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Biomedical subjects

L Várnagy

Publications and source records attributed to L Várnagy.

At least 19 recordsLinked to original sources

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate.

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Animals↗

Embryonic toxicity of a dimethoate containing insecticide formulation and Cu-sulphate in chicken after individual or combined administration.

The aim of this study was to determine the individual and combined toxic effects of a dimethoate containing insecticide formulation and Cu-sulphate on the development of chicken embryos. The test materials were injected directly into the air-chamber in a volume of 0.1 ml/egg, or eggs were treated by immersion technique on day 12. Applied concentration of Cu-sulphate was 0.01% and the concentration of insecticidE was 0.1%. After the injection treatment of a dimethoate containing insecticide on day 12 of incubation, the average body mass of embryos significantly decreased. The simultaneous injections of Cu-sulphate and a dimethoate containing insecticide a statistically significant reduction in embryonic body mass occurred. Embryonic mortality did not increase after the individual injection of test materials, while the combined injection of Cu-sulphate and a dimethoate containing insecticide killed 30% of embryos treated. After the individual and combined immersion treatment of Cu-sulphate and a dimethoate containing insecticide, the average body mass of embryos did not decrease significantly as compared to the control. After the combined immersion treatment the incidence of embryonic mortality and the number of embryos with developmental anomalies did not differ markedly from the control. In summary, it can be established that the combined injection treatment of Cu-sulphate and a dimethoate containing insecticide caused higher embryotoxicity with respect to the test of the combined immersion treatment of test materials.

Animals↗

Toxicity of a mancozeb containing fungicide formulation and CU-sulphate to chicken embryos after administration as single compounds or in combination.

Environmental pollution of metal modelled by copper-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on chicken embryos after administration as a single compounds or in combination. The test materials were injected into the air-chamber in a volume of 0.1 ml/egg on day 12 of incubation. The concentration of copper-sulphate was 0.01%. The applied concentration of Dithane M-45 fungicide formulation was 0.2%. Evaluation was done on day 19 of the hatching period. The combined administration of copper-sulphate and the fungicide formulation did not cause a significant reduction in body weight as compared to the control data and the results from individual toxicity study of the test materials. After the combined administration of copper-sulphate and the fungicide formulation the rate of embryomortality was 40%. The incidence of developmental anomalies were sporadic. Light microscopic findings exhibited a degenerative change in the liver tissue of combined administration group. Activities of GPT and GOT enzymes increased markedly in the combined administration group. In summary, it can be established that the interaction of copper-sulphate and an 80% mancozeb containing fungicide formulation (Dithane M-45) caused higher embryomortality with respect to the test of individual toxicity of copper-sulphate and fungicide in our study.

Alanine Transaminase↗

Toxicity and degradation of benefin in chicken embryos.

The herbicide formulation Flubalex (20% benefin) was applied, ROSS 308 embryonated hen eggs were treated on day 12 of incubation period. The pesticide was diluted in water to a concentration level of 3.0%, and the emulsion was injected into the air space in a volume of 0.1 ml/egg, or hen's eggs were treated by the immersion technique. Residues of benefin were measured in the samples on days 13, 15 and 19 of the incubation of chicken embryos, and morphological examinations were performed simultaneously. After the immersion treatment the mortality rate of embryos was remarkable compared to the injection treatment. Analytical chemistry data showed the concentration of the active ingredient which was 3.5 times higher on day 13 of incubation in the samples after immersion treatment than after the injection of benefin. This resulted an increased incidence rate of mortality. On day 19 of hatching period the benefin concentration was practically similar independently of treatment method. No macro- and microscopic alterations were seen.

Animals↗

Teratogenicity testing of BI 58 EC (38% dimethoate) in chicken embryos with special respect to degradation of the active ingredient.

The insecticide formulation BI 58 EC was tested for teratogenicity in chicken embryos, with particular reference to degradation of the active ingredient (dimethoate) after the treatment of embryonated eggs. The pesticide was diluted in water to a concentration level of 0.8%, and the emulsion was injected into the air space in a volume of 0.1 ml/egg, or hen's eggs were treated by the immersion technique. Residues of dimethoate were measured in the samples on days, 13, 15 and 19 of the incubation of chicken embryos, and morphological examinations were performed simultaneously. Analytical chemistry data indicated a slower degradation of dimethoate in embryos after the immersion of eggs, and cyllosis was remarkable in this group among the sporadic developmental anomalies. The liver tissues of both treated groups exhibited severe fatty infiltration.

Abnormalities, Drug-Induced↗

One-generation reproduction toxicity study of mancozeb and lead acetate.

The reproduction toxicity of lead acetate and 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on rats. The lead acetate was applied in diet at the following dose groups: Control-1,000-5,000-10,000 mg/kg. Three treatment and a control groups were applied, 4,500 mg/kg Dithane M-45 was administered in all the dose levels simultaneously in diet. The basis of the method was the OECD Guideline for Testing of Chemicals No. 415. Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals diminished significantly before the pregnancy period. This tendency was also seen on males after the combination treatment. Remarkable body weight growth of female animals was observed during lactation period at the two high dose levels. Diminished body weight data of offsprings were measured after treatment at the end of the lactation period. The histological examination showed a general tubulonephrosis in the trial. Summing up, it can be established the administration of fungicide Dithane M-45 did not increase the toxicity of lead acetate.

Animals↗

Teratogenicity testing of dimethoate containing insecticide formulation (BI 58 EC) in chicken embryos.

BI 58 EC insecticide formulation was tested for teratogenicity in chicken embryos after the treatment of embryonated eggs. The pesticide was diluted in water to 0.8% concentration level, and the emulsion was injected into air space in a volume of 0.1 ml/egg or hen eggs were treated by the immersion technique. The morphological examinations were done on the days 13, 15 and 19 of incubation of chicken embryos. BI 58 EC produced an increased embryo mortality after the treatment which was the most expressive on day 15 of incubation. The trend of embryo weight showed similarity in the control and treated groups after both treatments. The developmental anomalies were sporadic and dose-effect dependency was not seen. Light microscopic findings exhibited a degenerative change in the liver tissue of both treated groups. In summary, the 38% dimethoate containing pesticide formulation (BI 58 EC) was toxic to the developing embryo at 0.8% concentration in our study.

Abnormalities, Drug-Induced↗

Teratogenicity test of dimethoate containing insecticide formulation and heavy elements (Cu, Cd) in chicken embryos after administration as single compounds or in combination.

The teratogenic effects of heavy elements (Cu-sulphate, Cd-sulphate) and a 38% dimethoate containing insecticide formulation (Bi 58 EC) were studied on chicken after administration as a single compounds or in combination. The test materials were injected directly into the airchamber with an injector on day 12 of incubation. Applied concentrations of heavy elements (Cu-sulphate, Cd-sulphate) were: 0.01-0.001% and the concentration of pesticide was 0.1%. Final volume was 0.1 ml/egg. Evaluation was done on day 19 of incubation. After the administration of heavy elements (Cu-sulphate, Cd-sulphate) on day 12 of incubation, the average body mass of embryos significantly decreased at all the treated dose groups as compared to the control. Embryonic mortality did not increase at all the two dose levels of Cu-sulphate and at 0.001% conc. of Cd-sulphate, while the highest concentration of Cd-sulphate killed 20% of embryos treated. The number of embryos with developmental anomalies did not differ markedly from the control. The simultaneous administration of heavy elements (Cu-sulphate, Cd-sulphate) and dimethoate containing insecticide a statistically significant reduction in embryonic body mass occurred at all the treated dose groups. The incidence of developmental anomalies was markedly higher after the simultaneous use of heavy elements (Cu-sulphate, Cd-sulphate) and dimethoate containing formulation than in tests based on the separate use of heavy elements. Embryonic mortality increased at all the treated dose groups and reached almost 20% rate. In summary, it can be established that the simultaneous administration of heavy elements (Cu-sulphate, Cd-sulphate) and the dimethoate containing insecticide caused higher toxicity with respect to test of individual toxicity of heavy elements.

Abnormalities, Drug-Induced↗

Interaction of Dithane M-45 (mancozeb) and lead acetate during a teratogenicity test in rats.

The teratogenic effects of lead acetate (Trial 1) and the possible teratogenic effect of this compound administered in combination with a fungicide containing 80% mancozeb (Trial 2) were studied in rats. The test substances were administered by gavage on Days 6-15 of gestation. In Trial 1, five groups were treated with lead acetate administered at doses of 0.1, 0.5, 1.0, 10.0 and 1000.0 mg/kg body weight (bwkg), respectively. In Trial 2, lead acetate was applied at doses of 0.1, 10.0 and 1000.0 mg/bwkg, respectively. In the latter case the dose of the pesticide was 750 mg/bwkg in all treated groups. Lead acetate was not teratogenic after a single administration. Combined administration of lead acetate and mancozeb gave rise to the following toxic effects: average maternal weight decreased during pregnancy, the ratio of live fetuses decreased after the two lowest doses, and fetal mortality increased in the lowest and in the highest dose groups. The ratio of fetal resorption was higher in all the treated groups than in the control group. A significant decrease occurred in average fetal and placental weight in each treated group as compared to the control. Maternal toxicity was expressed in paralysis of the hindlimbs in the two lowest dose groups. Maternal mortality was between 16.7 and 23.3% at the three dose levels. Phocomelia and hernia cerebri occurred as characteristic fetal developmental anomalies in all the treated groups. It is concluded that the joint administration of lead acetate and a mancozeb-containing fungicide can cause maternal toxicity, embryotoxicity and characteristic teratogenic effects.

Abnormalities, Drug-Induced↗

Effect of immersion fluid temperature on the chicken embryo in teratogenicity tests: short communication.

The influence of immersion fluid temperature on the development of the chicken embryo was studied on the day most commonly used for treating incubated eggs in teratological trials. Embryonated eggs were immersed in tap water for 30 min on the 12th day of incubation at 22-25 degrees C or at incubation temperature without a waiting time or after 30 min. The incubation was then continued and the eggs were processed on day 19 of the incubation period. Treatment of eggs at 22-25 degrees C caused a significant increase in embryonic mortality, while the 30-min waiting time did not exert an influence on embryogenesis.

Animals↗

Histological examination of CAM treated with irritative pesticides.

The potential irritancy of compounds may be detected by observing adverse changes which occur in the chorioallantoic membrane (CAM) of the egg after exposure to tested chemicals. In our experiment irritating pesticides (Fusilade S, Karathene LC) and a technical component of pesticide (Trend) are tested and their effects are examined on tissue structure of CAM. After 10-11 days of incubation of chicken embryos the chorioallantoic membrane becomes trilaminar. The outer layer is chorionic epithelium between the two rows of cuboidal cells, thin-walled vascular sinuses can be found. In the intermediate layer, the mesenchyme, well-developed blood vessels can be seen. The inner layer is formed by allantoic epithelium. After the treatment with Fusilade S the wall of the blood vessels was damaged, and blood diffused from the blood vessels. After the treatment with Karathane LC rupture of the wall of the blood vessels could be seen and blood appeared around the blood vessels. Blood vessels of the yolk sac were frequently damaged under CAM.

Allantoin↗

In vitro ocular irritation toxicity study of some pesticides.

The use of animals in toxicological screening is a controversial issue. The Draize eye irritation test receives particular criticism because of the injuries inflicted on the test animals. In recent years various in vitro methods have been developed to replace the heavily criticised Draize rabbit eye test for irritation testing. One of the best-studied alternative methods is the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). In the present studies comparative screening was performed with a set of pesticides to establish parallel data on in vitro (HET-CAM) and in vivo (Draize) results. The tested pesticides included Arelon 500 FW (isoproturon), Banvel 480 (dicamba), Dikamin D (2.4 D), Karathane LC (dinocap), Ronstar (oxadiazon) and Modown 4 F (bifenox). In most cases a good correlation was found between the HET-CAM assessment and results of the Draize rabbit eye test. Although the current form of the HET-CAM test is a valuable prescreen method for predicting the ocular irritation potential of chemicals, and can be used for reducing the number of experimental animals, a number of technical problems must still be addressed before these systems can replace whole animal tests. The HET-CAM test can be a useful component of a battery of tests needed for replacing the Draize rabbit eye test.

Animal Testing Alternatives↗

Model field study of Sumithion 50 EC and Fusilade S on pheasants.

Toxicological studies on wild animals play an important role in the ecotoxicological examination of pesticides. The applied model tests enable the assessment of toxicological consequences with particular regard to the life and nutrition of wild animals in the ploughed field among plants treated with pesticides. The application of different pesticide formulations on plough-land may pose a simultaneous chemical burden to wild birds. In this model study, manifestations of the interaction between an insecticide and a herbicide were studied in pheasants. The birds were placed on lucerne in cages (48 m2) and sprayed once. The applied doses were: Sumithion 50 EC 1 litre/ha + Fusilade S 6 litres/ha (practical doses) and Sumithion 50 EC 5 litres/ha + Fusilade S 30 litres/ha. The analytically determined pesticide concentration of the lucerne was taken as a basis in the further treatment of fodder. The fodder of pheasants contained the following chemicals: 85 mg/kg Sumithion 50 EC + 510 mg/kg Fusilade S and 425 mg/kg Sumithion 50 EC + 2250 mg/kg Fusilade S. Sporadic deaths observed among the pheasants were of traumatic origin and not due to a toxic effect. The decrease of body weight was significant only at the higher dose levels. Acetylcholinesterase (AChE) activity of the blood decreased significantly in both dose groups. On the basis of the results obtained it can be established that at the dose level used in the practice the pesticides studied do not give rise to a toxic interaction in pheasants.

Acetylcholinesterase↗

Degradation of some pesticides in avian embryos.

On day 9 or 12 of the hatching period different pesticides (parathion, methyl-parathion, carbendazim, 2,4-D-amine Na, phosmethylane) were applied in ecotoxicological trials. The formulations were either injected into the air space of pheasant, quail or hen eggs or hen eggs were treated by the immersion technique. The residues of pesticides were measured in samples on days 13, 14 and 16 of incubation of chicken and pheasant embryos, while the Japanese quail embryos were analysed on days 10-14 of incubation. Analytical chemistry data showed a varying degradation rate of the compounds in avian embryos of the same species. The residues directly affect the embryos, disturbing their normal development and causing pathophysiological and morphological changes.

2,4-Dichlorophenoxyacetic Acid↗

Embryonic toxicity of insecticide Sumithion 50 EC and herbicide Fusilade S in pheasants after individual or combined administration.

The purpose of this work was to determine the individual and combined effects of insecticide Sumithion 50 EC (50% fenitrothion) and herbicide Fusilade S (12.5% fluazifop-P-butyl) on the development of pheasant embryos. Eggs were treated by injection of various concentrations of pesticides into the air space on day 12 of incubation. Pathological examination of embryos was carried out on day 23 of the hatching period. Mortality rate, body weight data and morphological alterations were evaluated after the macroscopic examination. The skeletal staining method was used to detect deformities. The two pesticides used in combination moderated the toxic/teratogenic effects of individual treatment.

Animals↗

Toxicity of the herbicides Flubalex, Fusilade S and Maloran 50 WP to chicken embryos after administration as single compounds or in combination.

The teratogenic effects of three herbicides (Flubalex, Fusilade S and Maloran 50 WP) were studied in chicken embryos. Each of the three test substances was administered on days 0 and 12 of incubation. Treatment was followed by evaluation on day 19. The compounds were injected into the air-chamber of eggs at three different concentrations. The medium concentration corresponded to that usually applied in chemical plant protection. In order to determine the combined toxicity of the three herbicides, the medium concentration of Maloran 50 WP and three different concentrations of Flubalex of Fusilade S each were administered simultaneously at a final volume of 0.1 ml per egg, at similar times. Evaluation was done on day 19. In tests of individual toxicity, after injection on day 0 of incubation Maloran 50 WP and Flubalex caused a significant reduction in body mass, while Maloran 50 WP and Fusilade S resulted in marked embryonic mortality. After injection on day 12, the medium and the highest concentration of Flubalex and the highest concentration of Fusilade S caused a marked increase in embryonic mortality. The developmental anomalies were of sporadic nature: their incidence increased only after Flubalex treatment, irrespective of the time of administration. The combined administration of Maloran 50 WP and Flubalex on day 0 resulted in a significant or marked body mass reduction in all groups. Embryonic mortality increased substantially after treatment with the highest dose of Flubalex, while all three concentrations of the other two herbicides led to similar results. When treatment was performed on day 12, the two highest concentrations of Flubalex and the highest concentration of Fusilade S caused expressed embryonic mortality. The developmental anomalies did not show a dose-dependent effect in any of the test series.

Animals↗

Effects of repeated oral doses of Dikamin D (2,4-D-amine Na) on rats.

The toxic effects of repeated, increasing oral doses of Dikamin D (72% 2,4-D-amine Na), a broad leave herbicide product used world-wide, were evaluated on rats by the method of Lim et al. (1961). A comparison of the determined acute oral LD50 and the calculated subchronic oral LD50 values revealed a definite tolerance of the experimental animals to the test compound. This finding indicates that repeated oral treatment is capable of increasing the test animal's metabolizing capacity, which accounts for the development of tolerance.

2,4-Dichlorophenoxyacetic Acid↗

Biochemical examination of muscle samples from pheasant embryos affected by Wofatox 50 EC (50% parathion-methyl).

On day 12 of incubation 0.4% and 4.0% aqueous emulsions of Wofatox 50 EC (50% parathion-methyl) were injected into the air space of pheasant eggs. The eggs were opened on day 23 of the incubation period and samples were obtained from both the cervical and the femoral muscles. Atrophy was detected only in the cervical muscles by light microscopic evaluation. Calcium ion concentration was higher in the cervical musculature, but this parameter did not show significant dose-dependent changes. The activity of creatine kinase (CK) was significantly decreased only in the cervical musculature. The obtained biochemical data might result from a secondary atrophy of the cervical muscles.

Animals↗