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Rats fed on atherogenic diets containing 2% cholesterol and 0.5% cholic acid with or without 0.15% thiouracil were exposed to carbon disulphide (CS2) vapours (1 mg/l of air), five hours a day, six days a week for 6-10 months. Serum and aorta lipid contents were determined, and the extent of atherosclerotic changes was investigated. The following effects of chronic exposure to CS2 were found: (1) slower gain in body weight when rats were fed on atherogenic diet; (2) greater increase in serum cholesterol content (after thiouracil supplemented diet); (3) moderate increase in total cholesterol content in the aorta wall with a significantly increased esterified cholesterol fraction but none in phospholipid level in this tissue; and (4) more advanced lipid infiltrates of coronary arteries and endocardium, the latter predominantly in the aortic valves. These results together with data from previous studies indicate that metabolism of arterial lipids participates in the process of artheroma formation after chronic exposure to CS2 vapours.

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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.

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In animal experiments pneumoconiogenic properties of metallurgic and Portland cement dust, produced in Poland, were investigated. Experimental pneumoconiosis was developed by intratracheal single administration, to white rats, of 50 mg of dust suspended in 0.6 ml of NaCl physiological solution. The control groups were composed of animals to whom intratracheally physiological NaCl solution, TiO2 dust and two quartz dusts of varying fibrogenic properties--weak and mild, were administered. The content of crystalline silica, as determined chemically, was approx. 3% in both cement samples. X-ray diffraction did not show any content of crystalline phases in the cements, TiO2 dust contained rutile, whereas both quartz dusts contained about 100% alpha-quartz. After 3 months the animals were sacrificed. Wet lungs weight and hydroxyproline content in lungs were determined. In addition, mediastinal nodes and lungs were examined histologically. Cement dust was found to exhibit weak fibrogenic properties, not different significantly from fibrogenic properties of inert TiO2. Nevertheless increases in fibrogenic effect of cement dusts were significantly higher as compared to the control group (geometric mean hydroxyproline content in the control group was 2.52 +/- 0.06 mg, 4.50 +/- 0.09 in the Portland cement and 4.88 +/- 0.06 in metallurgic cement. Histological changes in lungs, due to cement effect are not progressive, expressing merely inflammatory reaction to dust. Nevertheless despite weak fibrogenic properties the cement dust provokes lesions of macrophages in lungs.

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In the studies carried out lipids content in blood serum and aorta wall as well as morphological changes in coronary vessels of CS2 exposed rats have been evaluated. The 10-month-exposure to CS2 at a concentration of 0,8--0,9 mg/l has been found to result in: (1) increased concentration of total and free cholesterol, cholesterol esters, triglycerides and phospholipids in blood serum; (2) increase in total cholesterol and significant rise in the level of cholesterol esters in the aorta wall; (3) a relative increase in serum VLDL, LDL and decrease in HDL fraction. Histological estimation has demonstrated in serial sections of hearts of the CS2 exposed animals thickened walls of left coronary artery branches with no lipid deposits. In two animals focal steatosis of aortic bulb wall and aortic valves and lipids droplets in endothelium of ascending aorta and coronary vessels have been found.

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Male rats were exposed to vinyl chloride at the concentrations of 50, 500, and 20 000 ppm, 5 hours daily, 5 days a week for 10 months. Morphological lesions in the liver and the testes detected by light and electron microscope and depression in body weight increase intensified with the duration of exposure. Increased relative weights of some organs and slight hematological and biochemical changes in blood during the course of the experiment were also observed. Some toxic effects including morphological liver injuries arose at the smallest exposure level, i. e., 50 ppm. Assuming 50 ppm as the threshold concentration for rats, the 5 ppm level has been estimated as the safe exposure limit in industry in relation to systemic effects of vinyl chloride.

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General acute toxicity, irritating, and allergic effects of 3-cyanpyridine were studied. LD50 after oral administration amounts to 1185 mg/kg of body weight, 3-cyanpyridine is absorbed through the intact skin: administration of 3-cyanpyridine solution into rabbit skin caused death of animals. Histopathologic studies showed reversible liver and kidney injuries after single administration of lethal and sublethal doses. 3-cyanpyridine significantly irritates damaged skin and in a solid state produces an irreversible cornea opacity. Allergic effect was not found.

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White rats were intratracheally injected with 50 mg of apatite or phosphorite dust. The animals were killed 3, 6 and 10 months after the injection. Fibrogenic properties were evaluated on the basis of biochemical and histopathological studies. It was found that the dusts under examination after 3 months of experiment induced a statistically significant increase of wet and dry lungs weight, of hydroxyproline and lipids content in the lungs, and intrathroacic lymph nodes as compared with the control group. After 3 and 10 months, a further but statistically insignificant increase of hydroxyproline content in lungs and of wet lung weight was observed, as compared with animals in the 3--months experiment. The obtained values of fibrogenic action indices for apatite and phosphorite dusts were quite similar to the values obtained in animals injected with inert dust of titanium dioxide. They were 4--5 times lower than the indices obtained after administrating the river sand--a dust of strong fibrogenic properties. Histopathological studies primarily revealed inflammatory changes in bronchial and peribronchial tissue, and focal emphysematous changes, whereas no features of a progressive development of fibrous changes in lungs. The MAC values of 6 mg/m3 for phosphorite dust of 8 mg/m3 for apatite dust--were suggested.

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Fibrogenic effect of two natural amorphous silica dusts-diatomite from deposits near Leszczawka (Poland) and silica earth (from the USA) was tested on the rats. Pneumoconiosis was produced by intratracheal introduction of 50 mg dust, at a single dose. Fibrogenic effect was assessed after 3, 6 and 9 months after introduction of dust. Analysis of diatomite dust carried out with X-ray diffraction method showed the presence of quartz in a quantity not exceeding 5%, while in silica earth dust from the USA no silica critalline structures were found. Development of fibrogenic changes in lungs of the rats assessed with hydroxyproline (collagen) increase and weight increment of wet lungs was small. The increment of the indices was twice higher as compared with their increment found in the lungs of control animals but lower than in the rats which were given cristalline silica dusts. In histopathological examinations no progressive lung fibrosis was found though some signs of destruction and necrobiosis in some cells were noticed.

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Fibrogenic properties of two dusts of synthetic hydrated amorphous silicas, Ze-O-Sil (French production) and Arsil (Polish production) were studied. Experimental silicosis was induced by intratracheal administration to rats of a single dust dose (50 mg in 0.6 ml NaCl). Fibrogenic properties were tested 3, 6, 9 months after administration of the dust. X-ray diffraction and chemical tests did not reveal any form of crystalline. Si02 in the composition of the investigated dusts. The dusts tested as compared with quartz, were characterized by a great solubility up to 211 mg/l, which made the dust excretion from the lungs easy; after 6 month-experiment approximately 1.2 mg of Arsil dust and about 28 mg of quartz dust residue was found. Fibrogenic properties of Arsil dust, represented by wet lungs weight increase and hydroxyproline content in lungs, were more pronounced than those of Ze-O-Sil. Hydroxyproline content 3 months after administration of Arsil, Ze-O-Sil, TiO2 and weak quartz amounted to 7.3 mg, 5.1 mg, 3.8 mg and 6.0 mg, respectively. Histological and ultrastructural investigations demonstrated that disseminated, multifocal granulomas were the basic reaction to both dusts; no clear histological signs of cytolytic action on the cells of dust granulomas were found. In the lungs no silicotic nodules or degeneration of changes were revealed. Neither biochemical tests nor histological examinations revealed a progressive development of fibrous connective tissue. In result of the studies the authors suggest 2 mg/m3 as a MAC value for Arsil dust instead of 10 mg/m3--the value which has been hitherto used.

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