Toxicity reversibility

TNF-a converting enzyme, 38,153 toll-like receptor (TLR) signaling, 45, 191 topical microbicides, 40, 277 topoisomerase, 21, 247 44, 379 toxicity, mathematical models, 18, 303 toxicity reversal, 15, 233... 

Characterize toxicities (delayed toxicity/ reversibility of toxicity). 

There were signs of opiate toxicity, reversible with naloxone, in an 80-year-old woman after concomitant treatment with amitriptyline and co-codamol (codeine plus paracetamol) (SEDA-18, 79). 

Shaul WL, Wandell M, Robertson WO. Dextromethorphan toxicity reversal by naloxone. Pediatrics 1977 59(1) 117-18. 

Reversible versus irreversible toxicity Reversible toxic effects are those that can be repaired, usually by a specific tissue s ability to regenerate or mend itself after chemical exposure, while irreversible toxic effects are those that cannot be repaired. 

Creation of low toxic reverse-transcriptase inhibitory nucleosides that prevent the emergence of drug-resistant HIV variants 06Y716. 

Cowger, M. (1971). Mechanism of bihrubin toxicity on tissue culture cells factors that affect toxicity, reversibility by albumin, and comparison with other respiratory poisons and surfactants. 

Some toxicological data for cyclic ketones are shown in Table 16. Interestingly, toxicity is shown to increase with ring size. This is in reverse order of relative reactivity. 

Hydrolysis is a significant threat to phosphate ester stabiHty as moisture tends to cause reversion first to a monoacid of the phosphate ester ia an autocatalytic reaction. In turn, the fluid acidity can lead to corrosion, fluid gelation, and clogged filters. Moisture control and filtration with Fuller s earth, activated alumina, and ion-exchange resias are commonly used to minimise hydrolysis. Toxicity questions have been minimised ia current fluids by avoiding triorthocresyl phosphate which was present ia earlier natural fluids (38). 

Toxicity. Lethality is the primary ha2ard of phosphine exposure. Phosphine may be fatal if inhaled, swallowed, or absorbed through skin. AH phosphine-related effects seen at sublethal inhalation exposure concentrations are relatively small and completely reversible. The symptoms of sublethal phosphine inhalation exposure include headache, weakness, fatigue, di22iness, and tightness of the chest. Convulsions may be observed prior to death in response to high levels of phosphine inhalation. Some data are given in Table 2. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

Transient effects are those where there is repair of toxic physical injury or the reversal of induced biochemical aberrations. 

Copper sulfate, in small amounts, activates the zinc dust by forming zinc—copper couples. Arsenic(III) and antimony(TTT) oxides are used to remove cobalt and nickel they activate the zinc and form intermetaUic compounds such as CoAs (49). Antimony is less toxic than arsenic and its hydride, stibine, is less stable than arsine and does not form as readily. Hydrogen, formed in the purification tanks, may give these hydrides and venting and surveillance is mandatory. The reverse antimony procedure gives a good separation of cadmium and cobalt. 

Lldoc ine. Lidocaine hydrochloride, an anilide, was originally introduced as a local anesthetic in 1943 and found to be a potent antiarrhythmic in 1960. The compound is a reverse amide of procainamide. Lidocaine is generally considered to be the dmg of choice in the treatment of ventricular arrhythmias and those originating from digitalis glycoside toxicity (1,2,15—17). 

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