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Oral. Oral administration is often referred to as administration per os (PO). Compounds can be administered mixed in the diet, dissolved in drinking water, by gastric gavage, by controlled-release capsules, or by gelatin capsules. In the rst two cases, either a measured amount can be provided or access can be ad libitum (available 24 hours per day), with the dose estimated from consumption measurements. For certain tests pair-feeding of controls should be considered; that is, controls are permitted only the amount of food consumed by treated animals. In any case it is essential to consider possible nutritional effects caused by reduction of food intake due to distasteful or repellent test materials. In gastric gavage, the test material is administered through a stomach tube or gavage needle; if a solvent is necessary for preparation of dosing solutions or suspensions, the vehicle is administered also to control animals. Dermal. Dermal administration is required for estimation of toxicity of chemicals that may be absorbed through the skin, as well as for estimation of skin irritation and photosensitization. Compounds are applied, either directly or in a suitable solvent, to the skin of experimental animals after hair has been removed by clipping. Often dry materials are mixed with water to make a thick paste that can be applied in a manner that ensures adequate contact with the skin. Frequently the animals must be restrained to prevent licking and hence oral uptake of the material. Solvent and restraint controls should be considered when stress is involved. Skin irritancy tests may be conducted on either animals or humans, using volunteer test panels for human tests.

Measures of lack of t from tests of chi-squared type J Statist Planning Inference, 10:151 166, 1984..

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32. H. Mann and A. Wald. On the choice of the number of class intervals in the application of the chi-square test. Ann. Math. Statist., 13:306 317, 1942. 33. V. Paxson. Empirically derived analytic models of wide-area TCP connections: extended report. Technical Report LBL-34086, Lawrence Berkeley Laboratory, 1993. 34. V. Paxson. Empiricall derived analytic models of wide-area TCP connections. IEEE=ACM Trans. Networking, 2(4):316 336, 1994. 35. V. Paxson and S. Floyd. Wide-area traf c: the failure of Poisson modeling. IEEE=ACM Trans. Networking, 3(1):226 244, 1995. 36. K. Park. G. Kim, and M. E. Crovella. On the relationship between le sizes, transport protocols, and self-similar network traf c. In Proceedings IEEE International Conference on Network Protocols, pp. 171 180, 1996. 37. V. N. Padmanabhan and J. C. Mogul. Improving HTTP latency. Comput. Networks ISDN Syst., 28(1=2):25 35, December 1995. 38. B. K. Ryu and A. Elwalid. The importance of long-range dependence of VBR video traf c in ATM traf c engineering: myths and realities. In SIGCOMM Symposium on Communications Architectures and Protocols, pp. 3 14, 1996. 39. D. W. Scott. On optimal and data-based histograms. Biometrika, 66:605 610, 1979. 40. A. Shaikh, J. Rexford, and K. G. Shin. Evaluating the overheads of source-directed qualityof-service routing. Technical Report, University of Michigan, 1998. 41. W. Willinger, M. S. Taqqu, W. E. Leland, and D. V. Wilson. Self-similarity in high-speed packet traf c: analysis and modeling of Ethernet traf c measurements. Statist. Sci., 10(1):67 85, 1995. 42. W. Willinger, M. S. Taqqu, R. Sherman, and D. V. Wilson. Self-similarity through highvariability: statistical analysis of Ethernet LAN traf c at the source level. IEEE=ACM Trans. Networking, 5:71 86, 1997.

Inhalation The respiratory system is an important portal of entry, and for evaluation purposes animals must be exposed to atmospheres containing potential toxicants The generation and control of the physical characteristics of such contaminated atmospheres is technically complex and expensive in practice The alternative direct instillation into the lung through the trachea presents problems of reproducibility as well as stress and for these reasons is generally unsatisfactory Inhalation toxicity studies are conducted in inhalation chambers The complete system contains an apparatus for the generation of aerosol particles, dusts, or gas mixtures of de ned composition and particle size, a chamber for the exposure of experimental animals, and a sampling apparatus for the determination of the actual concentration within the chamber All these devices present technical problems that are dif cult to resolve For rat studies, a particle size of 4 microns is usually targeted.

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