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Accidental death caused by the absorption of 2,4-dichlorophenol through the skin.

A case involving an accidental fatality resulting from skin absorption of 2,4-dichlorophenol in a factory is presented. The compound was quantified using gas chromatography after separation on a SP-1240 DA column and detection with flame ionization. Confirmation was obtained with mass spectrometry. Blood concentration was 24.3 mg/l. Other drugs, including ethanol, were not detected.

Accidents, Occupational↗

Effect of chlorinated phenol derivatives on various cell models.

Chlorinated phenol derivatives were found to display a cytotoxic effect on numerous cell models, such as chlorococcal algae, cyanobacteria, bacteria, micromycetes, plant and animal cells. Their cytotoxic effects will increase with chlorination and with the presence of a methoxy group.

Allium↗

Application of the exploratory data analysis for evaluating the toxicity of chlorinated phenol derivatives by various cell models.

Exploratory data analysis based on multivariate statistical analysis techniques was introduced as a new approach to expressing the toxicity of chemical substances at the simultaneous acceptance of various cell models. Using principal component analysis and cluster analysis methods the toxicity of chlorinated phenol derivatives on employing some of the cell models (chlorococcal algae, cyanobacteria, bacteria, micromycetes, plant and animal cells) was characterized. The previous empirical experience that the toxicity of chlorinated phenol derivatives will increase with a growing degree of chlorination and that the presence of the methoxy group will cause a lowering of the toxic effect was demonstrated. The relationship between groups of tests used was presented.

Allium↗

Cooperative inhibition of acetylcholinesterase activities by hexachlorophene in human erythrocytes.

Hexachlorophene (HCP), pentachlorophenol (PCP), 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP) all hemolyzed washed human erythrocytes and inhibited acetylcholinesterase (AchE) activities in erythrocyte membrane. HCP was much more potent in either effect than any other compound examined. The inhibition of AchE activities by HCP was reversed on adding albumin. The dose-response curves by HCP and PCP were sigmoidal, indicating cooperative inhibition, while those by 2,4,5-TCP and 2,4,6-TCP were not. Furthermore, the cooperativity of the inhibition by HCP was greater than by PCP. Differing from that by PCP, the cooperativity of inhibition increased depending on the temperature (13, 25, 37 degrees C) and decreased when the membrane was treated with Triton X-100. The cooperativity was also decreased in the presence of albumin. On a Scatchard plot analysis, erythrocyte membranes appeared to have multiple binding sites of different affinities for HCP; binding of HCP to the low affinity site [dissociation constant (Kd) 4.7 x 10(-5) M] seemed to be responsible for the observed cooperative inhibition of AchE activities. Neither neostigmine nor fenitrothion altered the cooperativity. HCP seems to be the most potent cooperative inhibitor of AchE in human erythrocyte membranes known to date. HCP may be useful to examine AchE and milieu in human erythrocyte membranes.

Adult↗

Further research on the photo-SPME of triclosan.

In this study the photoinduced degradation of triclosan has been investigated by photo-solid-phase microextraction (photo-SPME). In photo-SPME, photodegradation is carried out on the SPME fibre containing the target compound. Triclosan was extracted from aqueous solutions by use of polydimethylsiloxane SPME fibres and these were subsequently exposed to UV irradiation (power 8 W, wavelength 254 nm) for different times (from 2 to 60 min). The photodegradation kinetics of triclosan were investigated, the photoproducts generated were tentatively identified, and the photochemical behaviour of these products was studied by use of this on-fibre approach followed by gas chromatographic-mass spectrometric analysis. Eight photoproducts were tentatively identified, including chlorinated phenols, chlorohydroxydiphenyl ethers, 2,8-dichlorodibenzo-p-dioxin, and a possible dichlorodibenzodioxin isomer or dichlorohydroxydibenzofuran. The main photodegradation mechanisms were postulated and photodegradation pathways proposed. The effect of pH on triclosan degradation and on triclosan-to-dioxin conversion was also investigated. Triclosan degradation occurred, and generation of 2,8-dichlorodibenzo-p-dioxin was confirmed, throughout the pH range studied (from 3 to 9).

Anti-Infective Agents, Local↗

Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004.

The pharmacological activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel mutated at glycine 551 (G551D-CFTR) was studied in the presence of the benzimidazolone derivative NS004 and compared to that of wild-type (wt) CFTR. Using iodide ((125)I) efflux and whole-cell patch-clamp techniques we found dose-dependent stimulation of phosphorylated wt-CFTR channels by NS004 with an EC(50) approximately 11 microM. With non-phosphorylated CFTR, the effect of NS004 was apparent only at concentration >100 microM. In G551D-CFTR-expressing CHO cells, neither forskolin (from 0.1 to 10 microM) nor NS004 (from 0.1 to 200 microM) added separately were able to stimulate channel activity. However, in the presence of 10 microM forskolin, NS004 stimulated G551D-CFTR activity in a dose-dependent manner with an EC(50) approximately 1.5 microM. We also determined the half-maximal effective concentration of forskolin ( EC(50) approximately 3.2 microM) required to stimulate G551D channel activity in presence of 1.5 micro M NS004. No inhibitory effect was observed at high concentration of NS004 with both wt- and G551D-CFTR. Whole-cell recordings of CFTR chloride currents from cells expressing wild-type or G551D-CFTR in the presence of NS004 were linear, time- and voltage-independent. The inhibitory profile of G551D-CFTR channel activity was similar to that of wild type, i.e., inhibition by glibenclamide (100 microM) and DPC (250 microM) but not by DIDS (200 microM) nor calixarene (100 nM). These results show that NS004 activates wt-CFTR channel and restores G551D-CFTR channel activity, the potency of which depends on both the concentration of NS004 and the phosphorylation status of CFTR.

Animals↗

Partitioning of tetrachlorophenol into lipid bilayers and sarcoplasmic reticulum: effect of length of acyl chains, carbonyl group of lipids and biomembrane structure.

We report results of a partitioning study of 2,3,4,6-tetrachlorophenol (TeCP). In the study we explored (1) the effect of the length of acyl chains of lipids (C16:1 - C24:1) and alkanes (C6-C16), (2) the role of the carbonyl group of lipids, and (3) the effect of molecular structure of the sarcoplasmic reticulum membrane on TeCP partitioning. Mole fraction partition coefficients have been measured using equilibrium dialysis for un-ionized (HA), and ionized (A) species, Kp(x) (HA), Kp(x) (A). Their values are concentration-dependent. Partition coefficients were analyzed in terms of a model that accounts for saturation of membrane associated with the finite area of partition site, and electrostatic interactions of (A-) species with charged membrane. Limiting values of partition coefficients, corresponding to infinite dilution of solute, Kp(x0) (HA), Kp(x0) (A) were obtained. Kp(x0) (HA) and Kp(x0) (A ) measure the strength of solute-membrane interactions. Studies were done with single-layered vesicles of lipids with variable chain length: 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (C16:1), 1,2-dioleoyl-sn-glycero-3-phosphocholine (C18:1), 1,2-dierucoyl-sn-glycero-3-phosphocholine (C22:1), and 1 ,2-dinervonoyl-sn-glycero-3-phosphocholine (C24:1), and egg-PC. Kp(x0) for transfer of TeCP from water into lipid membranes was found to be independent of the length of acyl chains, whereas Kp(x0) for transfer from water into alkanes increased with the length of alkane. The effect of the carbonyl CO group of lipids on partitioning was measured using 1,2-di-o-octadecenyl-sn-glycero-3-phosphocholine (CO absent) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (CO present) liposomes. Carbonyl groups, known to change dipolar potential, had no effect on partitioning. Partition coefficients of un-ionized and ionized forms of TeCP were invariant to the presence of proteins and other membrane components of sarcoplasmic reticulum (SR) membrane.

Animals↗