Vyd. 1. 245 s. : il. ; 20 cm
- MeSH
- butadieny škodlivé účinky toxicita MeSH
- dioxany škodlivé účinky toxicita MeSH
- hodnocení rizik MeSH
- karcinogeny MeSH
- kosmetické přípravky chemie škodlivé účinky toxicita MeSH
- kosmetické techniky škodlivé účinky MeSH
- kyseliny ftalové škodlivé účinky toxicita MeSH
- parabeny škodlivé účinky toxicita MeSH
- zdravé chování MeSH
- životní styl MeSH
- Publikační typ
- populární práce MeSH
- Konspekt
- Hygiena. Lidské zdraví
- NLK Obory
- estetická medicína
- toxikologie
The rationale for cytogenetic monitoring to determine if safe maximum allowable concentrations (MAC) of genotoxic chemicals are being maintained in a workplace is that exposure levels that do not increase chromosomal aberration frequencies are without harmful effects. Such monitoring, widely used in occupational health programs in the Czech Republic (CR), includes workers exposed to 1,3-butadiene (BD) or other chemicals. Studies of BD exposed workers in the years 1992, 1993, 1994, 1998, and 2004 compared mean frequencies of cells carrying chromosomal aberrations (frequency of aberrant cells=%AB.C.) in exposed workers with those in non-exposed matched controls in the same plant or in other individuals living in the region of the same petrochemical industry. Workers potentially exposed to acrylonitrile at this site were also evaluated in 2000, along with another unexposed matched control group. The %AB.C. values of exposed workers and their controls were also compared with reference values determined for normal individuals (ages 20-59 years) throughout the CR. Substantial discrepancies were noted between subjects in the region of the petrochemical industry (exposed workers and controls) for the years 2000 and 2004 and the reference CR-wide normal values that had been determined during an earlier time period. The matched non-exposed controls at the petrochemical industry site showed a mean %AB.C. value of 1.56+/-1.23% (N=25) in 1998; this rose to a mean of 2.65+/-2.29% (N=33) in 2000. In 2004, values for non-exposed matched controls at the industry site were 2.64+/-1.75% for males (N=25) and 2.38+/-1.74% (N=26) for females. However, the earlier determined CR-wide %AB.C. mean reference values for normal individuals were 1.77+/-1.16% (N=1305) for the interval 1977-1988 and 1.45+/-1.17% (N=2140) for the interval 1991-1999. As both reference values are substantially lower than those determined in 2000 and 2004 for the non-exposed matched controls at the petrochemical industry site, an analysis of the CR-wide mean normal individual reference values for this same 2000-2004 period was conducted. Unexpectedly, it was found that this reference value too had risen to 1.95+/-1.36% (N=1045) and was comparable to the concurrent matched control values at the petrochemical industry site where the monitoring studies were conducted. This substantial increase in %AB.C. values in 2000 and 2004, therefore, has occurred throughout the CR and is probably unrelated to chemicals uniquely present at the petrochemical industry site.
- MeSH
- akrylonitril škodlivé účinky MeSH
- butadieny škodlivé účinky MeSH
- časové faktory MeSH
- chemický průmysl MeSH
- chromozomální aberace MeSH
- dospělí MeSH
- financování organizované MeSH
- genetické techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty mikrobiologie účinky záření MeSH
- maximální přípustná koncentrace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
Results of a recent molecular epidemiological study of 1,3-butadiene (BD) exposed Czech workers, conducted to compare female to male responses, have confirmed and extended the findings of a previously reported males only study (HEI Research Report 116, 2003). The initial study found that urine concentrations of the metabolites 1,2-dihydroxy-4-(acetyl) butane (M1) and 1-dihydroxy-2-(N-acetylcysteinyl)-3-butene (M2) and blood concentrations of the hemoglobin adducts N-[2-hydroxy-3-butenyl] valine (HB-Val) and N-[2,3,4-trihydroxy-butyl] valine (THB-Val) constitute excellent biomarkers of exposure, both being highly correlated with BD exposure levels, and that GST genotypes modulate at least one metabolic pathway, but that irreversible genotoxic effects such as chromosome aberrations and HPRT gene mutations are neither associated with BD exposure levels nor with worker genotypes (GST [glutathione-S-transferase]-M1, GSTT1, CYP2E1 (5' promoter), CYP2E1 (intron 6), EH [epoxide hydrolase] 113, EH139, ADH [alcohol dehydrogenase]2 and ADH3). The no observed adverse effect level (NOAEL) for chromosome aberrations and HPRT mutations was 1.794 mg/m(3) (0.812 ppm)--the mean exposure level for the highest exposed worker group in this initial study. The second Czech study, reported here, initiated in 2003, included 26 female control workers, 23 female BD exposed workers, 25 male control workers and 30 male BD exposed workers (some repeats from the first study). Multiple external exposure measurements (10 full 8-h shift measures by personal monitoring per worker) over a 4-month period before biological sample collections showed that BD workplace levels were lower than in the first study. Mean 8-h TWA exposure levels were 0.008 mg/m(3) (0.0035 ppm) and 0.397 mg/m(3) (0.180 ppm) for female controls and exposed, respectively, but with individual single 8-h TWA values up to 9.793 mg/m(3) (4.45 ppm) in the exposed group. Mean male 8-h TWA exposure levels were 0.007 mg/m(3) (0.0032 ppm) and 0.808 mg/m(3) (0.370 ppm) for controls and exposed, respectively; however, the individual single 8-h TWA values up to 12.583 mg/m(3) (5.72 ppm) in the exposed group. While the urine metabolite concentrations for both M1 and M2 were elevated in exposed compared to control females, the differences were not significant, possibly due to the relatively low BD exposure levels. For males, with greater BD exposures, the concentrations of both metabolites were significantly elevated in urine from exposed compared to control workers. As in the first study, urine metabolite excretion patterns in both sexes revealed conjugation to be the minor detoxification pathway (yielding the M2 metabolite) but both M1 and M2 concentration values were lower in males in this second study compared to their concentrations in the first, reflecting the lower external exposures of males in this second study compared to the first. Of note, females showed lower concentrations of both M1 and M2 metabolites in the urine per unit of BD exposure than did males while exhibiting the same M1/(M1+M2) ratio, reflecting the same relative utilization of the hydrolytic (producing M1) and the conjugation (producing M2) detoxification pathways as males. Assays for the N,N-(2,3-dihydroxy-1,4-butadyl) valine (pyr-Val) hemoglobin (Hb) adduct, which is specific for the highly genotoxic 1,2,3,4-diepoxybutane (DEB) metabolite of BD, have been conducted on blood samples from all participants in this second Czech study. Any adduct that may have been present was below the limits of quantitation (LOQ) for this assay for all samples, indicating that production of this important BD metabolite in humans is below levels produced in both mice and rats exposed to as little as 1.0 ppm BD by inhalation (J.A. Swenberg, M.G. Bird, R.J. Lewis, Future directions in butadiene risk assessment, Chem. Biol. Int. (2006), this issue). Results of assays for the HB-Val and THB-Val hemoglobin adducts are pending. HPRT mutations, determined by cloning assays, and multiple measures of chromosome level changes (sister-chromatid exchanges [SCE], aberrations determined by conventional methods and FISH) again showed no associations with BD exposures, confirming the findings of the initial study that these irreversible genotoxic changes do not arise in humans occupationally exposed to low levels of BD. Except for lower production of both urine metabolites in females, no female-male differences in response to BD exposures were detected in this study. As in the initial study, there were no significant genotype associations with the irreversible genotoxic endpoints. However, as in the first, differences in the metabolic detoxification of BD as reflected in relative amounts of the M1 and M2 urinary metabolites were associated with genotypes, this time both GST and EH.
- MeSH
- acetylcystein analogy a deriváty moč MeSH
- benzen analýza MeSH
- butadieny aplikace a dávkování škodlivé účinky MeSH
- chemický průmysl * MeSH
- chromozomální aberace účinky léků MeSH
- dospělí MeSH
- genotyp MeSH
- hemoglobiny metabolismus MeSH
- hypoxanthinfosforibosyltransferasa genetika MeSH
- lidé MeSH
- molekulární epidemiologie MeSH
- mutace genetika MeSH
- pohlavní dimorfismus * MeSH
- pracovní expozice škodlivé účinky statistika a číselné údaje MeSH
- pracovní síly MeSH
- styren analýza MeSH
- toluen analýza MeSH
- výměna sesterských chromatid účinky léků genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- biologické markery MeSH
- butadieny * škodlivé účinky MeSH
- chromozomální aberace * MeSH
- epidemiologické monitorování MeSH
- epidemiologické studie MeSH
- glutathion-S-transferasa fí * MeSH
- hodnocení rizik MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- poškození DNA * MeSH
- pracovní expozice * MeSH
- rostlinné gumy * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- butadieny aplikace a dávkování metabolismus škodlivé účinky MeSH
- inhalační expozice MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely u zvířat MeSH
- myši MeSH
- nádory mortalita MeSH
- systém (enzymů) cytochromů P-450 MeSH
- testy karcinogenity metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH