뷰틸파라벤

Cosmetics ingredient -> Emulsifier; Preservative/Stabilizer

Cosmetic ingredients (Butylparaben) -> CIR (Cosmetic Ingredient Review)

Preservative

log Kow = 3.57

3.57

3.32

Small, colorless crystals or powder

Crystalline powder

Finely divided solid

less than 1 mg/mL at 63 °F (NTP, 1992)

Crystalline powder; solubility in water: approx 1:125 /Butylparaben calcium salt/

Crystalline powder; solubility in water: approx 1:110 /Butylparaben magnesium salt/

In water, 2.07X10+2 mg/L at 20 °C

Very slightly soluble in water

SOLUBILITY IN WATER: 0.15 G/100 G @ 80 °C

156.00 to 157.00 °C. @ 3.50 mm Hg

156-157 °C (3.5 mm Hg)

This chemical does not meet GHS hazard criteria for 35.6% (479 of 1344) of reports.

Danger

H315 (60.4%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, 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 1344 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Benzoic acid, 4-hydroxy-, butyl ester

Hazard Traits - Endocrine Toxicity; Reproductive Toxicity

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

REACH registered substance: butyl 4-hydroxybenzoate (EC: 202-318-7)

Substance: Butyl 4-hydroxybenzoate

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

SYMPTOMS: Symptoms of exposure to this compound include skin sensitivity reactions, contact dermatitis, urticaria and angioedema. It can cause skin and eye irritation. Dilute solutions of this type of compound may be painful and cause irritation when applied to the eye.

Parabens are an uncommon cause of allergic contact dermatitis; [Marks, p. 115] A skin irritant; Causes liver injury in feeding studies of mice; [HSDB] A skin and eye irritant; A potential skin sensitizer; [CAMEO] An eye and mild skin irritant; May cause skin sensitization; [eChemPortal: ERMA] Parabens can induce allergic contact dermatitis, mainly in chronic dermatitis and wounded skin. [Kanerva, p. 1822-3]

Butyl p-hydroxybenzoate 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 b) 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.

Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 2. 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]

Adams TB et al; The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives used as flavor ingredients. Food Chem Toxicol 43 (8) 1241-71 (2005). This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) to re-evaluate the safety of more than 1,700 GRAS flavoring substances under conditions of intended use.

FAO/WHO Joint Expert Committee on Food Additives; WHO Food Additives Series 48: Hydroxy- and alkoxy-substituted benzyl derivatives (2001).[Available from, as of March 2, 2007: http://www.inchem.org/pages/jecfa.html]

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 continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer safety standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Butyl 4-hydroxybenzoate is found on List D. Case No: 4071; Case 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): Butyl 4-hydroxybenzoate; AI Status: The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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.

Keep container tightly closed in a dry and well-ventilated place.

Preserve in well-closed containers.

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: Do not let product enter drains. 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.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: 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 quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and 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 company; Contaminated packaging: Dispose of as unused product.

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: Do not let product enter drains.

Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

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 BUTYLPARABEN (7 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

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: 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).

Butylparaben concentrations below the quantitation limit (0.02 ng/mL) to 0.48 ng/mL and below the quantitation limit to 0.41 ng/L in urine samples from children from the United States and China, respectively. Levels in adults were below the quantitation limit to 29.5 and below the quantitation limit to 11.0 ng/mL, respectively(1). Butylparaben had a frequency of detection of 69% in urine samples from a group of US male and female adults sampled from 2003 to 2005(2).

The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti-androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha-dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing.

Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) (ranging from 10(-9) to 10(-7) m [1-100 nm; 0.39-39 ng/mL ]) and butylparaben (BP) (ranging from 10(-8) to 10(-5) m [10 nm-10 um; 1.9 ng m/L to 1.9 ug/ mL ]), alone and in combination, on isolated mouse preantral follicle and human granulosa cell (hGC) cultures to study direct effects on follicle growth and ovarian steroidogenesis. Our results revealed that, in follicle culture, DEHP and BP attenuate estradiol output but only when present together. DEHP decreases progesterone concentrations in the spent media of hGC cultures, an effect that was attenuated when BP was added together with DEHP. Although changes in steroidogenesis were observed, no effects on follicular development or survival were noted in the culture systems. We suggest that BP and DEHP act with additive effect to decrease estradiol production whereas at later stages of follicle development BP blocks the effect of DEHP in hGCs resulting in decreased progesterone output. Taken together our results suggest that DEHP and BP adversely affect steroidogenesis from the preantral stage onward and the effects of these chemicals are both stage-dependent and modified by co-exposure.

To evaluate the estrogenic activities of several chemicals such as 17beta-estradiol (E2), rho-nonylphenol, bisphenol A, butylparaben, and combinations of these chemicals, /the authors/ used recombinant yeasts containing the human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127]. ... E2 was most active in the recombinant yeast assay, followed by rho-nonylphenol, bisphenol A, /and/ butylparaben. The combinations of some concentrations of 17beta-estradiol as a strong estrogen and bisphenol A or butylparaben as a weak estrogen showed additive estrogenic effects. Also, the combinations of some concentrations of nonlyphenol and butylparaben and combination of butylparaben and bisphenol A showed additive effects in the estrogenic activity. Therefore, the estrogenic activities of the combinations of two chemicals were additive, not synergistic.

Exposure to endocrine disrupting chemicals (EDCs) during development can have negative consequences later in life. In this study we investigated the effect of perinatal exposure to mixtures of human relevant EDCs on the female reproductive system. Rat dams were exposed to a mixture of phthalates, pesticides, UV-filters, bisphenol A, butylparaben, as well as paracetamol. The compounds were tested together (Totalmix) or in subgroups with anti-androgenic (AAmix) or estrogenic (Emix) potentials. Paracetamol was tested separately. In pre-pubertal rats, a significant reduction in primordial follicle numbers was seen in AAmix and PM groups, and reduced plasma levels of prolactin was seen in AAmix. In one-year-old animals, the incidence of irregular estrous cycles was higher after Totalmix-exposure and reduced ovary weights were seen in Totalmix, AAmix, and PM groups. These findings resemble premature ovarian insufficiency in humans, and raises concern regarding potential effects of mixtures of EDCs on female reproductive function.

Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use -propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 uM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 uM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 uM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 uM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we include mixed exposures. This study emphasizes that risk assessment of compounds should take mixture effects into account.

EC50; Species: Salmo trutta (Brown Trout) sexually immature organism; Conditions: freshwater, flow through, 13 °C; Concentration: 68 ug/L for 10 days; Effect: biochemistry, increased vitellogenin

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 8700 ug/L for 24 hr (95% confidence interval: 8400-9100 ug/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 7800 ug/L for 48 hr (95% confidence interval: 7300-8300 ug/L) />99% purity/

LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 7600 ug/L for 72 hr (95% confidence interval: 7200-8200 ug/L) />99% purity/

For more Ecotoxicity Values (Complete) data for BUTYLPARABEN (8 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 520(SRC), determined from a structure estimation method(2), indicates that butylparaben is expected to have low mobility in soil(SRC). The pKa of butylparaben is 8.47(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 butylparaben from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.0X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Butylparaben is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the Zahn-Wellens test, 100% biodegradation was attained in 6 days using analogous methyparaben(6), suggesting that biodegradation in soil may be an important environmental fate process for butylparaben(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 520(SRC), determined from a structure estimation method(2), indicates that butylparaben is 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 6.0X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of 100(SRC), from its log Kow of 3.57(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Using the Zahn-Wellens test, 100% biodegradation was attained in 6 days using analogous methyparaben(7), suggesting that biodegradation in water may be an important environmental fate process for butylparaben(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), butylparaben, which has an estimated vapor pressure of 2.5X10-4 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 butylparaben 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 0.7 days(SRC), calculated from its rate constant of 1.6X10-11 cu cm/molecule-sec at 25 °C(SRC) (that was derived using a structure estimation method(3). Particulate-phase butylparaben may be removed from the air by wet and dry deposition(SRC). Butylparaben contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

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 %...Butylparaben...

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: HUMAN EXPOSURE AND TOXICITY: Butylparaben was a skin irritant in man. Experimental studies in volunteers failed to uncover any sensitizing potential, but sensitization to butylparaben has been demonstrated in dermatitis patients. ANIMAL STUDIES: A low acute oral toxicity was seen in mice treated with the ester whereas the sodium salt was of moderate toxicity. In mice, there were effects on the spleen and thymus as well as liver damage. Butylparaben in the diet produced cell proliferation in the forestomach of rats, but it was noncarcinogenic in a mouse chronic feeding study. It was not mutagenic in Ames bacterial tests. In one in vitro study, sperm were not viable at concentrations as low as 1 mg/mL for butylparaben. Epididymis and seminal vesicle weight decreases were reported in rats given a 1% oral butylparaben dose; and decreased sperm number and motile activity in F(1) offspring of rats maternally exposed to 100 mg/kg per day were reported. Decreased sperm numbers and activity were reported in F(1) offspring of female rats given Butylparaben by subcutaneous injection at 100 or 200 mg/kg per day, but there were no abnormalities in the reproductive organs. Butylparaben does bind to estrogen receptors in isolated rat uteri, but with an affinity orders of magnitude less than natural estradiol. ECOTOXICITY STUDIES: 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. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100 ug/L n-butylparaben, i-butylparaben for 14 days. In a rainbow trout Oncorhynchus mykiss increases in average plasma vitellogenin levels were seen at oral exposure to 9 mg butylparaben/kg for 2 days. In other experiment, butylparaben was estrogenic at 10 mg/kg bw in rainbow trout.

/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 163 ng/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 630 ug/L of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10 ug/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-butylparaben for 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.

/AQUATIC SPECIES/The estrogenic effect of butylparaben was investigated in a rainbow trout Oncorhynchus mykiss test system. Butylparaben was administered orally to sexually immature rainbow trout every second day for up to 10 days in doses between 4 and 74 mg/kg for 2 days and in the water at 35 and 201 ug/L for 12 days. Plasma vitellogenin was measured before and during the exposures and the concentrations of butylparaben in liver and muscle were determined at the end of experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 9 mg butylparaben/kg for 2 days. The ED50 values for increase in vitellogenin synthesis were 46, 29 and 10.5 mg butylparaben/kg for 2 days, respectively, at day 3, 6 and 12. Exposure to 201 ug butylparaben/L increased vitellogenin synthesis, but exposure to 35 ug/L did not. Butylparaben showed little tendency to bioaccumulation in rainbow trout; less than 1 ppt of the total amount of butylparaben administered orally at 51 mg/kg for 2 days over the 12 days experimental period was retained in liver at the end of the experiment. After 12 days exposure to 35 and 201 ug butylparaben/L, plasma concentrations were 9 and 183 ug/L, respectively, and for the fish exposed to 201 ug/L there was a positive correlation between concentrations of vitellogenin and butylparaben in the plasma. On the assumption that butylparaben removed from the water phase during water exposure were taken up into the fish, butylparaben uptake rates in the fish exposed to 35 and 201 ug butylparaben/L were 13 and 78 mg/kg/day, respectively.

/AQUATIC SPECIES/ The xenobiotics 4-tert-octylphenol, bisphenol A, propylparaben, butylparaben and butylbenzylphthalate induce the production of vitellogenin in rainbow trout after injection and/or water exposure. Exposure of fish to estrogenic chemicals via the food route has, however, received little attention. In these studies it is investigated if estrogenic responses in rainbow trout are also seen after dietary exposure to these chemicals. In separate experiments sexually immature rainbow trout were held in a flow-through system over a 12 days period and fed every second day with food containing one of the compounds. The doses tested were: ... 5, 10, 15, 30 and 60 mg butylparaben/kg bw. ... Blood samples were taken throughout the experiment to assess vitellogenin production (ELISA). Liver and muscle samples were taken to assess (LC/MS) internal doses of the compounds exerting estrogenic effects. ... Butylparaben was estrogenic at 10 mg/kg bw. ...

/AQUATIC SPECIES/ Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been found to be weakly estrogenic. Batch activated-sludge treatment and batch chlorination were carried out to roughly determine the removal efficiency of a wastewater treatment plant. Combining the removal efficiency with the estimated annual consumption and the unaltered excretion ratio, the maximum predicted environmental concentration (PEC) was estimated. Conventional acute/chronic toxicity tests were conducted using Japanese medaka (Oryzias latipes), daphnia (Daphnia magna), and green algae (Pseudokirchneriella subcapitata) for n-butylparaben, isobutylparaben, and benzylparaben. Medaka vitellogenin assays were also conducted for the three compounds and DNA microarray analysis was carried out to examine the effects of benzylparaben on gene expression. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100, and 100 ug/L n-butylparaben, isobutylparaben, and benzylparaben for 14 days, respectively, while the expression levels of genes encoding proteins such as p53, cytochrome P450 3A40, and choriogenin-L increased for concentrations higher than 4 ug/L of benzylparaben. Furthermore, the predicted no-effect concentration (PNEC) was calculated using the lethal or effect concentration 50 (LC50 or EC50) values and no-effect concentrations (NOECs) obtained in the toxicity tests for these compounds. The maximum concentrations found in the aquatic environment or sewage effluent (MEC eff) were used to carry out preliminary environmental risk assessment. The calculated MEC/PNEC ratio suggests the necessity of further study such as a more detailed large-scale monitoring and chronic toxicity tests including reproduction inhibition and endocrine disruption.

For more Ecotoxicity Excerpts (Complete) data for BUTYLPARABEN (6 total), please visit the HSDB record page.

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/[USEPA; ICSS Dashboard Application; Available from, as of September 8, 2016: http://actor.epa.gov/dashboard/]

Average concentrations of butylparaben in 21 influent and effluent samples from wastewater treatment plants on the Turia River, Valencia, Spain were 15 ng/L (21 samples positive) and not detected, respectively. Sampling was conducted in October, 2012; limit of quantitation effluent = 0.5(1). The compound was detected at a range of 50-723, <1 and <0.3-6 ng/L in influent, final effluent and surface waters, respectively, in the UK(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of butylparaben can be estimated to be 520(SRC). According to a classification scheme(2), this estimated Koc value suggests that butylparaben is expected to have low mobility in soil. The pKa of butylparaben is 8.47(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).

Butyl p-hydroxybenzoate 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 b) 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.

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 continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer safety standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Butyl 4-hydroxybenzoate is found on List D. Case No: 4071; Case 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): Butyl 4-hydroxybenzoate; AI Status: The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

In mice, rats, rabbits, or dogs, butyl paraben is excreted in the urine as unchanged benzoate, p-hydroxybenzoic acid, p-hydroxyhippuric acid (p-hydroxybenzoylglycine), ester glucuronides, ether glucuronides, or ether sulfates.

By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /4-Hydroxybenzoates (Parabens)/

The penetration and metabolism of butylparaben using viable, full-thickness human skin /is described/. ... A total of 21% of the radiolabel penetrated to the receptor fluid after 24 hr. ... the principle metabolite, hydroxybenzoic acid, was detected in the receptor fluid, with barely detectable levels of butylparaben and no ethylparaben, in this study of full-thickness skin. ... This work was repeated to again examine the penetration and metabolism of butylparaben (0.4%) in an oil/water emulsion applied to the same full thickness viable human skin ... A finite dose (10 L/cm ) of the 2 emulsion was applied to the skin surface and remained in contact over a 24 hr period without occlusion. (14)C-butylparaben (labeled in the carbon ring) was measured in the receptor fluid. A mean value of 14.9% (+ or - 3.73%) of the radioactive label penetrated the full thickness human skin after 24 hr. The principle metabolite, hydroxybenzoic acid, was found in the receptor fluid (mean of 15.2% + or - 5.23%) of all 10 replications (skin donated from two individuals), but barely detectable levels of the parent butylparaben (mean of 0.225% 0.063%) were found only in 5 of 10 replications. The authors interpreted these results to confirm the near complete first-pass metabolism of butylparaben to p-hydroxybenzoic acid in human skin.

... A study /was conducted/ of the in vitro dermal penetration and metabolism of methylparaben and butylparaben in rat and human skin. For each paraben, an oil in water emulsion with both radiolabeled ( C in the carbon 14 ring) and non-radiolabeled paraben was prepared to a target concentration (0.8% for methylparaben and 0.4% for butylparaben). Skin samples (10 replicates for rat skin and 13 replicates for human skin) were mounted in flow-through diffusion cells. Test emulsions were applied evenly at 10 L/cm , one time, with no occlusion. Samples of the receptor 2 fluid from a single skin were pooled, along with reference standards, were mixed with acetonitrile, filtered, and analyzed for methylparaben, butylparaben, and hydroxybenzoic acid using liquid chromatography coupled with mass spectroscopy. ... For Butylparaben, 52.3% was metabolized to hydroxybenzoic acid, with only 5.5% as unmetabolized butylparaben. Metabolism was different in human skin ... For butylparaben, 32.8% appeared as hydroxybenzoic acid and 49.7% as unmetabolized butylparaben.

For more Metabolism/Metabolites (Complete) data for BUTYLPARABEN (9 total), please visit the HSDB record page.

Butyl-4-hydroxybenzoate has known human metabolites that include (2S,3S,4S,5R)-6-(4-butoxycarbonylphenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid.

3QPI1U3FV8

BUTYLPARABEN

Established Pharmacologic Class [EPC] - Standardized Chemical Allergen

Physiologic Effects [PE] - Increased Histamine Release

Physiologic Effects [PE] - Cell-mediated Immunity

Chemical Structure [CS] - Allergens

By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /4-Hydroxybenzoates (Parabens)/

After butylparaben is intravenously infused into the dog, nonhydrolyzed butylparaben is found in brain, spleen, and pancreas. In liver, kidney, and muscle, it is immediately hydrolyzed to p-hydroxybenzoic acid. Six hours after oral administration of 1.0 g/kg to dogs, the peak plasma concentration of free and total butyl paraben (15 and 141 ug/cu cm) is reached. After 48 hr, butylparaben is eliminated.

Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability of coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butylparaben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of hydrophilic paraben.

Intravenous (IV) injections at 50 mg/kg methylparaben, ethylparaben, propylparaben, or butylparaben were administered to groups of three or more fasted dogs. Similarly, these compounds were administered orally at a dose of 1.0 g/kg. Blood and urine were analyzed at predetermined intervals. Immediately following IV injection, very little ester remained in the blood. Metabolites were detectable in the blood up to 6 hr postinjection and 24 hr postingestion. Recovery of all esters but butylparaben ranged from 58 to 94% of the administered dose. Absorption was essentially complete. Recovery of butylparaben after oral administration was 40% and 48 after IV administration. The authors considered this finding a result of less effective hydrolysis of butylparaben. Dogs given 50 mg/kg were then killed and the distribution of esters and metabolites to organs was determined. Pure ester was recovered only in the brain, spleen, and pancreas. High concentrations of metabolites were detected in the liver and kidneys. With in vitro assays, it was found that esterases in the liver and kidneys of the dog were extremely efficient in hydrolyzing parabens --- complete hydrolysis after 3 minutes for all parabens except butylparaben, which took 30 to 60 minutes. No accumulation of parabens was observed in the tissues of dogs given orally 1 g/kg/day methylparaben or propylparaben for 1 year. The rate of urinary excretion of esters and metabolites in these dogs increased to such an extent that after 24 hr, 96 % of the dose was excreted in the urine. This is contrasted with dogs given a single dose of paraben in which the 96 % excretion level was not attained until 48 hr. When 10 % methylparaben or propylparaben in hydrophilic ointment was applied to the skin of a white rabbit for 48 h, esters and metabolites were not detected in the kidneys.

For more Absorption, Distribution and Excretion (Complete) data for BUTYLPARABEN (9 total), please visit the HSDB record page.

CIR ingredient: Butylparaben

Used as an antifungal agent, preservative in antiseptic creams, food preservative, and pharyngeal antiseptic; [HSDB] The parabens (methyl, ethyl, propyl, and butyl) were the most widely used preservatives in cosmetics (0.1% to 0.8%) until their sensitizing potential was recognized; [Marks, p. 115]

Cancelled-- no longer contained in any registered pesticide products for use in the US; [HSDB]

Farming (Pesticides) [Category: Industry]

For butylparaben (USEPA/OPP Pesticide Code: 061205) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

The active ingredient is no longer contained in any registered pesticide products ... "cancelled."

(1972) 2.6X10+6 G (PRINCPL CUSTMS DISTS)

(1975) 9.54X10+5 G (PRINCPL CUSTMS DISTS)

(1972) 1.0X10+7 G (SALES)

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#982]

Butylparaben is prepared by esterifying p-hydroxybenzoic acid with butyl alcohol in the presence of an acid catalyst, such as sulfuric acid, and an excess of the specific alcohol.

Parabens are prepared by esterifying PHBA /parahydroxybenzoic acid/ with the corresponding alcohol in the presence of an acid catalyst, such as sulfuric acid, and an excess of the specific alcohol. The acid is then neutralized with caustic soda, and the product is crystallized by cooling, centrifuged, washed, dried under vacuum, milled, and blended. /Parabens/

Calcium and magnesium salts are available.

Trade Names: Butoben, Butyl butex, Butyl chemosept, Butyl parasept, Butyl tegosept, Nipabutyl, Preserval B, Solbrol B, SPF, Tegosept B, and Tegosept butyl.

Cosmetics product ingredient: Butylparaben (butyl 4-hydroxybenzoate)

Information on 80 consumer products that contain Butylparaben in the following categories is provided:

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENTFood Additives -> PRESERVATIVE -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENTFood Additives -> PRESERVATIVE -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENTFood Additives -> PRESERVATIVE -> JECFA Functional Classes

Cosmetics -> Preservative

Benzoic acid, 4-hydroxy-, butyl ester: ACTIVE

Butylparaben appears to be best antifungicidal agent among the parabens.

The parabens are most active against molds and yeasts. They are less effective against bacteria, especially gram-negative bacteria. /Parabens/