Clioquinol

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.

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.

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)

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.

In dogs, clioquinol caused decrease of visual acuity, with vacuolation and loss of axons in the optic tract. There seems to be agreement that peripheral nerves are not primarily affected, but that long tracts in the spinal cord show degeneration, and that the relatively short axons of the optic nerves are especially vulnerable. The seemingly unique distribution has been termed central distal axonopathy. Demyelination follows axon degeneration.

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.

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/

Used as a medicinal cream, ointment, or powder; [HSDB]

MEDICATION (VET)

MEDICATION

Use (kg; approx.) in Germany (2009): >250

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-: ACTIVE

Sterilizable substitute for iodoform.