1,2-Dipalmitoyl-rac-glycerol

SECTION 2: Hazards identification

CHEMWATCH HAZARD RATINGS Min Max Flammability: 1 Toxicity: 0 Body Contact: 0 Min/Nil=0 Low=1 Reactivity: 1 Moderate=2 High=3 Chronic: 2 Extreme=4 CANADIAN WHMIS SYMBOLS EMERGENCY OVERVIEW RISK Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

Potential Acute Health Effects

SWALLOWED The material has NOT been classified as "harmful by ingestion". This is because of the lack of corroborating animal or human evidence. Use in food, and as food additive indicates high degree of tolerance. EYE Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. SKIN The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting. Open cuts, abraded or irritated skin should not be exposed to this material. Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected. INHALED The material is not thought to produce adverse health effects or irritation of the respiratory tract (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting. Inhalation hazard is increased at higher temperatures. Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled. Inhalation of oil droplets/ aerosols may cause discomfort and may produce chemical pneumonitis. Fine mists generated from plant/ vegetable (or more rarely from animal) oils may be hazardous. Extreme heating for prolonged periods, at high temperatures, may generate breakdown products which include acrolein and acrolein-like substances.

Potential chronic health

There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment. Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Synthetic 1,2-diglycerides of short chain (C6, C8, C10) fatty acids are activators of protein kinase C (PKC). PKC is a serine-threonine kinase which also requires calcium ion for its activation. Activated PKC phosphorylates proteins of the cellular signal cascade, which eventually induce expression of growth regulatory genes. This, in turn, may promote the growth of tumours. Structural analogues of the 1,2-diglycerides, such as the phorbol esters, have been shown to strongly promote such an event. Glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dierucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate, and glyceryl stearate succinate are diacylglycerols (also known as diglycerides or glyceryl diesters) that function as skin conditioning agents-emollients in cosmetics. Only glyceryl dilaurate (up to 5%), glyceryl diisostearate (up to 43%), glyceryl dioleate (up to 2%), glyceryl distearate (up to 7%), and glyceryl stearate lactate (up to 5%) are reported to be in current use. Production proceeds from fully refined vegetable oils, which are further processed using hydrogenation and fractionation techniques, and the end products are produced by reacting selected mixtures of the partly hydrogenated, partly fractionated oils and fats with vegetable-derived glycerine to yield partial glycerides. In the final stage of the production process, the products are purified by deodorization, which effectively removes pesticide residues and lower boiling residues such as residues of halogenated solvents and aromatic solvents. Diglycerides have been approved by the Food and Drug Administration (FDA) for use as indirect food additives. Nominally, these ingredients are 1,3-diglycerides, but are easily isomerised to the 1,2-diglycerides form. The 1,3-diglyceride isomer is not a significant toxicant in acute, short-term, subchronic, or chronic animal tests. Glyceryl dilaurate was a mild primary irritant in albino rabbits, but not a skin sensitiser in guinea pig maximization tests. Diacylglycerol oil was not genotoxic in the Ames test, in mammalian Chinese hamster lung cells, or in a rodent bone marrow micronucleus assay. An eye shadow containing 1.5% glyceryl dilaurate did not induce skin irritation in a single insult patch test, but mild skin irritation reactions to a foundation containing the same concentration were observed. A trade mixture containing an unspecified concentration of glyceryl dibehenate did not induce irritation or significant cutaneous intolerance in a 48-h occlusive patch test. In maximization tests, neither an eye shadow nor a foundation containing 1.5% glyceryl dilaurate was a skin sensitiser. Sensitisation was not induced in subjects patch tested with 50% w/w glyceryl dioleate in a repeated insult, occlusive patch test. Glyceryl palmitate lactate (50% w/v) did not induce skin irritation or sensitization in subjects patch tested in a repeat-insult patch test. Phototoxicity or photoallergenicity was not induced in healthy volunteers tested with a lipstick containing 1.0% Glyceryl rosinate. Two diacylglycerols, 1-oleoyl-2-acetoyl-sn-glycerol and 1,2-dipalmitoyl-sn-glycerol, did not alter cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 g/ml. In the absence of initiation, Glyceryl distearate induced a moderate hyperplastic response in randomly bred mice of a tumor-resistant strain, and with 9,10-dimethyl- 1,2-benzanthracene (DMBA) initiation, an increase in the total cell count was observed. In a glyceryl monoester study, a single application of DMBA to the skin followed by 5% glyceryl stearate twice weekly produced no tumors, but slight epidermal hyperplasia at the site of application. Glyceryl dioleate induced transformation in 3-methylcholanthrene-initiated BALB/3T3 A31-1-1 cloned cells in vitro. A tumour- promoting dosing regimen that consisted of multiple applications of 10 mol of a 1,2-diacylglycerol (sn-1,2-didecanoylglycerol) to female mice twice daily for 1 week caused more than a 60% decrease in protein kinase C (PKC) activity and marked epidermal hyperplasia. Applications of 10 umol sn-1,2-didecanoylglycerol twice weekly for 1 week caused a decrease in cytosolic PKC activity, an increase in particulate PKC activity, and no epidermal hyperplasia. In studies of the tumour-promoting activity of 1,2-diacylglycerols, dose and the exposure regimen by which the dose is delivered play a role in tumor promotion. The 1,2-diacylglycerol–induced activation of PKC may also relate to the saturation of the fatty acid in the 1 or 2 position; 1,2-Diacylglycerols with two saturated fatty acids are less effective. Also, the activity of 1,2-diacylglycerols may be reduced when the fatty acid moiety in the structure is a long-chain fatty acid. A histological evaluation was performed on human skin from female volunteers (18 to 56 years old) who had applied a prototype lotion or placebo formulation, both containing 0.5% Glyceryl Dilaurate, consecutively for 16 weeks or 21 weeks. Skin irritation was not observed in any of the subjects tested. Biopsies (2 mm) taken from both legs of five subjects indicated no recognizable abnormalities of the skin; the epidermis was normal in thickness, and there was no evidence of scaling, inflammation, or neoplasms in any of the tissues that were evaluated. The available safety test data indicate that diglycerides in the 1,3-diester form do not present any significant acute toxicity risk, nor are these ingredients irritating, sensitizing, or photosensitising. Whereas no data are available regarding reproductive or developmental toxicity, there is no reason to suspect any such toxicity because the dermal absorption of these chemicals is negligible. 1,3-Diglycerides contain 1,2-diglycerides, raising the concern that 1,2-diglycerides could potentially induce hyperplasia. Data regarding the induction of PKC and the tumour promotion potential of 1,2-diacylglycerols increases the level of concern. Most of the diglycerides considered above,however, have fatty acid chains longer than 14 carbons and none have mixed saturated/unsaturated fatty acid moieties. In a 21-week use study of a prototype lotion containing 0.5% glyceryl dilaurate (a 14-carbon chain fatty acid) indicated no evidence of scaling, inflammation, or neoplasms in biopsy specimens. Also, DNA synthesis assays on glyceryl dilaurate and glyceryl distearate indicated that neither chemical altered cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 ug/ml. However the concentration of these ingredients can vary (up to 43% for glyceryl diisostearate in lipstick), the frequency of application can be several times daily, and the proportion of diglycerides that are inactive 1,3 isomers versus potentially biologically active 1,2 isomers is unknown; as a precaution it is believed that each use should be examined to ensure the absence of epidermal hyperplasia during product development and testing. In the absence of inhalation toxicity data on the glyceryl diesters it is thought that these ingredients can be used safely in aerosolised products because they are not respirable. 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 CIR Expert Panel considers all ingredients in this group to be safe. International Journal of Toxicology, Vol. 26, No. 3 Suppl, 1-30 (2007). Glycerol esters occur throughout nature and make up part of the normal diet.