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4-ヒドロキシ安息香酸メチル
4-ヒドロキシ安息香酸メチル · メチルパラセプト · ソルブロールM · ニパギンM · アビオル · ニパゲニン · ニパギン · テゴセプトM
識別子と物理属性
| CAS No. | 99-76-3 |
|---|---|
| 分子式 | C8H8O3 |
| 平均分子量 | 152.15 g/mol |
| 単同位体質量 | 152.04734412 g/mol |
| SMILES | COC(=O)c1ccc(O)cc1 |
| InChIKey | LXCFILQKKLGQFO-UHFFFAOYSA-N |
| PubChem CID | 7456 |
| ChEMBL | CHEMBL325372 |
| ChEBI | CHEBI:31835 |
| EC No. | 202-785-7 |
| DTXSID | DTXSID4022529 |
| 現地名 | 4-ヒドロキシ安息香酸メチル |
化学・物理的性質
| XLogP | 2 |
|---|---|
| 極性表面積 | 46.5 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 3 |
| 回転可能結合数 | 2 |
| 重原子数 | 11 |
| 形式電荷 | 0 |
| 複雑度 | 136 |
| 物質分類 | Other Uses -> Preservatives |
| 化粧品 | Cosmetics ingredient -> ColorantFragrancePreservative/StabilizerCosmetic ingredients (Methylparaben) -> CIR (Cosmetic Ingredient Review) |
| SpringerMaterials Properties | Boiling point |
| 香料 | Fragrance Ingredient (Methyl p-hydroxybenzoate) -> IFRA transparency List |
| 農薬 | Agrochemicals -> Pesticide active substancesActive substance -> EU Pesticides database: Not approvedBiocide |
| LogP（分配係数） | log Kow = 1.96 |
| 臭い | Odorless or has faint characteristic odor無臭またはかすかな焦げ。無臭、またはかすかな炭、焦げる臭い |
| 味 | Slight burning taste |
| 食品添加物 | ANTIMICROBIAL AGENT, FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food |
| Color/Form | White needlesColorless crystals or white crystalline powderNeedles from dil alcohol |
| 溶解度 | In water, 2.50X10+3 mg/L at 25 °CSolubility in water (w/w): 0.25% at 20 °C0.30% at 25 °CSolubilities in various solvents[Table#2967]Slightyl soluble in watervery soluble in ethanol, ether, acetonesoluble in trfluoroacetic acidFor more Solubility (Complete) data for METHYLPARABEN (6 total), please visit the HSDB record page.2.5 mg/mL at 25 °Cエタノール：可溶0.1M 無色透明水にわずかに溶ける。 |
| Animal Drugs | Pharmaceuticals -> UK Veterinary Medicines Directorate List |
| 融点 | 125-128 °C (lit.) |
| 沸点 | 298.6 °C |
| 密度 | 1,46g/cm |
| 蒸気圧 | 0.000005 hPa (20 °C) |
| FEMA | 2710 | METHYL P-HYDROXYBENZOATE |
| 屈折率 | 1.4447 (estimate) |
| 引火点 | 280°C |
| 貯蔵条件 | room temp |
| pKa（酸解離定数） | pKa 8.15(H2O,t =20.0) (Uncertain) |
| 外観・状態 | 結晶性粉末 |
| 色 | 白～ほぼ白 |
| pH | 5.8 (H2O, 20°C) (saturated solution) |
| 由来生物 | synthetic |
| 凝固点 | 131℃ |
| Merck | 14,6107 |
| BRN | 509801 |
| ヘンリー定数 | 4.5×103 mol/(m3Pa) at 25℃, HSDB (2015) |
| 安定性 | 安定。強酸化剤、強塩基とは相容れない。 |
| 主な用途 | フレーバーそして香料 |
| 化粧品成分の機能 | 防腐剤香料 |
| InChI | 1S/C8H8O3/c1-11-8(10)6-2-4-7(9)5-3-6/h2-5,9H,1H3 |
| InChIKey | LXCFILQKKLGQFO-UHFFFAOYSA-N |
| SMILES | COC(=O)c1ccc(O)cc1 |
| LogP（分配係数） | 1.98 at 20℃ |
| CAS データベース | 99-76-3(CAS DataBase Reference) |
| NISTの化学物質情報 | Benzoic acid, 4-hydroxy-, methyl ester(99-76-3) |
| EPAの化学物質情報 | Methylparaben (99-76-3) |
化学的特性
Methylparaben occurs as colorless crystals or a white crystalline powder. It is odorless or almost odorless and has a slight burning taste. Soluble in alcohol,ether; slightly soluble in water, benzene, and carbontetrachloride.
安全性と法規制
| GHS 分類 | This chemical does not meet GHS hazard criteria for 31.5% (1035 of 3282) of reports.WarningH315 (53.8%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 3282 reports by companies from 32 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | Chemical: Benzoic acid, 4-hydroxy-, methyl esterHazard Traits - Endocrine ToxicityReproductive ToxicityDirective (EC) No 114/2003Benzoic acid, 4-hydroxy-, methyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzoic acid, 4-hydroxy-, methyl ester 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)2007/442Status: Active Update: 19-12-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/14310 |
| その他の安全情報 | IMAP assessments - Parabens: Human health tier II assessment |
| 有害性の概要 | Parabens are an uncommon cause of allergic contact dermatitis[Marks, p. 115] Food use limited to 0.1%[Hawley] Observations from animal studies include mild skin and eye irritation and a low order of toxicity in high-dose oral studiesSkin sensitization has been reported from cosmetics and topical medicationsA moderate eye irritant (saturated aqueous solution)Practically non-toxic in animal studies: Oral LD50 (mouse) >8000 mg/kg (Effects included flaccid paralysis and ataxia.)[HSDB] An eye and mild skin irritantMay cause skin sensitization[eChemPortal: ERMA] Parabens can induce allergic contact dermatitis, mainly in chronic dermatitis and wounded skin. [Kanerva, p. 1822-3] An irritant[MSDSonline] |
| FDA 要件 | Methylparaben is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and 2) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.Substances classified as antimycotics, when migrating from food-packaging material shall include: methylparaben.Substance added directly to human food affirmed as generally recognized as safe (GRAS). The ingredient is used in food at levels not to exceed good manufacturing practices. Current good manufacturing practice results in a maximum level of 0.1 percent in food.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: methylparaben is included in topical antifungal drug products.This substance is generally recognized as safe for use at a level not exceeding 0.1 percent in accordance with good manufacturing or feeding practice. |
| Special Reports | Cosmetic Ingredient ReviewFinal Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products. Int J Toxicol 27 Suppl 4: 1-82 (2008)[Available from, as of November 21, 2016: http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf] |
| FIFRA 要件 | Residues of methyl p-hydroxybenzoate are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Preservative for formulations.Residues of methyl p-hydroxybenzoate are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. Use: Preservative. Limit: Meets specifications of Food Chemicals Codexnot to exceed 0.1% in formulations.As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Butyl 4-hydroxybenzoate is found on List D. Case No: 4071Case Status: No products containing the pesticide are actively registered ... The case /is characterized/ 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 (AI): Methyl 4-hydroxybenzoateAI Status: The active ingredient is no longer contained in any registered pesticide products ... "cancelled." |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides |
| Hazard Classes and Categories | Skin Irrit. 2 (53.8%)Specific target organ toxicity - Single exposure - Category 3 (Narcotic effects)Hazardous to the aquatic environment (Acute) - Category 3 |
| Skin, Eye, and Respiratory Irritations | Methylparaben ... as saturated aq soln ... noted to be moderately irritating to eye ... . |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents, strong bases |
| 消火手順 | 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. |
| 保管条件 | Keep container tightly closed in a dry and well-ventilated place. |
| 清掃方法 | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. 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. |
| 処分方法 | 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: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. 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.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. 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: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.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.For more Preventive Measures (Complete) data for METHYLPARABEN (6 total), please visit the HSDB record page. |
| Allowable Tolerances | Residues of methyl p-hydroxybenzoate are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Preservative for formulations.Residues of methyl p-hydroxybenzoate are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. Use: Preservative. Limit: Meets specifications of Food Chemicals Codexnot to exceed 0.1% in formulations. |
| Personal Protective Equipment (PPE) | Eye/face protection: Safety glasses with side-shields conforming to EN166. 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: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| 体内負荷 | Methylparaben had a frequency of detection of 99% in urine samples from a group of US male and female adults sampled from 2003 to 2005(1).Concentration of urinary p-hydroxybenzoic acid and methylparaben in children and adults from the United States and China(1).[Table#2963] |
| 相互作用 | ... Using human intestinal (Caco-2) cells, it was observed that hydrolysis of parabens to p-hydroxybenzoic acid is reduced markedly by ethanol concentrations that can occur in the human intestine, 0.25-0.5% (v/v). Ethanol concentrations of 1.0-2.5% (v/v) were optimal for transesterification to ethylparaben in Caco-2 cell homogenates. The kinetics of the transesterification reaction with regard to ethanol concentration (0-20%), time, pH (3-9), protein concentration (1-5 mg/mL) and substrate concentration (6.25-200 uM) as well as the effects of different alcohols were studied. The Km and Vmax values for transesterification with ethanol for methyl, propyl, butyl, heptyl and octyl parabens were 449.7, 165.7, 86.1, 24.2 and 45.9 uM and 114.4, 37.5, 19.5, 7.5 and 7.6 umol/hr/mg Caco-2 cell protein, respectively. The Vmax values for transesterification of methylparaben with ethanol, propan-1-ol, butan-1-ol were 114.4, 5.1 and 4.9 umol/hr/mg, respectively. ... The clinical or toxicological implication is that, following co-ingestion of ester compounds with ethanol, transesterification could provide the basis for a previously unrecognized drug-alcohol interaction.... /The authors/ investigated the effects of ultraviolet-B (UVB) exposure on methylbaraben (MP)-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24 hr, exposed to UVB (15 or 30 mJ/cm2) and further cultured for another 24 hr. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. ... Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, nitric oxide (NO) production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.It has been hypothesized recently that succinylcholine-associated increases in intracranial pressure (ICP) are caused by the paraben preservatives contained in multidose vials. /The authors/ tested that hypothesis in a standard feline model to determine the effects on ICP of equal-volume injections of preservative-free succinylcholine, succinylcholine with preservatives from multi-dose vials that contain both propylparaben and methylparaben, these preservatives alone at five times the dose contained in the succinylcholine, and normal saline. The preservatives alone increased ICP by 0.08 +/- 0.08 mm Hg (+/- standard errornot significant). Normal saline had no effect on ICP. Preservative-free succinylcholine and succinylcholine with preservatives increased ICP by 4.2 +/- 0.10 and 3.8 +/- 0.07 mm Hg respectively (P less than 0.01 compared to the preservatives alone and normal saline). The 99% upper confidence limit for the increase in ICP induced by the preservatives alone was 0.42 mm Hg. This result suggests /, to the authors/ that parabens do not cause or substantially augment the ICP increase associated with succinylcholine administration.To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes.For more Interactions (Complete) data for METHYLPARABEN (7 total), please visit the HSDB record page. |
| 生態毒性値 | EC50Species: Daphnia magna (Water Flea)Conditions: freshwater, static, pH 7.6-8.0, dissolved oxygen 100% saturatedConcentration: 11400 ug/L for 24 hr (95% confidence interval: 10600-47600 ug/L)Effect: intoxication, immobilization /formulation/Concentration: 11200 ug/L for 24 hr (95% confidence interval: 5730-22000 ug/L)Species: Daphnia magna (Water Flea)age <24 hr neonateConditions: freshwater, static, 21 °C, pH 7.45, hardness 100 mg/L CaCO3Concentration: 70000 ug/L for 24 hrEffect: intoxication, immobilization /99% purity/Concentration: 41100 ug/L for 48 hrFor more Ecotoxicity Values (Complete) data for METHYLPARABEN (7 total), please visit the HSDB record page. |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 87(SRC), determined from a structure estimation method(2), indicates that methylparaben is expected to have high mobility in soil(SRC). The estimated pKa of methylparaben is 8.5(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of methylparaben from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.2X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Methylparaben is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.4X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the Zahn-Wellens test, 100% biodegradation was observed in 6 days following a 2-day acclimation period(6) suggesting that biodegradation may be an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 87(SRC), determined from a structure estimation method(2), indicates that methylparaben 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 2.2X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 9(SRC), from its log Kow of 1.96(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using the Zahn-Wellens test, 100% biodegradation was observed in 6 days following a 2-day acclimation period(7) suggesting that 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), methylparaben, which has an estimated vapor pressure of 2.4X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase methylparaben 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 one day(SRC), calculated from its rate constant of 1.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase methylparaben may be removed from the air by wet and dry deposition(SRC). Methylparaben contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| 有害作用 | Neurotoxin - Other CNS neurotoxin |
| 毒性の概要 | The CIR Expert Panel concluded that the following 20 parabens are safe in cosmetics in the present practices of use and concentration described in the safety assessment when the sum of the combined concentration of parabens in any given formulation does not exceed 0.8 %...Methylparaben...Safe for use in cosmetics, with qualificationsIDENTIFICATION AND USE: Methylparaben is a methyl ester of p-hydroxybenzoic acid. It is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics. HUMAN EXPOSURE AND TOXICITY: Parabens are reported to cause contact dermatitis reactions in some individuals on cutaneous exposure. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposurehowever, the mechanism of this sensitivity is unknown. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking. ANIMAL STUDIES: Acute toxicity studies in animals indicate that methylparaben is practically non-toxic by both oral and parenteral routes. In a population with normal skin, methylparaben is practically non-irritating and non-sensitizing. In chronic administration studies, no-observed-effect levels (NOEL) as high as 1050 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5700 mg/kg is posited. Methylparaben did increase chromosomal aberrations in a Chinese Hamster ovary cell assay. Methylparaben was noncarcinogenic when injected subcutaneously in mice or rats, or when administered intravaginally in rats. Methylparaben was nonteratogenic in rabbits, rats, mice, and hamsters. It is not embryotoxic. Methylparaben failed to produce any effect in uterotrophic assays in two laboratories, but did produce an effect in other studies from another laboratory. In one in vitro study, sperm were not viable at concentrations as low as 6 mg/mL methylparaben, but an in vivo study of 0.1% or 1.0% methylparaben in the diet of mice reported no spermatotoxic effects. Methylparaben was studied using rats at levels in the diet up to an estimated mean dose of 1141.1 mg/kg per day with no adverse testicular effects. ECOTOXICITY STUDIES: Medaka vitellogenin assays and DNA microarray analysis were carried out for methylparaben and found induction of significant vitellogenin in male medaka at 630 ug/L of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10ug/L of methylparaben. |
| Average Daily Intake | Estimated daily intakes of methylparaben from indoor dust (13 cities, 4 countries) from the United States, China, Korea and Japan (all ng/kg bw/day)(1).[Table#2962] |
| 生態毒性抜粋 | /AQUATIC SPECIES/ The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by means of two toxicity bioassays: Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. The median effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to 62 mg/L in the D. magna test and from 0.0038 to 5.9 mg/L in the V. fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and n-propylparaben, the most commonly used preservatives in cosmetics, toward D. magna was 3.9- and 2.8-fold that of their corresponding parent compounds. Toxicity toward D. magna showed a linear relationship with log P, indicating that toxicity increases with increasing hydrophobicity. On the other hand, the correlations of toxicity toward V. fischeri with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens. A complete assessment of the ecological and toxicological risks of parabens may require the examination of chlorinated parabens as well as the parent pollutants, as described in the present study./AQUATIC SPECIES/ The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg/L, respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg/L and from 1.2 to 19 mg/L, respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2BnP) elicited a significant decrease in offspring numbers even at their lowest concentration testedthe NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg/L for MP, BnP, and Cl2BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent responsetheir NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0.0012 to 0.2, with the highest value observed in MP. This suggested that there are negligible environmental risks for aquatic organisms at current use levels./AQUATIC SPECIES/ In the present study, aquatic concentrations of seven parabens were determined in urban streams highly affected by treated or untreated domestic sewage in Tokushima and Osaka, Japan. The detected highest concentrations were 670, 207, and 163ng/L for methylparaben, n-propylparaben, and n-butylparaben, respectively in sampling sites with watershed area of no sewer system in Tokushima. Conventional acute/chronic toxicity tests were conducted using medaka (Oryzias latipes), Daphnia magna, and Psuedokirchneriella subcapitata for four parabens, which was consistent with our previous study on three parabens, n-butylparaben, i-butylparaben, and benzylparaben. The aquatic toxicity on fish, daphnia, and algae was weaker for the parabens with a shorter alkyl chain than those with a longer alkyl chain as predicted by their hydrophobicity. Medaka vitellogenin assays and DNA microarray analysis were carried out for methylparaben and found induction of significant vitellogenin in male medaka at 630ug/L of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10ug/L of methylparaben. Measured environmental concentrations (MECs) of seven parabens in Tokushima and Osaka were divided by predicted no effect concentrations (PNECs) and hazard quotient (MEC/PNEC) was determined for individual parabens. The MEC/PNEC was highest for n-propylparaben and was 0.010 followed by n-butylparaben (max. of 0.0086) and methylparaben (max. of 0.0042). The sum of the MEC/PNEC for the seven parabens was 0.0049. Equivalence factors were assigned for each paraben on the basis of the toxicity of n-butylparabenfor each species, and n-butylparaben equivalence was calculated for the measured environmental concentrations. The MEC/PNEC approach was also conducted for the n-butylparaben-based equivalence values. The maximum MEC/PNEC was 0.018, which is lower than the trigger level for further detailed study such as large-scale monitoring for chronic toxicity tests including full-life cycle tests for fish. |
| 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 September 8, 2016: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | The average concentration of methylparaben in 21 influent and effluent samples from wastewater treatment plants on the Turia River, Valencia, Spain were 334 ng/L (21 samples positive) and 11 ng/L (21 samples positive), respectively. Sampling was conducted in October, 2012limit of quantitation effluent = 1.0(1). The compound was detected at a range of 2642-11,601, <3-50 and <0.3-68 ng/L in influent, final effluent and surface waters, respectively, in the UK(2). |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of methylparaben can be estimated to be 87(SRC). According to a classification scheme(2), this estimated Koc value suggests that methylparaben is expected to have high mobility in soil. The estimated pKa of methylparaben is 8.5(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ In vitro studies suggest that the preservatives methylparaben and propylparaben included in some multidose vials of succinylcholine are the cerebral vasodilators responsible for the increases in intracranial pressure (ICP) documented after succinylcholine administration. To test this hypothesis, ... cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) with inhaled 133-Xenon and transcranial Doppler /were measured/ respectively in healthy humans before and after the intravenous administration of methylparaben and propylparaben. ... No change /was found/ in either CBF or CBFV after the paraben injections and therefore /it was/ concluded that it is unlikely that the rise in ICP seen with succinylcholine is caused by cerebral arterial vasodilatation from the preservatives methylparaben and propylparaben./HUMAN EXPOSURE STUDIES/ ... Methylparaben, ethylparaben, propylparaben, and butylparaben were each applied to the backs of 50 humans at concentrations of 5, 7, 10, 12, and 15 percent in propylene glycol. Test compounds were applied daily for 5 days, and patches were then removed and the sites scored. The concentrations of individual parabens that produced no irritation were methylparaben, 5 %ethylparaben, 7 %propylparaben, 12 5% and butylparaben, 5%. Higher concentrations produced some evidence of irritation. In a repeated insult patch test (RIPT), each paraben at the "no effect" concentration above was applied to the skin of 50 subjects (25M/25F) for 4 to 8 hr every other day for 3 weeks (10 applications). Following a 3-week rest, the materials were reapplied at induction concentrations for 24 to 48 hr. No sensitization was reported./HUMAN EXPOSURE STUDIES/ Methylparaben and ethylparaben, in increasing concentrations, were studied for their effect on the oral mucous membrane of 39 subjects. They described toxic limit concentrations for methylparaben and ethylparaben of 5 and 10%, respectively. One subject had a reaction of the oral mucous membrane to methylparaben./SIGNS AND SYMPTOMS/ ... used in region of eyes ... occasionally cause redness & swelling of eyelids from allergic contact dermatitis.For more Human Toxicity Excerpts (Complete) data for METHYLPARABEN (27 total), please visit the HSDB record page. |
| 水環境危害等級（WGK） | 1 |
| TSCA 収載状態 | TSCA listed |
| RTECS 番号 | DH2450000 |
| 輸送番号（UN） | UN 2769 |
| 毒性 | LD50 orally in Rabbit: 2100 mg/kg |
| PRTR法 | 第一種指定化学物質 |
| 税関コード | 29182930 |
| 危険文句（R） | 36/37/38-20/21/22-36 |
| 化審法 | (3)-1585 |
| 危険表示 | Xi,Xn |
| 安全措置（S） | 26-36-24/25-39 |
| 自然発火温度 | >600 °C |
| 環境リスク評価 | 4-ヒドロキシ安息香酸メチル(99-76-3) |
| 危険等級 | Aquatic Chronic 2 |
| 貯蔵分類 | 11 - Combustible Solids |
| 有害物質データ | 99-76-3(Hazardous Substances Data) |
用途
解説
食品・医薬品・化粧品の防腐剤として使用される有機化合物の総称。メチルパラベン・プロピルパラベンなど。正式名称は、パラオキシ安息香酸エステル。小学館 デジタル大辞泉について 情報 | 凡例
用途
化粧品?医薬の防カビ剤
用途
保存料、防腐剤。
天然物の起源
Reported present in cloudberry, yellow passion fruit juice, white wine, botrytised wine and Bourbon vanilla.
使用
Methylparaben and propylparaben are the most common of these. parabens is one of the most commonly used group of preservatives in the cosmetic, pharmaceutical, and food industries. Parabens provide bacteriostatic and fungistatic activity against a diverse number of organisms, and are considered safe for use in cosmetics, particularly in light of their low sensitizing potential. An evaluation of preservatives for use in leave-on cosmetic preparations lists parabens among the least sensitizing. The range of concentrations used in cosmetics varies between 0.03 and 0.30 percent, depending on the conditions for use and the product to which the paraben is added.Methylparaben is one of the most popular preservatives in beauty products and food items. According to the National Library of Medicine, the ingredient occurs naturally in a handful of fruits—like blueberries—though it can also be created synthetically.It's found in everything from cream cleansers and moisturizers to primers and foundations and helps these products maintain their effectiveness. Rabach says that it's chock-full of anti-fungal and antibacterial properties, which work wonders to extend the shelf life of skincare, haircare, and cosmetic products.
一般的な説明
Methyl paraben is basically a methyl ester of p-hydroxybenzoic acid. It is non-toxic, and non-carcinogenic in nature. It is a stable, non-volatile compound and finds application as an anti-microbial preservative in foods, drugs and cosmetics. It is readily absorbed through the skin and gastrointestinal tract. Upon hydrolyzation, it is hydrolyzed to p-hydroxybenzoic acid, and the conjugates formed get rapidly excreted in the urine.
製法・合成法
製造方法
Methylparaben is produced through the methanol esterification of p-hydroxybenzoic acid in the presence of sulfuric acid. The materials are heated in a glass-lined reactor and distilled under reflux. The resulting acid is neutralized with caustic soda, then crystallized through cooling. The crystallized product is centrifuged, washed, dried under vacuum, milled and blended, all in corrosion-resistant equipment to avoid metallic contamination.
純化方法
Fractionally crystallise the ester from its melt, and recrystallise it from *benzene, then from *benzene/MeOH and dry it over CaCl2 in a vacuum desiccator. [Beilstein 10 IV 360.]