Maneb toxicity

The fungicides Maneb and Zineb are dithiocarbamates of low acute toxicity but with troublesome contaminant and degradation problems from ethylene thiourea, a carcinogen. The neurotoxic metabolite, carbon disulfide, is another potential hazard of their use. 

Maneb has effects on various organ systems. Its primary mechanism of toxicity is via skin contact, leading to contact dermatitis, erythema, and even dermal sensitization. Maneb has also been shown to have teratogenic and reproductive effects. Exposure to pregnant animals has been shown to have adverse effects on the fetus. Maneb exposure has also been... 

The acute toxicity of maneb is rather low, and thus acute intoxication is unlikely to occur. 

Maneb is practically nontoxic by ingestion. Via the dermal route, it is slightly toxic. Contact with maneb leads to inflammation and/or irritation of the skin, eyes, and respiratory tract. Acute exposure to maneb may lead to effects such as hyperactivity, incoordination, loss of muscular tone, nausea, vomiting, diarrhea, loss of appetite, weight loss, drowsiness, slowed reflexes, and respiratory paralysis. 

In general the acute oral and dermal toxicity of maneb for most mammals is relatively low. The acute oral LD50 for rats is > 5000 mg kg The acute dermal LD50 for rabbits is > 5000 mg kgand for rats is > 10 000 mg kg It is a moderate skin and... 

Since the acute toxicity of maneb is relatively low as is with most dithiocarbamates, acute intoxication in... 

Chronic exposure to maneb has been related to reproductive, embryotoxic teratogenic, and neurotoxic effects. Although the toxicity associated with maneb exposure is low, it has been shown that in combination with other toxicants such as metals, other fungicides and herbicides the effects of maneb may be more pronounced, leading to more severe deficits. 

In vitro systems have been developed to try and understand the mechanism of action of maneb. In particular, the mechanism of toxicity of maneb on the central nervous system using synaptosomal and mitochondrial preparations from brain tissue has been utilized. These studies have shown that maneb has adverse effects on the dopaminergic system, via mechanisms that relate to mitochondrial inhibition and altered neurotransmitter uptake. The genotoxic, cytotoxic, and neurotoxic effects of maneb have been studied using a variety of primary cultures as well as cell lines, including human lymphocytes. As noted above, maneb has little mutagenic potential. 

Maneb is however highly toxic to fish and other aquatic species. The 96 h LC50 for maneb is 1 mg 1 in bluegill sunfish. The reported 48 h LC50 is 1.9mgl in rainbow trout and 1.8mgl in carp. Maneb-treated crop foliage may also be toxic to livestock. 

US Environmental Protection Agency (October 1988) Pesticide Fact Sheet Maneb. Office of Pesticides and Toxic Substances, Office of Pesticide Programs, US EPA, Washington, DC. 

Human natural killer (NK) lymphocytes are vital to immune system defense against viral infection. They are also crucial in protecting against primary tumor formation. In vitro exposures to low levels of two organotin pesticides, tributyltin (4.76) and triphenyltin (4.19), and two carbamate pesticides, maneb (0.62) and ziram (1.23), produced significant loss of cytotoxic function of NK cells after 6 days of exposure. The toxicities of the pesticides also increased very significantly with exposure durations J51 It should be noted that exposure to ziram can come from other sources. It is used as an additive in rubber products such as latex gloves. 

Nabam was originally described in 1943. When mixed with zinc or manganese sulfate, zineb or maneb is formed, respectively. The mixed salt of zinc and manganese, mancozeb is used quite extensively. The alkyl-enebis(dithiocarbamate)s have a low mammalian toxicity (e.g., LD50 = 8000 mg/kg for rats) but are considered to be carcinogenic, notably through the metabolite ethylenethiourea, which is formed by cooking. 

Carbamates, first synthesized in the 1930s and commercialized in the 1960s, constitute the most recently developed class of anticholinesterase insecticides. Developed to replace the more dangerous CH and OP insecticides, their toxic principle derived from the effects on humans of the Calabar bean used in the West African trial by ordeal (Ecobichon 1997). Carbamates inhibit nervous tissue cholinesterases, but less irreversibly than OP insecticides, resulting in reduced toxicity (Ecobichon 1997). Common carbamate names include carbaryl, methomyl, and maneb. 

Larsson et al. (1976) conducted an acute reproductive toxicity study in pregnant Sprague-Dawley rats and NMRI mice using maneb and mancozeb. The fungicides were administered in two different experiments (preliminary and final) by gavage, dissolved in water. The preliminary experiment involved doses of maneb at 0, 340, 650, 1,200 mg/kg/day, or mancozeb at 0, 300, 580, or 1060 mg/kg/day on gestation day 9 or 13... 

Pacces Zaffaroni et al. (1978) investigated the percutaneous toxicity of maneb in solution to the adult newt, Triturus cristatus. When incubated in water containing 20, 40, 60, 80, or 100 ppm maneb, the newts suffered deaths in a dose-dependent fashion, with 50% of the male newts dead in 8.4—8.8 hours at 100 ppm and in 255 hours at 20 ppm. The females were not as susceptible to the lethal action of the fungicide, with 50% dying in 28.5 hours at 100 ppm, and some newts still alive after 5 months at 20 ppm. No studies were located concerning death following dermal exposure of animals to mancozeb. 

Vascular congestion and inflammatory cells were present in the cavity and the lung wall in 16% of newts exposed percutaneously to 40-100 ppm maneb for up to several days in an acute toxicity study (Pacces Zaffaroni et al. 1978). 

Maneb or mancozeb. The reader is referred to Section 2.2.1.2 for a discussion of musculoskeletal effects in humans following dermal exposure to maneb or mancozeb. Arias and Zavanella (1979) and Zavanella et al. (1984) have reported severe skeletal deformities in newts with amputated limbs that were incubated in varying concentrations of maneb. However, these experiments were performed as a model for developmental toxicity of environmental pollutants therefore, these reports are discussed fully in Section 2.2.3.6. No studies were located regarding musculoskeletal effects following dermal exposure to mancozeb in animals. 

Inhalation and oral MRL values for acute, intermediate or chronic exposures to either MMT, maneb or mancozeb have not been derived. There are currently insufficient data regarding the systemic toxicity and carcinogenicity of these compounds via inhalation or oral exposures and no reliable data concerning current enviromnental or occupational exposures with appropriate dose-response information. 

The majority of oral and inhalation studies for selected organic manganese compounds (MMT, maneb and mancozeb) in humans and animals indicate that these compounds do not cause significant injury to heart, stomach, blood, muscle, bone, skin or eyes. Injection studies in humans using mangafodipir at clinical doses show that the compound does not have significant systemic toxicity. At increased doses in animals, the compound does not cause significant injury to blood, muscle, bone, skin or eyes. 

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