26 research outputs found
ΠΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ½ΠΎΠΉ ΡΠ΅ΠΊΠ»Π°ΠΌΡ Π² ΠΠ½ΡΠ΅ΡΠ½Π΅ΡΠ΅
Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΏΡΡΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΠΎΠΉ ΠΊΠ°ΠΌΠΏΠ°Π½ΠΈΠΈ Π½Π° ΠΏΠ»ΠΎΡΠ°Π΄ΠΊΠ°Ρ
ΠΏΠΎΠΈΡΠΊΠΎΠ²ΡΡ
ΡΠΈΡΡΠ΅ΠΌ. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΊ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π±ΠΎΡΠ΅ΠΉ Π³ΡΡΠΏΠΏΡ ΠΊΠ»ΡΡΠ΅Π²ΡΡ
ΡΠ»ΠΎΠ², ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π² ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΡΡ
ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ΠΈΡΡ
, ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠΎΡΡΠ°Π²Π° Π³ΡΡΠΏΠΏΡ. ΠΡΡΠ°Π±ΠΎΡΠ°Π½Ρ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ ΠΏΠΎ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΈ ΡΠ΅Π½Ρ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ΠΈΡ Π½Π° ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΠΎΠΌ Π°ΡΠΊΡΠΈΠΎΠ½Π΅ Google. ΠΡΠΏΠΎΠ»Π½Π΅Π½Π° ΠΏΡΠΎΠ²Π΅ΡΠΊΠ° ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΡΡ
ΡΠ΅ΡΠ΅Π½ΠΈΠΉ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄Π°Π½Π½ΡΡ
ΠΊΠΎΠΌΠΌΠ΅ΡΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΡΠΌΡ, Π·Π°Π½ΠΈΠΌΠ°ΡΡΠ΅ΠΉΡΡ ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ½ΠΎΠΉ ΡΠ΅ΠΊΠ»Π°ΠΌΠΎΠΉ Π½Π° ΠΏΠ»ΠΎΡΠ°Π΄ΠΊΠ΅ ΠΏΠΎΠΈΡΠΊΠΎΠ²ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ.Π ΠΎΠ·Π³Π»ΡΠ½ΡΡΠΎ ΡΠ»ΡΡ
ΠΈ ΠΏΡΠ΄Π²ΠΈΡΠ΅Π½Π½Ρ Π΅ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΠΎΡ ΠΊΠ°ΠΌΠΏΠ°Π½ΡΡ Π½Π° ΠΏΠ»ΠΎΡΠ°Π΄ΠΊΠ°Ρ
ΠΏΠΎΡΡΠΊΠΎΠ²ΠΈΡ
ΡΠΈΡΡΠ΅ΠΌ. ΠΠ°ΠΏΡΠΎΠΏΠΎΠ½ΠΎΠ²Π°Π½ΠΎ ΠΏΡΠ΄Ρ
ΡΠ΄ Π΄ΠΎ ΡΠΎΡΠΌΡΠ²Π°Π½Π½Ρ ΡΠΎΠ±ΠΎΡΠΎΡ Π³ΡΡΠΏΠΈ ΠΊΠ»ΡΡΠΎΠ²ΠΈΡ
ΡΠ»ΡΠ², Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π½ΠΈΡ
Ρ ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΠΈΡ
ΠΏΡΠΎΠΏΠΎΠ·ΠΈΡΡΡΡ
, ΡΠΎΠ·ΡΠΎΠ±Π»Π΅Π½ΠΈΠΉ ΠΌΠ΅Ρ
Π°Π½ΡΠ·ΠΌ Π·ΠΌΡΠ½ΠΈ ΡΠΊΠ»Π°Π΄Ρ Π³ΡΡΠΏΠΈ. ΠΠΈΡΠΎΠ±Π»Π΅Π½ΠΎ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΡΡ Π· ΡΠΎΡΠΌΡΠ²Π°Π½Π½Ρ ΠΉ ΠΊΠΎΡΠ΅ΠΊΡΡΡ ΡΡΠ½ΠΈ ΠΏΡΠΎΠΏΠΎΠ·ΠΈΡΡΡ Π½Π° ΡΠ΅ΠΊΠ»Π°ΠΌΠ½ΠΎΠΌΡ Π°ΡΠΊΡΡΠΎΠ½Ρ Google. ΠΠΈΠΊΠΎΠ½Π°Π½ΠΎ ΠΏΠ΅ΡΠ΅Π²ΡΡΠΊΡ Π·Π°ΠΏΡΠΎΠΏΠΎΠ½ΠΎΠ²Π°Π½ΠΈΡ
ΡΡΡΠ΅Π½Ρ Π½Π° ΠΎΡΠ½ΠΎΠ²Ρ ΠΏΡΠ°ΠΊΡΠΈΡΠ½ΠΈΡ
Π΄Π°Π½ΠΈΡ
ΠΊΠΎΠΌΠ΅ΡΡΡΠΉΠ½ΠΎΡ ΡΡΡΠΌΠΈ, ΡΠΎ Π·Π°ΠΉΠΌΠ°ΡΡΡΡΡ ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ½ΠΎΡ ΡΠ΅ΠΊΠ»Π°ΠΌΠΎΡ Π½Π° ΠΏΠ»ΠΎΡΠ°Π΄ΡΡ ΠΏΠΎΡΡΠΊΠΎΠ²ΠΎΡ ΡΠΈΡΡΠ΅ΠΌΠΈ.During article were examined new ways of Internet search system advertising efficiency increasing. Have been suggested method of creation optimal keywords workgroup(which are used in advertising sentences) approach. Have been worked out recommendations for bid fixing and correction. on Google advertising auction. Suggested conceptions were tested and implemented on real busyness information of internet-advertising company, which is mostly concentrated on context advertisin
ΠΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ Π½Π°Π±ΡΡΠ·Π³Π±Π΅ΡΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π² ΠΠΎΠ²ΠΎΠ°Π²ΡΡΡΠΈΠΉΡΠΊΠΎΠΌ ΠΠ΅ΡΠΎΠ΄Π΅ Π’ΡΠ½Π½Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ (NATM)
Π£ ΡΡΠ°ΡΡΡ ΠΏΡΠΎΠ°Π½Π°Π»ΡΠ·ΠΎΠ²Π°Π½Ρ ΡΡΡΡ Ρ ΠΎΡΠ½ΠΎΠ²Π½Ρ ΠΏΡΠΈΠ½ΡΠΈΠΏΠΈ ΠΠΎΠ²ΠΎΠ°Π²ΡΡΡΡΠΉΡΡΠΊΠΎΠ³ΠΎ ΠΠ΅ΡΠΎΠ΄Ρ Π’ΡΠ½Π΅Π»ΡΠ²Π°Π½Π½Ρ (NATM), ΡΠΎ ΡΠΈΡΠΎΠΊΠΎ Π·Π°ΡΡΠΎΡΠΎΠ²ΡΡΡΡΡΡ Π² Π·Π°ΡΡΠ±ΡΠΆΠ½ΡΠΉ ΠΏΡΠ°ΠΊΡΠΈΡΡ Π±ΡΠ΄ΡΠ²Π½ΠΈΡΡΠ²Π° ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ½ΠΈΡ
ΡΡΠ½Π΅Π»ΡΠ². Π’Π°ΠΊΠΎΠΆ ΡΠΎΠ·Π³Π»ΡΠ½ΡΡΠΎ Π·Π°ΡΡΠΎΡΡΠ²Π°Π½Π½Ρ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΡΡ ΡΠΎΡΠΊΡΠ΅ΡΡΠ²Π°Π½Π½Ρ, ΡΠΊΠ° Π»Π΅ΠΆΠΈΡΡ Π² ΠΎΡΠ½ΠΎΠ²Ρ ΠΌΠ΅ΡΠΎΠ΄Ρ.Essence and basic principles of New Austrian Tunnelling Method (NATM), which widely used in foreign practice building of transport tunnels, is analysed in the article. Application of gunite
technology, being the basis of method, is also considered
Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals
Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause-effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman's reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause-effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.Peer reviewe
The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls
In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs
Evaluation of relative effect potencies (REPs) for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessment
Toxic equivalency factors (TEFs) are generally applied for estimating human risk of dioxins and dioxin-like compounds using systemic (e.g., blood) levels, even though these TEFs are established based on intake doses in rodent studies. This review shows that systemic relative effect potencies (REPs) can deviate substantially from intake REPs, but are similar to in vitro-derived REPs. Interestingly, the in vitro REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) are up to one order of magnitude higher than their in vivo REPs and WHO-TEFs, based on oral intake. In addition, clear species-differences in in vitro REPs were apparent for some congeners. Especially the human-derived REP for polychlorinated biphenyl 126 is one to two orders of magnitude lower than rodent REPs and its current WHO-TEF. Next, suggested adapted systemic or human-specific TEFs for these congeners were applied to calculate changes in systemic TEQ concentrations in studies from the USA, Germany and Japan and compared with either the JECFA TDI or USEPA RfD of TCDD. Overall, the effect of such TEF changes for these three congeners on total TEQ roughly balances each other out in the general population. However, results may be different for situations in which a specific group of congeners dominates. For those congeners that show a distinct deviation between either intake and systemic REPs or between rodent- and human-based in vitro REPs, we propose that especially REPs derived from human-based in vitro models are weighted more heavily in establishing systemic or human-specific TEF values to improve human health risk assessment
Tissue distribution of dioxin-like compounds: potential impacts on systemic relative potency estimates
Relative effect potencies (REPs) for dioxins and dioxin-like compounds based on tissue concentration or internal dose ( REPs) can be considered of high relevance for human risk assessment. Within the EU-project SYSTEQ, REPs for 1,2,3,7,8-pentachlorodibenzodioxin (PeCDD), 2,3,4,7,8,-pentachlorodibenzofuran (4-PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,3',4,4',5-pentachlorobiphenyl (PCB 118) and 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) were calculated based on a plasma, adipose tissue or liver concentration in Sprague Dawley rats and C57bl/6 mice three days after a single oral dose. Compound-specific distribution as well as differences in accumulation and elimination can influence the tissue concentration and thereby the relative potency estimate of a congener. Here, we show that distribution patterns are generally similar for the tested congeners between the SYSTEQ dataset and other studies using either a single dose or subchronic dosing. Furthermore, the responding concentration for TCDD in single dose studies is comparable to the responding concentrations reported in subchronic studies. In contrast with data for laboratory rodents, available distribution data for humans in the general population display little or no hepatic sequestration. Because hepatic sequestration due to CYP1A2 protein binding may affect the amount of congener that is bioavailable for the AhR to produce hepatic responses, estimates of relative potencies between congeners with differing degrees of hepatic sequestration based on hepatic responses may be misleading for application to human risk assessment. Therefore, extra-hepatic concentration in blood serum/plasma or adipose tissue together with a biological extra-hepatic response might give a more accurate prediction of the relative potency of a congener for human responses under environmental conditions
Comparison of Intake and Systemic Relative Effect Potencies of Dioxin-like Compounds in Female Mice after a Single Oral Dose
BACKGROUND: Risk assessment for mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) is performed using the toxic equivalency factor (TEF) approach. These TEF values are derived mainly from relative effect potencies (REPs) linking an administered dose to an in vivo toxic or biological effect, resulting in "intake" TEFs. At present, there is insufficient data available to conclude that intake TEFs are also applicable for systemic concentrations (e. g., blood and tissues). OBJECTIVE: We compared intake and systemic REPs of 1,2,3,7,8-pentachlorodibenzodioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3', 4,4', 5-pentachlorobiphenyl (PCB-126), 2,3', 4,4', 5-pentachlorobiphenyl (PCB-118), and 2,3,3', 4,4', 5-hexachlorobiphenyl (PCB-156) in female C57BL/6 mice 3 days after a single oral dose. METHODS: We calculated intake REPs and systemic REPs based on administered dose and liver, adipose, or plasma concentrations relative to TCDD. Hepatic cytochrome P450 1Al-associated ethoxyresorufin-O-deethylase (EROD) activity and gene expression of Cyp1a1, 1a2 and 1b1 in the liver and peripheral blood lymphocytes (PBLs) were used as biological end points. RESULTS: We observed up to one order of magnitude difference between intake REPs and systemic REPs. Two different patterns were discerned. Compared with intake REPs, systemic REPs based on plasma or adipose levels were higher for PeCDD, 4-PeCDF, and PCB-126 but lower for the mono-ortho PCBs 118 and 156. CONCLUSIONS: Based on these mouse data, the comparison between intake REPs and systemic REPs reveals significant congener-specific differences that warrants the development of systemic TEFs to calculate toxic equivalents (TEQs) in blood and body tissues
Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female rats after a single oral dose
Risk assessment for mixtures of dioxin-like compounds uses the toxic equivalency factor (TEF) approach. Although current WHO-TEFs are mostly based on oral administration, they are commonly used to determine toxicity equivalencies (TEQs) in human blood or tissues. However, the use of "intake" TEFs to calculate systemic TEQs in for example human blood, has never been validated. In this study, intake and systemic relative effect potencies (REPs) for 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3β²,4,4β²,5-pentachlorobiphenyl (PCB-126), 2,3β²,4,4β²,5-pentachlorobiphenyl (PCB-118) and 2,3,3β²,4, 4β²,5-hexachlorobiphenyl (PCB-156) were compared in rats. The effect potencies were calculated based on administered dose and liver, adipose or plasma concentrations in female Sprague-Dawley rats 3 days after a single oral dose, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatic ethoxyresorufin-O-deethylase activity and gene expression of Cyp1a1, 1a2, 1b1 and aryl hydrocarbon receptor repressor in liver and peripheral blood lymphocytes were used as endpoints. Results show that plasma-based systemic REPs were generally within a half log range around the intake REPs for all congeners tested, except for 4-PeCDF. Together with our previously reported systemic REPs from a mouse study, these data do not warrant the use of systemic REPs as systemic TEFs for human risk assessment. However, further investigation for plasma-based systemic REPs for 4-PeCDF is desirable