Glycyrrhetinic Acid

The Basics On Glycyrrhetinic Acid

What is Glycyrrhetinic Acid?

One of the components of licorice root extract.

What are other names for Glycyrrhetinic Acid?

(3B,20B )-3-HYDROXY-11-OXO-OLEAN-12-EN-29-OIC ACID, (3B,20B)- OLEAN-12-EN-29-OIC ACID, 3-HYDROXY-11-OXO-, 3-HYDROXY-11-OXO- (3B,20B)- OLEAN-12-EN-29-OIC ACID, ENOXOLONE, GLYCYRRETINIC ACID, GLYCYRRHETIC ACID, GLYCYRRHETINIC ACID, OLEAN-12-EN-29-OIC ACID, 3-HYDROXY-11-OXO-, (3.BETA.,20.BETA.)-, OLEAN-12-EN-29-OIC ACID, 3-HYDROXY-11-OXO-, (3B,20B)-, and URALENIC ACID

What is Glycyrrhetinic Acid used for?

Glycyrrhiza Glabra (Licorice) Root Extract, also known as Licorice root oil, is oil extracted for the Glycyrrhiza Glabra or Licorice plant. This herb is native to the Mediterranean, southern and central Russia, and Asia Minor to Iran. Many species are now grown throughout Europe, Asia, and the Middle East.

How Glycyrrhetinic Acid is classified

Antioxidants, Skin-Soothing

Recommendations for using Glycyrrhetinic Acid during pregnancy and breastfeeding

Limited data suggests no known risk

 

Glycyrrhetinic Acid During Pregnancy

What we know about using Glycyrrhetinic Acid while pregnant or breastfeeding

Limited information available.

FDRL (1971b) studied the developmental toxicity potential of Ammonium Glycyrrhizate in four species of mammals. Pregnant CD-1 outbred mice received 0, 27, 90, 300, or 1000 mg/kg/day Ammonium Glycyrrhizate by oral gavage on gestation days 6 through 15 (n = 19 to 21 pregnant dams/dose group). The fetuses were removed by caesarian section on gestation day 17 and examined. There was no effect on maternal or fetal survival and no remarkable observation upon visceral and skeletal examinations of the fetuses. Pregnant Wistar rats received 0, 27, 90, 300, or 1000 mg/kg/day Ammonium Glycyrrhizate by oral gavage on gestation days 6 through 15 (n = 21 to 22 pregnant dams/dose group). The fetuses were removed by caesarian section on gestation day 20 and examined. There was no effect on maternal or fetal survival and no remarkable observation upon visceral and skeletal examinations of the fetuses. Pregnant golden hamsters received 0, 27, 90, 300, or 1000 mg/kg/day Ammonium Glycyrrhizate by oral gavage on gestation days 6 through 10 (n = 21 to 23 pregnant dams/dose group). The fetuses were removed by caesarian section on gestation day 15 and examined. There was no effect on maternal or fetal survival. Aside from dose-dependent delayed cranial ossification, no remarkable observation upon visceral and skeletal examinations of the fetuses was noted. Pregnant Dutch-belted rabbits received 0, 27, 90, 300, or 1000 mg/kg/day Ammonium Glycyrrhizate by oral gavage on gestation days 6 through 18 (n = 10 to 12 pregnant dams/dose group). The fetuses were removed by caesarian section on gestation day 29 and examined. There was no effect on maternal or fetal survival and no remarkable observation upon visceral and skeletal examinations of the fetuses (FDRL 1971b). In the previously mentioned Monlux (1974) study where rats were fed Glycyrrhizate, exposure to up to 4% Ammonium Glycyrrhizate in utero did not cause any observed developmental defects. Mantovani et al. (1988) studied the teratogenicity of Ammonium Glycyrrhizate in Sprague-Dawley rats. Pregnant rats received drinking water containing 0, 10, 100, or 250 mg/ml Ammonium Glycyrrhizate on gestation days 7 through 17. The actual exposure levels, based on water consumption calculations, were 0, 21.33, 238.8, and 679.9 mg/kg/day, respectively. Dams were killed on gestation day 20. Dams and fetuses were examined. Water consumption was increased in dams of the 238.8 and 679.9 mg/kg/day groups. Fetuses exposed to Ammonium Glycyrrhizate did not have changes in the rate of external malformations, body weight, or degree of ossification, compared to controls. The incidence of external hemorrhages was increased in fetuses of the low- (21.33 mg/kg/day) and high- (679.9 mg/kg/day) dose groups (p < 0.01), but not in the middle- (238.8 mg/kg/day) dose group. Renal variants and ectopic kidneys were observed in fetuses of the lowest-dose group (p < 0.05). High-dose fetuses also had ectopic kidneys. Skeletal examinations revealed a dose-dependent increase in sternebral variants, significant (p < 0.01) in the middle- and high-dose groups. The lowest observed effect level in this study was 21.33 mg/kg/day. Itami et al. (1985) gave pregnant Wistar rats 0%, 0.08%, 0.4%, or 2% Disodium Glycyrrhizate mixed in feed on gestation days 0 through 20 (n = 8 to 11 pregnant dams/dose group). There was no treatment-related effect on any of the following parameters: number of corpora lutea, number of implants, number of live fetuses, number of intrauterine dead fetuses per litter, sex ratio, fetal body weights, placental weights, degree of ossification, live birth index, survival rate, and pup body weight gain up to 8 weeks postpartum. The authors concluded that Disodium Glycyrrhizate was not teratogenic in rats under the treatment conditions of this study.

General safety info about Glycyrrhetinic Acid from CIR

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents—miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24- OH-Glycyrrhetinic Acid, not more than 20 μg/g of heavy metals and not more than 2 μg/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a β-glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11β-hydroxysteroid dehydrogenase-2 (11β-OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in Received 30 November 2006; accepted 5 March 2007. 1Reviewed by the Cosmetic Ingredient Review Expert Panel. Address correspondence to F. Alan Andersen, Cosmetic Ingredient Review, 1101 17th Street, NW, Suite 412, Washington, DC 20036, USA. animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD50 for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD50 was >610 mg/kg. The oral LD50 in rats was reported to be 610 mg/kg. Higher LD50 values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day−1 in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day−1 for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day−1) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, 79 80 COSMETIC INGREDIENT RERIEW nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed >500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.

Use this, not that!

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