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PubMedDate not supplied

Metabolism of styrene oxide in different human fetal tissues.

Epoxide hydrolase and glutathionetransferase activities toward [7-3H]styrene 7,8-oxide were measured in the microsomal and cytosolic fractions, respectively, of human fetal liver, lungs, kidneys, adrenal glands, gut, and placenta. Both activities were present at significant rates in all the tissue specimens studied. Epoxide hydrolase activities in the liver (5.98 +/- 0.62 nmol/min/mg) and the adrenal glands (3.57 +/- 0.46 nmol/min/mg) were considerably higher than the corresponding activities in the lungs, kidneys, gut, and placenta, in which organs the mean values ranged from 0.27 to 0.55 nmol/min/mg. The glutathionetransferase activity was more uniformly distributed among the various tissues. It ranged between 5.56 +/- 0.46 and 4.21 +/- 0.39 nmol/min/mg in the liver, the adrenals, the kidneys, the lungs and the placenta. The gut had, however, significantly lower activity than the other tissues (2.56 +/- 0.24 nmol/min/mg). Our data demonstrate differences in the ontogenic development of the styrene oxide metabolism between man and animals and thus, they point out the lack of relevance of fetal animal studies for prediction of human fetal metabolism. The hepatic and extra-hepatic capacity of the human fetus to detoxify epoxides may be biologically important in view of the fact that xenobiotics traversing the placenta to a great extent reach the fetal organs directly (through the venous duct) without preceding passage through the liver.

Epoxide Hydrolases↗
PubMed1998

[Effect of arterial administration of a high molecular weight anti-tumor agent styrene maleic acid neocarzinostatin for multiple small liver cancer].

To assess the characteristics of a zinostatin derivative, 29 patients with multiple hepatocellular carcinoma of 3 cm or less in diameter were treated with intra-arterial injection of the high molecular weight anti-tumor agent, styrene-maleic acid neocarzinostatin, mixed with Lipiodol. Computerized tomography 3 months after the first therapy showed complete accumulation of Lipiodol in 8 patients (27.6%), 50% to 99% accumulation in 4 (13.8%), 10 to 49% in 10 (34.5%), and less than 10% in 7 (24.1%). After repeated injections, Lipiodol accumulation of the entire area of the original tumor was found in 11 patients (37.9%). The degree of Lipiodol accumulation depended on the angiographic vascularity of the tumor and on the images of computerized tomogram during arterial portography. Although complete accumulation of Lipiodol was found in all tumors in 10 (58.8%) of the 17 patients with well-demarcated round-shaped hypervascularity, only one (8.3%) of 12 patients with ill-demarcated tumors could achieve complete accumulation of the Lipiodol in the tumors. Taking into account the fact that hypervascularity on angiograms is closely correlated with the degree of Lipiodol accumulation on computerized tomograms obtained later, well-demarcated round-shaped liver cancer is the best candidate for styrene-maleic acid neocarzinostatin therapy among various stages of liver cancer.

Adult↗
PubMed1984

Styrene metabolism in man: gas chromatographic separation of mandelic acid enantiomers in the urine of exposed persons.

D- and L-mandelic acid are separated by gas chromatography as isopropyl ester or isopropyl ester-isopropyl urethane on capillary columns, coated with Chirasil -Val. For its determination in urine the isopropyl ester procedure gives better results because other components of the urine do not cause interference. Thus D- and L-mandelic acid in the urine of exposed workers could be detected and verified by means of GC/MS. Occupational styrene exposure near the MAK-value (100 ppm) results in a L/D-enantiomer-ratio in urine of nearly 1.5.

Chromatography, Gas↗
PubMed1987

Quantitation of urinary metabolites of toluene, xylene, styrene, ethylbenzene, benzene and phenol by automated high performance liquid chromatography.

An automated high performance liquid chromatographic method (HPLC) for the direct determination of urinary concentrations of hippuric acid (HA), and o-, m- and p-methyl hippuric acids (MHAs), metabolites of toluene and o-, m-, and p-xylenes, and of urinary phenyl glyoxylic acid (PGA) and mandelic acid (MA), metabolites of styrene or ethylbenzene, is described. Methanol was added to urine, the mixture was centrifuged and the supernatant was injected into HPLC. A stainless-steel column packed with octadecyl silanized silicate was used and the mobile phase was a mixed solution of 5 mM potassium phosphate monobasic/acetonitrile (90/10). The method is simple and specific. Urine can be analyzed without solvent extraction. Analysis can be performed satisfactorily within 45 min for samples containing HA, MHAs, PGA and MA, and within 15 min for those containing HA, PGA and MA. Another automated HPLC method for the determination of urinary concentrations of phenylsulfate (PhS) and phenylglucuronide (PhG), metabolites of benzene and phenol, is also described. Urine was centrifuged and the supernatant was injected into HPLC. A column packed with octadecyl silicate and a mobile phase of 50 mM of potassium phosphate monobasic/acetonitrile (85/15) were used. The whole analyses and quantitative determination can be performed within 15 min for samples containing PhS and PhG in the worker's urine with a simple mobile phase. The accuracy and precision in the present methods by the use of automated HPLC were satisfactory.

Autoanalysis↗
PubMed1993

Study of the neurobehavioural toxicity of styrene at low levels of exposure.

Thirty workers in a dockyard exposed to concentrations of styrene lower than the TLV-TWA of 50 ppm and 30 control workers not subject to exposure but employed by the same company were subjected to three psychometric tests on one Monday morning and evening. The results were usually better in the evening than in the morning in both groups, which proves the lack of acute intoxication at the end of the day at this level of exposure. On the other hand, all of the tests conducted on the exposed subjects are significantly less good than those on the controls. The results suggest the existence of minor but significant organic mental disorders in the subjects exposed to a mean dose of 30 ppm in this study. These results are inconsistent with those of several recent studies. The advisability of lowering the TLV of 50 ppm in discussed.

Adult↗
PubMed1988

Effect of styrene and other alkyl benzene derivatives on oxidation of FAD- and NAD-linked substrates in rat liver mitochondria.

The effect on energetic metabolism of rat liver mitochondria (RLM) of styrene and other aliphatic benzene derivatives, i.e. toluene, ethylbenzene, alpha-methylstyrene and butylbenzene, is studied. It is shown that these compounds uncouple oxidative phosphorylation and this effect is connected with the stimulation of passive entry of protons into mitochondria. The relationship between hydrophobicity of these compounds and their biological activity and mechanism of uncoupling effect are discussed.

Adenosine Triphosphatases↗
PubMed1992

High-performance liquid chromatographic separation of detritylated oligonucleotides on highly cross-linked poly-(styrene-divinylbenzene) particles.

Detritylated oligonucleotides were separated by reversed-phase high-performance liquid chromatography on highly cross-linked polystyrene-based particles having a mean particle diameter of 2.3 microns. The addition of poly(vinyl alcohol) during polymerization, which resulted in the presence of hydroxyl groups on the surface of the poly(styrene-divinylbenzene) beads, was necessary to obtain baseline resolution of phosphorylated oligodeoxyadenylic acids with a chain length of up to 30 bases. The impact of temperature was investigated and optimum resolution was achieved at 40 degrees C. At pH 7.0, the retention times of oligonucleotides were found to depend on the ratio of bases and to increase in the order of C less than G less than A less than T. Under the same conditions, it was possible to separate phosphorylated from dephosphorylated oligonucleotides, the former being eluted earlier. Recoveries ranged from 92 to 100%.

Base Sequence↗
PubMed1986

A pharmacokinetic model of styrene inhalation with the fugacity approach.

The physiologically based pharmacokinetic model of J. C. Ramsey and M. E. Andersen (1984, Toxicol. Appl. Pharmacol. 73, 159-175) of styrene inhalation in rats, with extrapolation to humans, was reformulated with the chemical equilibrium criterion of fugacity instead of concentration to describe compartment partitioning. Fugacity models have been used successfully to describe environmental partitioning processes which are similar in principle to pharmacokinetic processes. The fugacity and concentration models are mathematically equivalent and produce identical results. The use of fugacity provides direct insights into the relative chemical equilibrium partitioning status of compartments, thus facilitating interpretation of experimental and model data. It can help to elucidate dominant processes of transfer, reaction and accumulation, and the direction of diffusion. Certain model simplifications become apparent in which compartments which remain close to equilibrium may be grouped. Maximum steady-state tissue concentrations for a known exposure may be calculated readily. It is suggested that pharmacokinetic fugacity models can complement conventional concentration models and may facilitate linkage to fugacity models describing environmental sources, pathways, and exposure routes.

Adipose Tissue↗
PubMed1992

Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays.

Species differences in dispositional factors such as distribution, metabolism and excretion may often account for species differences in the toxic responses to foreign chemicals. In this study we compared the genotoxic responses of cyclophosphamide (CP) and styrene (ST) between Porton rats and LACA Swiss mice in three in vivo assays (bone marrow micronucleus (MN), sperm morphology (SM) and sister-chromatid exchange (SCE) assays). The sensitivities of the three assays were compared by the doses of the compounds required to elicit a significant genotoxic response. The baseline levels for the MN, SCE and SM assays were 1.1-1.4 and 1.2-1.3 MNPCEs/1000 PCEs, 0.23-0.24 and 0.20-0.21 SCEs/chromosome, 3.5-5.7% and 1.6-1.9% abnormal sperm in mice and rats, respectively. CP was a potent genotoxin in the MN and SCE assays but weakly genotoxic in the SM assay. At comparable doses, the rat was approximately 3-, 2.5- and 1.8-fold more sensitive to CP than mice in the MN, SM and SCE assays, respectively. ST produced weak genotoxic responses in all assays in mice and only in the SM and SCE assays in rats. The mice were more sensitive to ST in the MN and SM assays, while it was difficult to compare the species in the SCE assay. For both compounds the sensitivity of the three assays, in decreasing order, were SCE greater than MN much greater than SM. For CP the relative responses in the Porton rats and LACA Swiss mice were qualitatively similar to previous reports. Although the use of different strains may explain differences between the studies in the magnitude of the responses observed. The results for ST in the rat shows that the choice of genotoxic endpoint can determine whether a response is detectable. Moreover, the discrepancies between the results for ST in this study and others, suggest that as well as using a battery of in vivo tests, it may be prudent to select more that one strain or species to fully assess a compound's ability to produce DNA damage.

Animals↗
PubMed1992

Cytogenetic studies of mice exposed to styrene by inhalation.

The data for the in vivo genotoxicity of styrene (STY) are equivocal. To evaluate the clastogenicity and sister-chromatid exchange (SCE)-inducing potential of STY in vivo under carefully controlled conditions, B6C3F1 female mice were exposed by inhalation for 6 h/day for 14 consecutive days to either 0, 125, 250 or 500 ppm STY. One day after the final exposure, peripheral blood, spleen, and lungs were removed and cells were cultured for the analysis of micronucleus (MN) induction using the cytochalasin B-block method, chromosome breakage, and SCE induction. Peripheral blood smears were also made for scoring MN in erythrocytes. There was a significant concentration-related elevation of SCE frequency in lymphocytes from the spleen and the peripheral blood as well as in cells from the lung. However, no statistically significant concentration-related increases were found in the frequency of chromosome aberrations in the cultured splenocytes or lung cells, and no significant increases in MN frequencies were observed in binucleated splenocytes or normochromatic erythrocytes in peripheral blood smears.

Administration, Inhalation↗
PubMed1993

Combined effects of solvents on the rat's auditory system: styrene and trichloroethylene.

Because exposures to toxic agents typically involve more than one substance, it is necessary to know if combined exposures pose different risks than those to single agents. Many solvents have been implicated in central nervous disorders and some of them are known to produce hearing loss, probably mediated by damage to cochlear hair cells. Hearing loss was studied by recording the brainstem auditory evoked response (BAER) in male Long Evans rats exposed 8 h/day for 5 days to mixtures of styrene (STY) and trichloroethylene (TCE). Dose groups included air or solvent pairs (STY/TCE) in the following concentrations (ppm): (0:3000), (250:2250), (500:1500), (750:750) and (1000:0). Decreased BAER amplitude, indicative of hearing loss, was correlated with blood levels of total solvent. The effects were as predicted by a linear dose-addition model, indicating neither synergistic nor antagonistic interactions at the concentrations studied.

Acoustic Stimulation↗
PubMed1989

pEG plasmid involved in styrene degradation: molecular dimorphism and integration of a segment into the chromosome.

In the Pseudomonas fluorescens strain ST the ability to utilize styrene as the sole carbon source is due to the presence of a plasmid, pEG. In the present report we show that pEG contains two inverted repeat sequences and we present evidence indicating that the catabolic genes are localized in these repeats. The region separating the inverted repeats can assume alternative orientations. In the chromosome of strain ST, a 3 kbp region is homologous to sequences present at one end of the plasmid repeats. This region is present in one copy in the chromosome and could be a specific site for integration of the plasmid. We suggest that this sequence, which is present twice in the pEG plasmid and once in the chromosome, might be a transposon-like element.

Biodegradation, Environmental↗
PubMedDate not supplied

Inactivity of styrene in the mouse sperm morphology test.

Male F1-mice (C3H/He X C57B1/6J) were exposed to styrene by inhalation (150 and 300 ppm; 6 h per day; 5 days) or intraperitoneally (175, 350 and 700 mg/kg per day, 5 days). No statistically significant increase was detected in the frequency of abnormal sperm heads 3 weeks (spermatids exposed) or 5 weeks (late spermatogonia/early spermatocytes exposed) after the beginning of the exposures.

Animals↗
PubMed1992

Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene.

A high-performance liquid chromatographic method is described for the simultaneous determination of six urinary metabolites of several aromatic chemicals: phenol (from benzene), hippuric acid (from toluene), 3-methylhippuric acid (from xylene), mandelic and phenylglyoxylic acid (from styrene) and 4-nitrophenol (from nitrobenzene). Reversed-phase liquid chromatography was performed in an isocratic mode at 1 ml/min on a 5-microns C18 column using two mobile phases: (A) acetonitrile-1% phosphoric acid (10:90); (B) acetonitrile-1% phosphoric acid (30:70). Phase A separates the six metabolites well, but phase B allows to a more rapid and reproducible simultaneous determination of phenolic compounds than phase A. For these compounds a prior enzymic hydrolysis step using Helix pomatia juice is performed to hydrolyse their sulphate and glucuronate conjugates. The reproducibility and the specificity are both excellent. Furthermore, the method is rapid, economical and easily automated. The proposed method appears very suitable for the routine monitoring of workers exposed to these chemicals on the basis of the biological threshold limit values.

Benzene↗
PubMed1998

Ultrastructural changes in the spermatozoa of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride.

Changes in the physical characteristics of semen and ultrastructure of the spermatozoa of langur monkeys after vas occlusion with styrene maleic anhydride (SMA), a polymer with pH-lowering action, are reported. Vas occlusion resulted in severe reversible hypospermia. Severe oligospermia was observed in the majority of animals (five of eight) in the first ejaculation, 30 days after vas occlusion, and in two animals in the second ejaculation, 60 days after vas occlusion. Subsequent monthly ejaculations for 5 months revealed uniform azoospermia. The voided spermatozoa were immotile and supravital staining confirmed necrospermia. Scanning electron microscopy (SEM) revealed severe coiling of tail, rupture of acrosomal envelope, and bent midpiece associated with damaged mitochondrial sheath. Observations by transmission electron microscopy (TEM) revealed vacuolization in the nucleus, membrane damage in the acrosome, loss of segmented columns, and numeric aberrations in the centriole of the neck, as well as degeneration of mitochondrial sheath and axoneme in the midpiece, and absence of outer plasma membrane in the midpiece and tail. The results indicate that the necrospermic status of the spermatozoa during initial ejaculations may offer instant sterility after vas occlusion with SMA.

Animals↗
PubMed1990

Psychosis following styrene exposure: a case report of neuropsychological sequelae.

A patient with a significant history of substance abuse was exposed to styrene and other solvents in the workplace. He became acutely psychotic, experiencing visual hallucinations. The psychosis was controlled with neuroleptic medications and avoidance of solvent exposure, but he continued to show significant deficits in visual-spatial and memory abilities. These deficits cleared with time away from the workplace. The case is of interest in terms of neuropsychological sequelae of solvent exposure and potential interaction of solvents with alcohol and recreational drugs.

Adult↗
PubMed1998

Parts-per-trillion determination of styrene in yoghurt by purge-and-trap gas chromatography with mass spectrometry detection.

Headspace sampling methods prior to capillary gas chromatography have been widely used for the determination of volatile compounds present in very different kinds of samples. This paper describes an automated and rapid system to determine volatiles from yoghurt. Thirty-five volatile organic compounds (VOCs) were identified in polystyrene cups used for yoghurt packaging and 42 VOCs from yoghurt samples. Quantitation of styrene in several samples from the Spanish retail market was carried out.

Chromatography, Gas↗