チアムリン

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.

Protect from direct sunlight. Store at controlled room temperature, 59 deg - 77 °F (15 deg -25 °C).

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature: 2-8 °C.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

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. Contaminated packaging: Dispose of as unused product.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

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.

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: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined admin, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous admin of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the admin of 50 mg/kg monensin alone.

Studies were carried out to investigate the effects of monensin & tiamulin, & the simultaneous admin of both compounds on microsomal enzymes in rats. In Phase I of the experiments the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monesin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes. In a few cases, slight inhibition of certain enzyme activities was seen. Tiamulin provoked a dose-dependent hepatic enzyme induction. The combined admin of monensin & tiamulin at low doses (10 & 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities. The enzyme induction was more pronounced in females than in males. The results suggest that the simultaneous admin of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.

Tiamulin is an antibiotic frequently used in veterinary medicine. The drug has been shown to produce clinically important interactions with other compounds that are administered simultaneously. An NIH/3T3 cell line, stably expressing human cytochrome P450 (EC 1.14.14.1) cDNA (CYP3A4), was used to study the effect of tiamulin on CYP3A4 activity. The 6 beta-hydroxylation activity of testosterone, which is increased in CYP3A4-expressing cells compared to vector-transfected cells, showed reduced activity after incubation with 1 microM tiamulin and was completely reduced to background level after incubation with 2, 5 and 10 microM tiamulin. The CYP3A4-expressing cell line was used in combination with a shuttle vector containing the bacterial lacZ' gene to study the effect of tiamulin on CYP3A4-mediated mutagenicity of aflatoxin B1. The mutation frequency of aflatoxin B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no effect was observed on the mutation frequency of the direct mutagen ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing cell line showed stabilization of CYP3A4 protein after incubation with tiamulin, supporting the hypothesis that the mechanism of inhibition is by binding of tiamulin to the cytochrome.

In poultry, tiamulin interferes with monensin and salinomycin metabolism, and if the drugs are fed together, they become toxic.

For more Interactions (Complete) data for TIAMULIN (10 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 36,000(SRC), determined from a structure estimation method(2), indicates that tiamulin is expected to be immobile in soil(SRC). The estimated pKa of tiamulin is 9.51(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Tiamulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Tiamulin had a biodegradation half-life of 16 days in soil based on a 120 day aerobic biodegradation soil test(5), however, under anaerobic conditions tiamulin was not biodegraded(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 36,000(SRC), determined from a structure estimation method(2), indicates that tiamulin is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.51(3) indicates tiamulin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation form from water surfaces is not expected to be an important fate process(SRC). Tiamulin has estimated hydrolysis half-lives of 180 and 18 days at pH values of 7 and 8, respectively(2). According to a classification scheme(4), an estimated BCF of 640(SRC), from an estimated log Kow of 4.75(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Based on biodegradation studies in soil, tiamulin may biodegrade under aerobic conditions in water(5).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tiamulin, which has an estimated vapor pressure of 4.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tiamulin may be removed from the air by wet and dry deposition(SRC). Tiamulin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Tiamulin, when administered in the drinking water for five consecutive days, is an effective antibiotic for the treatment of swine dysentery associated with Brachyspira (formerly Serpulina or Treponema) and for treatment of swine pneumonia due to Actinobacillus pleuropneumoniae. As a feed additive, it is used to cause increased weight gain in swine. HUMAN EXPOSURE AND TOXICITY: Topical administration of a 0.05% formulation of tiamulin did not cause skin irritation or sensitization. Another study was carried out in 6 healthy male human volunteers. Three volunteers were given 5 oral doses progressing from 0.125 to 7.2 mg/kg bw with 72 hours between each dose. The remaining volunteers were given a single oral dose in the range of 8.2 to 10.7 mg/kg bw tiamulin. There was no substance-related changes in blood pressure, serum chemistry or electrocardiograms. ANIMAL STUDIES: Overdoses of tiamulin have produced transitory salivation, vomiting and an apparent calming effect on the pig. In a subchronic study, rats were fed diets containing 0.5 or 30 mg tiamulin/kg bw/day for 26 weeks. Further groups of rats received 180 mg/kg bw/day for 10 weeks, followed by 270 mg/kg bw/day for 16 weeks; one group was necropsied at the end of treatment, the remaining rats were maintained on untreated control diets for a further 4 or 8 weeks. There were increases in serum cholesterol and in water intake in the 180 mg/kg bw group. When the dose was increased to 270 mg/kg bw/day, the effects included increased serum alkaline phosphatase, alanine phosphatase, alanine aminotransferase and aspartate aminotransferase. Abdominal distension, dense feces and increased urine specific gravity were also observed. Absolute and relative liver weights were increased in both sexes and fatty infiltration of the liver was observed on histopathological examination. In a chronic study, dogs were given daily oral doses of 0, 3, 10 or 30 mg/kg bw/day of tiamulin for 54 weeks. In the groups given 10 and 30 mg/kg bw/day, occasional emesis was observed, serum potassium concentrations were decreased and electrocardiograms showed prolongation of the QT interval. Serum lactate dehydrogenase (LDH) was significantly increased; there was no increase in the cardiac-related isoenzyme LDH1. Rats were fed diets containing tiamulin at concentrations designed to provide intakes of 0, 2, 8 or 32 mg/kg bw/day of tiamulin for 30 months. There was no significant dose-related trend in the incidence of any tumor type. In another study, mice were fed diets containing the equivalent of 0, 1, 6 or 48 mg/kg bw/day of tiamulin for up to 123 weeks. There was no significant dose-related trend in the incidence of any tumor type. Pregnant female rats were given daily oral doses of 0, 30, 100 or 300 mg/kg bw/day from days 6 to 15 of gestation. At 300 mg/kg bw/day there were minor signs of maternal toxicity. At this dose level, the mean fetal weight was reduced and there was an increased incidence of retarded skeletal development. There was no evidence of teratogenicity. Pregnant female rabbits were given daily oral doses of 0, 30, 55 or 100 mg/kg bw/day from days 6 to 18 of gestation. Doses of 55 mg/kg bw/day and above caused the deaths of some dams and maternal body weight gain was reduced. Litter size and fetal weights were reduced at 55 mg/kg bw/day and above. There was no evidence of teratogenicity at any dose level. Several reproductive studies were performed in pigs. Breeding sows were fed a diet containing 200 mg/kg feed from days 84 to 92 of gestation, another group was maintained on a diet containing 16 mg/kg bw/day from 2 days after mating for 6 weeks, and further groups were given tiamulin in the drinking water at a dose of 8.8 mg/kg bw/day for various periods during gestation and in some cases up to weaning of the offspring. There were no adverse effects on health of the sows, pregnancy, parturition, letter size, growth and survival of the piglets, estrus cycle or subsequent breeding performance. When given to breeding boars, at a diet containing 16 mg/kg bw/day for 14 days, there were no effects on health status, libido or semen quality. Tiamulin did not induce gene mutations in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 or TA1538. An in vitro assay for gene mutation at the HPRT locus of V79 Chinese hamster cells also gave negative results. In an in vivo micronucleus test in mice tiamulin had no effect on the frequency of micronucleated polychromatic erythrocytes.

Tiamulin was detected in 10% of samples from 90 waste water treatment plants at 20-44.3 ng/L; samples were collected throughout Europe (1 from Slovenia; 2 each from Cyprus, Germany, Greece, Hungary, Ireland, Italy, Portugal; 3 from Lithuania and Spain; 5 from France and Switzerland; 6 from Austria and Finland; 7 from the Czech Republic, 11 from the Netherlands and Sweden; 18 from Belgium) in 2010(1). Tiamulin was detected at 0.09 ng/L in the influent samples collected from a wastewater treatment plant located in Beijing, China(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of tiamulin can be estimated to be 36,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that tiamulin is expected to be immobile in soil. The estimated pKa of tiamulin is 9.51(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Tiamulin in swine waste water had log Kd values of 1.54-1.58, 5-10% of tiamulin was partitioned to the suspended solids phase(5).

/HUMAN EXPOSURE STUDIES/ A study was carried out in 6 healthy male human volunteers. Three volunteers were given 5 oral doses progressing from 0.125 to 7.2 mg/kg bw with 72 hours between each dose. The remaining volunteers were given a single oral dose in the range of 8.2 to 10.7 mg/kg bw tiamulin. There was no substance-related changes in blood pressure, serum chemistry or electrocardiograms.

/HUMAN EXPOSURE STUDIES/ In a patch study in humans, topical administration of a 0.05% formulation did not cause skin irritation or sensitization.

AEROBIC: Tiamulin has a biodegradation half-life of 16 days in soil based upon a 120-day aerobic biodegradation soil test(1).

ANAEROBIC: Tiamulin was not biodegraded under anaerobic conditions maintained for 180 days at 20 °C digested in liquid manure(1).

SEDIMENT: Tiamulin was detected in sediment samples from the Bay of Cadiz, Spain in samples collected March and September of 2011; all concentrations were 0.10 mg/kg or less; samples were from 6 locations (Chiclana de la Frontera, Puerto Real, Cadiz, two locations at El Puerto di Santa Maria and Rota)(1).

An estimated BCF of 640 was calculated in fish for tiamulin(SRC), using an estimated log Kow of 4.75(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

An estimated pKa of 9.51(1) indicates tiamulin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation form from water and moist soil surfaces is not expected to be an important fate process(SRC). The Henry's Law constant for the neutral species of tiamulin is estimated as 4.2X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that the neutral form of tiamulin is expected to be essentially nonvolatile from water and moist soil surfaces(3). Tiamulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-14 mm Hg(SRC), determined from a fragment constant method(2).

Tiamulin. Oral dosage form new animal drugs. Conditions of use in swine.

A tolerance of 0.6 part per million is established for 8-alpha-hydroxymutilin (marker compound) in liver (target tissue) of swine.

Tiamulin. New animal drug for use in animal feeds. Conditions of use in swine.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Tiamulin is included on this list.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Tiamulin hydrogen fumarate is included on this list. /Tiamulin hydrogen fumarate/

Antibiotic approved for use as a growth enhancer in poultry and livestock.

Food efficiency/growth promotion in swine.

Used against dysentery and mycoplasma infections in sheep, swine, cattle, and chickens

Effective in the treatment of swine dysentery and mycoplasmal arthritis /Tiamulub funarate/

For more Uses (Complete) data for TIAMULIN (7 total), please visit the HSDB record page.

Derivative of Pleuromutilin ... Preparation: H. Egger, German patent 2248237 corresponds to USA patent 3919290 (1973, 1975 both to Sandoz).

Tiamulin is a diterpene antibiotic containing an eight-membered carbocyclic ring. It is a derivative of pleuromutilin, an antibiotic substance produced by Pleurotus mutilis and P. passeckerianus.

Tiamulin Soluble Powder: 45% in 2.28 ox packets (29.1 g tiamulin per packet); Denagard Liquid Concentrate, TiaGard; (OTC).

Tiamulin Solution: 12.3% tiamulin hydrogen fumarate in an aqueous base in 32 oz bottles; Denagard Liquid Concentrate, TiaGard; (OTC).

Tiamulin Medicated Premix: 10 g/1 lb in 35 lb bags; Denagard 10; (OTC).