maneb 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

Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week. The gravid rats were randomly divided into three groups (one control and two experimental groups). A mixed solution of paraquat-maneb was administered twice a week by lavage at a dose of 10 or 15 mg kg(-1) bodyweight (containing 30 or 45 mg kg(-1) bodyweight maneb, respectively) from day 6 after pregnancy till ablactation. Maternal weight gain and offspring bodyweights were not affected by the drugs. However, behavioral tests showed that reaction latency and mistake frequency increased after treatment. Intuitively, we found significant changes in the hippocampal neurons in the morphological observation. Taking into account the interaction of the related genes in the cAMP-PKA-CREB pathway, we used a variety of methods to detect the gene and protein levels. Reduced expression of cAMP and related genes and proteins in the hippocampus and serum was also observed. These results indicate that PQ-MB stimulates cAMP to reduce the production of PKA, thus reducing the phosphorylation of CREB and inhibiting the activation of other elements (BDNF, C-JUN, and C-FOS). These changes lead to hippocampal damage and impaired abilities (learning, cognition, and memory). Our results demonstrate that PQ-MB induces hippocampal toxicity in the early life of rats, and they thus provide a theoretical foundation for further investigation of the bathypelagic mechanism involved and measures that can be taken to avoid PQ-MB neurotoxicity.

Topics: Animals; Behavior, Animal; Biomarkers; Body Weight; Cognition; Female; Fungicides, Industrial; Herbicides; Hippocampus; Immunohistochemistry; Learning; Male; Maneb; Maternal Exposure; Memory; Paraquat; Pregnancy; Prenatal Exposure Delayed Effects; Rats

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

Dithiocarbamate are widely used as fungicides because of their efficacy against a broad spectrum of fungi and their associated plant diseases. Maneb is one of Ethylenebisdithiocarabamate (EBDCs). Males domestic rabbits received (by gavage) 2, 3, 5 and 8 mg/kg body weight of maneb, for a period of 5 weeks. Total body weights were measured at 48 h interals. At the end of the experimental period, animals were sacrified and some of organs such as, liver, testes, spleen and the kidney were weighted. The obtained data reveal that the used fungicide induces a remarkable increase in body weight of all the treated animals, particularly with the higher dose as compared with control group. An increase in plasma triglycerides, glucose and of cholesterol levels has been recorded. Moreover, a reduction in the weight of kidneys and testes in animals receiving 5 and 8 mg/kg, while a remarkable increase in the weight of the liver has been observed. Thyroxin concentrations underwent a significant reduction in treated individuals. A very significant reduction in, the number, speed and mobility of spermatozoa accompanied with a high ratio of spermatozoa deformation in the treated groups was noticed. In conclusion, administration of maneb causes thyroid pathology and affects the biology of sperms with histological deformation of testes.

Topics: Animals; Biological Assay; Body Weight; Dose-Response Relationship, Drug; Environmental Exposure; Fungicides, Industrial; Hypothyroidism; Male; Maneb; Organ Size; Rabbits; Random Allocation; Sperm Count; Sperm Motility; Testis; Time Factors

Oxidative stress has been implicated in the pathogenesis of Parkinson disease based on its role in the cascade of biochemical changes that lead to dopaminergic neuronal death. This study analyzed the role of oxidative stress as a mechanism of the dopaminergic neurotoxicity produced by the combined paraquat and maneb model of the Parkinson disease phenotype. Transgenic mice overexpressing either Cu,Zn superoxide dismutase or intracellular glutathione peroxidase and non-transgenic mice were exposed to saline, paraquat, or the combination of paraquat + maneb twice a week for 9 weeks. Non-transgenic mice chronically exposed to paraquat + maneb exhibited significant reductions in locomotor activity, levels of striatal dopamine and metabolites, and dopaminergic neurons in the substantia nigra pars compacta. In contrast, no corresponding effects were observed in either Cu,Zn superoxide dismutase or glutathione peroxidase transgenic mice. Similarly, the increase in levels of lipid hydroperoxides in the midbrain and striatum of paraquat + maneb-treated non-transgenic mice was not detected in either Cu,Zn superoxide dismutase or glutathione peroxidase transgenic mice. To begin to determine critical pathways of paraquat + maneb neurotoxicity, the functions of cell death-inducing and protective mechanisms were analyzed. Even a single injection of paraquat + maneb in the non-transgenic treated group modulated several key pro- and anti-apoptotic proteins, including Bax, Bad, Bcl-xL, and upstream stress-induced cascade. Collectively, these findings support the assertion that protective mechanisms against paraquat + maneb-induced neurodegeneration could involve modulation of the level of reactive oxygen species and alterations of the functions of specific signaling cascades.

Topics: Animals; Apoptosis; bcl-X Protein; Blotting, Western; Body Weight; Cerebral Cortex; Corpus Striatum; Dopamine; Fungicides, Industrial; Glutathione Peroxidase; Herbicides; Hydrogen Peroxide; Immunohistochemistry; Lipid Metabolism; Lipid Peroxidation; Maneb; Mesencephalon; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Neurodegenerative Diseases; Neurons; Oxidative Stress; Paraquat; Parkinson Disease; Proto-Oncogene Proteins c-bcl-2; Serotonin; Signal Transduction; Substantia Nigra; Superoxide Dismutase; Tyrosine 3-Monooxygenase

Idiopathic Parkinson's disease (PD) is associated with advanced age, but it is still unclear whether dopaminergic neuronal death results from events initiated during development, adulthood, or represents a cumulative effect across the span of life. This study hypothesized that paraquat (PQ) and maneb (MB) exposure during critical periods of development could permanently change the nigrostriatal dopamine (DA) system and enhance its vulnerability to subsequent neurotoxicant challenges. C57BL/6 mice were treated daily with saline, 0.3 mg/kg PQ, 1 mg/kg MB or PQ + MB from post-natal (PN) days 5 to 19. At 6 weeks, a 20% decrease in activity was evident only in the PQ + MB group, with a further decline (40%) observed at 6 months. A subset of mice were re-challenged as adults with saline, 10 mg/kg PQ, 30 mg/kg MB, or PQ + MB 2 x a week for 3 weeks. Mice exposed developmentally to PQ + MB and rechallenged as adults were the most affected, showing a 70% reduction in motor activity 2 weeks following the last rechallenge dose. Striatal DA levels were reduced by 37% following developmental exposure to PQ + MB only, butfollowing adult re-challenge levels were reduced by 62%. A similar pattern of nigral dopaminergic cell loss was observed, with the PQ + MB treated group exhibiting the greatest reduction, with this loss being amplified by adult re-challenge. Developmental exposure to PQ or MB alone produced minimal changes. However, following adult re-challenge, significant decreases in DA and nigral cell counts were observed, suggesting that exposure to either neurotoxicant alone produced a state of silent toxicity that was unmasked following adult re-exposure. Taken together, these findings indicate that exposure to pesticides during the PN period can produce permanent and progressive lesions of the nigrostriatal DA system, and enhanced adult susceptibility to these pesticides, suggesting that developmental exposure to neurotoxicants may be involved in the induction of neurodegenerative disorders and/or alter the normal aging process.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Cell Count; Chromatography, High Pressure Liquid; Dopamine; Fungicides, Industrial; Herbicides; Homovanillic Acid; Immunohistochemistry; Male; Maneb; Mice; Mice, Inbred C57BL; Motor Activity; Paraquat; Parkinson Disease; Phenotype; Serotonin; Tyrosine 3-Monooxygenase

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 absence of any compelling basis for a heritable basis of idiopathic Parkinson's disease (PD) has focused attention on environmental exposures as causative agents. While the herbicide paraquat has repeatedly been implicated, its impact on dopamine systems following systemic exposures is equivocal. The restricted focus on paraquat also ignores the extensive geographical overlap of its use with other agrichemicals known to adversely impact dopamine systems, including ethylenebisdithiocarbamate fungicides such as maneb. The present study sought to determine whether combined exposures to paraquat and maneb would produce additive effects and support a multiple-hit environmental contribution to PD. C57BL/6 mice were exposed to either paraquat (5-10 mg/kg) or maneb (15-30 mg/kg) i.p. alone or in combination once a week for 4 weeks. Sustained decreases in motor activity immediately following injections were consistently observed only with combined exposures, with activity levels returning to control values 24 h later. Concurrently, levels of dopamine and metabolites and dopamine turnover were increased immediately post-injection only by combined exposures, and returned to control levels or below within 48 h. Reductions in tyrosine hydroxylase immunoreactivity, measured 3 days after the last injection, resulted only from combined exposure and were detected in dorsal striatum, but not in the nucleus accumbens. The fact that combined exposures resulted in potentiated effects that appear to target nigrostriatal dopamine systems suggests that these combinations may be important environmental risk factors for Parkinsonism. These findings also raise questions about the adequacy of current risk assessment guidelines for these chemicals which are based on effect levels derived from exposures to single agents.

Topics: Animals; Body Weight; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Environmental Exposure; Lung; Male; Maneb; Mice; Mice, Inbred C57BL; Motor Activity; Neostriatum; Neural Pathways; Neurons; Paraquat; Parkinsonian Disorders; Risk Factors; Substantia Nigra; Time Factors; Tyrosine 3-Monooxygenase

Experimental evidence supporting 1,1'-dimethyl-4,4'-bipyridinium [paraquat (PQ)] as a risk factor for Parkinson's disease (PD) is equivocal. Other agricultural chemicals, including dithiocarbamate fungicides such as manganese ethylenebisdithiocarbamate [maneb (MB)], are widely used in the same geographical regions as paraquat and also impact dopamine systems, suggesting that mixtures may be more relevant etiological models. This study therefore proposed that combined PQ and MB exposures would produce greater effects on dopamine (DA) systems than would either compound administered alone. Male C57BL/6 mice were treated twice a week for 6 weeks with intraperitoneal saline, 10 mg/kg paraquat, 30 mg/kg maneb, or their combination (PQ + MB). MB, but not PQ, reduced motor activity immediately after treatment, and this effect was potentiated by combined PQ + MB treatment. As treatments progressed, only the combined PQ + MB group evidenced a failure of motor activity levels to recover within 24 hr. Striatal DA and dihydroxyphenylacetic acid increased 1-3 d and decreased 7 d after injections. Only PQ + MB reduced tyrosine hydroxylase (TH) and DA transporter immunoreactivity and did so in dorsal striatum but not nucleus accumbens. Correspondingly, striatal TH protein levels were decreased only by combined PQ + MB 5 d after injection. Reactive gliosis occurred only in response to combined PQ + MB in dorsal-medial but not ventral striatum. TH immunoreactivity and cell counts were reduced only by PQ + MB and in the substantia nigra but not ventral tegmental area. These synergistic effects of combined PQ + MB, preferentially expressed in the nigrostriatal DA system, suggest that such mixtures could play a role in the etiology of PD.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Body Weight; Carrier Proteins; Cell Count; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Drug Administration Schedule; Drug Synergism; Glial Fibrillary Acidic Protein; Gliosis; Injections, Intraperitoneal; Lung; Male; Maneb; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Motor Activity; Nerve Tissue Proteins; Nucleus Accumbens; Paraquat; Parkinson Disease, Secondary; Substantia Nigra; Tyrosine 3-Monooxygenase; Ventral Tegmental Area

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

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

Topics: Animals; Body Weight; Brassica; Female; Fetus; Gestational Age; Maneb; Microsomes, Liver; Organ Size; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Thiocarbamates

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

Topics: Animals; Body Weight; Female; Maneb; Pregnancy; Rats; Teratogens; Thiocarbamates; Thyroid Gland

Rats, dose-dependent on maneb during pregnancy and lactation (20, 110, 200 or 290 ppm maneb in their food) obtained water or 20 percent alcohol to drink. The animals given pure water indicated no effect. Alcohol in combination with the same concentrations of maneb in the food raised embryotoxicity and produced retardation of the skeletons and postnatal growths in the F1-generation. There was dose-dependent coergistic effect in the breeding results from the alcoholic mothers. The practical significance of this over 15-fold higher susceptibility of alcoholic animals is discussed.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Drug Synergism; Embryo, Mammalian; Ethanol; Female; Maneb; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Thiocarbamates

Topics: Age Factors; Animals; Animals, Newborn; Avoidance Learning; Behavior, Animal; Body Weight; Brain Chemistry; Cholinesterases; Conditioning, Operant; Corticosterone; Emotions; Exploratory Behavior; Fungicides, Industrial; Male; Maneb; Rats; Thiocarbamates