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Other Uses -> Animal Feed Additives

Antioxidant

Plant Growth Regulators

Active substance -> EU Pesticides database: Not approved

Pesticide (Ethoxyquin) -> USDA PDB

1.029 to 1.031 at 77 °F (NTP, 1992)

1.029-1.031 AT 25 °C/25 °C

253 to 257 °F at 2 mmHg (NTP, 1992)

123-125 °C AT 2 MM HG

less than 32 °F (NTP, 1992)

Approximately 0 °C

7.48 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

7.48 (AIR= 1)

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

Chemical: Quinoline, 6-ethoxy-1,2-dihydro-2,2,4-trimethyl-

Regulation (EC) No 1831/2003 (amended)

Ethoxyquin is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

2008/941, 2011/143/EU

REACH registered substance: Ethoxyquin (EC: 202-075-7)

Ethoxyquin: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this compound include skin irritation. It can cause eye irritation. It can also cause skin sensitization (allergic reactions), lacrimation, depression, reproductive effects, liver effects, kidney effects and thyroid effects. Dermatitis may also occur.

Allergic contact dermatitis reported in a feed mill worker; [Kanerva, p. 1793] A skin irritant; May cause reversible changes to the liver; Reports of contact dermatitis in animal feed employees; [HSDB] May polymerize on exposure to light and air; A skin and eye irritant; May cause skin sensitization; [CAMEO] Strongly associated with cases of occupational contact dermatitis; Causes increased liver enzymes in animal experiments; [Reference #2]

Ethoxyquin is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) when intended for use in or on food it is of appropriate food grade and is prepared and handled as a food ingredient.

Ethoxyquin in animal feeds may be safely used in accordance with conditions prescribed in 21 CFR Part 573.

Ethoxyquin in certain dehydrated forage crops may be safely used in accordance with conditions prescribed in 21 CFR Part 573.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Ethoxyquin is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA, as amended in 1988. Case No: 0003; Pesticide type: Herbicide; Registration Standard Date: 03/01/81; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Ethoxyquin; Data Call-in (DCI) Date(s): 08/20/90, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

A tolerance is established for residues of the plant regulator ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) from preharvest or postharvest use in or on apples and pears.

Acute Tox. 4 (100%)

Acute toxicity - category 4

Acute toxicity (Oral) - Category 4

Acute Tox. 4 *

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

ELEVATION OF EPOXIDE HYDRATASE ACTIVITY IS OBTAINED BY IP OR ORAL TREATMENT OF MICE WITH ETHOXYQUIN. THIS ELEVATION IS PREVENTED BY CONCOMITANT TREATMENT WITH CYCLOHEXIMIDE.

SINGLE ORAL DOSE OF ETHOXYQUIN (200 MG/KG) TO RATS INHIBITED HEPATIC MICROSOMAL HYDROXYLATION OF THIABENDAZOLE, ANILINE & BIPHENYL BY 65, 40 & 40% IN VITRO AT 1 HR AFTER DOSAGE. ORAL ETHOXYQUIN (400 MG/KG) DELAYED ABSORPTION OF & DECR PLASMA CONCN OF THIABENDAZOLE.

The effects of dietary administration of ethoxyquin on aflatoxin B1 metabolism, DNA adduct formation and removal and hepatic tumorigenesis were examined in male Fischer rats. Rats were fed a semipurified diet containing 0.4% ethoxyquin for 1 wk, gavaged with 250 ug of aflatoxin B1 per kg 5 times a wk during the next 2 wk, and finally restored to the control diet 1 wk after cessation of dosing. At 4 mo, focal areas of hepatocellular alteration were identified and quantitated by staining sections of liver for gamma-glutamyl transpeptidase. Treatment with ethoxyquin reduced by greater than 95% both area and volume of liver occupied by gamma-glutamyl transpeptidase-positive foci. Utilizing the same multiple dosing protocol, patterns of covalent modifications of DNA by aflatoxin B1 were determined. Ethoxyquin produced a dramatic reduction in the binding of aflatoxin B1 to hepatic DNA: 18-fold initially and 3-fold at the end of the dosing period. Although binding was detectable at 3 and 4 mo postdosing, no effect of ethoxyquin was observed, suggesting that these persistent adducts are not of primary relevance to aflatoxin B1 carcinogenesis. Analysis of nucleic acid bases by high-performance liquid chromatography revealed no qualitative differences in adduct species between treatment groups. The inhibitory effect of ethoxyquin on aflatoxin B1 binding to DNA and tumorigenesis appears related to induction of detoxication enzymes. Rats fed 0.4% ethoxyquin for 7 days showed a 5-fold increase in hepatic cytosolic glutathione S-transferase (GST)-specific activities. Multiple molecular forms of glutathione S-transferase were induced, and concomitant elevations in messenger RNA levels coding for the synthesis of glutathione S-transferase subunits were observed. Correspondingly, billary elimination of aflatoxin B1-glutathione conjugate was increased 4.5-fold in animals on the ethoxyquin diet during the first 2 hr following oral administration of 250 micrograms of aflatoxin B1 per kg. Thus, induction by ethoxyquin of enzymes important to aflatoxin B1 detoxication, such as glutathione S-transferase can lead to enhanced carcinogen elimination, as well as reductions of aflatoxin B1-DNA adduct formation and subsequent expression of preneoplastic lesions, and, ultimately, neoplasia.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=91-53-2]

SKIN IRRITANT. MAY PRODUCE REVERSIBLE LIVER CHANGES.

CASES OF CONTACT DERMATITIS DUE TO ADDITIVES IN ANIMAL FEED SUBSTANCES ARE DESCRIBED OCCURRING IN ANIMAL FEED WORKERS. THERE ARE 2 CASES OF SENSITIVITY TO ETHOXYQUIN.

ITS CHRONIC TOXICITY IS APPARENTLY LOW, 0.2% IN DIET CAUSING TRANSIENT DEPRESSION IN GROWTH RATE OF RATS. AT AUTOPSY, DAMAGE WAS APPARENT IN KIDNEYS, LIVER & THYROID GLAND IN MANY MALES BUT IN NONE OF FEMALES ... .

/IN RATS FED A DIET CONTAINING 0.2% OF SANTOQUIN/ SOME TUMORS WERE FOUND AFTER CONTINUOUS ADMIN ... .

ORAL ADMIN OF ETHOXYQUIN TO RATS INCR EPOXIDE HYDRATASE ACTIVITY IN LIVER MICROSOMES. T/2 OF INCR 3-4 DAYS. AN INCR OF THIS ENZYME WAS ALSO PRODUCED IN MICE BY IP ADMIN.

DIETARY ADMIN OF 0.5% ETHOXYQUIN MARKEDLY ENHANCED RAT HEPATIC UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES.

For more Non-Human Toxicity Excerpts (Complete) data for ETHOXYQUIN (12 total), please visit the HSDB record page.

1

OPP

0.04

OPP

Ethoxyquin

1

7000

Children

0.04

200

Ethoxyquin is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) when intended for use in or on food it is of appropriate food grade and is prepared and handled as a food ingredient.

Ethoxyquin in animal feeds may be safely used in accordance with conditions prescribed in 21 CFR Part 573.

Ethoxyquin in certain dehydrated forage crops may be safely used in accordance with conditions prescribed in 21 CFR Part 573.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Ethoxyquin is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA, as amended in 1988. Case No: 0003; Pesticide type: Herbicide; Registration Standard Date: 03/01/81; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Ethoxyquin; Data Call-in (DCI) Date(s): 08/20/90, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

A tolerance is established for residues of the plant regulator ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) from preharvest or postharvest use in or on apples and pears.

MAJOR METABOLIC REACTION WAS DEETHYLATION OF ETHOXYQUIN WHICH PRODUCED 6-HYDROXY-2,2,4-TRIMETHYL-1,2-DIHYDROQUINOLINE & 2,2,4-TRIMETHYL-6-QUINOLINE. OTHER REACTIONS WERE HYDROXYLATION TO FOUR DIFFERENT HYDROXYLATED METABOLITES & ONE DIHYDROXYLATED METABOLITE.

An avg of 28 & 36% of dose of radioactivity was recovered in bile in 12 & 24 hr respectively following intragastric admin of (14)C-ethoxyquin to bile duct cannulated rats. Biliary radioactive substances included, in addn to unchanged ethoxyquin...8-hydroxyethoxyquin; hydroxylated 8-hydroxyethoxyquin; 6-ethoxy-2,2,4-trimethylquinolone; hydroxylated 6-ethoxy-2,2,4-trimethyl-8-quinolone; 6-ethoxy-2,4-dimethylquinoline; and 2,2,4-trimethyl-6-quinolone.

FEEDING TRIAL IN COWS WAS CONDUCTED TO DETERMINE WHETHER ETHOXYQUIN OR ITS RESIDUES ARE TRANSFERRED FROM FEED TO MILK WHEN ADDED TO COW FEED AT 0.015% OF DRY MATTER INTAKE. LESS THAN 7 UG ETHOXYQUIN/L WAS DETECTED IN MILK BY FLUORIMETRY & BY THIN-LAYER CHROMATOGRAPHY.

(14)C-ETHOXYQUIN WAS DISTRIBUTED THROUGHOUT MOST TISSUES & BLOOD AT 0.5 HR AFTER ADMIN TO RATS. HIGHEST RADIOACTIVITY THROUGHOUT EXPERIMENT WAS OBSERVED IN LIVER, KIDNEY, GI TRACT & ADIPOSE TISSUE. THERE WAS NO ACTIVITY IN CNS. OF DOSE INGESTED BY RAT 2.2 & 0.2% WERE FOUND IN LIVER AT 0.5 HR & 6 DAYS RESPECTIVELY FOLLOWING DOSE. HEPATIC PEAK IN RADIOACTIVITY WAS MEASURED AT 8 HR; & AFTER 6 DAYS 7.5% OF THIS LEVEL WAS STILL PRESENT IN LIVER. 6 DAYS AFTER ADMIN TO RATS RESIDUES OF ETHOXYQUIN & METABOLITES WERE PRESENT IN KIDNEY CORTEX, INTESTINES, LUNG, VARIOUS ADIPOSE TISSUES & BLOOD.

The compound is readily absorbed, metabolized, and excreted in urine and feces.

Ethoxyquin residue levels in the mouse tissue were determined by the HPLC-fluorometric detection method. Mice were given powdered feed containing 0, 0.125, and 0.5% ethoxyquin hydrochloric acid and the ethoxyquin residue levels in liver kidney, lung, and brain tissues were determined after 2, 4, 6, 10, and 14 wk (4 mice/group). The tissue samples were homogenized in 10 volumes (w/v) of acetonitrile-water (7:3 v/v) centrifuged and the supernatants were stored in a freezer for 2-3 hr or until the two layers separated; then the clear upper layers were analyzed. The mean ethoxyquin residue levels in the tissue ranged 0.84-4.58 ug ethoxyquin/g liver and 0.11-0.92 ug ethoxyquin/g brain. The relative weight of the liver (5.21-7.07% body weight) and the hepatic glutathione level (5.99-7.83 uM GSH/g tissue) of mice that received ethoxyquin were significantly higher than those of the controls (4.67-5.05% body weight and 4.30-5.78 uM GSH/g tissue, respectively). The mean hepatic mitochondrial glutathione levels of the higher ethoxyquin feeding group following dietary administration of ethoxyquin for 14 wk, was approximately twofold (1.68 nM GSH/mg protein) of both the control and the lower ethoxyquin feeding groups (0.83 and 0.74 nM GSH/mg protein, respectively.

Used as an additive to animal feed; [Kanerva, p. 1793] Used as an antioxidant for food and feed and as anti-degradation agent for rubber; [Merck Index] Also used as a post-harvest dip for apples and pears; [ChemIDplus] Registered in the US as an antioxidant for the control of post-harvest scald (browning) in pears; Also registered with the FDA as a preservative for animal feed, dehydrated crops, sorghum, and for color preservation in chili powder, paprika, and ground chili; [Reference #2]

Farming (Pesticides) [Category: Industry]

For ethoxyquin (USEPA/OPP Pesticide Code: 055501) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

MEDICATION (VET):

ANTIOXIDANT IN FEED & FOOD; ANTIDEGRADATION AGENT FOR RUBBER

Antioxidant, used as post-harvest fruit-drop to prevent common scald of apples & pears in storge; Formerly added to poultry feeds & forage crops

USEPA/OPP Pesticide Code 055501; Trade Names: Stop-scald.

Emulsifiable concentrate

Quinoline, 6-ethoxy-1,2-dihydro-2,2,4-trimethyl-: ACTIVE

2,4-DIMETHYL-6-ETHOXYQUINOLINE, A REACTION PRODUCT OF ETHOXYQUIN, OCCURS IN COMMERCIAL FEEDS & COULD INTERFERE IN ANALYSIS OF MIXED COMMERCIAL FEEDS FOR AFLATOXIN.

THE USE OF ETHOXYQUIN AS FEED ADDITIVE MAY AGGRAVATE POTENTIAL MYCOTOXIN HAZARDS IN CONTAMINATED FEEDSTUFFS BY ALTERING THE TYPE & QUANTITY OF AFLATOXIN PRODUCED.

/ Stop Scald /trade name / discontinued