Acute intoxication due to exposure to maneb and zineb. A case with behavioral and central nervous system changes.

The dithiocarbamates are considered chemicals of low toxicity. They are known to cause dermatitis, conjunctivitis, rhinitis, pharyngitis, and bronchitis in humans. Central nervous system effects in humans have not been found, but some cases have been reported in experimental animals. This case report concerns a 42-year-old man previously in good health, who sprayed a combined dithiocarbamate of maneb and zineb on a cucumber plantation twice during a week, the second time with a more concentrated solution than the first. Behavioral changes appeared after he walked through the sprayed area following the first application, and loss of consciousness, convulsions, and right hemiparesis with diffuse slow rhythm in the electroencephalogram occurred after the second exposure. Both the behavioral and central nervous system symptomatology disappeared spontaneously after a few days. An electroencephalogram was normal two weeks later. The absence of a positive previous history of the patient, the sudden appearance and spontaneous disappearance of the symptoms, and the apparent dose-response relationship strongly suggested that maneb and zineb were the cause of the illness.

[Subchronic toxic effect of the grain fungicide PF-70 on the electrolyte barrier of the gastric mucosa in rats]. / Wplyw podprzewleklego zatrucia fungicydem do zbóz PF-70 na bariere elektrolitowa blony sluzowej zoladka szczurów.

The fungicide for corn PF-70 contains 21% of sulphur, 8.4% of mancozeb, and 0.6% of triadimefon . The aim of the study was to determine the effect of the fungicide on the gastric mucosa electrolyte barrier in rats. Mucosa lesion is known to be one of the risk factors of chronic peptic ulcer disease. The experiments were carried out on 80 rats of Wistar strain. The animals were divided into 5 groups--males and females, separately. The fungicide was given for 13 weeks, at the following doses: 100, 400, 1600, and 6400 mg of active substance per 1 kg of fodder. The gastric mucosa electrolyte barrier was examined by determining the transmural electric potential differences (PD) in mucosa before and after treatment with 150 mmlo of hydrochloric acid and 40 mmol of acetylsalicylic acid solutions. No changes in general condition of the animals were observed. An increase in fodder consumption was observed in males receiving the fungicide at doses of 1600 and 6400 mg per 1 kg of fodder. Females exhibited a decrease in body mass after intoxication at concentration of 6400 mg/kg fodder. A decrease in PD was found in all groups intoxicated with the fungicide, irrespective of the animal sex.

Life threatening central nervous system manifestations and hypothermia due to maneb intoxication in a child: a case report.

Maneb, manganese ethylene-bis-dithiocarbamate, is a fungicide pesticide used in the agriculture and bulb flower culture sector. Toxicological effects for humans have been reported in literature and are diverse. They vary from allergic reactions (dermatitis, conjunctivitis, and bronchitis), central nervous system effects (muscarinic, nicotinic, central and extrapyramidal) and renal toxicity (acute renal failure).A 7-year old girl was admitted to the pediatric intensive care unit because of status epilepticus. Physical examination showed respiratory insufficiency, convulsions, and severe hypothermia (32.5 degrees C). The patient was intubated and her convulsions were successfully treated with benzodiazepines. Except for a combined metabolic and respiratory acidosis and hyperglycemia, diagnostic investigations on admission (full blood count, electrolytes, liver and renal functions, cerebrospinal fluid investigation, toxicology screening of blood and urine for barbiturates and benzodiazepines, blood culture, herpes PCR, and a CT scan of the brain) were normal. Within 24 hours, there was a complete recovery of all neurological signs. Within 72 hours, the patient was discharged from the hospital. Liquid chromatography-mass spectrometric investigation of her blood showed amounts of maneb, which can explain all symptoms and signs. However, effects of this magnitude on the central nervous system have not previously been reported in humans.

Acute renal failure and maneb (manganous ethylenebis[dithiocarbamate]) exposure.

A 62-year-old man spread maneb on about 200 sq m of garden and subsequently was taken to the emergency clinic with complaints of oliguria, diarrhea, and hoarseness. Based on the clinicobiochemical data, he was found to have acute renal failure; the serum levels of BUN, creatinine, and potassium were 144.3 mg/dL, 14 mg/dL, and 5.8 mEq/L, respectively. The ST segment depression in V4-6, reciprocal ST segment elevation in V1-3, and inverted T waves in V5 and V6 were recorded on ECGs. Both the renal failure and the ECG abnormalities disappeared after hemodialysis. The possibility exists that the maneb caused the acute renal failure.

Acute central nervous system changes due to intoxication by Manzidan (a combined dithiocarbamate of Maneb and Zineb).

A 42-year old man sprayed Manzidan (a combined dithiocarbamate of Maneb and Zineb) on a cucumber plantation, twice during a week. Behavioural changes appeared after the first application, and loss of consciousness, convulsions and right hemiparesis after the second application with diffuse slow rhythm in the EEG. Both the behavioural and CNS symptomatology disappeared spontaneously after a few days. The previous history of the patient, the sudden appearance and spontaneous disappearance of the symptoms and a dose-response relationship strongly suggest that Maneb and Zineb were the cause of the illness.

[Changes in the gonads and reproductive capacity of white rats after oral maneb poisoning]. / Promeni v gonadite i v sposobnostta za reproduktsiia na beli plukhove sled oralna intoksikatsiia s maneb.

Changes in the gonads and reproduction capacity of white rats following oral intoxication with maneb are studied. The preparation at doses 1/10, 1/50, 1/100 and 1/5000 LD50 is administered to the starting generation of white rats twice weekly. Changes in the gonads--biochemical, histological, histoenzymatic and electron microscopic--are established, as well as a capacity for reproduction of the starting I and II offspring. The results show a clearcut gonadotropic effect of the preparation, manifested by morphological changes in the starting generation, and by changes in fertility, gestation, survival and lactation of the starting I and II offspring.

[Ovarian activity of Drosophila melanogaster Meigen (Diptera), during a chronic intoxication with four fungicides: anatomical and cytological study]. / [Ovarian activity of Drosophila melanogaster Meigen (Diptera), during a chronic intoxication with four fungicides: anatomical and cytological study]

Two types of reactions were observed on the alteration of Drosophila vitellogenesis by the four fungicides used in this study. Dithane M45 resulted in stimulation associated with egg retention. However, the other three fungicides (Benlate, Bouillie bordelaise and Euparène) resulted in inhibition to a varying degree. Although the inhibition was comparatively limited due to Benlate it induced an egg retention. The inhibition was very high due to Bouillie bordelaise and Euparène. With Bouillie bordelaise an egg retention occured together with the reduction of vitellogenesis and caused an increase in the rate of the follicle resorption. The latter depended on the duration of treatment. With Euparène, no egg retention was observed and the toxicity was only noticed on vitellogenesis.

[35S-cysteine incorporation into protein synthesis of the liver and testes in subacute oral poisoning with zineb, maneb and mancozeb]. / Prouchvane na vkliuchvaneto na 35S-tsistein v beltuchniia sintez na cherniia drob i testisite pri podostro oralno trovene s tsineb, maneb i mankozeb.

35S-cysteine incorporation in the protein synthesis of liver and testes is studied in groups of 20 white rats each, following 14--day poisoning with dithiocarbamates, at doses 1/5 LD50, as follows: group one, cineb - o,180 g/kg, maneb - 0,140 g/kg, and mankozeb - 0,260 g/kg. Protein incorporation in liver and testes is studied after decapitation of the animals, within two hours of intraperitoneal 35S-cysteine injection at dose 15 micro C per rat. Liver and testes undergo appropriate treatment after the method of Munro et al./10/, as modified by Sheitanov /9/, and counting is done with VAZ--310. The results point to a varying degree of cysteine incorporation increase in the protein synthesis of liver and testes. It is attributed to a variety of dystrophic and necrobiotic changes in the tissues of either of the organs, taking place under the effect of dithiocarbamate preparations. An enhancement of regenerative processes in the above mentioned organs, associated with intensified protein synthesis, is by no means ruled out. Differences established in the intensity of amino acid incorporation correlate with the degree of protein synthesis disorders, mostly in terms of the effect of maneb preparations.

The effect of poisoning with Dithane M-45 on oxygen uptake and energy balance in adult rats.

Adult white rats were kept on natural diet containing various doses of Dithane M-45 (Mn and Zn ethylene-bisdithiocarbamate). Oxygen uptake (VO2), metabolic rate and energy balance were determined at intervals of several days. Oxygen uptake and metabolic rate were not significantly changed in animals receiving Dithane M-45 in concentrations of 5 and 50 ppm but they were significantly decreased in the animals kept on the diet containing the preparation in concentrations of 500, 2000 and 5000 ppm. The authors conclude that changes in body weight of animals after poisoning with Dithane M-45 are due, both to reduced supply and requirements for energy.

Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype.

While advancing age is the only unequivocally accepted risk factor for idiopathic Parkinson's disease, it has been postulated that exposure to environmental neurotoxicants combined with ageing could increase the risk for developing Parkinson's disease. The current study tested this hypothesis by exposing C57BL/6 mice that were 6 weeks, 5 months or 18 months old to the herbicide paraquat, the fungicide maneb or paraquat + maneb, a combination that produces a Parkinson's disease phenotype in young adult mice. Paraquat + maneb-induced reductions in locomotor activity and motor coordination were age dependent, with 18-month-old mice most affected and exhibiting failure to recover 24 h post-treatment. Three months post-treatment, reductions in locomotor activity and deficits in motor coordination were sustained in 5-month-old and further reduced in 18-month-old paraquat + maneb groups. Progressive reductions in dopamine metabolites and dopamine turnover were greatest in 18-month-old paraquat + maneb and paraquat groups 3 months post-treatment. Increased tyrosine hydroxylase enzyme activity compensated for striatal tyrosine hydroxylase protein and/or dopamine loss following treatment in 6-week-old and 5-month-old, but not 18-month-old paraquat and paraquat + maneb mice. Numbers of nigrostriatal dopaminergic neurons were reduced in all age groups following paraquat alone and paraquat + maneb exposure, but these losses, along with decreases in striatal tyrosine hydroxylase protein levels, were progressive in 18-month-old paraquat and paraquat + maneb groups between 2 weeks and 3 months post-exposure. Collectively, these data demonstrate enhanced sensitivity of the ageing nigrostriatal dopamine pathway to these pesticides, particularly paraquat + maneb, resulting in irreversible and progressive neurotoxicity.