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Thiram

Publication Date: 9/93

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

  1. Hayes, W.J. and E.R. Laws (ed.). 1990. Handbook of Pesticide Toxicology, Vol. 3, Classes of Pesticides. Academic Press, Inc., NY.
  2. Hallenbeck, W. H. and K. M. Cunningham-Burns. 1985. Pesticides and human health. Springer-Verlag.
  3. Howard, P.H. (ed.). 1989. Handbook of Environmental Fate and Exposure Data for Organic Chemicals, Vol. III: Pesticides. Lewis Publishers, Chelsea, MI.
  4. 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).
  5. Meister, R.T. (ed.). 1992. Farm Chemicals Handbook '92. Meister Publishing Company, Willoughby, OH.
  6. 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.
  7. National Institute of Safety and Health (NIOSH). 1986. Registry of toxic effects of chemical substances (RTECS).
  8. Occupational Health Services, Inc. 1991 (May 3). MSDS for Thiram. OHS Inc., Secaucus, NJ.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Wagner, S.L. 1983. Clinical toxicology of agricultural chemicals. Environmental Health Sciences Center. Oregon State University. NJ: Noyes Data Corporation.