Ketoconazole｜Huagongshe

Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용

HCID 47576생성일: 2026년 10월 27일

Ketoconazole

(-)-R 41400 · (-)-Ketoconazol · (-)-KETOCONAZOLE · ( ) Ketoconazole,()Ketoconazole · Levoketoconazole [(-)-Ketoconazol · Ethanone, 1-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]-

https://huagongshe.com/ko/chemical/47576

Ketoconazole 분자 구조식

식별자 및 물리적 특성

CAS No.	142128-57-2
분자식	C26H28Cl2N4O4
평균 분자량	531.4 g/mol
단동위원소 질량	530.1487608 g/mol
SMILES	CC(=O)N1CCN(c2ccc(OC[C@@H]3CO[C@@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1
InChIKey	XMAYWYJOQHXEEK-ZEQKJWHPSA-N
PubChem CID	47576
ChEMBL	CHEMBL157101
ChEBI	CHEBI:47518
EC No.	265-667-4
DTXSID	DTXSID60161949

화학 및 물리적 성질

XLogP	4.3
극성 표면적	69.1
수소 결합 공여자 수	0
수소 결합 수용자 수	6
회전 가능 결합 수	7
무거운 원자 수	36
형식 전하	0
복잡도	735
LogP(분배 계수)	4.35log Kow = 4.34
Color/Form	Crystals from 4-methylpentanone
용해도	0.0866 mg/LSolubility in water: noneDMSO:33.33(Max Conc. mg/mL)62.72(Max Conc. mM)
Decomposition	When heated to decomposition it emits toxic fumes of /hydrogen chloride and nitrogen oxides/.
녹는점	146146 °C148-152 °C
증기압	Vapor pressure, Pa at 25 °C: (negligible)
Physical Description	SolidCOLOURLESS CRYSTALS OR POWDER.
Ionization Efficiency	Positive3.9792360622.7Thermo LTQElectrospray ionizationformic acid (5.3nM)
물리적 상태	Solid
색상	White to off-white

안전 및 규제

GHS 분류	DangerH301: Toxic if swallowed [Danger Acute toxicity, oral]H360F *: May damage fertility [Danger Reproductive toxicity]H373 : May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]P203, P260, P264, P270, P273, P280, P301+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)
규제 정보	Hazard Traits - Reproductive ToxicityAuthoritative List - EC Annex VI CMRs - Cat. 1BReport - if used as a fragrance or flavor ingredientKetoconazole: Does not have an individual approval but may be used under an appropriate group standard
기타 안전 정보	IMAP assessments - Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis-: Human health tier I assessmentIMAP assessments - Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis-: Environment tier I assessment
화재 위험	Not combustible.
화재 가능성	Not combustible.
FDA 요건	The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ketoconazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including ketoconazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
EC 분류	Symbol: T, NR: 60-25-48/22-50/53S: 53-45-60-61Note: E
UN 분류	UN Hazard Class: 6.1UN Pack Group: III

Hazard Classes and Categories

Acute Tox. 3 (98.5%)Repr. 1B (78.1%)Repr. 1B (20.4%)STOT RE 2 (97.8%)Aquatic Acute 1 (97.8%)Aquatic Chronic 1 (98.5%)Reproductive toxicity - category 1BAcute toxicity - category 3Specific target organ toxicity (repeated exposure) - category 2Hazardous to the aquatic environment (acute) - category 1Hazardous to the aquatic environment (chronic) - category 1Acute Tox. 3 *STOT RE 2 *Aquatic Chronic 1

응급 조치	Fresh air, rest.Rinse and then wash skin with water and soap.Rinse with plenty of water (remove contact lenses if easily possible).Rinse mouth. Give a slurry of activated charcoal in water to drink. Refer immediately for medical attention.

소화 절차	Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

보관 조건

Store at controlled room temperature 15 deg - 25 °C (59 deg - 77 °F). Protect from moisture.Ketoconazole topical cream should be stored at a temperature less than 25 °C and should not be frozen. The cream should not be stored at high temperatures (eg, warmer than 37 °C), since creams generally separate at these temperatures. Ketoconazole 2% shampoo should be stored at temperatures not exceeding 25 °C and should be protected from lightthe 1% shampoo should be stored between 2-30 °C and should be protected from light and freezing.Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C.

정리 방법

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

처리 방법

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.Waste treatment methods. Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

누출 처리	Personal protection: filter respirator for organic gases and particulates adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

Preventive Measures

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

상호 작용

Because gastric acidity is necessary for the dissolution and absorption of ketoconazole, concomitant use of drugs that decrease gastric acid output or increase gastric pH (e.g., antacids, antimuscarinics, histamine H2-receptor antagonists, proton-pump inhibitors, sucralfate) may decrease absorption of ketoconazole resulting in decreased plasma concentrations of the antifungal. Concomitant use of antacids, antimuscarinics, histamine H2-receptor antagonists, proton-pump inhibitors (e.g., omeprazole, lanosprazole), or sucralfate is not recommended in patients receiving ketoconazole.Elevated plasma concentrations of digoxin have been reported in patients receiving ketoconazole. Although it is unclear whether concomitant use of ketoconazole caused these increased concentrations, digoxin concentrations should be monitored closely in patients receiving the antifungal agent.Like other imidazole derivatives, ketoconazole may enhance the anticoagulant effect of coumarin anticoagulants. When ketoconazole is used concomitantly with these drugs, the anticoagulant effect should be carefully monitored and dosage of the anticoagulant adjusted accordingly.Concomitant use of mefloquine (single 500-mg dose) and ketoconazole (400 mg once daily for 10 days) in healthy adults increased the mean peak plasma concentration and AUC of mefloquine by 64 and 79%, respectively, and increased the mean elimination half-life of mefloquine from 322 hours to 448 hours. Because of the risk of a potentially fatal prolongation of the corrected QT (QTc) interval, the manufacturer of mefloquine states that ketoconazole should not be used concomitantly with mefloquine or within 15 weeks after the last mefloquine dose.For more Interactions (Complete) data for KETOCONAZOLE (51 total), please visit the HSDB record page.

Hepatotoxicity

Mild and transient elevations in liver enzymes occur in 4% to 20% of patients on oral ketaconazole. These abnormalities are usually transient and asymptomatic and uncommonly require dose adjustment or discontinuation. Clinically apparent hepatotoxicity from ketaconazole is well described in the literature and is estimated to occur in 1:2,000 to 1:15,000 users. The liver injury typically presents with an acute hepatitis-like picture 1 to 6 months after starting therapy. While most cases present with a hepatocellular pattern of injury, cholestatic forms have been described. Rash, fever and eosinophilia are rare as is autoantibody formation. Recovery upon stopping therapy may be delayed and generally takes 1 to 3 months. Severe cases with acute liver failure and death or need for emergency liver transplantation have been described.Likelihood score: A (well established cause cause of clinically apparent liver injury).

생태독성 수치	EC50Species: Daphnia magna (Water Flea) age <24 hr neonateConditions: freshwater, static, 20 °CConcentration: 8100 ug/L for 24 hr (95% confidence interval: 4600-10800 ug/L)Effect: intoxication, immobilization /100% purity/Concentration: 1510 ug/L for 48 hr (95% confidence interval: 1160-1910 ug/L)

환경 거동

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,000(SRC), determined from a log Kow of 4.34(2) and a regression-derived equation(3), indicates that ketoconazole is expected to have slight mobility in soil(SRC). The estimated pKa of 3.96(4) indicates that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of ketoconazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.6X10-20 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Ketoconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.4X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Ketoconazole was found to be biodegraded under sewage treatment plant conditions(5), suggesting biodegradation may be an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,000(SRC), determined from a log Kow of 4.34(2) and a regression-derived equation(3), indicates that ketoconazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 5.6X10-20 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 340(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Ketoconazole was found to be biodegraded under sewage treatment plant conditions(7), suggesting biodegradation may be an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ketoconazole, which has an estimated vapor pressure of 6.4X10-14 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 ketoconazole may be removed from the air by wet and dry deposition(SRC). Ketoconazole contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

유해 작용

Systemic ketoconazole administration most commonly causes gastrointestinal side effects. These include nausea, vomiting, constipation, abdominal pain, dry mouth, flatulence, and tongue discoloration. It can also cause adrenal insufficiency due to its role in the inhibition of enzymes in the steroid synthesis pathway. Decreases in cortisol synthesis can lead to orthostatic hypotension. In high doses, it can also cause gynecomastia in males. Ketoconazole can cause severe liver injury and jaundice.Hypersensitivity reactions have also been reported, such as anaphylaxis and urticaria. High-dose ketoconazole has been shown to cause an increase in long bone fragility and lead to fracture. Other side effects include alcohol intolerance, decreased platelet count, epistaxis, fatigue, hot flash, hyperlipidemia, insomnia, myalgia, nervousness, paresthesia, and peripheral edema. Topical ketoconazole can cause dermatological reactions, including pruritis, stinging, and dryness at the application site. There are also reports of dry hair, dry scalp, and oily hair when using ketoconazole-containing shampoo. Less common adverse effects include abnormal hair texture, alopecia, angioedema, contact dermatitis, eye irritation, headache, hypersensitivity reaction, impetigo, and pyogenic granuloma.

Milk Concentrations	EXPERIMENTAL: Ketoconazole has been shown to be excreted in the milk.EXPERIMENTAL: Infant exposure to ketoconazole in human milk was calculated to be 0.4% on average (maximum 1.4%) of those expected from therapeutic doses given directly to infants. ...

독성 요약

IDENTIFICATION AND USE: Ketokonazole is used as antifungal medication. HUMAN EXPOSURE AND TOXICITY: Transient increases in serum AST, ALT, and alkaline phosphatase concentrations may occur during ketoconazole therapy. Serious hepatotoxicity has occurred in patients receiving oral ketoconazole, including cases that were fatal or required liver transplantation. Hepatotoxicity may be hepatocellular (in most cases), cholestatic, or a mixed pattern of injury. Although ketoconazole-induced hepatotoxicity usually is reversible following discontinuance of the drug, recovery may take several months and rarely death has occurred. Symptomatic hepatotoxicity usually is apparent within the first few months of ketoconazole therapy, but occasionally may be apparent within the first week of therapy. Some patients with ketoconazole-induced hepatotoxicity had no obvious risk factors for liver disease. Serious hepatotoxicity has been reported in patients receiving high oral ketoconazole dosage for short treatment durations and in patients receiving low oral dosage of the drug for long durations. Many of the reported cases of hepatotoxicity occurred in patients who received the drug for the treatment of tinea unguium (onychomycosi or the treatment of chronic, refractory dermatophytoses. Ketoconazole-induced hepatitis has been reported in some children. Usual dosages (ie, 200-400 mg daily) of ketoconazole have been reported to transiently (for 2-12 hours) inhibit testicular testosterone synthesis. A compensatory increase in serum luteinizing hormone (LH) concentrations may occur. Dosages of 800-1200 mg daily have been reported to have a more prolonged effect on testosterone synthesisin one study in males receiving these high dosages, serum testosterone concentrations remained at a subnormal level (ie, less than 300 ng/dL) throughout the day in about 30% of those receiving 800 mg daily and in all of those receiving 1200 mg daily. Oligospermia, decreased libido, and impotence often occuThe Food and Drug Administration warns that oral dosing of ketoconazole can lead to hepatotoxicity and adrenal insufficiency and that ketoconazole-associated hepatotoxicity is common. There are many off-label uses for ketoconazole. Therefore, careful selection of ketoconazole as a treatment is necessary due to serious hepatoxic side effects.Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. (A1990, A1991, A1992, A1993)

생태독성 발췌

/AQUATIC SPECIES/ The use of N-substituted imidazoles is widespread, and imidazole and triazole fungicides have been detected in the aquatic environment and shown to bioaccumulate in fish. ...The effects of the model imidazole, ketoconazole, on drug-metabolizing cytochrome P450 (CYP) forms /were investigated/ ... focused on cytochrome P4501A (CYP1A) and cytochrome P4503A (CYP3A) expression and activities in juvenile rainbow trout and in adult killifish. The CYP1A expression (mRNA, protein) and activity was induced in rainbow trout, whereas in killifish no effect of ketoconazole on CYP1A protein expression was observed. A biphasic dose-response relationship was observed between ketoconazole exposure and hepatic CYP1A-mediated ethoxyresorufin O-deethylase (EROD) activity in rainbow trout in vitro and in vivo, implying that higher doses of ketoconazole inhibit CYP1A activities. Slight induction of CYP3A protein levels was observed in rainbow trout exposed in vivo to ketoconazole. However, the CYP3A-mediated benzyloxy-4-[trifluoromethyl]-coumarin (BFC) O-debenzyloxylase activity was reduced in rainbow trout and killifish treated with ketoconazole. In vitro inhibition studies confirmed that ketoconazole was a potent inhibitor of both CYP3A and CYP1A enzyme activities in these species. This study showed that ketoconazole induced CYP1A and CYP3A expression in rainbow trout. However, the most pronounced effect of ketoconazole was a 60 to 90% decrease in CYP3A catalytic activities in rainbow trout and in killifish./AQUATIC SPECIES/ This study focuses on effects of two classes of xenobiotics, azole fungicides and xenoestrogens, both of which have been detected in the aquatic environment. ...Rainbow trout (Oncorhynchus mykiss) /were exposed/ to two different pharmaceutical representatives of these two classes, such as the imidazole ketoconazole and the synthetic estrogen analogue, 17alpha-ethynylestradiol (EE(2)). Juvenile rainbow trout were i.p. injected with a single low dose of EE(2) (2.5 ug/kg), alone or in combination with ketoconazole (100 mg/kg). Hepatic microsomal CYP1A and CYP3A protein expressions were analyzed in Western blots using polyclonal antibodies (PAb) and enhanced cheminoluminescence. CYP1A activities were analyzed using the ethoxyresorufin-O-deethylase (EROD) assay and CYP3A activities were analyzed using the benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) assay. Plasma vitellogenin (vtg) and sex steroid hormones (i.e. 17beta-estradiol, testosterone and 11-keto-testosterone) were analyzed using commercially available ELISA-kits. The vtg mRNA expression was analyzed using quantitative (Q)-PCR. The dose of EE(2) selected had little or no effect on the estrogen receptor (ER) mediated vtg induction. However, in combination with ketoconazole this threshold-dose of EE(2) resulted in significantly elevated plasma vtg levels, 6 days post injection. Exposure to ketoconazole resulted in up to nine-fold induction of CYP1A after 3 days. However, this nine-fold induction was not reflected on the CYP1A catalytic activity, where exposure to ketoconazole resulted only in a two-fold increase in activity. Ketoconazole increased CYP3A protein levels 1.5-fold and decreased BFCOD activities by 80% at days 3 and 6. Treatment with ketoconazole and EE(2) alone and in combination had no significant effect on sex steroid hormones, compared to vehicle-treated fish. This study demonstrates that exposure to ketoconazole compromises the function of key enzymes involved/AQUATIC SPECIES/ An understanding of the effects of toxic mixtures of endocrine disrupting chemicals (EDCs) on aquatic organisms is challenging as these organisms are exposed to multiple classes of contaminants in their natural habitat. The aim of the present study was to evaluate the interactions of two classes of EDCs, 17beta-estradiol (E2) and ketoconazole (KTC), on endocrine function in male goldfish (Carassius auratus), including vitellogenesis, metabolic capability and serum steroid synthesis. Changes in vitellogenin (VTG) concentration, liver 7-ethoxyresorufin-O-deethylase (EROD) activity and circulating serum E2 level were examined. The expression of related genes was also determined using quantitative real-time polymerase chain reaction. Exposure to E2 caused a significant increase in VTG concentrations which corresponded with the gene expression of VTG and estrogen receptor (ER) in males, which were further elevated after combined exposure to E2 and KTC, indicative of a synergetic relationship. Exposure to E2 also resulted in a distinct increase in serum steroid biosynthesis and associated cytochrome P450 (CYP) aromatase expression after 10 days. However, these changes were inhibited by the presence of KTC, which acted as a steroidogenic inhibitor in fish. Moreover, KTC significantly decreased liver EROD activity and increased the related gene expression of CYP1A. However, these KTC-mediated metabolic reactions in goldfish were up-regulated following exposure to KTC in combination with E2. These findings reveal complex interactions on endocrine functions in male goldfish when exposed to multiple contaminations and may provide a better understanding of the effects of toxic mixtures./AQUATIC SPECIES/ Ketoconazole (KTC) is a model pharmaceutical representing imidazole and triazole pesticides, which inhibit fungal growth through blocking a cytochrome P450 (CYP)-mediated step in ergosterol biosynthesis. Several of these fungicides have been shown to be reversible inhibitors of CYPs in vertebrates (primarily mammals), including CYP isoforms involved in the pathway that converts cholesterol to active sex steroids. In these studies, we assessed the effects of KTC on aspects of steroidogenesis and reproductive function in the fathead minnow (Pimephales promelas). Exposure of spawning adults to the fungicide for 21 days significantly decreased egg production at a water concentration as low as 25 ug/L. Despite evidence of reduced ex vivo testosterone production by gonads from KTC-exposed fathead minnows, circulating plasma concentrations of sex steroids (testosterone, 17beta-estradiol) were not affected. Exposure to KTC caused an increase in the gonadosomatic index in both sexes and, in males, the fungicide caused a marked proliferation of interstitial (Leydig) cells. In addition, mRNA transcripts for two key steroidogenic enzymes, cytochrome P450 side-chain cleavage (CYP11A) and cytochrome P450 c17a hydroxylase/17,20 lyase (CYP17), were elevated by exposure to KTC. Both the changes in transcript levels and proliferation of gonad tissue represent potential adaptive or compensatory responses to impaired steroidogenic capacity. Overall our data indicate that, although KTC does adversely affect steroidogenesis and reproduction in the fathead minnow, the fish can compensate to some degree to mitigate effects of the fungicide. This has important implications for the interpretation of data from tests with endocrine-active chemicals.For more Ecotoxicity Excerpts (Complete) data for KETOCONAZOLE (8 total), please visit the HSDB record page.

Signs and Symptoms	Cough.Redness.Nausea. Headache. Dizziness. Vomiting. Diarrhoea.Side effects of the potential hepatotoxicity of Ketoconazole include abdominal pain or tenderness, clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, swelling of the feet or lower legs, unusual tiredness or weakness, and yellow eyes or skin. (L1536)