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1-(5,6,7,8-Tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-on
TONALIDE · Tonalid · 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)etha... · AHTN · Ganolide · FIXOLIDE · Tetralide · Extralide
Identifikatoren & physikalische Daten
| CAS No. | 1506-02-1 |
|---|---|
| Summenformel | C18H26O |
| Durchschnittliche Molmasse | 258,4 g/mol |
| Monoisotopische Masse | 258,19836545 g/mol |
| SMILES | CC(=O)c1cc2c(cc1C)C(C)(C)C(C)CC2(C)C |
| InChIKey | DNRJTBAOUJJKDY-UHFFFAOYSA-N |
| PubChem CID | 89440 |
| ChEMBL | CHEMBL3184267 |
| ChEBI | CHEBI:88666 |
| EC No. | 216-133-4 |
| DTXSID | DTXSID7041544 |
| Lokaler Name | 1-(5,6,7,8-Tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-on |
Chemische & physikalische Eigenschaften
| XLogP | 5,3 |
|---|---|
| Polarare Oberfläche (TPSA) | 17,1 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 1 |
| Frei drehbare Bindungen | 1 |
| Schwere Atome | 19 |
| Formalladung | 0 |
| Komplexität | 366 |
| LogP (Verteilungskoeffizient) | log Kow = 5.70 |
| Geruch | Odor type: musk |
| Dichte | The relative density will be between the bulk density and its density in molten form: 600 < D < 960 kg/cu m0.919±0.06 g/cm3(Predicted) |
| Color/Form | White to off-white crystalline solid |
| Löslichkeit | In water, 1.25 mg/L, temp not specifiedChloroform (Slightly), Ethyl Acetate (Slightly) |
| Siedepunkt | The boiling temperature at atmospheric pressure is 326 +/- 4 °C.124 °C(Press: 1 Torr) |
| Decomposition | When heated to decomposition it emits acrid smoke and irritating vapors. |
| Schmelzpunkt | 54.5 °C550C |
| Dampfdruck | 0.000512 [mmHg]5.12X10-4 mm Hg, temp not specified0.068Pa at 25℃ |
| Henry-Konstante | Henry's Law constant = 1.4X10-4 atm-cu m/mol at 25 °C (est VP/WS)7.0×10-2 mol/(m3Pa) at 25℃, HSDB (2015) |
| Physical Description | Large CrystalsOther SolidSolid with an odor of musk[HSDB] |
| Stability/Shelf Life | Stable under recommended storage conditions. |
| Lagerbedingungen | Sealed in dry,Room Temperature |
| Aggregatzustand | Solid |
| Farbe | White to Off-White |
| Geruch | musky, warm, radiant, tenacious odor |
| Hauptanwendungen | cleaning productscosmeticsflavors and fragrancesfood and beveragespersonal care |
| Kosmetik-Inhaltsstoffe Funktionen | PERFUMINGFRAGRANCE |
| InChI | 1S/C18H26O/c1-11-8-16-15(9-14(11)13(3)19)17(4,5)10-12(2)18(16,6)7/h8-9,12H,10H2,1-7H3 |
| InChIKey | DNRJTBAOUJJKDY-UHFFFAOYSA-N |
| SMILES | CC1CC(C)(C)c2cc(C(C)=O)c(C)cc2C1(C)C |
| LogP (Verteilungskoeffizient) | 5.4 at 25℃ |
| CAS Datenbank | 21145-77-7 |
| NIST chemische Informationen | Ethanone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)-(21145-77-7) |
| EPA chemische Informationen | Ethanone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)- (21145-77-7) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 2.1% (38 of 1807) of reports.WarningH302 (97.7%): Harmful if swallowed [Warning Acute toxicity, oral]H400 (90.7%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]H410 (97.9%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 1807 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 38 of 1807 reports by companies.There are 12 notifications provided by 1769 of 1807 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatorische Informationen | Chemical: Ethanone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)-Ethanone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Ethanone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)Status: Active Update: 01-02-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/12034Status: Cease Manufacture Update: 21-05-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/12808 |
| Weitere Sicherheitsinformationen | IMAP assessments - Tonalide: Human health tier II assessmentIMAP assessments - Tonalide and related polycyclic musks: Environment tier II assessment |
| Gefahrenübersicht | A mild eye irritant, based on animal studies[CHEMINFO] Causes liver injury in high-dose animal experiments[RTECS] May be safely used as a fragrance in cosmetics up to 12%[European Commission] Included in list of fragrance substances with negative human data, i.e. patch tests of patients with suspected contact allergy to fragrance ingredients which yielded negative results.[EC: Scientific Committee on Consumer Safety: Fragrance allergens in cosmetic products (2011)] May cause irritation[MSDSonline] |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides. |
| Hazard Classes and Categories | Acute Tox. 4 (97.7%)Aquatic Acute 1 (90.7%)Aquatic Chronic 1 (97.9%)Acute Tox. 4 (98.5%)Aquatic Acute 1 (67.6%)Aquatic Chronic 1 (75.6%)Aquatic Chronic 2 (23.1%)Acute toxicity (ingestion) - category 4Acute toxicity (Oral) - Category 4Serious eye damage/eye irritation - Category 2Specific target organ toxicity - Repeated exposure - Category 2 (liver, haemal system)Hazardous to the aquatic environment (Acute) - Category 1Hazardous to the aquatic environment (Long-term) - Category 1 |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents. |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. |
| Lagerbedingungen | Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Solids. |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Entsorgungsverfahren | SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in air, soil or watereffects on animal, aquatic and plant lifeand conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.Product: Offer surplus and non-recyclable solutions to a licensed disposal companyContaminated packaging: Dispose of as unused product. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required.Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: General industrial hygiene practice.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. |
| Personal Protective Equipment (PPE) | Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| Körperbelastung | Polycyclic musks, including chemicals such as tonalide, have been detected in human milk at a concentration range of 8 to 189 ug/kg(1). Tonalide was detected in Danish human milk samples collected in 1999 at an average concentration of 19.5 ug/kg fat (2.25-37.9 ug/kg fatmedian 17.5 ug/kg fat)(2). Tonalide was detected in adipose tissue of 81% of Korean women evaluated between May 2007 and May 2008, at a mean concentration of 12 ng/g, median 9.9 ng/g, and range <2-51 ng/g(3). Tonalide was determined in a total of 14 human adipose tissue samples at concentrations ranging from 8-31 ug/kg fat in 8 females (ages 41-70 years) and 8-33 ug/kg fat in 6 males (ages 30-84 years)in 5 human milk samples (mothers ages 28-32 years) at concentrations ranging from 11 to 58 ug/kg fat(4). Exposure of infants via mother's milk was calculated from data collected from 101 milk samples, assuming a daily milk consumption of 0.7 L milk, the calculated total daily intake for tonalide was in the range of 50-1350 ng with a median 250 ng(5).Concentrations of HHCB and AHTN in human adipose fat collected from New York City were measured ... Concentrations of HHCB and AHTN in human adipose fat samples ranged from 12 to 798 and from <5 to 134 ng/g, on a lipid weight basis, respectively. A significant correlation existed between the concentrations of HHCB and AHTN in human adipose fat. Concentrations of HHCB and AHTN were not positively correlated with age or gender of the donors.... This study examined the concentrations of six polycyclic musks in blood samples from healthy volunteers. Blood was taken from hundred healthy students of the Medical University of Vienna. The lipophilic fraction was extracted and after purification analyzed by GC-MS. Study participants also completed a questionnaire on the use of cosmetics, about nutrition and other life-style aspects. Two compounds -- galaxolide and tonalide -- were identified in higher percentages of the blood plasma samples. Maximum plasma levels over 100 ng/L were also only found for galaxolide (4100 ng/L) and tonalide (800 ng/L). Women showed significantly higher levels than men.... An increasing number of studies show that /7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline/ (AHTN) accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. |
| Wechselwirkungen | ... In the present study the subchronic hepatotoxicity of AHTN administered to rats at doses within the human exposure range was evaluated. For this purpose female and male juvenile Wistar rats were exposed to AHTN (300 ug/kg body weight per day, i.p.) alone or to a single dose of diethylnitrosamine (DEN) (100 mg/kg body weight, ip) followed by AHTN (1, 10, 100 or 300 ug/kg body weight per day, ip) for 90 days. Thereafter the liver architecture as well as the presence of placental glutathione S-transferase (GST-P)-positive hepatic lesions was assessed. In male animals receiving AHTN alone or in combination with DEN the number of GST-P-positive single hepatocytes was similar to that in untreated rats, while GST-P-positive mini-foci and foci were not observed. In the case of female rats the number of GST-P-positive single hepatocytes and mini-foci in AHTN-treated rats was similar to that in untreated animals ... |
| Ökotoxizitätswerte | LC50Species: Lepomis macrochirus (Bluegill sunfish)Conditions: flow throughConcentration: 0.314 mg/L for 21 daysSpecies: Pimephales promelas (Fathead minnow) 32 day post-hatch larvaeConcentration: 0.100 mg/L for 36-day overall /Conditions of bioassay not specified in source examined/EC50Species: Daphnia magna /(Water flea)/Conditions: semistaticConcentration: 0.244 mg/L for 21 daysEffect: reproductionSpecies: Acartia tonsa (calanoid copepod)Concentration: 2.5 mg/L for 48 hr /Conditions of bioassay not specified in source examined/For more Ecotoxicity Values (Complete) data for Tonalide (6 total), please visit the HSDB record page. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.9X10+4(SRC), determined from a structure estimation method(2), indicates that tonalide is expected to be immobile in soil(SRC). Volatilization of tonalide from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 5.12X10-4 mm Hg(3), and water solubility, 1.25 mg/L(3). However, adsorption to soil is expected to attenuate volatilization(SRC). Tonalide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). A 14% Theoretical BOD using activated sludge in the Closed Bottle test(4) suggests that biodegradation is not an important environmental fate process in soil(SRC).FIELD STUDY: In a field experiment using sludge from a waste water treatment plant incubated in reed beds for 13 months, tonalide was recalcitrant(1).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.9X10+4(2), indicates that tonalide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 5.12X10-4 mm Hg(4), and water solubility, 1.25 mg/L(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 15 hours and 9 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 230 days if adsorption is considered(5). According to a classification scheme(6), measured BCF values of 597-1,069(4,7), suggest the potential for bioconcentration in aquatic organisms is high to very high(SRC). A 0% theoretical BOD using the Japanese MITI test(4) suggests that biodegradation is not an important environmental fate process in water(SRC).AQUATIC FATE: The synthetic polycyclic musks HHCB and AHTN are potential chemical markers for domestic wastewater contamination of surface waters. Understanding their environmental behavior is important to evaluate their suitability as markers. This study focuses on the quantification of the processes that lead to an elimination in lakes. Rate constants for all relevant processes were estimated based on laboratory studies and models previously described. In lake Zurich, during winter time, both compounds are eliminated primarily by outflowing water and due to losses to the atmosphere. In summer, direct photolysis represents the predominant elimination process for AHTN in the epilimnion of lake Zurich (quantum yield, 0.12), whereas for HHCB, photochemical degradation is still negligible. HHCB and AHTN were then measured in effluents of Swiss wastewater treatment plants (WWTPs), in remote and anthropogenically influenced Swiss surface waters, and in Mediterranean seawater using an analytical procedure based on SPE and GC-MS-SIM with D6-HHCB as internal standard (LODs for natural waters, 2 and 1 ng/L, respectively). In winter, concentrations of HHCB and AHTN in lakes (<2-47 and <1-18 ng/L, respectively) correlated with the anthropogenic burden by domestic wastewater (ratio population per water throughflow), demonstrating the suitability of these compounds as quantitative, source-specific markers. In summer, however, no such correlations were observed. Vertical concentration profiles in lake Zurich indicated significant losses in the epilimnion during summer, mainly for AHTN, and could be rationalized with a lake modeling program (MASASlight), considering measured, average loads from WWTP effluents (0.80 +/- 0.22 and 0.32 +/- 0.11 mg person(-1) d(-1) for HHCB and AHTN, respectively) and the estimated rate constants for elimination processes.ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tonalide, which has a vapor pressure of 5.12X10-4 mm Hg(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase tonalide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 22 hours(SRC), calculated from its rate constant of 1.8X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase tonalide may be removed from the air by wet and dry deposition(SRC). Tonalide contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, it may be susceptible to direct photolysis by sunlight(SRC). |
| Lebensmitteluntersuchungswerte | Continually detected biologically persistent nitromusksgalaxolide (HHCB), tonalide (AHTN) and musk ketone (MK), antimicrobial triclosan (TCS), and antihistamine diphenhydramine (DPH) were examined for the first time in edible fillets originating from eight fish species grown in salt- and fresh-water. The sampled fish collected from local grocery stores were homogenized, extracted, pre-concentrated and analyzed by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). The presence of the target compounds in fish extracts was confirmed based on similar mass spectral features and retention behavior with standards. Internal standard based calibration plots were used for quantification. The HHCB, AHTN, TCS and DPH were consistently observed with concentration of 0.163-0.892, 0.068-0.904, 0.189-1.182, and 0.942-7.472 ng/g, respectively. These values are at least 1-3 orders of magnitude lower than those obtained in environmental fish specimens. The MK was not detected in any fish. |
| Unerwünschte Wirkungen | 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. |
| Milk Concentrations | Polycyclic musks, including chemicals such as tonalide, have been detected in human milk at a concentration range of 8 to 189 ug/kg(1). Tonalide was detected in Danish human milk samples collected in 1999 at an average concentration of 19.5 ug/kg fat (2.25-37.9 ug/kg fatmedian 17.5 ug/kg fat)(2). Tonalide was detected in 101 human milk samples collected from 1996 to 2003 with median concentration of 10.9 ng/g lipid and a range <3.0-53.0 ng/g lipid(3). Tonalide was determined in 5 human milk samples (mothers ages 28-32 years) at concentrations ranging from 11 to 58 ug/kg fat(4).... An increasing number of studies show that /7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline/ (AHTN) accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Tonalide is a solid with a musk odor. It is used as a fragrance in cosmetics, detergents, fabric softeners, household cleaning products and air fresheners. HUMAN STUDIES: No irritation was observed after repeated occlusive applications as well as no phototoxic reactions. High concentrations of tonalide can affect steroidogenesis in vitro using the H295R cell line. Tonalide was not genotoxic in the micronucleus test with human lymphocytes in vitro with or without metabolic activation. ANIMAL STUDIES: Tonalide did not produce erythema or edema when tested on the skin of rabbits. In tests for photoirritation in the rabbit clear phototoxicity was seen at 5% in ethanol. Moderate redness and slight to moderate chemosis of the conjunctivae was seen in rabbits in an eye irritation test. A single high dose of tonalide leads to acute hepatic damage in rats. In other experiment, rats were treated with doses 1260, 1588, 2000 or 2520 mg/kg bw and observed for 14 days. The majority of animals showed lethargy, piloerection, hunched position, oscillated movements, shaggy coat and emaciation. Other occasional signs included green urine, hypothermia, half-closed eyes, difficult breathing and increased breathing, prostration and lacrimation. In a 2-week study, groups of 5 male and female rats were administered dietary doses of 0, 33, 88 and 169 mg/kg bw/day for males and 0, 32, 91 and 150 mg/kg bw/day for females. All animals in the high dose group had marked reduction in food consumption and body weight losses. Food consumption and body weight losses were slightly reduced at the mid-dose. In a two generation developmental study in rats, there were no adverse effects to the dams or offspring up to and including the highest dose level (20 mg/kg bw/day). In genotoxicity studies no positive responses were observed except for cells with structural aberrations in the in vitro cytogenetics assay in CHO cells with metabolic activation. ECOTOXICITY STUDIES: In Dreissen |
| Ökotoxizitätsauszüge | /AQUATIC SPECIES/ Large quantities of personal care products (PCPs) are used daily and many of their chemical ingredients are subsequently released into marine environments. Cultures of the marine microalga Tetraselmis suecica were exposed for 24 hr to three emerging compounds included in the main classes of PCPs: the UV filter benzophenone-3 (BP-3), the disinfectant triclosan (TCS) and the fragrance tonalide (AHTN). Concentrations tested, expressed as cellular quota (pg/cell), ranged from 5 to 40 for BP-3, from 2 to 16 for TCS and from 1.2 to 2.4 for AHTN. A small cytometric panel was carried out to evaluate key cytotoxicity biomarkers including inherent cell properties, growth and metabolic activity and cytoplasmic membrane properties. BP-3 caused a significant increase in growth rate, metabolic activity and chlorophyll a fluorescence from 10 pg/cell. However, growth and esterase activity decreased in cells exposed to all TCS and AHTN concentrations, except the lowest ones. Also these two compounds provoked a significant swelling of cells, more pronounced in the case of TCS-exposed cells. Although all treated cells remained viable, changes in membrane potential were observed. BP-3 and AHTN caused a significant depolarization of cells from 10 to 1.6 pg/cell, respectivelyhowever all TCS concentrations assayed caused a noticeable hyperpolarization of cells. Metabolic activity and cytoplasmic membrane potential were the most sensitive parameters. It can be concluded that the toxicological model used and the toxicological parameters evaluated are suitable to assess the toxicity of these emerging contaminants./AQUATIC SPECIES/ This study demonstrates the effects of synthetic polycyclic musks such as Galaxolide (HHCB), Tonalide (AHTN), Traseolide (ATII), Celestolide (ADBI), Phantolide (AHMI) and Cashmeran (DPMI), both on the early life stage and on gene expression in the livers of male medaka (Oryzias latipes). The toxicity ranking (the 96-hr median lethal concentration) of the chemicals tested on 24-hr-old medaka larvae descended in the order HHCB (0.95 mg/L)=ATII (0.95 mg/L)>AHTN (1.0 mg/L)>AHMI (1.2 mg/L)>ADBI (2.0 mg/L)>>DPMI (12 mg/L), indicating high acute toxicity of these compounds on the early life stages of medaka. Expression analysis of hepatic vitellogenin (VTG) protein showed potential estrogenic effects upon the addition of AHTN and HHCB, indicative of the induction of VTG synthesis in the livers of male medaka. We also investigated mRNA expression levels of two estrogen receptor (ER) subtypes (ERalpha and beta), two VTGs (VTG I and II), pregnane X receptor (PXR), and two cytochromes P450 (CYP) 3As (CYP3A38 and 3A40) in the livers of male medaka treated with AHTN and HHCB at 5, 50 and 500 ug/L. Quantitative real-time PCR analyses revealed that hepatic ERalpha, VTG I, VTG II, and CYP3A40 mRNA responded to 500 ug/L of AHTN and/or HHCB after 3 days exposure, whereas no effects of these compounds on ERbeta, PXR, and CYP3A38 mRNA transcription were observed. These results suggest that certain polycyclic musks, including AHTN and HHCB, induce the expression levels of hepatic ERalpha and VTG mRNA/protein and modulate expression levels of CYP3A40 mRNA in the livers of male medaka./AQUATIC SPECIES/ Chinese sturgeon (Acipenser sinensis) was listed as a Grade I protected animal in China in 1989, and the observed intersexual phenomenon and sex ratio deviation have suggested that chemicals have posed a risk as environment pollutants. This study analyzed seven musk fragrances in liver, muscle, heart, gonad, stomach, intestines, adipose, gill, pancreas, kidney, gallbladder, and roe from 13 female Chinese sturgeons, and the toxicokinetic behavior of musks were studied and compared with some organochlorines. Of the seven musks, HHCB, AHTN, and musk xylene were detected, and the highest concentrations were observed in adipose tissue: from 33.7 to 62.1 ng/g wet weight (ww), from 1.0 to 5.4 ng/g ww, and from 1.1 to 13 ng/g ww, respectively. Similar to the tissue distribution of DDTs and HCB, musks were detected frequently in high lipid content tissues such as roe, adipose, and liver, suggesting that tissue distribution of musks is controlled by the affinity to lipids. The concentration ratios based on lipid weight between roe and adipose were estimated to be 0.47 for HHCB, 0.58 for AHTN, and 0.51 for musk xylene, and those for the total DDTs and HCB were 0.27 and 0.61, which were relatively low compared with mammals. Relatively high concentrations of p,p'-DDE (68.4-449 ng/g ww) were detected in 10 of total 11 samples, which would cause the feminization of Chinese sturgeons during embryonic development. It was found that lipid-corrected concentrations of HHCB, AHTN, p,p'-DDE, and p,p'-DDD increased with age in female sturgeon, of which the trends were similar to those in fishes and different from those in mammals./AQUATIC SPECIES/ Synthetic musks are widely used as perfuming agents in products, such as cosmetics, detergents, and soaps. The increased detection of these substances in the aquatic environment and their high bioconcentration potential raises concerns about potential effects on aquatic species. This work aimed at assessing the interactions of the most widely used musks: nitromusks (musk xylene, musk ketone) and polycyclic musks (celestolide, galaxolide, and tonalide) with fish enzymatic systems involved in both xenobiotic and endogenous metabolism. Therefore, CYP catalyzed pathways were investigated in carp liver microsomes (CYP1A, CYP3A), ovarian microsomes (CYP19) and testicular mitochondria (CYP17 and CYP11beta) using standard substrates. Phase II activities (UDP-glucuronosyltransferases and sulfotransferases) were determined in carp liver microsomes and cytosol, respectively. Polycyclic musks (galaxolide and tonalide) were stronger inhibitors of CYP3A- (IC(50): 68-74 uM), CYP17- (IC(50): 213-225 uM), CYP11beta- and CYP19-catalyzed activities than nitromusks, while the latter showed higher ability to interfere with CYP1A (IC(50): 35-37 uM). The sulfation of estradiol was also significantly inhibited by tonalide and galoxolide (IC(50): 140-294 uM). Overall, polycyclic musks showed the highest potential to interfere with those activities involved in the synthesis and metabolism of steroids while nitromusks mainly interfered with xenobiotic metabolism (CYP1A-catalyzed reactions). The obtained data suggest that CYP isoforms are potentially sensitive targets of synthetic musk substances in fish.For more Ecotoxicity Excerpts (Complete) data for Tonalide (18 total), please visit the HSDB record page. |
| Animal Concentrations | Tonalide was detected in blubber from 8 finless porpoise (Neophocaena phocaenoides) and 3 porpoise fetus samples, collected from the Ariake Sea and Yatsushire Sea, Japan, at concentrations of less than 2.3 ng/g(1). |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of July 27, 2017: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | One US sewage treatment plant reported influent levels of tonalide as 12,500 ng/L and after primary gravitational settling and activated sludge treatment an effluent concentration of 1326 ng/L(1). A US sewage treatment plant reported tonalide effluent concentration of 1555 ng/L after primary gravitational settling and trickling filter treatment(2). Another US sewage treatment plant reported tonalide effluent concentrations of 1010 ng/L after primary gravitational settling and oxidation ditch treatment(1). A third US sewage treatment plant reported tonalide effluent concentrations of 1710 ng/L after primary gravitational settling and rotating biological contractor treatment(1). Water quality data compiled from the Retrieval (STORET) Data Warehouse and the USGS National Water Information System (NWIS) reports monitoring data for tonalide(2)effluent concentrations for tonalide between 2010 and 2013 ranged from 0.022 to 0.18 ug/L, sludge concentrations for tonalide between 2011 and 2012 ranged from 21 to 228 ug/kg(2). Tonalide was detected in effluent samples collected over a 3-day period from an activated sludge wastewater treatment plant in Loveland, OH in September 1997 and from a trickling filter wastewater treatment plant in Glendale, OH in October 1997 at concentrations of 1180 and 1660 ng/L, respectively(3). Tonalide was detected in the effluent from a variety of types of European and U.S. wastewater treatment plants, at concentrations ranging from 1,235 to 1,645 ng/L and from 1,010 to 1,710 ng/L, respectively, various sampling dates between Sept 1997-Sept 1999(4). In October 2005, tonalide was detected in samples collected from waste water treatment plants located in 2 moderately populated cities in New York State at average concentrations of 1900 and 994, 1400 and 1010, 713 and 555, 12.6 and 2.73, in the influent, primary clarification, effluent, and combined sludge samples, respectively(5). Tonalide was detected in 80% of the samples taken from 10 WWTP influTonalide was detected in a Westphalia, Germany sewage treatment plant at 320 ng/L in the influent and at 360 ng/L in the effluent, samples collected Aug 1999(1). Tonalide was found in sewage treatment effluent from samples taken Jun-Dec 1999 in Sweden at 42-104 ng/L, and from samples taken Jan 2002 from Canada at 110-520 ng/L(2). Tonalide was found in German effluents taken Jun 24, 1997 and July 29, 1997 at 1900 and 1700 ng/L, respectively(2). Tonalide was identified in a German sewage pond influent at 1500 ng/L and in effluent at 640 ng/L(2). A European sewage treatment plant reported tonalide effluent concentrations of 1440 ng/L after primary gravitational settling and activated sludge treatment(2). Another European sewage treatment plant reported tonalide effluent concentration of 1235 ng/L after primary gravitational settling and carousel treatment(2). A third European sewage treatment plant reported tonalide effluent concentration of 1645 ng/L after primary gravitational settling and trickling filter treatment(2). Raw influents had a median of 4.0 ug/L and effluents had a median of less than detection limit in samples from the Netherlands(3). Switzerland effluents had a median concentration of 1.4 ug/L(3). Tonalide concentrations in the influent and effluent of a German sewage plant were 1,900 and 1,700 ng/L and the influent and effluent levels in the associated sewage pond were 1,500 and 600 ng/L(4). Tonalide was detected in the effluent from a variety of types of European and U.S. wastewater treatment plants, at concentrations ranging from 1,235 to 1,645 ng/L and from 1,010 to 1,710 ng/L, respectively, various sampling dates between Sept 1997-Sept 1999(5). Monitoring reports published in 2004 and 2007 indicate that tonalide was detected in liquid and solid phase samples, at concentrations of 700-1700 ng/L and 4750 ng/L respectively, from sewage a treatment plant in Galicia located northwest of Spain(6). In November 2004, average concentrations for tonalide ofThe polycyclic musk fragrance compounds HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyrantrade name, e.g. galaxolide) and AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene, trade name, e.g. tonalide) and the transformation product of HHCB (HHCB-lactone) were analysed in surface water samples and sewage treatment plants (STP) effluents in the Ruhr megalopolis. The STPs were the dominant source for these pollutants. In the part of the river where the drinking water is extracted from the river, about 60 ng/L HHCB, 10 ng/L AHTN and 20-30 ng/L HHCB-lactone were found as typical riverine concentrations, while none of the compounds were detected near the spring of the river. On the other hand sewage treatment plant effluents exhibited concentrations up to 600 ng/L. The STP's effluent resulted in elevated concentrations in some parts of the river and in the lakes into which they discharge. As some of the plants emit HHCB-lactone with a significantly changed enantiomeric pattern, biotransformation of HHCB to HHCB-lactone occurs in some waste water treatment plants operating with activated sludge. In those parts of the river where no relevant discharges of waste water or fresh water takes place neither the concentration nor the pattern changes significantly. This holds true especially for the HHCB versus HHCB-lactone ratios which indicates degradation less than 15% of the HHCB inventory in the river Ruhr itself. In other rivers, such as the Rhine, higher levels of HHCB-lactone in comparison to HHCB were detected (ratio 1 : 1). |
| Wassergefährdungsklasse (WGK) | 3 |
| TSCA-Inventar-Status | TSCA listed |
| RTECS-Nr. | KM5805024 |
| R-Sätze (R) | 22 |
| Gefahrensymbole | Xn |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 21145-77-7(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Tonalide is used for non-alcoholic perfumes.