Cycloheximid

log Kow = 0.55

0.55

Plates from amyl acetate, water or 30% methanol

Crystals

10 to 50 mg/mL at 68 °F (NTP, 1992)

At 2 °C (g/100 ml): water 2.1; amyl acetate 7; sol in chloroform, ether, methanol, ethanol; insol in saturated hydrocarbons

INSOL IN PETROLEUM ETHER

Isopropyl alcohol 5.5 g/100 ml; acetone 33.0 g/100 ml; cyclohexanone 19.0 g/100 ml (@ 20 °C)

In water, 2.1X10-4 mg/l @ 25 °C

Solubility in water, g/100ml at 2 °C: 2.1

247 to 250 °F (EPA, 1998)

119.5-121 °C; also listed as 115-16 °C

Glistening plates from methanol; mp: 148-149; specific optical rotation: +22 deg @ 25 °C/D (2.3% in methanol) /Cycloheximide acetate/

119.5-121 °C

Specific optical rotation: -3.38 deg @ 29 °C/D (9.47% in methanol); +6.8 deg @ 25 °C/D (2% in water)

Specific optical rotation: -33 deg @ 25 °C/D (1% in chloroform)

Cycloheximide appears as colorless crystals. Used as a fungicide and as a anticancer drug. (EPA, 1998)

Colorless solid; [ICSC] White to beige powder; [MSDSonline]

COLOURLESS CRYSTALS.

170.1 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID6024882]；169.4 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID6024882]

160.7 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；170.77 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；165.69 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；170.47 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Elemental composition: C: 64.04%; H: 8.24%; N: 4.98%; O: 22.75%

/Cycloheximide/ activity is destroyed by boiling in aqueous soln at pH 7 for 1 hr, but shows no loss of activity after 15 min boiling. At pH 2 /cycloheximide/ activity is not degraded by boiling for 1 hr.

IT HAS INTERESTING PROPERTY OF FORMING STABLE DERIV SUCH AS THE ACETATE, OXIME, & SEMICARBAZONE THAT ARE ACTIVE AS FUNGICIDES.

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]；H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]；H360D ***: May damage the unborn child [Danger Reproductive toxicity]；H411: Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P264, P270, P273, P280, P301+P316, P318, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Danger

Chemical: 2,6-Piperidinedione, 4-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-, [1S-[1.alpha.(S*),3.alpha.,5.beta.]]-

Hazard Traits - Developmental Toxicity; Reproductive Toxicity；Authoritative List - EC Annex VI CMRs - Cat. 1B; Prop 65；Report - regardless of intended function of ingredient in the product

Cycloheximide: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

When exposed to heat, it emits toxic fumes, including nitrogen oxides. (EPA, 1998)

Gives off irritating or toxic fumes (or gases) in a fire.

A skin and eye irritant; May be very toxic by ingestion; [ICSC] A skin irritant; At lethal doses, causes bloody diarrhea, tremors, excitement, coma, and cardiovascular collapse; LD50 = 500 mg/kg in monkeys and dogs, but only 2 mg/kg in rats; [HSDB] Extremely toxic (probable oral lethal dose in humans is 5-50 mg/kg, or 7 drops to 1 teaspoonful for a 150-lb. person); [CAMEO] An irritant; May cause skin sensitization; May cause damage to liver and spleen, and have effects on the blood; [MSDSonline] Toxic to embryo of mice at a maternal dose of 30 mg/kg; Inhibits maturation of amphibian spermatocytes; [REPROTOX]

In 1988, Congress amended FIFRA to strengthen and accelerate EPA's reregistration program. The nine-year reregistration scheme mandated by "FIFRA 88" applies to each registered pesticide product containing an active ingredient initially registered before November 1, 1984. List A consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA had issued Registration Standards prior to the effective date of FIFRA 88. List: A; Case: Cycloheximide; Case No.: 0038; Pesticide type: Fungicide; Registration Standard Date: 6/1/83; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active Ingredient: cycloheximide; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled."

(Non-Specific -- Fungicides, Poison B Solid) Avoid breathing dusts and fumes from burning material. Keep upwind. Wear self-contained breathing apparatus. Avoid bodily contact with the material. Wear full protective clothing.；(Non-Specific -- Fungicides, Poison B Solid) Use agent suitable for surrounding fire. Use alcohol foam, carbon dioxide, or dry chemical. Use water in flooding quantities as fog. (EPA, 1998)

In case of fire in the surroundings, use appropriate extinguishing media.

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Induce vomiting (ONLY IN CONSCIOUS PERSONS!). Rest.

Warning: Effects may be delayed for 6 to 24 hours. Caution is advised.；Signs and Symptoms of Acute Cycloheximide Exposure: Signs and symptoms of acute exposure to cycloheximide may include increased salivation, nausea, vomiting, diarrhea, and dark, bloodstained stools. Dermal effects may range from erythema (redness) to sloughing. Central nervous system excitement, including tremor, may be noted. Liver and kidney damage, coma, and cardiovascular collapse are also possible.；Emergency Life-Support Procedures: Acute exposure to cycloheximide may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination.；Inhalation Exposure:；1. Move victims to fresh air. Emergency personnel should avoid self-exposure to cycloheximide.；2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.；3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.；4. Transport to a health care facility.；Dermal/Eye Exposure:；1. Remove victims from exposure. Emergency personnel should avoid self- exposure to cycloheximide.；2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.；3. Remove contaminated clothing as soon as possible.；4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes.；5. Wash exposed skin areas THOROUGHLY with soap and water.；6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.；7. Transport to a health care facility.；Ingestion Exposure:；1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.；2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.；3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of cycloheximide is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step

In situ amelioration: Seek professional environmental engineering assistance through EPA's Environmental Response Team (ERT), Edison, NJ, 24-hour phone number (201) 321-6660. Contain and isolate spill to limit spread. Construct clay/bentonite swale to divert uncontaminated portion of the watershed around contaminated portion. Isolation procedures include construction of bentonite, polyethylene-lined dams, interceptor trenches, or impoundments. ... Conduct bench-scale and pilot-scale tests prior to decontamination program implementation. Solids must be removed in settling basins. Treatment alternatives for diluted contaminated waters include powdered activated carbon sorption, granular activated carbon filtration, and impoundment in a lined pit with leachate collection system and domed cover.

Treatment alternatives for contaminated soils include well point collection and treatment of leachates as for contaminated waters; bentonite/cement ground injection to immobilize spill, physical removal of immobilized residues, and placement in alined pit with leachate collection system and domed cover.

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.

Evacuate danger area! Consult an expert! Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT wash away into sewer. Sweep spilled substance into covered sealable containers. Carefully collect remainder. Then store and dispose of according to local regulations.

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

CHLORDANE IS REPORTED TO CAUSE RAPID LOSS OF ACTIVITY /OF CYCLOHEXIMIDE/.

Pretreatment of rats with ... spironolactone & ethylestrenol ... protected against the fungicide cycloheximide.

LD50 Mallard duck oral 82.5 mg/kg (95% confidence limit 54.3-126 mg/kg), 3-4-mo old males /sample purity 88.7%/

LD50 Pheasant oral 9.38 mg/kg (95% confidence limit 6.91-12.7 mg/kg), 4-mo old females /sample purity 88.7%/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 47(SRC), determined from a log Kow of 0.55(2) and a regression-derived equation(3), indicates that cycloheximide is expected to have very high mobility in soil(SRC). Volatilization of cycloheximide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.8X10-18 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Cycloheximide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.5X10-13 mm Hg(SRC), determined from a fragment constant method(5). Cycloheximide, present at 100 mg/l, reached 1% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(6), suggesting slow biodegradation in soil(SRC). Cycloheximide is stable in neutral and acid conditions, but is rapidly decomposed by alkali at room temperature to form 2,4-dimethylcyclohexanone(7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 47(SRC), determined from a log Kow of 0.55(2) and a regression-derived equation(3), indicates that cycloheximide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.5X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). At a concentration of 50 ug/l, cycloheximide had a BCF of <0.3 while at 5 ug/l it had a BCF of <2.8 in orange-red killi fish(5). According to a classification scheme(6), these BCF values suggest bioconcentration in aquatic organisms is low(SRC). Cycloheximide, present at 100 mg/l, reached 1% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(5), suggesting slow biodegradation in water(SRC). Cycloheximide is stable in neutral and acid solutions, but is rapidly decomposed under alkaline conditions(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cycloheximide, which has an estimated vapor pressure of 4.5X10-13 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 cycloheximide may be removed from the air by wet and dry deposition(SRC).

Neurotoxin - Other CNS neurotoxin；Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

Redness. Pain.

Redness. Pain.

Diarrhoea. Unconsciousness.

The Koc of cycloheximide is estimated as 47(SRC), using a log Kow of 0.55(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that cycloheximide is expected to have very high mobility in soil. Cycloheximide was classified as a relatively mobile compound in soil based upon a measured Rf value of 0.89 as determined by soil thin-layer chromatography (TLC) in Hagerstown silty clay loam soil(4).

Produced by Streptomyces griseus ...

Cycloheximide is produced in cultures of the streptomycin-producing strains of Streptomyces griseus(1).

Hyaluronic acid synthesis was studied in cultured skin fibroblasts derived from normal subjects. ... Treatment of cells with cycloheximide under conditions in which protein synthesis is inhibited by greater than or equal to 90% had no effect on hyaluronic acid synthesis. ...

No human poisonings have been reported.

CYCLOHEXIMIDE @ 10-4 MOLAR INHIBITED LEUCINE INCORPORATION IN SLICES OF HUMAN LUNG TUMORS, REGENERATING RAT LIVER & HEPATOMAS.

Cycloheximide's production and use as a fungicide(1) may have resulted in its direct release to the environment through various waste streams(SRC). Cycloheximide is produced as a byproduct during the production of streptomycen(1); therefore, waste releases from streptomycen production may release cycloheximide to the environment(SRC).

Chemical: 2,6-Piperidinedione, 4-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-, [1S-[1.alpha.(S*),3.alpha.,5.beta.]]-

Hazard Traits - Developmental Toxicity; Reproductive Toxicity；Authoritative List - EC Annex VI CMRs - Cat. 1B; Prop 65；Report - regardless of intended function of ingredient in the product

Cycloheximide: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

In 1988, Congress amended FIFRA to strengthen and accelerate EPA's reregistration program. The nine-year reregistration scheme mandated by "FIFRA 88" applies to each registered pesticide product containing an active ingredient initially registered before November 1, 1984. List A consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA had issued Registration Standards prior to the effective date of FIFRA 88. List: A; Case: Cycloheximide; Case No.: 0038; Pesticide type: Fungicide; Registration Standard Date: 6/1/83; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active Ingredient: cycloheximide; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled."

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Cycloheximide is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

STIMULATED TRANSPORT OF NUCLEAR RIBONUCLEOPROTEIN COMPLEXES TO CYTOPLASM AFTER ADMIN CYCLOHEXIMIDE TO RATS WAS STUDIED. ADMIN OF 2 MG/KG CYCLOHEXIMIDE CAUSED A DECR IN CONTENT OF TOTAL LIVER NUCLEAR RIBONUCLEOPROTEIN COMPLEX WITHIN 2 HR. THE OVERALL DECR WAS DUE TO AN INCREASED TRANSPORT INTO THE CYTOPLASM, NOT DECREASED SYNTHESIS. OTHER RESULTS SUGGEST THAT DURING INHIBITORY PHASE OF PROTEIN SYNTHESIS, GENE TRANSCRIPTION CONTINUES & GENE PRODUCT IS TRANSPORTED TO CYTOPLASM FOR TRANSLATION.

CYCLOHEXIMIDE (2-5 MG/KG BODY WT) CAUSED COMPLETE INHIBITION OF PROTEIN SYNTHESIS IN RAT LIVER WITHIN 30 MIN, & THE LABELING OF NUCLEAR PROTEINS WAS STRONGLY INHIBITED. UNDER THESE CONDITIONS, THE AMT OF NUCLEOLAR 45 S PRE-rRNA & ITS OROTATE-(14)C LABELING REMAINED UNAFFECTED FOR AT LEAST 4 HR, INDICATING THAT INITIALLY THE RATES OF SYNTHESIS & PROCESSING OF 45 S PRE-rRNA WERE NOT APPRECIABLY ALTERED. DRASTIC ALTERATIONS IN THE 45 S PRE-rRNA PROCESSING PATHWAYS OCCURRED AT THE EARLY STAGES OF CYCLOHEXIMIDE ACTION. THE CHANNELING OF NUCLEAR PRE-rRNA ALONG ALTERNATIVE PROCESSING PATHWAYS IS UNDER STRINGENT CONTROL BY THE CONTINUOUS SUPPLY OF CRITICAL PROTEINS.

CYCLOHEXIMIDE IS A POTENT INHIBITOR OF PROTEIN SYNTHESIS IN FUNGI & ANIMALS. IT CAUSES AN INCREASE IN ADRENAL RNA, INCREASED PRODUCTION OF GLUCOCORTICOIDS ... & DECREASE IN PYRUVATE UTILIZATION IN ISOLATED ADIPOSE TISSUE.

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.

Antibiotic compound isolated from Streptomyces griseus; [Merck Index] Used as a fungicide, plant growth regulator, protein synthesis inhibitor, and to stimulate the natural abscission process (pre-harvest use on citrus); [HSDB]

Farming (Pesticides) [Category: Industry]

For Cycloheximide (USEPA/OPP Pesticide Code: 043401) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Fungicide; plant growth regulator; as protein synthesis inhibitor

/Cycloheximide/ is used in laboratory media as a selective agent to permit isolation of pathogenic and non-pathogenic fungi from specimens such as sputa and feces which may be other fungi.

Cycloheximide has a limited application in treatment of downy mildew of onions and shoot blight of Japanese larch.

Antibiotic substance isolated from beers of streptomycin-producing strains of Streptomyces griseus: Leach et al, J Am Chem Soc 69, 474 (1947); Ford, Leach, J Am Chem Soc 70, 1223 (1948); Whiffen et al, US patent 2,574,519 (1951 to Upjohn). Production, assay and antibiotic activity: Whiffen, J Bacteriol 56, 283 (1948). Improved production method: Kominek, US patents 3,915,802-3 (both 1975 to Upjohn). ... synthesis of dl- and l-forms: Johnson et al, J Am Chem Soc 88, 149 (1966).

USEPA/OPP Pesticide Code 043401; Trade Names: Acti-dione; Acti-aid; ENT-15541; Acti-dione BR; Acti-dione PM; Actispray; Hizarocin; Kaken; Naramycin A; NSC-185; U 4527.

Discontinued names: Acti-Aid, Acti-dione, ... Actispray, Hizarocin

7.7% WETTABLE POWDER; ACTI-DIONE FERRATED (UPJOHN) 4% WT/WT CYCLOHEXIMIDE, 96% EXSICCATED FERROUS SULFATE USED FOR TREATMENT OF TURF. ACTI-DIONE THIRAM (0.75%, 75.00% & 24.25% INERT INGREDIENTS) TURF FUNGICIDE; ACTI-DIONE PM (0.027%) POWDERY MILDEW CONTROL ON ORNAMENTALS. ACTI-AID CITRUS ABSCISSION AGENT (COMPONENT A 4.22% WT/WT WATER SOL FORMULATION AND A SEPARATE COMPONENT B- SURFACTANT).

This ... compound is ... formulated as an oily soln ... & water-sol tablets.

For more Formulations/Preparations (Complete) data for CYCLOHEXIMIDE (21 total), please visit the HSDB record page.