Olaquindox

263.25

263.25

245-832-7

G3LAW9U88T

634933

DTXSID3040726

Pale yellow crystals

29339900

95.7

-2.13 (est)

Light yellow crystalline powder,Odorless

1.2755 (rough estimate)

209 °C

343.3ºC

>204.4ºC

1.65

Insoluble in most organic solvents.

0-6°C

2.99X10-14 mm Hg at 25 deg C (est)

Henry's Law constant = 1.38X10-27 atm-cu m/mol at 25 °C (est)

pKa = 10

Emits toxic vapors of NOx when heated to decomposition.

22-43-42

36/37-22

VD1582000

Xn

Stable under recommended storage conditions.

P261, P264, P270, P272, P280, P285, P301+P312, P302+P352, P304+P341, P321, P330, P333+P313, P342+P311, P363, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

|Danger|H302 (97.67%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P285, P301+P312, P304+P341, P330, P342+P311, and P501|Aggregated GHS information provided by 43 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]

Skin protection: Handle with gloves.|Eye/face protection Face shield and safety glasses: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Olaquindox was tested for but not detected in effluents from 8 waste water treatment plants located in five Canadian cities, specifically the Greater Vancouver Regional District, British Columbia; Calgary, Alberta; Burlington, Peterborough and Windsor, Ontario; sampling was conducted in 2002(1).

IDENTIFICATION AND USE: Olaquindox, an antibiotic belonging to the quinoxaline group, is a growth promoter used in pig breeding. HUMAN EXPOSURE AND TOXICITY: There has been reports of both allergic contact dermatitis and photocontact dermatitis following occupational exposure to olaquindox. A farmer developed a photoallergic contact eczema to olaquindox, which progressed to a persistent light reaction. In another case, olaquindox caused a photoallergic contact eczema and subsequently a chronic photosensitive dermatitis with increased UV-A- and UV-B-sensitivity in a breeder of small pigs. ANIMAL STUDIES: Male mice were given oral doses of 2500-5000 mg/kg bw olaquindox. Only 1/10 mice died at the lowest dose used while 100% lethality was noted at the highest dose. Signs of toxicity included decreased activity, lowering of the eyelids, and irregular breathing. Animals died 2-14 days after olaquindox administration. Discolored livers and yellowish-green intestinal contents were noted on gross examination. Similar findings were made when groups of male rats were given olaquindox in a similar manner at doses of 1400-2000 mg/kg bw. Male and female mice were fed diets containing 0, 300, 600, 1200, 2400 and 4800 ppm olaquindox. Signs of toxicity included shaggy fur, dyspnea and reduced motility. A marked reduction in body weight occurred at the highest dietary level in both sexes, and in males given 1200 and 2400 ppm. During the study 1/20 females died at the 600 ppm level as did 18/20 and 5/20 males and females, respectively, at the 1200 ppm level. All the mice given the two highest doses died. No deaths occurred in other groups. At necropsy, hemorrhagic lungs were the main findings. Male and female mice were given diets containing 0, 40, 120 or 360 ppm olaquindox for life. No increased tumor incidence was found in animals given 40 or 120 ppm dietary olaquindox but at 360 ppm there was an increase in the total number of tumors and in the number of animals with benign tumors (pulmonary adenoma and adrenal cortical adenoma in males and in pulmonary adenoma and ovarian granulosa cell tumors in females). There were no increases in the incidence of any malignant tumor types. Female pregnant FB rats were given oral doses of 0, 20, 60 or 180 mg/kg b.w./day olaquindox by gavage from day 6 to day 15 of gestation. Fetuses were delivered by Caesarean section on day 20 of gestation. The pregnant rats given the highest daily dose showed reductions in body weights or rate of weight gain. These animals also showed a higher incidence of resorptions and lower numbers of live fetuses. Fetal weights were lower in the high dose animals. These indices were similar to controls and to rats given 20 or 60 mg/kg bw/day olaquindox. The incidence of malformations in fetuses from dams given 20 or 60 mg/kg bw/day olaquindox was similar to controls but at the highest dose level there was an elevated incidence of malformed fetuses, with 5 malformations reported at a dose level of 180 mg/kg bw/day. In this study, therefore, there was a teratogenic effect at the highest dose level given to pregnant rats (180 mg/kg bw/day) on days 6-15 of gestation. Olaquindox has produced positive results in a number of studies designed to test for reverse mutations in bacteria, including the Ames test with Salmonella typhimurium strains. A positive result has been noted in a forward mutation assay with Escherichia coli. In vivo assays with mouse bone marrow or Chinese hamster spermatogonia as the target tissues have demonstrated the clastogenic activity of olaquindox. Olaquindox was positive in several micronucleus tests in the mouse following oral or inhalation exposure, and in the rat after intraperitoneal injection. Olaquindox has been tested in two dominant lethal assays in the male mouse but a weak positive result was observed in only when a high dose 1 g/kg bw was employed. Positive lethal mutations also occurred when female mice were treated orally with olaquindox despite the use in one study of doses lower than that which effected a positive result in the male mouse (200 and 500 mg/kg bw). Positive results have been obtained in a sister chromatid exchange test using Chinese hamster V79 cells indicating that olaquindox may induce DNA damage. Positive results in bacterial assays including the SOS chromotest confirm this possibility. However, there is no evidence that olaquindox covalently binds to DNA in the rat in vivo. ECOTOXICITY STUDIES: Toxicity of olaquindox was investigated on the freshwater Daphnia magna with a No Observed Effect Concentration of 1000 mg/L.

LD50 Cat (male + female) sc 500 mg/kg bw|LD50 Cat (male + female) oral 1000 mg/kg bw|LD50 Rabbit (male + female) sc 1000-2500 mg/kg bw|LD50 Rabbit (male + female) oral 1000-2000 mg/kg bw|For more Non-Human Toxicity Values (Complete) data for OLAQUINDOX (10 total), please visit the HSDB record page.

/AQUATIC SPECIES/ The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC), streptomycin (ST), sulfadiazine (SU), tetracycline (TC), tiamulin (TI) and tylosin (TY) was tested in accordance to the ISO (1989) and OECD (1996) standard procedures. The acute toxicities (48-hr EC50 value, mg/L) in decreasing order were OA (4.6), TI (40), SU (221), ST (487), TY (680) and OTC (approximately 1000). NOECs were 340 mg/L for TC and 1000 mg/L for M and OL. Toxic effect on reproduction occurred generally at concentrations, which were one order of magnitude below the acute toxic levels. The chronic toxicity (EC50 values, mg/L) in the D. magna reproduction test in decreasing order were TI (5.4), SU (13.7), TC (44.8) and OTC (46.2). The NOECs (mg/L) obtained in the reproduction test with OA, ST, TY and M were 0.38 for OA, 32 for ST, 45 for TY and 250 for M. The observed toxicity of OA to D. magna indicates that this substance, which is a commonly used feed additive in fish farms, has a potential to cause adverse effects on the aquatic environment.

Olaquindox's production may result in its release to the environment through various waste streams(SRC). Its use as a growth stimulant fed to pigs(1) will result in its direct release to the environment through the use of swine manure as fertilizer on farm fields(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc range of 46-116(2) indicates that olaquindox is expected to have very high to high mobility in soil(SRC). Volatilization of olaquindox from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-27 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Olaquindox is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation half-lives of 5.8 to 8.8 days in soil slurries, some mixed with swine manure(5) suggest that biodegradation may be an important environmental process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), a Koc range of 46-116(2) indicates that olaquindox is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.4X10-27 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its estimated log Kow of -2.13(6) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation half-lives of 5.8 to 8.8 days in soil slurries, some mixed with swine manure(7) suggest that biodegradation may be an important environmental process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), olaquindox, which has an estimated vapor pressure of 3.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase olaquindox may be removed from the air by wet and dry deposition(SRC). Olaquindox absorbs UV light at 375 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Olaquindox may undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(1). Olaquindox absorbs UV light at 375 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). After 10 hours exposure to day light, 10 mg/L of olaquindox in aqueous solution was completely removed and several metabolites were formed(3).

An estimated BCF of 3 was calculated in fish for olaquindox(SRC), using an estiamted log Kow of -2.13(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Olaquindox exhibited measured Koc values of 104, 116, 86 and 46 in sandy loam (Askov; clay 11.3%, silt 10.7%, fine sand 37.9% OC 1.6%, pH 6.1); sandy loam (Flakkebjerg; clay 16.9%, silt 19.1%, fine sand 38.5% OC 1.1%, pH 5.6); sand (Lundgaard; clay 5.2%, silt 4.8%, fine sand 24.4% OC 1.4%, pH 5.6) and loamy sand (Borris; clay 5.8%, silt 8.7%, fine sand 42.6% OC 1.5%, pH 6.3), respectively(1). According to a classification scheme(2), these Koc values suggest that olaquindox is expected to have high to very high mobility in soil(SRC). Log Kd values of 1.31 and 0.08 have been measured in pig manure and sandy soil-sandy loam soil, respectively(3). Another study reported Kd values of 0.007 in Lundgaard and Askov soils(4).

The Henry's Law constant for olaquindox is estimated as 1.4X10-27 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that olaquindox is expected to be essentially nonvolatile from water or moist soil surfaces(2). Olaquindox is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-14 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to olaquindox may occur through inhalation and dermal contact with this compound at workplaces where olaquindox is produced or used(SRC). The general population exposure via ingestion of food-producing animals fed olaquindox should be low or non-existent; the drug is rapidly metabolized in animals and intended to be withheld from finisher feeds(1,2)

The compound /olaquindox/ is used as a growth promoter in pigs.

Experiments with (3-1)4C-olaquindox intraduodenally administered to rats with bile duct fistulas suggested that around 18% of the dose was excreted in the bile. Similar findings were made after intravenous dosing. Distribution occurred in a generalized manner throughout the body after oral dosing and most of the radioactivity had disappeared by 24 hours. Autoradiography revealed the highest amount in the rat kidney at 4 hours, indicative of the extent of urinary excretion already noted. Slightly elevated concentrations were also observed in liver, testes, adrenals and hair follicles.|After pigs were given diets containing up to 45 ppm olaquindox for the duration of the fattening period, the highest levels were found in the liver (0.14 ppm) and kidney (0.28 ppm) 6 hours after withdrawal. By 24 hours the levels were below the limit of detection (0.1 ppm). Similar results were noted when pigs were given diets containing 10 ppm olaquindox.|When pigs were dosed at levels in the range of those recommended in use (up to 100 ppm in the diet) for up to 20 weeks, relatively high levels were found in the kidney (around 2000 ppb) with relatively moderate levels in the liver (300 ppb) when the animals were killed six hours after drug withdrawal. When killed 2 days after withdrawal, levels had fallen to below the limits of detection (50 ppb) in liver, kidney and muscle. Pigs given diets containing olaquindox at levels in excess of those recommended (160 or 250 ppm) for up to 4 weeks also had high initial levels in kidney, liver and muscle but these had fallen to below the limits of detection by day 2 after withdrawal.|Olaquindox was rapidly absorbed when given orally to pigs. Over 90% of an oral dose of 2 mg/kg bw was eliminated in the urine within 24 hours, which is indicative of rapid and extensive absorption. The remainder was excreted in the feces. Maximum plasma levels were attained within 1-2 hours of dosing (1-2 ppm). This was followed by a rapid decline in plasma levels reaching around 0.03 ppm by 24 hours and 0.005-0.01 ppm by 48 hours. Radioactivity was present in all tissues when examined 2 days after dosing, but the levels were extremely low. In the kidney and liver, levels of 110 and 52 ppb were found, while levels in muscle were only 9 ppb. After 8 days, levels in liver and kidney had fallen to 27 and 12 ppb, respectively, while those in muscle were in the range of 2.5 ppb. By 28 days after dosing only low levels were found in kidney and muscle (0.9 and 0.5-0.8 ppb, respectively) with slightly higher concentrations in the liver (2 ppb).|For more Absorption, Distribution and Excretion (Complete) data for OLAQUINDOX (6 total), please visit the HSDB record page.

The biotransformation of olaquindox has been investigated only in the pig. The majority of an oral dose of olaquindox (70%) was excreted in the urine unchanged. The major metabolites appeared to be the reduced compounds, the 1- or 4-mono-N-oxides (16%). Three other compounds thought to be carboxylic acid derivatives made up the remainder. Later work led to the elucidation of the structures of these metabolites in the pig. Again the major urinary component after oral dosing was olaquindox with about 7% present as the 4-mono-N-oxide. Omega oxidation produced the 2-carboxymethylaminocarbonyl compound and its 4-mono-N-oxide derivative (6%). Some of the corresponding 1-mono-N-oxide moiety of the 2-carboxymethylaminocarbonyl was also noted (1%). The remaining metabolite was the di-desoxy derivative of 2-carboxymethylaminocarbonyl compound, 2-carboxymethylaminocarbonyl-3- methyl quinoxaline (>1%).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. 3. replace fluid losses resulting from gastroenteritis with IV crystalloids. 4. Maintain steady urine flow with fluids to alleviate crystalluria from overdoses of sulfonamides, ampicillin, or amoxicillin. /Antibacterial agents/|For more Antidote and Emergency Treatment (Complete) data for OLAQUINDOX (6 total), please visit the HSDB record page.

/CASE REPORTS/ Olaquindox, an antibiotic belonging to the quinoxaline group, is a growth promoter used in pig breeding. A farmer developed a photoallergic contact eczema to it, which progressed to a persistent light reaction. Besides this, we found a photosensitivity to chlorpromazine, a tranquillizer that is also used in pig breeding. In addition, after using potent light-protective drugs containing UV-A and UV-B filters, this patient developed a (photo)allergy to different filter substances. The photoallergy to olaquindox was caused by mixing a food additive containing olaquindox with the pigswill for both young and adult animals. We point out the dangers (potent photoallergen, cancer induction) resulting from the widespread use of this substance in the EC.|/CASE REPORTS/ There has been one report of allergic contact dermatitis and one of photocontact dermatitis following occupational exposure to olaquindox. Both occurred in pig workers exposed to the substance in the animal feed.|/CASE REPORTS/ The diagnosis of photodermatosis is generally facilitated by the typical localization of the eruption. The causal agent can usually be identified by history taking, allowing eviction and cure. It may be difficult to find the causal agent in cases with a sequential course. The occupational and/or recreational environment may provide helpful information. We present two cases of photodermatosis related to the occupational environment. A 50-year-old woman and a 29-year-old man were farm workers. both consulted for photoinduced eczema. The eczema was triggered by episodic manipulation of an antibiotic used widely for preparing animal feed. The standard allergy tests were negative. The photobiology exploration led to the diagnosis of photoallergy to olaquindox, a growth promotor added to animal feed. The course was favorable after eviction or protection against the product, providing a complementary proof of its triggering effect. We emphasize the contribution of photobiological explorations in difficult cases with an occupational background. Generally, these patients are unaware of the composition of the products manipulated, such as feed additives.|/CASE REPORTS/ There have been no previous reports of photosensitivity following photoallergy to airborne olaquindox in a large group. 15 pig breeders, with photo-distributed dermatitis related to olaquindox dust, were investigated to study the nature, promoting factors, & course of this disease. Minimal erythema doses for UVA & UVB were established before photopatch testing & at intervals thereafter. All patients presented with olaquindox-induced photoallergy. In 14 cases, this was followed by prolonged increased sensitivity to UVA. 7 patients also displayed an increased sensitivity to UVB. 13 farmers came into contact with olaquindox in mineral feed (1000 mg/kg) & only 2 in final feed (50 mg/kg). 8 patients avoided further contact with olaquindox because of warnings in the media. Allergies & photoallergies to other occupational substances preceded or followed olaquindox (photo)allergy. Because of their increased sensitivity to light, most of these farmers used sunscreens, & 2 of them developed (photo)allergy to UV-absorbers. As a result of our studies, we recommend photopatch testing for olaquindox in pig breeders with photo-distributed dermatitis. This would enable the early recognition of photoallergy to olaquindox & the prevention of persistent light reaction.|/CASE REPORTS/ The antibiotic olaquindox, an ingredient added to porker feed to increase overall performance, caused a photoallergic contact eczema and subsequently a chronic photosensitive dermatitis with increased UV-A- and UV-B-sensitivity in a breeder of small pigs. Through the use of sun creams he developed an additional (photo)allergic contact eczema to the sunscreens contained in the creams.

2-(N-2'-hydroxyethylcarbamoyl)-3-methylquinoxaline- di-N-oxide

The World Health Organization has concluded that residues resulting from the use of olaquindox in food-producing animals under conditions of good practice in the use of veterinary drugs were temporarily acceptable.|Olaquinodox is extensively metabolized. It is intended for use in starter and/or grower rations but not in finisher rations.

HPLC simultaneous analysis of synthetic antibacterials in meat and fish with solid phase extraction.

Veterinary Drug -> GROWTH_PROMOTER; -> JECFA Functional Classes|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Veterinary Drug -> GROWTH_PROMOTER;