6-プロピル-2-チオウラシル

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.

Commercially available propylthiouracil tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably between 15-30 °C.

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.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations. SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for PROPYL THIOURACIL (6 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 PROPYL THIOURACIL (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/

In addition to blocking hormone synthesis, propylthiouracil inhibits the peripheral deiodination of thyroxine to triiodothyronine. Methimazole dose not have this effect and can antagonize the inhibitory effect of propylthiouracil.

We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.

Female Sprague-Dawley rats, 50-60 days of age, were given 7,12-dimethylbenz[ a]anthracene (DMBA) in sesame oil by oral gavage at a dose of 6.5, 10, 13.5 or 15 mg per animal. Propylthiouracil was given in the drinking-water at concentrations between 0.5 and 4.0 mg/100 mL for various times before and after the DMBA treatment, ranging from 17 days before DMBA up to the end of the study at 4 months. Severe hypothyroidism produced by administration of propylthiouracil at the higher dose from 7 days before DMBA up to study termination reduced the mammary tumor incidence from 68/108 in rats given DMBA only to 3/45 in those given DMBA plus propylthiouracil.

Two groups of 21 male inbred Wistar rats, 6 weeks of age, were fed basal diet containing propylthiouracil [purity not specified] at a concentration of 0.15% either alone or in combination with a single intraperitoneal injection of N-nitrosobis(2- hydroxypropyl)amine (NBHPA) at the start of the study at a dose of 2.8 g/kg bw. Two additional groups received the initiating dose of NBHPA alone or basal diet alone (control group). The animals were maintained for 20 weeks, at which time the survival rate was 100%. Thyroid follicular-cell tumors occurred in 21/21 rats given NBHPA plus propylthiouracil, 4/21 given NBHPA only (p<0.05) and 0/21 given propylthiouracil only or no treatment. Of the rats given NBHPA plus propylthiouracil, seven of those bearing thyroid tumors had thyroid carcinomas.

For more Interactions (Complete) data for PROPYL THIOURACIL (7 total), please visit the HSDB record page.

Propylthiouracil has been associated with transient, asymptomatic elevations in serum aminotransferase levels, typically during the first 3 months of therapy. These elevations are rarely clinically significant and usually resolve even with continuation of therapy. Propylthiouracil is also capable of causing clinically apparent, idiosyncratic liver injury at a rate estimated to be at least 1 per 1000 persons exposed. The onset of hepatotoxicity is usually within 2 to 12 weeks of starting, and the pattern of enzyme elevations is typically hepatocellular, although cholestatic and mixed patterns have also been described (Cases 1 to 3). In some cases, onset is months or more than a year after initiating therapy, sometimes shortly after dose modification. Rash, fever and eosinophilia are not uncommon, but are rarely prominent or severe. Some cases of propylthiouracil hepatotoxicity present with autoimmune features including antinuclear antibody and hyperglobulinemia, perhaps because of the background of autoimmune thyroid disease. While most patients start to improve with stopping therapy, many cases are severe and some have been associated with acute liver failure with death or need for emergency liver transplantation (Case 4). Liver injury from propylthiouracil appears to be more common and perhaps more severe in children and adolescents than in adults. Rates of acute liver failure due to propylthiouracil are estimated to be 1:10,000 in adults and as high as 1:2000 in children.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a structure estimation method(2), indicates that propyl thiouracil is expected to have very high mobility in soil(SRC). Volatilization of propyl thiouracil from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Propyl thiouracil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.9X10-8 mm Hg(SRC), determined from a fragment constant method(4). Propyl thiouracil was not degraded in a screening study using an activated sludge inoculum over a 4 week incubation period(5), suggesting biodegradation in soil will be slow.

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a structure estimation method(2), indicates that propyl thiouracil is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.1X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), BCF values of <2 to <4 measured in fish(6), suggest bioconcentration in aquatic organisms is low(SRC). Propyl thiouracil was not degraded in a screening study using an activated sludge inoculum over a 4 week incubation period(6) suggesting biodegradation in water will be slow. The potential for direct photolysis in sunlit surface water exists since propyl thiouracil absorbs light greater than 290 nm(7); however, no rates for this potential reaction were located(SRC,2006).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), propyl thiouracil, which has an estimated vapor pressure of 6.9X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase propyl thiouracil may be removed from the air by wet and dry deposition(SRC). Propyl thiouracil absorbs light >290 nm and may be susceptible to direct photolysis in air(3).

Acute liver injury: Reported cases have shown PTU to be associated with acute liver failure and death. PTU has a black box warning for this issue. There are cases reported in pregnancy, adults, and children. Hence, caution is necessary with its use, especially in the first six months of the start of therapy. Since the onset is unpredictable and variable, regular monitoring is not recommended. Educate the patient regarding the potential symptoms to come and visit the physician for anorexia, pruritis, right upper quadrant pain, nausea, vomiting, light-colored stool, and dark urine. Stop the drug at the first appearance of these symptoms and perform laboratory tests: biochemical (bilirubin, alkaline phosphatase) and hepatocellular injury markers (AST, ALT).

Propylthiouracil is distributed into milk; however, some studies indicate that the extent of distribution is only about 0.007-0.077% of a single dose.

Propylthiouracil (PTU) concentration measured in blood and milk from 9 lactating women after oral administration of 400 mg. Apparently, PTU is not concentrated in human breast milk and recommended dosages to mother result in minimal and presumably clinically insignificant doses to suckling infant.

Propylthiouracil is the drug of choice in nursing women, since very small amt of the drug appear in breast milk and do not appear to affect thyroid function in the suckling baby.

There is no information regarding the lethal dose (LD50), serum level concentration of PTU associated with overdose symptoms, or the amount of single drug dose assumed to be causing overdose symptoms. Symptoms reported are nausea, vomiting, epigastric distress, headache, fever, and arthralgia. Patients are also at risk of developing ANCA-associated vasculitis, agranulocytosis, or acute hepatic injury may occur. In the event of overdose, consider the possibility of drug interaction or abnormal pharmacokinetics in the patient. Patients may also develop symptoms of severe hypothyroidism. Patient treatment is supportive as there is no antidote available, and the clinician should also stop the drug.

Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.

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/

Using a structure estimation method based on molecular connectivity indices(1), the Koc for propyl thiouracil can be estimated to be 23(SRC). According to a classification scheme(2), this estimated Koc value suggests that propyl thiouracil is expected to have very high mobility in soil(SRC).

/HUMAN EXPOSURE STUDIES/ In a survey of 331 hyperthyroid patients treated with antithyroid drugs and later with thyroidectomy, four malignant thyroid lesions were detected in patients diagnosed with Grave's disease, whose drug therapy had continued for at least 1 year.

/OTHER TOXICITY INFORMATION/ In humans, hypothyroidism causes irreversible mental retardation and various neuromotor disabilities.

/SIGNS AND SYMPTOMS/ Other rare but serious reactions include toxic hepatitis, vasculitis (often antineutrophil cytoplasmic antibody-positive) and a drug-induced lupus syndrome.

/SIGNS AND SYMPTOMS/ In general, overdosage of propylthiouracil may be expected to produce effects that are extensions of common adverse reactions. Nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, and pancytopenia have been reported. Agranulocytosis is the most serious adverse effect associated with propylthiouracil overdosage. Exfoliative dermatitis and hepatitis have also occurred.

For more Human Toxicity Excerpts (Complete) data for PROPYL THIOURACIL (18 total), please visit the HSDB record page.

Medication, thyroid inhibitor

MEDICATION

MEDICATION (VET)

Use (kg; approx.) in Germany (2009): >100

Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease).

... Small amounts of thiourea present as an impurity.

Small amounts of thiourea may be present in propylthiouracil as an impurity.

Propylthiouracil is available in US as USP grade containing 98-100.5% active ingredient on dried basis...

Oral: Tablets 50 mg (available by nonproprietary name)