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Background: Previous studies on the associations of per- and polyfluoroalkyl substances (PFASs) and heavy metals with lipid profiles among adolescents have been scarce. We sought to investigate the associations of PFASs and heavy metals with blood lipid levels in a representative sample of Korean adolescents., Methods: Data from the Korean National Environmental Health Survey (2018-2020) were used. Concentrations of PFASs [perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDeA)], lead, and mercury were measured in serum, whole blood, and urine samples, respectively. Linear regression, Bayesian kernel machine regression (BKMR), and k-means clustering analyses were employed to evaluate the associations between pollutants and lipid levels., Results: In the linear regression analyses, PFOA levels were associated with higher low-density lipoprotein cholesterol (LDL-C) levels; PFOS with higher total cholesterol (TC) levels; PFNA with higher TC, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) levels; PFDeA with higher TC, LDL-C, non-HDL-C, and high-density lipoprotein cholesterol levels; and mercury with higher TC and non-HDL-C levels. The BKMR analysis revealed that the PFAS and heavy metal mixture was associated with higher LDL-C levels (1.8% increase in LDL-C at the 75th percentile of all PFAS and heavy metal concentrations compared to their median values, 95% credible interval: 0.5, 3.1), primarily driven by the effect of PFDeA. Compared to individuals in the low pollutant exposure cluster (geometric mean levels of PFOA, PFOS, PFHxS, PFNA, PFDeA, lead, and mercury were 2.7 μg/L, 6.2 μg/L, 1.6 μg/L, 0.7 μg/L, 0.4 μg/L, 0.8 μg/dL, and 0.3 μg/L, respectively), those in the high pollutant exposure cluster (5.1 μg/L, 10.7 μg/L, 3.7 μg/L, 1.3 μg/L, 0.6 μg/L, 0.9 μg/dL, and 0.4 μg/L, respectively) demonstrated higher TC levels (2.5% increase in TC, 95% confidence interval: 0.1, 5.0) in the k-means clustering analysis., Conclusion: Due to the limitations of this study, such as its cross-sectional design, these results should be interpreted cautiously and confirmed in future studies before drawing implications for public health strategies aimed at promoting health during adolescence and later in life., Competing Interests: Declarations. Ethics approval and consent to participate: The survey protocol was reviewed and approved by the Research Ethics Committee of the National Institute of Environmental Research (No. NIER-2018-BR-003–02), and written informed consent was obtained from all participants. This study, using publicly available de-identified data from the KoNEHS, was approved by the Institutional Review Board of Severance Hospital (No. 4–2024-0588). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background : Exposure to environmental pollutants such as metals and Per- and Polyfluoroalkyl Substances (PFAS) has become common and increasingly associated with a decrease in the estimated Glomerular Filtration Rate (eGFR), which is a marker often used to measure chronic kidney disease (CKD). However, there are limited studies involving the use of both eGFR and the urine albumin creatinine ratio (uACR), which are more comprehensive markers to determine the presence of CKD and the complexity of pollutant exposures and response interactions, especially for combined metals and PFAS, which has not been comprehensively elucidated. Objective : This study aims to assess the individual and combined effects of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), Cadmium (Cd), Mercury (Hg), and Lead (Pb) exposure on CKD using data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018. Methods : We employed the use of bivariate logistic regression and Bayesian Kernel Machine Regression (BKMR) in our analysis of the data. Results : Logistic regression results revealed a positive association between PFOA and CKD. Our BKMR analysis revealed a non-linear and bi-phasic relationship between the metal exposures and CKD. In our univariate exposure-response function plot, Cd and Hg exhibited a U and N-shaped interaction, which indicated a non-linear and non-additive relationship with both low and high exposures associated with CKD. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that Cd had a U-shaped relationship with CKD at different quantiles of Pb, Hg, PFOA, and PFOS, indicating that both low and high levels of Cd is associated with CKD, implying a non-linear and complex biological interaction. Hg's interaction plot demonstrated a N-shaped association across all quantiles of Cd, with the 75th quantile of Pb and the 50th and 75th quantiles of PFOA and PFOS. Furthermore, the PIP results underscored Cd's consistent association with CKD (PIP = 1.000) followed by Hg's (PIP = 0.9984), then PFOA and PFOS with a closely related PIP of 0.7880 and 0.7604, respectively, and finally Pb (PIP = 0.6940), contributing the least among the five environmental pollutants on CKD, though significant. Conclusions : Our findings revealed that exposure to environmental pollutants, particularly Hg and Cd, are associated with CKD. These findings highlight the need for public health interventions and strategies to mitigate the cumulative effect of PFAS and metal exposure and elucidate the significance of utilizing advanced statistical methods and tools to understand the impact of environmental pollutants on human health. Further research is needed to understand the mechanistic pathways of PFAS and metal-induced kidney injury and CKD, and longitudinal studies are required to ascertain the long-term impact of these environmental exposures.

Concerns are heightened from detecting environmentally persistent man-made per- and polyfluoroalkyl substances (PFAS) in drinking water systems around the world. Many PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), remain in the human body for years. Since 1999-2000, assessment of exposure to PFOS, PFOA, and other select PFAS in the U.S. general population has relied on measuring PFAS serum concentrations in participants of the National Health and Nutrition Examination Survey (NHANES). Manufacturers have replaced select chemistries ("legacy" PFAS) with PFAS with shorter biological half-lives (e.g., GenX, perfluorobutanoate [PFBA]) which may efficiently eliminate in urine. However, knowledge regarding exposure to these compounds is limited. We analyzed 2682 urine samples for 17 legacy and alternative PFAS in 2013-2014 NHANES participants ≥6 years of age. Concentrations of some of these PFAS, measured previously in paired serum samples from the same NHANES participants, suggested universal exposure to PFOS and PFOA, and infrequent or no exposure to two short-chain PFAS, perfluorobutane sulfonate and perfluoroheptanoate. Yet, in urine, PFAS were seldom detected; the frequency of not having detectable concentrations of any of the 17 PFAS was 67.5%. Only two were detected in >1.5% of the population: PFBA (13.3%) and perfluorohexanoate (PFHxA, 22.6%); the 90th percentile urine concentrations were 0.1 μg/L (PFBA), and 0.3 μg/L (PFHxA). These results suggest that exposures to short-chain PFAS are infrequent or at levels below those that would result in detectable concentrations in urine. As such, these findings do not support biomonitoring of short-chain PFAS or fluorinated alternatives in the general population using urine, and highlight the importance of selecting the adequate biomonitoring matrix., (Published by Elsevier Ltd.)

We analyzed paired serum, urine, and hair samples from 94 Korean children and adults to investigate levels of 11 perfluoroalkyl acids (PFAAs). The effects of demographic factors and dietary habits on PFAA exposure were also assessed based on the paired samples. The total PFAA concentrations were 2.4-31 ng/mL in serum, not detected-9.5 ng/mL in urine, and 0.48-15 ng/g in hair. Levels of perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), which have short carbon chains, were 1.5-5 fold higher in urine and hair than in serum. The PFAA concentrations in serum exhibited a decreasing trend with age from young childhood to adolescence, followed by an increasing trend after adolescence. For most PFAA species, concentrations in serum were higher in adult males than in adult females (p < 0.01). No sex difference was evident in the urine and hair samples. In addition, there was no age difference in the urine samples, but in the hair samples, we observed higher concentrations of PFAAs in children than in the other age groups (p < 0.01). The consumption rates of fish and water showed significant correlations with serum (positive correlation) and hair (negative) concentrations, respectively. No relationships between serum and hair/urine levels for most PFAAs were observed, except between serum and hair levels for perfluorooctanoic acid (PFOA)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS), man-made chemicals with variable length carbon chains containing the perfluoroalkyl moiety (C n F 2n+1 -), are used in many commercial applications. Since 1999-2000, several long-chain PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have been detected at trace levels in the blood of most participants of the National Health and Nutrition Examination Survey (NHANES)-representative samples of the U.S. general population-while short-chain PFAS have not. Lower detection frequencies and concentration ranges may reflect lower exposure to short-chain PFAS than to PFOS or PFOA or that, in humans, short-chain PFAS efficiently eliminate in urine. We developed on-line solid phase extraction-HPLC-isotope dilution-MS/MS methods for the quantification in 50 μL of urine or serum of 15 C 3 -C 11 PFAS (C 3 only in urine), and three fluorinated alternatives used as PFOA or PFOS replacements: GenX (ammonium salt of 2,3,3,3,-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoate, also known as HFPO-DA), ADONA (ammonium salt of 4,8-dioxa-3H-perfluorononanoate), and 9Cl-PF3ONS (9-chlorohexadecafluoro-3-oxanonane-1-sulfonate), main component of F53-B. Limit of detection for all analytes was 0.1 ng/mL. To validate the method, we analyzed 50 commercial urine/serum paired samples collected in 2016 from U.S. volunteers with no known exposure to the chemicals. In serum, detection frequency and concentration patterns agreed well with those from NHANES. By contrast, except for perfluorobutanoate, we did not detect long-chain or short-chain PFAS in urine. Also, we did not detect fluorinated alternatives in either urine or serum. Together, these results suggest limited exposure to both short-chain PFAS and select fluorinated alternatives in this convenience population., (Copyright © 2018. Published by Elsevier Ltd.)

Paired serum and urine samples were collected from workers in a fluorochemical plant from 2008 to 2012 (n = 302) to investigate the level, temporal trends, and half-lives of PFAAs in workers of a fluorochemical plant. High levels of perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonate (PFOS) were detected in serum with median concentrations of 764, 427, and 1725 ng mL -1 , respectively. The half-lives of PFAAs in workers were estimated by daily clearance rates and annual decline rates of PFAAs in serum by a first-order model. The geometric mean and median value for PFHxS, PFOA, and PFOS were 14.7 and 11.7, 4.1 and 4.0, 32.6 and 21.6 years, respectively, by the daily clearance rates, and they were 3.6, 1.7, and 1.9 years estimated by annual decline rates. The half-lives estimated by the limited clearance route information could be considered as the upper limits for PFAAs, however, the huge difference between two estimated approaches indicated that there were other important elimination pathways of PFAAs other than renal clearance in human. The half-lives estimated by annual decline rates in the present study were the shortest values ever reported, and the intrinsic half-lives might even shorter due to the high levels of ongoing exposure to PFAAs.

Dicarboxylic acids are an important source of information about metabolism and potential physiopathological alterations in children with autism spectrum disorders (ASDs). We measured the concentration between dicarboxylic adipic and suberic acids in children with an ASD and typically-developing (TD) children and analyzed any relationships between the severity of the core symptoms of ASDs and other clinical features (drugs, supplements, drugs, or diet). The core symptoms of autism were evaluated using the DSM-IV criteria, and adipic acid and suberic acid were measured in urine samples. Overall, no increase in the concentration of adipic acid in children with ASDs compared to TD children, however when considering vitamin B supplementation in ASD there were significantly increased level of urinary adipic acid in children with an ASD not taking vitamin B supplementation compared to supplemented children or to TD children. No significant difference were observed in suberic acid. Interestingly, the increase in adipic acid concentration was significantly and indirectly correlated with the severity of the deficit in socialization and communication skills in children with an ASD. Therefore, therapeutic treatments aimed at decreasing adipic acid concentration might not be beneficial for treating the core symptoms of ASDs., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Although levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human blood are well documented, information on elimination of these chemicals is limited. In this study, PFOS and PFOA were analyzed in 81 whole blood-urine paired samples from general adults and pregnant women in Tianjin, China. PFOS and PFOA were detected in 48 and 76% of adult urine (AU) samples, with geometric mean (GM) concentrations of 0.011 and 0.008 ng/mL, respectively; whereas relatively low PFOS and PFOA concentrations were found in maternal urine (MU) samples, with GM concentrations of 0.006 and 0.003 ng/mL, respectively. For PFOA, the coefficients of Pearson's correlation between whole blood concentrations and creatinine-adjusted and creatinine-unadjusted urinary concentrations were 0.348 (p = 0.013) and 0.417 (p = 0.002), respectively. The GM urinary elimination rates of PFOS (PFOSUER) and PFOA (PFOAUER) were 16 and 25%, respectively, for adults. These results indicate that urine is an important pathway of excretion of perfluoroalkyl substances (PFASs). The partitioning ratios of PFAS concentration between urine and whole blood (PFASU/B) in pregnant women (PFOSU/B, 0.0004; PFOAU/B, 0.0011) were significantly lower (p = 0.025 for PFOSU/B, p = 0.017 for PFOAU/B) than the ratios found in non-pregnant women (PFOSU/B, 0.0013; PFOAU/B, 0.0028). Furthermore, our results suggest a clear gender difference in the urinary elimination of PFOA, with male adults (31%) having significantly higher PFOAUER than that of female adults (19%). PFOSUER was significantly inversely correlated with age (r = -0.334, p = 0.015); these findings suggest that urinary elimination of PFOS is faster in young adults than in the elderly.

Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Activation of the peroxisome proliferator activated receptor alpha (PPARα) resulting from exposure to PFOA has been extensively studied in rodents. However, marked differences in response to peroxisome proliferators prevent extrapolation of rodent PPARα activation to human health risks and additional molecular mechanisms may also be involved in the biological response to PFOA exposure. To further explore the potential involvement of such additional pathways, the effects of PFOA exposure on urinary metabolites were directly compared with those of other well-known PPARα agonists. Male rats were administered PFOA (10, 33, or 100 mg/kg/d), fenofibrate (100 mg/kg/d), or di(2-ethylhexyl) phthalate (100 mg/kg/d) by gavage for 3 consecutive days and allowed to recover for 4 days, and overnight urine was collected. Greater urinary output was observed exclusively in PFOA-treated rats as the total fraction of PFOA excreted in urine increased with the dose administered. Assessment of urinary metabolites (ascorbic acid, quinolinic acid, 8-hydroxy-2'-deoxyguanosine, and malondialdehyde) provided additional information on PFOA's effects on hepatic glucuronic acid and tryptophan-nicotinamide adenine dinucleotide (NAD) pathways and on oxidative stress, whereas increased liver weight and palmitoyl-CoA oxidase activity indicative of PPARα activation and peroxisomal proliferation persisted up to day five after the last exposure.

Rainbow trout (Oncorhynchus mykiss) confined to respirometer-metabolism chambers were dosed with perfluorooctanoate (PFOA) by intra-arterial (i.a.) injection and sampled to obtain concentration time-course data for plasma, urine, and expired water. The data were then analyzed by compartmental modeling to estimate rates of renal and branchial clearance. Averaged across all animals, the renal clearance rate (1.35mL/h/kg) was more than ten times greater than the branchial clearance rate (0.12mL/h/kg). The average whole-body elimination half-life was 12.6d, which is somewhat longer than values obtained in previous studies with smaller trout. The tissue distribution of PFOA was assessed by collecting tissues at the end of chambered exposures and in a separate tissue time-course experiment. From the time-course study it appeared that an internal steady-state was established within 24h of i.a. injection. Consistent with previous studies, the rank order of PFOA concentration in tissues at steady state was: plasma>liver>kidney>muscle. In a second set of chambered experiments, fish were exposed to PFOA in water to determine the rate of branchial uptake. Branchial uptake rates were too low to assess directly by measuring PFOA concentrations in inspired and expired water. Uptake rate constants (mean 0.19L/d/kg; 0.1% uptake efficiency) were therefore estimated by compartmental modeling using plasma concentration time-course data and model parameters derived from the elimination experiments. It is clear from this effort that elimination of PFOA by trout occurs primarily via the renal route. This finding is consistent with numerous studies of mammals and suggests that trout possess membrane transporters that facilitate the movement of PFOA from plasma to urine., (Published by Elsevier B.V.)

Serum and urine samples from 120 children aged 5-13 years from Dae-gu, Korea, were analyzed for 16 perfluorinated compounds (PFCs). The total PFC concentrations in the serum were 4.26-29.70 ng/mL, and perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS, which was dominant overall, at 6.58 ng/mL), and perfluoroundecanoic acid (PFUndA) were detected in all serum samples. The total PFC concentrations in the urine ranged from below the detection limit to 14.9 ng/mL, and perfluoropentanoic acid (PFPeA) was predominant. The PFOS (p < 0.005) concentration was higher in the serum of children than that of Korean adults aged 20-29. Some of the PFC concentrations in the serum correlated negatively with body mass index and tended to increase with the duration of breastfeeding. However, there were no gender-specific differences in the PFC concentrations and no correlations between PFC concentrations in serum and urine., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry., (Copyright © 2012 John Wiley & Sons, Ltd.)

Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulative compounds that have been associated with adverse health outcomes. In human blood, PFAAs exist as both linear and branched isomers, yet for most linear homologues, and for all branched isomers, elimination rates are unknown. Paired blood and urine samples (n = 86) were collected from adults in China. They were analyzed by a sensitive isomer-specific method that permitted the detection of many PFAAs in human urine for the first time. For all PFAAs except perfluoroundecanoate (PFUnA), levels in urine correlated positively with levels in blood. Perfluoroalkyl carboxylates (PFCAs) were excreted more efficiently than perfluoroalkane sulfonates (PFSAs) of the same carbon chain-length. In general, shorter PFCAs were excreted more efficiently than longer ones, but for PFSAs, perfluorooctanesulfonate (PFOS, a C8 compound) was excreted more efficiently than perfluorohexanesulfonate (PFHxS, a C6 compound). Among PFOS and perfluorooctanoate (PFOA) isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer. A one-compartment model was used to estimate the biological elimination half-lives of PFAAs. Among all PFAAs, the estimated arithmetic mean elimination half-lives ranged from 0.5 ± 0.1 years (for one branched PFOA isomer, 5m-PFOA) to 90 ± 11 years (for one branched PFOS isomer, 1m-PFOS). Urinary excretion was the major elimination route for short PFCAs (C ≤ 8), but for longer PFCAs, PFOS and PFHxS, other routes of excretion likely contribute to overall elimination. Urinary concentrations are good biomarkers of the internal dose, and this less invasive strategy can therefore be used in future epidemiological and biomonitoring studies. The very long half-lives of long-chain PFCAs, PFHxS, and PFOS isomers in humans stress the importance of global and domestic exposure mitigation strategies.

Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES). We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling. PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet. These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society., (© 2013.)

Because of the disadvantages of invasive sampling, it is desirable to explore non-invasive matrices for human biomonitoring of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The aim of this study was to evaluate the application of nail, hair and urine for human biomonitoring of PFOS and PFOA. The concentrations of PFOS and PFOA in matched nail, hair, urine and serum samples collected from 64 donors were measured. The chemicals of interest were detected with high detection frequency in these matrices (90%-100%) except for PFOA in urine samples (56%). Generally, the gender influences on the levels of PFOS and PFOA in these non-invasive matrices were in agreement with that in serum. For PFOS, the coefficients of Spearman correlation between serum samples and nail, hair and urine samples were 0.786 (p<0.001), 0.545 (p<0.001) and 0.302 (p<0.05), respectively. For PFOA, the correlation was only observed between nail samples and serum samples with a correlation coefficient of 0.299 (p<0.05). The results suggested that nail has more potential than hair and urine to be applied in human biomonitoring for PFOS and PFOA in general populations., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

8-(N-2-hydroxy-5-chlorobenzoyl)-amino-caprylic acid (5-CNAC), a compound lacking pharmacological activity enhances the absorption of salmon calcitonin, when co-administered. Disposition and biotransformation of 5-CNAC was studied in six healthy postmenopausal women following a single oral dose of 200mg (14)C-radiolabeled 5-CNAC (as disodium monohydrate salt). Blood, plasma, urine and feces collected over 7 days were analyzed for radioactivity. Metabolite profiles were determined in plasma and excreta and metabolite structures were elucidated by LC-MS/MS, LC-(1)H NMR, enzymatic methods and by comparison with reference compounds. Oral 5-CNAC was safe and well tolerated in this study population. 5-CNAC absorption was rapid (t(max)=0.5h; C(max)=9.00 ± 2.74 μM (mean ± SD, n=6) and almost complete. The elimination half-life (t(½)) was 1.5 ± 1.1h. The radioactive dose was excreted mainly in urine (≥ 90%) in form of metabolites and 0.071% as intact 5-CNAC. Excretion of radioactivity in feces was minor and mostly as metabolites (<3%). Radioactivity in plasma reached C(max) (35.4 ± 7.9 μM) at 0.75 h and declined with a half-life of 13.9 ± 4.3h. 5-CNAC accounted for 5.8% of the plasma radioactivity AUC(0-24h). 5-CNAC was rapidly cleared from the systemic circulation, primarily by metabolism. Biotransformation of 5-CNAC involved: (a) stepwise degradation of the octanoic acid side chain and (b) conjugation of 5-CNAC and metabolites with glucuronic acid at the 2-phenolic hydroxyl group. The metabolism of 5-CNAC in vivo could be reproduced in vitro in human hepatocytes. No metabolism of 5-CNAC was observed in human liver microsomes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Urinary dicarboxylic acids are an important source of information about metabolism and potential problems especially connected with energy production, intestinal dysbiosis, and nutritional individuality in autistic children. A diet rich in vitamins and macroelements is a new idea of intervention in autism. The objective of the present study was to test the hypothesis that vitamin B2, vitamin B6, and magnesium supplementation is effective in reducing the level of dicarboxylic acids in the urine of autistic children. We examined the levels of succinic, adipic, and suberic acids in the urine of autistic children before and after vitamin supplementation. Thirty children with autism received magnesium (daily dose, 200 mg), vitamin B6 (pyridoxine; daily dose, 500 mg), and vitamin B2 (riboflavin; daily dose, 20 mg). The treatment was provided for a period of 3 months. Organic acids were determined using gas chromatography/mass spectrometry. Before supplementation, the levels of succinic, adipic, and suberic acids in the urine of autistic children were 41.47 ± 50.40 μmol/mmol creatinine, 15.61 ± 15.31 μmol/mmol creatinine, 8.02 ± 6.08 μmol/mmol creatinine; and after supplementation, the levels were 9.90 ± 8.26 μmol/mmol creatinine, 2.92 ± 2.41 μmol/mmol creatinine, and 2.57 ± 3.53 μmol/mmol creatinine, respectively. The results suggest that the supplementation reduces the level of dicarboxylic acid in the urine of autistic children., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A method for the analysis of 12 perfluorinated compounds (PFCs) in human urine by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated. One mL 2% formic acid in methanol was added into the urine. After ultrasonication and centrifugation, the samples were purified by a solid phase extraction column and examined by UPLC-MS/MS. The target compounds were quantified by stable isotope dilution technique. The linear range was 0.05 -50 microg/L for the 12 PFCs and the correlation coefficient > or = 0.992. The limits of detection of 12 PFCs were in the range of 0.44 - 3.47 ng/L. The matrix recoveries of the method for the 12 PFCs in three spiked levels (20, 100, 500 ng/L) ranged from 80.3% to 116.2%. The relative standard deviations (RSDs, n = 5) were between 5.5% and 13.8%. The sensitive and accurate method was successfully applied to the analysis of PFCs in human urine.

Background: The Breast Cancer and the Environment Research Centers (BCERCs) include collaborators from basic sciences, epidemiology, and the community, conducting studies to investigate whether environmental exposures are associated with the timing of puberty. A pilot study of a subset of the study participants assessed the feasibility of measuring selected biomarkers of exposure in blood and urine in girls 6-8 years of age. In the Greater Cincinnati study population, we found an elevated serum concentration of perfluorooctanoate (PFOA) among > 90% of young girls living in a small community., Objectives: The research team deliberated whether and how to report the PFOA findings to our study families. We will address the issues considered in our decision, as well as the formats we used to present the findings., Methods: The results were verified as we searched for potential sources of the elevated PFOA levels. As a research team, we grappled with issues regarding the reporting of unexpected results, derived from unknown sources and with unknown clinical significance. Ultimately, we did decide to present these findings to the study families through a well-developed communication plan., Discussion: Research team members came from a variety of experiences and backgrounds, which led to different interpretations about the clinical, ethical, and public health issues surrounding these findings. The ethical debates centered around the precautionary principle, the right to know, and do no harm., Conclusions: Given advances in environmental biomarker technologies and greater use of the transdisciplinary research model, a communication plan must be developed for those involved as study participants.

The number of studies involving the analysis of perfluorooctanoic acid (PFOA) has increased recently because PFOA is routinely detected in human blood samples from around the world. Recent studies with mice have shown that dosing pregnant dams with PFOA during gestation gives rise to a dose-dependent mortality in the litters, a reduction in neonatal body weight for the surviving pups, and subsequent deficits in mammary gland development when compared to control animals. The actual body burdens of PFOA in dams and pups associated with these endpoints have not been determined, in part due to a lack of robust analytical methods for these matrices. The goal of the current study was to develop reliable methods with acceptable performance characteristics for the analysis of PFOA in several matrices relevant to pregnant mouse studies. Dam and pup serum, amniotic fluid, urine, milk, mammary tissue, and whole mouse pups were isolated for method development and analysis. The resulting method provided excellent accuracy (92.1-111%) and reproducibility (relative standard deviation 4.3-21%) making them very useful for future studies. These methods were then applied to dosed animal fluids and tissues in order to conduct a thorough evaluation of the pharmacokinetics in utero. Resulting tissue specific measurements of PFOA in serum, amniotic fluid, urine, milk, mammary tissue, and whole pup homogenate will be used to more completely describe the dose-response relationships for the most sensitive health outcomes and inform pharmacokinetic models that are being developed and evaluated.

Objective: To report health outcomes of 30 years (1978-2007) of medical surveillance of workers engaged in a perfluooctanoic acid (PFOA) production plant., Methods: Fifty-three males workers (20 to 63 years) were submitted every year to medical examination and blood chemical chemistry tests, and serum PFOA dosage., Results: In the latest survey PFOA serum levels ranged from 0.20 to 47.04 microg/mL in currently exposed workers, and from 0.53 to 18.66 microg/mL in those formerly exposed. No clinical evidence of any specific trouble or disease has been recorded over the 30 years, and all the biochemical parameters, including liver, kidney and hormonal functions, turned out to be within the reference ranges, but a significant association of total cholesterol and uric acid with and PFOA serum level was evidenced., Conclusions: A probable interference of PFOA on intermediate metabolism deserves further investigations.

Selecting the appropriate pharmacokinetic (PK) model given the available data is investigated for perfluorooctanoic acid (PFOA), which has been widely analyzed with an empirical, one-compartment model. This research examined the results of experiments [Kemper R. A., DuPont Haskell Laboratories, USEPA Administrative Record AR-226.1499 (2003)] that administered single oral or iv doses of PFOA to adult male and female rats. PFOA concentration was observed over time; in plasma for some animals and in fecal and urinary excretion for others. There were four rats per dose group, for a total of 36 males and 36 females. Assuming that the PK parameters for each individual within a gender were drawn from the same, biologically varying population, plasma and excretion data were jointly analyzed using a hierarchical framework to separate uncertainty due to measurement error from actual biological variability. Bayesian analysis using Markov Chain Monte Carlo (MCMC) provides tools to perform such an analysis as well as quantitative diagnostics to evaluate and discriminate between models. Starting from a one-compartment PK model with separate clearances to urine and feces, the model was incrementally expanded using Bayesian measures to assess if the expansion was supported by the data. PFOA excretion is sexually dimorphic in rats; male rats have bi-phasic elimination that is roughly 40 times slower than that of the females, which appear to have a single elimination phase. The male and female data were analyzed separately, keeping only the parameters describing the measurement process in common. For male rats, including excretion data initially decreased certainty in the one-compartment parameter estimates compared to an analysis using plasma data only. Allowing a third, unspecified clearance improved agreement and increased certainty when all the data was used, however a significant amount of eliminated PFOA was estimated to be missing from the excretion data. Adding an additional PK compartment reduced the unaccounted-for elimination to amounts comparable to the cage wash. For both sexes, an MCMC estimate of the appropriateness of a model for a given data type, the Deviance Information Criterion, indicated that this two-compartment model was better suited to describing PFOA PK. The median estimate was 142.1 +/- 37.6 ml/kg for the volume of the primary compartment and 1.24 +/- 1.1 ml/kg/h for the clearances of male rats and 166.4 +/- 46.8 ml/kg and 30.3 +/- 13.2 ml/kg/h, respectively for female rats. The estimates for the second compartment differed greatly with gender-volume 311.8 +/- 453.9 ml/kg with clearance 3.2 +/- 6.2 for males and 1400 +/- 2507.5 ml/kg and 4.3 +/- 2.2 ml/kg/h for females. The median estimated clearance was 12 +/- 6% to feces and 85 +/- 7% to urine for male rats and 8 +/- 6% and 77 +/- 9% for female rats. We conclude that the available data may support more models for PFOA PK beyond two-compartments and that the methods employed here will be generally useful for more complicated, including PBPK, models.

Perfluorooctanoic acid, an environmental contaminant, is found in both wild animals and human beings. There are large species and sex differences in the renal excretion of perfluorooctanoic acid. In the present study, we aimed to characterize organic anion transporters 1-3 (OAT1-3) in human beings and rats to investigate whether the species differences in the elimination kinetics of perfluorooctanoic acid from the kidneys can be attributed to differences in the affinities of these transporters for perfluorooctanoic acid. We used human (h) and rat (r) OAT transient expression cell systems and measured the [(14)C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, K(m), were 48.0 +/- 6.4 microM for h OAT1; 51.0 +/- 12.0 microM for rOAT1; 49.1 +/- 21.4 microM for hOAT3 and 80.2 +/- 17.8 microM for rOAT3, respectively. These data indicate that both human and rat OAT1 and OAT3 have high affinities for perfluorooctanoic acid and that the species differences in its renal elimination are not attributable to affinity differences in these OATs between human beings and rats. In contrast, neither hOAT2 nor rOAT2 transported perfluorooctanoic acid. In conclusion, OAT1 and OAT3 mediated perfluorooctanoic acid transport in vitro, suggesting that these transporters also transport perfluorooctanoic acid through the basolateral membrane of proximal tubular cells in vivo in both human beings and rats. Neither human nor rat OAT2 mediated perfluorooctanoic acid transport. Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid.

Objectives: To establish a reversed phase high performance liquid chromatographic method with pre-column ultraviolet derivatization for the determination of perfluorooctanoic acids (PFOA) in sewage and urine., Methods: PFOA in sewage and urine formed an ion-pair with tetrabutylammonium (TBA) and were extracted into MTBE. The PFOA then reacted with omega-bromoacetophenone (omega-BAP) in acetonitrile and produced materials quantifiable by HPLC with UV detector., Results: The detection limit of the proposed method was 7.0 microg/L with a relative standard deviation of less than 10%. The recoveries for real samples ranged from 85.3% to 116%., Conclusion: The proposed method is suitable for the determination of PFOA in sewage and urine.

Using nuclear magnetic resonance (NMR) spectroscopy, we investigated the importance of carbon chain length with regard to the hepatic effects associated with perfluoro-n-carboxylic acids. Male F-344 rats were administered a single intraperitoneal dose of either perfluoro-n-heptanoic acid (C7-PFA), perfluoro-n-nonanoic acid (C9-PFA), or perfluoro-n-undecanoic acid (C11-PFA). Data from previous studies involving perfluoro-n-octanoic acid (C8-PFA) and perfluoro-n-decanoic acid (C10-PFA) are included for comparison. Food consumption/body weight was monitored daily for all groups. C9- and C11-PFA treatment yields a prolonged hypophagic response while C7-PFA shows a more acute response. Fluorine-19 NMR spectra of urine and bile samples show no evidence of fluorometabolites and suggest that the distribution of perfluorocarbons into urine or bile is dependent upon carbon chain length. The aqueous solubility of C7-PFA appears to facilitate rapid urinary excretion, similar to that observed for C8-PFA. The relative hydrophobicity of C9- and C11-PFA appears to favor biliary enterohepatic recirculation, yielding a more protracted toxicity, similar to C10-PFA. Phosphorus-31 NMR studies of liver in vivo and liver extracts show that perfluorocarbons of > or = C9 carbons produce a significant increase in liver phosphocholine concentration. These data are discussed with regard to the impact of these chemicals on hepatic phospholipid metabolism. Hepatic peroxisomal fatty acyl CoA-oxidase activity (FAO) was measured to determine if C7-, C9-, and C11-PFA are peroxisome proliferators. Data indicate that the induction of peroxisomal enzyme activity by perfluorocarbons requires a chain length greater than seven carbons. In general, these results demonstrate the significance of carbon chain length in the hepatotoxic response and provide clues toward understanding the processes involved in the biological activities associated with exposure to these compounds.

Three new metabolites of medium-chain fatty acid oxidation, 3-, 6- and 7-hydroxyoctanoyl beta-D-glucuronide, were identified in the urine of six infants who were fed a diet enriched in medium-chain triglycerides (MCT). Glucuronides were extracted from the urine by organic solvent extraction with ethyl acetate and by solid-phase extraction on Sep-Pak C18 cartridges. The compounds of interest were also purified from the organic solvent extract by preparative one-dimensional thin-layer chromatography. Cleavage of the glucuronides was achieved by either alkaline hydrolysis or enzymatic hydrolysis with beta-D-glucuronidase. The analyses of the trimethylsilylated derivatives were performed both by gas chromatography with flame ionization detection (GC/FID) and by gas chromatography/mass spectrometry (GC/MS). The structure of the hydroxyoctanoic acids was proved by comparison of their mass spectra with those of reference substances. Authentic 6-hydroxyoctanoic acid was synthesized. The presence of 6-hydroxyoctanoyl glucuronide shows that in addition to beta-oxidation, omega-oxidation and (omega-1)-hydroxylation, medium-chain fatty acids can be oxidized at the omega-2 position. The conjugation of medium-chain hydroxy-monocarboxylic acids with glucuronic acid has not been described in humans before.

Increased amounts of dicarboxylic acids are excreted in human urine under conditions of medium-chain triglyceride (MCT) feeding, abnormal fatty acid oxidation (FAO) and fasting. Criteria to distinguish dicarboxylic aciduria originating from MCT feeding and other conditions are needed in urinary organic acid profiling for detecting inborn errors of metabolism. Patterns of dicarboxylic aciduria in children under various conditions were compared. The relative amounts of medium-chain saturated dicarboxylic acids in urine are not reliable for identifying MCT-induced dicarboxylic aciduria. On the other hand, low ratios of unsaturated to saturated dicarboxylic acids (<0.1) and 3- hydroxydecenedioic to 3-hydroxydecanedioic acids were found to be useful in identifying dicarboxylic aciduria due to MCT ingestion. Additional unique features of dicarboxylic aciduria from MCT are low ratios of 3-hydroxydodecanedioic to 3-hydroxydecanedioic acid (<0.14) and 3-hydroxyadipic to adipic acid (<0.02).

The glycine conjugates of isocaproic, 4-methylhexanoic, 7-hydroxyoctanoic and 8-hydroxyoctanoic acids have been identified in the urine of children with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency using gas chromatography-mass spectrometry of the trimethylsilyl derivatives. A quantitative study showed that the glycine conjugates of isocaproic and 4-methylhexanoics acids were excreted during acute episodes and in smaller amounts when subjects were asymptomatic. The glycine conjugates of 7-hydroxyoctanoic and 8-hydroxyoctanoic acids were detectable during acute episodes. None of the conjugates was detected in controls or controls receiving a diet containing medium-chain triglycerides. It is suggested that the glycine conjugates of isocaproic acid and 4-methylhexanoic acid are metabolites of branched-chain fatty acids and that they are specific for MCAD deficiency.

There is a marked sex difference in the whole-body elimination of perfluorooctanoic acid (PFOA) in rats, with females excreting the perfluorinated acid much more rapidly (half life [t1/2] less than 1 day) than males (t1/2 = 15 days). Our objective was to determine if androgens or estrogens are involved in causing this sex difference in PFOA elimination. Castration of males greatly increased the elimination of [1-14C]PFOA (9.4 mumol/kg, i.p.) in urine, demonstrating that a factor produced by the testis was responsible for the slow elimination of PFOA in male rats. Castration plus 17 beta-estradiol had no further effect on PFOA elimination whereas castration plus testosterone replacement at the physiologic level reduced PFOA elimination to the same level as rats with intact testes. Thus, in male rats, testosterone exerts an inhibitory effect on renal excretion of PFOA. In female rats, neither ovariectomy nor ovariectomy plus testosterone affected the PFOA urinary elimination, demonstrating that the inhibitory effect of testosterone on PFOA renal excretion is a male-specific response. Probenecid decreased the high rate of PFOA renal excretion in castrated males but had no effect on male rats with intact testes. We conclude that testosterone is a key determinant of the sex difference in PFOA elimination in rats.

Medium-chain triglycerides (MCTs) are absorbed and metabolized differently from long-chain triglycerides (LCTs). Recent data indicate that MCTs may be useful as a dietary substitute in a variety of clinical disorders. The current studies were undertaken to characterize urinary organic acid excretion in patients with non-insulin-dependent diabetes mellitus during 4 d of an LCT or MCT diet. Urinary excretion of the dicarboxylic acids adipic, suberic, and 3-hydroxysebacic and the (omega-1) hydroxylation products 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, was increased during MCT feeding as compared with LCT feeding. Urinary suberic and 7-hydroxyoctanoic acid excretions were increased 55- and 30-fold, respectively, during the MCT-substituted diet. Urinary organic acid profiles provide information on the fate of lipids during MCT feeding and may also be useful in assessing complicance during clinical trials employing MCT-substituted diets.

Five urine samples were collected in clinically quiet periods over a period of one year from a patient suffering from D-glyceric acidemia, and investigated for presence or absence of glycine-conjugates. The findings of isovalerylglycine, 2-methylbutyrylglycine, isobutyrylglycine, and tiglylglycine are interpreted as indications of intracelluar accumulations of isovaleryl-CoA, 2-methylbutyryl-CoA and isobutyryl-CoA. Similarly, the findings of elevated amounts of butyric acid and hexanoic acid together with butyrylglycine, hexanoylglycine, and suberic acid suggest intracellular accumulations of straight-chain acyl-CoA's. It is therefore suggested that this child has a common derangement in his acyl-CoA dehydrogenase (in addition to his primary defect). As possible secondary consequences of this, two points can be mentioned: firstly hyperglycinemia, from which the patient suffered, and secondly, diminished tendency to ketosis, a condition from which the child never suffered, not even in connection with severe intercurrent disease.

Perfluorinated fatty acids have been used commercially as corrosion inhibitors, wetting agents, fire extinguishers and surface active agents. In an earlier study the male rats were more susceptible to the toxic effects of perfluorooctanoic acid (PFO) than females. PFO-concentrations in the plasma suggested that there was a sex related difference in the urinary elimination rate. Active tubular secretion was observed only in the female kidney. The aim of the present study was to compare the urinary elimination of PFO between the two sexes during subchronic administration to the Wistar rat. PFO was administered by gavage to 48 newly-weaned animals at 0 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg for 28 consecutive days. The urine was collected on the 7th and 28th day of the study. At the end of the study, blood was collected by cardiac puncture. At necropsy, tissue specimens for histopathologic examination were collected from the controls and from the group receiving 30 mg/kg of PFO daily. Unlike the female rats, on the 7th day of the study all three groups of male rats excreted significant less PFO than their daily dose of PFO, which suggested that the males had not reached a steady state by seven days. On the 28th day, the males excreted an amount of PFO equal to their daily dose. The PFO concentrations in the plasma of the male animals suggested that the binding sites of PFO may become saturated at the chronic daily dose level of 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

The urinary excretion of perfluorooctanoic acid (PFOA) was studied in male Wistar rats after castration and oestradiol administration as well as in intact females and males. During the first 24 hr females excreted 72 +/- 5% (N = 6) of a single intraperitoneal dose of PFOA (50 mg/kg) in urine whereas the intact males excreted only 9 +/- 4% (N = 6). After castration followed by oestradiol administration (500 micrograms/kg every 2nd day for 14 days), the males excreted PFOA in urine in similar amounts as the females (68 +/- 14% at 24 hr, N = 10). Oestradiol treatment of non-castrated males produced similar results (61 +/- 19% at 24 hr, N = 10). Also castration without oestradiol administration significantly enhanced the renal PFOA excretion, but not as effectively as oestradiol treatment. After 96 hr, the concentration of PFOA in serum of intact males was 17-40 times higher than in the serum of other groups. PFOA was similarly bound by the proteins in the serum of females and males. Phase II metabolism of PFOA was not shown either in males or females.

Octanoyl-beta-D-glucuronide was identified in the urine of five patients with hypoketotic hypoglycemia and dicarboxylic aciduria due to a defective beta-oxidation of medium-chain fatty acids. Two subjects who ingested large amounts of medium-chain triglycerides also excreted large amounts of the glucuronide. The substance was extracted from the urine with ethyl acetate and analyzed by: (1) gas chromatography/mass spectrometry (GC-MS) of the trimethylsilyl derivative and (2) preparative one-dimensional thin-layer chromatography followed by enzymatic hydrolysis with beta-glucuronidase and again GC-MS. A quantitative analysis was performed indirectly by measuring the urinary bound octanoate after the removal of octanoylcarnitine. Octanoylglucuronide represents an additional mechanism for the detoxification of octanoate; its formation may be of help for the maintenance of carnitine homeostasis in patients with medium-chain acyl-CoA dehydrogenase deficiency.

Urinary analysis of the pattern of 23 organic acid metabolites derived from fatty acids in three patients with general (medium-chain) acyl-CoA dehydrogenase deficiency was performed. Although there exist quantitative differences in the excreted amounts of the different metabolites in the three patients the qualitative picture was the same. The excretion of adipic, suberic and sebacic acids was substantial, whereas that of dodecanedioic acid was within or just above control limit. The monounsaturated C6-C10-dicarboxylic acid excretion was only marginally or not increased. 5-OH-hexanoic acid and hexanoylglycine were excreted in excessive amounts, whereas 7-OH-octanoic acid, 9-OH-decanoic acid, octanoylglycine and decanoylglycine were excreted in limited amounts. The excreted amounts of 6-OH-hexanoic, 8-OH-octanoic and 10-OH-decanoic acids were not or only marginally elevated compared to controls. In one of the patients the excretion of ethylmalonic and methylsuccinic acids was enhanced, whereas the excretion of these two acids in the two other patients was comparable to that in controls. The urinary excretion of hexanoic, octanoic, decanoic and dodecanoic acids was just a little above the control limit, whereas the esterified hexanoic and octanoic acids were excreted in appreciable amounts. It is argued that the microsomal omega- and omega-1-oxidation systems are involved in the dicarboxylic and omega-1-OH-monocarboxylic acids formation at C10 and C12 level and that the C8-C6-dicarboxylic and omega-1-OH-monocarboxylic acids are formed from higher chained acids by beta-oxidation in both mitochondria and peroxisomes.

The compound 2,2,4-trimethylpentane (2,2,4 TMP) is reported to be especially potent in inducing kidney lesions in male rats (1,2). Although the pathology produced by 2,2,4 TMP has been examined (1), there are no reports concerning the metabolism of 2,2,4 TMP by the male rat. The eight principal urinary metabolites of 2,2,4 TMP found in the urine of Fischer 344 male rats are: 2,2,4-trimethyl-1-pentanol, 2,4,4-trimethyl-1-pentanol, 2,4,4-trimethyl-2-pentanol, 2,2,4-trimethyl-1-pentanoic acid, 2,4,4-trimethyl-1-pentanoic acid, 2,4,4-trimethyl-2-hydroxy-1-pentanoic acid, 2,2,4-trimethyl-5-hydroxy-1-pentanoic acid and 2,4,4-trimethyl-5-hydroxy-1-pentanoic acid.

A patient with recurrent severe hypoglycemia resembling Reye's syndrome was found to have large accumulations of omega -- 1 hydroxy and keto acids in serum and urine that persisted following clinical recovery. A deficiency of mitochondrial medium chain acyl CoA dehydrogenase activity is proposed on the basis of evidence obtained using gas chromatographic mass spectrometric techniques. Analytical data is presented that will allow the recognition of ths variant presenting in other patients.

In addition to the previously described metabolites, octanoyl glucuronide was identified in the urine of four children who received medium-chain triglycerides. Octanoyl glucuronide in the urine of a child after ingestion of medium-chain triglycerides (C8:C10, 3:1) was quantitated as octanoic acid after glucuronidase treatment by means of gas chromatography/mass spectrometry. The urinary excretion increased rapidly to a maximum 1-2 h after ingestion, and decreased thereafter. During 0-3 h, 6.11 mumol of octanoyl glucuronide was excreted, which comprised 0.034% octanoic acid administered as glyceride, and 0.07% octanoic acid was postulated to be excreted as glucuronide within 24 h. Neither decanoyl glucuronide nor hexanoyl glucuronide was detected. Glucuronidation of branched medium-chain fatty acids, whose beta-oxidation is hindered, has been described previously. The present findings show that even straight-chain fatty acids undergo glucuronidation, although to a lesser extent, in addition to omega-oxidation and beta-oxidation.