scholarly journals Physiology-based toxicokinetic modelling of aluminium in rat and man

2021 ◽  
Author(s):  
Christoph Hethey ◽  
Niklas Hartung ◽  
Gaby Wangorsch ◽  
Karin Weisser ◽  
Wilhelm Huisinga
Keyword(s):  
Risk Assessment ◽  
Animal Studies ◽  
Quantitative Risk Assessment ◽  
Mixed Effect ◽  
Naturally Occurring ◽  
Substance Dependent ◽  
Quantitative Understanding ◽  
Intravenous And Oral Administration ◽  
Chloride Salts

AbstractA sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope 27Al, both in animals and man. These limitations are absent in studies with 26Al as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans—especially in toxicological relevant tissues like bone and brain—is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of 26Al tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated 26Al dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous 26Al data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.

Neurodevelopmental Assessment in Kindergarten in Children Exposed to General Anesthesia before the Age of 4 Years

2016 ◽  
Vol 125 (4) ◽  
pp. 667-677 ◽  
Author(s):  
M. Ruth Graham ◽  
Marni Brownell ◽  
Daniel G. Chateau ◽  
Roxana D. Dragan ◽  
Charles Burchill ◽  
...  
Keyword(s):  
Animal Studies ◽  
General Anesthetic ◽  
Mixed Effect ◽  
Logistic Regression Models ◽  
Multiple Exposures ◽  
Increased Risk ◽  
Independent Association ◽  
Developmental Domains ◽  
Single Versus

Abstract Background Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. Methods The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. Results A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, −0.7; 95% CI, −0.93 to −0.47; P < 0.0001) and language/cognition (estimate, −0.34; 95% CI, −0.52 to −0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. Conclusions These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.

scholarly journals Quantitative Risk Assessment of Carcinogenicity of Urethane (Ethyl Carbamatc) on the Basis of Long-term Oral Administration to B6C3F1Mice

1991 ◽  
Vol 82 (4) ◽  
pp. 380-385 ◽  
Author(s):  
Kouki Inai ◽  
Koji Arihiro ◽  
Yukio Takeshima ◽  
Shuji Yonehara ◽  
Yoshiro Tachiyama ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Oral Administration ◽  
Quantitative Risk Assessment

scholarly journals Method for Assessment of Risk of Auto-Roads’ Functionality Loss in Territories of Long-Term (Eternal) Permafrost in Connection with Projected Climatic Changes

2016 ◽  
Vol 5 (5) ◽  
pp. 27-37 ◽  
Author(s):  
Трофименко ◽  
Yuri Trofimenko ◽  
Якубович ◽  
A. Yakubovich
Keyword(s):  
Risk Assessment ◽  
Air Temperature ◽  
Statistical Simulation ◽  
Climatic Changes ◽  
Climatic Conditions ◽  
Permafrost Zone ◽  
Quantitative Risk Assessment ◽  
Legal Documents ◽  
Cryolithic Zone

The risk of auto-roads’ functionality loss in the territories of the long-term (eternal) permafrost in connection with predicted climatic changes is estimated on road structure’s reliability value with use of the existing regulating legal documents. The quantitative risk assessment of functionality loss has been carried out by methods of probabilistic and statistical simulation for the main auto-roads in permafrost zone. It has been shown that in the climatic conditions typical for Russia’s cryolithic zone, increase in air temperature by 1 degree causes an essential increase of risk for an auto-road’s functionality loss. Temperature regime’s contrast change is the second significant factor influencing the risk.

scholarly journals Assessment of the physical vulnerability of buildings affected by slow-moving landslides

2020 ◽  
Vol 20 (9) ◽  
pp. 2547-2565
Author(s):  
Qin Chen ◽  
Lixia Chen ◽  
Lei Gui ◽  
Kunlong Yin ◽  
Dhruba Pikha Shrestha ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Beam Theory ◽  
Quantitative Risk Assessment ◽  
Landslide Risk ◽  
Physical Vulnerability ◽  
Vulnerability Curve ◽  
Length Width ◽  
Slow Moving ◽  
Physical Responses

Abstract. Physical vulnerability is a challenging and fundamental issue in landslide risk assessment. Previous studies mostly focus on generalized vulnerability assessment from landslides or other types of slope failures, such as debris flow and rockfall, while the long-term damage induced by slow-moving landslides is usually ignored. In this study, a method was proposed to construct physical vulnerability curves for masonry buildings by taking the Manjiapo landslide as an example. The landslide's force acting on the buildings' foundation is calculated by applying the landslide residual-thrust calculation method. Considering four rainfall scenarios, the buildings' physical responses to the thrust are simulated in terms of potential inclination by using Timoshenko's deep-beam theory. By assuming the landslide safety factor to be landslide intensity and inclination ratio to be vulnerability, a physical vulnerability curve is fitted and the relative function is constructed by applying a Weibull distribution function. To investigate the effects of buildings' parameters that influence vulnerabilities, the length, width, height, and foundation depth and Young's modulus of the foundation are analysed. The validation results on the case building show that the physical vulnerability function can give a good result in accordance with the investigation in the field. The results demonstrate that the building length, width, and foundation depth are the three most critical factors that affect the physical vulnerability value. Also, the result shows that the higher the ratio of length to width of the building, the more serious the damage to the building. Similarly, the shallower the foundation depth is, the more serious the damage will be. We hope that the established physical vulnerability curves can serve as tools for the quantitative risk assessment of slow-moving landslides.

scholarly journals Risk assessment and remediation of NAPL contaminated soil and groundwater

ChemTexts ◽  
2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Stephen Leharne
Keyword(s):  
Risk Assessment ◽  
Aqueous Phase ◽  
Organic Liquid ◽  
Liquid Waste ◽  
Vapour Phase ◽  
Petroleum Products ◽  
Quantitative Risk Assessment ◽  
Organic Liquids ◽  
Molecular Components

AbstractThe presence of water-immiscible organic liquids—commonly called non-aqueous phase liquids or NAPLs—in soils and groundwater, is a worldwide environmental problem. Typical examples of NAPLs include: petroleum products, organic solvents and organic liquid waste from laboratories and industry. The molecular components of NAPLs present in soils, rocks and groundwater are readily transferred to the vapour and aqueous phases. The extent to which they do this is determined by their solubility (which is quite limited) and vapour pressure (which can be quite high). These molecular components, once dispersed in the vapour phase or dissolved in the aqueous phase, can provide a long-term source of harm to biotic receptors. The object of this lecture text is to examine how we can assess the degree of harm using quantitative risk assessment and how NAPL contaminated environments can be restored through the use of chemical, biological and physical remediation technologies. Graphical abstract

A semi-quantitative risk assessment model for the outbreak of grass carp hemorrhage

2013 ◽  
Vol 19 (3) ◽  
pp. 521-527 ◽  
Author(s):  
Song YANG ◽  
Shuqin WU ◽  
Ningqiu LI ◽  
Cunbin SHI ◽  
Guocheng DENG ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Grass Carp ◽  
Assessment Model ◽  
Quantitative Risk Assessment ◽  
Risk Assessment Model

Risk assessment of Campylobacter species in shellfish: identifying the unknown

1997 ◽  
Vol 35 (11-12) ◽  
pp. 29-34 ◽  
Author(s):  
P. Teunis ◽  
A. Havelaar ◽  
J. Vliegenthart ◽  
G. Roessink
Keyword(s):  
Risk Assessment ◽  
Quantitative Risk Assessment ◽  
Contamination Level ◽  
Risk Of Infection ◽  
Worst Case ◽  
Considerable Uncertainty ◽  
Risk Estimates ◽  
Consumption Data ◽  
Campylobacter Infection ◽  
Campylobacter Spp

Shellfish are frequently contaminated by Campylobacter spp, presumably originating from faeces from gulls feeding in the growing or relaying waters. The possible health effects of eating contaminated shellfish were estimated by quantitative risk assessment. A paucity of data was encountered necessitating many assumptions to complete the risk estimate. The level of Campylobacter spp in shellfish meat was calculated on the basis of a five-tube, single dilution MPN and was strongly season-dependent. The contamination level of mussels (<1/g) appeared to be higher than in oysters. The usual steaming process of mussels was found to completely inactivate Campylobacter spp so that risks are restricted to raw/undercooked shellfish. Consumption data were estimated on the basis of the usual size of a portion of raw shellfish and the weight of meat/individual animal. Using these data, season-dependent dose-distributions could be estimated. The dominant species in Dutch shellfish is C. lari but little is known on its infectivity for man. As a worst case assumption, it was assumed that the infectivity was similar to C. jejuni. A published dose-response model for Campylobacter-infection of volunteers is available but with considerable uncertainty in the low dose region. Using Monte Carlo simulation, risk estimates were constructed. The consumption of a single portion of raw shellfish resulted in a risk of infection of 5–20% for mussels (depending on season; 95% CI 0.01–60%). Repeated (e.g. monthly) exposures throughout a year resulted in an infection risk of 60% (95% CI 7–99%). Risks for oysters were slightly lower than for mussels. It can be concluded that, under the assumptions made, the risk of infection with Campylobacter spp by eating of raw shellfish is substantial. Quantitative risk estimates are highly demanding for the availability and quality of experimental data, and many research needs were identified.

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