GLYCERIN

In a survey of 4 laboratories of the use of vehicles in in vivo experiments, the highest no-observed-adverse-effect levels (NOAEL) of various routes of administration were assembled.22 The oral NOAELs for glycerin were 15 g/kg for rats and 500 mg/kg for guinea pigs for 1 month and 500 mg/kg for 90 days for mice (Table 4). The highest subcutaneous NOAELs were 10 mg/kg rats and mice. Acute Toxicity Non-Human The reported oral LD 50 of glycerin ranged from 2530-58 400 mg/kg in rats; there were no deaths at 24 000 mg/kg in one study (Table 5).2,18,23-27 The reported oral LD 50 of glycerin ranged from 4090->38 000 mg/kg in mice, 27 000 mg/kg in rabbits, and 77 500 mg/kg in guinea pigs.2,18,23,24,26-29 The dermal LD 50 of glycerin in rats was reported to be >21 900 mg/kg and >18 700 mg/kg in rabbits.2,26 The approximate Lt 50 for rats was determined to be 423 min for exposure to glycerin vapors at 11.0 mg/L.4 The intraperitoneal LD 50 of glycerin in rats ranged from 4420-10 100 mg/kg and 8600-9500 mg/kg in mice.2 The subcutaneous LD 50 of glycerin was 100 mg/kg in rats and ranged from 91-100 mg/kg in mice.2,29 The intravenous LD 50 of glycerin ranged from 5200-6600 mg/kg in rats, 4250-6700 mg/kg in mice, and was 53 000 mg/kg in rabbits.2 Oral – Human The LD LO of glycerin was reported to be 1428 mg/kg for humans.2 There were no signs of toxicity when subjects (n=10 men, 4 women) were administered glycerin (30 mL; 95% in orange juice) after each of 3 meals in 1 day.3  Distributed for comment only -- do not cite or quote Adverse effects following the oral administration of glycerin (dose not provided) include mild headache, dizziness, nausea, vomiting, thirst, and diarrhea.15 Headache may result from cerebral dehydration, which may be prevented or relieved … [kırpıldı - bölüm toplam 13151 karakter]

Definition and Structure Glycerin (CAS No. 56-81-5) is the polyhydric alcohol that conforms generally to the structure in Figure 1.1 The molecular formula is C 3 H 8 O 3 . Glycerin (also referred to as glycerol in the literature) is a simple polyol compound that has three hydroxyl groups. Figure 1. Glycerin Glycerin is naturally occurring in all animals and plant matter in combined form as glycerides in fats and oils, or, in intracellular spaces as lipids.2 While the compounds are identical, there is naturally occurring glycerin, derived from plants and animals, and synthetic glycerin, obtained from non-triglyceride sources.5 Physical and Chemical Properties Glycerin is a clear, syrupy liquid (Table 1).3,6 It can be in a crystallized state, but seldom is because of its tendency to supercool, and the pronounced effect of small amounts of water depressing the freezing point.2 Glycerin has solvent properties similar to those of water and simple aliphatic alcohols, because of its 3 hydroxyl groups.5 The compound is completely miscible with water, methanol, ethanol, and the isomers of propanol, butanol, and pentanol. Glycerin is also fully miscible with phenol, glycol, propanediols, amines, and heterocyclic compounds containing a nitrogen atom in the ring (eg pyridine, quinoline). Glycerin is less soluble in acetone, diethyl ether, and dioxane, and is almost insoluble in hydrocarbons, long-chain aliphatic alcohols, fatty oils, and halogenated solvents such as chloroform. Method of Manufacture Natural glycerin is obtained as a byproduct in the conversion of fats and oils to fatty acids or fatty acid methyl esters.5 Multiple methods exist for the manufacture of glycerin. The starting materials for synthetic production of glycerin … [kırpıldı - bölüm toplam 12762 karakter]

CIR final (2014): The CIR Expert Panel concluded that glycerin is safe in the present practices of use and concentration described in this safety assessment in cosmetics.

Acute Toxicity Studies Details of the acute oral toxicity studies summarized below can be found in Table 4. The acute oral LD50 values for 20 and 25% Diglycerin, in water, were reported to be > 2000 mg/kg bw and > 5000 mg/kg bw (the highest dose tested), respectively, in two separate studies performed in rats in accordance with Organisation for Economic Cooperation and Development (OECD) test guideline (TG) 401.3,5 Male and female Wistar rats were administered a single 2000 mg/kg bw dose of 100% Polyglycerin-3 via gavage, in accordance with OECD TG 401.3,4 Decreased body weight was observed in 1 female and reduced weight gain was observed in 2 females on day 14. Abnormal gross pathological findings (details not provided) found in one female rat were considered possibly test-related; the LD50 value was determined to be > 2000 mg/kg bw. Female Sprague-Dawley rats were administered 2000 mg/kg bw of a polyglycerol mixture comprising mostly 50.8% Polyglycerin-3 and 28.2% Diglycerin via gavage, in accordance with OECD TG 423.3,4 No deaths or clinical abnormalities were observed and the LD50 was determined to be > 2000 mg/kg bw. Short-Term Toxicity Studies Oral Glycerin (for read-across) Undiluted glycerin administered to Charles River female rats (10 test animals/group; 20 controls) at 0, 0.75, 1.5, or 3 mg/kg for 3 d, via gavage, caused a dose-dependent increase in the number of animals showing hyperemia, petechial hemorrhage, and erosions in the gastrointestinal tract.2 Male Wistar rats (24 test animals; 18 controls) were given glycerin in an amount equivalent to 53.4% carbohydrate in feed for 20 d. Controls were fed stock carbohydrate or a stock diet calculated to deliver the same calories as the glycerin diet. Controls gained weight at 6% per day, while glycerin-fed and pair-fed controls gained 3% body weight per day. Livers were 6% of the body weight in the glycerin-fed rats and 4.6% of the … [kırpıldı - bölüm toplam 8259 karakter]

Oral Glycerin (for read-across) Glycerin was tested in several oral developmental and reproductive toxicity studies.2 Groups of 25 female CD-1 mice were administered 12.8, 59.4, 276, or 1280 mg/kg/d glycerin, via gavage, on day 6 to day 15 of gestation; the NOAEL for maternal toxicity and teratogenicity was determined to be 1280 mg/kg/d. In another study, groups of 28 female Wistar rats received 13.1, 60.8, 282, or 1310 mg/kg/d glycerin, via gavage, on day 6 to day 15 of gestation; the NOAEL for maternal toxicity and teratogenicity was determined to be 1310 mg/kg/d. Groups of 25 female Dutch-belted rabbits received 11.8, 54.8, 254.5, or 1180 mg/kg/d glycerin, via gavage, on day 6 to day 18 of gestation; the NOAEL for maternal toxicity and teratogenicity was determined to be 1180 mg/kg/d. For all 3 studies, the number of implantations, resorptions, litter sizes, weights, sex ratio, as well as external, visceral, and skeletal abnormalities, were similar among groups. In a 2-generation reproductive study using rats (10/sex/group), glycerin was administered at 0 or 20% (~ 2000 mg/kg/d) in drinking water of the parent (F0) generation for 8 wk prior to mating and until the weaning of pups. No adverse effects on the reproductive efficiency of the parent F0 generation, or the growth, fertility, or reproductive performance of the untreated offspring (F1)generation were observed. Additionally, no histological changes occurred in the tissues, and the onset of estrus cycles, weight gain, and microscopic observations of the endocrine organs were comparable to those of the controls in both the F1 and F2 generations. All 10 females in the F0 generation, and 9 out of 10 females in the F1 generation became pregnant and the F0 generation had a litter size similar to controls (9.0 vs 8.1). Other Routes Glycerin (for read-across) In a reproductive toxicity study, groups of 12 male rats received 2 intratesticular injections of 50 - 200 µl glycerin, 7 d … [kırpıldı - bölüm toplam 2892 karakter]

EPA ToxValDB genotoxicity: positive - positive reports: 10, negative: 7, Ames: positive. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxCast ER model: NO estrogen receptor activity found (AUC agonist=0, antagonist=0). Tested in 18 in vitro assays. Caveat: this is an in vitro screening model with no dose or exposure context; it does NOT mean an effect occurs in humans at cosmetic use levels.