Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice

2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and solvents. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is believed to be responsible for 2BE toxicities associated with hemolysis of red blood cells. The objective of the study was to characterize the systemic disposition of 2BE and 2BAA in rats and mice during 2-year 2BE inhalation toxicity studies. Male and female F344 rats and B6C3F1 mice (6-7 weeks old) were exposed to target 2BE concentrations of 0, 31.2, 62.5, or 125 ppm (rats), or 0, 62.5, 125, or 250 ppm (mice), by whole-body inhalation for 6 h/day, 5 days/week for up to 18 months. Postexposure blood samples were collected after 1 day, 2 weeks, and 3, 6, 12, and 18 months of exposure. Postexposure 16-h urine samples were collected after 2 weeks and 3, 6, 12, and 18 months of exposure. A separate set of mice was kept in the control chamber and exposed to 2BE for 3 weeks when they were approximately 19 months old. Postexposure blood samples were collected after 1 day and 3 weeks of exposure and 16-h urine samples were collected after 2 weeks of exposure from these aged mice. Blood samples were analyzed for both 2BE and 2BAA and urine samples were analyzed for 2BAA using GC/MS, and their kinetic parameters were estimated through the curve-fitting method using SAS. Systemically absorbed 2BE was rapidly cleared from blood (t1/2-RAT < 10 min; t1/2-MOUSE < 5 min after the 1-day exposure) independent of exposure concentration. Proportional increases in AUC2BE relative to increases in exposure concentration indicated linear 2BE kinetics. In contrast, the rate of 2BAA elimination from blood decreased as the exposure concentration increased. Nonproportional increases in AUC2BAA also indicated that 2BAA is eliminated following dose-dependent, nonlinear kinetics. Overall, mice eliminated both 2BE and 2BAA from blood faster than rats. Sex-related differences in 2BAA elimination were most significant with rats, in that females were less efficient in clearing 2BAA from the blood. Differences in renal excretion of 2BAA are possibly responsible for the sex-related difference in the 2BAA blood profiles in rats. As exposure continued, the rates of elimination for both 2BE and 2BAA decreased in both species, resulting in longer residence times in the blood. When 19-month-old naive mice were exposed to 125 ppm, 2BE was rapidly cleared from the systemic circulation, exhibiting clearance profiles similar to young mice. However, old mice eliminated 2BAA from blood > 10 times slower than young mice after 1-day of exposure. This delayed elimination of 2BAA in old mice was less obvious after 3 weeks of exposure, suggesting that there might be other factors in addition to the age of animals that could influence the apparent difference in 2BAA kinetics between old and young mice. It was concluded that the elimination kinetics of 2BE and 2BAA following repeated 2BE exposure appear to be dependent on species, sex, age, time of exposure, as well as the exposure concentration.     

Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions

CAG/polyglutamine expansion is the mutational mechanism that causes a number of late-onset neurodegenerative diseases. Expanded CAG repeats are unstable: they vary in size between tissues and change in size upon transmission from parent to offspring. These mutations are thought to impart a dominant gain of function to the proteins in which they are located. Recent reports describing the first mouse models of these diseases promise to shed light on the molecular mechanisms underlying CAG-repeat instability, the pathways by which polyglutamine expansion causes cell death and the factors that determine the specificity of the neurodegeneration.     

Old paint removal and blood lead levels in children

AIM: To identify risk factors, particularly paint removal and clean up practices, for elevated blood lead levels in children, 12 to 24 months old, living in Wellington city. METHODS: Children living in residences more than 50 years old, where residential paint removal had taken place in the last two years, were recruited. Care givers were interviewed, a blood sample was taken from the child's arm and a dust wipe sample was collected from the kitchen floor. Blood and dust samples were analysed for lead content. RESULTS: Data were collected for 141 children (75% of those eligible). The mean blood lead level was 0.24 mumol/L (5.06 micrograms/dL). Higher blood levels were associated with lower income of the main family earner, playing outside, eating dirt and parental hobbies involving lead use. Children receiving regular medical treatment were at lower risk of lead absorption. With the exception of paint removal involving blow torches, none of the paint removal, clean up, or disposal practices was more strongly associated than the other methods with elevated blood lead levels in children living in the household. Dust wipes from the kitchen floor had little predictive value for blood lead level. CONCLUSIONS: High temperature methods of paint removal and parental hobbies involving lead are associated with higher lead levels in children. Given the availability of alternative means of paint removal, continuing use of high temperature methods is unnecessary. Further work is needed to assess lead absorption risks associated with hobbies involving lead.     

Supporting interactive presentation for distributed multimedia applications

In this paper we present IMP, a platform to support the authoring and run-time management of interactive multimedia applications in distributed environments. The multi-level platform model encourages slot-in extensibility to cater for the evolving environment. We illustrate with our prototype platform built above the Cambridge multimedia environment. The authoring model emphasises reusability, tailorability and use of environment features in a uniform way. We have shown the validity of our approach by constructing a variety of application types.     

Correction to: The influence of training level on manual fight in connection to performance,scan pattern,and task load

Cognition, Technology & Work - A correction to this paper has been published: https://doi.org/10.1007/s10111-021-00680-1     

Protection of lyocell against fibrillation. Part 1: Design, synthesis and application of novel crosslinking agents

Three known fibre crosslinking agents have been chemically modified in an attempt to correct technical and/or application deficiencies. The novel agents have been applied, in turn, to lyocell fibre by an exhaustion process, the wet abrasion resistance of each modified fibre measured and the results compared with Cibatex AE 4425 and with the bis-sulphatoethylsulphone dye Remazol Black B. Agents carrying the m -carboxypyridinium-1,3,5-triazine-2-oxido group were not of interest as they produced pale yellow fibres due to ring opening of the pyridinium ring during alkali fixation. The best all-round performer was 2,4-di( p - β -sulphatoethylsulphonyl)anilino-1,3,5-triazin-2(1 H )-one.     

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by ω3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chowad libitum were inoculated with 10⁶ MAT-LyLu cells (n=14) or saline (n=9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumorbearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7–14 (difference by dietary group: NTB,P<0.001; TB,P<0.001). During days 14–21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB,P<0.003; TB,P=0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P=0.05) and mean food intake during the study (P=0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean ±SEM 58±10 g loss,P<0.001), but not in TB animals on fish oil diets (8±18 g loss,P=0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistically significant (50±19 g,P<0.02), implicating that the fish oil enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB animals, regardless of diet, hepatic [P_i]/adenosine triphosphate] ratios measured by³¹P magnetic resonance spectroscopy (MRS)in vivo andin vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phosphate as determined by³¹P MRSin vitro were reduced. Ultrastructural studies of liver tissue revealed increased numbers of mitochondria and increased amounts of endoplasmic reticulum in the host liver of TB animals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachexia, but did not prevent the majority of³¹P MRS-detectable alterations in host liver metabolism.