zineb and Body-Weight

The cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development.. Mice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults).. Plasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides.. The additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression.

Topics: Animals; Body Weight; Endocrine Disruptors; Female; Fungicides, Industrial; Immune System; Insecticides; Male; Maneb; Mice; Organ Size; Pesticides; Pyrazoles; Spleen; Survival Analysis; Thymus Gland; Thyroxine; Zineb

Thyroid is an important homeostatic regulator of metabolic activities as well as endocrine mechanisms including those of reproduction. Present investigation elucidated the thyroid disrupting potential of a neonicotinoid imidacloprid and a dithiocarbamate mancozeb in a seasonally breeding wildlife bird, Red Munia (Amandava amandava) who is vulnerable to these two pesticides through diet (seed grains and small insects). Adult male birds were exposed to 0.5% LD50 mgkg(-1)bwd(-1) of both the pesticides through food for 30days during the preparatory and breeding phases. Weight, volume and histopathology of thyroid gland were distinctly altered. Disruption of thyroid follicles reflected in nucleus-to-cytoplasm ratio (N/C) in epithelial and stromal cells, epithelial cell hypertrophy and altered colloid volume. Impairment of thyroid axis was pesticide and phase specific as evident from the plasma levels of thyroid (T4 and T3) and pituitary (TSH) hormones. In preparatory phase, plasma TSH was increased in response to decrease of T4 on mancozeb exposure showing responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to feedback regulation. On imidacloprid exposure, however, plasma levels of both T4 and TSH were decreased indicating non-functioning of negative feedback mechanism. Increased plasma T3 in response to both the pesticides exposure might be due to synthesis from non-thyroidal source(s) in a compensatory response to decrease level of T4. In breeding phase, impairment of HPT axis was more pronounced as plasma T4, T3 and TSH were significantly decreased in response to both mancozeb and imidacloprid. Thus, low dose pesticide exposure could affect the thyroid homeostasis and reproduction.

Topics: Animals; Body Weight; Cell Nucleus Size; Environmental Exposure; Environmental Monitoring; Epithelial Cells; Fungicides, Industrial; Imidazoles; Male; Maneb; Neonicotinoids; Nitro Compounds; Organ Size; Passeriformes; Pituitary Gland; Stromal Cells; Thyroid Gland; Thyroid Hormones; Thyrotropin; Zineb

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight.

Topics: Animals; Body Mass Index; Body Weight; Computer Simulation; Feeding Behavior; Female; Hormones; Imidazoles; Lipid Metabolism; Lipids; Male; Maneb; Metabolism; Mice; Molecular Docking Simulation; Neonicotinoids; Nitro Compounds; Pesticides; PPAR gamma; Receptors, Thyroid Hormone; Signal Transduction; Zineb

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.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Lead; Male; Maneb; Organometallic Compounds; Pregnancy; Rats; Rats, Wistar; Reproduction; Zineb

The dithiocarbamates are known to cause dermatitis, conjunctivitis, rhinitis, pharyngitis and bronchitis in humans. The experimental group received Propineb (obtained from Bayer) concentrations of 400 ppm in distilled water five days a week (treatment time three weeks) administered orally by gasric pit. Acute oral LD50 for male rats has been found to be 8,500 mg/kg (Worthing, 1983). The control group (n = 10) received only distilled water. At ultrasonographical examination, there were no resorbed fetuses or stillborns during or after propineb administration. It can be clearly seen that the body weights of the experimental group of litters are lower than those of the control group (p < 0.001). However, the mean length of the experimental litters was identical to the control group of litters (p > 0.05). Under microscopical examination, increased keratinization and hyperplasia were observed in the epidermal cells.

Topics: Animals; Animals, Newborn; Biopsy; Body Weight; Epidermis; Female; Fungicides, Industrial; Hyperplasia; Keratins; Male; Maternal-Fetal Exchange; Pregnancy; Rats; Rats, Wistar; Skin; Teratogens; Ultrasonography, Prenatal; Zineb

Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the kidneys of fetus and fungicide-treated pregnant females showed a variety of histopathological effects. Moreover, the analysis of zinc (Zn) and manganese (Mn) concentrations (using inductively coupled plasma-atomic emission spectrometry) in the kidneys of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the kidney were higher than those of controls. However, the renal metal concentrations were significantly increased in the litters subjected to the fungicides during gestation, indicating that high levels of the trace metals in the organ of fetus may well be due to the fungicides easily passing the placental barrier.

Topics: Animals; Animals, Newborn; Body Weight; Female; Fetus; Fungicides, Industrial; Kidney; Male; Maneb; Manganese; Maternal-Fetal Exchange; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Zinc; Zineb

The effects of subchronic administration (90 d) of zineb were studied in male New Zealand White rabbits. Rabbits were allotted to 3 groups of 8 animals each and offered diets containing 0, 0.3 or 0.6% zineb. A marked decline in weight gain, hemoglobin concentration, hematocrit, and erythrocyte and leucocyte counts occurred at the highest zineb dosage. There was a dose-related depression in circulating thyroid hormones, whereas serum lipid concentration, particularly that of cholesterol and triglycerides, increased. Hepatic lipid concentration was considerably reduced in rabbits exposed to 0.6% zineb. Neither serum testosterone nor the activities of selected testicular enzymes showed changes suggestive of testicular involvement. Pathological changes were in agreement with biochemical findings; there was a marked dose-related enlargement of the thyroid showing histological colloid struma. An increase in relative weight and moderate glycogenosis were detected in liver, whereas no lesions occurred in testes. It was concluded that thyroid and liver are the main targets for zineb toxicity in the rabbit. Unlike the results from previous studies conducted on other food-producing species, repeated exposure of rabbits to zineb failed to cause testicular damage. This might be related to the inability of zineb to significantly accumulate in the testes.

Topics: Analysis of Variance; Animals; Body Weight; Liver; Male; Rabbits; Testis; Testosterone; Thyroid Hormones; Time Factors; Zineb

Groups of rats were treated with graded doses of zineb or aldicarb solely or in association with copper sulphate for nine consecutive weeks. Body weight gain was retarded and thymus gland weight was decreased in all treated groups. A pronounced synergism between copper sulphate and zineb was noticed in lowering the weights of thymus, testes, and adrenal glands. Various degrees of reduction in hemoglobin concentration, red blood cells and platelet counts occurred after treatment with the above-mentioned agrochemical regimen. Copper sulphate synergised the elevation of serum alkaline phosphatase (AP) activity, and bilirubin concentration as well the reduction of hemoglobin concentration by zineb. Alanine aminotransferase (ALT) activity was significantly increased, while cholinesterase (ChE) activity was decreased in all treated groups. Serum triglycerides (TGs) were lowered in rats treated with medium or high doses of zineb or aldicarb.

Topics: Adrenal Glands; Alanine Transaminase; Aldicarb; Alkaline Phosphatase; Animals; Bilirubin; Blood Cell Count; Body Weight; Cholinesterases; Copper; Copper Sulfate; Drug Interactions; Drug Synergism; Hemoglobins; Male; Organ Size; Rats; Thymus Gland; Triglycerides; Zineb

Topics: Administration, Oral; Animals; Body Weight; Hyperplasia; Hypertrophy; Iodide Peroxidase; Male; Maneb; Organ Size; Rats; Thyroid Gland; Thyroxine; Zineb

The carcinogenic potential of 5 pesticides was analyzed using a medium-term multi-organ bioassay for carcinogenicity. Male F344 rats were initially treated with 3 known carcinogens (diethylnitrosamine, N-methyl-N-nitrosourea and N-bis(2-hydroxypropyl)nitrosamine) during a period of 4 weeks to induce neoplastic changes in a variety of organs, and then given one of 5 pesticides in the diet for a further 16 weeks. Neoplastic and pre-neoplastic lesions were found in the thyroid, kidney and urinary bladder with propineb, in the forestomach, kidney and thyroid with captan and folpet. The number of glutathione S-transferase placental-form-positive liver-cell foci was significantly increased in the captan- and phosmet-treated groups. Based on these findings, captan and propineb can be considered as carcinogens and carcinogenicity is suspected for folpet and phosmet. These results are in concordance with reported long-term carcinogenicity for captan, folpet and propineb. Daminozide was considered not to be carcinogenic. Thus, the present assay of 20 weeks' duration is useful for the prediction of potential carcinogens.

Topics: Animals; Body Weight; Captan; Carcinogenicity Tests; Carcinogens; Cocarcinogenesis; Diethylnitrosamine; Liver; Liver Neoplasms, Experimental; Male; Methylnitrosourea; Models, Biological; Nitrosamines; Organ Size; Pesticides; Precancerous Conditions; Rats; Rats, Inbred F344; Zineb

Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas.

Topics: Administration, Topical; Animals; Body Weight; Fungicides, Industrial; Maneb; Mice; Papilloma; Skin Neoplasms; Survival Analysis; Zineb

A subacute toxicological study of the effects of the ethylene-bisdithiocarbamate-containing fungicide Dithane M-45 (80% mancozeb) was carried out in male Wistar rats. The rats were given Dithane mixed in the feed at doses of 0, 10, 50, 75, 113, 169, 253 or 379 mg/kg body weight for 12 wk. One-third of the rats given 379 mg Dithane/kg body weight died, and doses of greater than or equal to 169 mg/kg decreased the growth of the rats as well as the nutrient utilization. The relative weights of the liver and thyroid were significantly increased in rats given greater than or equal to 75 mg Dithane/kg body weight, and those of the kidneys, adrenals and testes were significantly increased in the two highest dose groups. The serum cholesterol level was increased significantly in groups given greater than or equal to 75 mg/kg, and doses of 113, 169 or 253 mg/kg caused the elevation of the triglyceride content of the liver. The two highest doses of Dithane decreased the detoxicating capacity of the liver. The function of the thyroids was impaired even by very small doses of Dithane: at a dose of 10 mg/kg body weight the quantity of iodine stored in the thyroids was decreased by 20%. At doses of greater than or equal to 50 mg/kg statistically significant decreases in thyroid iodine content were observed. Histological examination of the thyroids showed dose-dependent hyperplasia in rats treated with Dithane.

Topics: Animals; Blood Chemical Analysis; Body Weight; Iodine; Lipids; Liver; Male; Maneb; Mixed Function Oxygenases; Organ Size; Rats; Rats, Inbred Strains; Thiocarbamates; Thyroid Gland; Zineb

The effects of Mancozeb and Zineb, two dithiocarbamate fungicides used to protect vegetables, on rat thyroid and liver function were studied in an acute and a chronic trial. These compounds may be spontaneously or metabolically transformed to ethylene thiourea, a goitrogenic, mutagenic and teratogenic molecule. Sex linked differences in sensitivity and the possibility that toxicity might be potentiated through induction of the microsomal drug metabolising system by phenobarbitone were investigated. When compared with the findings of Ugazio et al. (1985) on the toxicity of ethylene thiourea, the results obtained in this study, bearing in mind the doses employed and the fact that no potentiation by phenobarbitone was observed, suggest that the risks associated with exposure to these two fungicides are less severe than had been supposed.

Topics: Animals; Body Weight; Drug Synergism; Female; Liver; Male; Maneb; Phenobarbital; Rats; Rats, Inbred Strains; Sex Factors; Thiocarbamates; Thyroid Gland; Thyroxine; Triglycerides; Triiodothyronine; Zineb

Crl:CD rats were exposed (whole body) to mancozeb by inhalation at 0, 1, 17, 55, 110, 890, or 1890/500 mg/m3 for 6 hr/day from Day 6 through 15 of gestation (sperm-positive vaginal smear considered Day 1). Dams were killed 1 day prior to natural delivery and fetuses were examined externally, viscerally, and skeletally for any alterations. Maternal toxicity, as evidenced by significantly decreased body weight gain, hindlimb paralysis, general debilitation, and death or termination in extremis, was noted among rats exposed to mancozeb at concentrations of 500 to 1890 mg/m3. Dams from the 55 and 110 mg/m3 groups exhibited decreased body weight gain and hindlimb weakness. There was no maternal toxicity for dams exposed at a concentration of 17 mg/m3. Embryofetal toxicity, as evidenced by a significantly increased incidence of totally resorbed litters, external hemorrhage, and wavy ribs, was noted at concentrations of 55 mg/m3 and above. The embryofetal toxicity occurred only at concentrations toxic to the dam. Among the groups exposed to mancozeb, the incidence of major malformations was not dose related. Hence, under the test conditions of this study, mancozeb was not found to be teratogenic and produced no toxicity unique to the conceptus.

Topics: Abnormalities, Drug-Induced; Animals; Atmosphere Exposure Chambers; Body Weight; Female; Fetal Resorption; Fetus; Maneb; Maternal-Fetal Exchange; Particle Size; Pregnancy; Rats; Teratogens; Zineb

The purpose of the work was to establish the eventual "metabolic toxicity" of pesticide-contaminated diets in the Rat. The liver metabolic response to various stimuli was compared in dithiocarbamate-fed animals and in non-contaminated ones. 112 weanling male Wistar CF rats were fed, during 15 days, with a demi-synthetic control diet. They were then divided into 4 lots:--the control group C, which went on to receive the same diet,--the nabame group N, the diet of which was supplemented with 275 ppm of the dithiocarbamate;--the thirame groupe R, receiving the control diet + 600 ppm thirame;--the zineb groupe Z, given the control diet + 3 600 ppm Zineb. The animals were fed with these diets during 14 days, their dithiocarbamate intake thus averaging 1/20 th of the per os LD 50/rat/day. At the end of this 2-week period, each of the 4 groups was divided into 4 sub-groups, all the animals were fasted overnight, then sacrified:--after no other treatment (sub-groups T);--30 minutes after an i.p. injection of 2.6 g/kg glucose (G);--after having been forced to walk in a restraint wheel for 50 minutes/hr during the 18 hrs of the night fast (sub-groups W);--after a 90 minutes exposure in a cold room (F). The weights of the animals, of their liver, heart, kidneys, adrenals and epididymal pads were recorded. In their liver, the following compounds were determined: water, proteins, total lipids, triglycerides, long-chain acyl-CoA, non-esterified fatty acids, total cholesterol, glycogen, glucose, alpha-glycerophosphate. The thirame rats had a lower food intake than the others and the smallest body weight, but their relative liver and kidneys weights were the highest. The nabame animals did not differ from the control ones but the zineb rats had the lightest epididymal fat pads. The primary effects of the dithiocarbamate diets on liver metabolism were apparently not the same in the 3 groups compared to the control ones: nabame and thirame increased glycogen, thirame increased the lipid compounds: long-chain actyl-CoA and triglycerides, where as zineb feeding resulted in an increase of glucose concentration and in a decrease of triglycerides and total lipids. Muscular exercise, or cold exposure, had the following effects compared to those they had in the control group: a greater glucose utilization in the nabame and thirame rats, a smaller glycogen and glucose utilization, associated with an increase of alpha-glycerophosphate, in the zineb animals. These results were consi

Topics: Adipose Tissue; Animals; Body Weight; Carbohydrate Metabolism; Epididymis; Fungicides, Industrial; Kidney; Lipid Metabolism; Liver; Male; Organ Size; Proteins; Rats; Thiocarbamates; Thiram; Zineb

Topics: Animals; Antibody Formation; Body Weight; Carbamates; Carbaryl; DDT; Fungicides, Industrial; Insecticides; Mice; Rabbits; Thiocarbamates; Zineb