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  • 1
    Electronic Resource
    Electronic Resource
    Models of Neurotoxicity: Extrapolation of Benchmark Doses in Vitro (2003)
    350 Main Street , Malden , MA 02148 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK . : Blackwell Publishing Inc.
    Risk analysis 23 (2003), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: In risk assessment, no observed exposure level (NOAEL) and benchmark dose (BMD) are usually derived either from epidemiological studies in humans or from animal experiments. In many in vitro studies, concentration-effect/response curves have been analyzed using different mathematical models finalized to the identification of EC50. In the present article, we propose a model to fit dose-response curves in vitro. The BMD approach has been used to compare the cell viability (MTT assay) of different rat (C6 and PC12, glial and neuronal, respectively) and human cell lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-hour exposure to the following neurotoxic substances: manganese chloride (MnCl2), methyl-mercury (Me-Hg), and the enantiomers of styrene oxide (SO). For all rat and human cell lines, the potency of the examined compounds was: MnCl2 〈 S-SO 〈 R-SO 〈 Me-Hg. A preliminary comparison with in vivo toxicity data for these substances gave rise to consistent results. Whereas a reasonable agreement between in vitro and in vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has been reported for Me-Hg and these appear to be either much higher or lower than the BMD for the MTT assay we observed invitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/1539-6924.00331
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  • 2
    Electronic Resource
    Electronic Resource
    Immunological changes among workers occupationally exposed to styrene (1995)
    Springer
    International archives of occupational and environmental health 67 (1995), S. 165-171 
    Details
    ISSN: 1432-1246
    Keywords: Lymphocyte subsets ; Natural killer activity ; Styrene ; Immunotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The functional status of the immune system was investigated in a group of 71 workers exposed to styrene and in 65 control subjects, recruited according to the same selection criteria and comparable as to sex, age, and confounding variables. Air and biological monitoring were used to characterize styrene exposure (median of the main urinary metabolites in the “next-morning” spot samples: 106 mg/g creatinine). Phenotypic analysis of peripheral blood lymphocytes (PBL) by automated flow cytometry revealed a reduced proportion of T lymphocyte subsets (CD3+, CD4+ and CD4+45+), with no changes in CD8+, and a higher proportion of B lymphocytes (CD19+) among styrene-exposed workers. The exposed workers showed a higher proportion of activation markers, namely DR and interleukin-2 receptors (CD25). Immunoglobulin subclasses were comparable in the two groups. An increased prevalence of abnormally low values was apparent for CD2+, CD3+, CD4+, CD4+45+ and CD11b subsets among workers exposed to styrene, whereas CD19+, DR+ and CD25+ showed an increased prevalence of abnormally high values. Natural killer-related phenotypes (CD56+, CD56+16+, and CD56+16−) were more expressed among styrene workers, with average increase of 30%. However, the frequency distribution of the lytic activity of natural killer cells against K-562 target cells was shifted towards lower values in the exposed workers as compared to control subjects. Dose-response relationships between indices of internal dose and prevalence of abnormal values were detectable for T lymphocyte subsets, NK phenotypes, and activation markers. These findings suggest that moderate exposure to styrene is associated with an altered distribution of lymphocyte subsets. The decreased proportion of T lymphocytes, mainly of T helper-inducer cells, could hamper regulatory functions, thus suggesting a negative modulation by styrene exposure. Since a proper balance between immunocycte subsets is important for immunological responses, such changes should be regarded as adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00626348
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  • 3
    Electronic Resource
    Electronic Resource
    On the need of a sampling strategy in biological monitoring: The example of hexane exposure (1993)
    Springer
    International archives of occupational and environmental health 65 (1993), S. S171 
    Details
    ISSN: 1432-1246
    Keywords: Biological monitoring ; Hexane ; 2,5-Hexa-nedione ; Occupational exposure ; Urinalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ambient and biological monitoring of hexane exposure were repeatedly carried out in 14 female shoe makers. Airborne hexane (Ci-H) was measured in 4-h samples collected by a diffusive method. Urinary spot samples were collected before, during (at noon), and at the end of a work shift. 2,5-Hexanedione (2,5HD) in urine collected at noon was poorly related to morning Ci-H. End-of-shift 2,5HD were also poorly related to afternoon air samples. The correlation was still relatively low when end-of-shift 2,5HD was related to 8-h TWA Ci-H (r= 0.44; P〈0.01 on a linear scale, and r-0.58, P〈 0.01 on a log-log scale). End-of-shift 2,5HD levels estimated on the basis of pre-shift values using a mathematical model were much higher (2.3 times on average) than those experimentally measured during the study period. Owing to its relatively long half-time, 2,5HD seems to be influenced not only by current exposure, but also by hexane absorbed during the day(s) preceding sampling. The lack of a sampling strategy may account not only for inconsistencies between environmental and biological data, but also for a possible misuse of biological monitoring when utilized for risk assessment. Despite sometimes poor correlations with Ci-H, 2,5HD may still be preferred to other indicators as a marker of effective internal dose. A sampling strategy should ensure that measured values are representative of the individual risk for adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381334
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  • 4
    Electronic Resource
    Electronic Resource
    Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers (1997)
    Springer
    International archives of occupational and environmental health 69 (1997), S. 209-214 
    Details
    ISSN: 1432-1246
    Keywords: Key words Plasma dopamine β-hydroxylase ; Platelet monoamine oxidases B ; Plasma prolactin ; Symptoms ; Styrene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Aim: A cross-sectional investigation was carried out to assess possible relations between styrene-induced changes in three peripheral markers of catecholaminergic dysfunction and self-reported symptoms of neurotoxicity. Subjects: Male workers (n=46) aged 14–60 (mean 29.5) years who had been exposed to styrene for an average of 6 (0.2–29) years were recruited in glassfiber reinforced plastics plants. A control group of 30 blue-collar workers aged 22–52 (mean 35) years and with no history of exposure to chemicals was recruited from local industries. Styrene exposure ranged from 5 to 120 ppm (8 h-TWA), the median level being relatively low (25 ppm, 8 h-TWA). Styrene metabolites, mandelic and phenylglycoxylic acids (MAPGA) in the “next morning” urine spot samples ranged from 32.0 to 931.1 mg/g creatinine (median 186.5). Methods: Platelet monoamine oxidases B (MAO B) and dopamine β-hydroxylase (DBH) activities were assessed using methods based on HPLC and electrochemical detection. Plasma prolactin (PRL) was measured by a commercially available immunoassay. Questionnaire 16 (Q16) was used to survey self-reported symptoms. Results: Although there was no difference in DBH activity between exposed workers and controls, the most highly exposed workers had significantly lower activity than control subjects. A tendency to lower platelet MAO B activity in exposed than in control subjects was observed. The prevalence of plasma DBH and platelet MAO B values below the lower reference limit was similar in the two groups. PRL values exceeding the upper reference limit were higher (14/46 vs 2/30) among styrene-exposed workers, who also exhibited significantly higher median levels (10.0 vs 5.7 μg/l) than control subjects. Although the number of reported symptoms was similar among exposed and control subjects, in the exposed group it was positively associated with urinary MAPGA (Rho=0.30, P=0.04). Of the three peripheral markers of catecholaminergic dysfunction, plasma DBH was the only parameter negatively related to both urinary MAPGA (F=9.56, P=0.003) and the number of reported symptoms (Rho=0.23, P=0.05). Conclusions: Plasma PRL appears to be a sensitive marker of styrene-induced tubero-infundibular dopaminergic dysfunction in male subjects. DBH in plasma and MAO B in platelets seem to be less suitable markers for biomonitoring effect at the individual level, although DBH was related to the number of reported symptoms and to internal dose. Further studies on a larger and more exposed population are necessary to clarify the significance of these markers for health and their predictive value with regard to both subjective disturbances and concurrently administered performance tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004200050138
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  • 5
    Electronic Resource
    Electronic Resource
    Urinary excretion of brush border antigens and other proteins in children with vesico-ureteric reflux (1992)
    Springer
    Pediatric nephrology 6 (1992), S. 30-32 
    Details
    ISSN: 1432-198X
    Keywords: Vesico-ureteric reflux ; Microproteinuria ; Brush border antigen ; Tubular alterations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was designed to evaluate the occurrence and the type of proteinuria in 82 children with vesico-ureteric reflux (VUR) with or without renal scars. The urinary excretion of the high molecular weight protein albumin was taken as an index of glomerular alterations and the excretion of retinol-binding protein (RBP), β2-microglobulin and brush border antigens (BBA) (measured by monoclonal antibody-based enzyme-linked immunosorbent assay) was taken as an index of tubular alterations. All such markers were increased in children with VUR and were related to the degree of renal function. Patients showing reduced creatinine clearance had very high levels of albuminuria, microproteinuria and BBA, with all these varialbles reciprocally correlated. In children with normal renal function however, only microproteins (not albumin or BBA) were slightly increased, thus indicating an isolated tubular defect without involvement of the proximal segment of the tubule. However, microprotein excretion did not correlate with the grade of scarring (99mtechnetiumdimercaptosuccinic acid scan), both RBP and β2-microglobulin excretion being normal in 75% of children with radioisotopic signs of renal lesions but increased in 17% of children without scars. Therefore, tubular proteinuria identifies different groups of children with VUR but is not related to renal scarring. Prospective studies will define the usefulness of proteinuria as a reliable indicator of renal outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00856825
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  • 6
    Electronic Resource
    Electronic Resource
    Regional alterations of brain catecholamines by styrene exposure in rabbits (1984)
    Springer
    Archives of toxicology 55 (1984), S. 173-177 
    Details
    ISSN: 1432-0738
    Keywords: Styrene ; Dopamine ; Norepinephrine ; Homovanillic acid ; Turnover ; Striatum ; Tuberoinfundibular system ; Adult rabbits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by α-methyl-p-tyrosine. Styrene exposure produced a marked and dose-dependent decrease in striatal and tuberoinfundibular dopamine, associated with a consistent increase in homovanillic acid content in the same regions. Norepinephrine levels were unaffected by styrene exposure. The observed increase in catabolism of dopamine cannot be explained by the turnover time, which was not significantly different in the exposed as compared to the control rabbits. Competition of a styrene metabolite with dopamine for the vesicular storage capacity or a selective destruction of dopaminergic terminals are suggested as the possible mechanisms for styrene neurotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316123
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