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Biomedical subjects

M Nehéz

Publications and source records attributed to M Nehéz.

At least 19 recordsLinked to original sources

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

Effect of dimethoate and O-demethyldimethoate on bone marrow cells of CFLP mice.

The organophosphorus pesticide dimethoate and its nonalkylating O-demethyl derivative were tested for their ability to induce chromosomal alterations in bone marrow cells of CFLP mice after ip administration. A single dose of 20 mg/kg dimethoate proved to be ineffective. However, doses of 60 mg/kg dimethoate or 69 mg/kg O-demethyldimethoate sodium salt significantly increased the aberration rates above those of the controls. The same effect was observed after a nontoxic dose of 690 mg/kg O-demethyldimethoate sodium salt. Considering the distribution of the several aberration types, these findings suggest that the alkylating properties of dimethoate only in part may be responsible for its cytogenetic activity.

Alkylation

The effects of five weeks treatment with dinitro-o-cresol- or trifluralin-containing pesticides on the germ cells of male mice.

The effects of two pesticides, the insecticide-herbicide Krezonit E, which contains 50% dinitro-o-cresol, and the herbicide Olitref, which contains 26% trifluralin (2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline), on the gonads and germ cells of male mice were studied. The pesticides were given twice a week for 5 weeks in i.p. doses of 0.6 mg kg-1 for Krezonit E and 6.0 mg kg-1 for Olitref. These doses are 1% of the i.p. LD50. Cytogenic analysis of germ cells carried out from 3 weeks onwards after the last treatment day showed that Olitref significantly increased the frequency of germinal chromosomal abnormalities at 6-7 weeks after treatment. This pesticide increased the frequency of autosomal univalents X/Y separations at meiotic metaphase and multivalent configurations. Krezonit E did not increase significantly the number of chromosomal abnormalities, although there was some increase at 3 weeks, mainly in the form of autosomal univalents.

Animals