Rat skins

Name CAS RTECS Skin (rabbit) Eye (rabbit) Oral (rat) Skin (rabbit) Dot... 

Since 1973, several authors have proved that there is a relationship between thermostability of collagen and the extent of hydroxylation of the proline residues31,34). Equilibrium measurements of the peptides al-CB 2 of rat tail and rat skin revealed a higher rm, for al-CB 2 (rat skin)157). The sequence of both peptides is identical except that in the peptide obtained from rat skin, the hydroxylation of the proline residues in position 3 has occurred to a higher extent than in the case of al-CB 2 (rat tail). Thus, a mere difference of 1.8 hydroxy residues per chain causes a ATm of 26 K. Obviously, there are different stabilizing interactions in the triple-helical state, that means al-CB 2 (rat skin) forms more exothermic bonds than al-CB 2 (rat tail) in the coil triple-helix transition. This leads to an additional gain of enthalpy which overcompensates the meanwhile occurring losses of entropy. 

In terms of local irritation effects, AOS are reported to result in marked irritation of the eyes at concentrations at or above 1.0%, with slight effects being observed at 0.1% [147,148,150]. Repeated application to rat skin over 15 days at concentrations of 20% or 30% did not result in any macroscopic changes. Microscopic examination, however, did show atrophy of the stratum... 

Lippe, I.T., Stabentheiner, A. and Holzer, P. (1993a). Role of nitric oxide in the vasodilator but not exudative component of mustard oil-induced inflammation in rat skin. Agents Actions 38, c22-24. 

Warren, J.B., Loi, R.K. and Coughlan, M.L. (1993). Involvement of nitric oxide synthase in the delayed vasodilator response to ultraviolet light irradiation of rat skin in vriv. Br. J. Pharmacol. 109, 802-806. 

O. Pillai, N. Kumar, C.S. Dey, S. Borkute, S. Nagalingam, and R. Panchagnula, Transdermal iontophoresis of insulin. Part 1 A study on the issues associated with the use of platinum electrodes on rat skin. J. Pharmacy Pharmacol. 55, 1505-1513 (2003). 

O Brien, R.D. and C.E. Dannelley. 1965. Penetration of insecticides through rat skin. Jour. Agricul. Food Chem. 13 245-247. 

The main depot for dioxin accumulation in mammals is the liver and adipose tissue. When dioxin is fed to rodents with fodder, about 10% of the dose comes in the liver. Should this toxic agent be applied on rat skin, 13% of the dose is absorbed in blood already in 5 hours, and 10% remains on skin surface. 

An increase in the elimination half-life in rats was achieved by blocking the benzylic position of the propionic acid chain by introduction of a cyclopropane ring 22 (%F = 88, Vdss = 1 L/kg, f1/2 = 6.3 h) however, in the case of 22, this led to a reduction in the receptor subtype selectivity (EC50 on SI Pi/1,5 = 0.21,123 and 5.1 nM, respectively). Similarly, blocking the benzylic position by cyclizing onto the phenyl ring to form indanylacetic acid 23 resulted in an improved elimination of half-life (%F — 71, Vdss = 0.4L/kg, f1/2 = 6.7h). Acid 23 showed a similar pharmacokinetic profile in the dog and showed efficacy in the rat skin transplantation model when combined with sub-therapeutic doses of CsA. Compound 23 has been reported to be efficacious in the rat EAE model when dosed therapeutically or prophylactically [94—96]. 

In addition to the main six experimental observations mentioned at the beginning of this Section, some other phenomenological features of the ECT of the cancerous tumors (e.g., grown on the rat skins) have been also noted, as follows 37... 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

The rat skin TER assay enables to reliably discriminate between skin corrosives and noncorrosive substances [148], The assay relies on the change in the bioelectrical properties of the skin in response to the application of test chemicals. For the measurements, small discs of rat skin are necessary onto which the substances are applied to the epidermal surface for up to 24 h. In... 

The TER assay of rat skin is a fully accepted replacement method of animal tests for skin corrosion. Hence, in the EU the TER assay is mandatory for the evaluation of test substances. Investigation of animals to test the corrosivity of chemicals and/or other substances is not permitted [151],... 

R. C. Scott, P. L. Batten, H. M. Clowes, B. K. Jones, and J. D. Ramsey. Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through rat skin. Fundam. Appl. Toxicol. 19 484-492 (1992). 

F.-X. Mathy, A.-R. Denet, B. Vroman, P. Clarys, A. Barel, R. Verbeeck, and V. Preat. In vivo tolerance assessment of skin after insertion of subcutaneous and cutaneous microdialysis probes in the rat. Skin Pharmacol. Physiol. 16 18-27 (2003). 

S. A. Hotchkiss, M. A. Chidgey, S. Rose, and J. Caldwell. Percutaneous absorption of benzyl acetate through rat skin in vitro. I. Validation of an in vitro model against in vivo data. Food Chem. Toxicol. 28 443-447 (1990). 

R. C. Scott, M. Walker, and P. H. Dugard. In vitro percutaneous absorption experiments A technique for the production of intact epidermal membranes from rat skin. J. Soc. Cosmet. Chem. Jpn. 37 35-41 (1986). 

ECVAM. News and Views. Statement on the scientific validity of the rat skin transcutaneous electrical resistance (TER) test (an in vitro test for skin corrosivity). ATLA 26 275-280 (1998). 

Bando H, Sahashi M, Yamashita F, Takakura Y, Hashida M (1997) In vivo evaluation of acyclovir prodrug penetration and metabolism through rat skin using a diffusion/bioconversion model. Pharm Res 14 56-62. 

When human skin was treated in vitro with 0.0013-0.0027 mg/cm2 [14C]-labeled phenol and left unoccluded, 20% of the radioactivity was absorbed when analyzed 72 hours later, while 7% remained on the skin surface (Hotchkiss et al. 1992). Covering the skin with a teflon cap resulted in the absorption of 47%, with 3% recovered in the skin. When rat skin was subjected to the same exposure regime in this study, 72 hours later 24% of the radioactivity was absorbed with 22% recovered in the skin when the skin was unoccluded, and 36% was absorbed with 3-4% recovered in the skin when the skin was occluded. 

Percutaneous absorption is another route of interest for the administration of peptides [158], with metabolism being a complicating factor [159]. Thus, [Leu5]enkephalin and Tyr-Pro-Leu-Gly-NH2 were rapidly degraded on the dermal side after penetration through rat skin preparations [160]. The use of inhibitors confirmed the involvement of serine proteases and metalloenzymes. 

DDT (dichlorodiphenyltrichloroethan e) Pesticide Well above 278 mg/Kg. - None identified EPA identified as of Moderate Toxicity 2000-5000 mg/Kg rat -skin LD50 Will naturally decay to DDE and then stop all further degradation... 

Semak I, Korik E, Naumova M, Wortsman J, Slominski A. 2004. Serotonin metabolism in rat skin characterization by liquid chromatography-mass spectrometry. Arch Biochem Biophys 421 61. 

Flandin F, Buffevant C and Herbage D (1984) A differential scanning calorimetry analysis of the age-related changes in the thermal stability of rat skin collagen. Biochim Biophys Acta 791, 205-211. 

No studies were located regarding the metabolic pathway of fuel oils in humans. In one animal study, fuel oil no. 2 applied to the skin of rats induced cutaneous aryl hydrocarbon hydroxylase activity in rat skin microsomal preparations by causing a three-fold induction of benzo(a)pyrene (BaP) 3-hydroxylase activity (Rahimtula et al. 1982). In addition, BaP 3-hydroxylase activity was selectively inhibited by -naphthoflavone, but not by metyrapone, suggesting that cytochrome P-448 enzymes are induced and may participate in the metabolism of this fuel oil (Rahimtula et al. 1982). 

The TER assay uses freshly isolated rat skin and is described in Section 4.5.3.2. 

EU test method B40, Skin corrosion in vitro), which includes two in vitro tests for skin corrosion, the rat skin TER assay and a test employing a human skin model (Section... 

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