Toxicokinetics of captan and folpet biomarkers in orally exposed volunteers

被引:17
作者
Berthet, Aurelie [1 ,2 ,3 ]
Bouchard, Michele [1 ,2 ]
Danuser, Brigitta [3 ]
机构
[1] Univ Montreal, Dept Sante Environm & Sante Travail, Fac Med, Chaire Anal & Gest Risques Toxicol, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Inst Rech Sante Publ, Fac Med, Montreal, PQ H3C 3J7, Canada
[3] Inst Work & Hlth, CH-1011 Lausanne, Switzerland
关键词
toxicokinetics; captan; folpet; tetrahydrophthalimide; phthalimide; phthalic acid; oral exposure; human; biomarker; PHTHALATE METABOLITES; RISK ASSESSMENT; WORKER REENTRY; HUMAN URINE; PESTICIDES; ABSORPTION; RATS; QUANTIFICATION; CALIFORNIA; HUMANS;
D O I
10.1002/jat.1653
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The time courses of key biomarkers of exposure to captan and folpet was assessed in accessible biological matrices of orally exposed volunteers. Ten volunteers ingested 1?mg kg-1 body weight of captan or folpet. Blood samples were withdrawn at fixed time periods over the 72?h following ingestion and complete urine voids were collected over 96?h post-dosing. The tetrahydrophthalimide (THPI) metabolite of captan along with the phthalimide (PI) and phthalic acid metabolites of folpet were then quantified in these samples. Plasma levels of THPI and PI increased progressively after ingestion, reaching peak values similar to 10 and 6?h post-dosing, respectively; subsequent elimination phase appeared monophasic with a mean elimination half-life (t1/2) of 15.7 and 31.5?h, respectively. In urine, elimination rate time courses of PI and phthalic acid evolved in parallel, with respective t(1/2) of 27.3 and 27.6?h; relatively faster elimination was found for THPI, with mean t(1/2) of 11.7?h. However, phthalic acid was present in urine in 1000-fold higher amounts than PI. In the 96?h period post-treatment, on average 25% of folpet dose was excreted in urine as phthalic acid as compared with only 0.02% as PI. The corresponding value for THPI was 3.5%. Overall, THPI and PI appear as interesting biomarkers of recent exposure, with relatively short half-lives; their sensitivity to assess exposure in field studies should be further verified. Although not a metabolite specific to folpet, the concomitant use of phthalic acid as a major biomarker of exposure to folpet should also be considered. Copyright (c) 2011 John Wiley & Sons, Ltd.
引用
收藏
页码:194 / 201
页数:8
相关论文
共 43 条
[1]   METABOLIC AND TOXIC BEHAVIORS OF PHTHALIMIDE DERIVATIVES IN ALBINO-RAT .2. PLACENTAL PASSAGE OF CHLOROMETHYL PHTHALIMIDE, OXYMETHYL PHTHALIMIDE, AND PHTHALIMIDE - THEIR FETAL METABOLISM [J].
ACKERMANN, H ;
FAUST, H ;
KAGAN, YS ;
VORONINA, VH .
ARCHIVES OF TOXICOLOGY, 1978, 40 (04) :255-261
[2]  
[Anonymous], 1991, Documentation of the threshold limit values and biological exposure indices, VI, P214
[3]   Gas-chromatography mass-spectrometry determination of phthalic acid in human urine as a biomarker of folpet exposure [J].
Berthet, Aurelie ;
Berode, Michele ;
Bouchard, Michele .
ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2011, 400 (02) :493-502
[4]   Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine [J].
Berthet, Aurelie ;
Bouchard, Michele ;
Schuepfer, Patrick ;
Vernez, David ;
Danuser, Brigitta ;
Huynh, Cong Khanh .
ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2011, 399 (06) :2243-2255
[5]   Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS [J].
Blount, BC ;
Milgram, KE ;
Silva, MJ ;
Malek, NA ;
Reidy, JA ;
Needham, LL ;
Brock, JW .
ANALYTICAL CHEMISTRY, 2000, 72 (17) :4127-4134
[6]   Quantification methods of folpet degradation products in plasma with HPLC-UV/DAD:: Application to an in vivo toxicokinetic study in rats [J].
Canal-Raffin, Mireille ;
Receveur, Mathilde ;
Martinez, Beatrice ;
Titier, Karine ;
Ohayon, Celine ;
Baldi, Isabelle ;
Molimard, Mathieu ;
Moore, Nicholas ;
Brochard, Patrick .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2008, 865 (1-2) :106-113
[7]  
Casarett LJ., 2008, Casarett and Doull's toxicology: The basic science of poisons, V7th, P883
[8]  
Chasseaud L, 1980, 51202 DPBP HUNT RES
[9]  
Chasseaud L, 1974, CHR174482 HUNT RES C
[10]   FATE OF CAPTAN AND FOLPET IN RATS AND THEIR EFFECTS ON ISOLATED LIVER NUCLEI [J].
COUCH, RC ;
SIEGEL, MR ;
DOROUGH, HW .
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, 1977, 7 (06) :547-558