Neško Nešković

Carbofuran in water: Subchronic toxicity to rats.

Carbofuran toxicity on rats was studied during subchronic exposure. Female and male rats were administered carbofuran in drinking water in concentrations of 25, 100 and 400ppm for a period of 90 days. Clinical symptoms, water consumption, body weight gain, organ weight, pathological and histopathological changes in the liver and kidneys were observed and biochemical and haematological examinations were carried out. The results obtained show that carbofuran administered to rats caused a significant decrease in water consumption as well as in brain, serum and erythrocyte cholinesterase activities. Statistically significant increases in relation to the control were found in the serum enzyme activities. The haematological data showed that carbofuran had no significant effect on Hb concentration and total RBC, but total WBC showed a significant statistical decrease. The histopathological changes in liver and kidneys were observed. However, cell regeneration in the liver and kidneys was found in all test groups.

Subacute toxicity of paraquat in rats—biochemical effects

The toxic effects of paraquat administered to rats in drinking water for a period of 30 days were studied. Paraquat had no effect on the body weight gain or on organ weights of rats. However, microsomal NADPH-cytochrome c reductase activity and cytochrome P-450 content were increased in rats given paraquat in drinking water. The obtained differences were statistically significant. Serum alkaline phosphatase activity was not significantly changed with respect to control animals but a statistically changed, with respect to control animals, statistically significant decrease was established in serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activity of test animals compared to values obtained for control groups. Hematological data showed that paraquat caused a decrease in hemoglobin concentration and total red blood cell number, while the total white blood cell number was significantly increased compared to values obtained for control animals.

The role of liver microsomal enzymes in the metabolism of parathion

Abstract The involvement of microsomal enzymes in the metabolism of the organophosphorus insecticide diethyl p -nitrophenyl phosphorothionate (parathion) by rat liver was studied. The effect of parathion on the activity of NADPH- and NADH-cyto-chrome c reductases in hepatic microsomes isolated from untreated and phenobarbital pretreated rats was determined. The results demonstrate that both NADH- and NADPH-linked (microsomal) electron transport components are involved in the oxidative metabolism of parathion. Phenobarbital pretreatment increased the rate of parathion metabolism. The activity of microsomal NADH-cytochrome c reductase was significantly higher than that of NADPH-cytochrome c reductase. Parathion had an inhibitory effect on both enzymes when applied directly to the microsomal suspension.

Toxicity of clomazone and its formulations to zebrafish embryos (Danio rerio)

Herbicides are the most widely used group of pesticides but after reaching water bodies they are able to cause adverse effects on non-target organisms. Different formulations using the same active ingredient are frequently available, which raises the issue of potential influence of different formulation types on herbicide toxicity. The present study evaluated the toxicity and teratogenic effects of the active ingredient clomazone and its two formulations (Rampa® EC and GAT Cenit 36 CS, both containing 360g a.i./l of clomazone) on zebrafish embryos. The crucial difference between the two formulation types is the way of active substance release. This investigation is the first report on zebrafish embryotoxicity of both clomazone and its formulations. The technical active ingredient and formulations caused mortality and diverse teratogenic effects, showing different levels of toxicity. The LC50 values for the technical ingredient, Rampa® EC and GAT Cenit 36 CS were 61.4, 9.6 and 92.5mg a.i./l, respectively. Spontaneous movements in 22 hpf embryos decreased under exposure to both the technical ingredient and formulations. A significant number of underdeveloped embryos was detected after exposure to clomazone and Rampa® EC, while no underdevelopment was noted in embryos exposed to GAT Cenit 36 CS. Exposure to the technical ingredient and formulations led also to a series of morphological changes and interfered with the growth of zebrafish embryos. The EC50 based on detection of edemas, spine and tail tip deformations and gas bladder absence (120hpf) was 12.1, 10.1 and 24.1mg/l for technical clomazone, Rampa® EC and GAT Cenit 36 CS, while teratogenicity index (TI) based on LC50/EC50 ratio was 5.1, 1 and 3.8, respectively. The data in this study showed that the emulsifiable concentrate formulation (Rampa® EC) caused statistically significantly higher toxicity, and the aqueous capsule suspension (GAT Cenit 36 CS) lower toxicity than technical clomazone. It indicates that different formulations with the same active ingredient may have different environmental impacts, which is why risk assessment based only on active ingredient toxicity might not be sufficient in terms of preventing formulation effects on the environment.

The Effect of Banol and Paraoxon on the Nadph-Cytochrome c Reductase Activity and Cytochrome P-450 Content in Rats

SummaryWe investigated the effect of banol and paraoxon on the activity of NADPH-cytochrome c reductase and cytochrome P-450 concentration in microsomes of rats treatedin vivo with these compounds alone, or in the presence of phenobarbitone.The results showed that banol reduced the NADPH-cytochrome c reductase activity and the concentration of cytochrome P-450, while paraoxon reduced the activity of NADPH-cytochrome c reductase, but increased the cytochrome P-450 concentration.Phenobarbitone stimulated an increased NADPH-cytochrome c reductase activity and cytochrome P-450 concentration. When applied with banol and paraoxon, phenobarbitone lowered their inhibitory effect.

Hematological effects of herbicide Avalon® (bentazon+dicamba) in rats

Hematological effects of the herbicide Avalon (GAL-57), a mixture of bentazon and dicamba, were tested on rats. Avalon was administered by gavage at three and four dose levels (250, 500, 1000 and 1250 mg/kg weight/day) for 28 and 90 days. Hematological parameters, number of erythrocytes, leukocytes and platelets, hemoglobin concentration, hematocrit and erythrocyte indexes (MCV, MCH and MCHC) were monitored. The results showed that the herbicide Avalon caused decrease in the values of hemoglobin, hematocrit and erythrocyte indexes (both males and females). The changes (mostly) correlated with the doses administered and, in most cases, a lower susceptibility of females than males was observed. The herbicide GAL-57 had no adverse effect on the number of leukocytes, erythrocytes and thrombocytes (both sexes, all doses tested). The results showed that the herbicide Avalon causes weak anemia to the animals tested. Reversibility was apparent during the recovery period of 28 days.

Acute oral toxicity study of GAL-57 (bentazon+dicamba) herbicide in rats.

An acute oral toxicity study of the herbicide GAL-57 (Avalon), a mixture of bentazon and dicamba as active ingredients, was investigated on rats, using a new method that has been used in the past several years (2001). Clinical observations symptoms and mortality were performed for all animals in different time intervals after treatment, and gross necropsy was performed at the end of observation period. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone, dyspnoea) of marked degree were noted after administration of 2000 mg/kg, and animals were dead in the period of 30-60 minutes after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behavior of animals (males and females) were normal, and it is not differ in reaction to the control. According to the methodology used in the present study, it could be concluded that the acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats, and the product was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System, and Category III of the EPA classification.

Subacute and subchronic toxicity of Avalon(®) mixture (bentazone+dicamba) to rats.

Subacute and subchronic toxicity of the herbicide Avalon(®), a mixture of bentazone and dicamba, were tested on rats. Avalon(®) was administered at dose levels of 250, 500 and 1000mg/kg body weight/day for 28 and 90 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were monitored together with biochemistry parameters. The results showed that the mixture caused increases in the activities of ALT, AST and ALP, elevated concentrations of sodium, albumin and albumin/globulin ratio in males. In females, ALT activity, cholesterol and phosphate levels were increased. The changes generally were dose related and, in most cases, females exhibited lower susceptibility than males. The effects of a mixture are, in the most cases, different from the effects of the individual substances. The effects of bentazone were not prevalent which would be expected taking the composition of the mixture into account.

EFFECTS OF DIETARY CYPERMETHRIN ON CHICKENS

In the following study effects of dietary cypermethrin in chickens were observed. Chickens were administered cypermethrin in the feed in nominal concentrations of 150, 300 and 600 ppm (mean measured concentrations: 130, 285 and 655 mg/kg feed) for a period of 28 days. The following parameters were monitored: clinical symptoms and mortality, feed consumption and body weight gain, liver weight, plasma ChE activity, hematological and biochemical effects. Any accumulation of cypermethrin in the liver, peritoneal fat, breast and leg muscle was monitored, as well. The results obtained showed that cypermethrin added to the chickens feed did not significantly affect feed intake, body weight gain and liver weight. Also, cypermethrin did not adversely affect the activity of plasma ChE and ALT in the serum. Serum AST activity was significantly increased in the treated chickens, in males at 300 and 600 ppm and in females at all three tested doses. ALP activity was significantly decreased in comparison with the control, in males at doses 300 and 600 ppm, but in females only at the dose of 600 ppm. Hematological data showed that cypermethrin induced a statistically significant increase only in PLT number (both sexes, all three doses tested). The obtained results also showed that cypermethrin did not accumulate in organs and tissues of chickens.

Subacute and Subchronic Toxicity of Dietary Bendiocarb in Rats

The toxic effects of dietary bendiocarb (2,2-dimethyl-1,3-benzodioxol-4-yl-methylcarbamate) (25 and 250 ppm) in rats were studied.