Toxicity, hepato

Safety/Toxicity Acute toxidty,i aquatic toxicity,2o carcmogenicity,2i chemical toxicity, hepato-toxicity,23 cytotoxicity,23 genotoxicity, mutagenicity,25.26 oral toxicity, percutaneous toxicity, phytotoxicity29... 

Chloroform is a potent volatile anaesthetic, but is little used due to its potential hepato-toxicity. It is used principally for the manufacture of chlorofluorohydrocarbon refrigerants ( Arctons and Freons ) and certain polymers. 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Li AP. A review of the common properties of drngs with idiosyncratic hepato-toxicity and the mnltiple determinant hypothesis for the manifestation of idiosyncratic drng toxicity. Chem Biol Interact 2002 142 7-23. 

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

Bolton, J. L. Valerio, L. G. Thompson, J. A. The enzymatic formation and chemical reactivity of quinone methides correlate with alkylphenol-induced toxicity in rat hepato-cytes. Chem. Res. Toxicol. 1992, 5, 816-822. 

Obtain a complete history of alcohol intake and hepato-toxic drug use, including over-the-counter products and dietary supplements. 

Hydroxylation may also take place at nitrogen atoms, resulting in hydroxyl-amines (e.g., acetaminophen). Benzene, polycyclic aromatic compounds (e.g., benzopyrene), and unsaturated cyclic carbohydrates can be converted by mono-oxygenases to epoxides, highly reactive electrophiles that are hepato-toxic and possibly carcinogenic. 

Toxicology. Chlorinated dibenzo-p-dioxins (CDDs) cause chloracne, may cause hepato-toxicity, immunotoxicity, reproductive toxicity, developmental toxicity, and central nervous system toxicity, and are considered to be a human carcinogen. 

Several studies have reported hepatic effects in animals after exposure to HMX. Hepatocyte hyperplasia and cytoplasmic eosinophilia were noted in rats and mice orally exposed to 1280 and 300mg/kg/day, respectively, for 14 days. Clear evidence of hepato-toxicity was observed at a higher dose of 8504mg HMX/kg/day, which resulted in cen-trilobular degeneration in male rats exposed for 14 days. Collectively, the data from animal studies indicate that the liver is adversely affected by exposure to moderate to high doses of HMX. 

Rabbits died from exposure to 5000 ppm for 3 hours but survived 3 hours at 2500ppm. Exposure to the higher concentrations caused irritation of mucous membranes, lacrima-tion, dyspnea, pulmonary rales, and, in a few animals, pulmonary edema convulsions were rare and of brief duration. Autopsy of animals exposed to lethal concentrations showed mild to severe liver damage and nonspecific changes in the kidneys. Nitroethane was not hepato-toxic after administration of 9mmol/kg to mice. ... 

Adverse effects include changes in libido and the occurrence of oedema, weight gain and gynecomastia, may occur. Androgens are potentially hepato-toxic, testosterone less than methyltestosterone and fluoxymesterone. Androgens can potentiate anticoagulant action. 

Albendazole selectively blocks glucose uptake and depletes glycogen stores. ATP formation is thus inhibited. It should be administered on an empty stomach for intraluminal parasites and with a fatty meal for tissue parasites. It is metabolized to an active sulfoxide metabolite resulting in very low Albendazole blood levels. Albendazole sulfoxide is excreted in the urine with an elimination half-life of about 8 h. Used for 1-3 days in doses recommended for intestinal worms the incidence of adverse effects is similar in treatment and control groups. Hepato-toxicity may occur, especially after the higher doses that are needed for hydatid disease. Also alopecia has been reported. 

Lenalidomide, a derivative of thalidomide, was introduced in 2004. Patients with multiple myeloma stage II/III, who have undergone at least one previous treatment can be treated with bortezomib or with lenalidomide in combination with dexamethasone. There is good oral absorptin with peak plasma levels at 0.5-4 hours. Lenalidomide is maily eliminated by the kidneys with a half-life of circa 3-9 hours. Teratogenicity cannot be excluded. Side effects include thrombosis, pulmonary embolus, and hepato-toxicity, as well as bone marrow toxicity resulting in neutropenia and thrombocytopenia. 

Antihepatotoxic activity. Water extract of the dried stem (bagasse), administered in-traperitoneally to mice at a dose of 25 mg/ kg, was active vs CCl -induced hepato-toxicity ° . 

Pemoline has effect of rare serious hepato-toxicity requires monitoring of liver function tests... 

A.M. Mosunov and A.V. Pozdnyakov used Enterosgel for acceleration of regression of hepato-depressive syndrome in patients with severe diffuse liver pathology, and reported shortened terms of disability of these patients from 29.4 3.8 to 18.3 2.4 days [81], A.B. Kaydulov and I.V. Vasilenko observed fast reduction of toxic and abstinent events as well as improved functional state of the Uver and decreased requirement for transfusion therapy in patients with alcoholic intoxication and in patients with abstinence syndrome of moderate severity, treated with Enterosgel [82]. 

Aliphatic carboxylic adds are an important and widely used class of commercial chemicals. The commertial uses of carboxylic acids include synthetic intermediates, lubricants, catalysts, and preservatives, to name just a few. Some carboxylic adds cause liver (hepato) toxicity, most notably valproic add (2-propylpentanoic add) (12), and 2-ethylhexanoic add, (13). Although relatively few carboxylic adds cause liver toxicity, when it does occur it can be severe [49]. 

Measurements in vivo, such as barbiturate sleeping times, are in agreement with these findings, sleeping times being longer in protein-deficient animals. Toxicity may also be influenced by such factors as a low-protein diet. For example, the hepa to toxicity of carbon tetrachloride is markedly less in protein-deficient rats than in normal animals, and this correlates with the reduced ability to metabolize the hepato toxin in the protein-deficient animals. 

However, the reverse is the case with the hepato toxicity of paracetamol, which is increased after a low-protein diet. This may be due to the reduced levels of glutathione in rats fed low-protein diets, which offsets the reduced amount of cytochromes P-450 caused by protein deficiency. 

The outcomes of the interaction between a chemical and a target molecule will depend both on the attributes and on the function of the target molecule. Thus, a covalent adduct could be formed, which might be recognized as a neo-antigen (e.g., see sect. "Halothane Hepato toxicity," chap. 7), or a mutation could be caused if the target is DNA [see sect. "Benzo(a)pyrene," chap. 7]. 

Thus, bromobenzene hepato toxicity is probably the result of metabolic activation to a reactive metabolite, which covalently binds to protein and other macromolecules and other cellular molecules. It may also stimulate lipid peroxidation, and biochemical effects, such as the inhibition of SH-containing enzymes, may also play a part. 

Carbon tetrachloride is a hepato toxic solvent, which causes centrilobular necrosis and fatty liver, liver cirrhosis, and tumors and kidney damage after chronic exposure. It is metabolized... 

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