メパクリン

LC50 Ictalurus punctatus (Channel catfish) 198 mg/L/24 hr (95% confidence limit: 169-232 mg/L); static

LC50 Ictalurus punctatus (Channel catfish) 70 mg/L/48 hr (95% confidence limit: 59.3-82.6 mg/L); static

LC50 Lepomis macrochirus (Bluegill) 120 mg/L/24 hr (95% confidence limit: 73-198 mg/L); static

LC50 Lepomis macrochirus (Bluegill) 79 mg/L/48 hr (95% confidence limit: 54.1-115.3 mg/L); static

For more Ecotoxicity Values (Complete) data for QUINACRINE (10 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 4.9X10+6(SRC), determined from a structure estimation method(2), indicates that quinacrine is expected to be immobile in soil(SRC). Estimated pKa values of 9.4 and 10.7 (amine groups)(3) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from moist soil surfaces is not expected to be an important fate process. Quinacrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-10 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 4.9X10+6(SRC), determined from a structure estimation method(2), indicates that quinacrine is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 9.4 and 10.7 (amine groups)(3) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. Cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4). According to a classification scheme(5), an estimated BCF of 5,400(SRC), from an estimated log Kow of 5.75(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(8). 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), quinacrine, which has an estimated vapor pressure of 1.8X10-10 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 quinacrine may be removed from the air by wet and dry deposition(SRC). Quinacrine absorbs at wavelengths >290 nm(3) and therefore may be expected to be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of quinacrine can be estimated to be 4.9X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that quinacrine is expected to be immobile in soil. The estimated pKa values for quinacrine are 9.4 and 10.7(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ ... People exposed to quinacrine dust in its manufacture have complained of seeing blue haloes or multicolored rings about lights. This has been attributed to brown particles 5-10 um in diameter deposited in the corneal epithelium. Discontinuation of exposure to quinacrine resulted in return of the corneas to normal, and relief of the assoc symptoms in all cases.

/SIGNS AND SYMPTOMS/ Although some adults have survived single quinacrine hydrochloride doses up to 25 g, a dose of 6.8 g has been fatal when given intraduodenally.Symptoms of acute quinacrine toxicity include CNS excitation with restlessness, insomnia, psychic stimulation, and seizures; GI disorders such as nausea, vomiting, abdominal cramps and diarrhea; vascular collapse with hypotension, shock, cardiac arrhythmias or arrest; and yellow skin pigmentation.

/SIGNS AND SYMPTOMS/ Reversible corneal edema or deposits, manifested by visual halos, focusing difficulty, and blurred vision, have been reported in patients receiving long-term quinacrine therapy for suppression of malaria. Retinopathy has been reported rarely in patients receiving high doses of quinacrine for prolonged periods in the treatment of certain chronic diseases, but not patients receiving the drug for cestodiasis or suppression or treatment of malaria.

/CASE REPORTS/ In two patients quinacrine is alleged to have caused optic neuritis, but this does not seem positively established. In one of these cases, a child having malaria, possibly pulmonary tuberculosis, and iridocyclitis in one eye, developed transient optic neuritis in the other eye after receiving several doses of quinacrine plus pamaquine. In the second case the patient was taking quinine as well as quinacrine for malaria. This patient had xanthopsia for 10 days before gradually becoming blind. Papilledema was the only abnormality observed in the fundus. In the course of a month after quinacrine was discontinued, vision recovered completely, although quinine was still being given.

For more Human Toxicity Excerpts (Complete) data for QUINACRINE (6 total), please visit the HSDB record page.

An estimated BCF of 5400 was calculated for quinacrine(SRC), using an estimated log Kow of 5.75(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Estimated pKa values of 9.4 and 10.7 (amine groups) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from moist soil and water surfaces is not expected to be an important fate process. Quinacrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-10 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Experimental administration of 0.375-0.5 g of quinacrine to dogs for 5-15 days produced disturbances in histology of optic nerves... These doses were, however, lethal for most of the animals.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ This study investigated whether the growth of transplanted mammary tumors is altered in rats by treatment with the antimalarial drugs chloroquine (CQ) and quinacrine (QN). Female inbred F344 rats were divided into three experimental groups. Animals were injected ip with either CQ, QN or normal saline for 5 days/week throughout the entire experimental period (25 days). After 7 days of drug treatment each rat received sc one 2 mm aliquot of R3230AC mammary adenocarcinoma in the mid-thoracic region. Eighteen days after implantation, all rats were sacrificed and tumors were excised, weighed and measured. The results indicate that weights and volumes of tumors as well as tumor to body weight ratios were significantly higher in CQ and QN treated animals than those in saline treated animals. The final body weights of rats treated with QN were significantly lower than those treated with saline. The prostaglandin E2 content of tumors was significantly reduced by CQ treatment. Erythrocyte glutathione reductase activity coefficient and reduced glutathione concentrations remained unaffected by both treatments. These results suggest that CQ and QN have significant stimulatory effects on the growth of mammary adenocarcinoma in rats.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 120 mg/kg of quinacrine were injected subcutaneously into rats on the 13th through the 19th gestational days. Fetal death was increased but no defective fetuses were found. The level of quinacrine in the fetal liver was only 9 ug as conpared to the maternal liver of 549 ug.

Small amt of unchanged drug is eliminated (l-form; apparently d-form is metabolized completely) by man and other animals. Several metabolites have been found in small amt, but there is some disagreement as to their structure.

Mepacrine yields 6-chloro-9-(4-ethylamino-1-methylbutyl amino)-2-methoxyacridine in rabbits

Agents used to treat tapeworm infestations in man or animals.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)

Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Absorbed rapidly from the gastrointestinal tract following oral administration.

Rapidly absorbed from the gastrointestinal tract following oral administration. Also rapidly absorbed after intrapleural administration.

Widely distributed; concentrates in the liver, spleen, lungs, and adrenal glands. Concentration in the liver may be 20,000 times that in the plasma. Also deposited in skin, fingernails, and hair. Cerebrospinal fluid (CSF) concentration are 1 to 5% of corresponding plasma level. Lowest concentrations are found in the brain, heart, skeletal muscles, and breast milk.

Less than 11% eliminated in the urine daily; acidification of urine increases urinary excretion of quinacrine by up to 14%; excreted slowly, significant amounts being excreted in the urine for 2 months or more after discontinuation of quinacrine. Small amounts also excreted in bile, sweat, and saliva.

Quinacrine crosses the placenta and concentrations of drugs in fetal tissue are similar to maternal concentrations.

A small amount of quinacrine is excreted in breast milk.