Captan and Folpet

Gordon, Elliot B.

doi:10.1016/b978-0-12-374367-1.00090-2

Cited by 22 publications

(21 citation statements)

References 101 publications

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“…In particular, the dermal kinetics of the two studied biomarkers of exposure to folpet, PI and phthalic acid, exhibited similar time profiles, indicating that they were governed by the same essential biological processes. However, phthalic acid was found to be present in much higher amounts than PI in urine, in line with the substantial metabolism of PI into acids documented by some authors following oral or intraperitoneal exposure (Ackermann et al, 1978;Chasseaud et al, 1991;Canal-Raffin et al, 2008;Gordon, 2010). In particular, Canal-Raffin et al (2008) reported an elimination half-life of on average 2.5 h for PI in plasma following a single intraperitoneal folpet dose of 10 mg kg −1 in Wistar rats.…”

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

confidence: 72%

“…This is corroborated by oral mass-balance data in animals following radiolabeled doses, with specific identification of metabolites in urine, showing in particular the presence of 3-hydroxy-4,5-cyclohexene-1,2-dicarboximide (3-OH-THPI) derivative as a more important metabolite (Lappin and Havell, 1990;Gordon, 2010).…”

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

confidence: 66%

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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fungicide was applied on 80 cm(2) of the forearm and left without occlusion or washing for 24 h. Blood samples were withdrawn at fixed time periods over the 72 h following application and complete urine voids were collected over 96 h post-dosing, for metabolite analysis.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 Dsupporting

confidence: 72%

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

confidence: 66%

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Berthet

Bouchard

Vernez

2011

J of Applied Toxicology

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“…According to model simulations and in line with Gordon (), the first biological process governing the kinetics of folpet is its almost instantaneous nonenzymatic breakdown into PI and thiophosgene. PI biotransformation into PA and PAA at the sites of entry (GI for oral exposure and dermis for dermal exposure) was also found to be relatively rapid.…”

Section: Discussionmentioning

confidence: 97%

“…From this nonenzymatic process, the ring metabolite phthalimide (PI) and a thiocarbonyl chloride are formed. The initial ring metabolite of folpet, PI, is rapidly hydrolyzed to phthalamic acid (PAA), and mainly in turn to phthalic acid (PA), according to animal studies (Gordon et al ., ; Zainal and Que Hee, ; Canal‐Raffin et al ., ; Gordon, ).…”

Section: Introductionmentioning

confidence: 99%

“…In humans, it is classified as probable human carcinogen (B2) by the US Environmental Protection Agency (1975,1990) based on an increased incidence of duodenum tumors in mice chronically exposed to high doses by gavage. It is also considered as a severe irritant of the eyes, skin, nose and throat (Lisi et al, 1987;Guo et al, 1996;Gordon, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Toxicokinetic modeling of folpet fungicide and its ring‐biomarkers of exposure in humans

Heredia-Ortiz

Berthet

Bouchard

2011

J of Applied Toxicology

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A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data.

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Pesticides

Costa¹

2020

Environmental Toxicants

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Captan and Folpet

Cited by 22 publications

References 101 publications

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Toxicokinetic modeling of folpet fungicide and its ring‐biomarkers of exposure in humans

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