3-メチルブタン酸(3S,4R,7R,8R,9S)-3-[(3-ホルミルアミノ-2-ヒドロキシベンゾイル)アミノ]-4,9-ジメチル-2,6-ジオキソ-7-ヘキシル-1,5-ジオキソナン-8-イル

(Non-Specific -- Pesticide, Solid, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Wear positive pressure breathing apparatus and special protective clothing. Remove and isolate contaminated clothing at the site.

(Non-Specific -- Pesticide, Solid, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Remove and isolate contaminated clothing at the site. Do not touch spilled material; stop leak if you can do so without risk. Use water spray to reduce vapors.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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.

0.031 [mg/m3]

0.34 [mg/m3]

2.1 [mg/m3]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Antimycin A at levels that abolish oxygen consumption had a slight, although statistically significant, inhibitory effect on the toxicity elicited by t-butylhydroperoxide in U937 cells. The protective effect was observed after 6 hr of post-treatment incubation, but was no longer apparent after 24 hr. Unexpectedly, these events were associated with a marked accumulation of DNA single-strand breaks produced by low levels of t-butylhydroperoxide. Both an oxygen- and a carbon-centred radical were found to arise during treatment with t-butylhydroperoxide, and their formation was significantly lowered by antimycin A. Thus inhibition of electron transport at the level of complex III appears (a) to decrease the formation of toxic species which mediate, at least partially, the lethal effects elicited by t-butylhydroperoxide, and (b) to enhance the formation of DNA-damaging species generated at low concentrations of t-butylhydroperoxide. Rotenone and cyanide, which respectively inhibit complexes I and IV, did not affect DNA damage elicited by t-butylhydroperoxide. These results suggest that DNA single-strand breaks do not mediate the toxicity of t-butylhydroperoxide, and that specific mitochondrial functions might modulate the formation of the toxic and of DNA-damaging species generated by organic hydroperoxides.

LC50 Anas platyrhynchos (Mallard duck) oral 2.9 mg/kg

LC50 Colinus virginianus (Northern bobwhite) oral 39 mg/kg

LC50 Anguilla rostrata (American eel) 3 ug/L/96 hr (95% confidence interval: 2-11 ug/L); static

LC50 Asellus intermedius (Aquatic sowbug) 11.8 ug/L/96 hr (95% confidence interval: 7.4-18.9 ug/L); static

For more Ecotoxicity Values (Complete) data for ANTIMYCIN A (22 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Stream-dwelling invertebrates were decimated by application of 10 ug/L of antimycin A for fish eradication in Ord Creek, AZ. Three years later, numbers, biomass and diversity of invertebrates were similar to pretreatment conditions, but possible taxanomic changes were indicated.

/AQUATIC SPECIES/ At 18 °C, the average control respiration rate of trout liver mitochondria was higher than that of channel catfish. The liver mitochondria of channel catfish and trout respond in a similar manner to antimycin concentrations from 10-100 ppb. Antimycin concentrations from 300 ppb-1 ppm caused a greater percent inhibition to the respiration of trout mitochondria (80-96%) than to catfish mitochondria (42-67%). At antimycin concentrations from 300 ppb-1 ppm, trout had control respiration rates almost double those of catfish and treatment rates lower than those of catfish.

/AQUATIC SPECIES/ Ten to 20 organisms of the ostracod species, Cypretta kawatai, were maintained in water-filled chambers to which antimycin A, Bayer 73, TFM, or mixtures of TFM and Bayer 73 had been added as acetone solutions. After 96 hr, the LC50 of antimycin A (7.4 mug/L. ) was 95. 5%, while that of TFM (7.1 mg/L) was 95.7% and that of Bayer 73 (1.16 mg/L) was 70%. The toxicity of a 50:50 mixture of TFM and Bayer 73 was simply additive, while that of a 98:2 mixture was slightly synergistic. The results indicate that the three toxicants would have no significant immediate effect on C. kawatai when employed at normal field concentrations for short periods of time. However, material loss of the ostracods would occur if the toxicants were to persist in their environment at application concentrations for more than 48 hr.

/ALTERNATIVE IN VITRO TESTS/ The effects of the metabolic poisons antimycin A (4.1 mug/mL) and 2-deoxyglucose (32.2 mM) on the uptake and vesicular storage of serotonin (5HT) in washed human platelets were examined. Within 15 s after the addition of the metabolic poisons, H3-5HT began to move from vesicles into the cytoplasm. By 30 min after poison addition, essentially all the platelet 5HT appeared to be cytoplasmic. The metabolic poisons acted rapidly to decrease plasma-membrane uptake of H3-5HT from the extracellular medium by approximately 20% within 1 min after their addition. This may represent a direct effect rather than one resulting from altered cytoplasmic or vesicular 5HT, since platelets with < 10% of the normal number of vesicular storage sites exhibited a similar reduction after addition of the metabolic poisons.

/ALTERNATIVE IN VITRO TESTS/ The effects of rotenone, antimycin A, potassium cyanide and 2,4-dinitrophenol, on human sperm motility, were studied using semen samples from healthy men. None of the /compounds/ inhibited sperm motility at concentrations used (10-6 to 10-3).

/ALTERNATIVE IN VITRO TESTS/ ... In this study we investigated the effects of a F0F1-ATPase inhibitor, oligomycin, and a mitochondrial respiratory chain complex III inhibitor, antimycin A, on NO-induced apoptosis. We used a normal rat gastric-epithelium cell line, RGM-1, treated with a pure NO donor, NOC-1 -1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene - in the presence or absence of oligomycin or antimycin A. Changes in the expressions of Bax or Bcl-2 proteins, release of cytochrome C from mitochondria into the cytosol, activation of caspase-3, and changes in the mitochondrial membrane potential (DeltaPsi) were measured with the use of Western blotting, c43 lorimetric assays, and a mitochondrial potential sensor, JC-1 dye. Treatment with NOC-18 induced dose-dependent apoptotic cell death in RGM-1 cells. Cell death was accompanied by mitochondrial depolarization, increases in Bax protein expression and cytochrome C leakage, and, subsequently, caspase-3 activation. Oligomycin and antimycin A prevented NO-induced apoptosis in a dose-dependent fashion by preventing cytochrome C release independent of Bcl-2 expression. However, neither compound affected the up-regulation of Bax protein. On the one hand, oligomycin treatment was not accompanied by a decline in DeltaPsi. On the other hand, antimycin A treatment decreased DeltaPsi regardless of NOC-18 treatment.

/ALTERNATIVE IN VITRO TESTS/ ...We investigated the effect of antimycin A, an inhibitor of mitochondrial energy production, on the number of fenestrae in cultured LSECs, /liver sinusoidal endothelial cells/, using high-resolution microscopy and immunocytochemistry. Prolonged incubation (>30 min) with antimycin A resulted in defenestrated cells and coincided with the appearance of F-actin dots, whereas the distribution of G-actin remained unchanged. Adenosine triphosphate (ATP) was depleted dramatically to <5% within 30 min within the LSECs. After treatment with antimycin A, unusual elevated fenestrated complexes were apparent, organized as a meshwork of anastomosing fenestrae at the center of and above the sieve plates. The position and appearance of these novel structures and their association with defenestration suggest that they are implicated in the process of defenestration.

/ALTERNATIVE IN VITRO TESTS/ In a patch-clamp study, we found antimycin A in low (1-2) uM concentrations decreased the open probability of the multiple conductance channel activity and the approximately 110 picosiemens channel of the inner mitochondrial membrane. Higher antimycin A concentrations (e.g. 10 uM) facilitated multiple conductance channel opening. These effects were reversible, and the binding site(s) are probably distinct from those responsible for the inhibition of the electron transport chain, since the latter are virtually irreversible.

/ALTERNATIVE IN VITRO TESTS/ ...Antimycin A did not interfere with cell accumulation of T3 but induced a 10-fold decrease of nuclear T3. This effect was due to a decrease of the apparent affinity constant of the T3 nuclear receptor.

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

LD50 Mouse iv 0.893 mg/kg

LD50 Mouse dermal 21 mg/kg

LD50 Mouse ip 0.82 mg/kg

LD50 Rat ip 0.8 mg/kg

LD50 Rat dermal 25 mg/kg

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. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Antimycin A is found on List D. Case No: 4121; Pesticide type: insecticide (piscicide); 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 RED document.; Active ingredient (AI): antimycin a; Data Call-in (DCI) Date(s): 9/28/93; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner. /RED scheduled for 3/2007/

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Antimycin A is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .