Atractylenolide III

248.32

248.32

DTXSID50223308

White to off-white powder or crystals

46.5

3.81 (est)

white to off-white

1.2±0.1 g/cm3

166-169 °C @ Solvent: Chloroform

424.6±45.0 °C at 760 mmHg

181.1±21.5 °C

1.558

methanol: soluble1mg/mL, clear, colorless

2-8°C

8.4X10-8 mm Hg at 25 deg C (est)

Henry's Law constant = 9.5X10-9 atm-cu m/mol at 25 °C (est)

NONH for all modes of transport

3

Stable under recommended storage conditions.

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Strong oxidizing agents

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).

Not flammable or combustible.

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Sweep up and shovel. Keep in suitable, closed containers for disposal.

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.|Provide appropriate exhaust ventilation at places where dust is formed.

Atractylenolide III is extracted from the Chinese medicinal plant Atractylodes macrocephala(1), Chinese Bai-Zhu(2). The compound is present in A. ovata rhizome(3).

Atractylenolide III's production and use as a medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a structure estimation method(2), indicates that atractylenolide III is expected to have moderate mobility in soil(SRC). Volatilization of atractylenolide III from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.5X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Atractylenolide III is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a structure estimation method(2), indicates that atractylenolide III 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 9.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 150(SRC), from an estimated log Kow of 3.81(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC). Atractylenolide III is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), atractylenolide III, which has an estimated vapor pressure of 8.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase atractylenolide III is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.7 hours(SRC), calculated from its rate constant of 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase atractylenolide III may be removed from the air by wet or dry deposition(SRC). Atractylenolide III contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of atractylenolide III with photochemically-produced hydroxyl radicals has been estimated as 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Atractylenolide III is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(2). Atractylenolide III contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 150 was calculated in fish for atractylenolide III(SRC), using an estimated log Kow of 3.81(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of atractylenolide III can be estimated to be 220(SRC). According to a classification scheme(2), this estimated Koc value suggests that atractylenolide III is expected to have moderate mobility in soil.

The Henry's Law constant for atractylenolide III is estimated as 9.5X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that atractylenolide III is expected to be essentially nonvolatile from moist soil and water surfaces(2). Atractylenolide III is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.4X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to atractylenolide III may occur through inhalation and dermal contact with this compound at workplaces where atractylenolide III is extracted or used. Use data indicate that the general population may be exposed to atractylenolide III via ingestion as a medication. (SRC)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ The rhizome of Atractylodes ovata (Bai Zhu in Chinese) is a widely used traditional Chinese herb in Taiwan as a tonic agent. In this paper, four sesquiterpenoids, namely atractylon, and atractylenolides I, II, and III, were isolated from the n-hexane extract of A. ovata and were evaluated for cytotoxic effects in vitro. Atractylon significantly inhibited the growth of human leukemia cell line HL-60 and mouse leukemia cell line P-388, and showed low cytotoxicity against primary cultures of normal human peripheral blood mononuclear cells at 15 ug/mL for 12 hr. Atractylon had a dose-dependent antiproliferative effect on the two tumor cell lines. In accordance with DNA fragment increases and PARP protein decreases, atractylon at 15 ug/mL for 6 hr induced apoptosis in HL-60 cells. Moreover, atractylon inhibited the viability of P-388 cells and induced apoptosis after 15 microg/ml treatment for 12 hr in an in vitro assay. However, atractylenolide I at 30 ug/mL for 12 hr also induced apoptosis in HL-60 and P-388 cells, but atractylenolides II and III showed no significant inhibition effects on tumor cell growth. As the above results suggested, atractylon and atractylenolide I were the major cytotoxic principle constituents of A. ovata on leukemia cell lines.|/ALTERNATIVE and IN VITRO TESTS/ The dried rhizome of Bai Zhu (Atractylodes ovata) is widely used as a Chinese herbal medicine. Two sesquiterpenolides of similar structures (atractylenolide I, AT-I; atractylenolide III, AT-III) were isolated from dried rhizome of Atractylodes ovata. Incubation of AT-I with recombinant human Cu,Zn-superoxide dismutase (rhCu,Zn-SOD) resulted in rhCu,Zn-SOD fragmentations and Zn releases. However, these were not observed in the AT-III reaction. The AT-1 showed dose-dependent cytotoxic activities (7.5, 15, and 30 ug/mL) on the human promyeloleukemic HL-60 cells while AT-III did not, and the IC50 of the former being 10.6 ug/mL (corresponding to 46 uM) on 12 hr-treated cells...

8 beta-hydroasterolide

A sensitive and reliable high-performance liquid chromatography-mass spectrometry (HPLC-MS) was developed and validated for simultaneous quantification of five main bioactive components, i.e., calycosin-7-O-beta-d-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral administration of Danggui Buxue Tang (DBT) extract. Plasma samples were extracted with solid-phase extraction (SPE) separated on an Inertsil ZORBAX C18 column and detected by MS with electrospray ionization (ESI) interface in negative selective ion monitoring (SIM) mode. Calibration curves offered linear ranges of two orders of magnitude with r2 > 0.99. The method had the lower limit quantification of 0.55, 0.46, 1.07, 1.12 and 4.6 ng/mL for calycosin-7-O-beta-d-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid, respectively, with precision less than 10%. The RSD of intra- and inter-day variations ranged from 2.10% to 6.19% and 2.37% to 6.72%. This developed method was subsequently applied to pharmacokinetic studies of the five compounds in rats successfully.|The petroleum ether-ether (1 : 1) extract of Atractylodis macrocephalae was screened by cell membrane chromatography (CMC) and subsequently separated by column chromatography (CC) and high performance liquid chromatography (HPLC). Five components were isolated and identified as atractylenolide III 1, atractylenolide I 2, 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol 3, 14-acetoxy-12-alpha-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol 4 and 14-acetoxy-12-beta-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol 5 by routine spectrometric methods. The data of 5 and (13)C-NMR data of 3 and 4 were reported... Further in vivo experiments showed that the five components exhibited significant inhibiting effects both on the ear edema induced by xylene and on the peritoneal capillary permeability induced by acetic acid in mice.