Clioquinol

305.5

305.50

153637

204-984-4

7BHQ856EJ5

759822|3531

DTXSID7022837

C65337

Brownish-yellow, bulky powder|Yellow brown needles from alcohol, acetic acid.|A voluminous, spongy, yellowish to white brownish powder

D - Dermatologicals|G - Genito urinary system and sex hormones|P - Antiparasitic products, insecticides and repellents|S - Sensory organs

2933492250

33.1

3.86

Iodochlorohydroxyquinoline is a cream-colored to brownish-yellow powder. Practically odorless. Decomposes at 178-179°C. Used as a topical anti-infective.

1.8959 (estimate)

178-179 °C

350.4±37.0 °C(Predicted)

165.7±26.5 °C

1.768

H2O: <0.1 g/100 mL at 20 ºC;soluble in DMSO (>25 mg/ml), boiling alcohol ((1:43)), methanol, and chloroform ((1:120)).

2-8°C

Oral-rat LD50: > 5000 mg/kg; Oral-Mouse LD50: 69 mg/kg

Combustible; Fire breaks down toxic nitrogen oxides, iodide and chloride fumes

Practically odorless

138.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Decompose at about 178-179 °C

Insoluble in water.

Amines, Phosphines, and Pyridines

IODOCHLOROHYDROXYQUINOLINE is incompatible with strong oxidizing agents, strong acids, acid chlorides and acid anhydrides (NTP, 1992). Darkens on exposure to light.

III

6.1(b)

UN 2811 6.1/PG 3

3

25

36/37/39-45

VC5075000

T

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

Clioquinol darkens on exposure to light.

Missing Phrase - N15.00950417

H301

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl clioquinol hydrocortisone and clioquinol nystatin, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Clioquinol hydrocortisone and clioquinol nystatin/

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H301 (33.85%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P273, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 130 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this material from exposure to light, and store it under ambient temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

highly toxic

... Use in those younger than 2 years of age is contraindicated.

Used as a topical antifungal treatment.

Amebicides; Anti-Infective Agents, Local|Clioquinol is used topically in the treatment of tinea pedis, tinea cruris, and other skin infections caused by dermatophytic fungi (ringworm).|MEDICATION (VET): has been used as an intestinal anti-infective.|Topical anti-infective; anti-amebic|For more Therapeutic Uses (Complete) data for CLIOQUINOL (7 total), please visit the HSDB record page.

Although clioquinol previously was used in the treatment of diaper rash (diaper dermatitis), use of the drug in children currently is not recommended, and use in those younger than 2 years of age is contraindicated.|Clioquinol generally appears to be well tolerated following topical application to the skin. Local irritation, rash, and sensitivity reactions have been reported occasionally. If any of these effects occurs, the drug should be discontinued and a physician consulted. Cross sensitivity with other hydroxyquinoline and quinoline derivatives (eg, certain antimalarials) and, occasionally, to iodides can occur. Clioquinol can stain the skin, and discoloration of the hair and nails has been reported rarely. Prolonged use of the drug can result in overgrowth of nonsusceptible organisms, which may require appropriate therapy. When clioquinol is used topically in fixed combination with hydrocortisone, the usual precautions associated with topical corticosteroid therapy should be observed.|Because of an association between oculotoxic/neurotoxic effects (eg, optic neuritis, optic atrophy, subacute myelo-optic neuropathy) and oral clioquinol therapy (usually at high dosages for prolonged periods) and the availability of effective alternative topical antifungals, use of clioquinol in children is not recommended, and use in those younger than 2 years of age is contraindicated.|Percutaneously absorbed clioquinol, which contains iodine, may interfere with certain thyroid function tests (eg, protein-bound iodine); therefore, the manufacturer recommends that at least 1 month elapse between discontinuance of topical therapy with the drug and performance of these tests. Clioquinol also may produce false positive results in the ferric chloride test for phenylketonuria when the drug is present in urine or the diaper.|For more Drug Warnings (Complete) data for CLIOQUINOL (8 total), please visit the HSDB record page.

Clioquinol is a broad-spectrum antibacterial with antifungal properties. Application of clioquinol to extensive or eroded areas of the skin may lead to increased protein-bound iodine (PBI) levels within 1 week. In addition, elevated PBI levels may occur when relatively small areas of the skin are treated with clioquinol for more than 1 week.

Topical absorption is rapid and extensive, especially when the skin is covered with an occlusive dressing or if the medication is applied to extensive or eroded areas of the skin. Clioquinol is absorbed through the skin in sufficient amounts to affect thyroid function tests.|Clioquinol is absorbed systemically following topical application to the skin. In 2 studies in which clioquinol combined with a corticosteroid was applied topically to the skin as a cream or ointment, it was estimated that about 2-3% of the dose was absorbed systemically. However, in another study in which the drug was applied alone to the skin as a 3% cream and covered with an occlusive wrap for 12 hr, it was estimated that about 40% of the dose was absorbed percutaneously during this period.|Patients with widespread dermatitis were treated with 15-20 g of 3% clioquinol ointment to 40% of the body area twice daily. The serum concentration increased to 0.8-1.2 ug/ml within 4 hr of application. In one patient, 15-20 mg was excreted in the urine daily mainly in the form of conjugated metabolites. This skin treatment resulted in a urinary excretion somewhat less than is obtained after a daily oral dose of 25 mg (one tablet) of clioquinol. Thus, 3-4% of the applied clioquinol was absorbed. 25% was excreted in the urine.

Clioquinol has known human metabolites that include Clioquinol O-glucuronide.

11-14 hr

Clioquinol is bacteriostatic, however, the precise mechanism of its action is unknown.

SYMPTOMS: Symptoms of exposure to this compound include changes in central nervous system electrical function and optic nerve damage. Other symptoms include abdominal discomfort, diarrhea, paresthesias in the legs (possibly progressing to paraplegia), loss of visual acuity (sometimes leading to irreversible blindness), characteristic green pigmentation of the tongue, feces and urine, sensory disturbances and subacute myelo-optic neuropathy. Irritation of the skin, eyes, mucous membranes and upper respiratory tract may occur. ACUTE/CHRONIC HAZARDS: This compound may be harmful by ingestion or inhalation. It is an irritant of the skin, eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits very toxic fumes of nitrogen oxides, carbon monoxide, carbon dioxide, hydrogen chloride gas and hydrogen iodide. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Emesis induction is indicated after adult ingestion of 1,500 to 1,800 mg of clioquinol if there is no coma, convulsions, or loss of gag reflex. Otherwise, gastric lavage with tracheal protection, activated charcoal, and cathartics. There are no data on the use of forced diuresis, hemodialysis, peritoneal dialysis, hemoperfusion, or exchange transfusion in the treatment of halogenated 8-hydroxyquinoline poisonings. There are no antidotes.

Beginning in 1956, an epidemic of a new GI neurologic syndrome, subacute myelo-optico-neuropathy, occurred in Japan. When it was publicly announced on August 7, 1970, approximately 10,000 cases had already been reported. Its etiologic agent was identified as iodochlorhydroxyquin. By September 8, 1970, all halogenated hydroxyquinolines were removed from the market in Japan. Since then, the epidemic has not recurred.|Criteria for the diagnosis of subacute myelo-optico-neuropathy. Cardiac Signs: Abdominal symptoms (abdominal pain, diarrhea, etc.) before the onset of neurological symptoms. Acute or subacute onset of bilateral ascending paresthesia and dysesthesia of the lower extremities. Other Major Signs: Impairment of deep sensation and weakness in the lower limbs, with or without pyramidal signs. Less commonly, sensorimotor disturbances in the upper limbs. Occasionally, one or more of the following: a. Bilateral impairment of vision. b. Disturbances of consciousness, convulsions, psychic symptoms, and other cerebral symptoms. c. Greenish discoloration of the tongue and feces. d. Sphincter disturbances. Protracted course with occasional relapses. No significant laboratory findings in blood and cerebrospinal fluid. Rare occurrence in children.|... There have been many similar cases of subacute myelo-optico-neuropathy scattered in various parts of the world affecting adults, with convincing histories relating clioquinol to disturbances of vision, with varying deg of spinal cord involvement. Visual disturbances have ranged from impairment of discrimination of colors to blindness from optic atrophy, with moderate involvement in the form of central scotomas with symmetrically reduced visual acuity. Clinical ophthalmoscopic abnormality appears to be limited to pallor of the disc in eyes with optic atrophy. In a number of cases there has been improvement of vision during several months after administration of clioquinol was discontinued. No treatment has been effective other than stopping administration of clioquinol.|Some of the earliest suspicions of toxicity affecting vision were in relation to children who were being treated for acrodermatitis enteropathica for long periods with large doses when their vision was found to be much impaired, and optic atrophy was diagnosed. Some children had difficulty in walking as well as poor vision. An investigating committee reported in 1974 knowledge of more than a dozen children with optic neuropathy from clioquinol. Less than half had symptoms of peripheral neuropathy.|A neurotoxicity dose response curve for iodochlorhydroxyquin can be constructed as follows: 750 mg/day for 4 wk or less little risk of toxic reactions. 750-1500 mg/day for less than 2 wk 1% have neurologic symptoms. 750-1,500 mg/day for over 2 wk 35% develop symptoms. 1800 mg/day for 5 days one patient developed symptoms. At higher doses onset of toxic reactions may begin within 24 hr after beginning therapy. The clinical symptoms associated with ingestion of halogenated hydroxyquinolines are primarily those of peripheral neuropathy or myelopathy, with occasional cerebral manifestations. Symptoms range from minimal dysesthesia to death and include optic atrophy.

5 Chloro 7 iodo 8 quinolinol

Topical Cream 3%, Iodochlorhydroxyquin Cream, CMC.|Topical Cream, 3% with Hydrocortisone 0.5%, Ala-Quin, Del-Ray; Vioform -Hydrocortisone Mild, Ciba; 3% with Hydrocortisone 1%, Corque, Geneva; Cortin, C & M Pharmacal; Hysone, Mallard; Vioform -Hydrocortisone; Ciba 3% with Hydrocortisone 1% and Pramoxine Hydrochloride 1% 1 + 1-F, Dunhall Lotion, 0.75% with Hydrocortisone 0.25%, UAD Lotion (with parabens and propylene glycol), UAD Laboratories Ointment, 3% with Hydrocortisone 1%, Vioform-Hydrocortisone, Ciba.|Cream and ointment, 3%|Clipquinol is available in the United States and elsewhere as a 3% ointment or cream and a powder.

8-Quinolinol, 5-chloro-7-iodo-: INACTIVE|Sterilizable substitute for iodoform.

Determination of clioquinol using GC equipped with a FID. Flow rate is 30 ml/min.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients