Retention, excretion and metabolism of phthalic acid administered orally to the rat

Williams, D. T.; Blanchfield, B.

doi:10.1007/bf01713035

Cited by 19 publications

(10 citation statements)

References 3 publications

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“…Ackermann et al (1978) also estimated a PI half-life of 2 h in rat fetuses following an oral administration of 2.5 mg kg −1 of 15 N-phthalimide to pregnant Wistar-strain albino rats and observed a fast metabolism of PI into phthalamic acid. This latter metabolite is then transformed to phthalic acid, the final ring metabolite of folpet (Williams and Blanchfield, 1974).…”

Section: Kinetics Of Biomarkers Of Exposure To Captan and Folpet In Dmentioning

confidence: 99%

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Berthet

Bouchard

Vernez

2011

J of Applied Toxicology

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To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10 mg kg(-1) dose of each fungicide was applied on 80 cm(2) of the forearm and left without occlusion or washing for 24 h. Blood samples were withdrawn at fixed time periods over the 72 h following application and complete urine voids were collected over 96 h post-dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24 h for THPI and 10 h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t(½) of 28.8 and 29.6 h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t(½) of 18.7 h. Over the 96 h period post-application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet.

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Section: Kinetics Of Biomarkers Of Exposure To Captan and Folpet In Dmentioning

confidence: 99%

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Berthet

Bouchard

Vernez

2011

J of Applied Toxicology

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“…For instance, its high aqueous solubility favors rapid and extensive pulmonary absorption and the high oxidation state limits further metabolism and helps maintain high measurable levels in blood or urine specimens. These properties are supported by pharmacokinetic research with an analogous chemical, phthalic acid, which is excreted unchanged in the urine of treated rats in substantial amounts (i.e., 20–25% of the dose) within 8 hr of treatment (Williams and Blanchfield, 1974). Scaling these results to humans would imply a sufficiently long half-life for routine detection in the urine of exposed individuals.…”

Section: Research Trendsmentioning

confidence: 95%

Factors and Trends Affecting the Identification of a Reliable Biomarker for Diesel Exhaust Exposure

Morgott

2014

Critical Reviews in Environmental Science and Technology

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The monitoring of human exposures to diesel exhaust continues to be a vexing problem for specialists seeking information on the potential health effects of this ubiquitous combustion product. Exposure biomarkers have yielded a potential solution to this problem by providing a direct measure of an individual's contact with key components in the exhaust stream. Spurred by the advent of new, highly sensitive, analytical methods capable of detecting substances at very low levels, there have been numerous attempts at identifying a stable and specific biomarker. Despite these new techniques, there is currently no foolproof method for unambiguously separating diesel exhaust exposures from those arising from other combustion sources.Diesel exhaust is a highly complex mixture of solid, liquid, and gaseous components whose exact composition can be affected by many variables, including engine technology, fuel composition, operating conditions, and photochemical aging. These factors together with those related to exposure methodology, epidemiological necessity, and regulatory reform can have a decided impact on the success or failure of future research aimed at identifying a suitable biomarker of exposure. The objective of this review is to examine existing information on exposure biomarkers for diesel exhaust and to identify those factors and trends that have had an impact on the successful identification of metrics for both occupational and community settings. The information will provide interested parties with a template for more thoroughly understanding those factors affecting diesel exhaust emissions and for identifying those substances and research approaches holding the greatest promise for future success.

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“…Analytical methods have already been developed to quantify PA as a urinary metabolite of phthalates, because it is also the final hydrolysis product of phthalates [12][13][14][15][16], but no method has been published for the quantification of total PA equivalents as a biomarker of folpet exposure to our knowledge. Therefore, the objectives of this study were i) to measure total PA equivalents in urine as a biomarker of folpet exposure by adapting existing gas chromatography -mass spectrometry [GC-MS] methods after oxidation of PI and PAA and trimethylsylation of PA molecule, and ii) to use this method to quantify the urinary excretion of total PA equivalents in volunteers exposed to folpet as well as iii) to assess worker exposure to this fungicide through biomonitoring.…”

Section: Introductionmentioning

confidence: 99%

Gas-chromatography mass-spectrometry determination of phthalic acid in human urine as a biomarker of folpet exposure

2011

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Agricultural workers are exposed to folpet, but biomonitoring data are limited. Phthalimide (PI), phthalamic acid (PAA), and phthalic acid (PA) are the ring metabolites of this fungicide according to animal studies, but they have not yet been measured in human urine as metabolites of folpet, only PA as a metabolite of phthalates. The objective of this study was thus to develop a reliable gas chromatography-tandem mass spectrometry (GC-MS) method to quantify the sum of PI, PAA, and PA ring-metabolites of folpet in human urine. Briefly, the method consisted of adding p-methylhippuric acid as an internal standard, performing an acid hydrolysis at 100 °C to convert ring-metabolites into PA, purifying samples by ethyl acetate extraction, and derivatizing with N,O-bis(trimethylsilyl)trifluoro acetamide prior to GC-MS analysis. The method had a detection limit of 60.2 nmol/L (10 ng/mL); it was found to be accurate (mean recovery, 97%), precise (inter- and intra-day percentage relative standard deviations <13%), and with a good linearity (R (2) > 0.98). Validation was conducted using unexposed peoples urine spiked at concentrations ranging from 4.0 to 16.1 μmol/L, along with urine samples of volunteers dosed with folpet, and of exposed workers. The method proved to be (1) suitable and accurate to determine the kinetic profile of PA equivalents in the urine of volunteers orally and dermally administered folpet and (2) relevant for the biomonitoring of exposure in workers.

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Retention, excretion and metabolism of phthalic acid administered orally to the rat

Cited by 19 publications

References 3 publications

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Factors and Trends Affecting the Identification of a Reliable Biomarker for Diesel Exhaust Exposure

Gas-chromatography mass-spectrometry determination of phthalic acid in human urine as a biomarker of folpet exposure

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