E X T O X N E T
Extension Toxicology Network
A Pesticide Information Project of Cooperative Extension Offices of
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University of California at Davis. Major support and funding was provided
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Assessment Program.
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Pesticide
Information
Profile
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Zineb
Publication Date: 9/93
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TRADE OR OTHER NAMES
Some trade names include Zinc ethylenebisdithiocarbamate (EBDC), Chem
Zineb, Devizeb, Discon-Z, Dithane Z-78, Lodaco, Mancozan, Parazate, Parzate,
Tiezene, Zebtox, Ziden, Zinosan, Aspor, Dipher, Hexathane, Kypzin and Lonacol.
REGULATORY STATUS
Zineb 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 zineb 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 home
garden uses of EBDCs have been canceled because the EPA has assumed that home
users of these pesticides do not wear protective clothing during application
(26). Toxicity data reviewed by the EPA as part of their Special Review of
EBDCs are included in this document under "Toxicological Effects."
A preharvest interval of 5 to 40 days, depending on the crop, is required
after application of zineb (24).
INTRODUCTION
The EBDCs are fungicides used to prevent crop damage in the field and to
protect harvested crops from deterioration in storage or transport (27).
Zineb is used to protect fruit and vegetable crops from a wide range of
foliar and other diseases. It is available in the U.S. as wettable powder and
dust formulations. Zineb can be formed by combining nabam and zinc sulfate in
the spray tank (22, 23).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
Zineb is slightly to moderately toxic when ingested (4, 22, 25).
Following a single large dose of zineb, rats and mice exhibited
incoordination, hyperactivity followed by inactivity, loss of muscle tone and
loss of hair (7, 22, 25). Sheep died within three weeks of being given oral
doses of 500 mg/kg of zineb.
In spray or dust forms, the EBDCs are moderately irritating to the skin
and to respiratory mucous membranes. poisoning from this class of chemicals
include itching, scratchy throat, sneezing, coughing, inflammation of the nose
or throat and bronchitis (10, 25, 29). Early symptoms from exposure of humans
to inhalation of zineb include tiredness, dizziness and weakness. More severe
symptoms include headache, nausea, fatigue, slurred speech, convulsions and
unconsciousness (25). There is no evidence of 'neurotoxicity,' that is nerve
tissue destruction or behavioral change, from the EBDCs (29). However, EBDCs
are partially chemically broken down, or metabolized, to carbon disulfide, a
neurotoxin capable of damaging nerve tissue (7). EBDC residues in or on foods
convert readily to ETU during commercial processing or home cooking (27).
Zineb is a skin and eye irritant and a dermal sensitizer. Cross
sensitization with maneb and mancozeb may occur (25). Mucous membrane
irritation has also been reported in humans (6). Absorption of large amounts
of zineb through the skin can lead to the same acute symptoms caused by
inhalation exposure (25).
The oral LD50 for zineb in rats is 1,850 to 8,900 mg/kg, for mice is
7,600 to 8,200 to 8,900 mg/kg, and 4,450 mg/kg for rabbits. The LClo
(inhalation) in rats is 800 mg/m3/4 hours. The dermal LD50 in rats is over
2,500 mg/kg, the highest dose that it is possible to administer (2, 11, 22, 23, 25).
CHRONIC TOXICITY
The survival, growth, and blood chemistry of dogs were not affected by
dietary levels up to 250 mg/kg for one year. However, thyroid size and weight
increases were observed at this dose level. No effects on the thyroid were
detected at 100 mg/kg (9, 22). In a two year study of rats fed 500 mg/kg,
diminished growth, kidney pathology, and increased thyroid weight and size
were observed (22). Sheep showed no adverse effects from dosages of 100 and
250 mg/kg/day for 19 weeks (22).
Occupational exposure to inhalation of zineb can lead to changes in liver
enzymes, moderate anemia and other blood changes, increased incidence of
poisoning symptoms during pregnancy, and chromosomal changes in the
lymphocytes (25). Liver functioning was affected in workers exposed to zineb.
Moderate anemia and other blood changes were also reported in 150 workers
exposed to zineb in a chemical plant (9). A five-month study of zineb showed
that concentrations of 20 and 200 mg/m3 caused a decrease in the activity of
cholinesterase, an essential enzyme of the nervous system. A maximum
permissible working air concentration of 0.5 mg/m3 is recommended by some
researchers (4).
Repeated or prolonged dermal exposure may cause dermatitis or
conjunctivitis (25). Farm workers who were repeatedly exposed to zineb, in
fields sprayed with 0.5% suspension of the fungicide, reported severe and
extensive contact dermatitis (19).
Ethylene bisdithiocarbamate pesticides (EBDCs), which include zineb, 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 zineb 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 (26). ETU can be produced when EBDCs are used on stored
produce, and also when fruit or vegetables with residues of these fungicides
are cooked (30).
Conversion of EBDCs into ETU can occur inside of spray tanks, during
cooking of produce or processing of crops bearing EBDC residues, or as EBDCs
are metabolized within the body. Residues of the EBDCs and of ETU can readily
be removed from produce by washing or peeling.
Disulfiram is an EBDC which is used in the treatment of alcoholics to
produce an intolerance to alcohol. Ingestion of disulfiram and alcohol
together causes symptoms of nausea, vomiting, headache, excessive sweating and
chills. Other EBDC compounds may cause similar symptoms when combined with
alcohol (22).
Reproductive Effects
It is advisable that pregnant women avoid exposure to zineb, as it can
damage the fetus, as well as cause adverse reproductive system effects (7, 9).
A single intraperitoneal injection of four mg of zineb in mice, during the
second half of pregnancy, resulted in abortions and weak offspring. Oral
doses of zineb, at a rate of 100 mg/kg/day for two months or more, produced
sterility, resorption of fetuses, abnormal tails in offspring (9, 25).
After oral ingestion, similar concentrations of ETU, a metabolite of
zineb, were found in both maternal and fetal tissues of rats. In pregnant
rats fed 5.0 mg/kg/day, the lowest dose tested, developmental toxicity was
observed in the form of delayed hardening of the skull bones in offspring.
Teratogenic Effects
Zineb is metabolized, or broken down chemically, to ethylene thiourea
(ETU), a chemical which can cause abnormal fetal development (7). Offspring
of rats given a near lethal oral dose of 2,000 mg/kg/day of zineb on days 11
or 13 of pregnancy, showed a high incidence of skeletal malformations, as well
as defects in the closing of the neural tube, an embryonic tube that
eventually develops into the brain and spinal cord (12). A single oral dose
of 8,000 mg/kg to rats on day 11 of gestation produced numerous deformities in
the offspring (22). Teratogenic tendencies were also seen when pregnant mice
were given intraperitoneal injections of 150 mg/kg. The teratogenic no-
observable effect level (NOEL) in rats was found to be 1,000 mg/kg for zineb
administered in single, daily oral doses (4).
ETU, the primary metabolite of zineb and other EBDC pesticides, has been
shown to be teratogenic in hamsters, but not in mice (26).
Mutagenic Effects
One of zineb's metabolites, ETU, is known to cause mutations (7).
Carcinogenic Effects
Liver and thyroid cancer, goiter, mutagenesis, and the development of
deformities, or 'teratogenesis,' can be caused by ETU, a chemical metabolite
of zineb (7).
Available data clearly show that low doses of zineb are not carcinogenic.
Very high doses have caused tumors in some test animals. In two strains of
mice, the maximum tolerated lifetime dose of zineb did not cause tumors. Oral
doses of 3,500 mg/kg/week for 6 weeks caused one of two mice strains tested to
develop benign lung tumors after three weeks (22). Two rat feeding studies
showed no evidence of tumor formation (23).
All of the EBDC pesticides can be degraded or metabolized into ethylene
thiourea (ETU), which has been classified as a probable human carcinogen by
the EPA (26, 27). Liver and thyroid cancer can be produced by ETU (7).
Marked increases in the incidence of liver tumors were observed in mice fed
32.3 mg/kg of ETU daily for 80 weeks. Rats fed 8.75 or 17.5 mg/kg daily for
18 months developed malignant thyroid tumors. In rats fed ETU at doses of 0.1,
1.25, 6.25, 12.5 or 25 mg/kg/day ppm for nearly 2 years, a dose related
increase in thyroid tumors was observed at the 12.5 and 25 mg/kg doses.
Female mice fed doses of 16.7 or 50 mg/kg/day ETU for up to 2 years exhibited
58 and 96% incidence of malignant liver tumors, respectively. In this same
study, there was also a significant increase in the incidence of thyroid
tumors at the 50 mg/kg dose level (26).
Organ Toxicity
Inhalation exposure to zineb may decrease the size of the bronchial
passages (9). Zineb appears to be harmful to the thyroid, liver and various
muscles. Liver and kidney injury was observed in autopsies done on sheep that
died after a three-week exposure to oral doses of 500 mg/kg zineb (9).
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) (22, 24, 29).
Fate in Humans and Animals
Approximately 68 to 74% of ingested material was recovered unchanged in
the feces, after administration at various dietary levels. It is estimated
that only 11 to 17% of an oral dose of zineb was absorbed into the body from
the gastrointestinal tract of the rat (9, 22). In general, the EBDC compounds
are so rapidly metabolized and excreted from the body, that blood detection is
difficult. There are, however, ways of detecting ethylene thiourea in urine
(10).
The ethylene bisdithiocarbamates break down in mammalian tissues into
ethylenethiourea, the metabolite which has caused goiter and cancer in
laboratory animals (9, 26).
ECOLOGICAL EFFECTS
Zineb is closely related to another fungicide, maneb, as they are both in
the same chemical class, ethylene-bis-dithiocarbamates (EBDCs). EBDCs are
noted for their environmental instability. In other words, they are readily
degraded in the environment and in mammalian tissue, into a variety of
breakdown byproducts, called 'degradates' or 'metabolites.' When heat is
applied to these chemicals, some of them are converted directly into ethylene.
Ethylene traces, or 'residues,' are commonly found on spinach and oranges.
Both cooking and naturally-occurring environmental processes can cause EBDCs
to break down in this way. Eleven to 26% of the original compound is believed
to be broken down by cooking to ethylenethiourea (ETU). ETU is a teratogen, a
chemical that has the potential to cause deformities in unborn offspring (19).
Based on this potentially harmful quality of zineb's chemical class, extra
care must be taken to both protect harvesters in treated fields, and to remove
fungicidal residues from harvested crops (10).
Zineb varies in its toxicity to animals, birds, and fish; it is more
toxic to fish than it is to birds.
Effects on Birds
Zineb is practically non-toxic to birds. The oral LD50 for zineb in
mallards and young pheasants is greater than 2,000 mg/kg (14).
Effects on Aquatic Organisms
The threshold value for perch-or the amount that these fish can tolerate
before toxicological effects appear-is 2 mg/l (or 2 ppm). For roach it is six
to eight mg/l (8).
Effects on Other Animals (Nontarget species)
Zineb is non-toxic to bees (1, 8, 23). Little or no reduction in the
numbers of beneficial predatory and parasitic arthropods was seen when zineb
was used in Nova Scotian orchards at recommended dosages. Mites appear to be
sensitive to zineb (11).
ENVIRONMENTAL FATE
The EBDCs are generally unstable in the presence of moisture, oxygen, and
in biological systems (28). 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, 19, 24).
Breakdown of Chemical in Soil and Groundwater
Zineb is subject to chemical breakdown (hydrolysis) and does not persist
in soil. It adsorbs strongly to soil particles and is usually does not move
below the upper layer of soil. For this reason, zineb is unlikely to
contaminate groundwater. Its bioactive half-life in the field is 16 days.
Within 4 months after a field planted with alfalfa was sprayed, 99.7% of the
applied zineb was lost (11, 20, 24). Results of an EPA review indicate that
zineb and/or its breakdown products have the potential to leach into
groundwater (15).
ETU, a metabolite of zineb, has been detected at 16 ppb in only one out
of 1,295 drinking water wells tested (26).
Breakdown of Chemical in Water
Zineb is practically insoluble in water (4). It is unstable in water and
hydrolyzes rapidly, producing ETU and other metabolites (24).
Breakdown of Chemical in Vegetation
Zineb is generally not poisonous to plants, except in zinc-sensitive
varieties, such as tobacco and cucurbits. Pears have been slightly injured by
this fungicide in a few cases (13). Ethylene thiourea (ETU) is the major
zineb metabolite in plants (8).
PHYSICAL PROPERTIES AND GUIDELINES
Zineb is a light-colored powder or crystal (4, 9, 23). It decomposes
when exposed to light, heat, and moisture (24, 21). Zineb should be stored in
a cool, dry place. Prolonged storage can contribute to its instability, if
conditions are not appropriate. Zineb does not ignite readily, but poses a
slight fire hazard when exposed to heat and flame (25). It should be kept
away from strong oxidizers, excessive heat, flames and sparks. Thermal
decomposition may release toxic oxides of nitrogen and sulfur. Zineb is
noncorrosive in the dry state, but in the presence of moisture, zineb is
corrosive to iron and copper (8, 25). It is not compatible with alkaline or
mercury compounds, although it is compatible with other fungicides and
insecticides (13). Zineb containers should not be reused (1).
Occupational Exposure Limits:
Occupational exposure limits for zineb have not been established by OSHA,
ACGIH or NIOSH (25).
Physical Properties:
| CAS #: | 12122-67-7 |
| H20 solubility: | practically insoluble in water (23); 10 mg/liter at room temperature (8) |
| Solubility in other solvents: | soluble in carbon disulfide, slightly soluble in pyridine (21, 23); practically insoluble in common organic solvents (8, 23) |
| Melting point: | Zineb decomposes before melting (21, 23) |
| Vapor pressure: | Negligible at room temperature (21); Less than 10 minus 7 mbar at 20 degrees C (8) |
| Kow: | log Kow: 1.78 (18) |
| Degradation rate constant (days-1): | 0.0512 (18) |
| Chemical Class/Use: | ethylene bisdithio-carbamate fungicide |
BASIC MANUFACTURERS
Rhone Poulenc Ag. Co.
PO Box 12014
2 T.W. Alexander Dr.
Research Triangle Park, NC 27709
Review by Basic Manufacturer:
Comments solicited: November, 1992
Comments received:
REFERENCES
Agway, Inc. Material safety data sheet on zineb formulations. No
date given. Chemical Division. Syracuse, NY.
Berg, G. L. (ed.). 1986. Farm chemicals handbook. Willoughby, OH:
Meister Publishing Co.
Pesticide Management and Education. An on-line pesticide information
database in CENET, Cornell Cooperative Extension Network. Cornell University,
Ithaca, NY.
Clayton, G. D. and F. E. Clayton (eds.). 1981. Patty's industrial
hygiene and toxicology. Third edition. Vol. 2: Toxicology. NY: John Wiley
and Sons.
Cornell University. 1987. 1988 New York State pesticide
recommendations. Forty-ninth annual pest control conference. Nov. 9, 10, 11.
Ithaca, NY.
Gosselin, R. E., et al. 1984. Clinical toxicology of commercial
products. Fifth edition. Baltimore, MD: Williams and Wilkins.
Hallenbeck, W. H. and K. M. Cunningham-Burns. 1985. Pesticides and
human health. NY: Springer-Verlag.
Hartley, D. and H. Kidd (eds.). 1983. The agrochemicals handbook.
Nottingham, England: Royal Society of Chemistry.
Hayes, W. J. 1982. Pesticides studied in man. Baltimore, MD:
Williams and Wilkins.
Morgan, D. P. 1982 (Jan.). Recognition and management of pesticide
poisonings. Third edition. U.S. Environmental Protection Agency.
Washington, DC: U.S. Government Printing Office.
Pimentel, D. 1971 (June). Ecological effects of pesticides on
nontarget species. Executive Office of the President's Office of Science and
Technology. Washington, DC: U.S. Government Printing Office.
Shepard, T.H. 1986. Catalog of teratogenic agents. Fifth edition.
Baltimore, MD: The Johns Hopkins University Press.
Thomson, W.T. 1985. Agricultural chemicals. Book IV. Fungicides.
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Tucker, R. and D.G. Crabtree. 1970. Handbook of toxicity of
pesticides to wildlife. USDA Fish and Wildlife Service. Bureau of Sport
Fisheries and Wildlife.
U.S. Environmental Protection Agency. 1988. Memorandum from E.F.
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Pesticides and Toxic Substances. "Data call-in for small-scale retrospective
ground-water monitoring."
______. 1987 (May 13). Memorandum from E. Neil Pelletier. Status of
EBDC fungicide registrations. Office of Pesticides and Toxic Substances.
Science Support Branch. Benefits and Use Division (TS-768-C). Washington, DC.
Photocopy.
______. 1986 (June). Pesticides fact book. (A-107/86-003). Office
of Public Affairs. Washington, DC.
______. 1984 (Dec.). User's manual for the pesticide root zone model
(PRZM). Release 1. Athens, GA: Environmental Research Laboratory.
Wagner, S.L. 1983. Clinical toxicology of agricultural chemicals.
Environmental Health Sciences Center. Oregon State University. NJ: Noyes
Data Corporation.
Witt, J. M. (ed.). 1985. Chemistry, biochemistry, and toxicology of
pesticides. Proceedings of an Extension Service Short Course at Oregon State
University. Pest Control Education Program. Eugene, OR.
Worthing, C.R. (ed.). 1983. The pesticide manual: A world
compendium. Croydon, England: The British Crop Protection Council.
Hayes, W.J. and E.R. Laws (eds.). 1990. Handbook of Pesticide
Toxicology, Vol. 3, Classes of Pesticides. Academic Press, Inc., NY.
Meister, R.T. (ed.). 1992. Farm Chemicals Handbook '92. Meister
Publishing Company, Willoughby, OH.
Howard, P.H. (ed.). 1989. Handbook of Environmental Fate and
Exposure Data for Organic Chemicals, Vol. III: Pesticides. Lewis Publishers,
Chelsea, MI.
Occupational Health Services, Inc. 1991 (21 Feb.). MSDS for Zineb. OHS
Inc., Secaucus, NJ.
U.S. Environmental Protection Agency. 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.
U.S. 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.
U.S. 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.
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.
McEwen, F.L. and G.R. Stephenson. 1979. The use and significance of
pesticides in the environment. NY: John Wiley and Sons, Inc.
Disclaimer: Please read
the pesticide label prior to use. The information contained at this web
site is not a substitute for a pesticide label. Trade names used herein
are for convenience only; no endorsement of products is intended, nor is
criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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