M. Nehéz

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.

Biological monitoring and health surveillance of a group of greenhouse pesticide sprayers

Repeated extensive medical examinations were carried out in 11 workers spraying organophosphate (OP), carbamate and pyrethroid pesticides in greenhouses during the whole year and in 10 control persons. On a questionnaire their social, health and family status and their working conditions were recorded. Before and after a regular spraying period with pyrethroids for 3 months the following tests were carried out: urinalysis, haematology, immunoglobulin (Ig) G, IgA and IgM levels, whole blood cholinesterase (ChE) activity, serum gamma-glutamyltransferase (GGT) activity, chromosome analysis and electrocardiography (ECG). Atmospheric concentrations of pyrethroids as well as their concentration in the blood and urine of pesticide workers were determined by means of gas-liquid chromatography (GLC). No abnormalities related to the work were found in the tests.

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.

The teratogenic and mutagenic effects of dinitro-o-cresol-containing herbicide on the laboratory mouse

Abstract Studies by the authors on the mutagenic effect of Krezonit E, a herbicide containing 50% dinitro- o -cresol, have already been reported. In the present study the following experimental investigation for clearing up the embryo-damaging effect of the compound are reported. Pregnant female mice were treated ip with Krezonit E on the 11th, and on the 4th, 9th, and 11th days of pregnancy. In another group the females were treated po with the same compound on the 11th–14th days of pregnancy. The results were compared with the results gained from the negative and the positive control groups. The preparation of the embryos was performed on the 18th day of pregnancy. For mutagenicity, the pregnant females were treated po in trimester I or II. The chromosomes were prepared from embryo liver. Along with assessing the frequency of the living and dead embryos, the obvious malformations, the ossifying anomalies and the chromosome aberrations were examined. The embryotoxic and teratogenic results in the treaded group do not differ significantly from those gained in the negative control group of the same strain. There were no significant differences in the chromosome damage when the treatment was applied in trimester I, whereas the ratio of the damaged cells increased significantly when the treatment was applied in trimester II.

Recent data on the examination of the mutagenic effect of a dinitro-o-cresol-containing pesticide by different test methods

The mutagenic effect of the 50% dinitro-o-cresol-containing pesticide Krezonit E was assessed by the following test methods: (1) human leukocyte cultures in vitro; (2) mouse bone-marrow chromosome preparations in vivo; and (3) examination of gametic mutations (a) in mouse test preparations, (b) with dominant lethality, and (c) by the examination of F1 embryonic chromosomes. According to the results the dinitro-o-cresol-containing pesticide is mutagenic. In all test systems aberrations both in the somatic and in the gametic cells could be detected. There was a significant increase in the rate of breaks and deletions and of the univalents in the diakinesis phase of meiosis found to be pathognomic by Schleiermacher [Humangenetik 3, 127–133 (1966)]. The chromosome aberrations of the F1 embryos were significantly higher in the first, second, and third week after the treatment of the male parent than in the control group. According to these findings the conclusion can be drawn that damage in the more mature forms of spermiogenesis can be better detected by examining the F1 embryonic chromosomes, while the aberrations of the early forms can be shown much better by dominant lethality.

Cytogenetic, genetic, and embryotoxicity studies with dimethyl 2,2,2-trichloro-1-(2,2,2-trichloro-1-hydroxyethoxy)-ethylphosphonate, 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.

A genetic toxicological study of pesticide workers

Epidemiological surveys and cytogenetic screening were carried out in agricultural workers using pesticides in open fields and in closed spaces respectively in four agricultural counties of Hungary. Some data of the chromosome analyses show the probability of mutagenic effects caused by pesticides. Chromosome aberrations were significantly more frequent in pesticide workers already in the first year of work. Significantly more aberrations were found in those workers having an inhibited acetylcholinesterase activity at the time of the chromosome test. In 14 persons using benomyl, numerical chromosome defects increased significantly in 48 h following spraying, as compared to controls. One year later, the pre‐spraying state was found again. Chromosome mutations were significantly more abundant also in tractor drivers and spray mixers working in orchards and plough‐lands. These finding emphasize the necessity of a strict observance of preventive measures in occupational, food and environmental hygiene.

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.

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.

The mutagenic effect of Trifluralin-containing herbicide on mouse germ cells in vivo

Abstract The mutagenic effect of the 26% Trifluralin-containing herbicide Olitref on mouse germ cells was investigated using three test methods: (a) spermatocyte chromosome examination; (b) dominant lethality test; and (c) F1-embryonic chromosome examination. One-third (0.20 g/kg) of the LD50 of Olitref was found mutagenic in the applied test. When a single dose of one-hundredth (0.006 g/kg) of the LD50 was injected in the spermatocyte examination, mutagenic change was also observed, but the results were only on the border of significance.