Morpholine

What Is It?

Morpholine is a clear, oily liquid. In cosmetics and personal care products, Morpholine may be used in the formulation of eyeliner, eye shadow, mascara, eye makeup remover and skin care products.

Why Is It Used?

Morpholine functions as a pHA measurement of the acidity or basicity of a substance. pH is the negative logarithm (base 10) of the concentration of hydrogen ions in solution. Water has a concentration of hydrogen ions of 1.0 x 10-7, and thus has a pH of 7. A pH of 7 is considered neutral, a pH lower than 7 is considered acidic, and a pH higher than 7 is considered basic. adjustor. It may also function as a surfactantAn ingredient that helps two substances that normally do not mix to become dissolved or dispersed in one another. Also called a surface active agent. and emulsifier.

Scientific Facts

Morpholine is a heterocyclic secondary amine. In addition to its use in cosmetics and personal care products, Morpholine derivatives have been used as insecticides, fungicides, herbicides, anesthetics, analgesics, and antiseptics.

Safety Information

The Food and Drug Administration (FDA) includes Morpholine on its list of direct food additives. It is permiteed in coatings, films and related substances. Morpholine is also an FDA approved indirect food additiveIndirect food additives are additives that may become part of the food in trace amounts due to its packaging, storage or other handling. For example, minute amounts of packaging substances may find their way into foods during storage. that may be used as a component of adhesives and paper and paperboard. The safety of Morpholine has been assessed by the Cosmetic Ingredient ReviewThe Cosmetic Ingredient Review (CIR) was established in 1976 as an independent safety review program for cosmetic ingredients. The CIR Expert Panel consists of independent experts in dermatology, toxicology, pharmacolgy and veterinary medicine. The CIR includes participation by the U.S. Food & Drug Administration and the Consumer Federation of America. (CIR) Expert Panel. The CIR Expert Panel evaluated the scientific data and concluded that the data were insufficient to support the safety of this ingredient as used in cosmetics and personal care products.

CIR Safety Review: The CIR Expert Panel noted that Morpholine that has not been neutralized (hydrogen bound to the nitrogen) was more irritating than Morpholine that has been neutralized (hydrogen bound to nitrogen replaced, for example with chloride). In short-term inhalation studies with varying concentrations of Morpholine, the effects observed included irritation of the mucous membranes and an increased respiratory rate. Chronic inhalation studies of Morpholine reported changes in the nervous system activity and arterial and peripheral blood pressure. At the high concentrations, Morpholine produced swelling of the alveolar cells and atrophy of lymphoid elements in the spleen. At lower concentrations, a decrease in the size of the lymph nodules in the spleen was noted. Morpholine was a weak positive mutagen in L5178 lymphoma assay, in BALB/3T3 malignant cellThe basic structural and functional unit of all organisms; cells may exist as independent units of life or may form colonies or tissues as in higher plants and animals. transformation, and fibroblastA type of cell found in connective tissue that is responsible for the formation of fibers. transformation assays, and in sister chromatid exchange assays, but was negative in bacteria with and without metabolic activation. At nontoxic doses, Morpholine did not increase the rate of DNA repair in hepatocytes. Results of other mutagenic assays varied with the system used. In humans, Morpholine was absorbed and was considered to be a skin and eye irritant, as well as a skin sensitizer.

A formulation containing 1% Morpholine indicated that the ingredient was neither an irritant nor sensitizer. The CIR Expert Panel acknowledged that cosmetics and personal care products containing Morpholine, in the presence of nitrate or other nitrosating agents, may give rise to N-nitrosomorpholine. N-nitrosomorpholine was mutagenic in a variety of test systems and simulataneous exposure to Morpholine and nitrites has caused a number of different cancers. A carcinogenic response was produced in a long-term feeding study of Morpholine in which nitrates were present in the diet. Because of the concern about potential nitrosamine formation and the lack of information on whether or not nitrosamines are present when Morpholine was used as a cosmetic ingredient, the CIR Expert Panel concluded that the data were insufficient to support the safety of Morpholine as used in cosmetics and personal care products.

More information about nitrosamines.

Link to FDA Code of Federal Regulations for Morpholine

Health Canada prohibits the use of Morpholine and its salts in cosmetics and personal care products.
http://www.hc-sc.gc.ca/cps-spc/person/cosmet/info-ind-prof/_hot-list-cri…

Morpholine and its salts are listed in the Cosmetics Directive of the European Union (see Annex II) and must not form part of the composition of cosmetics and personal care products.

Link to the EU Cosmetic Regulation:
http://europa.eu/legislation_summaries/consumers/product_labelling_and_p…

Resources

Find out more about the regulation of Food Additives by the Food and Drug Administration

Food Ingredients and Packaging: http://www.fda.gov/Food/IngredientsPackagingLabeling/default.htm

Food Contact Substances: http://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/defaul…

Substances Generally Recognized As Safe (GRAS“GRAS” is an acronym for the phrase Generally Recognized As Safe. Under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act (the Act), any substance that is intentionally added to food is a food additive, that is subject to premarket review and approval by FDA, unless the substance is generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of its intended use, or unless the use of the substance is otherwise excluded from the definition of a food additive.): http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/default.htm

Search the Code of Federal Regulations http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm

EU Cosmetics Inventory http://ec.europa.eu/consumers/cosmetics/cosing/