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Biomedical subjects

M Nehéz

Publications and source records attributed to M Nehéz.

At least 19 recordsLinked to original sources

A study on geno- and immunotoxicological effects of subacute propoxur and pirimicarb exposure in rats.

A 28-day oral exposure with 8.51, 3.40, and 0.851 mg/kg propoxur (PR) and 4.67, 1.87, and 0.467 mg/kg pirimicarb (PI) was performed in male Wistar rats, and the occurrence of numerical and structural chromosome aberrations and the changes in certain immune function parameters (plaque-forming cell (PFC) assay, delayed-type hypersensitivity reaction) and in some basic toxicological (body weight gain and weights of brain, thymus, lung, heart, liver, spleen, kidneys, adrenals, and popliteal lymph node) and hematological (white blood cells, red blood cells, hematocrit (Ht), mean cell volume of red blood cells (MCV) cell content of the femoral bone marrow) parameters were investigated. The high dose of PR increased the relative liver weight and the cell content of femoral bone marrow, and all three doses increased Ht and MCV. The applied doses of PI decreased the relative adrenal weight in a dose-dependent manner, and its highest dose increased the relative liver weight. Among the immune function parameters tested, PFC content of the spleen was decreased by high-dose PR and elevated by high-dose PI, whereas the maximum and the time course of the delayed-type hypersensitivity reaction showed no changes in this dose range. In the genotoxicological investigations only the high PR dose increased the number of numerical, but not the structural, chromosome aberrations. In addition to the changes in relative adrenal weight following PI treatment, the PFC assay showed the highest sensitivity for detection of the 4-week exposure with these carbamates. On the basis of our results, the immunotoxicological approach seems to have the same (PR) or higher (PI) sensitivity in early detection of the repeated low-dose exposure by these carbamates compared to the genotoxicological approach.

Animals↗

Simultaneous action of cypermethrin and two environmental pollutant metals, cadmium and lead, on bone marrow cell chromosomes of rats in subchronic administration.

The aim of the present study was to investigate the possible genotoxic effects, exerted by the pyrethroid cypermethrin and by either of the metals cadmium and lead alone or in combination, on bone marrow cell chromosomes in a subchronic experiment. Outbred male Wistar rats were treated per os for 4 weeks in a five-time per week schedule with 5.54, 11.08, or 22.16 mg/kg cypermethrin (1/100, 1/50, 1/25 LD50) alone, or in combination of 1/100 and 1/50 LD50 cypermethrin with 2.0 mg/kg cadmium chloride or 10 mg/kg lead acetate. On the day following the last treatment, the animals were sacrificed and bone marrow from the femur was prepared. Twenty metaphases from 10 animals per group were evaluated. The evaluation comprised the frequency of aberrant cells, the numerical and structural aberrations, and the alterations in relative organ weights. In the dosage used, cypermethrin and cadmium alone caused no significant increase in the chromosomal aberrations, and lead acetate caused an increase of the numerical aberrations only. Combination of cypermethrin and cadmium also failed to induce significant chromosomal effects. The cypermethrin + lead combination, however, induced a significant increase of structural chromosomal aberrations, predominantly of all acentric fragments. This lead to the conclusion that the simultaneous administration of lead and cypermethrin results in an enhanced genotoxic effect.

Animals↗

Simultaneous geno- and immunotoxicological investigations for early detection of organophosphate toxicity in rats.

Detectability of toxic effects by repeated doses of dimethoate (DM) and methylparathion (MPT) were investigated by geno-and immunotoxicological methods in male Wistar rats following a 28-day oral exposure. In the dose range of 28.2, 14.1, and 7.04, and 7.04 mg/kg/day DM, the two higher doses decreased the body weight gain. The top dose increased the weight of liver, kidneys, and testicles; the white blood cell count; and the cell content of the femoral bone marrow. From immune function parameters measured [IgM-plaque forming cells (PFC) assay, delayed-type hypersensitivity (DTH) reaction] only the maximum of the DTH reaction decreased at the top dose. Of the MPT doses (0.872, 0.436, and 0.218 mg/kg/day) the two higher ones increased the liver weight, and a dose-dependent increase was found in the MCV value. No evaluable changes in the examined immune function parameters were observed. Both substances increased the number of numerical but not the structural chromosome aberrations at lower dose levels (the two larger doses of DM, and all the three doses of MPT) than those ones which caused changes in the examined immune function parameters. According to these results, the genotoxicological approach seems to be more sensitive for detection of repeated-dose oral toxicity of the investigated two organophosphates than the immunotoxicological one.

Animals↗

Comparison of detection sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats.

Immuno- and genotoxicological effects of a 28-day oral treatment by equitoxic (1/10, 1/25, 1/50 LD50) doses of cypermethrin (55.4, 22.2, and 11.1 mg/kg) and permethrin (125.7, 50.3, and 12.6 mg/kg) were compared on male Wistar rats. Humoral and cell-mediated immunity were investigated by PFC assay and delayed type hypersensitivity (DTH) reaction (footpad swelling assay), and the genotoxic effects were studied by structural and numerical chromosome aberrations in bone marrow cells. The experimental system also involved certain general toxicological (body weight gain, organ weights) and haematological [white blood cell (WBC), red blood cell (RBC), haematocrit (Ht) and cell content of the femoral bone marrow] investigations. Among the immune function assays, only DTH reaction decreased at the two higher cypermethrin (CY) doses. These doses also increased the number of numerical chromosome aberrations of the bone marrow cells but did not change the number of structural aberrations. All CY doses decreased the mean cell volume (MCV) of RBCs and the Ht value. The two higher doses also reduced the WBC count in the peripheral blood. Permethrin (PE), in the applied dose range, had no effect on the examined immune function parameters, but all three doses increased the number of numerical chromosome aberrations. A dose-dependent increase in the liver weight, decreased MCV value, and elevated cell content of the femoral bone marrow were also observed. Under these experimental conditions, examination of chromosome aberrations proved to be less sensitive in detection of exposure by cypermethrin than applied immune function assays did. Permethrin, on the contrary, increased the number of numeric aberrations at all dose levels but had no effect on the immune function parameters examined.

Aneuploidy↗

Epidemiological investigations and experimental model studies on exposure of pesticides.

Authors carried on epidemiological examinations on plant protection workers to find early symptoms (biomarkers) of moderate contamination by pesticides. Measurement of changes in cholinesterase and gamma glutamyltransferase enzyme activity did not reveal that people were affected. Determination of chromosome abnormalities from peripheral lymphocytes disclosed numerical aberrations at an early stage and lasted after cessation of work for several months. There were differences in the results among different groups of plant protection workers, as well as among those working in open field or in glasshouses. Women, who carried out horticultural work in glasshouses after spraying showed some chromosome abnormalities too. Experimental rats treated chronically with organophosphates exhibited changes in spontaneous and evoked brain electrical activity (ECoG). Concerning the peripheral nervous activity, conduction velocity became slower, absolute and relative refractory periods became longer. These proved sensitive biomarkers too, which could be used in early detection of contamination.

Adolescent↗

The effect of dimethoate on bone marrow cell chromosomes of rats in subchronic four-generation experiments.

The effect of the insecticide dimethoate (O,O-dimethyl S-/N-methylcarbamoylmethyl phosphorodithioate) on bone marrow cells of four generations of rats was investigated. Male and female Wistar rats were treated for 6 weeks with 5 treatments per week via gavage at doses of 7.0, 9.33, and 14.0 mg/kg (1/ 100, 1/75, and 1/50 of the LD50). Chromosomes of 10 of the treated males were prepared. Other males (6-8 males per dose) were paired with females (11-16 females per dose). This represented the first (P) generation. During pregnancy and lactation females were treated with adequate doses of dimethoate. In F1 (70 males and 56 females), F2 (71 males and 62 females), and F3 generations (62 males and 44 females) treatment with dimethoate and the preparation of chromosomes (40 males per generation) were the same as those in the P generation. Following treatment with dimethoate in P and F1 generations, the number of numerical chromosome aberrations increased significantly. No significant changes in chromosome aberrations were found in F2 and F3 generations compared to the control groups. The frequency of numerical chromosome aberrations decreased considerably compared to the P generation at the dose of 14.0 mg/kg (1/50 of LD50).

Animals↗

The effect of dimethoate, dichlorvos, and parathion-methyl on bone marrow cell chromosomes of rats in subchronic experiments in vivo.

The three organophosphorous insecticides dimethoate, dichlorvos, and parathion-methyl were investigated in subchronic experiments on bone marrow cell chromosomes. In the literature these compounds were reported to exhibit both positive and negative results in mutagenicity tests demanding further investigations in subchronic tests. The treatment of different groups of male Wistar rats lasted for 6 weeks with 5 treatment days per week at doses of 1/100, 1/75, and 1/50 of the LD50. Following the last treatment, bone marrow cell chromosomes were prepared. The frequency of cells revealing any aberrations as well as numeric and structural aberrations were evaluated. In this test both dimethoate and dichlorvos demonstrated mutagenic effects following subchronic treatment of Wistar rats, while parathion-methyl at doses of 1/100, 1/75, and 1/50 of LD50 displayed no significant mutagenicity.

Animals↗

Investigations of the acute toxic, cytogenetic, and embryotoxic activity of buminafos.

The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)-phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic activity on different strains of mice. The oral LD50 value for male NMRI mice was determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000 mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in the bone marrow chromosome assay corresponds to negative findings in other mutagenicity tests.

Animals↗

Investigations on the acute toxic, cytogenetic, and embryotoxic activity of phenyl isocyanate and diethoxyphosphoryl isocyanate.

Phenyl isocyanate (I) and diethoxyphosphoryl isocyanate (II), used as intermediates in organic chemical syntheses, were tested for their acute toxic, cytogenetic, and embryotoxic activity on mice of different strains. The oral LD50 values for male CFLP mice were determined to be 196 mg/kg for I and 4080 mg/kg for II. Single oral doses of 1/40 and 1/20, respectively, of the LD50 of I (4.9 and 9.8 mg/kg) and II (102 and 204 mg/kg) did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice. After oral administration of 9.8 mg/kg I and 204 mg/kg II to pregnant Halle-AB-Jena and Halle-DBA mice at various days of gestation (4, 7, 11, or 15), none of the compounds tested were embryotoxic.

Animals↗

Cytogenetic examination of people working with agrochemicals in the southern region of Hungary.

The team performed medical examinations, including cytogenetic examinations, on 55 people working professionally with agrochemicals in eight farmers' cooperatives of County Csongrád in the southern region of Hungary. The people exposed to spraying in a closed space showed no increase in chromosome aberrations. There was an increase in chromosome aberrations in workers exposed to these agrochemicals in open fields. No conclusions regarding workers' health can be drawn from these data. Regulations designed to prevent accidents with agrochemicals are more effective for closed spaces than for the open fields.

Adult↗

Cytogenetic, genetic, and embryotoxicity studies with dimethyl 2,2,2-trichloro-1-(2,2,2-trichloro-1-hydroxyethoxy)-ethylphosphonat e, a hypothetical impurity in technical grade trichlorfon.

The hemiacetal (CH3O)2P(O)CHOCHOHCCl3)CCl3, a hypothetical contaminant in technical preparations of the organophosphorus pesticide trichlorfon, was tested for cytogenetic, mutagenic, and embryotoxic activity after ip administration to mice of different strains. A single dose of 81 mg/kg (0.2 mmol/kg) caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; a similar effect was induced by an equimolar single dose of chemically pure trichlorfon (51.5 mg/kg). At the same dosage level, the hemiacetal proved to be ineffective in the micronucleus test on fetal blood of DBA and AB Jena/Halle mice. In the dominant lethal mutation assay, a single dose of 81 mg/kg hemiacetal to males resulted in a slight increase in the fetal mortality of DBA mice, whereas AB Jena/Halle mice did not respond under these conditions. Four consecutive doses of 81 mg/kg hemiacetal to pregnant AB Jena/Halle mice at Days 2, 3, 4, and 5 of gestation caused only a very weak embryotoxic effect comparable to that of trichlorfon at equimolar dosage. On the basis of these results the hemiacetal tested may not be considered to represent a potential risk factor in technical grade trichlorfon.

Animals↗

Cytogenetic and embryotoxic effects of bromophos and demethylbromophos.

The organophosphorus pesticide bromophos and the tetramethylammonium and sodium salts of demethylbromophos were tested for cytogenetic and embryotoxic activity on mice of different strains. Single intraperitoneal (ip) doses of 183.0 mg/kg (0.5 mmol/kg) and 73.2 mg/kg (0.2 mmol/kg) bromophos caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; similar effects were produced by a single dose of 0.2 mmol/kg demethylbromophos tetramethylammonium salt and demethylbromophos sodium salt trihydrate, respectively, indicating that the cytogenetic activity of bromophos is not connected with its alkylating properties. After repeated ip or oral administration to pregnant mice of strains AB Jena/Halle and DBA, none of the tested compounds showed a marked influence on the total implantation losses, although in some cases the postimplantation losses were significantly increased.

Animals↗

The teratogenic, embryotoxic, and prenatal mutagenic effect of 3-methyl-4-nitrophenol in the mouse.

The teratogenic, embryotoxic, and prenatal mutagenic effects of 3-methyl-4-nitrophenol were investigated in CFLP strain pregnant mice treated with the compound at the dose of 3 X 25 mg/kg. After treatment on the 7th, 9th, and 11th days of pregnancy, the embryos were examined on the 18th day of pregnancy for obvious malformations and bone preparations were made with alizarin red S staining. The examination of chromosome aberrations in samples from liver cells of embryos was performed by the method of P.K. Datta, H. Rigger, and E. Schleiermacher (in Chemical Mutagenesis in Mammals and Man, F. Vogel and G. Röhrborn, eds., pp. 198-206, Springer-Verlag, Berlin/Heidelberg/New York, 1970). 3-Methyl-4-nitrophenol at the applied dosage did not result in teratogenic or prenatal chromosome damage in contrast to the damaging effect of 4,6-dinitro-o-cresol which was previously reported.

Abnormalities, Drug-Induced↗

A study of the mutagenic effect of 3-methyl-4-nitrophenol on the somatic cells of the mouse.

3-Methyl-4-nitrophenol is a resultant metabolite inside the organism when fenitrothion (O,O-dimethyl O-(3-methyl-4-nitrophenyl) thiophosphate)-containing pesticides undergo a chemical change due to the action of liver cell enzymes. It is also used as a basic compound for synthesis in the chemical industry. Groups of CFLP strain mice were treated ip with single doses (25 mg/kg) of this chemical in aqueous or alcoholic solution. Another group was treated ip with the same dose on ten weekly occasions. Chromosomes were prepared from the bone marrow cells 24 and 48 hr after the treatment. The results do not exclude the possibility of a mutagenic effect.

Animals↗

Additional data on the mutagenic effect of dinitro-o-cresol-containing herbicides.

In in vivo experiments in mice it was studied, on the one hand, whether 1 year after treatment with dinitro-o-cresol (DNOC)-containing herbicide it was possible to detect any increase in chromosome aberrations in the bone marrow cells of the mouse, and on the other hand, to learn the frequency of chromosome aberrations in the subsequent generations when the treatment of the male animals with DNOC-containing herbicide was continued in each generation and when it was discontinued before mating. The chromosome aberrations of the bone marrow cells of the treated mice were demonstrated even 1 year after the treatment. After the treatment of the male animals was continued in each subsequent generation, the chromosome aberrations in the embryos increased, whereas when it was discontinued, it decreased in the subsequent generations.

Animals↗