[Irritating effect and dermal toxicity of virkon, a disinfectant widely used in Poland]. / Ocena dzialania drazniacego i toksycznosci dermalnej Virkonu, preparatu dezynfekujacego szeroko stosowanego w Polsce.

The aim of the study was to define the threshold irritating effect of Virkon, a disinfectant widely used in Poland, on the rabbit's skin and eye, and its dermal toxicity in single exposure. The studies were carried out according to the OECD guidelines, modified by Krysiak. A 10% aqueous solution of Virkon in the conditions of multiple open exposure was defined as the threshold concentration evoking small inflammatory reaction. After a single administration of Virkon in aqueous solutions into the rabbit's eye, the value of sensitising effect index was 1.5 for 1% solution of the disinfectant in question which indicates weak inflammatory reaction. The study of dermal toxicity in a single exposure revealed neither animal death nor morphological changes in internal organs which suggests non-cutaneous absorption of Virkon. The present study may provide the basis for assessing dermatological changes in people exposed to disinfectants.

[Evaluation of allergic sensitivity to the virkon disinfectant preparation widely used in Poland]. / Ocena dzialania uczulajacego Virkonu preparatu dezynfekujacego, szeroko stosowanego w Polsce.

The aim of the study was to define the sensitising effect of Virkon, a disinfectant widely used in Poland, especially in hospitals. The study was carried out on guinea pigs, using the maximisation test according to Magnusson and Kligman, modified by Krysiak. The assessment of dermal changes presented in the percentage of sensitised animals, being thus far the criterion adopted by Magnusson and Kligman, has been expanded to include our own criteria covering the intensity of reactions of testing samples and the results of eosinophilic and basophilic tests in peripheral blood. Using these parameters and applying pathomorphological examinations it was possible to indicate the difference in the intensity of sensitising effect of Virkon, depending on the concentration used. The results of the study showed that 1% aqueous solution of Virkon is the optimum concentration for monitoring its sensitising effects in people having contact with this substance.

[The evaluation of the irritating and sensitizing effects of benzalkonium chloride]. / Ocena dzialania drazniacego i uczulajacego chlorku benzalkonium.

The aim of the study was to determine the threshold irritating effect of benzalkonium chloride on the rabbit's skin and eye, and its sensitizing effect on guinea pigs. The study was performed according to the OECD guidelines modified by Krysiak. As a threshold concentration of benzalkonium evoking slight inflammatory reaction on the skin in a single, closed exposure and in multiple, open exposure, the following values were adopted for its aqueous solutions: > 0.5-1%, and 05% respectively. Following the eye administration of 0.01% and 0.05% of benzalkonium aqueous solution a weak irritating and rapidly reversible effect was revealed. The study performed on guinea pigs indicated a sensitizing effect of 0.5%, 0.1% and 0.05% benzalkonium aqueous solutions. The effect differed depending on the concentration used. The evaluation covered the proportion of sensitized animals, the nature and intensity of dermal reaction, as well as peripheral blood eosinophil and basophil tests. The results showed that 0.1% benzalkonium aqueous solution is an optimum concentration for monitoring the sensitizing effect in humans being in contact with this substance.

Occupational allergy to aldehydes in health care workers. Clinical observations. Experiments.

The incidence of allergy to aldehydes (formaldehyde, glutaraldehyde, glyoxal) was examined in 280 health care workers suffering from skin lesions. Allergy was diagnosed in 64 (22.8%) patients. The majority of them (85.9%) were sensitive only to 1 aldehyde. Formaldehyde caused allergy slightly more frequently (13.9%) than glutaraldehyde (12.4%). Only 5 (1.9%) patients were sensitive to glyoxal. The irritant effect of aldehydes to the rabbit eye and skin was tested by the Draize and OECD methods. Formaldehyde and glutaraldehyde showed stronger irritant effect than glyoxal. The sensitizing activity of aldehydes was also confirmed in guinea pigs (using the Maximization Test and the OECD methods). Formaldehyde showed the strongest and most persistent reactions. Significantly higher eosinophil and basophil counts were found in the blood samples of the sensitized guinea pigs. Cytotoxicity of glutaraldehyde and glyoxal was tested on mouse 3T3-L1 fibroblasts by the Neutral Red Uptake and MTT Reduction Assay. It was shown that both aldehydes were cytotoxic, and that the cytotoxic effect of glutaraldehyde was stronger than that of glyoxal.

[Comparative studies on the usefulness of using a fixed dose and a stepwise method of dosing for evaluating acute chemical toxicity]. / Badania porównawcze przydatnosci stosowania metody ustalonej dawki i metody skokowej do oceny ostrego dzialania toksycznego substancji chemicznych.

Following the studies on four compounds, classified in three different groups of toxicity, the validity of the up-down method and the fixed dose procedure was compared to classic Litchfield and Wilcoxon tests. The study was based rather on a very careful clinical observation than on the estimation of animal mortality as recommended in DL50 test. The study showed a considerable consistency between classic tests and the up-down method and the fixed dose procedure. But the determination of acute toxicity of chemical compounds by means of alternative methods proved to be highly humanitarian, and it required much lower number of less suffering animals.

A subchronic toxicity study of Rokanol B-2 in rats.

The toxicity of Rokanol B-2 was assessed following its administration to rats via oral gavage. A preliminary study of acute toxicity was performed to determine suitable dosing regimen/dose levels for future repeated-dose toxicity studies. For this purpose rats (15 males and 7 females) received single doses of 2,000, 1,500, 1,000 or 500 mg/kg and were killed after 2 or 14 days. No deaths occurred during the observation time. Dose-related irritation to the stomach mucosa was found. For the subchronic toxicity assessment, Rokanol B-2 was administered at daily doses of 8, 40 or 200 mg/kg to 59 male and 56 female Wistar rats by oral gavage, 5 days per week for 90 days. An interim experiment was performed after 28 days of dosing. Five animals/sex/group were terminated and necropsied. Blood samples for clinical chemistry and haematology were obtained and lungs, heart, adrenals, kidneys, liver, spleen, stomach, intestine, testes (males), uterus and ovaries (females) were weighed and prepared for histopathological examination. After 90 days of dosing all remaining animals were killed and necropsied. Blood samples were taken for evaluation of haematology and clinical chemistry, and selected organs (same as above) prepared for subsequent histological examination. In the high-dose group (200 mg/kg/day) a statistically significant reduction in body weight gain and food consumption, an increased weight of the liver in the males and disturbances in haematological parameters in the females were observed. Ulcerations of the mucous membrane of the stomach and hyperkeratosis, and in a few cases, pseudopapillomatous epithelial proliferation of foregaster and exudate in the submucosa of the stomach were noted. In the mid-dose group (40 mg/kg/day) some disturbances in hematological parameters in females and histopathological changes in rats of both sexes similar, but to a lesser degree, to changes observed in high-dose animals were indicated. In the low-dose group (8 mg/kg/day) no significant treatment-related effects were observed. The results of this study indicate that Rokanol B-2 possessed an overall low degree of systemic toxicity when administered orally to rats for 90 days. The NOAEL, observed in this study, was estimated as 8 mg/kg/day.

[Evaluation of the irritative action of formaldehyde and glutaraldehyde aldehyde]. / Ocena dzialania drazniacego formaldehydu i aldehydu glutarowego.

The irritative effect of formaldehyde and glutaraldehyde on the rabbit skin was determined under conditions of a single, closed exposure and under conditions of multiple, open exposure. It was revealed that the irritative effect was dependent on the concentration used, application mode and exposure duration. Under conditions of a single, 4 and 24-hour, closed exposure, threshold concentration which was inducing only slight inflammatory reaction of skin was equal to 2% of aqueous solution for both formaldehyde and glutaraldehyde. Under conditions of a 10 open exposure, threshold concentration of irritative effect on the skin was determined as 5% aqueous solution for formaldehyde and 2.5% aqueous solution for glutaraldehyde. A single administration of 0.5% aqueous solution of formaldehyde and of 0.2% aqueous solution of glutaraldehyde into the rabbit's eye induced a slight and short lasting inflammatory reaction. These concentrations were recognised as threshold ones.

[A new method for evaluating acute toxicity intragastrically for classification of chemical substances]. / Nowe metody oceny ostrej toksycznosci droga dozoladkowa dla celów klasyfikacji substancji chemicznych.

The authors reviewed and presented a critical analysis of the literature on defining acute toxicity of chemicals after intragastrical administration by means of traditional methods and new ones such as fixed procedure, up-down, acute-toxic-classification. Rules and conditions for the evaluation of acute toxicity by means of these methods were presented as well as the way of defining a median, lethal dose administrated intragastrically for the purpose of chemical classification.

The effect of subchronic exposure to the rubber vulcanization fumes on guinea pig lungs.

The influence of 28 days' inhalatory exposure to rubber vulcanization fumes at a concentration of 100 mg/m3 on guinea pigs' lung morphology was investigated. Focal infiltrations of pulmonary parenchyma with lymphocytes, neutrophilic and eosinophilic granulocytes and macrophages were observed. Lymphatic tissue concentrations having the typical appearance of solitary lymphatic nodules were also seen. The use of the double sequential Alcian blue/safranin O staining method for the identification of the mast cells [MCs] revealed that only Alcian-blue-positive MCs were observed, regardless of the region of the lungs examined, both in control and exposed guinea pigs. No safranin-0-positive MCs were seen. However, the MCs number increased from 1934 +/- 91 cells/mm3 tissue in controls to a statistically significant (p less than 0.05) 2486 +/- 89 cells/mm3 tissue in exposed guinea pig lungs. It was accompanied by histamine content increase from 1.50 +/- 0.06 micrograms/g wet tissue weight and 2.45 +/- 0.18 micrograms/g wet tissue weight, respectively. The distribution of the lung MCs varied, showing a statistically significant (p less than 0.05) increase in their number in the intraalveolar septa: from 957 +/- 53 to 1369 +/- 74 cells/mm3 tissue and in the peribronchial and peribronchiolar spaces: from 204 +/- 36 to 359 +/- 42 cells/mm3 tissue.

[Experimental studies of toxic effects of 1,3,5-trioxane and 1,3-dioxolane. I. Acute toxic effect]. / Badania doswiadczalne nad toksycznym dzialaniem 1,3,5-trioksanu i 1,3-dioksolanu. I. Ostre dzialanie toksyczne.

The problems arising from occupational exposure to 1,2,3-trioxane and 1,3-dioxolane made it necessary to carry out complex studies on that issue. This paper is focussed on systemic and local effects of those compounds. The studies involved: 1) Determination of acute systemic toxic effects following intragastric administration of the test compounds (DL50) and inhalatory exposure (CL50) using the Litchfield and Wilcoxon method as well as determination of medium lethal dose (MDLder) following dermal administration of the test compounds after Deichmann and Le Blanca, 2) Determination of the intensity of acute primarily irritating effects upon skin and eye using the Draize et al method, as well as irritating effects under repeated exposure, 3) Determination of allergic effects using the Magnusson and Kligman method, as modified by B. Krysiak. The DL50 and CL50 values for 1,3,5-trioxane and 1,3-dioxolane come to 8.5 g/kg m.c. and 5.8 g/kg m.c. respectively, and CL50 greater than 26000 mg/m3 and 87000 mg/m3 of air. Of those two compounds only 1,3-dioxolane may be absorbed through intact skin. However, the medium lethal dose MDLder coming to 15 g/kg b.w. in the rabbit implies that the rate of skin absorption for that compound is too low to induce a severe poisoning. Locally, the compounds exhibit irritating effects upon the eyeball and eye protective apparatus. As regards the irritating effectus upon skin, only 1,3-dioxolane induces skin irritation under repeated exposure. Under experimental conditions, no dermatitis related to oversensitivity was found.

[Experimental studies of the toxic effects of 1,3,5-trioxane and 1,3-dioxolane. II. Cumulation of toxic effect]. / Badania doswiadczalne nad toksycznym dzialaniem 1,3,5-trioksanu i 1,3-dioksolanu. II. Kumulacja dzialania toksycznego.

The studies on the accumulation of toxic effects of TOX and DOX have been carried out with the Kagan and Stankiewicz method. For 7 months the rats were intragastrically administered, with a tube, 20% water solutions of TOX and DOX at 1/10, 1/40 and 1/80 DL50 doses; in addition, for 4 months they were given 100% DOX at 1/10 DL50 doses; Within the experiment, the animals' mortality, appearance and behaviour were observed and once a month their body weight was determined. After the exposure, haematological and biochemical studies along with the dissection determining the weight of some internal organs were carried out. The intoxication symptoms were found mainly in the animals obtaining DOX at the 1/10 DL50 dose. They were manifested by reduced body weight gain, slightly reduced activity of whole blood acetylcholinesterase and disturbed body equilibrium, weakly marked arched back, hypokinesis, slightly weakened muscular force and slight paresis of hind legs. On the other hand, the mortality rate did not show accumulated toxic effects for TOX and DOX.

[Neutrophil agglutination test in sensitized guinea pigs]. / Test zlepnosci granulocytów objetnochlonnych we krwi uczulonych swinek morskich.

Guinea pigs sensitized with DNCB, K2Cr2O7, epidian 5, hardener Z1 and dye B, in which epidermal tests confirmed sensitization, exhibited, 24 hours after the test termination, increased agglutination of neutrophils. In the blood of animals sensitized with dye B using the Polak and Türk, as well as Magnusson and Kligman techniques, percentage indices of agglutination, whether spontaneous or induced by adding 25 micrograms of the allergen, were 2,40 and 8,90 for DNCB, 6,72 and 13.30 for K2Cr2O7, 7.61 and 12.59 for epidian 5, 8.69 and 11.63 for hardener Z1, 1.38 and 2.15 and 2.17 and 3.21 for dye B. The average (from 6 control groups) number of neutrophils, both those self-agglutinated and those induced by allergen, was 2.54 and 3.24, respectively. No increase in neutrophils agglutination in guinea pigs sensitized with the Alekseeva and Sumska technique-exhibiting no allergy--was found. The results point to the usability of determinations of neutrophils agglutination in blood as an auxiliary index confirming sensitivity to a given allergen.

[Modified evaluation of allergic skin reactions]. / Ocena odczynu uczuleniowego skóry we wlasnej modyfikacji.

Our modified evaluation of the results of investigating experimental allergy includes, apart from the percentage of sensitized animals as in all hitherto applied evaluations, appraisal of "challenge" reactions and results of supplementary in vitro studies in the examined animals' blood. Basing on the formula of the percentage index of the total evaluation of the study - W% = (formula: see text) X100 (a - percentage of sensitized animals; b - index of the total evaluation of reactions intensity, c - results of auxiliary tests in peripheral blood), the effects of allergens were differentiated. Introduction of our own evaluating criteria enabled differentiation of the intensity of effects of the test allergens, which was unfeasible with the hitherto applied Magnusson and Kligman criterion.

Preliminary project of the standard minimal scope and methods of testing acute toxicity of industrial chemical substances.

The standard minimal scope of experimental toxicity evaluation of industrial chemicals has been proposed. On the basis of literature and own experience the authors propose that the minimal scope of toxicity testing should include determination of lethal doses and evaluation of morphological alterations of inner organs in acute experiments, as well as assessment of eye and skin irritation and contact sensitization. The main lines of uniform procedures are presented. Complementary tests of local and acute systemic toxicity are also recommended.

[Importance of experimental conditions in the evaluation of the acute irritating effect of chemical compounds]. / Znaczenie warunków doswiadczalnych w ocenie sily ostrego dzialania drazniacego zwiazków chemicznych.

The experiment was carried out on 36 white Vienna rabbits and 27 grey rabbits of Chinchilla strain. The test substances were: sulphuric acid, acetic acid, sodium hydroxide and oil M-26. A single dermal 24 rh closed (sides) exposure, and single dermal open (sides, ears) exposure were used. The cutaneous reaction to the substances was evaluated according to Draize's et al. (1944) conventional point scale. In addition, cutaneous eruptions that have not been covered by the classification, have been included, with reactions in per cent. The intensification of the inflammatory reaction was found to depend on the way of application and duration of exposure to a given substance. The single open application resulted in cutaneous eruptions of a lesser intensity than the single closed application of the same compounds, the concentration being the same. The skin of white rabbits was found to be similarly sensitive to the irritating effect of the chemicals as the skin of grey rabbits. The histopathological examinations allowed determining the nature and localization of changes and revealed, in some cases, skin pathologies, with no clear symptoms of irritating effects of the substances revealed macroscopically.

Practical aspects of selection of streptomyces mutants.

The methods of industrial strains selection on the basis of some regulatory mechanisms are presented. The selection of the producing S. erythreus mutants exhibiting higher activity for transformation of erythromycin C to erythromycin A is one of the examples for the practical use of the presented method. Some new techniques including isotopic methods are presented.

[Evaluation of acute and subacute toxic effects of polactine yellow G]. / Ocena ostrego i podostrego toksycznego dzialania zólcieni polaktynowej G.

In acute experiment the following results were obtained: the DL50 value after intragastric administration -- 8.2 g/kg of body weight, after intraperitoneal administration -- 1.33 g/kg of body weight. In the studies on acute effect irritating skin and eye of a rabbit -- only a slight inflammatory reaction in conjunctivae was found. Studies on sensitizing effect carried out on guinea pigs did not reveal any symptoms which would give evidence of an alergic effect of the dye. Lima's test did not reveal any cumulative effects of polactine G Yellow, 8-weeks experiment on 30 male rats, administered with 0.5 g/kg and 1.6 g/kg, gave the following results: in the group of rats exposed to 1.6 g/kg an increased excretion of phenol red with urine, lowered activity of aminotranspherases (AspAT and A1AT), increased activity of lactic dehydrogenase and alkaline phosphatase in the blood serum and increased relative liver weight and relative and absolute weight of the kidney. In the group of rats exposed to 0.5 g/kg of polactine yellow G, increased alkaline phosphatase in blood serum and increased relative and absolute liver weight was found. In histopathological studies in acute and subacute experiment, a damage to gastric wall was found. In addition, an increased damage to parenchymatous organs, of reversible degeneration nature, was found.

[Acute toxic effects of trimethyl and triethyl phosphites]. / Ocena ostrego toksycznego dzialania fosforynu trójmetylowego i fosforynu trójetylowego.

The studies on toxic properties of trimethyl and triethyl phosphities involved: determination of acute general toxic effect on white rats following intragastric and intraperitoneal administration of these compounds, based on DL50 test, determination of damaging effect direction, by histopathological examination of animals' internal organs, determination of intensity of primarily irritating action on the skin, eye and conjunctiva, as well as sensitizing effect on guinea-pigs. DL50 value for trimethyl phosphite following intragastric administration was found to be 2.45 g/kg and following intraperitoneal administration--2.25 g/kg; for triethyl phosphite these values were: 4.00 g/kg after intragastric administration and 1.50 g/kg after intraperitoneal administration, respectively. In local action both phosphites mildly irritate the skin, eye and conjunctiva. A weak sensitizing effect of triethyl phosphite was found. Trimethyl and triethyl phosphites have general toxic effects. A particular direction of their action is demonstrated by acroparalysis. Apart from general action they were found to show systemic action and induce parenchymatous degeneration of the liver and kidneys, whatever route of administration. Administered intragastrically, they result in mucosa necrosis, ulceration and fibrino-purulent exudate, exfoliating the mucosa.