Aranka Hudák

Studies on the embryotoxic effects of ortho-, meta- and para-xylene

Abstract CFY rats were exposed to inhalation of ortho -, meta -, or para -xylene at 150, 1500, or 3000 mg/m 3 concentration for 24 h/day from day 7 to day 14 of pregnancy. Additional groups of 3 rats were exposed to o -xylene at 150, 1500, or 3000 mg/m 3 concentrations for 2 h only on the 18th day of pregnancy. In this latter group of rats exposed to o -xylene 18th day of pregnancy, the o -xylene concentration in the blood of the rats was proportional to that in the atmosphere. The solvent crossed the placenta; it was present in the fetal blood and amniotic fluid. All the 3 xylene isomers inhaled at the highest concentration brought about toxic effects in the mother animals. All the 3 isomers brought about the retardation of fetal development: a decrease in the weight of the fetuses, an increase in the incidence of the symptoms of skeletal retardation, a decrease in the activity of different enzymes, succinic dehydrogenase, alkaline- and acid phosphatase and glucose 6-phosphatase, characteristic features of the functional maturity of the nephron. Retardation of the fetuses was dose-dependent, but also dependent on the chemical structure of the particular isomer; their effectiveness was para -, ortho - and meta -xylene in the decreasing order of potency. None of the isomers proved to be teratogenic. Meta - and para -xylene inhalation at the highest concentration increased the incidence of extra ribs. Preimplantation fetal loss was increased by meta - and para -xylene, meta -xylene at the highest concentration interfered with the process of implantation, while para -xylene exposure resulted in an increased postimplantation loss of the fetuses. Ortho -xylene inhalation was without effect on the incidence of the extra ribs, either on implantation, or on the pre- and postimplantation fetal losses.

LEAD INTOXICATION EPIDEMIC CAUSED BY INGESTION OF CONTAMINATED GROUND PAPRIKA

OBJECTIVE Report of a lead intoxication epidemic caused by ingestion of contaminated ground paprika. DESIGN Retrospective study of case histories. SETTING Institutional, toxicological and medical referral center for ambulatory and hospitalized care. PATIENTS One hundred forty-one adults consumed paprika contaminated with lead tetroxide (red lead). INTERVENTIONS Intravenous calcium disodium versenate (edetic acid). MAIN OUTCOME MEASURES Measurement of zinc protoporphyrin:heme ratio of whole blood and the blood lead level. EDTA mobilization test. RESULTS Fifty-three patients had symptoms and signs of lead poisoning. The most common clinical signs were colic and/or anemia. Twenty-six persons showed increased lead absorption without clinical symptoms and signs. Chelation therapy with calcium disodium versenate resulted in complete clinical recovery. CONCLUSION Lead-contaminated ground paprika, not previously described as a cause of alimentary lead intoxication, may cause symptomatic poisoning.

Effects of Whole-Body 50-Hz Magnetic Field Exposure on Mouse Leydig Cells

The main goal of this study was to evaluate the possible effect of whole-body magnetic field (MF) exposure on the steroidogenic capacity of Leydig cells in vitro. In four separate experiments, male CFLP mice were exposed to sinusoidal 50-Hz, 100-μT MF. The duration of exposure was 23.5 h/day over a period of 14 days. At the end of the exposure, interstitial (Leydig) cells were isolated from the testicles of the sham-exposed and exposed animals. The cells were cultured for 48 h in the presence or absence of 1, 10, or 100 mIU/ml human chorionic gonadotropin (hCG). The luteinizing hormone (LH) analog hCG was used to check the testosterone (T) response of the sham-exposed controls and to evaluate the possible effect of the whole-body MF exposure on the steroidogenic capacity of Leydig cells in vitro. Testosterone content of the culture media and blood sera was measured by radioimmunoassay (RIA). In the cultures obtained from MF-exposed animals, the hCG-stimulated T response was significanly higher (p < 0.01) compared with the sham-exposed controls, while the basal T production of cells and the level of serum T remained unaltered. No MF exposure—related histopathological alterations were found in testicles, epididymes, adrenals, prostates, and pituitary glands. The MF exposure did not affect the animal growth rate and the observed hematologic and serum chemical variables. Our results indicate a presumably direct effect of whole-body MF exposure on the hCG-stimulated steroidogenic response of mouse Leydig cells.

Follow-up biological and genotoxicological monitoring of acrylonitrile- and dimethylformamide-exposed viscose rayon plant workers

In order to investigate the genotoxic effects of occupational acrylonitrile (ACN) and dimethylformamide (DMF) exposures, clinical serum and urine parameters and genotoxicological endpoints such as chromosome aberration (CA), sister chromatid exchange (SCE), high frequency SCE (HFC), cell cycle kinetics, and UV‐induced unscheduled DNA synthesis (UDS) were followed up three times during a 20‐month period in peripheral blood lymphocytes (PBL) of 26 workers (13 maintainers and 13 fiber producers) occupationally exposed to ANC and/or DMF in a viscose rayon plant, 26 matched control subjects, and six industrial controls (all males). Six of the 26 exposed subjects were hospitalized because of liver dysfunction that had developed due to inhalative DMF exposure. The rate of smoking was estimated on the basis of serum thiocyanate (SCN) levels. Average peak air ACN and DMF concentrations were over the maximum concentration limits at the time of both investigations. Urine ACN and monomethyl‐formamide (MMF) excretions of the exposed subjects were almost doubled after work shifts. An increase in lymphocyte count (in months 0 and 7), and severe alterations in the liver function were observed in the exposed subjects. In PBLs the proliferative rate index (PRI) was already increased in month 0 compared with the controls. In each study, significant increases in CA and SCE frequencies, as well as increases in UDS were found in PBLs of the exposed subjects. The frequencies of chromatid breaks and acentric fragments further increased in month 7 and remained constantly elevated in month 20. Increased yields of both chromatid and chromosome‐type exchange aberrations first appeared in month 20, when HFCs were 2.72 times more frequent in fiber producers than in maintainers. The role of some important biological confounding factors (age, white blood cell count, and hematocrit) and lifestyle confounding factors (smoking and drinking habits) were subjected to an analysis of variance during the second study. Increased CA, SCE, and UDS were found both in control and exposed smokers when current smoking was established on the basis of the serum SCN levels. The cytogenetic data suggest that occupational exposures to ACN and DMF induce considerable genotoxic consequences and may increase the cancer risk in the exposed human populations. Environ. Mol. Mutagen. 31:301–310, 1998

The effect of toluene on the liver assayed by quantitative morphological methods

Abstract The liver-damaging effect of ip and sc injected doses of pro anal quality toluence as well as the toluene used in the Tisza Chemical Works was investigated in CFY male rats with quantitative morphological methods. An approximately linear correlation was found between the common logarithm of ip injected toluene doses and the increase in number and total area of mitochondria per unit cytoplasmic area as well as the increse in number of matrix granules per mitochondrion. The mean mitochondrial area did not change. The nuclear density and the nucleus/cytoplasm ratio increased in response to large ip toluene doses. An approximately linear correlation was found between the common logarithm of both ip and sc injected toluene doses and the decrease in nuclear volume. The karyometric statistical curves were characteristically double peaked. The application of quantitative morphological methods in toxicology is recommended, the results of which should not, however, be interpreted independently.

EFFECTS OF SODIUM DIETHYLDITHIOCARBAMATE ON TYPE II PULMONARY EPITHELIAL CELLS IN VITRO

Dithiocarbamates (DDTC) are chemicals widely used in the form of pesticides, therapeutic and chelating agents, and scavengers. Since DDTC interfere with SH, Cu, and Zn enzymes due to chelating properties, it was of interest to clarify, in primary culture of type II alveolar pneumocytes, the effect of this compound upon enzymes of glutathione cycle, Cu, Zn-superoxide dismutase, and the membrane structure of cells. DDTC significantly inhibited the activity of superoxide dismutase and the activity of gamma-glutamyl transpeptidase, glutathione reductase, and alkaline phosphatase, whereas an increase in the activity of glutathione peroxidase was found. The membranes of pneumocytes type II were injured. Data show that DDTC adversely affected type II pneumocyte function and structure.

Evaluation of delta-aminolaevulinic acid excretion in random urine samples of children.

Urinary delta-aminolaevulinic acid (δ-ALA) excretion was evaluated in random urine samples of 191 healthy children, aged 2–14 years, with blood lead levels <0.8 μmol/l (mean ± SD: 0.34±0.13), erythrocyte zinc-protoporphyrin <70 μmol/mol haem (mean ± SD: 50.4±8.0) and blood haemoglobin >6.8 mmol/l (mean ± SD: 8.2±0.5). It was found that uncorrected δ-ALA concentration and δ-ALA/creatinine ratio are age-dependent, whereas the ratio of δ-ALA/logarithm of creatinine concentration (mean ± SD: 55.3±13.5 μmol/log mmol) is independent of age and sex. The authors recommend the use of this parameter for the assessment of δ-ALA excretion in random urine samples in children