Ethoxyquin

Ethoxyquin

1. Identity, Chemical Profile, and Physical Forms

Ethoxyquin (abbreviated EQ) is a fully synthetic, quinoline-based antioxidant compound. Its IUPAC name is 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, and it is registered with the Chemical Abstracts Service under CAS number 91-53-2, with the molecular formula C₁₄H₁₉NO and a molecular weight of 217.31 g/mol. It is known by numerous synonyms, including EMQ, Santoquin, Santoflex AW, Santoflex A, Stop-Scald, Nix-Scald, Quinol, Niflex, Permanax 103, Antioxidant EC, and USAF B-24, among others.

Ethoxyquin is a clear, viscous, light yellow to dark brown liquid with an unpleasant, mercaptan-like smell that causes irritation of the skin and eyes. It is absorbed through the skin and is moderately toxic by ingestion. It darkens on exposure to light and air and tends to polymerize, particularly at temperatures above 160°C, producing a hazardous exothermic reaction. It is soluble in organic solvents but has limited solubility in water.

Its chemical structure features a 1,2-dihydroquinoline backbone, which contributes to its antioxidant properties. The commercial additive contains ≥91% ethoxyquin, ≤8% ethoxyquin polymers, and ≤3% p-phenetidine. Ethoxyquin is not derived from any botanical or natural source; it is entirely a product of chemical synthesis. It is available in liquid form for direct incorporation into feed formulations, commonly supplied in drums.

2. Historical Development and Context of Use

Ethoxyquin was originally developed in the rubber industry to prevent rubber from cracking due to the oxidation of isoprene. The Monsanto Company (USA), taking into account its high antioxidant efficiency and stability as well as low costs of synthesis, refined it later for use as a preservative in animal feeds, because it protects against lipid peroxidation and stabilizes fat-soluble vitamins (A and E).

Ethoxyquin has been widely used in animal nutrition since the 1950s. Initially developed as a preservative to prevent the oxidation of fats and fat-soluble vitamins in animal feeds, its primary role has been to extend shelf life and maintain the nutritional quality of feed ingredients, particularly in pet foods and aquaculture diets.

Ethoxyquin was initially registered as a pesticide in 1965 as an antioxidant used as a deterrent of scald in pears through post-harvest indoor application via a drench and/or impregnated wrap. Ethoxyquin is also regulated by the Food and Drug Administration for its use as a preservative in animal feed, dehydrated crops and sorghum, and as an antioxidant for the preservation of color in the production of chili powder, paprika, and ground chili.

Due to the increased use of this antioxidant, it was nominated by the FDA for carcinogenicity testing. Tests were carried out by Monsanto Company, and after that in 1977 the FDA requested optional lowering of the maximum level of EQ in complete dog foods from the allowed 150 ppm (0.015%) to 75 ppm (0.0075%). Starting in the late 1980s, ethoxyquin was identified by dog breeders and owners as a potentially dangerous synthetic preservative. Depending on the source of information, ethoxyquin was believed to be responsible for reproductive problems, autoimmune disorders, behaviour problems, and various types of cancers in dogs and cats. These concerns prompted renewed regulatory scrutiny and further scientific investigation.

Ethoxyquin has a complicated regulatory history: still permitted in the United States at limited concentrations, but suspended entirely in the European Union since 2017.

Because ethoxyquin is a synthetic chemical compound and not a botanical or traditional herbal preparation, it has no traditional ethnobotanical history of use in any human medical or nutritional tradition. It was never employed in folk medicine, herbal practice, or traditional dietary systems. Its entire history of use is industrial and agricultural, beginning in the mid-twentieth century. All human exposure has occurred incidentally — through consumption of animal products derived from ethoxyquin-treated feed, or through direct occupational handling.

3. Key Constituents and Active Compounds

Ethoxyquin is a single defined chemical entity, not a complex botanical extract. However, it generates several important transformation products (TPs) both in feed formulations and in biological systems that are relevant to its pharmacology and toxicology.

3.1 Parent Compound

The parent compound EQ (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) is itself the primary active antioxidant agent. EQ is considered a highly effective antioxidant and has a very long shelf life.

3.2 Oxidation and Metabolic Transformation Products

The main products of EQ oxidation which can be observed in stored feeds or in fish meal are: EQ dimer (EQDM; 1,8′-di(1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline)) and quinone imine (QI; 2,6-dihydro-2,2,4-trimethyl-6-quinolone).

In Atlantic salmon, parent EQ (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline), quinone imine (QI), de-ethylated EQ (DEQ; 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline) and EQDM (EQ dimer) were found to be the ubiquitous metabolites of dietary EQ, with EQDM as the main metabolite. A rapid decrease in the level of EQ (half-life of 2.4 days) was balanced by an increase in EQDM, giving an unchanged net sum following two weeks of depuration. The mandatory 14-day depuration period prior to slaughtering of farmed salmon in Norway was not sufficient for complete elimination of EQ-derived residuals. Post-depuration, EQDM accounted for 99% of the sum of the two compounds in all treatment groups; the possible toxicological effects of EQDM were not fully known at that time.

Antioxidants are by nature unstable chemicals degraded progressively during feed protection and converted by oxidation to other chemical structures (transformation products), sometimes endowed with antioxidative properties (e.g., 1,8′-ethoxyquin dimer (EQDM), ethoxyquin quinone imine (EQI) and dihydroethoxyquin (DHEQ)). The genesis of these transformation products in feeds is highly variable, depending on many physical and chemical parameters associated with the composition and technological treatments of the feed.

The toxicological profile of the EQDM is considered similar to that of EQ, while the EQI shows structural alerts for mutagenicity, carcinogenicity and DNA binding and thus should be more seriously considered.

4. Mechanisms of Action

4.1 Free-Radical Scavenging and Lipid Peroxidation Inhibition

Ethoxyquin interrupts the chain reaction of lipid oxidation by reacting with unstable oxygen molecules (free radicals) that drive fat breakdown. When it neutralizes a free radical, ethoxyquin transforms into a dimer compound that itself has moderate antioxidant activity, essentially extending its protective action.

The oxidation products of EQ also possess antioxidative properties. EQDM and QI show approximately 69% and 80% of EQ's efficacy, respectively, in studies performed on fish meal.

4.2 Induction of Phase II Detoxification Enzymes

Ethoxyquin acts as a synthetic antioxidant which inhibits chemically induced carcinogenesis, where it exerts its chemopreventive action by inducing glutathione synthetase and the phase II drug metabolizing enzyme, glutathione S-transferase (GST).

Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) enhances the activities of glutathione S-transferases and certain other enzymes. Each of these compounds protects rodents against mutagenic and carcinogenic metabolites. This induction mechanism, studied in the early 1980s in rodent hepatic tissue, established the basis for the subsequent interest in ethoxyquin as a potential chemopreventive agent.

Changes in the expression of glutathione S-transferase (GST) gene were observed after feeding animals with EQ-containing feed. The alterations in GST activity caused by EQ were documented in Atlantic salmon, in rodents, and in non-human primates. In addition to UDP-glucuronosyltransferase (UDPGT) and GST, some other enzymes are involved in phase II metabolism of EQ, for example, NADP(H):quinone oxidoreductase and epoxide hydrolase.

4.3 Ferroptosis Inhibition

A more recently characterized mechanism is ethoxyquin's ability to act as a radical-trapping antioxidant that inhibits ferroptosis — a form of regulated cell death driven by iron-dependent lipid peroxidation. Ferroptosis, a form of regulated cell death induced by the accumulation of lipid peroxides, has been recognized as a major pathophysiology of doxorubicin-induced cardiomyopathy (DIC). Ethoxyquin is a lipophilic antioxidant widely used for food preservation and may be a potential therapeutic drug for preventing DIC.

Ethoxyquin prevented doxorubicin-induced cell death, accompanied by suppression of malondialdehyde (MDA) and mitochondrial lipid peroxides induced by doxorubicin. Ethoxyquin also significantly prevented doxorubicin-induced cell death without any suppression of caspase cleavages representing apoptosis. In DIC mice, ethoxyquin treatment ameliorated cardiac impairments such as contractile dysfunction and myocardial atrophy, and lung congestion. Ethoxyquin also suppressed serum lactate dehydrogenase and creatine kinase activities, decreased the levels of lipid peroxides such as MDA and acrolein, inhibited cardiac fibrosis, and reduced TUNEL-positive cells in the hearts of DIC mice.

4.4 Genoprotective Effects (Preclinical)

In vitro studies have demonstrated ethoxyquin's ability to shield human lymphocytes from DNA damage induced by hydrogen peroxide, reducing the formation of micronuclei. In vivo experiments have shown that ethoxyquin can effectively mitigate chromosome aberrations, micronuclei formation, and dominant lethal mutations caused by cyclophosphamide in various animal species, including mice, rats, and Chinese hamsters. These findings are entirely preclinical and have not been translated to human clinical trials.

5. Scientific Evidence by Area of Application

5.1 Antioxidant Preservation in Animal Feed and Aquaculture

The most extensively documented and practically applied function of ethoxyquin is its use as a feed antioxidant. Ethoxyquin is a potent antioxidant extensively utilized in animal and fish feeds. Its primary role is to safeguard against lipid peroxidation and fat rancidity in poultry, salmon, and beef. It preserves the activity of fat-soluble vitamins such as natural carotene, vitamin A, and vitamin E in feed.

Ethoxyquin was authorised in the EU as a feed additive for all animal species and categories until 2017 for its antioxidant properties. In addition, it is used to prevent spontaneous combustion of fish meal during transportation by sea. This anti-combustion use arises from the fact that fish meal rich in unsaturated lipids can undergo exothermic oxidation during ocean freight, and ethoxyquin stabilizes these lipids.

Evidence strength: The antioxidant efficacy of EQ in feed systems is well-established through decades of industrial and academic study. However, as EFSA noted in 2015, formal efficacy data at proposed use levels under EU regulatory standards were not always available in required form. Ethoxyquin is a potent antioxidant; however, no data at the time confirmed its efficacy at the proposed use level for the purposes of EU re-authorization.

5.2 Chemoprevention (Preclinical Studies)

Ethoxyquin has been studied extensively in animal models for its potential to suppress chemically induced carcinogenesis, particularly cancers of the liver and forestomach. This body of work spans from the early 1980s to the present.

A key early study (PubMed PMID 3084413) examined rat hepatocarcinogenesis. Rats were initially given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body weight) and fed basal diet containing 0.02% 2-acetylaminofluorene from week 2 to week 8, and were subjected to partial hepatectomy at the end of week 3. From week 12 to week 36, they were given basal diet containing 0.8% ethoxyquin, among other test compounds. The incidence of hepatocellular carcinoma (HCC) was significantly decreased in the group given ethoxyquin. Quantitative analysis of the number and area of HCC per unit liver area revealed a significant decrease in the area of HCC in the ethoxyquin group. The results suggest that ethoxyquin exerted an inhibitory effect on the development of HCC.

Further rodent research has focused on aflatoxin B1 (AFB1) carcinogenesis. A study published in Cancer Research in 1986 (PMID 2873884) investigated modulation of aflatoxin metabolism and hepatic tumorigenesis in rats fed ethoxyquin, identifying induction of glutathione S-transferases as a key mechanism. Both oltipraz and ethoxyquin induced aflatoxin B1–glutathione conjugating activity in the livers of some marmoset monkeys treated in experimental conditions. However, animals treated in vivo with oltipraz, but not ethoxyquin, exhibited a significant reduction (53% average) in AFB-DNA adduct formation relative to the control animals (p < 0.05). This primate study illustrates that translational potential of rodent findings may not fully carry over to higher mammals.

Evidence strength: All chemopreventive data are derived from in vitro cell systems and in vivo animal models (rodents, fish, non-human primates). No controlled human clinical trials have evaluated ethoxyquin as a chemopreventive agent. The animal data, while suggestive of biological activity, cannot be extrapolated to human cancer prevention recommendations.

5.3 Cardioprotection Against Doxorubicin-Induced Ferroptosis

A 2022 preclinical study (PMID 35881422) examined whether ethoxyquin could prevent ferroptosis in the context of doxorubicin-induced cardiomyopathy (DIC). Researchers investigated the inhibitory action of ethoxyquin against GPx4-deficient ferroptosis and its therapeutic efficacy against doxorubicin-induced cell death in cultured cardiomyocytes and cardiotoxicity in a murine model of DIC. The findings showed significant protective effects, and the authors concluded that ethoxyquin is a competent antioxidant for preventing ferroptosis in DIC and can be its prospective therapeutic drug.

Evidence strength: This area of research is entirely preclinical — limited to cell culture and a murine model. No human data exist. The study provides mechanistic insight into ethoxyquin's radical-trapping capacity but the clinical relevance in humans has not been established.

5.4 Genoprotection (Preclinical)

Animal and in vitro studies have examined whether ethoxyquin protects against chromosomal damage induced by known mutagens. In vitro studies have demonstrated its ability to shield human lymphocytes from DNA damage induced by hydrogen peroxide, reducing the formation of micronuclei. In vivo experiments have shown that ethoxyquin can effectively mitigate chromosome aberrations, micronuclei formation, and dominant lethal mutations caused by cyclophosphamide in mice, rats, and Chinese hamsters.

Evidence strength: Preliminary; all from in vitro and animal models. No human genoprotective trials have been conducted with ethoxyquin.

5.5 Hepatoprotection (Preclinical — Derivative Compounds)

Research into deethylated ethoxyquin (DEQ) and other derivatives has explored hepatoprotective properties. One study was the first, to the authors' knowledge, to show the hepatoprotective properties of DEQ derivatives mediated by the inhibition of NLRP3-inflammasome assembly and restoration of redox homeostasis of the liver tissues. This was conducted in a rat model of carbon tetrachloride-induced liver injury.

Evidence strength: Very early stage; animal data only. No human studies.

5.6 Anti-Scald Treatment in Pears and Apples (Agricultural Application)

The use of ethoxyquin is not permitted in foods intended for human consumption, except for preserving powdered paprika and chili color and using it as an anti-scald agent in pears and apples (inhibition of "brown spot" development). D'Anjou pears treated with 1,000 ppm of ethoxyquin stayed scald-free for four months, while untreated fruit developed the disorder after just three months.

6. Body Systems and Health Areas

• Hepatic system: EQ modulates hepatic phase I and phase II biotransformation enzymes (notably GST, UDPGT, NQO1, epoxide hydrolase). Animal models show potential for both hepatoprotection (via GST induction against aflatoxin) and hepatotoxicity at high doses.
• Cardiovascular system: Preclinical evidence indicates inhibition of ferroptosis-driven cardiomyocyte death associated with doxorubicin cardiotoxicity (murine model).
• Immune/haematopoietic system: EQI (ethoxyquin quinone imine) has been associated in regulatory review with toxic effects on red blood cell production in animal studies.
• Genotoxic/carcinogenic risk concerns: The metabolite EQI carries structural alerts for mutagenicity and DNA binding; the impurity p-phenetidine is a possible mutagen.
• Skin/dermal: EQ is a documented occupational skin sensitizer; allergic contact dermatitis has been documented in workers at animal feed mills, farms, and packing facilities.
• Renal and reproductive systems: High-dose animal studies have reported changes in kidney and reproductive tissue; reports from dog owners to FDA (from 1988 onward) described thyroid and reproductive dysfunction, though causality was not formally established.

7. Metabolism, Bioavailability, and Tissue Residues

The expression pattern of both phase I and phase II enzymes involved in EQ metabolism may vary in different animals and should be considered in relation to the ratio of parent EQ and its metabolites (DEQ, QI, and EQDM) in the liver.

Analysis of EQ metabolism performed using HPLC showed the detection of four compounds, of which two were quantified: parent EQ and EQ dimer (EQDM). Two metabolites were identified as de-ethylated EQ (DEQ) and quinone imine, but these were not quantified.

It was shown that ethoxyquin was rapidly degraded or metabolized in pear tissue, but the parent compound itself was not translocated into the pulp of fruit where the residues were detected (less than 0.5% of total radioactive residue was EQ).

Because EQ is used as a feed antioxidant it can be found in other products intended for human consumption like fish meal, fish oils, and other oils, fats, and meat. EQ cannot be used in any food for human consumption (except spices, e.g., chili), but it can pass from feed to farmed fish, poultry, and eggs, so human beings can be exposed to this antioxidant.

The levels of the parent compound (EQ) in meat of farmed animals are usually lower than the Maximum Residue Level (MRL), but EQ oxidation products are usually not controlled. It was shown that EQDM and other EQ residues can be present in different animal tissues.

In 2017, reports from the Swiss Department for Regional Affairs laboratory, service of consumption and veterinary affairs, showed that farmed salmon often exceeded the set limits for ethoxyquin contamination by several orders of magnitude and that health effects of the chemical on the human body were not studied in sufficient detail.

8. Regulatory-Reported Dosages and Permitted Levels

Ethoxyquin has not been evaluated in formal human clinical dose-finding or pharmacokinetic studies. The following figures are regulatory and industrial use levels only, as reported in official sources:

• The maximum quantity of ethoxyquin "to be used and to remain in or on the treated article [complete animal food and forage] shall not exceed 150 parts per million (ppm)" per 21 CFR 573.380 and 573.400 (U.S. FDA).
• For dog food specifically, the FDA requested that manufacturers voluntarily lower their use to 75 ppm, half the legal ceiling.
• Studies were undertaken to determine whether even lower EQ levels (between 30 and 60 ppm) would provide antioxidant protection for dog food.
• Per 21 CFR 172.140, the established tolerances for ethoxyquin residue in or on animal products intended for human consumption are as follows: 5 ppm in or on the uncooked fat of meat from animals (except poultry); 3 ppm in or on the uncooked liver and fat of poultry; 0.5 ppm in or on the uncooked muscle meat of animals; 0.5 ppm in poultry eggs; zero in milk.
• An acceptable daily intake (ADI) of EQ for humans (0–0.005 mg/kg body weight per day), based on results obtained from studies in dogs, was established in 1998.
• Under EU regulatory assessment, ethoxyquin was intended for use in all animal species as an antioxidant at a maximum content of 50 mg/kg.
• In the preclinical ferroptosis study (PMID 35881422), ethoxyquin was studied in cell culture and murine systems; no human-equivalent dose was established.
• In rodent hepatocarcinogenesis studies, dietary EQ was administered at 0.8% in basal diet (from week 12 to week 36).
• Values of LD₅₀ for EQ include 1700 mg/kg bw (rats, oral gavage), >2000 mg/kg bw (rats, dermal treatment, 24 h), ~900 mg/kg bw (mice, intraperitoneal administration).

9. Safety Considerations

9.1 Genotoxicity of Parent Compound and Metabolites

The substance ethoxyquin itself is considered non-genotoxic. EFSA, however, found that one of its metabolites, ethoxyquin quinone imine (EQI), could be genotoxic — meaning it may damage DNA. The structure–activity analysis performed by the EFSA FEEDAP Panel on EQI by the OECD QSAR toolbox revealed structural alerts for the formation of reactive oxygen species and for mutagenicity, carcinogenicity, and DNA binding.

9.2 The p-Phenetidine Impurity

The EU suspension followed an EFSA opinion published in 2015 in which experts could not conclude on the safety of the additive due to an overall lack of data and the presence of p-phenetidine. The presence of p-phenetidine, an impurity that remains in the additive after the manufacturing process and is a possible mutagen (likely to cause mutations in the genetic material of animals and humans), meant that the experts of EFSA's Panel on Additives and Products or Substances used in Animal Feed could not rule out risks to animals with long life expectancy and those reared for reproduction.

9.3 Regulatory Status and EU Prohibition

With a new EU regulation, Regulation 2017/962 (which in June 2017 suspended the authorization of ethoxyquin as a feed additive for all animal species and categories) was repealed. In 2017, the EU made this decision due to a lack of data to assess the safety of this synthetic additive, and a deadline was given to carry out and present new studies. However, after several years of analysis, it was not possible to establish that ethoxyquin does not have adverse effects on the health of animals, people, or the environment. The evaluation of ethoxyquin showed that the authorization requirements established by Regulation (EC) 1831/2003 are not met, and consequently its use as an antioxidant in feed was refused.

9.4 Occupational Skin Sensitization and Dermatitis

Ethoxyquin is not a dermal irritant per se, but is considered a potential irritant to eyes and other mucous membranes and a skin sensitiser. People who handle ethoxyquin directly face dermal risk. Multiple cases of dermatitis have been documented among workers handling freshly sprayed apples still wet with ethoxyquin solutions. The EFSA 2015 opinion also cited a published case report (Alanko et al., 1998, Contact Dermatitis, 39, 263–264) of occupational "multi-vitamin allergy" caused by ethoxyquin in an animal feed mill worker, and a further case (Rubel and Freeman, 2007) of allergic contact dermatitis in a farmer handling chicken feeds containing EQ.

9.5 Animal Toxicity Findings at High Doses

A 2013 research summary by scientists at the University of Łódź, Poland, of health effects in animals and humans exposed to varying levels of ethoxyquin reported: loss of weight, changes in liver, kidney, alimentary duct, urinary bladder and mitochondria, anemia, lethargy, discolored urine, skin or fur, increase in mortality, detrimental effect on immunity, and induction of allergies (contact exposure).

The symptoms observed by dog owners and veterinarians and reported to the FDA included liver, kidney, thyroid and reproductive dysfunction, teratogenic and carcinogenic effects, allergic reactions, and a host of skin and hair abnormalities. It should be noted that these reports were anecdotal and not confirmed by controlled trials; they prompted regulatory action and further study rather than constituting definitive toxicological conclusions.

9.6 Consumer Exposure via Animal Products

Because there was not enough data on whether p-phenetidine accumulates in meat, milk, or eggs from animals fed ethoxyquin-treated diets, EFSA could not rule out a risk to people eating those products. The agency also flagged concerns about contamination of aquatic ecosystems, particularly around sea-cage fish farms, and a risk to organisms living in marine sediment.

9.7 Human Exposure Context

Human exposures are estimated to be at least 1000-fold below those associated with any neoplastic actions in laboratory animals, and thus it has been assumed that they are not harmful for human beings. However, this assessment was made on the basis of the parent compound EQ and did not fully account for the metabolite EQI or the impurity p-phenetidine, which remained the basis for the EFSA inconclusive safety assessment.

9.8 Physical Stability Concerns

Ethoxyquin darkens on exposure to light and air and tends to polymerize, particularly at temperatures above 160°C, producing a hazardous exothermic reaction. This limits its use in certain high-temperature processing contexts.

10. Summary of Evidence Landscape

Ethoxyquin is a well-characterized synthetic antioxidant with a clearly defined chemistry, a documented industrial and agricultural history, and a growing body of preclinical research. Its antioxidant efficacy in feed preservation is not disputed. Its chemopreventive and cardioprotective biological activities are mechanistically coherent and reproducible in animal and cell models, but no human clinical trials have evaluated ethoxyquin for any therapeutic or preventive health indication. The totality of evidence relevant to human health outcomes is, therefore, confined to toxicology and regulatory risk assessment rather than evidence-based therapeutic use.

The compound occupies an ambiguous regulatory position: permitted at trace residue levels in animal-derived foods and as a direct food additive in spices under U.S. FDA regulation, but fully prohibited as a feed additive in the European Union following repeated inconclusive safety assessments. The core unresolved scientific questions concern the toxicological fate of EQI and p-phenetidine at physiologically relevant exposures.

References

• Błaszczyk A, Augustyniak A, Skolimowski J. Ethoxyquin: An Antioxidant Used in Animal Feed. International Journal of Food Science. 2013;2013:585931. PMC4745505.
• Pickett CB, et al. Increased synthesis of glutathione S-transferases in response to anticarcinogenic antioxidants. Proc Natl Acad Sci USA. 1983;80(8):2122-6. PMID: 6822548.
• Tadokoro T, Ikeda M, Abe K, et al. Ethoxyquin is a Competent Radical-Trapping Antioxidant for Preventing Ferroptosis in Doxorubicin Cardiotoxicity. J Cardiovasc Pharmacol. 2022;80:690-699. PMID: 35881422.
• Imaida K, et al. Inhibitory effects of ethoxyquin, 4,4'-diaminodiphenylmethane and acetaminophen on rat hepatocarcinogenesis. Carcinogenesis. 1986;7(3):401-6. PMID: 3084413.
• European Food Safety Authority (EFSA). Ethoxyquin: EFSA safety assessment inconclusive. EFSA Press Release, November 2015.
• EFSA FEEDAP Panel. Safety and efficacy of ethoxyquin (6‐ethoxy‐1,2‐dihydro‐2,2,4‐trimethylquinoline) for all animal species. EFSA Journal. 2015;13:4272.
• EFSA FEEDAP Panel. Safety and efficacy of a feed additive consisting of ethoxyquin for all animal species (FEFANA asbl). EFSA Journal. 2022;20(3):7183. PMC8892239.
• European Commission. Commission Implementing Regulation (EU) 2017/962 of 7 June 2017 suspending the authorisation of ethoxyquin as a feed additive.
• BTSA Biotecnologías Aplicadas S.L. The EU definitively prohibits the use of ethoxyquin. August 2025.
• U.S. FDA. Labeling and Use of Ethoxyquin in Animal Feed (21 CFR 573.380, 573.400, 172.140). Updated 2024.
• U.S. EPA. Pesticides – R.E.D. Facts: Ethoxyquin. Reregistration Eligibility Decision Fact Sheet.
• FAO/WHO Joint Meeting on Pesticide Residues (JMPR). Ethoxyquin: Toxicological Monograph. 1998. InChem.
• NIST WebBook. Ethoxyquin (CAS 91-53-2). National Institute of Standards and Technology.
• Bohne VJB, et al. Accumulation and depuration of the synthetic antioxidant ethoxyquin in the muscle of Atlantic salmon (Salmo salar L.). Aquaculture. 2008;279:97-106. PMID: 18329775.
• Wang Z, et al. Analysis of ethoxyquin and its oxidation products in swine tissues by GC-MS/MS. J Anim Sci Biotechnol. 2021;12:18. PMC7809739.
• Bohne VJB, et al. Hepatic Biotransformation and Metabolite Profile during a 2-Week Depuration Period in Atlantic Salmon Fed Graded Levels of Ethoxyquin. Toxicological Sciences. 2006;93(1):11-20.
• Sobeh M, et al. Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis. PMC7829797.
• EFSA. EFSA reassesses safety of the feed additive ethoxyquin. News release, March 2022.