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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Pesticide
Information
Profile
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Thiram
Publication Date: 9/93
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TRADE OR OTHER NAMES
The full chemical name for thiram is tetramethylthiuram disulfide.
Common names include thiram (USA), thiuram (Japan), and TMTD (USSR), TMT and
TMTDS. Trade names include AAtack, Arasan, Aules, Fermide 850, Fernasan, FMC
2070, Hexathir, Mercuram, Micropearls, Nomersan, Pomarsol, Puralin, Rezifilm,
Rhodiasan Express, Spotrete, Tersan, Thiosan, Thiotex, Thiramad, TMTD 50
Borches, Thirasan, Thirame, Thiuramin, Tiuramyl, Tirampa, TMTC, Trametan,
Tuads and Tulisan (1, 5)
REGULATORY STATUS
Thiram 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 thiram 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
(10). Toxicity data reviewed by the EPA as part of their Special Review of
EBDCs are included in this document under "Toxicological Effects."
Pesticide products containing thiram must bear the signal word "Caution"
on the product label (5).
INTRODUCTION
Thiram belongs to the ethylene bisdithiocarbamate (EBDC) chemical class.
The EBDCs are fungicides used to prevent crop damage in the field and to
protect harvested crops from deterioration in storage or transport (7).
Thiram is used as a seed protectant and to protect fruit, vegetable,
ornamental and turf crops from a variety of fungal diseases. It is also used
as an animal repellent to protect fruit trees and ornamentals from damage by
rabbits, rodents and deer. Thiram is available as dust, flowable, wettable
powder, water dispersible granules, and water suspension formulations and in
mixtures with other fungicides (1, 5).
Thiram has been used in the treatment of human scabies, as a sun screen
and as a bactericide applied directly to the skin or incorporated into soap
(1).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
Thiram is moderately toxic by ingestion, but it is highly toxic if
inhaled. Acute exposure in humans may cause headaches, dizziness, fatigue,
nausea, diarrhea and other gastrointestinal complaints. In rats and mice,
large doses of thiram produced muscle incoordination, hyperactivity followed
by inactivity, loss of muscular tone, labored breathing and convulsions.
Most animals died within 2 to 7 days (1, 8).
Thiram is irritating to the eyes, skin and respiratory tract. It is a
skin sensitizer. Symptoms of acute inhalation exposure to thiram include
itching, scratchy throat, hoarseness, sneezing, coughing, inflammation of the
nose or throat, bronchitis, dizziness, headaches, fatigue, nausea, diarrhea
and other gastro-intestinal complaints. Persons with chronic respiratory or
skin disease are at increased risk from exposure to thiram (4, 8, 10).
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 stomach pains, nausea, vomiting, headache, and
slight fever. Other EBDC compounds may cause similar symptoms when combined
with alcohol (1). Workers exposed to thiram during application or mixing
operations within 24-hours of moderate alcohol consumption have been
hospitalized with symptoms. Exposure to EBDCs in combination with alcohol can
cause dermatitis (1).
EBDCs are partially chemically broken down, or metabolized, to carbon
disulfide, a neurotoxin capable of damaging nerve tissue (2). EBDC residues
in or on foods convert readily to ETU during commercial processing or home
cooking (11).
The lethal concentration fifty, or LC50, is that concentration of a
chemical in air or water that kills half of the experimental animals exposed
to it for a set time period. The 4-hour inhalation LC50 for thiram is 500
mg/m3. Concentrations of 1,500 mg thiram/m3 of air or higher are an immediate
threat to life or health. 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 thiram in rats is 560 to
1000 mg/kg, in mice is 1,350 mg/kg, in rabbits is 210 mg/kg, and in cats is
230 mg/kg. The dermal LDlo for rabbits is 1 gm/kg and the dermal LD50 is
greater than 5,000 mg/kg (2, 5).
CHRONIC TOXICITY
In addition to the symptoms of acute exposure, symptoms of chronic
exposure to thiram in humans include drowsiness, confusion, loss of sex drive,
incoordination, slurred speech and weakness. Repeated or prolonged exposure
to thiram can also cause allergic reactions such as dermatitis, watery eyes,
sensitivity to light and conjunctivitis (1, 8).
Except for the occurrence of allergic reactions, harmful chronic effects
from thiram have been observed in test animals only at very high dosages. In
one study, a dietary dose of 125 mg/kg/day thiram was fatal to all rats within
17 weeks. Levels of 1,000 ppm (about 49 mg/kg/day) fed to rats for two years
did not cause death, but did produce weakness, muscle incoordination and
paralysis of the hind legs. The NOEL for this study was 100 ppm (4.9
mg/kg/day). Rats fed 52-67 mg/kg/day for 80 weeks exhibited hair loss and
paralysis and atrophy of the hind legs. Symptoms of muscle incoordination and
paralysis from thiram poisoning have been shown to be associated with
degeneration of nerves in the lower lumbar and pelvic regions. Day-old white
leghorn chicks fed 30 and 60 ppm for 6 weeks exhibited bone malformations. In
a one year feeding study with dogs, the NOEL was 200 (about 4 mg/kg/day) (1).
At doses of 0.1 of the LD50 for 15 days, thiram in rabbits reduced blood
platelet and white blood cell counts, suppressed blood formation and slowed
blood coagulation (1).
Ethylene bisdithiocarbamate pesticides (EBDCs), which include thiram,
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 thiram 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 (10). ETU can be produced when EBDCs are used on stored
produce, and also when fruit or vegetables with residues of these fungicides
are cooked (4).
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.
Reproductive Effects
Oral doses of approximately 1,200 mg/kg/day thiram to mice on days 6 to
17 of pregnancy caused resorption of embryos, retarded fetal development, and
cleft palate, wavy ribs, and curved long bones of the legs in offspring. This
dose is higher than the LD50 for thiram in rats (see Acute Toxicity). In
another study, doses of 132 mg/kg/day for 13 weeks produced infertility in
male mice, while doses of 96 mg/kg for 14 days delayed the estrous cycle in
females (1). The feeding of 1,000 ppm thiram from day 16 of pregnancy to 21
days after birth caused reduced growth and survival of the pups. Pups that
were transferred to untreated dams at birth remained healthy, while pups
transferred from untreated to treated dams were injured (1).
Teratogenic Effects
Maternal doses of 125 mg/kg thiram were teratogenic in hamsters, causing
incomplete formation of the skull and spine, fused ribs, abnormalities of the
legs, heart, great vessels and kidneys (1).
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 (10).
Mutagenic Effects
Thiram has been found to be mutagenic in some test organisms but not in
others (1).
Carcinogenic Effects
When administered to mice at the highest dose possible, thiram was not
carcinogenic (1). Dietary levels as high as 125 mg/kg/day for two years did
not cause tumors in rats (1).
Thiram can react with nitrate under mildly acidic conditions, like those
in the human stomach, to form n-nitroso-dimethylamine, which has been shown to
be carcinogenic in test animals (8).
All of the EBDC pesticides can be degraded or metabolized into
ethylenethiourea (ETU), which has been classified as a probable human
carcinogen by the EPA (10, 11). 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 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 (10).
Organ Toxicity
Two independent studies have shown evidence of damage to the liver by
thiram in the form of decreased enzyme activity and increased liver weight
(1). Thiram may also cause damage to the nervous system, blood, liver and
kidneys (8).
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) (1, 3).
Fate in Humans and Animals
In the body, carbon disulfide is formed from thiram and contributes to
the toxicity of thiram to the liver (1).
The ethylene bisdithiocarbamates break down in mammalian tissues into
ethylenethiourea, the metabolite which has caused goiter and cancer in
laboratory animals (10, 9).
ECOLOGICAL EFFECTS
Effects on Birds
No information was found.
Effects on Aquatic Organisms
Thiram is toxic to fish (5). Thiram is not expected to bioconcentrate
in aquatic organisms (3).
Effects on Other Animals (Nontarget species)
Thiram is non-toxic to bees (5).
ENVIRONMENTAL FATE
The EBDCs are generally unstable in the presence of moisture, oxygen,
and in biological systems (12). 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 (10, 13).
Breakdown of Chemical in Soil and Groundwater
Thiram is nearly immobile in clay soils or in soils high in organic
matter. Because it is only slightly soluble in water (30 mg/l) and has a
strong tendency to adsorb to soil particles (Koc = 383 g/ml), thiram is not
expected to contaminate groundwater. The soil half-life for thiram is 15
days. Thiram degrades more rapidly in acidic soils and in soils high in
organic matter. In a humus sandy soil, at pH 3.5 , thiram decomposed after 4
to 5 weeks, while at pH 7.0, thiram decomposed after 14 to 15 weeks. Thiram
persisted for over two months in a sandy soils, but disappeared within one
week from a compost soil. The major metabolites of thiram in the soil are
copper dimethyl-dithiocarbamate, dithiocarbamate, dimethylamine and carbon
disulfide (3, 9).
In soil, thiram will decompose by microbial action or by hydrolysis
under acidic conditions. Thiram will adsorb strongly to soils and will not
volatilize from wet or dry soil surfaces (3).
Breakdown of Chemical in Water
In water, thiram is rapidly broken down by hydrolysis and
photodegradation, especially under acidic conditions. Thiram may adsorb to
suspended particles or to sediment (3).
ETU, a metabolite of thiram, has been detected at 16 ppb in only one out
of 1,295 drinking water wells tested (10).
Breakdown of Chemical in Vegetation
No information was found.
PHYSICAL PROPERTIES AND GUIDELINES
Thiram is a white to yellow crystalline powder with a characteristic
odor (8).
Thiram is stable under normal temperatures and pressures, but it poses a
slight fire hazard when exposed to heat or flame. It does not ignite readily,
but it may burn. Containers may explode in the heat of a fire (8).
Occupational Exposure Limits:
| OSHA: | 5 mg/m3 TWA (8) |
| ACGIH: | 1 mg/m3 TWA (8) |
| NIOSH: | 5 mg/m3 recommended TWA (8) |
Physical Properties:
| CAS #: | 137-26-8 (3) |
| Specific gravity: | 1.29 at 20 degrees C (8) |
| H20 solubility: | slightly soluble in water; 30 mg/l at 25 degrees C (2, 3) |
| Solubility in other solvents: | Slightly soluble in carbon disulfide, diethyl ether and ethanol.
Soluble in acetone and chloroform and most organic solvents.
Insoluble in dilute alkali, gasoline and aliphatic hydrocarbons (2, 8). |
| Soil half-life: | 15 days (9) |
| Melting point: | 155-156 degrees C (311-315 degrees F) (1, 3, 8) |
| Boiling point: | 129 degrees C (264 degrees F) at 20 mm Hg (3, 8) |
| Flashpoint: | 138 degrees C (280 degrees F) (8) |
| Vapor pressure: | Negligible at 20 degrees C (8). Less than 7.5 x 10-6 mm Hg at 25 degrees C (3) |
| Soil Koc: | 383 g/ml (9) |
| Chemical Class: | EBDC/thiocarbamate |
BASIC MANUFACTURER
Atochem North America, Inc.
Three Parkway, Room 619
Philadelphia, PA 19102
Review by Basic Manufacturer:
Comments solicited: October, 1992
Comments received:
REFERENCES
Hayes, W.J. and E.R. Laws (ed.). 1990. Handbook of Pesticide
Toxicology, Vol. 3, Classes of Pesticides. Academic Press, Inc., NY.
Hallenbeck, W. H. and K. M. Cunningham-Burns. 1985. Pesticides and
human health. Springer-Verlag.
Howard, P.H. (ed.). 1989. Handbook of Environmental Fate and
Exposure Data for Organic Chemicals, Vol. III: Pesticides. Lewis Publishers,
Chelsea, MI.
McEwen, F. L. and G. R. Stephenson. 1979. The use and significance
of
pesticides in the environment. NY: John Wiley and Sons, Inc. National
Institute of Safety and Health (NIOSH). 1986. Registry of toxic effects of
chemical substances (RTECS).
Meister, R.T. (ed.). 1992. Farm Chemicals Handbook '92. Meister
Publishing Company, Willoughby, OH.
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.
National Institute of Safety and Health (NIOSH). 1986. Registry of
toxic effects of chemical substances (RTECS).
Occupational Health Services, Inc. 1991 (May 3). MSDS for Thiram.
OHS Inc., Secaucus, NJ.
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.
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.
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.
Wagner, S.L. 1983. Clinical toxicology of agricultural chemicals.
Environmental Health Sciences Center. Oregon State University. NJ: Noyes
Data Corporation.
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criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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