Gy. Ungváry

On the Embryotoxic Effects of Benzene and Its Alkyl Derivatives in Mice, Rats and Rabbits

Groups of CFY rats were exposed to inhalation of ethylbenzene at 600, 1200 or 2400 mg/m3 or xylene at 250, 1900 or 3400 mg/m3 or Aromatol at 500, 1000 or 2000 mg/m3 atmospheric concentration for 24 h/day from day 7 to day 15 of pregnancy, or for 2-4 hours only on the 18th or 20th day of gestation. CFLP mice and NZ rabbits were exposed to inhalation of 500 mg/m3 or 1000 mg/m3 benzene, toluene, ortho-, meta-, para-xylene, ethylbenzene, xylene or Aromatol for 24 h/day from day 6 to day 15 of pregnancy. Untreated animals and groups inhaling pure air served as controls. All components of the xylene and Aromatol crossed the placenta and were present in fetal blood and amniotic fluid, as well. The maternal toxic effects at all solvents were moderate and dose dependent. All solvents (at higher concentrations) brought about skeletal and weight retardation in fetuses of rats and mice. At highest concentration some solvents increased the post-implantation loss in rats and mice. All solvents caused spontaneous abortion in rabbits at 1000 mg/m3 atmospheric concentration. Only ethylbenzene and Aromatol increased the malformation rate in rats and mice. No other solvent applied proved to be teratogenic either in mice, rats or rabbits.

Age dependent accumulation of cadmium in the human ovary

Cadmium (Cd) was determined by atomic absorption spectrophotometry in small pieces (< 1 g) of healthy human ovaries excised for histologic examination. Cd levels in the ovary increased linearly between 30 and 65 years of age. Below 30 years, there was no age dependent increase and over 65 a tendency was observed for ovarian Cd levels to decrease. There was no difference in the Cd content of fresh luteal and nonluteal tissue taken from regularly cycling ovaries. In smokers, the amount of Cd in the ovaries was elevated compared to nonsmokers. In multiparous women (more than 3 children) a tendency of decreased Cd ovarian levels was observed. There was no difference between ovarian Cd content of physical and mental workers. It can be proposed that Cd may be a risk factor for conception and pregnancy in women in their forties.

Non-fibrous zeolite induced experimental pneumoconiosis in rats.

A study was made on the pulmonary pathological reactions after intratracheal introduction of non-fibrous zeolite into CFY rats in long-term sequential investigations (1st week; 1st, 3rd, 6th months and 1st year). After treatment at the end of the 1st week non-specific confluating bronchopneumonia followed by a storage type reaction developed at the end of the 1st month. In the later periods in addition to storage character mild pulmonary fibrosis has been observed. At the end of the 1st year, transmission electron microscopy and X-ray microanalysis verified that aluminium and silicon ratio in zeolite storaged in the macrophages of the lungs was the same as found in natural zeolite (1:6). In the lungs of 3 animals atypical hyperplasia developed; therefore an in vivo study of the carcinogenic effect of non-fibrous zeolite seemed justified.

Biological effects of the respirable dusts from ore mines

The biological effects of ore dusts were examined on peritoneal macrophages in vitro and on rat lung in vivo. The methylene blue adsorption of the dust samples, cytotoxicity, and phospholipid and hydroxyproline content of the lung were determined. It was realized that the examined ore samples had cytotoxic effects and from the in vitro results one can get information about the type of damage to be expected in the lung tissue. It is supposed that the examined ore dusts are less dangerous and slower acting than quartz, but they cause progressive fibrosis. The in vivo biochemical experiments do not give information about the type of damage to be expected in lung tissue; and the data on ore, bentonite, and coal do not differ from each other. To determine the typical biochemical changes caused by quartz, we obtain the most valuable information by determination of lung weight and phospholipid, phosphatidylcholine, and hydroxyproline content.

Short term in vivo method for prediction of the fibrogenie effect of different mineral dusts

The effect of intratracheal introduction of different metal and mineral dusts and the change in activity of pulmonary acidic phosphatase have been studied as a function of time (72 h, 2 weeks, 1, 12, 20 months). The activity and localization of acid phosphatase were compared with the degree of pulmonary damage caused by dusts. The degree of fibrosis was determined on the basis of the composition of cells and fibres, according to Belt and Kings classification. Due to the membrane-damaging effect of DQ 12 silica and mixed dusts (enargite and porphyry rock dusts) an increase in acid phosphatase activity of macrophages could be observed at the end of the first month. At the same time non-fibrogenic or only mild fibrogenic dusts (bentonite, corundum, scarnic rock dust) caused a decrease or disappearance of tissue acid phosphatase activity. It has been stated that there is a very close correlation between the change in pulmonary acidic phosphatase activity and the progression of pulmonary fibrosis due to exposure to mineral dusts. The above investigations have been most useful in predicting the subsequent effect of rock patterns, emphasizing at the same time the importance of in vivo long term experiments.

Behavioural effects of prenatal exposure to carbon disulphide and to aromatol in rats.

The neurotoxic effects of prenatal organosolvent inhalation were studied in rats, because of the expectation that a developing organism may be more sensitive than the adult to the induction of functional deficits. The aim was to determine whether prenatal exposure to the new organosolvent mixture, Aromatol, and the well known neurotoxic carbon disulphide, would impair reflex ontogeny or produce neurobehavioural dysfunctions in the offspring. Development of gait, motor coordination, and activity, avoidance learning and swimming were tested in the offspring of CFY rat mothers, exposed to CS2 inhalation (0, less than 10, 700 and 2000 mg/m3) and to Aromatol (0, 600, 1000 and 2000 mg/m3) on days 7-15 gestation. Prenatal CS2 inhalation induced dose related perinatal mortality of pups. Eye opening and the auditory startle were retarded. There were immature gait, motor incoordination, diminished open field activity and altered behavioural patterns on day 21 and 36 but they were nearly age-appropriate on day 90. As signs of disturbed learning ability, there were diminished performance and lengthened latency of the conditioned avoidance response, related to the concentrations administered. Contrary to expectations, prenatal Aromatol inhalation had no effect on maturation of gait, behaviour patterns, or learning ability.

The Effect of Benzene and its Methyl Derivatives on the MFO System

Many industrial chemicals, pesticides, food additives and other environmental chemical compounds are known to cause liver enlargement, proliferation of smooth endoplasmic reticulum (SER) in hepatocytes and to induce the hepatic microsomal enzyme system. The degree of the enlargement of the liver and of the proliferation of SER in hepatocytes, as well as that of enzyme induction of the hepatic microsomal system, depend on several factors (quantity of the compounds, chemical structure of the substances, species, age, sex of animals, etc.). Short-term exposure to the methyl derivatives of benzene (toluene, ortho-xylene) results in adaptive changes in the liver to their toxic effects such as an increase of the relative liver weight, proliferation of SER of hepatocytes, increased concentration of cytochrome P-450 and b-5, and increased activity of the MFO system (Ungvary et al. 1976, 1980). In this study we compared the effects of benzene and its methyl derivatives on hepatic enzyme induction during the initial phase of poisoning, to see if there was a correlation between the type of enzyme induction response and the number and steric orientation of methyl groups.

The effect of acetylsalicylic acid on the development of the skeletal system in rats

The authors wished to clarify the cause of micro- and phocomelia developing in rat fetuses following administration of acetylsalicylic acid. It has been proved by histological examinations that the positive ground substance of the epiphyseal cartilage, detected by Rivanol reaction, became disarranged or negative. The sulphation of glycosaminoglycans was diminished or inhibited by acetylsalicylic acid in the chondrocytes depending on the dose applied. The conclusion has been drawn that the malformation developed is due to the reduced production of sulphated mucopolysaccharides.