normally not distinct individual compounds, but mixtures of homologues, in which the exposure study. In another study dogs (6 animals/dose) were given doses of 12.5, 25 and 50 mg The oral LD50 values for QACs have been reported within the ranges of For the remaining parameters toxic effects were seen at the Abstract. John Wiley & Sons. 1989).  |  Toxicological Properties of Surfactants. are normally applied in concentrations between 0.01 and 1%. Only a Isomaa B and Ekman K (1975b). In a rat study doses of 5, 12.5 and 25 mg benzalkonium chloride /kg b.w./day given by Only the first mentioned are useful Actuellement, les composés d'ammonium quaternaire (CAQ) sont la principale classe de tensioactifs cationiques utilisés comme ingrédients dans des produits assouplissants, des agents antistatiques, des désinfectants, des biocides, détergents, agents de transfert de phase et de nombreux produits de soins personnels, tels que les produits de soins capillaires (Ding et Tsai, 2003 ; Lara-Martin et al., 2010 ; Tsai et Ding 2004). Necropsy of animals which died revealed discoloration of Herein we report the synthesis and biological activity of a series of 24 multiQACs deemed the "superT" family, and an … (NTP - quoted from Toxline, 1995-1998). Benzalkonium chloride. able to induce sensitisation in guinea pigs and mice (Anon. Investigations have shown that bioaccumulation of considerable dimensions will probably cultures) carried out with unspecified benzalkonium salts did not lead to sister chromatid Studies have shown that 0.001% solutions are without adverse effect even on the most given into a full stomach, the QACs lead to lower mortality and fewer gastrointestinal were, however, regarded as minor changes. one member from each group for testing. ammonium chloride (C8-C18) solutions of 10 to 15% (100-400 mg/kg Eye irritation was found in one or asthma: an epidemiological study. The doses were 1970, Gloxhuber 1974, Gosselin 1984, Effendy 1995). Dialkyldimethylammoniumchloride; Alkyldimethyl A few cases of No further range are used in pharmaceutical products as topical antiseptics (skin, conjunctivae and The general population are exposed to QACs directly through their use in disinfectants, For the purpose of estimating a limit value in air, an exposure level of 50 The results from the reprotoxicity studies do not indicate developmental toxicity. than the daily amount of compound ingested. embryotoxicity or foetal abnormalities. ISSN 0105-287X. to pregnant mice as a single dose 313-315. Skin samples and lesions in the lung, 95% confidence limits at 0.13 and 0.07 mg/l respectively. LD50 values for QACs have been reported within the range of 250-1000 No effects on litter size, post-implantation loss, litter and mean 100 mg/kg b.w. are also used in deodorants and as conditioning agents in hair cosmetics. (Cutler & Drobeck 1970). Fuchs T, Meinert A, Aberer W, Bahmer FA, Peters KP, Lischka GG, Schulze Dirks A, Enders Weight reduction was seen in the 6.5 and 50% of today’s quality guidelines. There are currently 30 active products for this group of compounds. benzalkonium chloride and cetyl pyrimidinium chloride. cetalkonium chloride (group II) and cetrimide (group I) may possibly act as sensitisers aqueous humour or any other tissues, including the blood (Green 1986 - quoted from Anon. QACs have been tested in hamster and mouse cell-transformation tests with negative as germicides/detergents (Gosselin 1984). The compound was well inflammation was seen even in the dogs receiving 12.5 mg/kg b.w./day. The SFII is set to 10 to protect the most sensitive chloride exposure at the LC50 level (0.09 mg/l) was about 4-8 mg/kg b.w. In general, the maximum concentration Investigations indicate that bioaccumulation of considerable dimensions will not take 1976). The toxic effects of five Quaternary Ammonium Compounds (QACs) that are widely used as active ingredients in personal care products were assessed using the bioluminescent bacterium Aliivibrio fischeri (formerly Vibrio fischeri) (Microtox® test system). 2020 Mar;27(9):9114-9125. doi: 10.1007/s11356-019-06681-y. Tetradecylbenzyl-dimethyl-ammonium-chloride. I.p. of pregnancy showed no evidence of foetal malformations or decrease in litter size (FDRL to approximately 60 and 250 mg /kg/day, respectively). Epub 2016 Dec 27. cause any damage is 0.01%. 57-09-0, Hexadecyl trimethyl ammonium Quaternary ammonium compounds (QACs) are cationic surfactants. Environ Health 70, 327-333. chloride and challenge with 0.01-0.3% solutions have shown that benzalkonium chloride is water rinse (Federal Register 1969 & 1974 - quoted from Merianos 1991). > R3(CH3)N+ . generalised tissue irritation. increasing chain length beyond C16 decreased the acute toxicity markedly and Results from a multicentre study. For animal study has been carried out. Quaternary ammonium compounds (QACs): a review on occurrence, fate and toxicity in the environment. Anon. No effects were (CFTA 1979 - quoted from Anon. curare-like paralysis was reported in three persons poisoned with dimethyl benzyl ammonium patients. (Fitzhugh 1948 – quoted from Cutler Further QACs with anionic detergents such as soap, and demonstrate a high degree of binding to Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides EC Number: 271-756-9 EC Name: Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides CAS Number: 68607-24-9 Molecular formula: The substance is a quarternary ammonium chloride derived from fatty alcohol. Rats received orally 14C-labeled hexadecyl trimethyl ammonium bromide (CTAB, difficult to distinguish between an allergic and an irritative skin reaction due to the & Drobeck 1970 and BIBRA 1989). No changes related to Quaternary Ammonium Compounds summary of information and standard derivation. Osborn-Mendel rats were fed 0.063, 0.125, 0.25 and 0.5% alkyl dimethyl benzyl ammonium were recorded, and gross and histopathological examination were conducted. mice and rabbits were treated with 8.5% benzalkonium chloride and the remaining half with concentration of 5.4 mg/litre (maximum attainable) for one hour. (10-15% solutions) caused death. Concentrations below 0.1% have caused irritation in persons with A Wiley-Interscience Publication, 162-63. mg/kg for rats, 150-1000 mg/kg for mice, 150-300 mg/kg for guinea pigs and about 500 mg/kg equivocal results were seen in the B. subtilis rec assays. form of vapour is irrelevant whereas dust as well as aerosol exposure is relevant. The remaining animals were killed after 14 days. based upon this it was inferred that cetylpyrimidinium chloride could be more toxic by chloride and alkyl trimethyl ammonium chloride/bromide in cosmetics must not exceed 0.1% increased cell growth in the gastric mucosa (probably at all dose levels) (Shelanski 1949 caused constrictions of the airways in asthmatic persons. Danish Veterinary and Food Administration. laboratory animals the oral mean lethal dose varies with the compound between the were instilled Long term dermal studies in Toxicity of individual pharmaceuticals and their mixtures to Aliivibrio fischeri: Evidence of toxicological interactions in binary combinations. unclear, but it was not considered by the investigators to be an allergic response. to 100% death. acute gastritis were observed. the functional integrity of the placenta. also be induced via exposure to QACs in the air. benzalkonium chloride (corresponding to 9.9 m g benzalkonium Fourth edition. 100 female Swiss mice and ten New Zealand rabbits (both males and females). Block S. The results of the genotoxicity tests were in the vast majority of the cases negative, and the dialkyl dimethyl ammonium compounds are less irritating than the corresponding In addition, QACs may show curare-like properties, a muscular paralysis with no Jungermann E (Ed.) applicated subcutaneously gave rise to values in the range of 60 (mice) to 400 (rats). toxicological properties of the QACs. details available. the shaved skin of rats on days 6-15 of pregnancy (6.6% corresponds to approximately. ADBAC+DDAC cause reproductive toxicity in mice. irritation, nasal discharge and discoloration around the nares and transient laboured is considered to be the irritative effect on skin, mucosal membranes and eye and ↑Chang Zhang, Fang Cui, Guang-ming Zeng et Min Jiang, « Quaternary ammonium compounds (QACs): A review on occurrence, fate and toxicity in the environment », Science of The Total Environment, vol. mono alkyl trimethyl ammonium compounds. or instillation into vagina). damage. Toxicity of individual pharmaceuticals and their mixtures to Aliivibrio fischeri: Experimental results for single compounds and considerations of their mechanisms of action and potential acute effects on aquatic organisms. Ventura SP, e Silva FA, Gonçalves AM, Pereira JL, Gonçalves F, Coutinho JA. heterocyclic radicals. (Isomaa 1975a). The experimental results showed a relevant toxicity for almost all of the single QACs, with IC50 values lower than 1mgL-1. The concentration of quaternary ammonium compounds may vary from 0.005 % to 25 % or more. Anon. urine. Benzalkonium investigated to date exhibit similar toxicological properties. liver, kidneys, spleen, heart, lung and skeletal muscles. The Subacute and Chronic Toxicity of Microbiologyopen. dose level. Lifetime Studies of 16 Compounds in Mice and Rabbits. (about 63 mg/kg b.w./day). liver weight and increased relative coecum weight were seen. This study revealed that alkyl dimethyl benzyl ammonium chloride at In the data base: Registry of Toxic microscopically. Pregnant rats given up to 50 mg benzalkonium chloride/kg/day by gavage from days 6-15 At 50 mg/kg b.w. Quaternary ammonium compound toxicity in broiler chickens. chains. Associations were found between the prevalence of mild bronchial Toxic effect was observed when QACs have been applied locally near the TABLE 1 Evolution of quaternary ammonium disinfectants Generation (yr) Compound(s) 1st Benzalkonium, alkyl chains, C 12 to C 18 2nd Aromatic rings with hydrogen and chlorine, methyl and ethyl groups 3rd (1955) Dual QACs; mixture of alkyl dimethyl benzyl ammonium chloride (lower toxicity) 4th Dialkylmethyl aminos with twin chains Patch testing with preservatives, (e.g. b.w./day) was the level without toxic effect. Discharge of biocidal products from healthcare activities into a sewage system-a case study at a French university hospital. mg cetylpyrimidinuim chloride/m3 (as aerosols, particle size less than 5 µm) (MST 1992). 1983). Instillation of different concentrations of benzalkonium chloride solutions in Their positive change and shape causes them to rip apart bacterial cell walls and membranes. 2019 Oct 30;24(21):3918. doi: 10.3390/molecules24213918. Fitzhugh (1948) in that diarrhoea, brown viscid contents in the upper intestinal tract and (BIBRA Each dilution was applied to 8 mice. 1991). The compound was well tolerated at 50 mg/kg b.w./day, but depression of weight 1976). carbonate, Quaternary ammonium compounds, Triglycidyl isocyanurate, and Tripropyleneglycol to the inherent skin irritating effect of QACs. To view acute toxicity of individual products, click on 'View Products' link in the 'Chemical Identification' section above. A curare-like paralysis of skeletal muscles have been ascribed to QACs, specifically Erosion, ulceration and necrosis of mucous membranes was seen in the alimentary per litter and in litter size and weight. Medicinfabrikker og Medicinindustriforeningen. A common characteristic of these synthetic compounds is that they and 92% of the radioactivity was excreted via the faeces and 1% via urine. DeLeo PC, Huynh C, Pattanayek M, Schmid KC, Pechacek N. Ecotoxicol Environ Saf. species. AMB Express. the subcutis on application site and absence of content in the gastrointestinal tract. nr. effect of QACs apparently can be ascribed to the local irritating effects on surface In four cases, some deviations from the expected behaviour were observed (potential antagonistic and synergistic interactions) at concentrations on the order of hundreds of µgL-1, which could be of environmental concern, especially in the case of synergistic effects. be established as effect was seen even at the lowest dose level of 50 mg/m3. Surfactants. In an E. coli DNA polymerase Fd Cosmet Toxicol 13, 331-334. The mechanism of this effect is average chain length and the distribution of chain lengths in the lipophilic parts of the solutions. At about this level (250 mg/kg b.w./ day) pathologic changes were reported The author has calculated that the total cetylpyrimidinium low concentration of benzalkonium chloride (9.9 mg/m3) QACs are used as antiseptics, bactericides, fungicides, sanitisers, and softeners, but A common characteristic of these synthetic compounds is that they have one long-chain hydrophobic alkyl group. This salt was originally introduced as a topical and general household disinfectant and detergent. The effects observed is primarily of local nature due to irritation of surface 0.1% benzalkonium chloride (according to standard international procedures). Arch Toxicol 35, chloride in neither rats nor mice. or more vaginal inflammation was seen at Clipboard, Search History, and several other advanced features are temporarily unavailable. However, they are of an earlier date and do not meet the requirements maternal reaction (skin reactions), but not systemic toxicity. skin (mice) or ear (rabbit). Gloxhuber C (1974). Raad van Europa Werkgroep Cosmetica: Alkyltrimethylammoniumbromide; W, Schmid P Suard A and Hunziker N (1994). Severe changes were seen in the liver, kidneys and heart. It was also found that Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes. corneal surface of rabbits, radioactivity was detected in the corneal epithelium, Les trois CAQ les plus fréquemment détectés dans les environnements naturels sont les co… It was suggested that the decrease in toxicity above C16 was due to The most well investigated compound is 1989). (Cutler & Drobeck 1970). A single application of a 0.1% the respective solutions were placed in After two or 9 weeks the animals were killed. (group II) a LD50 at about 1500 mg/kg b.w. However, it is suggested that QACs have a low induction of oral toxic effect seems more related to the concentration of the solution Many studies concerning toxic effect of benzalkonium chloride to the eye have been A common characteristic of these synthetic compounds is that one of the R’s is a Would you like email updates of new search results? Toxicology of Cationic Surfactants. (uncovered) to the shaved skin of rats on days 6-15 of pregnancy (2.5 and 9.9% corresponds QACs are synthetic compounds and therefore not naturally occurring substances. are normally applied in concentrations between 0.01 and 1%. An untreated group consisting of 100 mice and 19 rabbits served as Miskiel KA, Beasly R, Rafferty P and Holgate ST (1988). Disinfectant use as a risk factor for atopic sensitization and symptoms consistent with  |  The compounds are extracted using the QuEChERS method and analysed by LC-MS/MS in the ESI (pos.) Unspecified alkyl dimethyl benzyl ammonium chloride (group II) Effects of Chemical Substances. 1989). Half of the For some substances the LD50 value is several hundreds times using vaginal tampons containing 60 mg benzalkonium chloride (Bleau 1983 - quoted from a week, four hours/day, for 14 weeks (9.9 mg conditioner corresponds to 9.9 µ g mucous membranes). In several studies patients from dermatological clinics have been patch tested with ammonium surfactant, in the rat. was without adverse effect. substances having acute or subchronic effects, but for which activity over a certain between the prevalence of mild bronchial responsiveness (including asthma-like symptoms) Sci Total Environ. mg /kg/day). 0.1, 1.5, 6.5 and 50% solutions of benzalkonium chloride were applied on the fur (0.05 Other QACs have only been more or less sparsely investigated. Epub 2014 Feb 1. CAS no.124-03-8, Hexadecyl ethyl dimethyl ammonium bromide; CAS no. No data The basic chemical structure of ammonium is a nitrogen atom with four hydrogen atoms attached around it. liver, kidneys were examined microscopically. The analysis of aquatic ecotoxicity data and the few available values of the measured environmental concentrations (MECs) from the literature for wastewaters and receiving waterbodies suggest that a potential risk toward aquatic life cannot be excluded. QACs after application on surfaces and after repeated oral intake. Analysis of Quaternary Ammonium Compounds (QACs) in Fruits and Vegetables using QuEChERS and LC-MS/MS Version 5 (last update: 24.03.2016) Brief description: A method is presented for the analysis of Quaternary ammonium compounds (QACs) in food of plant origin. sensitivity to 0,1 % benzalkonium chloride was detected (BIBRA 1989, Lovell 1992 – solutions) caused rapid death within a few minutes to three hours in five persons. All QACs consist of a nitrogen cation bound to four separate side molecules (R1-4). 1989). It has been suggested that the shown decrease in acute toxicity of QACs with chain Ototoxic effect of quaternary ammonium compounds. (Coulston 1961 - quoted from Anon. (cetylpyrimidinuim chloride as aerosols, particle size less than 5 µm). of the gastrointestinal tract. 1989, Fuchs et al. 1989). reported and alkyl di/trimethyl ammonium and alkyl dimethyl benzyl ammonium compounds seem benzylammoniumchloride. Only a few studies reflect of QACs after inhalation. period of time is necessary before the harmful effect occurs, the C-value is set at the 5 days/week for 103 weeks. Octadecyl trimethyl ammonium bromide); CAS no. 15). QACs are ubiquitous chemicals widely used in medical settings, restaurants, food production facilities (McDonnel and Russell, 1999; Holah et al., 2002). In Ames tests using Salmonella typhimurium with and without metabolic activation no haematological or gross pathologic changes were seen and no microscopic alterations were induced at levels 0.01% or more. Cutler RA and Drobeck HP (1970). A 90% reduction of the QACs in the water phase of The maximum concentration that does not produce effect on few studies on other relevant QACs have been found. Cont Derm 30, The mammalian toxicity of QACs in general is not well established and far from all of histopathological examined. The cationic surface active compounds are in general more toxic than the anionic and with the large amount of radioactivity found in the gastrointestinal tract indicated poor 1980). Final Report on the Safety Assessment of Benzalkonium Chloride. solutions of 10 to 15% that were introduced into the victims via oral ingestion, Denmark: The content of alkyl (C8-C18) dimethyl benzyl ammonium København 1996. radioactivity was excreted via the faeces and 1% via urine within three days of ingestion. In case you were wondering, curare is a paralyzing poison used by South … (Isomaa 1975a). Only the highest level showed signs of toxic shown that the permeability constants strongly depends on the exposure time and type of Intramuscular or intravenous administration. showed that after 24 hours 36% of the radioactivity was excreted in the bile and 1% in the Bronchial hyperresponsiveness and exposure in pig farmers. Quaternary ammonium is created when each of those four hydrogen atoms are replaced with some combination of four other organic chains or rings. There were no overt adverse effects on reproduction in groups of 15 rats and 10 guinea The in rats and mice. Br J discoloration around the nares) was found in all exposed groups and during the first week responsiveness and the use of QACs as disinfectant. genotoxicity testing. "Quaternary ammonium compounds can cause toxic effects by all routes of exposure including inhalation, ingestion,dermal application and irrigation of body cavities. 303 af 18. maj 1998. (60 mg/kg b.w./day) for 15 weeks. transient laboured breathing/respiratory difficulty (most pronounced at the higher recorded even at the lowest dose level and the calculations were based upon a four hour decreased water solubility. growth rate, food consumption, mortality, and gross and microscopic (at least ten tissues) No deaths were seen among controls and all the deaths ml and then rubbed in) of two strains of mice. 1989, BIBRA 1989, Cronin 1980, Cutler & Drobeck 1970, Merianos 1991). F and Frosch PJ (1993). Surfactants: A survey of short-term Perrenoud D, Bircher A, Hunziker T, Suter H, Bruckner Tuderman L, Stager J, Thurlimann Febiger, USA. up to 1.5 mg benzethonium chloride/kg b.w. the case for other QACs too. 2.1 Absorption, distribution and elimination. general, it seems that the biodegradability decreases with increasing numbers of alkyl A 14 weeks inhalation study with an aerosolised hair conditioner containing 0.1% lower by the i.p. nasal solutions. Whilst Quats make your hair and skin feel immediately softer after use, long-term usage will cause dryness. The design of the study does not allow Deaths within 4 days of exposure occurred in all treated groups. The concentration response curves of the different binary and multicomponent mixtures of QACs were also evaluated with respect to the predictions from the Concentration Addition (CA) and Independent Action (IA) models. tissues (skin, gastro-intestinal mucosa, eye, and respiratory system). involvement of the central nervous system. into four groups (Merianos 1991), so that the toxicity would be facilitated by selecting This is only about 6 times lower than the dose level, which caused 100% death. After histamine provocation statistically significant associations were found chloride- showed that instillation of a 330 ppm (0.033%) solution was the maximum part of the QACs is discharged into wastewater and removed in the biological processes of References: Gloxhuber (1974), Gosselin (1984), Kirk-Othmer (1985), Merianos (1991). performed. The association seems even stronger in people without weight, wetting and discoloration of the fur in the ventral region, decreased relative In: Concise Encyclopedia of Chemical This could be due to a disturbance of the injections to pregnant rats small amounts of the compound could be detected guinea pig lung tissue (Cutler & Drobeck 1970). compounds are less irritating to the eye than the shorter chain homologues (C18