Methylthiouracil

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: If you spill this chemical, dampen the solid spill material with 5% ammonium hydroxide, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% ammonium hydroxide to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% ammonium hydroxide followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U164, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for METHYLTHIOURACIL (7 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for METHYLTHIOURACIL (9 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

THERE EXISTS AN INVERSE RELATIONSHIP BETWEEN IODINE CONTENT OF DIET & MTU THYROID TUMORIGENICITY.

METHYLTHIOURACIL ADMIN PROMOTED INDUCTION OF CERVICO-VAGINAL SARCOMAS & EPITHELIAL TUMORS BY LOCAL APPLICATION OF 9,10-DIMETHYL-1,2-BENZANTHRACENE.

METHYLTHIOURACIL ADMIN SIMULTANEOUSLY WITH CARBON TETRACHLORIDE PREVENTED CARBON TETRACHLORIDE-INDUCED CHRONIC HEPATOTOXICITY IN RATS.

THEOPHYLLINE POTENTIATES EFFECT OF THYROID STIMULATING HORMONE AT LEVEL OF THYROID ADENYL CYCLASE SYSTEM. GOITROGENIC EFFECT OF 0.05% METHYLTHIOURACIL WAS INCR BY SIMULTANEOUS ADMINISTRATION OF THEOPHYLLINE.

TERRESTRIAL FATE: If methylthiouracil is released to soil, it will be expected to be highly mobile in soil(1,SRC) based upon an estimated Koc of 138 which was calculated(2,SRC) from a water solubility of 533.2 mg/l at 25 °C(3) using a recommended regression equation(2,SRC). It may, therefore, leach to groundwater(1,SRC). It is not known whether the compound will photooxidize or biodegrade in soil or volatilize from moist near-surface soil(SRC). But it may slowly biodegrade in natural waters and soil based upon the slow biodegradation of the structurally similar 2-thiouracil by activated sludge from municipal treatment plants(4). Methylthiouracil should not be susceptible to hydrolysis in water based upon a measured neutral hydrolysis rate constant of 9.7X10-6 hr-1 at 25 °C which corresponds to a half-life of 8.8 years(5).

AQUATIC FATE: If it is released to water, methylthiouracil may be susceptible to direct photolysis in surface water based upon its absorption of light at wavelengths greater than 290 nm in methanol solution(1). It should not bioconcentrate in aquatic organisms based upon a BCF of 18 which can be calculated(3,SRC) for methylthiouracil from a water solubility of 533.2 mg/l at 25 °C(2) using a recommended regression equation(3). It should not adsorb to sediment or suspended particulate matter based upon a Koc of 138 which can be calculated(3,SRC) for methylthiouracil from a water solubility of 533.2 mg/l at 25 °C(2) using a recommended regression equation(3). It is not known whether the compound will photooxidize or biodegrade in water(SRC). But it may slowly biodegrade in natural waters and soil based upon the slow biodegradation of the structurally similar 2-thiouracil by activated sludge from municipal treatment plants(4,SRC). Methylthiouracil should not be susceptible to hydrolysis in water based upon a measured neutral hydrolysis rate constant of 9.7X10-6 hr-1 at 25 °C which corresponds to a half-life of 8.8 years(5).

ATMOSPHERIC FATE: Methylthiouracil may be susceptible to direct photolysis in the atmosphere based upon its absorption of light at wavelengths greater than 290 nm in methanol solution(1). Methylthiouracil will be expected to be susceptible to photooxidation in the atmosphere based upon an estimated rate constants for the vapor phase reactions of two of its possible tautomeric forms with photochemically produced hydroxyl radicals and ozone(2,3,SRC). The overall half-lives for the vapor phase reaction of these possible forms of the compound with photochemically produced hydroxyl radicals and ozone have been estimated to range between 2.1 and 3.8 hr at atmospheric concentrations of 5X10+5 hydroxyl radicals per cu cm and 7X10+11 ozone molecules per cu cm(2,3,SRC).

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Based upon a water solubility of 533.2 mg/l at 25 °C(1), a Koc of 138 can be calculated for methylthiouracil using a recommended regression equation(2,SRC). Based upon this estimated Koc, methylthiouracil will be expected to be highly mobile in soil(3,SRC) and will not be expected to significantly adsorb to soil, sediment or suspended particulate matter(3,SRC).

A 36-YR OLD FEMALE WAS TREATED FOR HYPERTHYROIDISM THROUGH FIRST PERIOD OF PREGNANCY. FETUS REMOVED IN 5TH MONTH. THYROID GLAND OF FETUS WAS HYPERPLASTIC, WEIGHING 335 MG (NORMS UP TO 260 MG).

A 25 YR-OLD PREGNANT WOMAN SUFFERING FROM HYPERTHYROIDISM WAS TREATED WITH 600-100 MG/DAY UNTIL PARTURITION. SHE DEVELOPED A MARKED GOITER DURING THE TREATMENT; THERE WAS NO THYROID ENLARGEMENT IN HER CHILD.

Release of methylthiouracil to the environment may occur as a result of its production and use as a drug that has been used in the past to treat human hyperthyroidism(1,2). As of 1970, the compound was more broadly used outside the U.S(2). No evidence was found that indicates that methylthiouracil has ever been produced commercially in the U.S.(2,SRC).

No data were found concerning the biodegradation of methylthiouracil either in natural media or in laboratory screening tests(SRC). Methylthiouracil may slowly biodegrade in natural waters and soil based upon the slow biodegradation of the structurally similar 2-thiouracil by activated sludge from municipal treatment plants(1,SRC).

Methylthiouracil

Group 2B: Possibly carcinogenic to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2001

2000

Based upon a water solubility of 533.2 mg/l at 25 °C(1), a BCF of 18 can be calculated for methylthiouracil using a recommended regression equation(2,SRC). Based upon this estimated BCF, methylthiouracil will not be expected to bioconcentrate in aquatic organisms(SRC).

Due to a lack of data, the tendency for methylthiouracil to volatilize from water and moist near-surface soil cannot be estimated(SRC). Based upon a report that the compound readily sublimes(1), however, loss of methylthiouracil from surfaces and dry near-surface soil may occur via sublimation(SRC).

... 14 MICE, AFTER ... TREATMENT FOR 42 WK /WITH MTU IN DRINKING WATER/, WERE GIVEN THYROID POWDER FOR ADDITIONAL 20 WK; 12 MICE DEVELOPED INVOLUTED ADENOMAS OF THYROID, & 7 HAD ECTOPIC THYROID TISSUE IN LUNG.

IN 9-MO OLD LONG-EVANS FEMALE RATS TREATED WITH DAILY DOSE ... OF 2.5 MG MTU GIVEN IN LOW-IODINE DIET, MALIGNANT THYROID TUMORS ... OBSERVED IN 8/24 ANIMALS & MARKED NODULAR CHANGES IN THYROID IN 15/24 RATS.

MALE & FEMALE LISTER HOODED RATS OF 10 WK OF AGE GIVEN ... MTU (APPROX 0.1%) CONTINUOUSLY IN DRINKING WATER STARTING 24 HOURS AFTER THEY HAD RECEIVED ... 5, 30 OR 100 UCI (131)IODINE BY IP INJECTION. ... WITH ... 30 MICROCURIES (131)IODINE + MTU, ALL 20 SURVIVORS HAD ADENOMAS /OF THYROID/, 5 ... MALIGNANT. FURTHER INCR IN DOSE OF (131)IODINE ... /NO/ INCR MALIGNANCY.

... 3-MO OLD FEMALE HAMSTERS WERE ADMIN 0.2% MTU IN DRINKING-WATER, ALONE OR IN COMBINATION WITH SINGLE IP INJECTION OF 10 MICROCURIES (131)IODINE GIVEN 24 HR BEFORE MTU ADMIN, WHICH WAS CONTINUED OVER A PERIOD OF 52 WEEKS. ... MTU-INDUCED ADENOMAS WERE CHIEFLY OF A PAPILLIFEROUS TYPE AND WERE LOCALIZED IN THE PERIPHERAL ZONE OF GLAND. THYROID CARCINOMAS IN (131)IODINE + MTU GROUP SHOWED MARKED INFILTRATIVE GROWTH INTO CAPSULE OF THE GLAND OR INTO THE NEARBY SOFT TISSUE. SOME TUMOR CELLS WERE FOUND TO HAVE INVADED MEDIUM AND LARGE BLOOD VESSELS, AND LUNG METASTASES WERE ALSO OBSERVED.

For more Non-Human Toxicity Excerpts (Complete) data for METHYLTHIOURACIL (12 total), please visit the HSDB record page.

As stipulated in 40 CFR 261.33, when methylthiouracil, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).