Rabbits elimination

Body tissue possibly takes up benzyl alcohol rapidly and releases it slowly into the bloodstream. Rabbits when given 1 g (subcutaneously) of benzyl alcohol eliminated 300 00 mg of hippuric acid within 24 h. Rabbits eliminated 65.7% of a dose of 0.4 g of benzyl alcohol as hippuric acid in the urine. The plasma half-life of benzyl alcohol administered as a 2.5% solution in saline was found to be 1.5h in dogs injected intravenously at doses of 52 and 105 mgkg ... 

A study in rabbits, with supporting in vitro experiments, suggests 2,4-DNP binds to serum proteins concentrations of 2,4-DNP in the eye are related to the unbound 2,4-DNP, but there appears to be a blood-aqueous humor barrier preventing free diffusion (Gehring and Buerge 1969b). This barrier was more effective in mature than in immature rabbits. In addition, the mature rabbit eliminated 2,4-DNP more rapidly from serum and the eye. Differences in sensitivity of animals to the cataractogenic properties of 2,4-DNP may be related to the levels of 2,4-DNP attained in the eye. 

Dichloromethotrexate (XXXII, mol. wt. 523) is a folic acid antagonist and its metabolism and excretion in the rat. dog, mouse, and rabbit have been studied using the C1-Iabeled compound (Oliverio and Davidson, 1962). Table XXIX shows that the three former species excrete about 60-80% of a dose of dichloromethotrexate in the bile, while the rabbit eliminates about 40% by this route. There is a species difference in the... 

Human sensitization studies were negative at 10% solution (47). Undiluted benzyl alcohol produces moderate dermal irritation in guinea pigs and mild dermal irritation in rabbits (48,49). Severe eye irritation was noted in a rabbit study (50). Acute oral rat LD q values were reported between 1.23 and 3.10 g/kg (50—52). A dermal rabbit LD q value of 2.0 g/kg has been reported (49). Rats died after 2 h when exposed to a 200-ppm vapor concentration (53). Benzyl alcohol is readily oxidized in animals and humans to benzoic acid [65-85-0] which is then conjugated with glycine [56-40-6], and rapidly eliminated in the urine as hippuric acid [495-69-2] (54). 

Intravenous administration of endosulfan (7 3 ratio of a- and P-isomers) in rabbits produced slower elimination of the a-isomer (Gupta and Ehrnebo 1979). Excretion of the two isomers occurred primarily via the urine (29%) with much less excreted via the feces (2%). Given the earlier evidence in rats and mice describing the principal route of elimination of endosulfan and its metabolite to be via the feces, the differences in the excretion pattern in this study may be attributable to differences in exposure routes, to species differences, or to both. Nevertheless, studies in laboratory animals suggest that both renal and hepatic excretory routes are important in eliminating endosulfan from the body. Elimination of small doses is essentially complete within a few days. 

Anand et al. 1987). The authors hypothesized that the ocular effects associated with endosulfan may be a result of prolonged hypertension (although no data on blood pressure were presented, and there is no other information to indicate that chronically administered endosulfan induces hypertension) or an endosulfan-induced vitamin A deficiency (which was observed in this study). Although the rabbit may represent a uniquely sensitive species, the possibility that long-term exposure of persons at hazardous waste sites to endosulfan may result in adverse effects on ocular tissues cannot be eliminated. 

Smith, T.W. Lloyd, B.L. Spicer, N. and Haber, E. Immuno-genicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon. Clin Exp Immunol 36 384-396, 1979. 

Elimination from the vitreous occurs by one of two pathways. This can be visualized by injecting fluorescent compounds and examining the concentration distribution in frozen sections obtained after a steady state has been established [230]. If the major route of elimination is by means of the re-tina/choroid, at steady state the lowest concentration would be in the vicinity of the retina. The contours observed in frozen sections of the rabbit eye obtained after intravitreal injection of fluorescein exhibit this pattern, with the highest concentration immediately behind the lens (Fig. 16A). Compounds not chiefly eliminated through the retina exit the vitreous by passive diffusion and enter the posterior aqueous, where they are eliminated by the natural production and outflow of aqueous humor. In such a situation, the contours would be perpendicular to the retina, with the highest concentration towards the rear of the vitreous cavity. This appears to be the case for fluorescently labeled dextran polymer, whose contours decrease in concentration toward the hyaloid membrane (Fig. 16B). 

Lead is also eliminated in the bile (Klaassen and Shoeman 1974). In the rat, excretion occurs in the urine, with greater excretion in the feces following intravenous administration (Castellino and Aloj 1964 Klaassen and Shoeman 1974 Morgan et al. 1977). As the dose increases, the proportion of the lead excreted into the gut via bile increases, then plateaus at 3 and 10 mg/kg (Klaassen and Shoeman 1974). Biliary excretion of lead is suggested to be a saturable process (Gregus and Klaassen 1986). Excretion of lead in the bile by dogs amounted to approximately 2% of that by rats, and biliary excretion of lead by rabbits amounted to approximately 40% of that by rats (Klaassen and Shoeman 1974). 

Administration is by direct injection of 0.05 ml product into the eye (intravitreal injection), initially once every 2 weeks and subsequently once every 4 weeks. Animal studies (rabbits) indicated that the product is cleared from the eye over the course of 7-10 days, with direct nuclease-mediated metabolism representing the primary route of elimination. The most commonly observed side effect is ocular inflammation, which typically occurs in one in every four patients. 

Excretion kinetics of chlordane are complex, and different isomers exit through different pathways (USEPA 1980, 1988). In rats, chlordane elimination was almost complete 7 days after receiving single oral doses up to 1 mg/kg body weight (BW) 24 hours after treatment, 70% of the r/. v-chlordane and 60% of the trans-chlordane had been excreted (WHO 1984). In rodents, chlordane and its metabolites were usually excreted in feces, regardless of the administration route the cis-isomer was excreted slightly faster than the trans-isomer, although identical metabolites seemed to be formed (Menzie 1969, 1980 USEPA 1980 WHO 1984 Nomeir and Hajjar 1987). In rabbits, however, up to 47% of the administered dose was voided in the urine, and cis- and /ran.v-chlordanc were excreted at the same rate (Nomeir and Hajjar 1987). 

Hirom [71,72] demonstrated more than three decades ago that the route of excretion of xenobiotics is dependent upon MW by testing up to 75 compounds in rat, guinea-pigs, and rabbits. Lower MW compounds (< 350) were mainly eliminated in the urine (>90%). As MW increased from 350 to 450, a sharp increase in the fraction of compound eliminated in the bile occurred, and for MW > 450, compounds were eliminated 50-100% in the bile in all three species. Smith [73] correlated the log of free metabolic and renal clearance (ml/min/kg) with log D, and found a similar relationship. Metabolic clearance increases with increasing log D, while renal clearance decreases with increasing log D. 

In humans the clearance rate of Hb is higher than that of HpHb (L4, Lll). Murray et al. (M6) found this also to hold for rabbits and, by studying the elimination in nephrectomized animals, they also proved that the difference was not due to urinary loss of Hb. Analysis of the organs proved that the HpHb complex and Hb were assimilated mainly in the liver and were catabolized with an early reappearance of the iron as transferrin iron within 30 minutes. The free Hb accumulated also in the tubular cells of the kidneys. No data have been published suggesting that the spleen is of any appreciable importance in this respect. No typical exponential clearance of the HpHb complex from plasma was observed (L10, Lll) in the first few experiments. Lathem and Worley (L4) found that HpHb disappeared at a simple exponential rate in 5... 

The carbon-fluorine bond is relatively resistant to metabolism. In vitro studies with rabbit, rat, and human hepatic microsomes and rat hepatocytes (Olson and Surbrook 1991 Olson et al. 1990a, 1990b) identified the major route of metabolism of HFC-134a as oxidation by P-450 2E1 to 2,2,2,1-tetrafluoroethanol elimination of hydrogen fluoride or fluoride ion yields 2,2,2-trifluoroacetaldehyde, which is further oxidized to trifluoroacetic acid. 

Each test substance will be screened in order to eliminate potentially corrosive or severely irritating materials from being studied for eye irritation in the rabbit. 

The extent of drug absorption following nasal administration depends to a reasonable extent on the ease with which a drug molecule crosses the nasal epithelium without degradation or rapid clearance by the mucociliary clearance system. The effects of these two elimination components are more pronounced for proteins and peptides. The nasal administration of drugs, especially proteins and peptides, as well as other molecules has been studied with excised tissues harvested from rabbit, cow, sheep, and pig species (Table 5.2). A... 

Data are available for rabbits (Deichmann 1944) and rats (Hughes and Hall 1995 Liao and Oehme 1981). In these species, distribution is rapid, with peak tissue concentrations achieved in most tissues within 1 hour after dosing. The highest peak concentrations and fraction of administered dose are found in the liver >90% of the administered dose is eliminated from tissues within 24 hours. 

The absorption (following administration by oral, intramuscular and intravenous routes), distribution and elimination of the drug has been studied by radiotracer techniques in rats and rabbits [283, 284]. The substituted benzoic acid was labelled with and the alkanolamine remnant with Almost all radioactivity was recovered from the urine even after oral administration. 

Elimination of P743 from the intravascular compartment is best described by a biphasic model in rabbits (Fig. 11). 

Analyses of species differences in the toxicokinetics of compounds eliminated by a single major metabolic pathway in humans have been performed by Renwick and coworkers using pubhshed data for compounds in four test species (dog, rabbit, rat, and mouse). 

Walton et al. (2001a) examined data for compounds eliminated by the cytochrome P450 isoenzymes CYP1A2 in humans. Absorption, bioavailabihty, and route of excretion were generally similar between humans and the test species for each of the substances (caffeine, paraxanthine, theobromine, and theophylline). However, interspecies differences in the route of metabolism, and the enzymes involved in this process, were identified. The magnitude of difference in the internal dose, between species, showed that values for the mouse (10.6) and rat (5.4) exceeded the fourfold default factor for toxicokinetics, whereas the rabbit (2.6) and the dog (1.6) were below this value. 

Walton et al. (2004) determined the extent of interspecies differences in the internal dose of compounds, which are eliminated primarily by renal excretion in humans. Renal excretion was also the main route of elimination in the test species for most of the compounds. Interspecies differences were apparent for both the mechanism of renal excretion (glomemlar filtration, tubular secretion, and/or reabsorption), and the extent of plasma protein binding. Both of these may affect renal clearance and therefore the magnitude of species differences in the internal dose. For compounds which were eliminated unchanged by both humans and the test species, the average difference in the internal dose between humans and animals were 1.6 for dogs, 3.3 for rabbits, 5.2 for rats, and 13 for mice. This suggests that for renal excretion the differences between humans and the rat, and especially the mouse, may exceed the fourfold default factor for toxicokinetics. 

No studies were located regarding excretion following oral exposure to 1,3,5-TNB in animals. Following administration of a single oral dose of C-1,3-DNB to rabbits and rats, radioactivity accounting for more than 80% and 63% of the dose, respectively, was excreted in urine, indicating that the main route of excretion is via the urine (Nystrom and Rickert 1987 Parke 1961). Elimination of 1,3-DNB metabolites in urine was rapid and occurred within 48 hours. The major urinary metabolites in rabbits were 2,4-diaminophenol, 1,3-phenylenediamine, and 1,3-nitroaniline (Parke 1961). 

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