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.
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Pesticide
Information
Profile
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Metiram
Publication Date: 9/93
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TRADE OR OTHER NAMES
Carbatene, NIA 9102, Polyram, Polyram-Combi, Zinc metiram. Due to
changing regulations, these names may not be up-to-date; check with most
recent EPA approved common name/trade name source (i.e. National Pesticide
Information Retrieval System) or the Farm Chemicals Handbook for current trade
names.
REGULATORY STATUS
Metiram 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 metiram 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
(17). Toxicity data reviewed by the EPA as part of their Special Review of
EBDCs are included in this document under "Toxicological Effects."
Products containing metiram must display the signal word "Caution."
INTRODUCTION
The EBDCs are fungicides used to prevent crop damage in the field and to
protect harvested crops from deterioration in storage or transport (18).
Metiram is effective against a broad spectrum of fungi and is used to protect
fruits, vegetables, field crops, and ornamentals from foliar diseases and
damping off. In the U.S., use is limited to potatoes and roses (6, 12).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
Metiram is moderately toxic by ingestion (14). Metiram is not
significantly absorbed through the skin. Less than 1% of a 240 mg/kg dose,
applied topically, was absorbed through the skin of rats after 8 hours (16).
Metiram can cause skin and mucous membrane irritation. Skin, eye and
inhalation exposure should be avoided (3).
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 metiram in rats is 2,850 to 10,000 mg/kg, in mice
it is 2,630 to 5,400 mg/kg, in guinea pigs it is 2,400 to 4,800 mg/kg, and in
rabbits it is 620 mg/kg. Two hundred mg/kg was the largest dose which did not
cause symptoms in rabbits (3). The skin, or 'dermal' LD50 for metiram in
rabbits was greater than 8,000 mg/kg, and in rats it was greater than 2,000
mg/kg (1, 3, 12, 14).
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 (14, 20). There is no evidence of
'neurotoxicity', nerve tissue destruction or behavior change, from the EBDCs
(20). However, EBDCs are partially chemically broken down, or metabolized, to
carbon sulfide, a neurotoxin capable of damaging nerve tissue (19). EBDC
residues in or on foods convert readily to ETU during commercial processing or
home cooking (18).
CHRONIC TOXICITY
When rats were fed a 1,000 mg/kg diet of metiram for two weeks, five days
per week, no symptoms of illness were produced. However, damage to health,
including enlargement of the thyroid gland, was caused at 10,000 mg/kg (3).
No ill-effect was observed in dogs that received 45 mg/kg daily of the
fungicide for 90 days, or 7.5 mg/kg daily for 1.92 years (10). When metiram
was fed to rats at dietary doses of 0, 0.25, 1, 4, or 16 mg/kg, the only
effect observed was muscle atrophy in rats receiving 16 mg/kg. The NOEL level
in this study was 4 mg/kgday (16).
Prolonged or repeated exposure of the skin or eyes to metiram may cause
dermatitis or conjunctivitis (14).
Ethylene bisdithiocarbamate pesticides (EBDCs), which include metiram,
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 metiram 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 (17). ETU can be produced when EBDCs are used on stored
produce, and also when fruit or vegetables with residues of these fungicides
are cooked (21).
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 (21).
Reproductive Effects
Pregnant rats fed 80 and 160 mg/kg/day exhibited reduced rates of body
weight gain. Litter size was reduced for rats fed 0.25, 2 or 16 mg/kg
metiram. Rats receiving the 16 mg/kg dose also exhibited decreases in
parental body weight and in food consumption (16).
Teratogenic Effects
No teratogenic effects were found in female rats fed 0, 40, 80 and 160
mg/kg/day (16).
Teratogenic effects were seen in rats that were fed 10 mg/kg/day of the
principal breakdown product of metiram, ethylenethiourea (ETU) (9). In
pregnant rats fed ETU at 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 (17).
Mutagenic Effects
Metiram may be a mild mutagen. The majority of mutagenicity studies on
metiram have been negative. Out of six tests performed, only one highly
sensitive in vitro test indicated that metiram may be mutagenic (15, 16).
Carcinogenic Effects
All of the EBDC pesticides can be degraded or metabolized into
ethylenethiourea (ETU), which has been found to be cancer-producing in both
mice and rats and has been classified as a probable human carcinogen by the
EPA (9, 17, 18). Marked increases in the incidence of liver tumors were
observed in mice fed 32 mg/kg of ETU daily for 80 weeks. Rats fed 9 or 17.5
mg/kg daily for 18 months developed malignant thyroid tumors. In rats fed ETU
at doses of 0.1, 1.25, 7.5 or 25 mg/kg 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 17 or 50 mg/kg 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 (17).
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).
Enlargement of the thyroid gland was caused in rats fed 10,000 mg/kg of
metiram for two weeks (five days/week) (3). 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) (13, 20, 21).
Fate in Humans and Animals
Metabolic fate studies in rats indicate that metiram is readily absorbed
by the body and eliminated through the urine and feces. Residues remaining in
the body were highest in the kidneys, thyroid, and gastrointestinal tract and
were higher in females than in males (16).
The ethylene bisdithiocarbamates break down in mammalian tissues into
ethylenethiourea, ETU, a metabolite which has caused goiter and cancer in
laboratory animals (9, 17).
ECOLOGICAL EFFECTS
Effects on Birds
Metiram is slightly toxic to birds. The LC50 is the concentration of a
chemical in air or water that kills half of a population experimentally
exposed to it for a specific time period. The LC50 for both mallard ducks and
bobwhite quail is greater than 3712 ppm (12, 15, 16).
Effects on Aquatic Organisms
Metiram is slightly toxic to fish (6, 12). The LC50 for metiram in
harlequin fish is 32 mg/liter in 24-hours and 17 mg/l in 48-hours (3).
Effects on Other Animals (Nontarget species)
Metiram is practically nontoxic to bees; it can be used around bees with
minimum injury (5, 12, 15, 16).
ENVIRONMENTAL FATE
The EBDCs are generally unstable in the presence of moisture, oxygen, and
in biological systems (16). 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, 12, 13).
Breakdown of Chemical in Soil and Groundwater
Metiram is nearly insoluble in water (0.1 ug/ml), it adsorbs strongly to
soil particles (Koc = 500,000 g/ml), and it has a moderate a soil half-life
(20 days). Under normal conditions, metiram is not expected to contaminate
groundwater. It may enter surface waters if erosion of soil with adsorbed
metiram occurs (13).
Breakdown of Chemical in Water
ETU, the primary metabolite of metiram in water, has been detected at 16
ppb in only one out of 1,295 drinking water wells tested. The breakdown of
metiram to ETU is mainly by hydrolysis and not via photodegradation (15, 16, 17).
Breakdown of Chemical in Vegetation
Metiram is not poisonous to plants, when it is used at the recommended
rates of application (3). When the fungicide was applied at an excessive
rate, slight injury occurred on grapes and apples. Harvested crops do not
tend to have an off-flavor resulting from metiram use. Metiram has a
relatively long residual life (6).
PHYSICAL PROPERTIES AND GUIDELINES
Metiram is a noncorrosive, light yellow powder or solid, with an odor
typical of dithiocarbamates (1, 3, 12, 14). It is unstable to strong acids
and strong alkalis, or a combination of heat and moisture (3, 9). Metiram
may burn, but it does not ignite readily. Thermal decomposition products may
include toxic and corrosive fumes of ammonia, and toxic oxides of nitrogen and
sulfur (14).
Occupational Exposure Limits:
No occupational exposure limits for metiram have been established by
OSHA, ACGIH or NIOSH (14).
Physical Properties:
| CAS #: | 9006-42-2 |
| H20 solubility: | Practically insoluble in water (3, 14) -- 2.10-4 g/100 g water at 20 degrees C (12) |
| Solubility in other solvents: | soluble in pyridine (with decomposition) - practically insoluble in organic solvents (3, 12, 14) |
| Melting Point: | Decomposes above 120 degrees C (248 degrees F) (14) |
| Vapor pressure: | 7.5 x 10 to the minus 6 mm Hg (14). |
| Chemical Class/Use: | Carbamate - Ethylenebisdithiocarbamate/EBDC |
BASIC MANUFACTURER
BASF Corp.
Agricultural Products Group
PO Box 13528
Research Triangle Park, NC 27709-3528
Review by Basic Manufacturer:
Comments solicited: November, 1992
Comments received:
REFERENCES
Berg, G. L., ed. 1986. Farm Chemicals Handbook. Willoughby, OH:
Meister Publishing Company.
Cornell University. 1987. 1988 New York State pesticide
recommendations. Forty-ninth annual pest control conference. Nov. 9, 10, 11.
Ithaca, NY.
Hartley, D. and H. Kidd, eds. 1983. The Agrochemicals Handbook.
Nottingham, England: Royal Society of Chemistry.
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.
Morse, R. A. 1987. Bee poisoning. In 1988 New York State pesticide
recommendations. Forty-ninth annual pest control conference. Nov. 9, 10, 11.
Cornell University. Ithaca, NY.
Thomson, W. T. 1983. Herbicides. Agricultural Chemicals, Book II.
Fresno, CA: Thomson Publications.
USEPA. 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.
Wagner, S. L. 1983. Clinical toxicology of agricultural chemicals.
Environmental Health Sciences Center. Oregon State University. NJ: Noyes
Data Corporation.
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 (ed.). 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.
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.
Occupational Health Services, Inc. 1991 (21 Feb.). MSDS for Metiram.
OHS Inc., Secaucus, NJ.
US Environmental Protection Agency. 1988 (3 Oct.). Pesticide Fact
Sheet: Metiram. Office of Pesticides and Toxic Substances, US EPA,
Washington, DC.
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.
US 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.
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.
Hallenbeck, W. H. and K. M. Cunningham-Burns. 1985. Pesticides and
human health. Springer-Verlag.
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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