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Cosmetic ingredients (Dimethyl Succinate) -> CIR (Cosmetic Ingredient Review)

Emollient

Log Kow = 0.35

0.35

0.19

1.117 (USCG, 1999) - Denser than water; will sink

1.1202 @ 18 °C/4 °C

1.114-1.118

1.117

1.1202 @ 18°C

greater than or equal to 100 mg/mL at 73 °F (NTP, 1992)

SOL IN 120 PARTS WATER, 35 PARTS ALC

Slightly soluble in water, soluble in acetone, ethanol, very soluble in ethyl ether

25000 mg/L @ 20 °C (exp)

slightly soluble to soluble in water; slightly soluble in alcohol; miscible in oils

1 mL in 1 mL 95% alcohol (in ethanol)

This chemical does not meet GHS hazard criteria for 61.8% (730 of 1181) of all reports.

Warning

H319 (36.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)

Aggregated GHS information provided per 1181 reports by companies from 9 notifications to the ECHA C&L Inventory.

Warning

Chemical: Butanedioic acid, dimethyl ester

Butanedioic acid, 1,4-dimethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Butanedioic acid, 1,4-dimethyl 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)

Status: Active Update: 25-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/15043

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

Dimethyl succinate 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: 1) the quantity added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) when intended for use in or on food it is of appropriate food grade and is prepared and handled as a food ingredient.

DIMETHYL SUCCINATE reacts with acids to liberate heat along with methanol and succinic acid. May react with strong oxidizing acids to liberate enough heat to ignite the reaction products. Heat is also generated by the interaction with caustic solutions. Flammable hydrogen is generated with alkali metals and hydrides.

Eye Irrit. 2 (36.4%)

Flammable liquids - Category 4

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.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated 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.

16 [mg/m3]

230 [mg/m3]

1400 [mg/m3]

TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 37(SRC), determined from a measured log Kow of 0.35(2) and a recommended regression-derived equation(3), indicates that dimethyl succinate is expected to have very high mobility in soil(SRC). Volatilization of dimethyl succinate from moist soil surfaces(SRC) is not expected to be important given an estimated Henry's Law constant of 6.4X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Based upon a group contribution method for predicting the probability and rate of aerobic biodegradation(5), dimethyl succinate has been estimated to be highly biodegraded with complete biodegradation occurring over a period of weeks(SRC).

AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 37(SRC), determined from a measured log Kow of 0.35(2) and a recommended regression-derived equation(3), indicates that dimethyl succinate is not expected to adsorb to suspended solids and sediment in water(SRC). Dimethyl succinate is not expected to volatilize from water surfaces(3,SRC) based on an estimated Henry's Law constant of 6.4X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF value of 1.1(3,SRC), from a measured log Kow(2), suggests that bioconcentration in aquatic organisms is low(SRC). Based upon a group contribution method for predicting the probability and rate of aerobic biodegradation(6), dimethyl succinate has been estimated to be highly biodegraded with complete biodegradation occurring over a period of weeks(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dimethyl succinate, which has an estimated vapor pressure of 0.46 mm Hg at 25 °C(2,SRC), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dimethyl succinate 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 about 14 days(3,SRC).

The Koc of dimethyl succinate is estimated as approximately 37(SRC), using a measured log Kow of 0.35(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that dimethyl succinate is expected to have very high mobility in soil(SRC).

An estimated BCF value of 1.1 was calculated for dimethyl succinate(SRC), using a measured log Kow of 0.35(1) and a recommended regression-derived equation(2). According to a classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for dimethyl succinate is estimated as 6.4X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value indicates that dimethyl succinate will be essentially nonvolatile from water surfaces(2,SRC). Dimethyl succinate's Henry's Law constant(1,SRC) indicates that volatilization from moist soil surfaces is not expected to occur(SRC).

This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters. Young male rats were exposed, nose-only, to an aerosol/vapor mixture of dibasic esters at a concentration of 5,900 mg/cu m for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells.

Dibasic esters are a solvent mixture of dimethyl adipate, dimethyl glutarate and dimethyl succinate which causes a selective degeneration of the nasal olfactory epithelium in rats following a 90-day inhalation exposure. In short-term cultures of rat nasal explants, it has been demonstrated that dibasic esters cytotoxicity is due to a carboxylesterase-mediated activation. In the present study, the putative toxic metabolites of dibasic esters, the monomethyl esters and the dicarboxylic acids, were evaluated in the explant system at concentrations ranging from 10 to 50 mM. Mononethyl adipate, monomethyl glutarate, and monomethyl succinate induced increases in nasal explant acid phosphatase release, a biochemical index of cytotoxicity. The nasal explant-mediated metabolism of Mononethyl adipate and monomethyl glutarate to their corresponding diacids paralleled the increases in acid phosphatase release. A carboxylesterase inhibitor, bis(p-nitrophenyl)phosphate, inhibited both the cytotoxicity and the hydrolysis of and monomethyl glutarate in the nasal explant system. The metabolism and cytotoxicity of monomethyl succinate was not attenuated as effectively by bis(p-nitrophenyl)phosphate pretreatment. Adipate, glutarate, and succinate induced concentration-related increases in cytotoxicity in the nasal explant system. These dicarboxylic acids were neither metabolized nor utilized significantly by the nasal explants. Diacid-induced cytotoxicity was not attenuated by bis(p-nitrophenyl)phosphate pretreatment. This study further established the utility of the nasal explant system for evaluating cytotoxicity of organic esters in vitro. It was established that both the monomethyl ester and diacid metabolites are cytotoxic in rat nasal explants. Finally, it was concluded that although both the monomethyl esters and the diacids contribute to the cytotoxic potential of dibasic esters in vitro, it is critical to establish if one or both of these are formed in vivo in order to identify the ultimate toxic metabolite of dibasic esters.

Dimethyl succinate 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: 1) the quantity added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) when intended for use in or on food it is of appropriate food grade and is prepared and handled as a food ingredient.

Dibasic esters are a solvent mixture of dimethyl adipate; dimethyl glutarate, and dimethyl succinate used in the paint and coating industry. Subchronic inhalation toxicity studies have demonstrated that dibasic ester induce a mild degeneration of the olfactory, but not the respiratory, epithelium of the rat nasal cavity. Carboxylesterase-mediated hydrolysis of the individual dibasic esters is more efficient in olfactory than in respiratory mucosal homogenates. In the present study, an in vitro system of cultured rat nasal explants was utilized to determine if dibasic ester toxicity is dependent on a metabolic activation by nonspecific carboxylesterase. Explants from both the olfactory and the respiratory regions of the female rat nasal cavity were incubated for 2 hr in Williams' medium E containing 10-100 mM dimethyl adipate, dimethyl glutarate, or dimethyl succinate, dibasic ester caused a dose-related increase in nasal explant acid phosphatase release, a biochemical index of cytotoxicity. HPLC analysis demonstrated parallel increases in the carboxylesterase-mediated formation of monomethyl ester metabolites. Diacid metabolite production in the nasal explant system was not entirely concentration-dependent. Metabolite concentrations and acid phosphatase release were generally greater in olfactory than respiratory tissues. dibasic ester-induced cytotoxicity and acid metabolite production were markedly attenuated in nasal tissue excised from rats which were pretreated with bis(p-nitrophenyl)phosphate, a carboxylesterase inhibitor. This study presents a viable in vitro method for assessing organic ester cytotoxicity in the rat nasal cavity. It was shown that dibasic ester are weak nasal toxicants under the conditions of this system. It was further demonstrated that dibasic ester toxicity is dependent on a carboxylesterase-mediated activation. A similar mechanism was proposed for the nasal toxicity induced by other organic esters following inhalation exposure.

Inhalation exposure of rats to dibasic esters revealed lesions of the nasal olfactory epithelium similar to those observed with other ester solvents. Female rats are more sensitive to these effects than are male rats. It has been proposed that carboxylesterase conversion of inhaled esters within nasal tissues to organic acids may be a critical biochemical step in converting these chemicals to toxic substances. These experiments measured the kinetic parameters Vmax, Km, Ksi, and V/K for the hydrolysis of the dibasic esters in the target nasal tissue, olfactory mucosa, and nontarget tissue, respiratory mucosa. It was determined that under the conditions of these experiments, diacid metabolites are not formed. Esterase activity was inhibited by pretreatment with bis p-nitrophenyl phosphate. Vmax values for the three dibasic esters were 5- to 13-fold greater in olfactory mucosa than respiratory mucosa for male or female rats. V/K values were 4- to 11-fold greater in olfactory mucosa than respiratory mucosa for male or female rats. V/K was similar between male and female olfactory mucosa when dimethyl glutarate was used as the substrate. With dimethyl succinate or dimethyl adipate as the substrate, V/K for female olfactory tissue was 0.5- or 2-fold that of males, respectively. Differences in V/K were mainly due to decreases in KM associated with increasing carbon chain length. Substrate inhibition was observed at dibasic ester concentrations greater than approximately 25 mM, which are unlikely to be achieved in vivo. These results lend further support to the hypothesis that organic acid accumulation in the target tissue, olfactory mucosa, plays a significant role in the pathogenesis of dibasic ester-induced nasal lesions. The mechanism nay be applicable to a wide range of inhaled esters.

CIR ingredient: Dimethyl Succinate

Used as a solvent for fruit flavors and a synthetic flavor; [HSDB]

SOLVENT FOR FRUIT FLAVORS

SYNTHETIC FLAVOR

EPA Safer Chemical Functional Use Classes -> Solvents

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

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Plastics Material and Resin Manufacturing

Butanedioic acid, 1,4-dimethyl ester: ACTIVE

NON-ALCOHOLIC BEVERAGES 1.0-100 PPM; ICE CREAM, ICES, ETC 5.0 PPM; CANDY 15 PPM; BAKED GOODS 15 PPM; CHEWING GUM 5.0 PPM.

FEMA NUMBER 2396