7-Chlor-2',4,6-trimethoxy-6'-methyl-spiro(benzo-furan-2(3H),1'-(2)cyclohexen)-3,4'-dion

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.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Griseofulvin preparation should generally be stored at a temperature less than 40 degrees C, preferably between 15-30 degrees C; microsize griseofulvin oral suspension should be protected from freezing and stored in light-resistant containers. ... Should be stored in well-closed containers.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

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.

SRP: At the time of review, 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.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for GRISEOFULVIN (9 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

...METABOLISM /OF GRISEOFULVIN/ IS ACCELERATED BY...PRIMIDONE IN RATS AND MAN...

GRISEOFULVIN ACTED AS A COCARCINOGEN WITH SKIN APPLICATIONS OF 3-METHYLCHOLANTHRENE IN MICE...

Effects may be potentiated when alcohol is used concurrently with griseofulvin; also, concurrent use with griseofulvin may result in tachycardia, diaphoresis, and flushing.

/Coumarin- or indandione-derivative anticoagulants/ effects, may be decreased when these agents are used concurrently with griseofulvin; decrease is thought to be due to accelerated metabolism of anticoagulants secondary to stimulation of hepatic microsomal enzyme activity; prothrombin time should be monitored until a stable level is maintained; dosage adjustments may be necessary during and after griseofulvin therapy.

For more Interactions (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page.

Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with griseofulvin, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. Clinically apparent hepatotoxicity is rare and only isolated case reports have been published. The liver injury is typically cholestatic and usually arises within the first few months of therapy. Signs of hypersensitivity such as fever, rash and eosinophilia are rare but griseofulvin can include hypersensitivity reactions and at least one case of DRESS syndrome accompanied by serum aminotransferase elevations has been reported with its use. Published cases of griseofulvin induced liver injury have all been self-limited, recovery requiring 1 to 3 months. Griseofulvin can increase intrahepatic levels of protoporphyrin and induce acute attacks of porphyria in patients with acute intermittent porphyria in remission.

Overall, griseofulvin has few adverse effects. It most commonly causes gastrointestinal issues of nausea, vomiting, and diarrhea, as well as headaches and allergic reactions. Other adverse effects include photosensitivity, fixed drug eruption, petechiae, pruritus, and urticaria. It may cause a worsening of lupus or porphyria.

Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

PHOTOSENSITIVITY & PPT OF DISCOID LUPUS ERYTHEMATOSUS IN 1 PT WITH NO PREVIOUS EVIDENCE OF THE DISEASE; IN ANOTHER PT WITH KNOWN SYSTEMIC LUPUS ERYTHEMATOSUS FEVER & MALAISE AFTER TREATMENT WITH GRISEOFULVIN.

THE OCCURRENCE OF CHOLESTATIC JAUNDICE IN PT RECEIVING GRISEOFULVIN IS DESCRIBED. COMPLETE RECOVERY FOLLOWED DISCONTINUATION OF DRUG ADMIN.

Griseofulvin

Group 2B: Possibly carcinogenic to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2001

2000

2B, possibly carcinogenic to humans. (L135)

Drug Induced Liver Injury Rank (DILIrank 2.0)

Griseofulvin

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

...IT INTERFERES WITH CHITIN DEVELOPMENT IN MOSQUITO LARVAE.

TERATOGENIC ACTIVITY WAS OBSERVED MOST OFTEN WHEN PREPN WAS APPLIED ON 8TH-9TH DAY OF PREGNANCY. MALFORMATIONS OR SKELETON WERE DEMONSTRATED IN 46% OF FETUSES FOLLOWING AN ORAL 5 G/KG DOSE.

PHOTOSENSITIZING WAS STUDIED IN MICE BY A QUANTITATIVE IN VIVO METHOD. PHOTOTOXICITY IN VIVO, HITHERTO NOT DEMONSTRATED, WAS OBSERVED WITH GRISEOFULVIN.

FEEDING MICE GRISEOFULVIN INCR LIVER WT TO 9% OF BODY WT WITH PROPORTIONAL DECR IN MICROSOMAL PROTEIN/G LIVER WET WT. CYTOCHROME P-450 & B5 CONTENT WAS 50% & 200% OF THAT IN CONTROL MICROSOMES.

For more Non-Human Toxicity Excerpts (Complete) data for GRISEOFULVIN (21 total), please visit the HSDB record page.

Evaluation: There is inadequate evidence in humans for the carcinogenicity of griseofulvin. There is sufficient evidence in experimental animals for the carcinogenicity of griseofulvin. Overall evaluation: Griseofulvin is possibly carcinogenic to humans (Group 2B).

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).

MEDICATION (VET)

MEDICATION

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

Griseofulvin is used both in animals and in humans, to treat fungal infections of the skin (commonly known as ringworm) and nails. Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. Griseofulvin is reserved for cases with nail, hair or large body surface involvement. (Wikipedia)

ANTIBIOTIC SUBSTANCE PRODUCED BY PENICULLIUM GRISEOFULVUM DIERCKX AND BY P. JANCZEWSKII ZAL. (= P. NIGRCANS (BANIER) THOM.). ISOLATION: OXFORD ET AL, BIOCHEM J 33, 240 (1939); BRIAN ET AL, TRANS BRIT MYCOL SOC 29, 173 (1946); HOCKENHULL, DOREY ET AL, US PATENT 3,069,328-9 (1962 TO GLAXO).

DUSTS 1.5-3.5% WT/WT FOR USE AT 75 LB/ACRE. WETTABLE POWDERS, DISPERSIBLE CONCENTRATES (SOLN IN DIMETHYL FORMAMIDE WITH DISPERSING AGENT). /SRP: NOT APPROVED FOR USE ON CROPS IN US./

GRISEOFULVIN, USP (FULVICIN U/F, GRIFULVIN V, GRISACTIN), IS MARKETED IN CAPSULES CONTAINING 125 OR 250 MG & IN TABLETS CONTAINING 125, 250, OR 500 MG; IT IS ALSO AVAIL AS ORAL SUSPENSION (125 MG/5 ML). ... TABLETS INCORPORATING ULTRAMICROSIZED PREPN (FULVICIN P/G, GRIS-PEG) CONTAIN 125 OR 250 MG OF GRISEOFULVIN (EQUIVALENT TO 250 OR 500 MG OF PREPN...ABOVE).

BIOAVAILABILITY OF A 500 MG MICROSIZE FORMULATION WAS COMPARED TO 2 NEW ULTRAMICROSIZE FORMULATIONS. ONE 330 MG ULTRAMICROSIZE TABLET IS BIOEQUIVALENT TO 2 165 MG ULTRAMICROSIZE TABLETS & EITHER ULTRAMICROSIZE DOSAGE REGIMEN IS BIOEQUIVALENT TO 500 MG OF THE MICROSIZE FORMULATION.

THE BIOAVAILABILITY OF GRISEOFULVIN TABLETS SPRAY DRIED WITH 20% METHYLCELLULOSE WAS DETERMINED IN 10 RABBITS. COMPARED TO REGULAR TABLETS, DRUG ABSORPTION WAS GREATER IN THE SPRAY DRIED PREPN.

Tablet, 250 mg, 500 mg; suspension, 250 mg/ml /Grifulvin V/