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EBDCs (General Information) Mancozeb Research Report

                             E  X  T  O  X  N  E  T
                          EXTENSION TOXICOLOGY NETWORK

A Pesticide Information Project of Cooperative Extension Offices of 
Cornell University, Michigan State University, Oregon State University, 
and University of California at Davis.  Major support and funding was 
provided by the USDA/Extension Service/National Agricultural Pesticide 
Impact Assessment Program.



     Some trade names include Dithane M-45, Manzate 200, Mancozeb, Fore, 
Green-Daisen M, Karamate, Mancofol, Zimaneb, Manzeb, Policar, Dithane-
Ultra Nemispot, Nemispor, Riozeb, Mancozin, Manzin.  Common names 
include mancozeb and manzeb.


     Mancozeb is registered as a general use pesticide by the U.S. 
Environmental Protection Agency (EPA).  In July 1987, the Environmental 
Protection Agency announced the initiation of a special review of the 
ethylene bisdithiocarbamates (EBDCs), a class of chemicals to which 
mancozeb belongs.  This Special Review was initiated because of concerns 
raised by laboratory tests on rats and mice.  The EPA was concerned 
about a) potential effects on the general population from dietary 
exposure to residues left on food crops and b) potential occupational 
health risks to workers who handle and/or apply EBDC pesticides.  As 
part of the Special Review, EPA reviewed data from market basket surveys 
and concluded that actual levels of EBDC residues on produce purchased 
by consumers are too low to affect human health.  The EPA concluded its 
Special Review in April, 1992 with new label requirements for protective 
clothing to be worn by industrial and agricultural workers, and with the 
establishment of a 24-hour reentry period for agricultural workers.  
Many homegarden uses of EBDCs have been canceled because the EPA has 
assumed that home users of these pesticides do not wear protective 
clothing during application (18).  Toxicity data reviewed by the EPA as 
part of their Special Review of EBDCs are included in this document 
under "Toxicological Effects."

     Containers of this fungicide bear the  signal word "CAUTION" (2).


     The EBDCs are fungicides used to prevent crop damage in the field 
and to protect harvested crops from deterioration in storage or 
transport (21).  Mancozeb is used to protect many fruit, vegetable, nut 
and field crops against a wide spectrum of diseases, including potato 
blight, leaf spot, scab (on apples and pears) and rust (on roses).  It 
is also used for seed treatment of cotton, potatoes, corn, safflower, 
sorghum, peanuts, tomatoes, flax and cereal grains (2, 16, 17).  
Mancozeb is not taken up from the soil by plants (6).  It is a 
combination of two other chemicals of this class, maneb and zineb (9).  
Mancozeb is available as dusts, liquids, water dispersible granules, as 
wettable powders, and as ready-to-use (R-T-U) formulations (17).



     Mancozeb has a very low acute toxicity to mammals.  No 
toxicological effects were observed in a long term study with rats fed 
doses of 5 mg/kg (16).  The major routes of exposure to mancozeb are 
through the skin or from inhalation (13).  In spray or dust forms, the 
EBDCs are moderately irritating to the skin and respiratory mucous 
membranes.  Symptoms of poisoning from this class of chemicals include 
itching, scratchy throat, sneezing, coughing, inflammation of the nose 
or throat, and bronchitis (9, 19).  There is no evidence of 
'neurotoxicity,' nerve tissue destruction or behavior change, from the 
EBDCs (9).  However, dithiocarbamates are partially chemically broken 
down, or metabolized, to carbon disulfide, a neurotoxin capable of 
damaging nerve tissue (5).

     The amount of a chemical that is lethal to one-half (50%) of 
experimental animals fed the material is referred to as its acute oral 
lethal dose fifty, or LD50.  The oral LD50 for mancozeb ranges from 
4,500 to 11,200 mg/kg in rats.  When applied to the skin of rabbits, its 
dermal LD50 is 5,000 to 15,000 mg/kg (2, 13, 16, 17).  It is a mild skin 
irritant and sensitizer, and a mild to moderate eye irritant in rabbits 
(4).  Agricultural workers handling crops treated with mancozeb have 
developed sensitization rashes (16).


     In a two-year study dogs were fed doses of 0, 0.625, 2.5 or 25 
mg/kg of mancozeb.  Lower iodine uptake was observed after 24 months in 
dogs fed the two highest doses, while no difference was observed between 
those dogs fed 0 and 0.625 mg/kg (16).

     Mancozeb is comparable to another chemical, maneb, on which the 
following long-term studies have been conducted.  A two-year feeding 
study on rats indicated that 6.25 mg/kg of maneb in the diet is the no 
observable effect level (NOEL) for rats.  However, the next and highest 
level that was fed to rats in this two-year study did produce signs of 
poisoning.  A one-year feeding study in dogs concluded that 20 mg/kg/day 
is a NOEL for dogs.  Toxic effects were seen in the dogs at daily doses 
of 75 mg/kg and 250 mg/kg (4).

     The ethylene bisdithiocarbamate pesticides (EBDCs), which include 
mancozeb, are generally considered to have low short-term mammalian 
toxicity.  A major toxicological concern, however, is ethylenethiourea 
(ETU), an industrial contaminant  and a breakdown product of mancozeb 
and other EBDC pesticides.  In addition to having the potential to cause 
goiter, a condition in which the thyroid gland is enlarged, this 
metabolite has produced birth defects and cancer in experimental 
animals.  ETU has been classified as a probable human carcinogen by the 
EPA (18).  ETU can be produced when EBDCs are used on stored produce, 
and also when fruit or vegetables with residues of these fungicides are 
cooked (8).

Reproductive Effects

     In a three-generation rat study with mancozeb at a dietary level of 
50 mg/kg there  was reduced fertility but no indication of embryo toxic 
or teratogenic effects.  In another study in which pregnant rats were 
exposed to mancozeb by inhalation, toxic effects on the pups were 
observed  only at doses (55 mg/m3) that were also toxic to the dams 

Teratogenic Effects

     No teratogenic effects were observed in a three-generation rat 
study with mancozeb at a dietary level of 50 mg/kg (16).  Specific 
developmental abnormalities of the body wall, central nervous system, 
eye, ear and musculoskeletal system were observed in experimental rats 
which were given 1,320 mg/kg of mancozeb on the 11th day of pregnancy 
(10).  When it was inhaled at concentrations of 0.017 milligrams per 
liter (mg/l), mancozeb was not teratogenic to pregnant rats (4).  
Teratogenic activity was found in mice given 1,320 mg/kg of maneb (11).

     In pregnant rats fed 5.0 mg/kg/day, the lowest dose tested, 
developmental toxicity was observed in the form of delayed hardening if 
the bones of the skull in offspring.  ETU has also been shown to be 
teratogenic in hamsters, but not in mice (18).

Mutagenic Effects

     A data gap exists in the information available on the mutagenicity 
of mancozeb and ETU.  Mancozeb was found to be mutagenic in one set of 
tests, while in another it did not cause mutations (13).  Mancozeb is 
thought to be similar to maneb, which was not mutagenic in a test called 
the Ames Test (4).

Carcinogenic Effects

     Ethylenethiourea (ETU), a metabolite of the class of chemicals in 
which mancozeb is included, has caused cancer in experimental animals 
and has been classified as a probable human carcinogen by the EPA (9, 
13, 18, 21).

Organ Toxicity

     Several studies of the effects of EBDCs on test animals have shown  
rapid reduction in the uptake of iodine and swelling of the thyroid 
(i.e. goiter).  In one study, a marked reduction  of iodine uptake was 
measured 24-hours after administration of a large dose of maneb, another 
EBDC fungicide.  A 90-day study of the effects of ETU, a common 
metabolite of the EBDCs on rat thyroids revealed a NOEL of 5 ppm (0.25 
mg/kg/day) (9, 16, 18).

Fate in Humans and Animals

     The EBDC fungicides break down in mammalian tissues into ethylene 
thiourea, ETU, a metabolite which has caused goiter and cancer in 
laboratory animals (9, 18).

     Research shows that mancozeb is rapidly absorbed into the body from 
the gastrointestinal tract, distributed to various target organs and 
almost completely excreted in 96 hours.  ETU is the major metabolite.  
After a single dose, less than one ppm ETU residues were measured in the 
thyroid and liver.  After 24 hours, these residues were not detectable 
(13).  Blood detection of ethylene bisdithiocarbamate is rarely 
possible, although there are methods for detecting the metabolite 
ethylene thiourea in urine (9).


Effects on Birds

     Mancozeb is slightly toxic to birds on an acute basis (13).  The 
lethal concentration fifty (LC50) is the concentration of a material in 
air or water that kills half of a population that is experimentally 
exposed to the chemical for a given time period.  The five-day LC50 for 
mancozeb in bobwhite quail and mallard ducklings is greater than 10,000 
ppm (4).  The EPA is currently reviewing data on the effects of mancozeb 
on bird reproduction (18).

Effects on Aquatic Organisms

     Mancozeb is generally toxic to fish.  It is highly poisonous to 
warmwater fish and at least moderately toxic to coldwater fish.  Many 
end-use product labels warn of its toxicity to fish (13).  The EPA is 
currently reviewing data on the potential toxic effects of mancozeb on 
aquatic organisms (18).

Effects on Other Animals (Nontarget species)

     Mancozeb is harmful to wildlife but not hazardous to honey bees 
(6).  The 72-hour LC50 for mancozeb in crayfish is greater than 40 ppm; 
the 48-hour LC50 is 3.5 ppm in tadpoles (4).


     The EBDCs are generally unstable in the presence of moisture, 
oxygen, and in biological systems (22).  They rapidly degrade to ETU.  
This rapid degradation lowers the need for concern about the 
environmental fate of EBDCs and focuses such concern on ETU.  The EPA 
has either called for or is currently reviewing data on the behavior of 
ETU in the environment (9, 14, 18).

Breakdown of Chemical in Soil and Groundwater

     Because mancozeb is practically insoluble in water it is unlikely 
to infiltrate groundwater (17, 20).  Studies do indicate that ETU, a 
metabolite of mancozeb, has the potential to move through the soil as a 
result of groundwater movement, in a process called leaching (13).  ETU 
has been detected at 16 ppb in only one out of 1,295 drinking water 
wells tested (18).

     The breakdown of mancozeb in soil is assumed to be comparable to 
that of maneb, which has a half-life of four to eight weeks under normal 
field conditions (4).

Breakdown of Chemical in Water

     Mancozeb degrades in water with a half-life of one to two days at 
pH 5, 7 and 9 (13).  It should be kept out of lakes, streams and ponds 
and should not be applied where runoff is likely to occur (4).  This 
fungicide should not be stored or thrown away near or in water, since 
storage or disposal of mancozeb in or near bodies of water can cause 
contamination (2).

Breakdown of Chemical in Vegetation

     When used as directed, mancozeb is not poisonous to plants (6).  A 
24-hour reentry interval is required in mancozeb-treated crops because:  
(1) the fungicide is registered on crops which may present a great deal 
of residue exposure and (2) the mancozeb metabolite, ETU, has been shown 
to produce tumors, birth defects, cell mutations and thyroid effects 
(13).  The EBDCs can be broken down during  the cooking process as well 
as by natural environmental processes (14).


     Keep mancozeb out of reach of children, unprotected persons, 
livestock, and pets (4, 13).  Breathing of dust or spray mist from 
mancozeb should be avoided.  Contact with skin, eyes and clothing should 
also be avoided.  Protective clothing including long pants, long sleeve 
shirt, gloves, hat and boots should be worn during mixing, loading, 
application and early reentry into treated fields (13, 18).  Do not feed 
treated crop foliage to livestock (12).  Water, food or feed can be 
contaminated by storage or disposal of mancozeb near these commodities. 
Empty containers should not be reused.  They should be buried away from 
water supplies (2).

     Mancozeb is a grayish-yellow powder with a musty odor (19) which is 
practically insoluble in water as well as most organic solvents.  It is 
a polymer of maneb combined with zinc.  While it is relatively stable 
and noncorrosive under normal, dry storage conditions, it is decomposed 
at high temperatures by moisture and by acid.  Mancozeb may produce 
flammable products upon decomposition (4, 16).  It is also unstable in 
acidic conditions (7).  It should be stored in its original sealed 
containers in well-aired, dry storehouses or in shaded, aired places.  
The temperature of the material should not go above 25  to 30 degrees C.  
Mancozeb containers must be stacked so that air can move freely at the 
bottom and sides of piles.  As long as the product is stored in its 
unopened and undamaged original containers in well-ventilated places, 
its biological activity will remain stable for 2 years (2).

     Mancozeb is stable under most conditions. It may burn, but does not 
readily ignite, and containers may explode in the heat of a fire.  
Thermal decomposition products may include toxic oxides of carbon, 
nitrogen and sulfur.  Suspensions of mancozeb dust in the air can ignite 
or explode (19).

Occupational Exposure Limits:

OSHA:  5 mg/m3 ceiling (19)

ACGIH:  5 mg/m3 TWA (19)

NIOSH:  1 mg/m3 recommended TWA (19); 3 mg/m3 recommended STEL (19)

TLV:  5 mg (Mn)/m3 (1)

Physical Properties:

CAS #:  8018-01-7

H20 solubility:  dispersible, but practically insoluble in water (7, 8, 

Solubility in other solvents:  practically insoluble in most organic 
solvents (8)

Melting point:  Decomposes without melting (7)

Vapor pressure:  Less than 10 to the minus 5 power mbar at 20 degrees C

Chemical Class/Use:  Carbamate fungicide; Ethylene bisdithiocarbamate 


Du Pont Agricultural Products
Walker's Mill, Barley Mill Plaza
PO Box 80038
Wilmington, DE, 19880-0038

Review by Basic Manufacturer:

Comments solicited:  October, 1992
Comments received:  November, 1992


(1)  American Conference of Governmental Industrial Hygienists.  1986. 
Documentation of the threshold limit values and biological exposure 
indices for 1985-86.  Fifth edition.  Cincinnati, OH:  Publications 
Office, ACGIH.

(2)  Berg, G. L., ed.  1988.  Farm chemicals handbook.  Willoughby, OH:  
Meister Publishing Co.

(3)  Cornell University.  1987.  1988 New York State pesticide 
recommendations.  Forty-ninth annual pest control conference.  Nov. 9, 
10, 11.  Ithaca, NY.

(4)  DuPont de Nemours and Company.  1983.  Technical data sheet for 
mancozeb.  Biochemicals Department.  Wilmington, DE:  DuPont.

(5)  Hallenbeck, W. H. and K. M. Cunningham-Burns.  1985.  Pesticides 
and human health.  Springer-Verlag.

(6)  Harding, W. C.  1979.  Pesticide profiles, part one:  insecticides 
and miticides.  University of Maryland.  Cooperative Extension Service. 
Bulletin 267.

(7)  Hartley, D. and H. Kidd.  1983.  The agrochemicals handbook.  
Nottingham, England:  Royal Society of Chemistry.

(8)  McEwen, F. L. and G. R. Stephenson.  1979.  The use and 
significance of pesticides in the environment.  NY:  John Wiley and 
Sons, Inc.

(9)  Morgan, D. P.  1982 (Jan.).  Recognition and management of 
pesticide poisonings.  Third edition.  Washington, DC:  U.S. 
Environmental Protection Agency. U.S. Government Printing Office.

(10)  National Institute of Safety and Health (NIOSH).  1986.  Registry 
of toxic effects of chemical substances (RTECS).

(11)  Shepard, T.  1986.  Catalog of teratogenic agents.  Fifth edition. 
Baltimore, MD:  The Johns Hopkins University Press.

(12)  Thomson, W. T.  1985.  Agricultural Chemicals.  Book IV.  
Fungicides. Fresno, CA:  Thomson Publications.

(13)  U. S. Environmental Protection Agency.  1987 (April).  Pesticide 
fact sheet: Mancozeb.  Registration Standard.  Office of Pesticides and 
Toxic Substances.  Office of Pesticide Programs.  Washington, DC.

(14)  Wagner, S. L.  1983.  Clinical toxicology of agricultural 
chemicals.  Environmental Health Sciences Center.  Oregon State 
University.  NJ:   Noyes Data Corporation.

(15)  Worthing, C. R., ed.  1983.  The pesticide manual:  a world 
compendium. Croydon, England:  The British Crop Protection Council.

(16)  Hayes, W.J. and E.R. Laws (ed.).  1990.  Handbook of Pesticide 
Toxicology, Vol. 3, Classes of Pesticides.  Academic Press, Inc., NY.

(17)  Meister, R.T. (ed.).  1992.  Farm Chemicals Handbook '92.  Meister 
Publishing Company, Willoughby, OH.

(18)  US EPA.  1992 (March 2).  Ethylene bisdithiocarbamates (EBDCs); 
Notice of intent to cancel and conclusion of Special Review.  Federal 
Register 57(41):7434-7530.  US GAO, Washington, DC.

(19)  Occupational Health Services, Inc.  1991 (May 1).  MSDS for 
Mancozeb.  OHS Inc., Secaucus, NJ.

(20)  U. S. Department of Agriculture, Soil Conservation Service.  1990 
(Nov).  SCS/ARS/CES Pesticide Properties Database: Version 2.0 
(Summary).  USDA - Soil Conservation Service, Syracuse, NY.

(21)  US Environmental Protection Agency.  1988 (Oct.).  Guidance for 
the Registration of Pesticide Products Containing Maneb as the Active 
Ingredient.  Office of Pesticides and Toxic Substances, US EPA, 
Washington, DC.

(22)  US Environmental Protection Agency.  1988 (Oct.).  Guidance for 
the Reregistration of Pesticide Products Containing Metiram as the 
Active Ingredient.  Office of Pesticides and Toxic Substances, US EPA, 
Washington, DC.

     This PIP is part of the EXTOXNET Pesticide Information Notebook.  
For more information, contact the Pesticide Management Education 
Program, Cornell University, 5123 Comstock Hall, Ithaca, NY  14853-0901.

DISCLAIMER:  The information in this profile does not in any way replace 
or supersede the information on the pesticide product label/ing or other 
regulatory requirements.  Please refer to the pesticide product