Testolactone

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 4,100(SRC), determined from a structure estimation method(2), indicates that testolactone is expected to have slight mobility in soil(SRC). Volatilization of testolactone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.1X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Testolactone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 4,100(SRC), determined from a structure estimation method(2), indicates that testolactone 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 6.1X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 8.2(SRC), from an estimated log Kow of 2.1(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), testolactone, 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 atmosphere. Particulate-phase testolactone may be removed from the air by wet and dry deposition(SRC). Testolactone does not absorb light at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of testolactone can be estimated to be 4,100(SRC). According to a classification scheme(2), this estimated Koc value suggests that testolactone is expected to have slight mobility in soil.

An estimated BCF of 8.1 was calculated for testolactone(SRC), using an estimated log Kow of 2.1(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for testolactone is estimated as 6.1X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that testolactone is expected to be essentially nonvolatile from moist soil (SRC) and water surfaces(2). Testolactone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Delta 1- Testolactone, an androgen derivative without intrinsic hormonal action, is known to block the aromatization of androgens to estrogens. This study was designed to assess its effect upon serum testosterone and estradiol in the adult male rat. By itself, testolactone did not affect T/E2 levels in the dosages utilized. Daily injections of human chorionic gonadotropin for 15 days caused a tenfold rise in serum testosterone, although there was no increase in serum estradiol. When given along with human chorionic gonadotropin, testolactone did not alter the Leydig cell response. However, pretreatment of animals with testolactone increased the testicular response to human chorionic gonadotropin over that of saline treated animals. Studies were also carried out to delineate the sources of estrogen in the adult male rat. These experiments demonstrate that (1) the majority of estradiol is not testicular in origin but is derived from the adrenal; (2) the conversion of androgen precursors to estradiol in the rat is not affected by testolactone; and (3) in spite of no demonstrable inhibition of estradiol production, testolactone causes an increased Leydig cell responsiveness to human chorionic gonadotropin.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Testolactone has been shown to produce increased fetal mortality, abnormal fetal development, and mortality in growing pups when administered to rats at 5-15 times the usual human dosage; however, studies in rabbits at dosages of 2.5-7.5 times the usual human dosage demonstrated no teratogenic effects.

Anabolic steroids are not recommended for use during pregnancy, since studies in animals have shown that anabolic steroids cause masculinization of the fetus. Risk-benefit must be carefully considered. /Anabolic steroids/

Anabolic steroids should be used with caution in children and adolescents and only by specialists who are aware of their effects on bone maturation because of possible premature epiphyseal closure, precocious sexual development in males, and virilization in females. The epiphyseal maturation may be accelerated more rapidly than linear growth in children, and the effect may continue for 6 months after the medication has been discontinued. /Anabolic Steroids/

Anabolic steroids may decrease blood glucose concentrations; diabetic patients should be closely monitored for signs of hypoglycemia and dosage of hypoglycemic agent adjusted as necessary. /Anabolic steroids/

Testolactone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Testolactone does not absorb light at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The danger to health-care personnel from handling a hazardous drug stems from a combination of its inherent toxicity and the extent to which workers are exposed to the drug in the course of carrying out their duties. This exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/

Occupational exposure to testolactone may occur through dermal contact with this compound at workplaces where testolactone is produced or used. Exposure to the drug among the general population may be limited to those taking TESLAC (an anticancer agent) that contains testolactone as its active component or those taking testolactone (an anabolic steroid) for performance enhancement. (SRC)

Testolactone's production and use in the treatment of breast cancer and as an anabolic steroid may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C indicates testolactone will exist solely in the particulate phase in the atmosphere. Particulate-phase testolactone will be removed from the atmosphere by wet and dry deposition. Testolactone does not absorb light at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, testolactone is expected to have slight mobility based upon an estimated Koc of 4,100. Volatilization from water or moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 6.1X10-8 atm-cu m/mole. Testolactone is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data were not available. If released into water, testolactone is expected to adsorb to suspended solids and sediment based upon the estimated Koc. An estimated BCF of 8.2 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis occurs very slowly so therefore is not expected to be an important environmental fate process. Occupational exposure to testolactone may occur through dermal contact with this compound at workplaces where testolactone is produced or used. Exposure to the drug among the general population may be limited to those taking TESLAC (an anticancer agent) that contains testolactone as its active component or those taking testolactone (an anabolic steroid) for performance enhancement. (SRC)

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts of isomers is possible within the specific chemical designation. DEA Code #: 4000; Drug class: anabolic steroids.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl testolactone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Obtained by microbial transformation of progesterone, Reichstein's substance S, or testosterone.

Fried et al, US 2744120 (1956 to Olin Mathieson)

While data specific to testolactone were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

This is a controlled substance (anabolic steroid)... .

Synthetic analogs of androgens have been used by professional, as well as amateur, athletes for possible performance enhancement.

Anabolic Steroid Control Act of 2004. Public Law 108-358 (October 22, 2004)... includes /testolactone/ as an anabolic steroid