| GHS classification | DangerH302 (64.9%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P263, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 231 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H302: Harmful if swallowed [Warning Acute toxicity, oral] |
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| Regulatory information | Hazard Traits - CarcinogenicityDEA schedule III controlled substanceDirective (EC) No 74/2003Status: Active Update: 22-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/25237Testosterone: Does not have an individual approval but may be used under an appropriate group standard |
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| Other safety information | IMAP assessments - Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-: Human health tier I assessment |
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| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone cypionate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone cypionate/The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone enanthate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone enanthate/The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone undecanoate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone undecanoate/For more FDA Requirements (Complete) data for Testosterone (10 total), please visit the HSDB record page. |
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| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides. |
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| Hazard Classes and Categories | Acute Tox. 4 (64.9%) |
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| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents. |
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| Fire fighting procedures | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. |
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| Storage conditions | Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects.Commercially available testosterone preparations should be stored at a temperature less than 40 °C, preferably between 15-30 °Cfreezing of the sterile suspension and injections should be avoided. A precipitate may form if the injections are stored at a low temperaturehowever, this will dissolve after shaking and warming to room temperature. Use of a wet needle or syringe may cause the parenteral solutions to become cloudyhowever, this will not affect potency. |
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| Cleanup methods | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
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| Disposal methods | 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 company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubberContaminated packaging: Dispose of as unused product. |
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| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.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: Safety glasses with side-shields conforming to EN166. 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: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
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| Interactions | Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.Topical administration of 0.1% triamcinolone cream prior to application of a testosterone transdermal system did not alter absorption of testosteronehowever, pretreatment with topical administration of triamcinolone ointment substantially reduced absorption of testosterone.Administration of IM testosterone cypionate resulted in increased clearance of propranolol in one study. It is not known whether there is a potential for this interaction with topically administered testosterone gel. /Testosterone cypionate/Testosterone may potentiate the action of oral anticoagulants, causing bleeding in some patients. When testosterone therapy is initiated in patients receiving oral anticoagulants, dosage reduction of the anticoagulant may be required to prevent an excessive hypoprothrombinemic response. In patients receiving concomitant therapy with testosterone and anticoagulants, more frequent monitoring of INR and prothrombin time is recommended, especially during initiation or discontinuance of therapy.For more Interactions (Complete) data for Testosterone (10 total), please visit the HSDB record page. |
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| Health effects | In women, excess testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, breast tenderness or enlargement, decreased testes size, and urinary urgency. Chronically high levels of testosterone are associated with at least 2 inborn errors of metabolism including: Adrenal Hyperplasia Type 3 and Aromatase deficiency. |
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| Ecotoxicity values | EC50Species: Acartia tonsa (Calanoid Copepod) eggsConditions: saltwater, renewalConcentration: 1500 ug/L for 5 days (95% confidence interval: 1400-1800 ug/L)Effect: development, decreased larval development, slowed, retarded, delayed or non-developmentLC50Species: Acartia tonsa (Calanoid Copepod) adult age 10-12 daysConditions: saltwater, static, 20 °CConcentration: 5600 ug/L for 48 hr (95% confidence interval: 4700-6600 ug/L)Species: Neomysis integer (Opossum Shrimp) juvenile, length 2-4 mmConditions: saltwater, renewal, 15 °CConcentration: 1950 ug/L for 96 hr (95% confidence interval: 550-9080 ug/L) /formulated product/Species: Dugesia japonica (Flatworm) 0.8 cm body lengthConditions: freshwater, static, 25 °C, pH 7.8, hardness 136.5 mg/L CaCO3Concentration: 14800 ug/L for 24 hr />99% purity/For more Ecotoxicity Values (Complete) data for Testosterone (7 total), please visit the HSDB record page. |
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| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), a measured log Koc range of 3.25-3.52(2), corresponding to an average Koc of 2200(SRC), indicates that testosterone is expected to have low mobility in soil(SRC). Volatilization of testosterone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.5X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Testosterone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A 63% mineralization in 5 days using a sandy soil(5) suggests that biodegradation may be an important environmental fate process in soil(SRC). However, it has been reported that when swine slurry or municipal slurry is added to a loam soil at 10% v/w, mineralization of testosterone is suppressed(6).AQUATIC FATE: Based on a classification scheme(1), a measured log Koc range of 3.25-3.52(2), corresponding to an average Koc of 2200(SRC), indicates that testosterone is 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 3.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 72(SRC), from its log Kow of 3.32(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). A biodegradation half-life of 32 days in four municipal treatment plants exhibiting 55-65% mineralization of testosterone in 24 hours(8) suggests that biodegradation may be a moderate environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), testosterone, which has an estimated vapor pressure of 1.7X10-8 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 testosterone may be removed from the air by wet and dry deposition(SRC). Testosterone contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
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| Exposure routes | Endogenous, Injection |
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| Toxicity summary | IDENTIFICATION AND USE: Testosterone is an anabolic steroid for systemic use. It consists of odorless or almost odorless crystals or crystalline powder. Naturally-occuring anabolic steroids are synthesized in the testis, ovary and adrenal gland. Anabolic steroids are listed as Schedule III controlled substances. HUMAN EXPOSURE AND TOXICITY: The main risks associated with testosterone are those of excessive androgens: menstrual irregularities and virilization in women and impotence, premature cardiovascular disease and prostatic hypertrophy in men. Both men and women can suffer liver damage with oral anabolic steroids containing a substituted 17-alpha-carbon. Psychiatric changes can occur during use or after cessation of these agents. Acute overdosage can produce nausea and gastrointestinal upset. Chronic usage is thought to cause an increase in muscle bulk, and can cause an exaggeration of male characteristics and effects related to male hormones. There is no clear evidence that anabolic steroids enhance overall athletic performance. Precocious prostatic cancer has been described after long-term anabolic steroid abuse. Cases where hepatic cancers have been associated with anabolic steroid abuse have been reported. Testosterone may cause fetal harm when administered to pregnant women due to the potential for virilization of a female fetus. Androgenic effects including clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, abnormal vaginal development, and persistence of a urogenital sinus have occurred in the female offspring of women who were given androgens during pregnancy. The degree of masculinization is related to the amount of drug given to the woman and the age of the fetusmasculinization is most likely to occur in a female fetus when exposure to androgens occurs during the first trimester. ANIMAL STUDIES: The effect of testosterone on the prostate of castrated rats was described as a significant increase in prostatic weight which occurred after 6 wk treatment with testosterone. In female mice injected subcutaneously with 25 ug testosterone daily for the first five days after birth, 7/9 developed hyperplastic epithelial lesions, resembling epidermoid carcinomas at about 71 weeks of age. Chronic treatment of rats with testosterone produced a low prostate carcinoma incidence. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens. Daily subcutaneous injections for 4-8 days of total doses of 0.5-80 mg testosterone into rats between days 10 and 20 of gestation and of total doses of 1-55 mg testosterone propionate between days 12 and 19 of gestation resulted in resorptions, necrosis, lethality, post-partum mortality and various degrees of masculinization in female offspring. Deposteron (testosterone cypionate) was genotoxic and cytotoxic in mice. Testosterone acted both as a mitogenic and genotoxic agent in L929 cells.Testosterone is considered an anabolic steroid. It plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass, and the growth of body hair. High levels of testosterone can lead to masculinization in females or premature puberty in young boys. Chronically high levels in adults increase the incidence of heart attack, stroke and blood clots by lowering the level of HDL (good cholesterol) and increasing the level of LDL (bad cholesterol). Chronic high use of anabolic steroids (such as testosterone) appears to lead to cardiac myopathy and weakening the left ventricle. The development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), arises because of increased conversion of testosterone to estradiol by the enzyme aromatase. Reduced sexual function and temporary infertility can also occur in males.
The mechanism of testosterone’s action is as follows: Free testosterone is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of testosterone. Once bound, the ligand-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. |
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| Ecotoxicity excerpts | /AQUATIC SPECIES/ Endocrine disruptors are known to alter endogenous free and esterified levels of androgenic and estrogenic steroid hormones in aquatic mollusks. The origin of steroids in these animals, however, remains controversial. In the present study, free and esterified testosterone concentrations were measured in the hermaphroditic aquatic gastropod Lymnaea stagnalis exposed to molecules known for their androgenic (testosterone and tributyltin), anti-androgenic (cyproterone-acetate), and estrogenic (chlordecone) properties, by reference to their mode of action in vertebrates. In parallel, snail oviposition and fecundity were followed over a 21-day exposure period. Testosterone exposure resulted in increased esterified testosterone levels, whereas free testosterone concentrations remained stable. In contrast, cyproterone-acetate significantly increased the free form of testosterone with no changes in the esterified form, whereas chlordecone showed a tendency to reduce (though not significantly) esterified testosterone concentrations without changing free testosterone levels. Finally, tributyltin did not alter testosterone homeostasis. The production of egg clutches and eggs was significantly reduced only in the snails exposed to the highest concentrations of chlordecone (19.6 ug/L) and tributyltin (94.2 ng Sn/L). Overall, the present study demonstrates that uptake of testosterone from the exposure medium occurs in L. stagnalis. Moreover, it shows that cyproterone-acetate and, to a lesser extent, chlordecone can alter endogenous testosterone levels in this freshwater snail. However, the relationship between hormonal changes and snail reproduction has not been established. |
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| Signs and Symptoms | In women, testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, premature baldness, breast tenderness or enlargement, decreased testes size, and urinary urgency. |
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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 8, 2016: http://actor.epa.gov/dashboard/] |
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| Effluent Concentrations | Testosterone was detected in constructed water treatment plant effluents in Maryland in concentrations of 2.1 and 1.6 ng/L for wetland effluent and peat effluent, respectively(1). Testosterone was detected in raw sewage effluent water sampled in Tel Aviv, Israel in 1991 at concentrations ranging from 208-320 ng/L (third year of a drought)lower concentrations were measured in 1992 after the drought was over(2). The testosterone level in secondary effluent from a Tel Aviv, Israel treatment plant was 50 ng/L(2). |
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| Medical Surveillance | SRP: Workers exposed to testosterone during its manufacture as well as patients receiving androgen therapy should be monitored for gynecomastia, hepatic, renal, and cardiac dysfunction, aggressive or antisocial behavior, lipoprotein profiles and priapism. |
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| Soil Adsorption/Mobility | The soil absorption of testosterone was measured in several different soil samples(1). Log Koc values ranging from 3.25-3.52 were measuredthe average log Koc was 3.32(1), corresponding to a Koc value of 2,188(SRC). According to a classification scheme(2), this Koc value suggests that testosterone is expected to have low mobility in soil. In another study, 69-74% of applied C14-testosterone (0.406 and 0.738 mg/L) was retained in the top 5 cm of soil in a column experiment using an undisturbed, agricultural soil (Hamar sandy soil: 2.23% organic matter14.0% clay10.0% silt, 67% sand)(3). |
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