| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 8% (2 of 25) of reports.DangerH302 (56%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P264, P270, P280, P301+P317, P318, P319, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 25 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| Regulatorische Informationen | Status: Active Update: 10-09-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/24062L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-: Does not have an individual approval but may be used under an appropriate group standard |
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| Weitere Sicherheitsinformationen | IMAP assessments - L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-: Human health tier I assessment |
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| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including levothyroxine sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Levothyroxine sodium/ |
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| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), Hydrogen iodide |
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| Hazard Classes and Categories | Acute Tox. 4 (56%)Reproductive toxicity - Category 2 |
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| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents, Strong bases |
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| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
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| Lagerbedingungen | Store at 25 °C (77 °F)excursions permitted to 15 deg -30 °C (59 deg - 86 °F).Keep container tightly closed in a dry and well-ventilated place. |
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| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gasEnvironmental precautions: Do not let product enter drainsMethods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. |
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| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.Product: Offer surplus and non-recyclable solutions to a licensed disposal companyContaminated packaging: Dispose of as unused product. |
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| Preventive Measures | Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.Appropriate engineering controls: General industrial hygiene practice.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
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| Personal Protective Equipment (PPE) | Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
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| Wechselwirkungen | Antacids (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate), simethicone, and sucralfate bind thyroid agents in the GI tract and delay or prevent their absorption. Calcium carbonate may form an insoluble chelate with levothyroxine, resulting in decreased levothyroxine absorption and increased serum thyrotropin concentrationsin vitro studies indicate that levothyroxine binds to calcium carbonate at acidic pH levels. To minimize or prevent this interaction, some clinicians recommend that these agents be administered approximately 4 hours apart when the drugs must be used concurrently with thyroid agents.Serum concentrations of digitalis glycosides may be decreased in patients with hyperthyroidism or in patients with hypothyroidism in whom a euthyroid state has been achieved. Thus, therapeutic effects of digitalis glycosides may be reduced in these patients.Drugs that induce hepatic microsomal enzymes (e.g., carbamazepine, phenytoin, phenobarbital, rifampin) may accelerate metabolism of thyroid agents, resulting in increased thyroid agent dosage requirements. Phenytoin and carbamazepine also reduce serum protein binding of levothyroxine, and total- and free-T4 may be reduced by 20-40%, but most patients have normal serum concentrations of thyrotropin (thyroid-stimulating hormone, TSH) and are clinically euthyroid. /Thyroid agents/Bile acid sequestrants (e.g., cholestyramine resin, colestipol) bind thyroid agents in the GI tract and substantially impair their absorption. In vitro studies indicate that the binding is not readily reversible. To minimize or prevent this interaction, these agents should be administered at least 4 hours apart when the drugs must be used concurrently.For more Interactions (Complete) data for LEVOTHYROXINE (14 total), please visit the HSDB record page. |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 6600(SRC), determined from a structure estimation method(2), indicates that levothyroxine is expected to be immobile in soil(SRC). Estimated pKa values of 7.43 and 9.43(3), indicating that this compound will exist as a zwitterion in the environment. Volatilization from moist soil is not expected because the compound exists as an ion and ions do not volatilize. Levothyroxine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-16 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil ere not available(SRC, 2016).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 6600(SRC), determined from a structure estimation method(2), indicates that levothyroxine is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 7.43 and 9.43(3) indicate levothyroxine will exist as a zwitterion at pH values of 5 to 9 and, therefore, volatilization from water surfaces and bioconcetration are not expected to be an important fate processes. Biodegradation data in water were not available(SRC, 2016).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), levothyroxine, which has an estimated vapor pressure of 2.1X10-16 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 levothyroxine may be removed from the air by wet and dry deposition(SRC). Levothyroxine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
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| Unerwünschte Wirkungen | Generally, adverse events resulting from incorrect dosing (excessive dosing) often form a hyperthyroid-like picture or an allergic reaction to the excipient of the levothyroxine tablets. Levothyroxine 50 mcg tablets don't contain allergic excipients, so there is a decreased risk for immune reactions. Allergy to the excipients such as dye(tartrazine yellow), lactose, acacia, or even gluten in the levothyroxine tablet may infrequently occur. Hence, allergy or intolerance to levothyroxine can be managed by changing the product, including consideration of gel capsules.Among older persons treated with levothyroxine, levothyroxine at doses more than 75 mcg per day is associated with an increased risk of atrial fibrillation. |
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| Milk Concentrations | Levothyroxine (T4) is excreted into breast milk in low concentrations. ... |
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| Toxizitätsübersicht | IDENTIFICATION AND USE: Levothyroxine occurs as crystals or needles. As a drug, levothyroxine sodium is used as replacement or supplemental therapy in congenital or acquired hypothyroidism. It is also used in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. The injection form of levothyroxine sodium is indicated for the treatment of myxedema coma. Levothyroxine has also been used in veterinary medicine. HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of levothyroxine overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Studies indicate that careful attention is necessary when initiating the administration of levothyroxine sodium to very-low-birth-weight infants. Ingestion of levothyroxine in children typically follows a benign course, but overdose can result in significant complications, including seizures and arrhythmias, both of which should be monitored for. In one genotoxicity study, the ability of thyroxine to induce sister chromatid exchange and micronuclei was tested in cultured human lymphocytes. Thyroxine exhibited weak clastogenic effects only at high concentrations. ANIMAL STUDIES: A single acute overdose in small animals is less likely to cause severe thyrotoxicosis than chronic overdosage. Vomiting, diarrhea, transition from hyperactivity to lethargy, hypertension, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes may be noted in dogs and cats. In dogs, clinical signs may appear within 1-9 hours after ingestion. Four pregnant New Zealand white rabbits received intramuscular levothyroxine at 250 ug/kg on days 25 and 26 of gestation. Maternal and fetal plasma-free levothyroxine concentration was higher than in controls, with the highest concentration noted at 14 days of neonatal period. Treatment resulted in fetal hyperglycemia and depletion of fetal liver glycogen content. Animal studies have not been performed to evaluate levothyroxine carcinogenic potential, mutagenic potential or effects on fertility.Levothyroxine toxicity is rarehowever, it is most likely to occur in the setting of accidental ingestion by children or older adults. Thyroxine (T4) and triiodothyronine (T3) levels rise within 1 to 2 hours of ingestion. In the initial stage of overdose (6 to 12 hours post-ingestion), the common signs of toxicity would be tremulousness, tachycardia, hypertension, anxiety, and diarrhea. Rarely convulsions, thyroid storms, acute psychosis, arrhythmias, and acute myocardial infarction may occur. Laboratory workup usually reveals elevated serum total T4 and T3, suppressed serum TSH, and elevated Free T4 and Free T3. |
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| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of December 17, 2015: http://actor.epa.gov/dashboard/] |
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| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of levothyroxine can be estimated to be 6600(SRC). According to a classification scheme(2), this estimated Koc value suggests that levothyroxine is expected to be immobile in soil. Estimated pKa values of 7.43 and 9.43(3) indicate that this compound will exist almost entirely in the zwitterion form in the environment(3). |
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| Natural Pollution Sources | Thyroxine is an essential thyroid hormone for normal development and physiology and is regulated by the pituitary gland in mammals(1-3). |
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| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ The signs and symptoms of overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported./CASE REPORTS/ There is currently little literature pertaining to levothyroxine overdose apart from minor or accidental overdoses in the pediatric population. In particular, there is little information available on how to confidently differentiate levothyroxine overdose from endogenous causes of thyrotoxicosis when there is no history available at the time of assessment. We report a levothyroxine (15,800 ug) and citalopram (2,460 mg) overdose in a 55-year-old woman presenting with seizure and tachycardia in which the diagnosis was not initially suspected. Clinical data, including a long history of treated hypothyroidism and lack of a goiterand biochemical findings, such as an incompletely suppressed thyroid-stimulating hormone (TSH) level, despite a markedly elevated free thyroxine level (FT4), a normal sex hormone-binding globulin level at baseline, and an undetectable thyroglobulin, supported the diagnosis of thyrotoxicosis due to a massive exogenous thyroid hormone overdose. Treatment was given to decrease free triiodothyronine (FT3) conversion and increase thyroid hormone clearance with dexamethasone and cholestyramine. The patient made a full recovery. Levothyroxine overdose can result in subtle symptoms and signs clinically, even when in massive quantities. This can make diagnosis challenging. Biochemical features, such as the pattern of thyroid hormone elevation and thyroglobulin levels, help differentiate exogenous thyroid hormone overdose from endogenous causes of thyrotoxicosis./CASE REPORTS/ Exposure to thyroid products is common, but acute poisonings in adults are rare. Most cases of severe toxicity are related to prolonged, repeated exposure (either inadvertent or deliberate abuse). There are a few reports of toxicity in children following large (greater than 10 mg) single ingestions. Expect significant toxicity in children and adults who have ingested more than 2 to 4 mg of levothyroxine. However, in comorbid elderly patients, the threshold may be lower. In this paper we present acute overdose of levothyroxine in nine adult patients (aged 21-44 yearsmean--30.5 years)ingested doses were from 1.2 mg to 15 mg (mean--6.5 mg). Only in three cases (ingested doses were 5.68.0 and 15 mg) minor and mild clinical symptoms were observed and pharmacological treatment was necessary. No severe symptoms were observed in our group. Asymptomatic clinical course in patients who ingested more than 3 mg of levothyroxine probably was related to coingestion of benzodiazepins, beta-blockers, ACE inhibitors and ethanol. Serum free triiodothyronine (T3) level of 20 pg/ml (normal, 4.1 pg/ml) was reported following an overdose of 15 mg levothyroxine in day five. Normalization was observed in day eleven./CASE REPORTS/ We describe the course of a toddler who ingested a massive amount of levothyroxine and review treatment options for such overdoses. A 2 1/2-year-old boy presented shortly after an ingestion of up to 7.6 mg of levothyroxine (potentially as much as 700 ug/kg). He was initially asymptomatic, treated with oral charcoal 1 g/kg, and discharged home from the emergency department after a few hours. He returned approximately 24 hours later with a temperature of 38.5 °C, heart rate of 163 beats per minute, respiratory rate of 30 breaths per minute, and blood pressure of 136/70 mm Hg. He had a slightly decreased appetite and no signs or symptoms of infection. He was admitted to hospital and treated with oral acetaminophen. The initial free thyroxine (T4) was > 100 pmol/L and free triiodothyronine (T3) was 35.3 pmol/L. The patient had desquamation of the palms and soles, hair loss, and irritability during the month following the ingestion. Resolution of the elevated free T4 occurred by 12 days post-ingestion and normalization of the thyroid-stimulating hormone by 7 weeks post-ingestion. There were no long-term sequelae. Levothyroxine overdose can result in significant complications, including seizures and arrhythmias, both of which should be monitored for. However, as our case illustrates, massive ingestion of levothyroxine in children typically follows a benign course.For more Human Toxicity Excerpts (Complete) data for LEVOTHYROXINE (12 total), please visit the HSDB record page. |
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| Artificial Pollution Sources | Levothyroxine's production and administration as a medication to treat hypothyroidism and goiter in humans and animals(1) may result in its release to the environment through various waste streams(SRC). |
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| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)levothyroxineDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
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| Environmental Bioconcentration | Estimated pKa values of 7.43 and 9.43(1) indicate that levothyroxine will exist in the zwitterion form in the environment and, therefore, bioconcentration is not expected to be an important environmental fate process(SRC). |
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