Oripavine

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 7500(SRC), determined from a structure estimation method(2), indicates that oripavine is expected to be immobile in soil(SRC). The estimated pKa of oripavine is 8.38(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected of cationic oripavine because cations do not volatilize(SRC). Volatilization of the neutral oripavine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.9X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Oripavine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 7500(SRC), determined from a structure estimation method(2), indicates that oripavine is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 8.38(3) indicates oripavine will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation from water surfaces is not expected to be an important fate process(SRC). Volatilization of neutral oripavine from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.9X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Oripavine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 4(SRC), from an estimated log Kow of 1.5(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 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), oripavine, which has an estimated vapor pressure of 3.7X10-8 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 oripavine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone(SRC); the half-lives for these reactions in air are estimated to be 44 and 9.6 minutes(SRC), calculated from respective rate constants of 5.3X10-10 and 1.7X10-15 cu cm/molecule-sec at 25 °C(SRC) that were derived using a structure estimation method(2). Particulate-phase oripavine may be removed from the air by wet and dry deposition(SRC). Oripavine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Oripavine is an opiate and the major metabolite of thebaine. It is an important intermediate in the biosynthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine and oripavine, but not morphine and codeine. Therefore, the chemistry of oripavine has been studied intensively to synthesize opioid pharmaceuticals such as oxymorphone, naloxone, and buprenorphine. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: Oripavine possesses an analgesic potency comparable to morphine; however, it is not clinically useful due to severe toxicity and low therapeutic index. In both mice and rats, toxic doses caused tonic-clonic seizures followed by death, similar to thebaine. Oripavine has a potential for dependence which is significantly greater than that of thebaine but slightly less than that of morphine.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of oripavine can be estimated to be 7500(SRC). According to a classification scheme(2), this estimated Koc value suggests that oripavine is expected to be immobile in soil. The estimated pKa of oripavine is 8.38(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

An estimated BCF of 4 was calculated in fish for oripavine(SRC), using an estimated log Kow of 1.46(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low.

An estimated pKa of 8.38(1) indicates oripavine will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces of the cation is not expected to be an important fate process(SRC). The Henry's Law constant for oripavine is estimated as 2.9X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that neutral oripavine is expected to be essentially nonvolatile from water and moist soil surfaces(3). Oripavine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.7X10-8 mm Hg(SRC), determined from a fragment constant method(2).

/BEHAVIORAL STUDIES/ The dependence potential of thebaine is at least partially attributed to oripavine which is one of the principal metabolites of thebaine. The analgesic potency of oripavine in mice is found to be much higher than that of thebaine and comparable to morphine. The reinforcing effect of this substance also appears to be more potent than thebaine. In rats the physical dependence potential of oripavine at a dose of 4 mg/kg is almost comparable to that of morphine at 0.5 mg/kg. Studies carried out on monkeys show that oripavine possesses weak morphine-antagonist properties. Further pharmacological studies of the metabolites of thebaine are recommended.

/BEHAVIORAL STUDIES/ The analgesic activity of oripavine and phi-dihydrothebaine (5, 6, 8, 14-tetrahydro-4-hydroxy-3, 6-dimethoxy-17-methylmorphinan) has been studied in the mouse and rat with the hot-plate technique after sc drug administration. Peak analgesic effects in the mouse and rat were observed 20 min following drug administration, and the effect lasted about 40 to 60 min. Median analgesic (AD50) and lethal (LD50) doses and 95% confidence limits are presented. Oripavine and phi-dihydrothebaine appear to have analgesic potency of the same order as morphine in these species but have low therapeutic indexes because of severe toxicity. Toxic signs of oripavine and phi-dihydrothebaine in both species were clonic-tonic convulsions followed by death. The toxicity of oripavine, phi-dihydrothebaine, and morphine in the mouse did not appear to be antagonized by pretreatment with 1 mg/kg of naloxone given 10 min prior to the test drug. Toxicity does not appear to be mediated at the opiate receptor; however, oripavine did show some cross tolerance with morphine, but did not appear to suppress morphine abstinence in the mouse and rat.

The rate constant for the vapor-phase reaction of oripavine with photochemically-produced hydroxyl radicals has been estimated as 5.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 44 minutes at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of oripavine with ozone has been estimated as 1.7X10-15 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9.6 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Oripavine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Oripavine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to oripavine may occur through dermal contact with this compound at workplaces where oripavine is extracted or used. Use data indicate that the general population may be exposed to oripavine via its medicinal use. (SRC)

Oripavine's extraction and use as an intermediate in the production of opiates may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 3.7X10-8 mm Hg at 25 °C indicates oripavine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase oripavine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone; the half-lives for these reactions in air are estimated to be 44 and 9.6 minutes, respectively. Particulate-phase oripavine will be removed from the atmosphere by wet and dry deposition. Oripavine contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, oripavine is expected to have no mobility based upon an estimated Koc of 7500. The estimated pKa of oripavine is 8.38, indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil of cationic oripavine is not expected because cations do not volatilize. Volatilization of neutral oripavine from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.9X10-13 atm-cu m/mole. Oripavine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, oripavine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated pKa and Henry's Law constant. An estimated BCF of 4 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since thi

Chemical: Morphinan-3-ol, 6,7,8-,14-tetradehydro-4,5-epoxy-6-methoxy-17-methyl, (5.alpha.)-

DEA schedule II controlled substance

Status: Active Update: 29-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/24863

Schedule II 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. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any of the following substances whether produced directly or indirectly by extraction from substances of vegetable origin, or independently by means of chemical synthesis, or by a combination of extraction and chemical synthesis: (1) Opium and opiate, and any salt, compound, derivative, or preparation of opium or opiate excluding apomorphine, thebaine-derived butorphanol, dextrorphan, nalbuphine, nalmefene, naloxegol, naloxone, and naltrexone, and their respective salts, but including the following. Oripaavine (DEA Code Number: 9330) is included on this list.