노난디 산

Precautions: Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not ingest. Do not breathe dust. If ingested, seek medical advice immediately and show the container or the label. Keep away from incompatibles such as oxidizing agents. Storage: Keep container tightly closed. Keep container in a cool, well-ventilated area. Sensitive to light. Store in light-resistant containers.

Small spill: Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and dispose of according to local and regional authority requirements. Large spill: Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and allow to evacuate through the sanitary system.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

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.

Personal Protection: Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.

Personal Protection in Case of a Large Spill: Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product.

Engineering controls: Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit.

The cytotoxic effect of azelaic acid on murine melanoma cells in culture is due, at least in part, to an antimitochondrial action. ...The possibility that the addition of carnitine to the medium may increase the transport of azelaic acid into the mitochondria and thereby increase its cytotoxic effect /was investigated/. Using mitochondrial cross-sectional area measured from electron micrographs as a criterion for mitochondrial damage, /it was/ found that the addition of L-carnitine to the culture medium had no effect either alone or with a low (10-3 M) concentration of azelaic acid. At a high concentration (5 X 10-2 M) azelaic acid caused swelling and disruption of the mitochondria to such an extent that this was not increased by carnitine. At 10-2 M azelaic acid, however, some swelling of the mitochondria occurred which was significantly increased by the addition of carnitine. This indicates that carnitine-mediated transport of the diacid into the mitochondria had occurred. ...Carnitine may reduce the time or concentration needed for azelaic acid to have a toxic effect on the malignant melanocyte.

Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a log Kow of 1.57(2) and a regression-derived equation(3), indicates that 1,7-heptanecarboxylic acid is expected to have moderate mobility in soil(SRC). The pKa of 1,7-heptanecarboxylic acid is 4.55(4), indicating that this compound will exist almost entirely 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(5). Volatilization from moist soil is not expected because the acid exists as an anion and anions do not volatilize. 1,7-Heptanecarboxylic acid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.07X10-8 mm Hg(6). Biodegradation data were not available(SRC, 2008) but straight chain carboxylic acids are expected to readily biodergade(7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a log Kow of 1.57(2) and a regression-derived equation(3), indicates that 1,7-heptanecarboxylic acid is expected to adsorb to suspended solids and sediment(SRC). A pKa of 4.55(4) indicates 1,7-heptanecarboxylic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2008) but straight chain carboxylic acids are expected to readily biodergade(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,7-heptanecarboxylic acid, which has a vapor pressure of 1.07X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 1,7-heptanecarboxylic acid 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 40 hrs(SRC), calculated from its rate constant of 9.8X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 1,7-heptanecarboxylic acid may be removed from the air by wet or dry deposition(SRC). 1,7-Heptanecarboxylic acid does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an 1,7-heptanecarboxylic acid concentration of 25 ug/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose is systemically absorbed, the uptake of 1,7-heptanecarboxylic acid into maternal milk is not expected to cause a significant change from baseline 1,7-heptanecarboxylic acid levels in the milk.

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

The exact mechanism of action of azelaic acid is not known. It is thought that azelaic acid manifests its antibacterial effects by inhibiting the synthesis of cellular protein in anaerobic and aerobic bacteria, especially <i>Staphylococcus epidermidis</i> and <i>Propionibacterium acnes</i>. In aerobic bacteria, azelaic acid reversibly inhibits several oxidoreductive enzymes including tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid impedes glycolysis. Along with these actions, azelaic acid also improves acne vulgaris by normalizing the keratin process and decreasing microcomedo formation. Azelaic acid may be effective against both inflamed and noninflamed lesions. Specifically, azelaic acid reduces the thickness of the stratum corneum, shrinks keratohyalin granules by reducing the amount and distribution of filaggrin (a component of keratohyalin) in epidermal layers, and lowers the number of keratohyalin granules.

1,7-Heptanecarboxylic acid was detected in automobile exhausts from a 1982 Toyota Corolla Model 1.8 Liter gasoline engine and a 1971 Mercedes Benz 220 Model 2.2 Liter diesel engine which was rebuilt in 1982, at 3.9 and 51 nmol/cu m, respectively(1).

1,7-Heptanecarboxylic acid was identified as a directly emitted component in gas and particulate phases of pinene photooxidation aerosol products over a forest area at concentrations of 2.59 (6AM-12PM), 0.69 (12PM-6PM), 0.22 (6PM-6AM) ng/cu m, respectively; in aerosols - 0.47 (6AM-12PM), 0.16 (12PM-6PM), 0.31 (6PM-6AM) ng/cu m, respectively(1).

The Koc of 1,7-heptanecarboxylic acid is estimated as 170(SRC), using a log Kow of 1.57(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 1,7-heptanecarboxylic acid is expected to have moderate mobility in soil. The pKa of 1,7-heptanecarboxylic acid is 4.55(4), indicating that this compound will almost entirely exist 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(5).

URBAN/SUBURBAN: 1,7-Heptanecarboxylic acid exhibited seasonal variations in the atmosphere in Tokyo, Japan, as evidenced by concentrations ranging from 6.9 to 73 ng/cu m in samples collected from 1988-1989(1). 1,7-Heptanecarboxylic acid was detected in air samples from west Los Angeles, CA at concentrations of 0.12, 0.04, 0.07, 0.09, 0.11, 0.03, 0.02 and 0.15 nmol/cu m, on Jun 12, Jun 13-14, Oct 20-22, Oct 24, Oct 24-25, Oct 25-26, Oct 26-29 and Oct 29-30, 1984, respectively(2). It was detected in air samples from downtown Los Angeles, CA at concentrations of 0.27 and 0.13 nmol/cu m, on Oct 24 and Oct 24-25, 1984, respectively(2). 1,7-heptanecarboxylic acid was tested for in 12 air samples from various locations in southern California as part of that area's Children's Health Study (SCCHS) in 1995; concentrations of 0.9, 0.93, 0.35, 0.87, 0.76, 0.25, 1.07 ,1.28, 0.95, 0.92, 0.61 and 1.3 ng/cu m from an Alpine location, Atascadero, Lake Arrowhead, Lake Elsinore, Lancaster, Lompoc, Long Beach, Mira Loma, Riverside, San Dimas, Santa Maria and an Upland locations were reported(3). Sources quantified were gasoline-powered motor vehicle exhaust, diesel vehicle exhaust, wood smoke, vegetative detritus, tire wear and natural gas combustion(3). 1,7-Heptanecarboxylic acid was detected in 4 samples collected in winter and summer of 1992 in Tokyo, Japan at concentrations of 41, 46 ng/cu m (February 24-26), 43 and 48 ng/cu m (July 22-23)(4).

INDOOR: 1,7-Heptanecarboxylic acid was detected in air samples from a greenhouse in Los Angeles, CA at concentrations of 0.03 nmol/cu m, sampled on Dec 12, 1984; it was not detected on Dec 13, 1984(1).

/HUMAN EXPOSURE STUDIES/ Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10 g over 90 min) and 5 a bolus dose (1g). The 24 hr urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/hr were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/hr. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/hr. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition.

/HUMAN EXPOSURE STUDIES/ Six healthy male volunteers received a single topical treatment with 5 g of an anti-acne cream containing 20% azelaic acid onto the face, the chest and the upper back. One week later 1 g of azelaic acid was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured. Analysis included ether extraction of the urine, derivatization of extract and HPLC with UV detection. After topical application 2.2 +/- 0.7%, and after oral administration 61.2 +/- 8.8% of the dose had been excreted unchanged with the urine. By comparing both amounts, the percutaneous absorption of azelaic acid from the cream was assessed to 3.6% of the dermally applied dose.

/SIGNS AND SYMPTOMS/ Acute Potential Health Effects: Skin: May cause mild skin irritation. Eyes: May cause mild eye irritation. Inhalation: May cause respiratory tract irritation. Ingestion: May cause digestive tract irritation.

/ALTERNATIVE and IN VITRO TESTS/ The effects of zinc sulfate and azelaic acid on 5 alpha-reductase activity in human skin were studied using an in vitro assay with 1,2[3H]-testosterone as substrate. When added at concentrations of 3 or 9 mmol/L, zinc was a potent inhibitor of 5 alpha-reductase activity. At high concentrations, zinc could completely inhibit the enzyme activity. Azelaic acid was also a potent inhibitor of 5 alpha-reductase; inhibition was detectable at concentrations as low as 0.2 mmol/L and was complete at 3 mmol/L. An additive effect of the two inhibitors was observed. Vitamin B6 potentiated the inhibitory effect of zinc, but not of azelaic acid, suggesting that two different mechanisms are involved. When the three substances were added together at very low concentrations which had been shown to be ineffective alone, 90% inhibition of 5 alpha-reductase activity was obtained. If this inhibition is confirmed in vivo, zinc sulfate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin.

1,7-Heptanecarboxylic acid's production and use in organic synthesis, lacquers, alkyd resins, polyamides, polyester adhesives, low-temperature plasticizers and in urethane elastomers(1) may result in its release to the environment through various waste streams(SRC).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl azelaic acid, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Azelaic acid is an indirect food additive for use only as a component of adhesives.

CIR ingredient: Azelaic Acid

Found in rancid oleic acid; [Merck Index] Used in organic syntheses, lacquers, alkyd resins, low-temperature plasticizers, adhesives, polyamides, urethane elastomers, and for the treatment of acne; [HSDB] Natural component of foods such as whole grain cereals and animal products; [REPROTOX]

Painting (Pigments, Binders, and Biocides) [Category: Paint]

Azelaic acid is used in lacquers, alkyd resins, plasticizers, adhesives, polyamides, urethane elastomers, and organic syntheses. Azelaic acid is also used in treating of acne.

Organic synthesis, lacquers, product of hydrotropic salts, alkyd resins, polyamides, polyester adhesives, low-temperature plasticizers, urethane elastomers

Use (kg; approx.) in Germany (2009): >1000

2023: 5,000,000 - <10,000,000 lb

Nonanedioic acid is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7323]

Prepared by disruptive oxidation of ricinoleic acid

Oxidation of oleic acid by ozone

... Generally produced from naturally occurring fatty acids via oxidative cleavage of a double bond in the 9-position, eg, from oleic acid.

EPA Safer Chemical Functional Use Classes -> Processing Aids and Additives

Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern

Cosmetics -> Buffering

All Other Chemical Product and Preparation Manufacturing

Nonanedioic acid: ACTIVE

Occurs in rancid oleic acid