Evaluation of the toxicity of substituted benzthioanilides by using in vitro tests.

The cytotoxicity of 12 benzthioanilides substituted in the N-aromatic ring, and of two commercial preparations (imaverol and thiuram) for comparison, was studied with clone 81 cat cells, by determining the highest tolerated dose, and by using the neutral red uptake assay and the kenacid blue assay for total protein. The concentrations that induced 20%, 50% and 80% (IC20, IC50 and IC80) inhibition relative to controls were calculated from dose-response curves. For some compounds, rat LD50 values were also determined. All the benzthioanilide preparations showed in vitro toxicities lower than those of the fungicides imaverol and thiuram. It was confirmed that the cytotoxicities of the compounds depend on the type of substituent. The least toxic compound contained a CONHCH(2)CO(2)H substituent in the para position of the N-aromatic ring, and the most toxic compounds contained chloro and fluoro, or three chloro substituents in the anilide moiety. All the benzthioanilides tested showed fungistatic activity for dermatophytes; two of the compounds (compound 5 and compound 12) also inhibited the development of yeasts at concentrations lower than those which caused toxicity in vitro. The LD50 values and the cytotoxic concentrations in vitro were linearly related.

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography.

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life (t1/2 beta) after the intravenous injection was 4.2 +/- 0.5 h, the volume of distribution (Vd(ss) 1.1 +/- 0.2 L/kg and the total body clearance (ClB) 131.2 +/- 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 +/- 16%. The plasma maximum concentration (Cmax) 31.9 +/- 2.3 micrograms/mL was reached 2 h after the oral administration and the oral elimination half-life (t1/2 beta) was 4.7 +/- 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [3H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.

[Lead, cadmium, copper and zinc content in vegetables, gooseberry fruit and soil from gardening plots of Lublin]. / Zawartosc olowiu, kadmu, miedzi i cynku w warzywach, owocach agrestu oraz glebie ogrodów dzialkowych Lublina.

Lead, cadmium, copper and zinc contents in vegetables, fruits of gooseberries and in soil of Lublin gardening plots "Pionier" and "Podzamcze" both situated along heavy traffic streets, and "Pionier" additional to the close vicinity of automobile factory were determined by atomic absorption spectrophofometry. Statistical analysis of the results respected the streets or factory distances from the gardening plots, and the species of the vegetables. Levels of the determined elements in the most of the samples were lower than permitted by the Ministry of Health Regulation established in 1993. According to that Regulation a slight exceeding of zinc content in the red beetroots and in the overground parts of the leak were found. Lead content in the parsley root and in the dill was close to the tolerance limit. Both lead and cadmium of the soil of "Podzamcze" gardening plot significantly exceeded the levels considered as tolerable for unpolluted grounds, whereas the soil of "Pionier" contained lead close to limit of tolerance level.