Exposure to styrene. Uptake, distribution, metabolism and elimination in man.

Wigaeus, Ewa; Löf, Agneta; Bjurström, Rasmus; Nordqvist, Marianne

doi:10.5271/sjweh.2385

Cited by 84 publications

(44 citation statements)

References 25 publications

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“…The overall kinetics of styrene and its metabolites are in good agreement with previous studies [23,28,35]. We were not able to measure SO, because the hexane used for extraction of the blood samples was contaminated with small amounts of SO.…”

Section: Discussionsupporting

confidence: 90%

Stereochemical metabolism of styrene in volunteers

Wenker

Kežić

Monster

et al. 2001

Int Arch Occup Environ Health

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Stereochemical metabolism of styrene in volunteersWenker, M.A.M.; Kezic, S.; Monster, A.C.; de Wolff, F.A. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Objectives: To study the stereochemistry of styrene metabolism in volunteers, and its interindividual variability. Methods: Twenty healthy male volunteers (aged 18±37 years) were exposed to 360 mg/m 3 styrene for 1 h while they performed 50 W physical exercise. Venous blood was drawn during and for up to 2 h after exposure. Urine was collected at time-intervals up to 24 h after exposure. The following parameters were determined: styrene, free and conjugated styrene glycol (SG) in blood, and conjugated SG, mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine. Results: Average pulmonary retention of styrene was 62%. Excretion of the acidic metabolites MA and PGA accounted for 58% of the pulmonary uptake. The average maximum concentration (C max ) and area under the curve (AUC) of free (R)-SG in blood were 1.3 and 1.7 times higher than those of (S)-SG respectively; the half-life of (R)-SG was longer (82 vs 62 min, P < 0.005). C max and AUC of the conjugated SG enantiomers in blood did not di er, but again half-life for (R)-SG was longer (72 vs 64 min, P < 0.05). Cumulative excretion and renal clearance of conjugated (S)-SG in urine were three and four times higher, respectively, than that of (R)-SG. Cumulative excretion of (S)-MA was 1.6 times higher than (R)-MA. Interindividual di erences in the kinetic parameters of the metabolites were two-to threefold. Conclusions: The enantiomeric excess found was di erent for each metabolite under study, implying di erent enantioselectivity and/or enantiospeci®city of the enzymes and carrier-proteins involved in the biotransformation and excretion. The use of these metabolites as biological indicators for prediction of the enantiomeric excess of the toxic metabolite styrene-7,8-oxide (SO) is therefore not justi®ed. Interindividual di erences in the stereochemical metabolism of styrene are moderate.

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Section: Discussionsupporting

confidence: 90%

Stereochemical metabolism of styrene in volunteers

Wenker

Kežić

Monster

et al. 2001

Int Arch Occup Environ Health

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“…This result is in agreement with the relative concentrations in human blood at the end of a 2-h inhalation exposure when the level of styrene glycol is approximately 15 70 of the styrene concentration (35). The amount of conjugated styrene glycol as the percentage of the total amount of styrene glycol in human blood was 26.1 (SD 6.4) % after inhalation exposure (34); this value is in agreement with the conjugated fraction in mouse blood (table 1).…”

Section: Discussionsupporting

confidence: 79%

“…Recently we reported the occurrence of styrene-7,8-oxide in human blood ( 3 9 , and in the blood and other tissues of mice (17). After the initial findings of conjugated styrene glycol in rat urine (12, 21) styrene glycol has been determined as an in vivo metabolite of styrene in mouse tissues (16) and in blood from experimentally exposed volunteers and occupationally exposed workers (35,36). The main purpose of the present study was to detect styrene-7,8-oxide and, if possible, quantify this epoxide and its importance in the metabolism of styrene.…”

mentioning

confidence: 99%

“…The metabolism of styrene has been extensively studied, and epoxidation a t the -7,8-position has been suggested as the major metabolic pathway (14,15,20,22,33,35), a reaction preferentially catalyzed by microsomal cytochrome P-450 (14,30). Styrene-7,8-oxide (phenyloxirane) is hydrated to styrene glycol (I-phenyl-l,2-ethanediol) by microsomal epoxide hydratase (19,33).…”

mentioning

confidence: 99%

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Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene.

A¹,

Gullstrand²,

Lundgren³

et al. 1984

Scand J Work Environ Health

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LOF A, GULLSTRAND E, LUNDGREN E, BYFALT NORDQVIST M. Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene. Scand J Work Environ Health 10 (1984) 179-187. Styrene-7,8-oxide and its hydrated product styrene glycol were determined in mouse tissues at different times (0.5-5 h) after the intraperitoneal administration of 7-[I4C]-styrene (3.8 mnol/kg). In a study of the influence of dose on the metabolite pattern of styrene, mice were killed 2 h after a dose of 1.1, 2.3, 3.4, and 5.1 mmol/kg, respectively. The mouse tissues studied (blood, liver, kidney, lung, brain, subcutaneous adipose tissue) were isolated and extracted first with hexane to remove styrene and styrene-7,8-oxide and then with ethyl acetate to remove styrene glycol. P-Glucuronidase was used to liberate conjugated styrene glycol. A gas-liquid chromatographic method based on the use of an electron capture detector (GLC-EC) was used to quantify styrene glycol, as well as styrene-7,8-oxide, after hydrolysis. In addition all homogenates and extracts were assayed by radioactivity counting. Styrene-7,8-oxide and styrene glycol reached maximum concentrations within 2 h. The highest levels of styrene-7,8-oxide were detected in the kidneys and subcutaneous adipose tissue, while the lungs showed the lowest levels. Styrene glycol was found in the highest concentrations in the kidneys, liver, blood, and lungs. The concentration of unmetabolized styrene increased exponentially at higher doses. There seemed to be a linear increase with the dose of styrene-7,8-oxide and styrene glycol in all the tissues studied. The more polar metabolites occurred at relatively lower levels in the liver and kidneys at higher doses. In a complementary study the epoxide hydratase inhibitor trichloropropene oxide was added to the removed tissues, and the hexane extracts were analyzed for styrene-7,8-oxide both by GLC-EC and mass spectrometry (GLC-MS).

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“…The error of the headspace method was estimated to be ± 7 %. For further details see the report of Wigaeus et al (21). fined to 1 h immediately preceding the blood sampling ( figure 1).…”

Section: Styrene Concentration In Bloodmentioning

confidence: 99%

Biological monitoring of styrene metabolites in blood.

Löf¹,

Lundgren²,

Em³

et al. 1986

Scand J Work Environ Health

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LOF A, LUNDGREN E, NYDAHL E-M, BYFALTNORDQVIST M. Biological monitoring of styrene metabolites in blood. Scand J Work Environ Health (1986) 70-74. Ten men occupationally exposed to styrene in two glass-fiber reinforced plastics factories were studied during three consecutive workdays. The mean external exposure level was 99 mg/m", The total pulmonary uptake of styrene was estimated from measurements of the styreneconcentrationin inspiredair, the pulmonary ventilation,and the relative uptake. A gas chromatographic method based on electron capture detection was used to quantify styrene glycol,as wellas styrene-7,8-oxide, in blood. The concentration of styrene glycolappeared to be linearly related to the preceding uptake of styrene. When the uptake during 5 h immediately before the blood sampling was considered, the correlation coefficient (r) obtained the value of 0.90. The concentration of styrene-7,8-oxide wasat the detection limitof 0.02Itmolllin most samples. A weakercorrelationbetween the concentration of styrene in blood and the uptake during the hour immediately preceding the blood sampling was obtained (r=0.71).

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Exposure to styrene. Uptake, distribution, metabolism and elimination in man.

Cited by 84 publications

References 25 publications

Stereochemical metabolism of styrene in volunteers

Stereochemical metabolism of styrene in volunteers

Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene.

Biological monitoring of styrene metabolites in blood.

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