FDA Warning on DEA
The National Toxicology Program (NTP) completed a study in 1998 that found an association between topical application of Cocamide DEA and certain DEA-related ingredients and cancer in laboratory animals. For DEA-related ingredients, the NTP study suggests that the carcinogenic response is linked to possible residual levels of DEA. The NTP study did not establish a link between DEA and cancer risk in humans. FDA believes that there is currently no reason for consumers to be alarmed about the use of these substances in cosmetics. However, consumers who wish to avoid cosmetics containing DEA-related ingredients or DEA can do so by checking the following names, which are some of the most commonly used ingredients that may contain DEA (1):
- Cocamide DEA
- Cocamide MEA
- DEA-cetyl phosphate
- DEA Oleth-3 phosphate
- Lauramide DEA
- Linoleamide MEA
- Myristamide DEA
- oleamide DEA
- Stearamide MEA
- TEA-laurilsolfate
- triethanolamine
The most relevant studies on this ingredient have been selected with a summary of their contents:
A.Panico A, Serio F, Bagordo F, Grassi T, Idolo A, DE Giorgi M, Guido M, Congedo M, DE Donno A. Skin safety and health prevention: an overview of chemicals in cosmetic products. J Prev Med Hyg. 2019 Mar 29;60(1):E50-E57. doi: 10.15167/2421-4248/jpmh2019.60.1.1080.
Abstract. Introduction: Cosmetic products contain a wide range of chemicals to which we are exposed every day. The aim of the study was to determine the presence of potential dangerous substances which can cause adverse health effects by examining product labels. Materials and methods: A total of 283 products were collected from various shops in Lecce (Italy) and divided into 3 categories: rinse-off, leave-on and make-up. The label of every product was examined and a list including fragrances, preservatives and other chemicals of concern was created. Results: Fragrances were present in 52.3% of the examined products, mostly limonene (76.9%) and linalool (64.6%) but also citronellol (34.1%), geraniol (31.5%), coumarin (30%) and hexyl cinnamal (29.2%). Preservatives showed a rate of 60% and the most frequently identified were phenoxyethanol (48.7%), sodium benzoate (35.6%), potassium sorbate (22%), methylparaben (15.2%) and MI/MCI (9.9%). The other chemicals of concern were detected in 58% of products; included PEGs (62.3%), acrylate copolymer (34%), petrolatum (17.2%), polysorbates (14,8%), BHT (14.7%), ethylhextyl methoxycinnamate (13.6%), benzophenone-1 (3.7%), benzophenone-3 (4.9%), BHA (1.6%), cocamide DEA and toluene (1.2%). Conclusions: The use of many of these substances is allowed within certain limits, due to their toxicity at higher concentrations. Other important aspects should be considered as, for instance, the possibility of long-term effects. On the other hand, other substances may induce several acute adverse side-effects, i.e. contact dermatitis and allergic reactions. For these reasons, an enhancement of the criteria used for cosmetics formulation is required since many chemicals used singularly or combined are potentially unsafe.
Leung HW, Kamendulis LM, Stott WT. Review of the carcinogenic activity of diethanolamine and evidence of choline deficiency as a plausible mode of action. Regul Toxicol Pharmacol. 2005 Dec;43(3):260-71. doi: 10.1016/j.yrtph.2005.08.001.
Abstract. Diethanolamine (DEA) is a chemical used widely in a number of industries and is present in many consumer products. Studies by the National Toxicology Program (NTP) have indicated that lifetime dermal exposure to DEA increased the incidence and multiplicity of liver tumors in mice, but not in rats. In addition, DEA was not carcinogenic when tested in the Tg.Ac transgenic mouse model. Short-term genotoxicity tests have yielded negative results. In view of these apparent inconsistencies, we have critically evaluated the NTP studies and other data relevant to assessing the carcinogenic potential of DEA. The available data indicate that DEA induces mouse liver tumors by a non-genotoxic mode of action that involves its ability to cause choline deficiency. The following experimental evidence supports this hypothesis. DEA decreased the hepatic choline metabolites and S-adenosylmethionine levels in mice, similar to those observed in choline-deficient mice. In contrast, DEA had no effect in the rat, a species in which it was not carcinogenic at a maximum tolerated dose level. In addition, a consistent dose-effect relationship had been established between choline deficiency and carcinogenic activity since all DEA dosages that induced tumors in the NTP studies were also shown to cause choline deficiency. DEA decreased phosphatidylcholine synthesis by blocking the cellular uptake of choline in vitro, but these events did not occur in the presence of excess choline. Finally, DEA induced transformation in the Syrian hamster embryo cells, increased S-phase DNA synthesis in mouse hepatocytes, and decreased gap junctional intracellular communication in primary cultured mouse and rat hepatocytes, but all these events were prevented with choline supplementation. Since choline is an essential nutrient in mammals, this mode of action is qualitatively applicable to humans. However, there are marked species differences in susceptibility to choline deficiency, with rats and mice being far more susceptible than other mammalian species including humans. These differences are attributed to quantitative differences in the enzyme kinetics controlling choline metabolism. The fact that DEA was carcinogenic in mice but not in rats also has important implications for human risk assessment. DEA has been shown to be less readily absorbed across rat and human skin than mouse skin. Since a no observed effect level for DEA-induced choline deficiency in mice has been established to be 10 mg/kg/d, this indicates that there is a critical level of DEA that must be attained in order to affect choline homeostasis. The lack of a carcinogenic response in rats suggests that exposure to DEA did not reach this critical level. Since rodents are far more sensitive to choline deficiency than humans, it can be concluded that the hepatocarcinogenic effect of DEA in mice is not predictive of similar susceptibility in humans.
Libralato, G., Ghirardini, A. V., & Avezzù, F. (2010). Seawater ecotoxicity of monoethanolamine, diethanolamine and triethanolamine. Journal of hazardous materials, 176(1-3), 535-539.
Abstract. Monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) are compounds with potential acute, sub-chronic and chronic toxicity effects towards aquatic species. A literature review highlighted the existence of a gap in the knowledge on their toxicity with saltwater testing species. A battery of toxicity tests including the alga Phaeodactylum tricornutum Bohlin, the bivalve molluscs Crassostrea gigas (Thunberg) and Mytilus galloprovincialis (Lmk), and the crustacean Artemia franciscana, was considered to update and improve the existing ecotoxicological information. Data were provided as the Effective Concentration that induces a 50% effect in the observed population (EC50), Lowest Observed Effect Concentration (LOEC) and No Observed Effect Concentration (NOEC). EC50, LOEC and NOEC values were compared with a reviewed database containing the existing ecotoxicological data from saltwater organisms.
Burgess IF, Brunton ER, Brown CM. Laboratory and clinical trials of cocamide diethanolamine lotion against head lice. PeerJ. 2015 Nov 3;3:e1368. doi: 10.7717/peerj.1368.
Abstract. Context. During the late 1990s, insecticide resistance had rendered a number of treatment products ineffective; some companies saw this as an opportunity to develop alternative types of treatment. We investigated the possibility that a surfactant-based lotion containing 10% cocamide diethanolamine (cocamide DEA) was effective to eliminate head louse infestation. Settings and Design. Initial in vitro testing of the lotion formulation versus laboratory reared body/clothing lice, followed by two randomised, controlled, community-based, assessor blinded, clinical studies. Materials and Methods. Preliminary laboratory tests were performed by exposing lice or louse eggs to the product using a method that mimicked the intended use. Clinical Study 1: Children and adults with confirmed head louse infestation were treated by investigators using a single application of aqueous 10% cocamide DEA lotion applied for 60 min followed by shampooing or a single 1% permethrin creme rinse treatment applied to pre-washed hair for 10 min. Clinical Study 2: Compared two treatment regimens using 10% cocamide DEA lotion that was concentrated by hair drying. A single application left on for 8 h/overnight was compared with two applications 7 days apart of 2 h duration, followed by a shampoo wash. Results. The initial laboratory tests showed a pediculicidal effect for a 60 min application but limited ovicidal effect. A longer application time of 8 h or overnight was found capable of killing all eggs but this differed between batches of test material. Clinical Study 1: Both treatments performed badly with only 3/23 (13%) successful treatments using cocamide DEA and 5/25 (23.8%) using permethrin. Clinical Study 2: The single overnight application of cocamide DEA concentrated by hair drying gave 10/56 (17.9%) successes compared with 19/56 (33.9%) for the 2 h application regimen repeated after 1 week. Intention to treat analysis showed no significant difference (p = 0.0523) between the treatments. Over the two studies, there were 18 adverse events possibly or probably associated with treatment, most of which were increased pruritus after treatment. Conclusions. Cocamide DEA 10% lotion, even when concentrated by hair drying, showed limited activity to eliminate head louse infestation.
Grey KR, Hanson JL, Hagen SL, Hylwa SA, Warshaw EM. Epidemiology and Co-Reactivity of Novel Surfactant Allergens: A Double-Blind Randomized Controlled Study. Dermatitis. 2016 Nov/Dec;27(6):348-354. doi: 10.1097/DER.0000000000000226.
Abstract. Background: Surfactants are cleansing agents used in products such as shampoos and soaps. Objectives: The aims of this study were to identify positivity rates to 3 novel amide-containing surfactants (sodium lauroyl sarcosinate, isostearamidopropyl morpholine lactate, and disodium lauroamphodiacetate) and evaluate co-reactivity with other surfactants in patients with known surfactant sensitivity....Conclusions: Isostearamidopropyl morpholine lactate may be an important emerging allergen with sensitivity rates comparable with those of oleamidopropyl dimethylamine and dimethylaminopropylamine. Co-reactivity among surfactants was frequent except for cocamide DEA.
Niculescu MD, Wu R, Guo Z, da Costa KA, Zeisel SH. Diethanolamine alters proliferation and choline metabolism in mouse neural precursor cells. Toxicol Sci. 2007 Apr;96(2):321-6. doi: 10.1093/toxsci/kfl200.
Abstract. Diethanolamine (DEA) is a widely used ingredient in many consumer products and in a number of industrial applications. It has been previously reported that dermal administration of DEA to mice diminished hepatic stores of choline and altered brain development in the fetus. The aim of this study was to use mouse neural precursor cells in vitro to assess the mechanism underlying the effects of DEA. Cells exposed to DEA treatment (3mM) proliferated less (by 5-bromo-2-deoxyuridine incorporation) at 48 h (24% of control [CT]), and had increased apoptosis at 72 h (308% of CT). Uptake of choline into cells was reduced by DEA treatment (to 52% of CT), resulting in diminished intracellular concentrations of choline and phosphocholine (55 and 12% of CT, respectively). When choline concentration in the growth medium was increased threefold (to 210 microM), the effects of DEA exposure on cell proliferation and apoptosis were prevented, however, intracellular phosphocholine concentrations remained low. In choline kinase assays, we observed that DEA can be phosphorylated to phospho-DEA at the expense of choline. Thus, the effects of DEA are likely mediated by inhibition of choline transport into neural precursor cells and by altered metabolism of choline. Our study suggests that prenatal exposure to DEA may have a detrimental effect on brain development.
References___________________________________________________
(1) https://www.fda.gov/cosmetics/cosmetic-ingredients/diethanolamin
Cocamide DEA 
