit Toxicology LLP. Given this additional information, the authors explored whether systematic variations exist in UFR (measured in milliliters of urine produced per hour) as a function of age, sex, race/ethnicity, and body mass index (BMI) category. In addition, they tested their hypotheses by focusing on urinary concentrations and analyte excretion rates (measured in nanograms per hour, with and without adjustment for body weight) among different age groups for the chemicals bisphenol A and 2,5-dichlorophenol. They compared the results with those obtained by using conventional estimation methods, such as adjusting measurements based on urine levels of the metabolite creatinine, a surrogate for hydration status. The NHANES data analyzed in the current study included information on 14,631 participants aged 6 years and older. The authors found that both UFR and UFRBW varied by age and race/ethnicity, whereas only UFR varied by sex, and only UFRBW varied by BMI.2 This latter relationship illustrates a potential impediment to correctly discerning the relationship between a chemical exposure and a particular health variable: a chemical might affect that variable, but the variable itself might influence the measurement of the chemical. This phenomenon, sometimes called “reverse causation,” is highly relevant to reported associations between environmental chemicals and BMI-related conditions such as obesity, heart disease, and diabetes—many of which have been made based on NHANES data.6 As the assessments in the current study demonstrated, calculating analyte excretion rates could offset this problem. It is important to collect the information needed to estimate analyte excretion rates at the time samples are collected; otherwise, adjustments can’t be made to the raw data. The complexity revealed by the findings of the new study is a good thing, says Krista Christensen, an epidemiologist at the Wisconsin Division of Public Health. “This complexity will help researchers to better understand, analyze, and interpret their data—and this article is a great step forward in describing the considerations needed when using urinary biomarker data,” Christensen says. She was not involved in this study but used UFR calculations in another recent study.3 Aylward also indicates that the study raises some broader issues. “Biomonitoring data for chemicals has really exploded in the last fifteen years,” she says. “We’re now moving into a situation where we have a more sophisticated understanding of the physiological factors that might influence the concentrations of chemicals that can be measured. We’re trying to move from being naive consumers of biomonitoring data to being more sophisticated consumers of those data.”

Urinary biomonitoring of phosphate flame retardants: levels in California adults and recommendations for future studies.

Phosphate flame retardants (PFRs) are abundant and found at the highest concentrations relative to other flame retardant chemicals in house dust; however, little is known about the biological levels of PFRs and their relationship with house dust concentrations. These relationships provide insight into major exposure pathways and potential health risks. We analyzed urine samples from 16 California residents in 2011 for 6 chlorinated and nonchlorinated dialkyl or diaryl phosphates (DAPs), the expected major metabolites of the most prominent PFRs, and qualitatively screened for 18 other metabolites predicted from in vitro studies. We detected all 6 DAPs within the range of previously reported levels, although very few comparisons are available. We found weakly positive nonsignificant correlations between urine and dust concentrations and maxima urine corresponding to maxima dust for the pairs bis(1,3-dichloro-2-propyl) phosphate (BDCIPP)-tris(1,3-dichloro-isopropyl) phosphate (TDCIPP) and bis(2-chloroethyl) phosphate (BCEP)-tris(2-chloroethyl) phosphate (TCEP). Metabolite levels of PFRs were correlated for many PFR combinations, suggesting they commonly co-occur. As far as we know, this is the first study to measure these 6 DAP metabolites simultaneously and to detect other PFR metabolites in US urine samples. We recommend biomonitoring studies include these 6 DAPs as well as several additional compounds detected through qualitative screening and previous ADME studies. PFRs represent a class of poorly studied commercial chemicals with widespread exposure and raise concerns for health effects including carcinogenicity and neurotoxicity.

Urinary metabolomics revealed arsenic internal dose-related metabolic alterations: a proof-of-concept study in a Chinese male cohort.

Urinary biomonitoring provides the most accurate arsenic exposure assessment; however, to improve the risk assessment, arsenic-related metabolic biomarkers are required to understand the internal processes that may be perturbed, which may, in turn, link the exposure to a specific health outcome. This study aimed to investigate arsenic-related urinary metabolome changes and identify dose-dependent metabolic biomarkers as a proof-of-concept of the information that could be obtained by combining metabolomics and targeted analyses. Urinary arsenic species such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid and arsenobetaine were quantified using high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometry in a Chinese adult male cohort. Urinary metabolomics was conducted using HPLC-quadrupole time-of-flight mass spectrometry. Arsenic-related metabolic biomarkers were investigated by comparing the samples of the first and fifth quintiles of arsenic exposure classifications using a partial least-squares discriminant model. After the adjustments for age, body mass index, smoking, and alcohol consumption, five potential biomarkers related to arsenic exposure (i.e., testosterone, guanine, hippurate, acetyl-N-formyl-5-methoxykynurenamine, and serine) were identified from 61 candidate metabolites; these biomarkers suggested that endocrine disruption and oxidative stress were associated with urinary arsenic levels. Testosterone, guanine, and hippurate showed a high or moderate ability to discriminate the first and fifth quintiles of arsenic exposure with area-under-curve (AUC) values of 0.89, 0.87, and 0.83, respectively; their combination pattern showed an AUC value of 0.91 with a sensitivity of 88% and a specificity of 80%. Arsenic dose-dependent AUC value changes were also observed. This study demonstrated that metabolomics can be used to investigate arsenic-related biomarkers of metabolic changes; the dose-dependent trends of arsenic exposure to these biomarkers may translate into the potential use of metabolic biomarkers in arsenic risk assessment. Since this was a proof-of-concept study, more research is needed to confirm the relationships we observed between arsenic exposure and biochemical changes.

Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 2: Personal care product ingredients

An intensive study was conducted to provide data on intra- and inter-individual variation in urinary excretion of a series of ingredients in personal care products (parabens, triclosan, benzophenones) and bisphenol A (BPA, not expected to be an ingredient) in 8 volunteers over 6 days. Exposure diaries recorded use of personal care products with identified target analytes as ingredients. Participants' usual products were replaced with products without the target analytes for 2 of the 6 days. Urine void volumes and times were recorded. Methyl, ethyl, and n-propylparabens, triclosan, benzophenone-3, and BPA were frequently detected (≥70% of samples). Urinary concentrations of the parabens and triclosan were lower on product replacement days. First morning void concentrations correlated moderately to highly with 24-h composite concentrations for all analytes. Intraclass correlation coefficients (ICCs) for spot samples collected on days with usual product use were low for BPA (0.15), moderate for n-propylparaben and methylparaben (0.39 and 0.56, respectively), and high for ethylparaben, benzophenone-3, and triclosan (0.76, 0.81, and 0.934, respectively); ICCs were consistently higher on the basis of cr-adjusted concentrations. Hydration status adjustment methods were assessed by comparing unadjusted and adjusted concentrations to urinary excretion rates (ER, ng/kg-h) for all analytes and samples. Specific gravity-adjusted concentrations correlated slightly better with ER than creatinine-adjusted concentrations. Within-individual variation in biomarker concentrations was highest for methyl and ethylparabens (2 orders of magnitude variation in spot sample concentrations) and lower for the other analytes (1–1.5 orders of magnitude). This dataset provides insight into the design and interpretation of urinary biomonitoring studies for non-persistent chemicals.

Exposure to BPA in Children—Media-Based and Biomonitoring-Based Approaches

Bisphenol A (BPA) is used in numerous industrial and consumer product applications resulting in ubiquitous exposure. Children’s exposure is of particular concern because of evidence of developmental effects. Childhood exposure is estimated for different age groups in two ways. The “forward” approach uses information on BPA concentrations in food and other environmental media (air, water, etc.) combined with average contact rates for each medium. The “backward” approach relies on urinary biomonitoring, extrapolating backward to the intake which would have led to the observed biomarker level. The forward analysis shows that BPA intakes are dominated by canned food consumption, and that intakes are higher for younger ages. Mean intake estimates ranged from ~125 ng/kg-day for 1 year-olds to ~73 ng/kg-day among 16–20 years olds. Biomonitoring-based intakes show the same trend of lower intakes for older children, with an estimate of 121 (median) to 153 (mean) ng/kg-day for 2–6 years, compared with 33 (median) to 53–66 (mean) ng/kg-day for 16–20 years. Infant intakes were estimated to range from ~46 to 137 ng/kg-day. Recognizing uncertainties and limitations, this analysis suggests that the “forward” and “backward” methods provide comparable results and identify canned foods as a potentially important source of BPA exposure for children.

Health Risk Assessment and Urinary Biomarkers of VOCs Exposures among Outdoor Workers in Urban Area, Bangkok, Thailand

Volatile organic compounds (VOCs) are major source of ambient air pollutants in Bangkok, Thailand. Humans can be exposed to these pollutants by inhalation, ingestion, and dermal contact but mainly by inhalation. The scientists have paid much attention to the study of exposure to air pollutants in outdoor air because they have realized the seriousness of outdoor air pollution problems of acute and chronic health effects as cancer. The measurements of benzene, toluene, ethylbenzene, xylene (BTEX) and carbonyl compounds (CCs) at 16 sites with 144 subjects of 3 classes (motorcycle drivers, security guardsmen and street venders) were performed in Pathumwan district, central Bangkok during September and October 2012 by Gas Chromatography/Flame Ionized Detector (GC/FID) and High Performance Liquid Chromatography/Ultraviolet-Visible Detector (HPLC/UV-VIS). The ambient air concentrations of benzene, toluene, ethyl benzene, xylene, formaldehyde and acetaldehyde in urban area were 46.13, 91.10, 4.55, 58.27, 11.98 and 5.85 µg/m3 respectively. The outdoor workers had average lifetime cancer risk of benzene, ethylbenzene, formaldehyde and acetaldehyde at 1.67E05, 2.11E-07, 3.38E-06 and 7.93E-07 respectively which cancer risk of benzene and formaldehyde were higher than acceptable limit (1.00E-06). The security guardsmen, motorcycle drivers and street venders who work in the same area had cancer risk at 3.65E-05, 1.76E-05 and 1.01E-05 respectively The hazard quotient (HQ) of benzene, toluene, ethylbenzene, xylene, formaldehyde and acetaldehyde of all workers were 9.43E02, 9.57E-04, 4.43E-04, 4.04E-02, 1.42E-01 and 7.64E-01 respectively which all of them were lower than acceptable limit (HQ<1.00). In addition, the urinary biomonitoring concentrations of outdoor workers of trans,trans-muconic acid (tt-MA), hippuric acid, formaldehyde, acetaldehyde and formic acid were 1.66 mg/gCr, 0.51 g/gCr, 0.85 mg/gCr, 15.9 mg/gCr and 20.57 mg/gCr respectively. The tt-MA was strongly associated with benzene exposure (p<0.001) as well as hippuric acid was associated with toluene (p=0.001).

Considerations for estimating daily intake values of nonpersistent environmental endocrine disruptors based on urinary biomonitoring data

Human exposure to chemicals may be estimated by back-calculating urinary concentrations resulting from biomonitoring studies if knowledge of the chemical's toxicokinetic properties is available. In this paper, available toxicokinetic data for back-calculating urinary concentrations into daily intake values for bisphenol A (BPA), phthalates, parabens, and triclosan (TCS) are reviewed and knowledge gaps are identified. Human data is evaluated and presented with relevant animal data. Focus is on the recovery of the administered dose, the route of administration, and differences between humans and animals. Two human toxicokinetic studies are currently used to conclude that an oral dose of BPA is recoverable in urine and that no free BPA is present in plasma in spite of several contradicting biominotoring studies. Urinary recovery of an oral dose of phthalates in humans is complicated to assess due to extensive metabolism. In animals using (14)C-marked phthalates, near-complete recovery is observed. An oral dose of (14)C-marked parabens is also almost completely recovered in animals. In both humans and animals, however, two unspecific metabolites are formed, which complicates the back-calculation of parabens in humans. The recovery of both oral and dermal TCS in humans has been studied, but due to background levels of TCS, the back-calculation is difficult to perform. In conclusion, due to limited data, reasonable estimates of daily intake values based on urinary data are often not possible to obtain. Several knowledge gaps are identified and new studies are suggested. The route of administration used in toxicokinetic studies often does not match realistic scenarios.

Dietary predictors of young children’s exposure to current-use pesticides using urinary biomonitoring

Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-trichloro-2-pyridinol [TCP]), permethrin (3-phenoxybenzoic acid [3-PBA]), and 2,4-dichlorophenoxyacetic acid [2,4-D] in 135 preschool-aged children. TCP and 3-PBA are nonspecific biomarkers as they are also urinary metabolites of other pesticides. TCP, 3-PBA, and 2,4-D were detected in 99%, 64%, and 92% of the urine samples, respectively. Mean urinary TCP concentrations were statistically significantly higher in children consuming fresh apples (9.40±15.5 ng/mL versus 5.76±3.57 ng/mL, p=0.040) and fruit juices (8.41±11.5 ng/mL versus 4.11±2.77 ng/mL, p=0.020) ≥3 times a week compared to <3 times a week. For 3-PBA, mean urinary metabolite concentrations were statistically significantly greater in children consuming chicken/turkey meats (0.79±0.81 versus 0.41±0.39, p=0.013) ≥3 times a week compared to <3 times a week. No association occurred between the consumption of any food item and children's mean urinary 2,4-D concentrations by intake group. In conclusion, frequent consumption of fresh apples and fruit juices or chicken/turkey meats were significant dietary predictors of urinary levels of TCP or 3-PBA, respectively.

Isocyanate Exposure Assessment Combining Industrial Hygiene Methods with Biomonitoring for End Users of Orthopedic Casting Products

Previous studies have suggested a potential risk to healthcare workers applying isocyanate-containing casts, but the authors reached their conclusions based on immunological or clinical pulmonology test results alone. We designed a study to assess potential exposure to methylene diphenyl diisocyanate (MDI) among medical personnel applying orthopedic casts using two different application methods. Air, dermal, surface, and glove permeation sampling methods were combined with urinary biomonitoring to assess the overall risk of occupational asthma to workers handling these materials. No MDI was detected in any of the personal and area air samples obtained. No glove permeation of MDI was detected. A small proportion of surface (3/45) and dermal wipe (1/60) samples were positive for MDI, but were all from inexperienced technicians. Urinary metabolites of MDI [methylenedianiline (MDA)] were detected in three of six study participants prior to both a ‘dry’ and ‘wet’ application method, five of six after the dry method, and three of six after the wet method. All MDA results were below levels noted in worker or general populations. Our conclusion is that the risk of MDI exposure is small, but unquantifiable. Because there is some potential risk of dermal exposure, medical personnel are instructed to wear a minimum of 5-mil-thick (5 mil = 0.005 inches) nitrile gloves and avoid contact to unprotected skin. This could include gauntlets, long sleeves, and/or a laboratory coat.

Absorption and excretion of organophosphorous insecticide biomarkers of malathion in the rat: Implications for overestimation bias and exposure misclassification from environmental biomonitoring

Malathion is an organophosphorous (OP) insecticide widely used for crop protection. Its degradates, malathiondiacid (MDA), malathion monoacid (MMA), dimethylphosphate (DMP), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) are formed in strawberries and other produce. These same chemical biomarkers are measured in urine in human studies as quantitative measures of exposure. The excretion of malathion and its common biomarkers including MDA, MMA, DMP, DMTP and DMDTP at equal molar doses (73μmol/kg b.w.) was studied following oral dosing of female Holtzmann rats (240–300g). Following MDA administration, 36.3±5.4% was recovered as MDA, 0.05±0.02% as DMP, 5.5±0.3% as DMTP, 3.8±2.9% as DMDTP (mole percent), and totally 45.6±7.0% of administered dose in urine after 120h (over 94% in the first 24h). Following DMTP administration, 8.3±7.7% was recovered as DMP, 46.6±16.5% as DMTP, and totally 55.0±10.3% of administered dose in urine after 120h (over 92% in the first 24h). Similar results were obtained with other malathion biomarkers. Preformed biomarkers of malathion and other OP insecticides when ingested in produce are readily absorbed and excreted. Low level human dietary and non-occupational urine biomonitoring studies will be confounded by preformed pesticide biomarkers used to infer potential human pesticide exposure. This has profound implications for epidemiology studies where subject’s biomarker excretion is used as a surrogate for OP exposures that cannot be related to a particular insecticide residue.

Estimates of daily di-isodecyl phthalate (DIDP) intake calculated from urinary biomonitoring data

Biomonitoring of chemical species in biologic media can be a valuable tool in risk assessment since it informs directly on aggregate exposures. While advances in the analytical techniques required for biomonitoring have resulted in increased sensitivity for the detection of chemical species, the detection of a chemical substance in a biological medium (such as blood, urine or breast milk) does not mean that the chemical causes or is associated with an adverse health outcome. In this paper, intake estimates for di-isodecyl phthalate (DIDP), a high molecular weight general purpose plasticizer, were calculated from urinary biomonitoring data representing various population segments and geographic locales. From these data, intake estimates converge on a mean that is <1μg/kg/day (95th%<5μg/kg/day). This intake estimate is at least two orders of magnitude lower than the health-based exposure guidance values (38–150μg/kg/day) which have been proposed by regulatory authorities and other authoritative bodies as safe exposure levels.

Fate and distribution of fipronil on companion animals and in their indoor residences following spot-on flea treatments

Use of fipronil {5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile CAS 120068–37-3} topical pet products on dogs and cats introduces low level residues into residences. Distribution and fate studies of fipronil on pets and in residences were performed to evaluate potential determinants of human exposure. Fipronil, desulfinyl fipronil, fipronil sulfone and fipronil sulfide were measured on hair clippings and brushed hair. The derivatives usually represented <10% of fipronil applied. Cotton gloves worn over impervious nitrile gloves, cotton cloths placed indoors in locations frequented by pets, and cotton socks worn by residents as direct dosimeters collected fipronil and its derivatives listed above in low amounts during 4-week study periods. Subsequent acid hydrolysis urine biomonitoring did not reveal significant excretion of biomarkers at ppb levels. The human exposure potential of fipronil is low relative to levels of health concern.

Preformed Biomarkers Including Dialkylphosphates (DAPs) in Produce May Confound Biomonitoring in Pesticide Exposure and Risk Assessment

Low levels of pesticides and their metabolites/degradates occur in produce when pesticides are used in conventional or organic crop protection. Human dietary and nonoccupational urine biomonitoring studies may be confounded by preformed pesticide biomarkers in the diet. The extent of formation of putative urine biomarkers, including malathion specific (MMA, MDA; malathion mono- and diacids), organophosphorus generic (DMP, DMTP, DMDTP; dimethyl-, dimethylthio-, and dimethydithiophosphate), pyrethroid generic (3-PBA; 3-phenoxybenzoic acid), and captan-specific metabolites (THPI; tetrahydrophthalimide), was measured in produce samples containing the parent pesticide. Every produce sample of 19 types of fruits and vegetables contained biomarkers of potential human exposure. A total of 134 of 157 (85%) samples contained more molar equivalent biomarkers than parent pesticide. Malathion and fenpropathrin were sprayed (1 lb/A), and the time-dependent formation of pesticide biomarkers in strawberries was investigated under field conditions typical of commercial production in California. Malathion and fenpropathrin residues were always below established residue tolerances. Malathion, MMA, and MDA dissipated, while DMP, DMTP, and DMDTP increased, during a 20 day study period following the preharvest interval. The mole ratios of biomarkers/(malathion + malaoxon) were always greater than 1 and increased from day 4 to day 23 postapplication. Fenpropathrin and 3-PBA also dissipated in strawberries during each monitoring period. The mole ratios of 3-PBA/fenpropathrin were always less than 1 and decreased from day 4 to day 14. The absorption of pesticide biomarkers in produce and excretion in urine would falsely indicate consumer pesticide exposure if used to reconstruct dose for risk characterization.

Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections

Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing children's BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets.

Surveillance for Long-Term Health Effects Associated With Depleted Uranium Exposure and Retained Embedded Fragments in US Veterans

To ensure that all veterans with retained embedded fragments are properly monitored for potential health effects of embedded materials. Urine biomonitoring and health surveillance programs were developed to gather information about health risks associated with chemicals released from embedded fragments. Elevated systemic exposure to depleted uranium (DU) that continues to occur in veterans with DU fragments remains a concern, although no clinically significant DU-related health effects have been observed to date. Other metals and local tissue reactions to embedded fragments are also of concern. Knowledge gained from these programs will help to develop guidelines for surgical removal of tissue-embedded fragments.

한국인의 요중 크레아티닌 농도에 관한 연구 -국민건강영양조사 4기 자료 이용-

Objectives: Biomonitoring is used to assess human environmental exposures. Urinary biomonitoring data are typically adjusted to a constant creatinine concentration to correct for variable dilutions among spot samples. Our objective was to investigate urinary creatinine concentrations by region, gender, age and lifestyle. Methods: We studied urinary creatinine concentrations in 6,286 Koreans aged 20 years old and older who participated the fourth Korea National Health and Nutrition Survey (KNHANES IV) in 2009. Urinary creatinine concentration analysis used the Jaffe method. Results: The average urinary creatinine concentration of 6,286 Koreans was 158.99 mg/dl. The urinary creatinine concentration was significantly higher among men (184.97 mg/dl) than women (130.02 mg/dl). In both men and women, urinary creatinine concentrations were significantly different according to age group (p < 0.01). Whereas the urinary creatinine concentration of men significantly differed with smoking in adjusted comparison analysis, that of women significantly differed by education level. Ninety-two percent of urinary creatinine concentration was included within WHO guidelines effective range(30 mg/dl <TEX>${\leq}$</TEX> urinary creatinine concentration <TEX>${\leq}$</TEX> 300 mg/dl). In multiple regression analysis, creatinine was influenced by gender, age and body mass index (BMI). Conclusions: The urinary creatinine value obtained from representative samples of adult Koreans aged 20 year and older in KNHANES IV 2009 could be used as a reference value for other nationally studied surveys, such as abandoned metal mine surveys and surveys for industrial complexes.

A comprehensive review of intake estimates of di-isononyl phthalate (DINP) based on indirect exposure models and urinary biomonitoring data

Di-isononyl phthalate (DINP) is a high molecular weight general purpose plasticizer used principally in the manufacture of flexible polyvinyl chloride (PVC) articles. DINP metabolites can be measured in biological media such as blood and urine. However, measurement of a substance in the blood or urine does not by itself mean that the chemical causes or is associated with adverse health outcomes. This is particularly pertinent given the advances in modern analytical techniques whereby ever diminishing trace amounts of substances can be detected. Therefore, it is a scientific necessity that risk assessors understand the relationship of biomonitoring data to estimation of exposure so that appropriate comparisons can be made to the no observed adverse effects levels (NOAELs) or other points of departure from toxicological studies in animals. In this paper, estimates of daily DINP intake are calculated for various population segments based on urinary biomonitoring data and are compared to estimates of exposure based on indirect methods and to health-based exposure guidance values. In general, intake estimates converge on a mean of 1–2μg/kg/day regardless of source of exposure or population cluster; a value 2-orders of magnitude lower than health-based exposure guidance values, ranging from 120 to 290μg/kg/day, which have been established by regulatory authorities and other authoritative bodies as representing acceptable levels.

Assessing the Quantitative Relationships between Preschool Children’s Exposures to Bisphenol A by Route and Urinary Biomonitoring

Limited published information exists on young children's exposures to bisphenol A (BPA) in the United States using urinary biomonitoring. In a previous project, we quantified the aggregate exposures of 257 preschool children to BPA in environmental and personal media over 48-h periods in 2000-2001 at homes and daycares in North Carolina and Ohio. In the present study for 81 Ohio preschool children ages 23-64 months, we quantified the children's urinary total BPA (free and conjugated) concentrations over these same 48-h periods in 2001. Then, we examined the quantitative relationships between the children's intakes doses of BPA through the dietary ingestion, nondietary ingestion, and inhalation routes and their excreted amounts of urinary BPA. BPA was detected in 100% of the urine samples. The estimated median intake doses of BPA for these 81 children were 109 ng/kg/day (dietary ingestion), 0.06 ng/kg/day (nondietary ingestion), and 0.27 ng/kg/day (inhalation); their estimated median excreted amount of urinary BPA was 114 ng/kg/day. Our multivariable regression model showed that dietary intake of BPA (p = 0.04) and creatinine concentration (p = 0.004) were significant predictors of urinary BPA excretion, collectively explaining 17% of the variability in excretion. Dietary ingestion of BPA accounted for >95% of the children's excreted amounts of urinary BPA.

Evaluation of exposure reduction to indoor air pollution in stove intervention projects in Peru by urinary biomonitoring of polycyclic aromatic hydrocarbon metabolites

Burning biomass fuels such as wood on indoor open-pit stoves is common in developing regions. In such settings, exposure to harmful combustion products such as fine particulate matter (PM 2.5), carbon monoxide (CO) and polycyclic aromatic hydrocarbons (PAHs) is of concern. We aimed to investigate if the replacement of open pit stoves by improved stoves equipped with a chimney would significantly reduce exposure to PAHs, PM 2.5 and CO. Two stove projects were evaluated in Peru. Program A was part of the Juntos National Program in which households built their own stoves using materials provided. In Program B, Barrick Gold Corporation hired a company to produce and install the stoves locally. A total of 30 and 27 homes participated in Program A and B, respectively. We collected personal and kitchen air samples, as well as morning urine samples from women tasked with cooking in the households before and after the installation of the improved stoves. Median levels of PM 2.5 and CO were significantly reduced in kitchen and personal air samples by 47–74% after the installation of the new stoves, while the median reduction of 10 urinary hydroxylate PAH metabolites (OH-PAHs) was 19%–52%. The observed OH-PAH concentration in this study was comparable or higher than the 95th percentile of the general U.S. population, even after the stove intervention, indicating a high overall exposure in this population.