Mancozeb toxicity

Khan PK, Sinha SP. 1996. Ameliorating effect of vitamin C on murine sperm toxicity induced by three pesticides (endosulfan, phosphamidon and mancozeb). Mutagenesis ll(l) 33-36. 

No. Mancozeb is a broad-spectrum fungicide used as a protectant in many economically important crops but, because of its behaviour as a general cell toxicant, its conversion into a systemic would result in an unacceptable piiytotoxic crop response. 

Toxicity Mancozeb is practically nontoxic via the oral route, with an acute oral LD50 of greater than 5,000 mg/kg to greater than 11,200 mg/kg in rats. The acute dermal LD50 is greater than 10,000 mg/kg in rats and greater than 5,000 mg/kg in rabbits. It is a mild skin irritant and sensitizer and a mild to moderate eye irritant in rabbits. Workers with occupational exposure to mancozeb have developed sensitization rashes.2,17,52... 

Mancozeb has effects on various organ systems. Its primary mechanism of toxicity is via skin contact, leading to contact dermatitis and dermal sensitization. Mancozeb has also been shown to have teratogenic and reproductive effects. Mancozeb exposure also alters the reproductive and endocrine structures, leading to decreased fertility. Animals orally exposed to mancozeb showed thyroid hyperplasia, probably via its ability to inhibit the synthesis of thyroxin. Additionally, mancozeb exposure produces neurotoxicity via yet an unknown mechanism. 

The acute toxicity of mancozeb is rather low both in humans and experimental animals. Thus acute poisoning is highly unlikely unless large amounts are ingested. Mancozeb is slightly toxic via the dermal route. Contact with mancozeb leads to inflammation and/or irritation of the skin, eyes, and respiratory tract. Acute exposure to mancozeb 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, mancozeb is not very toxic acutely unless high levels of exposure occur. The acute LD50 for mancozeb is 4500 mg kg in laboratory animals. 

Since the acute toxicity of mancozeb is relatively low as is with most dithiocarbamates, acute intoxication in humans is unlikely to occur unless large amounts are ingested. Mostly mancozeb is known for its irritant and allergic potential in occupational exposures. Skin irritation and sensitization has been studied in humans and have shown mild erythema and itching. 

There is limited information regarding the chronic toxicity of mancozeb. It has been indicated that mancozeb has low toxicity in most experimental animals. Its major metabolite, ethylenethiourea (ETU), has been shown to produce carcinogenic and teratogenic effects in laboratory animals at high dose levels. 

Mancozeb is generally of low toxicity to most wildlife. It is practically nontoxic to birds and honey bees. It has a relatively high toxicity to fish. The 48 h LC50 for goldfish is 9 mg kg and for rainbow trout it is 2.2 mg kg... 

Mancozeb is toxic to some plants such as marigold at normal field application rates. Some genetic effects were seen in onion cells exposed to mancozeb. 

In another example, California agricultural workers who were exposed to the pesticides mancozeb and toxaphene had increased incidences of leukemia compared with those not so exposed j8°l In this instance as well, the workers were exposed to other pesticides and toxic chemicals. 

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. 

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. 

In a chronic carcinogenesis study in female Swiss mice, thrice weekly applications of technical grade mancozeb at a dose of 76 mg/kg active ingredient resulted in the increased mortality of treated subjects (Shukla et al. 1990). Eleven mice remained in a treatment group of 20 at 360 days of treatment fewer than 6 animals remained at 420 days of treatment. The deaths were reported to be related to the dermal toxicity caused by the mancozeb. 

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. 

Methods for reducing toxic effects have not been identified for MMT. Methods for reducing toxic effects following exposure to maneb or mancozeb have been identified in the case studies these methods are... 

Maneb or mancozeb. Table 4-2 lists the facilities in the United States that manufacture or process the fungicide maneb, the intended use, and the range of maximum amounts that are stored on site. The data in Table 4-2 are derived from the Toxics Release Inventory (TRI97 1999). Only certain types of facilities were required to report. Therefore, as with the list of manganese manufacturers or processors, this is not an exhaustive list. In 1997, 3 facilities (in Arizona, New Jersey, and North Dakota) reported repackaging maneb and storing between 10,000 and 99,999 pounds of it on site. One facility in Georgia... 

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